Imaging and Technology in Urology

Imaging and
Technology in
Urology
Sotonye Tolofari
Dora Moon
Benjamin Starmer
Steve Payne
Editors
Second Edition
123
Imaging and Technology in Urology
Sotonye Tolofari • Dora Moon
Benjamin Starmer • Steve Payne
Editors
Imaging and Technology

in Urology
Second Edition
Editors
Sotonye Tolofari Dora Moon
Northern Care Alliance Lancashire Teaching Hospitals NHS
Salford Care Organisation Foundation Trust
Manchester, UK Preston, UK
Benjamin Starmer Steve Payne

Liverpool University Hospitals Manchester University NHS
Liverpool, UK Foundation Trust
Manchester, UK
Springer-Verlag London 2012
ISBN 978-3-031-26057-5 ISBN 978-3-031-26058-2 (eBook)

https://doi.org/10.1007/978-3-031-26058-2
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature
Switzerland AG 2012, 2023
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Contents
Part I Imaging Radiology

1
Principles of X-ray Production and Radiation Protection �� 3
Paul M. Taylor
2
How to Perform a Clinical Radiograph and Use a C-arm �� 9
Paul M. Taylor
3 Contrast Agents�� 13
Anas Hattab
4
Dual Energy X-Ray Absorptiometry (DXA) �� 19
Nicholas Faure Walker and Richard Whitehouse
5
The Physics of Ultrasound and Doppler�� 25
Paul M. Taylor
6
How to Ultrasound a Suspected Renal Mass�� 31
Allen Ikwuagwu
7
How to Ultrasound a Painful Testicle and Mass�� 39
Allen Ikwuagwu
8
How to Do a Trans-Perineal Ultrasound Guided Biopsy of the
Prostate �� 47
Omar El-Taji, Samih Taktak, and John McCabe
9
How to Manage an Infected Obstructed Kidney�� 55
Louise E. Olson
10
Principles of Computed Tomography (CT) �� 59
Richard Hawkins
11
How to Do a CT Urogram (CT)�� 65
Varun Misra and Ryan Pathak
v
vi Contents
12
How to Do a Renal and Adrenal CT�� 71
13
How to Do a CT in a Patient with Presumed Upper Tract Trauma�� 77
Anas Hattab and Jonathan Smith
14
Principles of Magnetic Resonance Imaging (MRI)�� 83
Richard Hawkins
15
Safety in MR Scanning�� 89
Suzanne Phenna
16
Urological Applications of MRI Scanning �� 95
17
Vascular Embolisation Techniques in Urology�� 103
Symeon Lechareas
Part II Imaging Nuclear Medicine

18
Radionuclides and Their Uses in Urology�� 113
Matthew Memmott and Richard Lawson
19
Counting and Imaging in Nuclear Medicine �� 117
Christopher Mathews-Aspinall and Richard Lawson
20
Principles of Positron Emission Tomography (PET) Scanning �� 121
Phei Shan Chuah and Seshadri Nagabhushan
21
PET-CT Imaging in Prostate Cancer �� 127
Seshadri Nagabhushan and Phei Shan Chuah
22
Understanding the Renogram: How It’s Done and How to
Interpret It�� 133
Rakesh Sajjan and Mary Prescott
23
The Diuresis Renogram: How It’s Done and How to Interpret It�� 139
24
Understanding the DMSA Scan: How It’s Done and How to
25
How to Do a Radioisotope Glomerular Filtration Rate Study�� 147
Sarah Sargant and Richard Lawson
26
Understanding the Radionuclide Bone Scan: How It’s Done and How To
27
Renography of the Transplanted Kidney: How It’s Done and How to
Contents vii
28
Dynamic Sentinel Lymph Node Biopsy in Penile Cancer�� 165
Ben Ayres and Nick Watkin
Part III Technology Diagnostic Technology

29 Urinalysis�� 171
David G. Ross
30
Principles of Urine Microscopy and Microbiological Culture�� 177
Ffion E. Carlin and Cecilia M. Jukka
31 Urinary Flow Cytometry�� 183
Harry Rudman and Dora Moon
32 Urine Cytology �� 187
Nadira Narine and Durgesh N. Rana
33
Histopathological Processing, Staining and Immuno-Histochemistry 193
Tegan Miller
34 Tumour Markers�� 197
Alex Hoyle
35
Measurement of Glomerular Filtration Rate (GFR)�� 205
Stephen Brown
36
Assessment of Urinary Tract Stones�� 209
Robert C. Calvert
37
Principles of Pressure Measurement�� 215
Ian Pearce
38
Principles of Measurement of Urinary Flow �� 219
Timothy Napier-Hemy and Richard Napier-Hemy
39
How to Carry Out a Video Cystometrogram (VCMG) in an Adult�� 223
Magda Kujawa
40 Sphincter Electromyography (EMG)�� 229
Emma L. Foster, Katherine E. Burnett, and Christopher D. Betts
Part IV Technology Operative

41 Operating Theatre Safety�� 237
Steve Payne
42 Principles of Decontamination�� 241
Sotonye K. Tolofari
43
Patient Safety in the Operating Theatre Environment�� 247
Steve Payne
viii Contents
44 Venous Thromboembolic Prevention �� 253

Christian Longley
45 Anticoagulants and Their Reversal�� 261
Gidon Ellis
46 Haemostatic Agents, Tissue Sealants and Adhesives�� 267
Omer Abdalla and Suresh Venugopal
47 Transfusion in Urology�� 271
Craig Carroll, Jayne Peters, and Harriet Lucero
48
Cell Salvage in Urological Surgery�� 277
49
Principles of Urological Endoscopes�� 283
Hari L. Ratan
50 Rigid Endoscope Design�� 287
James Broome
51
Light Sources, Light Leads and Camera Systems�� 291
Hari L. Ratan
52
Peripherals for Endoscopic Use�� 295
Steve Payne
53
Peripherals for Laparoscopic Use�� 301
Dora Moon
54
Peripherals for Mechanical Stone Manipulation�� 305
Ciaran Lynch
55 Sutures and Clips �� 311
Bachar Zelhof
56 Contact Lithotripters�� 319
Tom Brophy and Steve Payne
57 Monopolar Diathermy �� 325
Luke Forster
58 Bipolar Diathermy �� 329
Luke Forster
59 Alternatives to Electrosurgery�� 333
Bachar Zelhof
60 Operative Tissue Destruction�� 337
Matthew Liew
61
Endoscopic Use of Laser Energy�� 341
Tev Aho and Omar Al Kadhi
Contents ix
62
Double J Stents and Nephrostomy �� 349
63
Urinary Catheters, Design and Usage�� 355
Benjamin Starmer
64 Urological Prosthetics�� 361
Ian Eardley
65 Mesh in Urological Surgery�� 367
Niyukta Thakare and Chris Harding
66
Irrigation Fluids and Their Hazards�� 373
Matthew Liew
67 Insufflants and Their Hazards�� 377
Yuhao Zhang and Stephen Bromage
68 Laparoscopic Ports�� 383
Euan Green
69
Principles of Robotic Surgery �� 387
Robin Weston
70
Setting Up Robotic Surgery�� 393
Robin Weston
71
Principles of Tissue Transfer for Urologists�� 397
Patrick Gordon, Wai Gin Lee, and David Ralph
Part V Technology Interventional

72
Neuromodulation by Sacral Nerve Stimulation�� 405
Katherine E. Burnett, Christopher D. Betts, and Emma L. Foster
73
Principles of Extracorporeal Shockwave Lithotripsy (ESWL) �� 409
Robert C. Calvert
74
How to Carry Out Shockwave Lithotripsy (SWL) �� 415
Robert C. Calvert
75 Novel Technologies for BPH�� 419
Craig Jones
76 Ablative Therapies �� 427
Nikhil Mayor and Taimur T. Shah
77 Principles of Radiotherapy�� 433
Martin Swinton and Andrew Hudson
78
Brachytherapy for Prostate Cancer �� 439
Mariam Obeid and Maria Serra
x Contents
79 Augmented Intravesical Drug Administration�� 447

Benjamin Starmer and Henry Lazarowicz
Part VI Technology of Renal Failure

80
Principles of Renal Replacement Therapy (RRT)�� 455
Mumtaz Patel
81
Principles of Peritoneal Dialysis �� 459
Dimitrios Poulikakos and David Lewis
82 Haemodialysis�� 465
Mumtaz Patel
83 Principles of Renal Transplantation�� 469
David Van Dellen and Jennifer Kingston
Part VII Assessment of Technology

84
Key Concepts in the Design of Randomised Controlled Trials�� 477
Kieran J. O’Flynn
85
Reporting and Interpreting Data from RCTs �� 483
Kieran J. O’Flynn
86 Health Technology Assessment (HTA) �� 489
Luke Vale, Diarmuid Coughlan, and Michael Drinnan
Appendices�� 493
List of Contributors
Omer Abdalla Liverpool University Hospitals NHS Foundation Trust,

Liverpool, UK
Tev Aho Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
Ben Ayres St George’s University Hospitals NHS Trust, London, UK
Christopher D. Betts Salford Care Organisation, Northern Care Alliance,
Salford, UK
Stephen Bromage Stockport NHS Foundation Trust, Stockport, UK
James Broome Salford Care Organisation, Northern Care Alliance, Manchester, UK
Tom Brophy Manchester Royal Infirmary, Manchester, UK
Stephen Brown Stockport NHS Foundation Trust, Stockport, UK
Katherine E. Burnett Salford Care Organisation, Northern Care Alliance,
Salford, UK
Robert C. Calvert Liverpool University Hospital NHS Foundation Trust,
Liverpool, UK
Ffion E. Carlin Liverpool University Hospitals NHS Foundation Trust,
Liverpool, UK
Craig Carroll Salford Care Organisation, Northern Care Alliance, Salford, UK
Phei Shan Chuah Liverpool University Hospitals NHS Foundation Trust,
Liverpool, UK
Diarmuid Coughlan Newcastle University, Newcastle upon Tyne, UK
David Van Dellen Manchester Royal Infirmary, Manchester University NHS
Foundation Trust, Manchester, UK
xi
xii List of Contributors
Michael Drinnan Newcastle upon Tyne Hospitals NHS Foundation Trust,

Newcastle upon Tyne, UK
Ian Eardley Leeds Teaching Hospitals NHS Trust, Leeds, UK
Gidon Ellis Royal Free London NHS Foundation Trust, London, UK
Omar El-Taji St Helens and Knowsley Teaching Hospitals NHS Trust, Prescot, UK
Luke Forster Frimley NHS Foundation Trust, Frimley Park Hospital, Frimley, UK
Emma L. Foster Salford Royal Hospital, Northern Care Alliance NHS Foundation
Trust, Salford, UK
Patrick Gordon Leeds Teaching Hospitals NHS Trust, Leeds, UK
Euan Green Salford Care Organisation, Northern Care Alliance, Manchester, UK
Anas Hattab Manchester University NHS Foundation Trust, Manchester, UK
Richard Hawkins Mid-Cheshire Hospitals NHS Foundation Trust, Crewe, UK
Alex Hoyle Salford Care Organisation, Northern Care Alliance, Salford, UK
Andrew Hudson Christie Hospital NHS Foundation Trust, Manchester, UK
Allen Ikwuagwu Royal Blackburn Hospital, Haslingden Road, Blackburn,
Lancashire, UK
Craig Jones Salford Care Organisation, Northern Care Alliance, Manchester, UK
Cecilia M. Jukka Liverpool University Hospitals Foundation Trust, Liverpool, UK
Omar Al Kadhi Norfolk and Norwich University Hospitals NHS Foundation
Trust, Norwich, UK
Jennifer Kingston Manchester University NHS Foundation Trust, Manchester, UK
Magda Kujawa Stepping Hill Hopsital, Stockport NHS Foundation Trust,
Stockport, UK
Richard Lawson Nuclear Medicine Centre, Manchester University NHS
Henry Lazarowicz Liverpool University Hospitals, Liverpool, UK
Symeon Lechareas Liverpool University Hospitals, Liverpool, UK
Wai Gin Lee University College London Hospitals NHS Foundation Trust,
London, UK
David Lewis Salford Care Organisation, Northern Care Alliance Foundation Trust,
Salford, UK
Matthew Liew Wrightington, Wigan and Leigh NHS Foundation Trust, Wigan, UK
List of Contributors xiii
Christian Longley Liverpool University Hospitals, Liverpool, UK

Harriet Lucero Salford Care Organisation, Northern Care Alliance, Salford, UK
Ciaran Lynch Liverpool University Hospitals, Liverpool, UK
Christopher Mathews-Aspinall Nuclear Medicine Centre, Manchester University
Hospitals, Manchester, UK
Nikhil Mayor Imperial College London (ICL), Charing Cross Hospital, Imperial
College Healthcare NHS Trust, London, UK
John McCabe St Helens and Knowsley Teaching Hospitals, Prescot, UK
Matthew Memmott Manchester University NHS Foundation Trust,
Manchester, UK
Tegan Miller Manchester Royal Infirmary, Manchester, UK
Varun Misra Salford Care Organisation, Northern Care Alliance NHS Trust,
Salford, UK
Dora Moon Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK
Timothy Napier-Hemy Salford Royal Hospital, Northern Care Alliance NHS
Foundation Trust, Salford, UK
Richard Napier-Hemy Manchester Royal Infirmary, Manchester University NHS
Nadira Narine Manchester University NHS Foundation Trust, Manchester, UK
Mariam Obeid The Christie NHS Foundation Trust, Manchester, UK
Kieran J. O’Flynn Salford Care Organisation, Northern Care Alliance,
Manchester, UK
Louise E. Olson Salford Royal Hospital, Northern Care Alliance NHS Foundation
Trust, Salford, UK
Mumtaz Patel Manchester University Hospitals NHS Foundation Trust,
Manchester, UK
Ryan Pathak Salford Care Organisation, Northern Care Alliance NHS Trust,
Salford, UK
Steve Payne Manchester Royal Infirmary, Manchester, UK
Ian Pearce Manchester Royal Infirmary, Manchester University NHS Foundation
Trust, Manchester, UK
Jayne Peters Manchester Foundation Trust, Manchester, UK
Suzanne Phenna Northern Care Alliance NHS Foundation Trust, Salford, UK
xiv List of Contributors
Dimitrios Poulikakos Salford Care Organisation, Northern Care Alliance

Mary Prescott Manchester University NHS Foundation Trust, Manchester, UK
David Ralph University College Hospital, London, UK
Durgesh N. Rana Manchester University NHS Foundation Trust, Manchester, UK
Hari L. Ratan Nottingham University Hospitals NHS Trust, Nottingham, UK
David G. Ross Salford Care Organisation, Northern Care Alliance NHS Foundation
Trust, Salford, UK
Harry Rudman Lancashire Teaching Hospitals Trust, Preston, UK
Rakesh Sajjan Manchester University NHS Foundation Trust, Manchester, UK
Sarah Sargant Manchester University NHS Foundation Trust, Manchester, UK
Maria Serra The Christie NHS Foundation Trust, Manchester, UK
Seshadri Nagabhushan Liverpool University Hospitals NHS Foundation Trust,
Liverpool, UK
Taimur T. Shah Imperial College Healthcare NHS Trust, London, UK
Jonathan Smith St James’s University Hospital, Leeds, UK
Benjamin Starmer Liverpool University Hospitals, Liverpool, UK
Martin Swinton Christie Hospital NHS Foundation Trust, Manchester, UK
Samih Taktak St Helens and Knowsley Teaching Hospitals, Prescot, UK
Paul M. Taylor Manchester University NHS Foundation Trust, Manchester, UK
Niyukta Thakare Newcastle Hospitals NHS Foundation Trust, Newcastle upon
Tyne, UK
Chris Harding Freeman Hospital, High Heaton, Newcastle upon Tyne, UK
Sotonye K. Tolofari Salford Care Organisation, Northern Care Alliance NHS
Luke Vale Newcastle University, Newcastle upon Tyne, UK
Suresh Venugopal Liverpool University Hospitals, NHS Foundation Trust,
Liverpool, UK
Nicholas Faure Walker Kings College Hospital NHS Foundation Trust,
London, UK
Nick Watkin St George’s University Hospitals NHS Trust, London, UK
List of Contributors xv
Robin Weston Liverpool University Hospitals NHS Foundation Trust,

Liverpool, UK
Richard Whitehouse Manchester Royal Infirmary, Manchester, UK
Bachar Zelhof Manchester University, NHS Foundation Trust, Manchester Royal
Infirmary, Manchester, UK
Manchester Royal Infirmary, Manchester University NHS Foundation Trust,
Manchester, UK
Yuhao Zhang Stockport NHS Foundation Trust, Stockport, UK
Part I
Imaging Radiology
Chapter 1
Principles of X-ray Production
and Radiation Protection
Paul M. Taylor
Plain radiography, intra-venous urography, computed tomography (CT), and fluo-

roscopy all use ionizing radiation to produce the images used to investigate and treat
patients with a wide variety of urological conditions. However, such image acquisi-
tion comes at the cost of radiation exposure with its associated risks. It is important
to understand the principles behind X-ray production and radiation protection to
make best use of these imaging modalities, while at the same time minimising the
radiation burden to the patient.
Principles of X-Ray Production
X-rays are part of the spectrum of electromagnetic radiation (Fig. 1.1), They are of
higher frequency (3 × 1019 to 1016 Hertz) and shorter wavelength (10−8 to 10−12 m)
than visible light. The higher frequency and associated higher energy values, typi-
cally in the range of 60–120 keV, allow them to penetrate tissue. The higher energy
values also provide an explanation why they are potentially damaging to these
tissues.
X-rays are produced in a glass tube which contains an anode and a cathode in a
vacuum (Fig. 1.2).
P. M. Taylor (*)
Manchester University NHS Foundation Trust, Manchester, UK
© The Author(s), under exclusive license to Springer Nature 3

Switzerland AG 2023
S. Tolofari et al. (eds.), Imaging and Technology in Urology,
https://doi.org/10.1007/978-3-031-26058-2_1
4 P. M. Taylor
Decreasing wavelength
Increasing frequency
Increasing energy
Wavelength (metres)
106 103 10 10–3 10–6 10–9 10–12 10–15
Visible Gamma
Radio Microwave Infra-red X-Rays
Light Rays
Fig. 1.1 X-Rays place in the electromagnetic spectrum
Collimator X-Ray beam
Glass Envelope Lead housing
Tungsten Anode Heated Cathode
Fig. 1.2 X-Ray generation and production of a beam for use in imaging
1 Principles of X-ray Production and Radiation Protection 5
The cathode is heated and this causes the release of free electrons. A very high
voltage is applied between the anode and the cathode. The free electrons are then
accelerated towards the anode where x-rays are produced by two mechanisms.
Bremsstrahlung or Breaking Radiation
This is produced by the sudden deceleration of electrons as they pass close to an

atomic nucleus. The resultant loss in kinetic energy results in the emission of X-rays.
However, the loss of energy is variable, and so the electrons produce a spectrum of
X-rays with different energy values. These are ineffective in producing an image.
Characteristic Radiation
This is produced when an incoming electron has sufficient energy to overcome the
binding energy of one of the electrons in the anode atom’s orbital shells. This orbital
electron then “drops” into a lower energy shell, and the resulting energy loss is
released as an X-ray with a particular fixed energy value. This radiation is of a spe-
cific wavelength and energy and can be used to produce an image.
X-ray Tube
The production of X-rays by this process is relatively inefficient and the majority of
the energy used is dissipated as heat. To ensure the heat is distributed evenly within
the anode, the anode rotates during X-ray production. X-ray tubes producing a high
output over an extended period of time, for example those used in CT systems, are
additionally cooled by external cooling systems.
The X-ray tube is encased in a protective lead housing to prevent X-rays ‘escap-
ing’ The emission of X-rays from the tube is controlled by a collimator. This is
usually adjustable in size and allows only X-rays involved in producing the image
to exit.
The exiting X-ray beam is directed to pass through the patient. Tissues of differ-
ent radiographic density within the patient cause attenuation of X-rays at different
rates. The radiographic density is related to the mean atomic number of the tissue.
For example, the X-ray beam is attenuated to a much greater degree by bone, due to
its high calcium content, than lung. This allows different tissue types to be differen-
tiated in the final image. Conversely the majority of soft tissues, are of similar mean
density and cannot be differentiated on conventional radiography.
6 P. M. Taylor
X-ray Detection
To produce an image from the X-ray beam emerging from the patient and, a detec-
tion system is required. In conventional radiography X-ray film is contained within
a cassette. A fluorescent screen made of phosphors lies in close contact with the film
and acts as a detector system. When the X-ray beam strikes the screen within the
cassette, light is emitted striking the film and producing a latent image. The film is
then developed to produce a hard copy X-ray film.
Modern radiography systems use either a reusable plate incorporating a photo-
stimulable phosphor which is scanned after exposure to produce an image
(Computed radiography-CR) or a matrix of individual detectors that produce a digi-
tal image directly without the use of an intermediate plate (Digital radiography-
DR). The latter is comparable to a digital camera.
Although X-ray attenuation is crucial to the formation of the image, it is also the
source of radiation dose to the patient. In addition, X-rays passing through the
patient are scattered in different directions and are a source of potential radiation
dose to other people in close proximity, including health-care professionals.
Radiation Protection
Ionising radiation can cause two distinguishable types of harm to the body, deter-
ministic and stochastic effects.
Deterministic Effects
These include skin erythema, cataracts and gonadal hypofunction. There is a thresh-
old dose below which no damage occurs (Table 1.1). Above this level the severity of
these effects depends on the total radiation dose. The dose is cumulative and the
lifetime radiation dose should be considered rather than the dose from an individual
examination.
Table 1.1 Thresholds for Lens cataracts >2.0 Sv

deterministic effects Skin erythema >2.0 Sv
Testes-Temporary sterility >0.15 Sv
Testes-Permanent sterility >3.5 Sv
1 Principles of X-ray Production and Radiation Protection 7
Stochastic Effects
Most significantly these include carcinogenesis and mutagenesis. These have no

threshold dose, even a single exposure can cause damage. The frequency of stochas-
tic effects increases with increasing dose, but their severity does not. Some tissues
(e.g. breast) are more sensitive to radiation induced carcinogenesis than others (e.g.
kidney).
Radiation dosimetry is complex but in routine practice is best measured in milli-
Sieverts (mSv). The theoretical lifetime risk of developing a fatal cancer caused by
radiation exposure has been estimated at approximately 1 in 20,000 per mSv.
It should be noted that although individuals receive a ‘normal’ dose of radiation
from the environment and cosmic radiation, diagnostic radiology procedures are
responsible for the greatest single manmade radiation dose to the population. The
yearly background radiation dose in the UK is approximately 2 mSv per person.
Regulations exist, which vary between countries, to prevent these unwanted
effects. In the UK, the regulations include:
Ionising Radiations Regulations 2017
These primarily relate to the protection of people in their place of work and is
enforced by the Health Security Authority. Radiation dose limits for employees are
determined, and if exceeded, this must be investigated and reported.
Ionising Radiation (Medical Exposure) Regulations 2017
These concern protection of patients and identify responsibilities for employers,

referrers, operators and practitioners. The referrer must supply sufficient informa-
tion for the practitioner to make an informed judgment that the exposure is justified.
An overarching principle of radiation protection is “ALARA’ keeping radiation
exposure “as low as reasonably achievable” to both staff and patients. In practice
this involves measures such as minimizing the number of X-ray exposures, using
non ionising imaging techniques if appropriate, ensuring adequate collimation of
the X-ray beam, keeping fluoroscopy time to a minimum, ensuring non-essential
staff are not in the room when X-ray exposures are made, ensuring staff move away
from the patient during exposure to minimize dose from scattered radiation and
wearing appropriate safety garments (e.g. lead aprons thyroid shields etc.).
8 P. M. Taylor
Table 1.2 Typical radiation Chest X-ray 0.02 mSv

doses used in clinical KUB X-ray 0.6 mSv
examinations
Intravenous urogram 3 mSv
Three phase CT urogram 15 mSv
Diagnostic reference levels (DRLs) exist which act as a guide to appropriate

patient doses for particular examinations (Table 1.2). These are set nationally,
although organisations often set their own lower levels. Exceeding a DRL for a
single examination is not usually an issue, but if DRLs are regularly exceeded, this
should be investigated.
Further Reading
The Ionising Radiations Regulations 2017. UK Statutory Instruments (2017) No. 1075. https://
www.legislation.gov.uk/uksi/2017/1075/contents/made
The Ionising Radiation (Medical Exposure) Regulations 2017. UK Statutory Instruments (2017)
No. 1322. https://www.legislation.gov.uk/uksi/2017/1322/made
Chapter 2
How to Perform a Clinical Radiograph
and Use a C-arm
Paul M. Taylor
Despite the widespread increased availability of CT and MRI, the plain radiograph
(e.g., the KUB abdominal film) remains a key diagnostic tool for the urologist. In
addition, the mobile image intensifier or C-arm allows real-time imaging to guide a
variety of urological procedures. Although a radiographer is commonly employed
to perform clinical radiographs and operate the C-arm, it is important that the urolo-
gist understands the principles behind their function to make best use of these
modalities and ensure safe use.
How to Perform a Clinical Radiograph
Before undertaking any radiographic examination, appropriate checks must be

undertaken to ensure that the correct patient and anatomical region is being radio-
graphed. For pre-menopausal women, if the abdomen or pelvis are to be irradiated,
it is also important to assess if there is any possibility of pregnancy.
Performing a clinical radiograph involves placing the appropriate body part of
the patient between an X-Ray tube and a detector. The components of the X-Ray
tube and detector were described in the Chap. 1.
The patient should be placed as close as possible to the detector. The detector
may be an X-Ray film, CR plate or a DR system. The X-Ray beam originates from
a point source in the X-Ray tube anode and diverges to fill the area of the detector.
By placing the patient close to the detector, the degree of magnification which
occurs due to the divergence of the beam is minimized. Proximity to the detector
also helps to maintain image quality by reducing the amount of scattered radiation
P. M. Taylor (*)

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_2
10 P. M. Taylor
reaching the detector. The distance from the X-Ray tube to the detector varies
depending on the examination but is typically 100 cm for an abdominal and 180 cm
for a chest radiograph.
The X-Ray beam is collimated as it leaves the X-Ray tube using an adjustable
collimator to ensure only the structures to be imaged are irradiated. This reduces
radiation dose to the patient and which degrades the image. Collimation of the x ray
beam is facilitated by a light beam which overlies to the X-Ray beam and can be
viewed by the operator.
Relevant markers (e.g. side, time of examination, position of patient) are placed
on the detector at a suitable site so as not to obscure any important image detail.
Prior to exposure, three variables need to be determined—tube current measured in
milliampere (mA), exposure time measured in seconds, and the peak tube voltage
measured in kilovolts (kVp).
The tube current measures the electrical current that flows through the cathode to
the anode and thus the number of electrons produced. The exposure time determines
the time for which X-Rays are produced. Tube current and exposure time determine
the total amount of X-Rays produced and are often considered together as mAs
(milliampere second). A larger mAs will be required for a larger patient. An inap-
propriate mAs will result in either an overexposed or underexposed film.
The tube voltage determines the potential difference between the cathode and
anode and affects the “power” of the X-Ray beam. Increasing the kVp increases the
penetrating power of the X-Rays. A higher kVp potentially reduces the radiation
dose to the patient but produces an image with less contrast which appears more
grey and less black and white.
Before the final exposure takes place, it is important to ensure that all people
present are adequately protected from extraneous irradiation. This may involve
standing behind a protective screen, leaving the examination room or wearing pro-
tective lead clothing.
For radiographs of the chest or abdomen the patient is asked to hold their breath
to avoid the image being blurred by respiratory motion.
Conventional hard copy films are less common now, and typically the final CR
or DR image will be stored on a Picture Archiving and Communication System
(PACS) and viewed on a dedicated workstation or networked computer. Recent
images are usually stored on a local server and older images on an off-site server
resulting in a “filmless” environment.
How to Use a C-arm
Image intensification systems are used to provide images during fluoroscopy

(screening). Compared to radiography they use a much smaller dose of radiation to
produce an image and allow constant updating of the image to produce a real time
moving image.
2 How to Perform a Clinical Radiograph and Use a C-arm 11
When X-Rays strike the front face of an image intensifier they cause light pho-
tons to be emitted from the detector input screen. The photons then strike a photo-
cathode and are converted into electrons. The electrons are accelerated by a high
voltage towards an output screen which converts the electrons back to light and an
image is produced. By this process one X-Ray photon at the input screen is con-
verted into several hundred thousand light photons at the output screen, enabling a
good quality image to be produced almost instantaneously.
Image intensification systems can be installed in fixed or mobile systems. The
latter is often referred to as a C-arm system. These are widely used in operating
theatres. There are specific considerations that apply to mobile fluoroscopic equip-
ment. In a C-arm, the X-Ray tube and the intensifier are tethered and able to rotate
whilst maintaining a fixed focal point, meaning projections at many different angles
can be obtained without moving the patient. To allow the system to be mobile the
X-ray tubes and intensifiers used in C-arms are smaller and lighter than those in
fixed systems. This in turn results in a reduction in image quality.
The device is controlled either by a handheld control or by foot pedals that allow
screening (real- time images) or image capture (single image for permanent copy).
Most C-arms require a key to operate them to prevent their use by unauthorized or
untrained staff. Screening may be continuous fluoroscopy, during which the X-Ray
beam is delivered constantly or pulsed fluoroscopy when the X-ray beam is deliv-
ered in short bursts (e.g., four frames per second), Pulsed fluoroscopy offers signifi-
cantly reduced radiation dose but produces a “jerky” image rather than the smooth
image provided by continuous fluoroscopy.
The C-arm is commonly used in the operating theatre, often with many people
present. Moreover, staff may be present for several procedures during a session and
may be involved in similar weekly sessions. Although the radiation dose received
for each procedure may be small it is possible for staff to receive a significant cumu-
lative dose over several years. It is therefore crucial to keep radiation dose as low as
possible.
Ways to decrease dose to staff and patients include:
1. Keep screening time to a minimum. Only screen when necessary and never
screen when not looking at the image.
2. Ensure the surgeon’s, and assistant’s, fingers are not in the primary beam.
3. Where possible use pulsed fluoroscopy rather than continuous fluoroscopy,
with as low frame rate as practicable.
4. Use collimation to image only the exact region of interest.
5. Use high kVp if possible. This will increase the penetrative ability of the X-Ray
beam, resulting in less absorption within the patient, but at the expense of image
contrast
6. Position the detector as close to the patient as possible. This will also increase
the quality of the image
7. Ensure all non-essential staff leave the operating theatre during screening.
8. Ensure remaining staff move as far away from the patient as possible to reduce
the dose from scattered radiation. The inverse square law applies—doubling the
distance reduces the radiation dose fourfold.
12 P. M. Taylor
9. Wear adequate protective garments, including thyroid shields.

10. If appropriate consult with the local radiation protection advisor to consider
whether individual dose monitoring may be advisable.
Further Reading
Joh JH. Endovascular intervention with a mobile C-Arm in the operating room. Vasc Specialist
Int. 2019;35(2):70–6.
Whitley SA, Dodgeon J, Meadows A, Cullingworth J, Holmes K, Jackson M, Hoadley G,
Kulshrestha R. Clark’s procedures in diagnostic imaging: a system-based approach. CRC
Press; 2020.
Chapter 3
Contrast Agents
Anas Hattab
Contrast agents are a heterogeneous group of pharmaceuticals used during radio-

logical procedures to enhance tissue definition, enabling clearer delineation of nor-
mal anatomy and better characterisation of abnormalities. There are three main
groups of contrast agents available: iodinated agents, gadolinium based agents and
micro-bubble particles.
Iodinated Agents
These are used as radiographic contrast agents. They are formed from organic acid
salts of iodine. The relatively high molecular weight of iodine I127 makes it radio
opaque. The initial use of sodium iodide as a contrast agent was limited by its toxic-
ity; in the 1990s non-ionic contrast media were introduced being both better toler-
ated and safer. Non-ionic, low or iso-osmolar iodinated media are 5–10 times safer
than the older, high osmolar ionic compounds.
When injected intravenously (IV) iodinated agents are rapidly eliminated by
renal excretion. They pass into the extra-vascular space and through the placenta but
do not penetrate the blood brain barrier. Iodinated agents can be injected intra-
arterially, directly into body cavities (e.g. bladder, ureter, biliary tree etc.), IV
or orally.
The timing of the images obtained during the contrast study is crucial in imaging
specific body structures during scanning. The selection of a specific contrast will be
determined by availability, local cost and application. Contrast agents are manufac-
tured in varying concentrations:
A. Hattab (*)
Manchester Royal Infirmary, Oxford Road, Manchester, UK
e-mail: anas.hattab@mft.nhs.uk

Switzerland AG 2023
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14 A. Hattab
• high concentration agents (high radio-opacity and viscosity)—used for IV

enhancement during CT
• low concentration agents (lower radio-opacity and viscosity)—used for direct
examinations such as urethrography and direct pyelography.
Iodinated agents are relatively safe with low overall rates of adverse reactions
(0.15%). Common and rare reactions are outlined in Table 3.1. Life threatening
reactions are rare with non-ionic contrast media, with the incidence between
0.004–0.04%. The risk of a severe reaction is greater after any previous contrast
reaction, regardless of its severity. Any reaction should be recorded in the patient’s
records, in the radiology report and on the radiology information system (RIS). The
patient should be made aware of the risk of further allergy to contrast administration
the MHRA should be informed.
Contraindications
Renal impairment. Iodinated agents carry a risk of acute kidney injury (CI-AKI).
The risk is increased in a patient with any of the following:
• chronic kidney disease (eGFR <40 ml/min)
• heart failure
• renal transplant
• age 75 years or older
• hypovolaemia
• increased dose of contrast
• repeated administration
• intra-arterial administration.
eGRF should be available for all non-emergency scans and performed within the
last 3 months. Nephrotoxicity can be reduced by ensuring adequate hydration, mini-
mising the dose administered, using a less nephrotoxic agent and volume expansion
with 0.9% sodium chloride.
Previous adverse reaction. Patients who give a history of a previous reaction to
contrast agents should not be given further doses. The use of pre-procedure steroids
and antihistamines does not reduce the frequency or severity of reactions. If intra-
vascular contrast is thought absolutely necessary, then a different contrast com-
pound to the one used previously should be chosen, with close medical supervision
during scanning and for 30 minutes after, making sure that all necessary emergency
medications are available.
Table 3.1 Recognised Common Rare

adverse reactions to iodinated Nausea & vomiting Bronchospasm
contrast media
Urticaria Laryngeal oedema
Skin rashes Anaphylaxis
3 Contrast Agents 15
Asthma. Patients with asthma have an increased risk of severe contrast reactions
by factor of 6 to 10. If the asthma is well controlled contrast can be administered
with the availability of nebulisers, IV bronchodilators and steroids, but contrast
should be avoided if poorly controlled.
Allergies. Patients with a history of documented multiple allergies or a single
severe allergy should not be given iodinated agents when possible. If thought neces-
sary, precautions similar to previous adverse reactions should be taken. There is,
however, no demonstrable cross reactivity between iodinated contrast and shellfish
or topical iodine sensitivity.
Thyroid disease. Intravascular contrast should not be given to patients with
hyperthryroidism. In thyroid cancer, iodinated contrast will preclude therapeutic
radio-iodine treatment for two months. Additionally, isotope thyroid imaging should
be avoided for two months following administration of iodinated contrast.
Pregnancy. Iodinated contrast passes through the placenta and can result in sup-
pression of the foetal thyroid. Thyroid function should be measured in the first week
after birth.
Diabetes mellitus. A rare complication is the development of lactic acidosis in
patients who are receiving Metformin. This is due to contrast induced acute kidney
injury (CI-AKI) leading to Metformin accumulation.
Gadolinium Based Contrast Agents (GBCAs)
The most widely used contrast agents for MR imaging are chelates of gadolinium, a
member of the rare-earth group of elements. Gadolinium compounds have similar
pharmaco-dynamics to iodinated agents and are renally excreted when given IV; they
may also be given orally. Gadolinium shortens the T1 and T2 relaxation times of tis-
sues in a dose dependent effect. At low doses the effect on T1 relaxation predomi-
nates, at higher doses the effect predominates on T2. The quantity administered is
therefore titrated against the patient’s body weight to ensure predictability of effect. In
general the greatest tissue enhancement is seen on T1 weighted images.
The incidence of adverse reactions to gadolinium compounds is low
(0.06–0.09%) and acute severe reactions is estimated to be 0.0025–0.005%. Of
particular concern, however, is the development of Nephrogenic Systemic Fibrosis
(NSF) in patients with renal impairment. This is a potentially fatal condition char-
acterised by the development of fibrotic tissue in the skin and muscles thought to
be due to the accumulation of free gadolinium. Gadolinium is contraindicated in
the following:
• severe renal impairment (eGFR <30 ml/min)
• acute kidney injury
• during the perioperative liver transplantation period
• neonates
• pregnancy.
Breastfeeding should be suspended for 24 hours following GBCAs administration.
16 A. Hattab
Micro-bubble Particles
Micro-bubble particles are used in Contrast-enhanced ultrasound (CEUS) to iden-

tify flow. Micro-bubbles are 1–4 micrometres in diameter and are formed from clus-
ters of small gas bubbles within a carbohydrate shell; the dissolution of the
carbohydrate determines the agents longevity in-vivo and the gas core determines
its echogenicity. Microbubble shells are metabolised by the liver and the gas core
exhaled. They are used in IV Doppler studies of the cardiac circulation and in the
characterisation of liver and renal lesions. They differ from other contrast agents as
they are retained only within blood circulation, and thus also named blood-pool
contrast agents (Fig. 3.1).
Micro-bubble particles are considered safe in patients with renal failure and
hyperthryroidism. Adverse reactions are rare and reported to be around 0.002%.
Contraindications include recent acute coronary syndrome, unstable ischaemic
heart disease, severe pulmonary hypertension and ARDS. Due to lack of data they
should be avoided in pregnant women, those breastfeeding or under 18 years of age.
Fig. 3.1 CEUS on the left, and B mode US on the right, of a solid lesion. There is clear peripheral
enhancement with a non-enhancing area of central necrosis
3 Contrast Agents 17
Further Reading
Guidance on gadolinium-based contrast agent administration to adult patients. Royal College of

Radiologists. 2019.
Standards for intravascular contrast agent administration to adults. Royal College of Radiologists.
Third edition; 2010.
Chapter 4
Dual Energy X-Ray Absorptiometry
(DXA)
Nicholas Faure Walker and Richard Whitehouse
DXA is a radiological investigation for the measurement of the mineral content of

the skeleton in order to diagnose and follow up osteoporosis. It can also measure the
fat and lean soft tissue content of the body. DXA is an important test to use in men
who have started, or are being considered for hormonal deprivation therapy for the
treatment of prostate cancer.
How Does It Work?
As a simple approximation, the body is composed of three materials:

1. Adipose tissue (fat)
2. Lean soft tissue (muscle, liver, spleen, kidneys, etc.)
3. Bone
The density of bone can be calculated via how much it absorbs ionizing radiation
in the form of X-rays. Soft tissues also absorb ionizing radiation. The quantity and
composition of soft tissues vary amongst individuals. A DXA scanner generates two
low-dose X-ray beams of different specific energies and intensities to measure the
absorption by bone and soft tissue. It can hence estimate the relative quantities of
N. F. Walker
Department of Urology, Kings College Hospital NHS Foundation Trust, London, UK
Faculty of Life Sciences & Medicine, School of Immunology & Microbial Sciences, King’s
College London, London, UK
R. Whitehouse (*)
Department of Radiology, Manchester Royal Infirmary, Manchester, UK
e-mail: richard.whitehouse@cmft.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_4
20 N. F. Walker and R. Whitehouse
Table 4.1 Factors influencing DXA measurements

X-ray attenuation is exponential. This complicates the maths but not the principle.
X-ray generation by X-ray tubes produces a spectrum of X-ray energies, the “effective” energy
of which increases as the beam passes through matter, due to greater attenuation of the lower
energy components. “Filtering” the beam into two different energies is consequently a gross
simplification.
X-ray generation by X-ray tubes is not constant, requiring continuous monitoring and
re-calibration.
Different manufacturer’s equipment give slightly different results—follow-up scans should be
on the same scanner.
Spine bone density measurement includes any aortic calcification, facet joint and end plate
osteophytes, and other “degenerative” phenomena that increase the measurement result. These
become greater with increasing age.
fat, lean, and bone tissue as well as the relative bone density. There are multiple
caveats which can complicate this explanation (Table 4.1).
In practice, the inferred bone density of an area of bone (aBMD) is a very accu-
rate reflection of the true mineral content of the bone and is extremely reproducible.
Patient Preparation for and DXA Scanning
Patients should be able to lie supine. The whole scan lasts 10 to 20 minutes. A large
scanning arm is passed over the body. Patients will need to keep still for about a
minute for each part of the scan to ensure images are not blurred. They should not
have had radionuclide or barium studies, lanthanum carbonate, or phosphate ene-
mas in the last week nor intravascular radiological contrast agents in the previous
day. Any clothes with metal zips or hooks will need to be removed. Otherwise, no
specific preparation is required. Typically, the hips, spine and in some instances, the
forearms are scanned.
How Are the Results Expressed?
Lean tissues and fat content are of interest in body composition studies, but bone
mineral density (BMD) measurement is the usual clinical use of DXA including in
men who have started or are being considered for hormonal deprivation therapy for
prostate cancer. For a region of interest, such as a single lumbar vertebra, the result
is expressed as:
1. Bone mineral content (BMC) in grams of mineral.
2. Area bone mineral density (aBMD) in grams of mineral per square centimetre of
projected scan area.
4 Dual Energy X-Ray Absorptiometry (DXA) 21
3. Z-score. This is a comparison of the patient’s aBMD with age, sex, and ethnicity
matched aBMD.
4. T-score. This is a comparison of the patient’s aBMD with sex-matched peak
bone density.
Z- and T-Scores—What Is the Difference and Why Use Them?
Bone density increases during childhood, reaching a peak in late adolescence or

early adulthood due to a combination of increasing mineralisation of bone, increas-
ing trabecular bone density, and increased bone size. In males, bone density then
decreases linearly with age. In women, there is a plateau in density, until the meno-
pause, followed by exponential decline with age. Comparing the patient’s result
with an age-, sex-, and ethnicity-matched database makes the result easier to
comprehend.
A Z-score of 0 indicates a result that lies on the mean value for matched normal
data. A score of −1, or less, means the patient’s bone density is one, or more, stan-
dard deviations below the matched mean value. Z-scores are used in determining
osteoporosis in younger men, premenopausal women, and children.
The T-score is calculated in a similar way, but the bone density is compared with
the sex-matched peak bone density, as this more closely reflects the risk of osteopo-
rotic fracture. A T-score of 0 indicates a result that lies on the mean value for sex-
matched peak bone density. A score of −1, or less, means the patient’s bone density
is one standard deviation, or more, below the peak bone density mean value. This is
the standard method of expressing BMD in postmenopausal women (Table 4.2).
About 30% of Caucasian postmenopausal women are labelled as osteoporotic,and
men who are hypogonadal are at risk of osteoporosis. Examples of hip and spine
DXA scans are produced both numerically and graphically (Fig. 4.1).
Table 4.2 The WHO classification of DXA results for Caucasian women
Normal bone T-score greater than −1
Osteopenia T-score between −1 and −2.5
Osteoporosis T-score less than −2.5
Severe (established) osteoporosis T-score less than −2.5 and 1+ osteoporotic fractures
22 N. F. Walker and R. Whitehouse
Fig. 4.1 Hip and spine DXA scans. The graphs demonstrate the patient’s results compared to
reference ranges. The horizontal yellow, orange, and red bands across these graphs are at T-score
intervals of 1; the blue zone is the normal range divided by Z-score intervals of 1, from +2 to −2.
The threshold for osteoporosis at a T-score of −2.5 is therefore halfway down the yellow band
Why Diagnose Osteoporosis in Someone with No Fractures?

Decreased BMD is a risk factor for developing an osteoporotic fracture.
Bisphosphonates are effective in treating low bone density, thereby reducing the
risk of the patient suffering a low-trauma fracture, something that may be caused by
twisting, bending, or even sneezing.
4 Dual Energy X-Ray Absorptiometry (DXA) 23
What Else Can a DXA Scanner Do?
Scanning the spine in a lateral projection can produce an image of sufficient quality
to use for vertebral morphometry at a low radiation dose. This allows measurement
of bone shape and size. Lateral DXA images of the vertebra can, therefore, be used
to identify established low-trauma vertebral fractures; this is important as these are
risk factors for clinically relevant fracture.
Further Reading
Adams JE. Dual energy X-ray absorptiometry. In: Grampp S, editor. Radiology of osteoporosis.
2nd ed. Berlin/Heidelberg: Springer; 2008. p. 105–24.
Kanis JA on behalf of the World Health Organization Scientific Group. Technical Report. World
Health Organization Collaborating Centre for Metabolic Bone Diseases, University of
Sheffield; UK: 2007. 2007. Assessment of osteoporosis at the primary health-care level. https://
www.nhs.uk/conditions/dexa-scan/what-happens/ taken 15.12.2021).
Chapter 5
The Physics of Ultrasound and Doppler
Paul M. Taylor
The increasing availability of inexpensive portable ultrasound systems with a wide

range of hardware and software options has allowed their widespread use in urol-
ogy. To optimise the image, increase the diagnostic confidence of the operator and
minimise interpretive errors it is necessary to understand the basic physics and tech-
nology underpinning these systems The principles underlying real time ultrasound,
Doppler ultrasound and elastography are described.
Production and Propagation of the Sound Wave
An ultrasound wave is produced by the application of a voltage across a piezo-

electric crystal which deforms converting electrical energy into sound energy. A
typical ultrasound transducer contains an array of several hundred crystals, ener-
gised sequentially, to produce a sound beam 1–2 mm in thickness and several cen-
timeters wide. The frequency of the sound produced is determined by the geometry
of the crystals.
Ultrasound waves are propagated through the body tissues at a variable speed
which is dependent on the tissue’s composition although it is similar in most soft
tissues. When the sound wave strikes an interface between tissues it may be trans-
mitted, refracted, absorbed or reflected. A proportion of the reflected sound will
pass back to the transducer where the piezoelectric process is reversed and the
sound is converted to an electrical impulse. This is used to generate the image. The
processes of refraction, absorption and reflection are collectively referred to as
attenuation.
P. M. Taylor (*)

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_5
26 P. M. Taylor
12 mHz probe 3 mHz probe
penetration resolution penetration resolution
Fig. 5.1 High-frequency probes give higher resolution images but to a shallower depth. Lower
frequency probes are able to penetrate more deeply but give lower resolution images
Transducer Selection
A fundamental consideration in all imaging techniques is how to maximise the reso-

lution of the system. Resolution is defined as the ability to differentiate two points.
In ultrasound images this differs between the axial and transverse planes. Axial
resolution (in the direction in which the sound wave travels) is determined by ultra-
sound frequency. Transverse resolution is determined by the transducer design.
Higher frequency ultrasound has a shorter wavelength and produces higher reso-
lution in the axial plane. However, absorption of sound is also related to its fre-
quency. Higher frequencies are absorbed more rapidly than lower frequencies and
penetrate the tissues less. Consequently, a high frequency (10–12 MHz) provides
optimal imaging for superficial structures (e.g. scrotum) whereas imaging of deeper
structures (e.g. kidneys) requires a lower frequency (3–5 MHz) to achieve adequate
penetration (Fig. 5.1).
Transducer Design
Two basic transducer designs are available.

A linear array transducer produces a rectangular image. The benefit of this design
is that transverse resolution is constant at any depth but the maximum image width
is limited by the size of the transducer. These transducers typically function at high
frequency and are used for superficial structures.
The second design is a curved array producing a sector-shaped image. This
allows wider beam generation with a smaller footprint, but at the expense of declin-
ing transverse resolution with increasing depth. Curved array transducers of lower
frequency are used for general abdominal examinations (Fig. 5.2).
5 The Physics of Ultrasound and Doppler 27
Linear Curved
Array Array
x
x
y y
Fig. 5.2 Linear and curved ultrasonic transducers. Image resolution is dependent upon the differ-
ence between x and y, so curved transducers give lower resolution the further away from the probe
Specialised transducers for intraoperative, transrectal or transvaginal examina-

tions are typically curved arrays but operate at higher frequencies to allow high
resolution images to be obtained with limited access.
Frame Rate
After each beam of sound is transmitted there is a delay while the sound travels
through the tissues and back to the transducer. The deeper the structures to be
imaged the longer the delay before the next beam and the lower the number of
images per second (frame rate) that can be used. In practice several frames are elec-
tronically summated to produce a composite image (frame averaging). This
increases the signal/ noise ratio and improves image quality. The depth of the tissues
imaged should be kept to a minimum to ensure adequate views of the relevant
organs to maximise frame rate and optimise the image.
Gain
As the beam passes through the tissues, and is attenuated, the reflections from
deeper structures are weaker than those from superficial structures on arriving back
at the transducer. Similar objects at different depths, would therefore, appear to be
28 P. M. Taylor
of different echogenicity. To overcome this the system amplifies the sound waves
from deeper tissues more than those from more superficial structures. As the depth
travelled by the sound is proportional to the time taken to return to the transducer
this is often referred to as time gain compensation (TGC). In order to overcome
heterogeneity of attenuation due to different body tissues the operator can override
the baseline TGC settings using a series of sliding or rotary controls.
Focus
The ultrasound beam, although thin, is not of uniform thickness and initially con-
verges, then diverges, as it travels away from the transducer. The point of maximum
convergence is the focal zone and is the area of highest resolution. The size and
position of the focal zone is dependent upon probe design but can be altered by the
operator.
Doppler Ultrasound
The Doppler principle determines that frequency of the sound received from, or
reflected by, a moving object varies proportionally to the velocity of the movement.
This is expressed in the Doppler equation
F = 2 f ( v / c ) cos ( Q ) ,
where
F is Doppler frequency shift
f is transmitted frequency from ultrasound probe
v is the velocity of moving reflector
c is the velocity of sound in the medium
Q is the angle between ultrasound beam and axis of flow
If the frequency and velocity of the transmitted sound are known, and the frequency
of the reflected sound is measured, the velocity can be calculated.
In practice the moving object most frequently studied by Doppler is blood flow
although it is possible to observe high velocity urine flow in ureteric jests entering
the bladder.
For each Doppler calculation several parameters can be determined: position,
amplitude, speed and direction of the moving object and the time the parameters
were calculated. It is not possible to display all these parameters simultaneously in
a single graphic display and three common displays are, therefore, used.
5 The Physics of Ultrasound and Doppler 29
Colour Flow Doppler
A large area, possibly the whole ultrasound image, is selected and a colour map is
superimposed in which two colours are used to represent flow towards and away
from the transducer with the intensity of the colour related to velocity with indi-
vidual pixels. Typically red is flow in the direction of the probe and blue away from
it. This is often used as preliminary observation to map the vascular anatomy and if
necessary to measure the angle between the ultrasound beam and the vessel to allow
a more accurate measurement of flow velocity by range gated Doppler.
Range Gated Doppler
A specific area is identified on the ultrasound image and the flow in this area is dis-
played as a histogram. Time is displayed on the x axis, velocity on the y axis and
amplitude is related to the displayed pixel intensity.
Power Doppler
This produces a coloured image similar to that produces by colour flow doppler.
However the colour map is determined not by flow velocity but by amplitude of the
signal. This is of particular value in the identification of high amplitude, low veloc-
ity flows due to venous blood.
Elastography
Ultrasound elastography can be used to measure the elasticity of tissues. Abnormal

tissues may be stiffer and less elastic than normal tissues. The elasticity of tissues is
measured by determining Young’s modulus This is calculated by dividing stress, the
force placed on the tissue, by strain, the amount of tissue deformation.
The technique is widely used in the identification and quantification of hepatic
fibrosis and may be useful in the detection and characterisation of tumours in the
breast thyroid and prostate.
Two different ultrasound techniques have been described which allow this calcu-
lation: shear wave elastography (also known as transient elastography) and strain
elastography (also known as static or compression elastography). To undertake elas-
tography specific hardware and software packages are required.
30 P. M. Taylor
Further Reading
Kremkau FW. Sonography principles and instruments. St. Louis: Elsevier Health Sciences; 2015.
Merton DA. Diagnostic medical ultrasound technology. Journal of Diagnostic Medical Sonography.
1997;13(5 Suppl):10–23.
Chapter 6
How to Ultrasound a Suspected Renal
Mass
Allen Ikwuagwu
Most renal masses found on ultrasound are entirely incidental and necessitate the
patient to undergo cross-sectional imaging (CT or MRI). But ultrasound can play an
important role in the characterisation of certain cystic lesions in equivocal CT scans,
as well as aiding image-guided renal biopsy.
Patient Preparation
• Confirm correct patient details on the ultrasound machine.

• A curvilinear probe should be selected, 3–6 MHz transducer depending on
patient habitus and the test pre-set set to kidneys or abdomen.
• The patient should be scanned initially in the supine position using breathing
techniques to allow for better visualisation of the kidneys during deep
inspiration.
–– If still not readily visualised, ask the patient to turn laterally either away or
towards you into a decubitus position, using the liver or spleen as acoustic
windows.
–– If still not visible, then a prone position should be adopted. Remember to ask
about previous clinical/surgical history in case the patient has a solitary kid-
ney or known variant anatomy.
A. Ikwuagwu (*)
Royal Blackburn Hospital, Haslingden Road, Blackburn, Lancashire, UK
e-mail: Allen.Ikwuagwu@elht.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_6
32 A. Ikwuagwu
Image Optimisation
The following points need to be considered prior to imaging:

• The organ of interest should be positioned centrally and occupy most of the image.
• These 5 main settings should be continuously adjusted during the study to ensure
adequate image optimisation:
–– Field of View: Maximise frame rate by reducing the field of view to concen-
trate on organ/region of interest thereby improving image resolution.
–– Focus: More recent machine models perform this automatically, if not, place
the focus position (usually a small marker/arrowhead at side of screen) to the
bottom of region/organ of interest to improve resolution.
–– Depth: Increase or decrease to make the region of interest occupy most of
the screen.
–– Overall Gain: This adjusts the image brightness, ideally, you do not want the
image too bright or dark.
–– Time Gain Control (TGC): Automatic on most new scanners. Maintains uni-
form organ echotexture by modulating returning echoes from varying depths,
increasing or decreasing brightness at these levels. If available, commence
with this at midline.
–– Magnification: Further image optimisation can be gained by magnifying the
region of interest when appropriate.
Scan Technique and Pathology
The kidneys should be assessed in both the longitudinal and transverse sections (LS
and TS), making sure to sweep through the entirety of the organ in both planes,
moving completely away from the organ (exophytic lesions can otherwise be
missed).
Representative images in LS and TS (including the upper, interpolar and lower
poles) planes should be acquired after thorough interrogation.
The renal cortex, medullary pyramids and pelvicalyceal system should be
assessed for masses, stones and hydronephrosis. The patient is usually scanned with
a full bladder (to aid urinary bladder assessment), if hydronephrosis is present
assess the kidney again following micturition. Persistent hydronephrosis may repre-
sent sequelae of a ureteric lesion, stone or pelviureteric junction obstruction (PUJO).
When a lesion is identified, be sure that the correct side is labelled on the study
and comment on the lesion’s position (upper, inter-polar or lower pole), if endo-
phytic/exophytic or mixed, it’s composition (cystic/solid/mixed) and vascularity
using colour/power doppler.
Contrast enhanced ultrasound can be extremely useful in identifying vascular-
ity - this methodology is discussed in further detail in Chap. 3.
6 How to Ultrasound a Suspected Renal Mass 33
Pseudotumours (Benign Variant Anatomy)
Dromedary humps (Fig. 6.1) involve the left kidney and manifest secondary to the
impression of the spleen against the upper pole renal cortex creating a hump caudal
to this. It is important to remember that the hump follows normal renal cortical
characteristics on all imaging modalities.
Columns of Bertin (Fig. 6.2) can be found bilaterally and represents continuation
of the normal renal cortex towards the renal sinus fat secondary to hypertrophy. This
extension of tissue resembles normal cortex and is isoechoic, obviating the need for
further investigations.
Fig. 6.1 Dromedary

hump. (Prominence of the
interpolar renal cortex
secondary to impression of
the spleen (note the more
hyperechoic echotexture of
the spleen (arrow head)).
This patient went on to
have a characterisation CT
scan which confirmed a
benign dromedary hump)
a b
Fig. 6.2 Column of Bertin. (extension of normal renal cortical parenchyma into the sinus fat (a)
with no sinister vascularity (b) in a patient with known column of Bertin)
34 A. Ikwuagwu
Persistent foetal lobulation is uncommon but appears as smooth indentation of

the renal cortex, this can be focal or multiple, unilateral or bilateral. The indenta-
tions overlie the space between the medullary pyramids and can be mistaken for
scarring, where the indentation tends to overlie the pyramid.
Other variants to be aware of include horseshoe kidneys, the most common
fusion anomaly, where the kidneys are connected at the midline by an isthmus of
tissue and as such the kidneys are usually positioned more medially and caudally
due to tethering of the isthmus by the inferior mesenteric artery. Duplex kidneys
represent incomplete fusion of the upper and lower pole moieties - keep in mind the
Weigert-Meyer rule.
Stones (Nephrolithiasis)
Unless causing symptoms of obstruction either at the calyceal, pelvis or ureteric

levels, renal stones tend to be an incidental finding (some calyceal stones may cause
discomfort without obstruction). Stones especially above 5 mm can be detected
with US. They present as hyperechoic (bright) foci (Fig. 6.3), casting a linear distal
acoustic shadow and demonstrate twinkle comet tail artefact with colour doppler.
Reducing the overall gain and increasing frequency can make them more
conspicuous.
a b c
Fig. 6.3 Stones (Examples of large hyperechoic stones demonstrating post acoustic shadowing.
The renal pelvis stone in (a) causes significant hydronephrosis (note the smaller lower pole caly-
ceal calculi). The large non-obstructing lower pole calculus (b) exhibits the twinkle comet tail
artefact with doppler (c)
Cysts
Simple cysts (Fig. 6.4) have a thin smooth wall with homogenous hypoechoic (dark)
content and cast post acoustic enhancement (brightness). Some simple cysts can
become complicated by haemorrhage or infection, especially common in patients
with polycystic kidneys, in which case they may contain debris or have thicker
walls, requiring further delineation with MR or CT.
When the wall of the cyst becomes irregularly thickened or the cyst contains
solid components/septae then further characterisation with contrast (either using
US/CT or MR) is required as per Bosniak cyst classification criteria.
It is worth noting that parapelvic (arising from the renal parenchyma and extend-
ing towards the renal sinus fat) and peripelvic (arising from the renal sinus and usu-
ally entail distended lymphatics) cysts can mimic hydronephrosis on US.
Solid masses
Focal pyelonephritis (nephronia) and renal abscesses can appear as masses on US

with heterogenous echogenicity and variable vascularity. The patient usually pres-
ents clinically unwell with features of sepsis and correlating raised inflammatory
markers. It is important to follow up these changes to ensure their resolution and no
underlying sinister lesion.
a b
Fig. 6.4 Cysts. Simple cortical renal cyst (a) with post acoustic enhancement (brightness). Para-
pelvic cyst (b) mistaken for hydronephrosis in an asymptomatic patient with normal renal func-
tion. A contrast enhanced delayed phase CT study confirmed para-pelvic cysts
36 A. Ikwuagwu
Angiomyolipoma’s (AML) (Fig. 6.5) are the most common benign renal lesion.
They can be bilateral, especially in patients with tuberous sclerosis (TS) and are
more common in conditions such as von Hippel Lindau syndrome (vHL),
Neurofibrmatosis type 1 (NF1) and lymphangiomyomatosis (LAM).
AMLs manifest as hyperechoic (unless fat poor) cortical lesions. Lesions above
4 cm are at increased risk of spontaneous haemorrhage. As renal cell cancers (RCC)
can have similar appearance to smaller AMLs further characterisation with MRI or
CT may be necessary, especially if calcification is present.
Renal cell cancers (RCC) (Fig. 6.6) are more common above the fifth decade and
tend to be focal lesions causing mass effect and distortion of the renal cortical out-
line depending on size. They have a variety of presentations but are mostly asymp-
tomatic. RCCs can appear bland or heterogenous with central necrosis, demonstrating
a hypoechoic centre. US cannot differentiate RCC from oncocytoma or other malig-
nant lesions including metastasis and as such staging CT and targeted biopsy if
amenable are often required.
Transitional cell cancers (TCC) are less common and exhibit an infiltrative
growth pattern, they are usually homogenous but with greater hyperechoic echo-
genicity compared to the cortex, preserving the renal shape but more prone to caus-
ing obstruction at the calyceal, pelvis or ureteric levels.
a b c
Fig. 6.5 Angiomyolipoma (AML). Hyperechoic cortical AML (a & b) within the upper pole of
the kidney which remained unchanged over 5 years. AMLs can also be partly exophytic depending
on size (c) demonstrating more heterogenous appearances
a b c
Fig. 6.6 Renal Cell Carcinoma (RCC). Whilst US is sensitive at detecting renal lesions, it cannot
differentiate between subtypes of RCC including (a) papillary & (b) clear cell from other lesions
such as oncocytomas (c) or even metastasis
Further Reading
Alty J, Hoey E. Practical ultrasound: an illustrated guide. CRC Press; 2013.

Chapter 7
How to Ultrasound a Painful Testicle
and Mass
Allen Ikwuagwu
Ultrasound is the primary imaging modality in the assessment of the male genital
tract. It is quick, readily available and does not involve ionising radiation. It is an
accurate tool in assessing for the causes of testicular pain and masses.
Patient Preparation
• A chaperone should be present.

• Ensure the correct patient has been chosen on the ultrasound machine as well as
the correct probe (Linear-array 10–14 MHz transducer) with the test preset on
‘testes’.
• The patient should lie supine, pulling the penis over their abdomen and out of the
way. It can be helpful to place a rolled sheet of paper towel underneath the testes
and over the apposing thighs.
• Ask the patient to demonstrate any palpated lumps and carefully examine the
region yourself to know where to focus on, noticing any associated overlying
skin changes.
• In the case of a painful testicle, it is often better to first scan the non-tender
testicle.
A. Ikwuagwu (*)
Royal Blackburn Hospital, Haslingden Road, Blackburn, Lancashire, UK
e-mail: allen.ikwuagwu@elht.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_7
40 A. Ikwuagwu
Image Optimisation
Some important points to be aware of prior to imaging:

• The organ of interest should be positioned centrally and occupy most of the image.
• 5 main settings to continuously adjust during the study to ensure adequate image
optimisation include:
–– Field of View: Maximise frame rate by reducing the field of view to concen-
trate on organ/region of interest thereby improving image resolution.
–– Focus: More recent machine models perform this automatically, if not, place
the focus position (usually a small marker/arrowhead at side of screen) to the
bottom of region/organ of interest to improve resolution.
–– Depth: Increase or decrease to make the region of interest occupy most of
the screen.
–– Overall Gain: This adjusts the image brightness, ideally, you do not want the
image too bright or dark.
–– Time Gain Control (TGC): Automatic on most new scanners. Maintains uni-
form organ echotexture by modulating returning echoes from varying depths,
increasing or decreasing brightness at these levels. If available, commence
with this at midline.
–– Magnification: Further image optimisation can be gained by magnifying the
region of interest when appropriate.
Technique
• Start by comparing the echotexture and size of both testicles on transverse sec-
tion (TS), especially when ischaemia/infarct suspected. Utilise the colour/power
Doppler to assess for normal vascularisation making sure the box covers both
testes. Decreased blood flow suggests ischaemia and increased blood flow,
inflammation. Remember, normal or increased blood flow cannot exclude a tor-
sion/de-torsion event so do not be falsely reassured. Prior to moving on, capture
representative images.
• If there is an abnormal or painful testicle, interrogate the presumed normal side
first. Understanding testicular anatomy and what a normal testicle should look like
(Fig. 7.1) is key to appreciating pathology. Look for the homogenous intermediate
testicular echotexture, whilst a thin consistent and smooth high echogenic testicu-
lar outline denotes a normal intact tunica albuginea (important to appreciate if
traumatic injury suspected). The mediastinum testis appears as a linear echogenic
intra-testicular structure running longitudinally across the body of the testis. This
can become more pronounced in older men and post vasectomy patients, present-
ing as tubular ectasia. The small anechoic cysts, lack of mass effect and vasculari-
sation differentiates this benign change from a more sinister lesion. Take
representative Longitudinal section (LS) and TS images, demonstrating normal
vascularity and ensuring you scroll through the entirety of the organ in both planes.
7 How to Ultrasound a Painful Testicle and Mass 41
a b c
Fig. 7.1 Normal testis. Normal testis demonstrating homogenous intermediate echogenicity (a)
and normal background vascularity (b). The epididymal head (c) is similar echogenicity to the
testis whilst the body and tall (d) are of lower (darker) echotexture
• The head of the epididymis is of similar echotexture to the testis and contains
converging tubules from the rete testis. The body and tail are echo poor (darker)
in comparison and extend to form the ductus (Vas) deferens and subsequently the
ejaculatory duct, connecting to the urethra at the verumontanum. Hence, infec-
tions here tend to be ascending and commonly involve the epididymal tail and
body more so than head. Again, take representative images of the head and body
of the epididymis, demonstrating normal vascularity (like that of a normal testis).
• Now that you have a good base for comparison, move on to the abnormal testicle.
Remember to use very light pressure when scanning in order to reduce patient
discomfort.
The Painful Testicle
The main causes of a painful testicle include trauma, infection, and vascular com-
promise/ischaemia usually in the form of torsion but can also present as sequelae to
trauma and inflammation.
Infection (epididymo-orchitis)
The tail and body of the epididymis (Fig. 7.2) are usually involved and often appear
swollen and of more heterogenous echotexture. Colour Doppler is useful to demon-
strate the increased vascularity, especially when compared to the normal side.
Sometimes there is an associated extra-testicular fluid collection (hydrocele), this can
42 A. Ikwuagwu
a b c
Fig. 7.2 Epididymo-orchitis. Swelling of the epididymal body and tail (b) which appears more
hypoechoic owing to oedema with significant hypervascularity. These appearances extend to
involve the testicle (a & c). Small to moderate volume associated hydrocele is better appreciated
on the TS image (c)
a b
Fig. 7.3 Torsion. The transverse section (TS) comparison of both testes allows you to appreciate
the subtle loss of normal intermediate echogenicity of the ischaemic left testicle (a), which dem-
onstrates lack of vascularity (b). Note that the ischaemic testicle doesn’t always have to appear
grossly swollen, the overlying tissues however are thickened
become septated or contain echogenic debris. Note any overlying soft tissue changes.
Orchitis in isolation is uncommon and if present, mumps infection should be considered.
Ischaemia
An important differential to consider is inflammation causing venous congestion

which can lead to infarction, in this scenario the testicle can become swollen,
hypoechoic and appear avascular, just like an ischaemic testicle (Fig. 7.3), so a thor-
ough history is essential. When the tunica vaginalis extends beyond the testis with a
higher attachment around the spermatic cord this can allow free movement and rota-
tion, leading to torsion of the testis and epididymis with the risk of ischaemia and
infarction, common in bell clapper deformity. Even if the testicle appears well
a b
Fig. 7.4 Intermittent torsion/detorsion. Intermittent torsion/detorsion in a 15y/o with recurrent

episodes of right iliac fossa pain radiating to the right groin and testicle (a), associated with nausea
and vomiting. The frequent occurrence, spontaneous resolution of symptoms and normal biochem-
istry clinically differentiates this swollen hypervascular appearance from orchitis. Note the normal
left testicle (b)
a b c
Fig. 7.5 Intra-testicular haematoma. At 2/7 post injury with a cricket ball (a). The heterogenous
echogenic haematoma becomes darker as it matures and contracts at 2 (b) and 5 (c) months post
injury, when it becomes barely visible. Follow up is important to ensure no underlying sinister
lesion. The hydrocele can take longer to resolve
perfused it’s important to follow the spermatic cord cranially into the groin to ensure
no swirling is present, suggestive of torsion. Intermittent torsion and detorsion can
occur (Figs. 7.3 and 7.4), resulting in a swollen often hyperaemic testicle, mimick-
ing infection.
Trauma
This can be a result of blunt or penetrating forces which can be encountered in

sports, road traffic and straddle injuries. A spectrum of injuries exists ranging from
extra-testicular haematomas to epididymal and intra-testicular injuries in the form
of contusions, haematomas (Fig. 7.5), fractures and ruptures; the disruption of the
44 A. Ikwuagwu
a b c
Fig. 7.6 Traumatic Testicular Injury. (a) Normal right testis, green arrows indicate uniform linear
intact echogenic tunica albuginea. (b) (LS) & (c) (TS); Traumatic injury to left testicle with disrup-
tion of the tunica albuginea towards the lower pole (yellow arrows). Note the small volume
hydrocele
tunica albuginea (Fig. 7.6) is indicative of testicular rupture. If conservative man-

agement is decided, then it is imperative to follow up these appearances to ensure
resolution and to exclude more sinister underlying disease.
The Testicular Mass
These lesions can be broadly characterised into 3 main categories:

• Extra-testicular masses, the most common of which is a lipoma and very rarely
sarcomas. Lipomas tend to appear as circumscribed hyperechoic lesions. If in
doubt, testicular MRI can further characterise these lesions.
• Epididymal masses include benign epididymal head cysts (Fig. 7.7), sperm gran-
ulomas (more common in post vasectomy patients) and infrequently adenoma-
toid tumours, the most common benign epididymal tumour.
• Intra-testicular masses (Fig. 7.8). Apart from simple intra-testicular cysts which
convey typical features of a simple cyst on ultrasound including a thin smooth
wall, homogenous anechoic (dark) fluid, post acoustic enhancement and lack of
vascularisation on colour doppler. Testicular masses are otherwise of great con-
cern and malignancy must be excluded. A good clinical history and tumour
markers may help but ultimately the more sinister lesions tend to be surgically
excised by way of orchidectomy. The few that remain are closely monitored.
a b
Fig. 7.7 Simple epididymal head cyst & hydrocoele. Simple epididymal head cyst (a) with thin
wall, anechoic fluid within and post acoustic enhancement (brightness) demonstrated by red
dashed line. Colour doppler demonstrated no associated vascularity. A large hydrocele (b) can also
present as a mass. This transilluminates and the testicle can often not be palpated
a b
c d
Fig. 7.8 Intratesticular masses. Clinical acumen is vital as these masses can be mistaken for trau-
matic injury or infection in the wrong circumstances. The most common malignant masses are
germ cell in nature. Images (a) & (b) convey a heterogenous part solid/cystic lesion with promi-
nent vascularity on a background of microlithiasis, histologically proven to be a Teratoma). Images
(c) & (d) demonstrate a more solid vascular mass, proven seminoma following orchidectomy. On
the opposite spectrum, images (e) and (f) show a well marginated, rounded lamellated avascular
lesion, typical of an epidermoid cyst which are mostly benign. Lesions that are multifocal or bilat-
eral as demonstrated in images (g) and (h) should prompt consideration of testicular metastases,
especially in older patients. This young patient who presented with testicular swelling and pain
was subsequently diagnosed with Burkitt lymphoma
46 A. Ikwuagwu
e f
g h
Fig. 7.8 (continued)
Further Reading
Alty J, Hoey E. Practical ultrasound: an illustrated guide. Boca Raton: CRC Press; 2013.
Chapter 8
How to Do a Trans-Perineal Ultrasound
Guided Biopsy of the Prostate
Omar El-Taji, Samih Taktak, and John McCabe
Over recent years trans-perineal prostate biopsy has emerged as the biopsy method
of choice. Although neglected for several decades in favor of transrectal ultrasound
biopsy, more recent data has revealed reduced complications and better sampling
when using the trans-perineal approach. This chapter illustrates the technique and
surgical approach for trans-perineal biopsy.
Introduction
Trans-perineal biopsy (TPBx) of the prostate has started to emerge as the biopsy
method of choice, replacing Trans-rectal Ultrasound guided biopsy of the prostate
(TRUSBx). Evidence suggests that TPBx has a significantly lower risk of infection
with ultimately a lower burden of expenditure, especially when done under a local
anesthetic. Techniques using a perineal brachytherapy template grid under general
anaesthesia (GA) or a free-hand ‘fan technique’ under local anaesthesia (LA) are
both well established. The development of freehand techniques for performing
TPBx, which employ a common access cannulae through the perineal skin, has
made it possible for this procedure to now be performed far more readily under
O. El-Taji · S. Taktak · J. McCabe (*)

St Helens and Knowsley Teaching Hospitals, Prescot, UK
e-mail: omar.el-taji@nhs.net; samih.taktak@nhs.net; john.mccabe@sthk.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_8
48 O. El-Taji et al.
LA. Many units have transitioned to TPBx and have started to perform these as an
independent office-based procedure. The increasing use of pre-biopsy multipara-
metric MRI is changing the diagnostic paradigm with data suggesting that TPBx is
at least equivalent to TRUSBx in the context of cancer detection, with studies also
reporting that TPBx offers superior detection of anterior tumors. TPBx offers a sys-
tematic and targeted method for diagnosing prostate cancer by enabling you to tar-
get and sample the whole of the peripheral zone, where 96% of cancers develop.
Indications for Trans-perineal Biopsy of the Prostate
• Abnormally elevated PSA and high PSA density (PSAD)

• Equivocal changes and PIRAD 4 or 5 Lesions on multiparametric MRI.
• Previous biopsies demonstrating prostatic intraepithelial neoplasia (PIN) or
atypical small acinar proliferation (ASAP).
• Diagnosis of suspected prostate cancer in patients with symptoms of metastatic
prostate cancer (often limited biopsy taken).
• As part of active surveillance for prostate cancer
Principles of Ultrasound and Probe Selection
TPBx uses a transrectal bi-planar ultrasonic transducer which is different to

TRUSBx which often uses a transrectal end-fire model. Most intra-cavity probes
used for trans-rectal ultrasound have a scanning angle of almost 180 degrees which
allows visualization of the entire gland in both transverse and sagittal sections. A
14 MHz transducer produces a high-resolution image with a contact image of
approximately 2 cm which is optimal for visualizing the prostate, especially the
peripheral zone where most prostate cancers arise.
Planes of Scanning
Complete evaluation should occur simultaneously in both transverse and sagittal

sections (Fig. 8.1) to assess for any capsular breach or hypoechoic areas within the
periphery of the prostate. This is often accomplished using a bi-planar transducer. In
the sagittal plane, a small amount of urine in the bladder facilitates the examination.
The seminal vesicles and vas are identified followed by the base of the prostate, this
is especially useful in both local anesthetic infiltration and biopsy device position-
ing prior to firing. The central zone comprises the posterior part of the gland and is
often hyper-echoic. The transition zone is in the central part of the gland and is
hypo-echoic. The junction of the transition and peripheral zone is distinct posteri-
orly and is characterized by a hyper-echoic region. The peripheral zone forms most
of the gland volume.
8 How to Do a Trans-Perineal Ultrasound Guided Biopsy of the Prostate 49
Fig. 8.1 Transverse and sagittal view of the prostate
Table 8.1 Complications specific to TPBx

After effect Risk
Haematospermia Almost all men (this can last up to 6 weeks)
Haematuria Almost all men (usually lasts a few days)
Perineal bruising Up to 50%
Temporary erectile dysfunction 5%
Urinary retention 1.5–5% (depending on method/ number of cores sampled)
Infection 0.5%
Patient Information
Patients should be informed of the risks (Table 8.1), benefits and alternatives and
give informed consent prior to the procedure.
Antibiotics
Antibiotic prophylaxis is not always routinely administered, but practice does vary
from centre to centre. There is increasing evidence supporting no requirement for
antibiotic prophylaxis. Some local practices, however, involves giving IV/IM
Gentamicin 120 mg prior to biopsy followed by a dose of 625 mg Co-Amoxiclav/
500 mg Ciprofloxacin, orally, following biopsy.
Positioning and Patient Preparation
The patient is positioned in a modified lithotomy position on a reclining chair with

legs in stirrups. The scrotum is lifted crainally and held in position with adhesive
tape with the scrotal skin protected by non-adhesive dressings. The prostate is then
examined. The perineal area is prepared with betadine wash. 10 mls of 1% lidocaine
with adrenaline is then infiltrated into the skin approximately 1.5 cm above the anal
verge and 1.5 cm either side of the midline.
In a free hand technique, a TP access system mountable device e.g.
PrecisionPoint™ (Perineologic, Cumberland, MD, USA) (Figs. 8.2 and 8.3) is then
placed on a bi-planer ultrasonic transducer. The transducer is then placed in the
rectum and the prostate and perineal tissue visualised. A spinal needle is then placed
Fig. 8.2 PrecisionPoint™

access system
Fig. 8.3 Biplanar transducer with mountable device during biopsy
under vision and used to deliver 15–20 mls of 1% lidocaine to sub-cutaneous tissue
and deep perineal muscle synchronously as the needle is advanced. Once the pros-
tate capsule is approached further local anaesthetic is instilled into the peri-prostatic
space. This is repeated on the contralateral side. The goal is to infiltrate laterally
towards the neurovascular bundles. This is known as a peri-prostatic block. Other
such techniques of anesthesia have been described e.g. the periapical triangle block
although none have been shown to be superior. On average 5 min should be left
prior to commencing biopsies in order to maximise anesthetic effect. Additional
local anesthetic should be available if the procedure is poorly tolerated.
Taking a Biopsy
The use of multiparametric MRI as an adjunct during TPBx is known as ‘cognitive

fusion’, that is, superimposing the MRI scans onto the ultrasound images “from
memory” and in real time.
Sampling the prostate with a fan technique whilst using a mounted device can
normally be performed with only two needle entries into the skin for the average
sized prostate whilst larger prostates may require additional entries to ensure ade-
quate sampling. The needle which is often incorporated into the mounting device is
used as an access sheath for the biopsy gun. A spring-driven 18-gauge needle core
biopsy device or gun is used. On deployment, the gun advances the needle 5 mm
and samples the subsequent 15 mm of tissue, with the tip extending 5 mm beyond
the tissue sampled. The biopsy sample is placed in 10% formalin.
On initial biopsies, tissue should be taken from the peripheral zone (as far lateral
and posteriorly as possible). Additional samples should be taken from clinically
suspicious areas on MRI. Commonly, 2–3 biopsies are taken from each of the base,
middle and apex of the prostate on either hemisphere. Biopsies from each region
should be labeled and sent separately with a further pot used for targeted biopsies.
Between 12 and 18 biopsies in total are normally taken with less than 8 cores con-
sidered to be inadequate for cancer detection. If cores are fragmented, shorter than
10 mm, or absent, another sample is normally performed at the same site.
Some units use a diclofenac100 mg suppository following the procedure for
analgesia.
Post-Procedure Care
Patients are observed for a minimum of 30 min post-procedure and must be able to
void before they are discharged. Patients are provided with contact details for a
Urology Nurse Specialist as a point of contact in case of any issues.
Template and Fusion Biopsy
Template biopsies are performed under general or regional anaesthetic using a

brachytherapy grid-stepper unit. 1 to 2 cores are taken from each 5 mm grid coordi-
nate to sample the whole prostate. The cores are potted and subsequently analyzed
in a zonal fashion using 20 modified Barzell zones.
Cognitive fusion is increasingly being replaced by fusion software systems.
These involve mapping the MRI image showing the location of the suspicious
lesion, onto the real time ultrasound image being produced by the transrectal ultra-
sound probe. Inaccurate segmentation of MRI images and registration, however, are
its major downfall, often leading to missing the lesions in question.
Some of the latest software systems have solved this issue with the use of multi-
modal elastic fusion and organ-based tracking. This allows the software to follow
the position of the prostate, not that of the probe, automatically compensating for
patient movement and prostate deformation. However, fusion biopsy software is
expensive, and the learning curve is often steep therefore its use is limited to only a
handful of units.
Further Reading
Basourakos SP, Alshak MN, Lewicki PJ, Cheng E, Tzeng M, DeRosa AP, et al. Role of prophy-
lactic antibiotics in transperineal prostate biopsy: a systematic review and meta-analysis. Eur
Urol Open Sci. 2022;37:53–63.
Starmer B, Iordan N, McCabe J. Comparing tolerability of local anaesthetic transperineal and
transrectal prostate biopsies. J Clin Urol. 2021; https://doi.org/10.1177/20514158211024075.
Tamhankar A, El-Taji O, Vasdev N, Foley C, Popert R, Adshead J. The clinical and financial impli-
cations of a decade of prostate biopsies in the NHS: analysis of Hospital Episode Statistics data
2008–2019. BJU Int. 2020;126:133–41.
Chapter 9
How to Manage an Infected Obstructed
Kidney
Louise E. Olson
A patient with an infected, obstructed kidney is a urological emergency. Urgent

decompression is usually required to prevent the complications associated with life
threatening infection and renal failure. The most common cause is an obstructing
ureteric calculus.
Initial Assessment
The initial assessment of patients who are unwell includes an A–E assessment as per
Care of the Critically Ill Surgical Patient (CCrISP) guidelines to diagnose, prioritise
and treat any threats to life.
• AIRWAY
• BREATHING
• CIRCULATION
• DISABILITY/CNS DYSFUNCTION
• EXPOSURE
L. E. Olson (*)
Department of Urology, Salford Royal Hospital, Northern Care Alliance NHS
e-mail: louise.olson2@srft.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_9
56 L. E. Olson
Management
The management of patients should be focused around ensuring there is good fluid
resuscitation, intravenous broad-spectrum antibiotics are commenced promptly and
early involvement of critical care if patients have respiratory and/or haemodynamic
compromise. The sepsis 6 pathway has been developed to ensure rapid and compre-
hensive care to patients identified to have a likely presentation of sepsis.
In brief, all patients require:
–– oxygen therapy
–– intravenous access + blood cultures taken
–– blood tests sent for FBC, U&Es, CRP and culture (and other blood tests thought
to be appropriate at patient assessment)
–– IV antibiotics and IV fluids
–– serial lactate measurements
–– urinary catheter may be required to monitor urine output
–– urinalysis and urine culture
Once patients are haemodynamically stable prompt radiological assessment with a
non-contrast CT scan will diagnose the cause of the infected, obstructed kidney. The
CT slices below show a hydronephrotic kidney with fat stranding and the offending
obstructing ureteric stone.
9 How to Manage an Infected Obstructed Kidney 57
Decompression
There are two main options for decompressing an infected, obstructed kidney:
• Retrograde ureteric stent
• Percutaneous nephrostomy
There is little evidence that one is superior to the other and it is common practice
that clinical decisions are made on resources available, the clinical status of the
patient and surgeon preference. There is only one randomised control trial that com-
pares different modalities for decompression. Pearle at al randomised 42 cases to
stent or nephrostomy who had an infected, obstructed kidney. The conclusions were:
–– No significant difference in time to treatment
–– Procedure time shorter for stent
–– One treatment failure in nephrostomy group
–– Time to normalisation of temperature and white cell similar in both groups
at 2 days
–– The length of stay was 4.5 days for nephrostomy and 3.2 days for stent
–– Stent was twice as expensive
The European Association of Urology states that stents and nephrostomies are
equally effective. It is well recognised that the management of an infected, obstructed
system should not be delayed and the definitive treatment of the stone should be
deferred until the patient is clinically well and infection free.
Factors to Consider When Deciding on Clinical Management
The following factors need to be considered when deciding on definite treatment for
the obstruction: Patient factors, stone factors and renal factors (Table 9.1).
PATIENT – Comorbidities & performance status

– Medications most notably antiplatelets and anticoagulants
– Pregnancy status
– Size of patient and skin to renal pelvic measurement
STONE – Size & density
– Location in ureter
– How are you likely to treat the stone in the future?
RENAL – Urea and electrolytes: present and baseline
– 1 or 2 kidneys
– Fluid status of patient
58 L. E. Olson
Table 9.1 Comparison of benefits and weakness of methods of ureteric decompression

Stent Nephrostomy
Usually general anaesthetic required thereby Can be performed under local anaesthesia
potentially increasing the morbidity to the
patient who is otherwise unwell
Performed by a urologist Requires an interventional radiologist
Renal pelvic pressure remains high Restores efficient peristalsis and maintains low
pressure in the renal pelvis
Ureter may be passively dilated to allow Access available for subsequent PCNL if
easier access of ureteroscope required
Cannot monitor urine output directly from Able to monitor urine output directly from
specific kidney specific kidney
No external bag Patient has external paraphernalia
Further Reading
Jameson J, Bryden D. Care of the Critically III Surgical Patient. 4th ed; 2017. https://sepsistrust.
org/wp-content/uploads/2018/06/ED-adult-NICE-Final-1107.pdf
Pearle MS, et al. Optimal method of urgent decompression of the collecting system for obstruction
and infection due to ureteral calculi. J Urol. 1998;160:1260.
Chapter 10
Principles of Computed Tomography (CT)
Richard Hawkins
CT is essential to urological diagnosis and treatment planning. CT uses X-rays

rotating round a patient in a gantry to acquire images on detectors opposite the
X-ray to produce an image “slice”. However, CT comes at a higher dose of radiation
compared to conventional X-ray. Technology has advanced to allow faster image
acquisition, reduced radiation dose and better tissue differentiation.
The increasing availability, speed and reliability of computed tomography has
resulted in its widespread use in urological imaging. Understanding the basic phys-
ics and technology behind this imaging modality, along with familiarity of scan
techniques and use of contrast, allows performance of the optimal scan for diagnos-
tic purposes.
X-rays are produced when fast moving electrons are stopped suddenly by impact
on a metal target. The kinetic energy of the electrons is converted into X-rays (1%)
and heat (99%). An X-ray tube consists of two electrodes sealed in a vacuum; the
negative electrode (cathode) a fine tungsten filament; and the positive electrode
(anode) a smooth flat metal target. The filament is heated and emits electrons by the
process of thermionic emission. The electrons are repelled by the negative cathode
and attracted by the positive anode. The voltage (typically 30–150 kV) between the
anode and cathode drives the current of electrons. Each electron arrives at the sur-
face of the target with a kinetic energy equivalent to the voltage (kV) between the
anode and cathode.
R. Hawkins (*)
Leighton Hospital, Mid Cheshire Hospitals NHS Foundation Trust, Crewe, UK
e-mail: richard.hawkins@mcht.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_10
60 R. Hawkins
Interaction with Matter
X-rays may be:

–– Transmitted: pass through unaffected.
–– Absorbed: transfer to the matter some or all their energy.
–– Scattered: diverted in a new direction, with or without loss of energy.
Attenuation is the fractional reduction in the intensity of the primary X-ray beam as
it passes through a medium.
Attenuation = absorption + scatter
The linear attenuation coefficient is related to the attenuating property of a material

i.e. how well it absorbs, scatters or transmits X-rays.
Physics of Computed Tomography
In computed tomography, a transverse slice of the patient is imaged, avoiding the

superimposition of adjacent structures that occurs in conventional radiography. The
slice is defined by a ‘sheet of X-rays’ produced by a narrow, well collimated, X-ray
fan beam rotated around the patient.
The X-ray beam is attenuated by absorption and scatter as it passes through the
patient. Detectors on the other side of the patient measure the X-ray transmission
through the patient. These measurements are repeated many times from different
directions whilst the tube is pulsed as it rotates 360 ° around the patient.
The slice is subdivided into a matrix of 512 × 512 volume elements (voxels). The
image is reconstructed by a computer as a corresponding matrix of 512 × 512 pic-
ture elements (pixels). A pixel is a representation of the average linear attenuation
coefficient of a voxel. The image is displayed as a matrix of pixels, the brightness or
grey scale value of each pixel represents the average linear attenuation coefficient of
the contents of the corresponding voxel.
CT numbers are assigned to each pixel in the image by a computer algorithm that
uses the measurements of the transmitted X-rays as data. CT pixel numbers are
proportional to the difference in average X-ray attenuation of the tissue within the
voxel and that of water. A Hounsfield Unit (HU) scale is used: water is assigned a
value of 0, the scale extends from −1000 HU for air to +3000HU for very dense
bone. This large range of densities is greater than the human eye can appreciate on
a display (around 720 shades depending on the display brightness) therefore win-
dowing is utilized to map the CT numbers to a greyscale on screen that highlights
particular structures. CT windows have a window width and a window centre. For
10 Principles of Computed Tomography (CT) 61
Figs. 10.1 and 10.2 CT KUB images using a soft tissue window (left) to demonstrate the renal
parenchyma and a bone window (right) to demonstrate the stones more clearly
example, a soft tissue window: W 400, C 40 versus a bone window W 2500, L 500.
These are usually stored as presets on CT workstations or PACS (Figs. 10.1
and 10.2).
Types of CT Scanner
First generation scanners used a single pencil beam falling on a single detector;
together they translated through 180 steps and then rotated 1 ° at a time through
360 °. This took a total scan time for one slice of 3–5 mins. Third generation scan-
ners are the ones most frequently used today. They employ a wide fan beam falling
on a larger array of many hundreds of detectors which do not translate but rotate
continuously through 360 ° around the patient. In fourth generation scanners, the
X-ray tube alone rotates through 360 ° around the patient who is positioned within
a continuous ring of several thousand stationary detectors.
Helical scanning is performed by moving the patient table at a constant speed
through the CT gantry whilst scanning continuously with an X-ray tube rotating
around the patient. A continuous volume of image data is acquired during a single
breath-hold. This technique dramatically improves the speed of image acquisition,
enables scanning during optimal contrast opacification and eliminates artefacts
caused by misregistration and variations in patient breathing. Volume acquisition
enables retrospective reconstruction of multiple overlapping slices, improving visu-
alization of small lesions and making three-dimensional images possible.
Multi-detector helical CT (MDCT) was another key advance in CT imaging; it
utilizes the principals of helical scanning but incorporates multiple rows of detec-
tors. This allows the acquisition of multiple slices per tube rotation, increasing the
speed at which an area of the patient can be covered. More recently this concept has
been taken further still with the advent of volumetric CT. These scanners use up to
320 rows of detectors to increase coverage up to 16 cm allowing whole organs such
as the heart, brain or kidneys to be scanned in a single rotation without table
movement.
62 R. Hawkins
Use of Contrast
Radio-opaque media are used to increase contrast between adjacent tissues.

Intravenous iodine-based contrast agents (which have a sufficiently high atomic
number to maximize absorption of X-rays) are administered in CT to enhance den-
sity differences between lesions and surrounding parenchyma, to demonstrate vas-
cular anatomy, vessel patency and to characterize lesions. Contrast administration
and the timing of scanning must be carefully planned to optimize differences in
enhancement patterns between lesions and normal tissues, and more specifically in
urological imaging to provide optimal imaging of the renal cortex, medulla or col-
lecting system depending on the clinical indication. This is particularly relevant
now that CT urography has replaced the conventional IVU.
Radiation Dose
The technological advances and increased utilization of CT carry the price of

increased radiation exposure to each patient imaged. Radiation exposure with CT is
approximately 3.5–4.5 mSv per scan depending on the machine used, the BMI of
the patient and the use of contrast material. These considerations mandate a respon-
sibility to the radiologist and referring clinician to limit CT to definite indications,
especially in children and pregnant women who are at greatest risk from radiation.
Low kV technique increases intrinsic image contrast and reduces dose, particu-
larly in smaller patients and should always be considered (automatic on the latest
scanners). Over time, and with the availability of increasing computing power, CT
reconstruction techniques have evolved from filtered back projection (fastest but
highest dose) to hybrid iterative reconstruction (fast but lower dose) to full model
based reconstruction (very low dose but very slow) and most recently deep learning
reconstruction (very low dose but relatively fast allowing real world use). Deep
learning reconstruction uses artificial intelligence in the form of a specially trained
neural network to reconstruct the CT data and remove noise from the images.
The latest advance is photon counting CT. This uses a brand-new type of detec-
tor, the photon counting detector which literally counts individual X-ray photons
and their specific energy as they reach the detector. This new detector is more effi-
cient and overcomes some of the limitations of previous detectors by providing very
high-resolution data without electronic noise, improving signal to contrast ratio and
reducing doses with intrinsic spectral information. The spectral information can be
used to look at material composition such as stone type and to perfectly separate
calcium from a vessel lumen (Figs. 10.3 and 10.4) (Figs. 10.5 and 10.6).
10 Principles of Computed Tomography (CT) 63
Figs. 10.3 and 10.4 Ultra low dose paediatric volumetric CT acquired in 1 rotation (0.1 s) using
deep learning reconstruction—DLP = 10 (0.15 mSv)—equivalent of 7 chest X rays
Figs. 10.5 and 10.6 Ultra low dose CT KUB reconstructed using deep learning reconstruction
(left) and filtered back projection (right)—DLP = 37.5 (0.56 mSv)—less than a plain X ray KUB
Further Reading
Brant WE, Helms CA. Fundamentals of diagnostic radiology. Lippencott: Williams and
Wilkins; 2007.
Farr RF, Allisy-Roberts PJ. Physics for medical imaging. Elsevier Limited: Saunders; 2004.
Goldman LW. Principles of CT and CT technology. J Nucl Med Technol. 2007;35(3):115–30.
McLeavy CM, Chunara MH, Gravell RJ, Rauf A, Cushnie A, Talbot CS, Hawkins RM. The future
of CT: deep learning reconstruction. Clin Radiol. 2021;76(6):407–15.
Willemink MJ, Persson M, Pourmorteza A, Pelc NJ, Fleischmann D. Photon-counting CT: techni-
cal principles and clinical prospects. Radiology. 2018;289(2):293–312.
Chapter 11
How to Do a CT Urogram (CT)
The CT Urogram is an important tool in the diagnostic assessment of the upper

urinary tract.
Introduction
CT urography (CTU) is now the standard radiology investigation for patients pre-
senting with unexplained haematuria, where there is a potential renal or post renal
cause. CTU has a sensitivity for detecting upper tract urothelial malignancy of about
96% and a specificity of 99%. This diagnostic accuracy is reduced for bladder
lesions therefore CTU should always be combined with cystoscopy.
The modern 64-slice (or greater) multidetector CT allows fast acquisition of
cross-sectional images and multiplanar reconstruction of the entire renal and uri-
nary tract in multiple phases of enhancement (related to the timing of image acquisi-
tion after injecting contrast). In addition, modern rendering software can create 3
dimensional outlines of just the urinary tract. Depending on the number of imaging
phases acquired, the CTU can also evaluate for other urinary tract pathology (renal
and ureteric stones, obstruction, congenital anatomical variants, infection of the kid-
neys and urinary tract) and help to offer alternative diagnoses of the abdomen and
pelvis. As with all forms of imaging that use radiation and iodinated contrast, risk
stratification for radiation dose and contrast related morbidity (allergic reaction,
nephropathy) needs to be considered. Alternative imaging modalities, where CTU
or iodinated contrast are contraindicated include CT without contrast, ultrasound
and Magnetic Resonance urography (MRU).
V. Misra · R. Pathak (*)

Salford Care Organisation, Northern Care Alliance NHS Trust, Salford, UK
e-mail: varun.misra2@nca.nhs.uk; ryan.pathak@srft.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_11
66 V. Misra and R. Pathak
Technique
CTU protocols vary across sites and countries but generally combine 2 to 4 phases
of image acquisition. The rationale for each phase is outlined below:
• Non contrast (also known as CT KUB, Fig. 11.1)—Used to identify calcified
lesions (renal and urinary tract stones, calcification within complex cysts or
lesions) and help to characterise enhancement properties of other lesions
(haematoma, urothelial malignancy, renal malignancy) when combined with
additional phases. The density of a stone can help to determine its composition
and aid urological management decision making.
• Arterial—This is an optional phase acquired through the kidneys or the whole
abdomen and pelvis. Renal Cell Carcinoma (RCC) is an arterial enhancing
tumour which can be more conspicuous in this phase. Transition Cell Carcinoma
(TCC) is hypovascular in other phases therefore some experts recommend arte-
rial imaging of the whole urinary tract to look for subtle arterial enhancement.
Fig. 11.1 Non Contrast CT demonstrating bilateral dense pelvicalyceal stones

11 How to Do a CT Urogram (CT) 67
Fig. 11.2 Excretory phase of the upper tract demonstrating a normal right pelvis and contrasting
soft tissue irregular thickening of the left renal pelvis
• Nephrogenic—Acquired 100 to 120 seconds after contrast administration.

During this phase there is maximal enhancement of the renal cortex, enabling
detection of small and subtle renal lesions which will appear less dense than sur-
rounding enhancing parenchyma.
• Urographic / Excretory (Fig. 11.2)—Acquired roughly 6–10 mins following
administration of the initial contrast bolus. During this phase positive density
contrast should maximally distend the pelvicalyceal system, ureters and bladder,
allowing detection of filling defects and subtle areas of urothelial thickening that
could represent a urothelial malignancy, or free-floating non enhancing low den-
sities (haematoma).
To summarise, a CTU can be performed by acquiring a non-contrast CT scan,
subsequently administering 100–150 ml IV contrast followed by 2 to 3 further
phases respectively. Risk stratification for the increased radiation dose exposure is
an important consideration for the radiologist. A relatively common 3 phase proto-
col using reconstruction techniques to limit dose can reduce the effective dose to
6.1 mSv. This is roughly 2–5 times greater than the yearly background radiation dose.
Split Bolus Protocol
One way of reducing radiation dose is by performing a “spit bolus” protocol. Rather
than a single 150 ml bolus of IV contrast, 2 boluses of 75 ml each are administered.
Following non-contrast CT the first 75 ml bolus is given. The second 75 ml bolus is
given 5–7 mins later. A further 90–100 seconds later the patient is scanned. This
produces images where contrast from the first bolus produces a urographic phase
and contrast from the second bolus produces a nephrogenic phase. Capturing two
phases of imaging in a single CT scan eliminates the need for a third CT scan to be
performed and hence significantly reduces the effective dose to the patient.
Technical Challenges
The urographic phase of imaging may be degraded by ureteric contraction and/or

inadequate distension of the pelvicalyceal system, ureters or bladder. This leads to
suboptimal images and limits diagnostic value. Various methods may be utilised to
try and maximise image quality. These include IV furosemide administration prior
to examination, IV saline (500–1000 ml) chaser following initial contrast bolus
administration and compression belts. These are all designed to maximise pelvi-
calyceal dilatation with contrast.
Image Presentation
A single CTU produces in the region of 500–700 images. Traditionally images are
initially presented in the axial plane. Multiplanar reformats to view the images in
coronal and sagittal planes is strongly recommended as small lesions may be missed
on axial slices alone. MIP (maximal intensity projection) images are useful for
detecting small lesions and assessing the vasculature. Finally, surface rendering
images (also known as cinematic rendering) can also be produced which may aid
surgeons in surgical planning (Fig. 11.3). Images should always be reviewed on a
dedicated workstation capable of producing such reconstructions/reformats.
11 How to Do a CT Urogram (CT) 69
Fig. 11.3 Cinematic rendering of a normal upper urinary tract where the bladder is underfilled and
catheterised
Further Reading
Barocas DA, Boorjian SA, Alvarez RD, et al. Microhematuria: AUA/SUFU guideline. J Urol.
2020;204:778.
Chlapoutakis K, Theocharopoulos N, Yarmenitis S, Damilakis J. Performance of computed tomo-
graphic urography in diagnosis of upper urinary tract urothelial carcinoma, in patients present-
ing with hematuria: Systematic review and meta-analysis. Eur J Radiol. 2010 Feb;73(2):334–8.
van der Molen AJ, Miclea RL, Geleijns J, Joemai RMSO, Am AJR, Roentgenol J. A survey of
radiation doses in CT Urography before and after implementation of iterative reconstruction.
AJR Am J Roentgenol. 2015;205(3):572.
Potenta SE, D’Agostino R, Sternberg KM, Tatsumi K, Perusse K. CT Urography for evaluation of
the Ureter. Radiographics. 2015;35(3):709–26.
Raman, SP, MD*, Fishman EK. Upper and lower tract urothelial imaging using computed tomog-
raphy urography. Urol Clin N Am 2018;45:389–405.
Chapter 12
How to Do a Renal and Adrenal CT
CT scanning is an essential tool in the diagnostic work up of renal and adrenal

lesions. Understanding the nuances between certain protocols of CT scanning helps
clinicians identify the most appropriate scan to provide the highest diagnostic yield.
CT Renal Study
Renal lesions are often incidentally identified on ultrasound, CT and MRI studies.
Roughly 14% of patients undergoing a CT scan will have an incidentally detected
renal lesion. Radiologists may be able to dismiss a large proportion of these lesions
as benign on non-dedicated imaging, however those which show concerning fea-
tures require formal characterisation. A “triple phase” of the kidneys is the gold
standard imaging technique for characterising renal lesions.
Protocol
A CT renal protocol consists of a non-contrast CT followed by injection of

100–150 ml IV contrast at 2–5 ml/second. Following contrast injection 2 further CT
scans are acquired at varying time points. These represent the corticomedullary (late
arterial phase) and nephrogenic phase (late portal venous) of enhancement. Some
institutions may also add a CT-Urogram (see chapter of CT Urogram).

Salford Care Organisation, Northern Care Alliance, Salford, UK

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_12
• Pre-contrast: acquired before administration of contrast. This phase allows for

identification of key features such as cystic density, macroscopic fat or calcifica-
tion and acts as a baseline from which to assess enhancement patterns of renal
lesions.
• Corticomedullary phase: Acquired roughly 30–40 s post contrast injection.
During this phase intense enhancement of the renal cortex is seen with minimal
enhancement of the medulla, allowing for differentiation between the two. This
allows identification of normal variants which may mimic renal masses, such as
a hypertrophied column of Bertin. Furthermore, hypervascular lesions, such as
clear cell RCC, will enhance intensely during this phase. Finally, vasculature
may be delineated allowing for pre-operative planning and identifying vascular
anomalies such as pseudoaneurysm and thrombus.
• Nephrogenic phase: Acquired roughly 100 s post contrast injection. During this
phase contrast enters the loop of Henle and collecting ducts, resulting in uniform
enhancement of the entire renal parenchyma. Most renal lesions will be best
detected during this phase.
Local practice will vary depending on resources, clinical situation, and approach
to radiation protection. A CT renal for mass characterisation should consist of at
least a non-contrast and nephrogenic phase.
Technical Considerations
Thin sections (e.g. 1.5 mm or smaller) are required to accurately assess for intrale-
sional fat. Attempting to assess for intralesional fat on thick sections, particularly in
small lesions, may lead to inaccurate assessment and potentially adverse outcomes
for patient.
New CT techniques which aim to reduce radiation dose, such as low dose CT,
should be used with caution. Low dose CT for example introduces noise to the
image which may obscure subtle lesions and may make benign, homogenous lesions
appear heterogenous and potentially aggressive.
Image Presentation
Most modern-day CT scans produce a large number of images, easily ranging into
several hundred. As discussed on the “How to perform a CT urogram” chapter,
multi-planar reformats are essential to detect small, subtle lesions. Similarly, MIP
(maximal intensity projections) aid in detecting subtle lesions and assessing vascu-
lature (Fig. 12.1).
12 How to Do a Renal and Adrenal CT 73
Fig. 12.1 Triple phase assessment (non-contrast, corticomedullary and nephrographic phases) of
a suspected right RCC
CT Adrenal Scan
Introduction
Adrenal lesions are frequently discovered incidentally on imaging performed for

non-adrenal pathologies. These incidentally detected adrenal lesions are known as
incidentalomas. Incidentalomas are detected on 5% of all CT imaging performed.
Given the ongoing exponential increase in the use of CT this represents a significant
number of patients.
The most detected incidentaloma is an adrenal adenoma, a benign lesion. The
majority (roughly 70%) of adrenal adenomas are lipid rich. Lipid rich adenomas can
usually be confidently diagnosed using a non-contrast CT as they measure <10 HU
(Hounsfield units). However, diagnostic dilemma occurs when an incidentaloma
measures >10 HU. This leaves us with an indeterminate incidentaloma which may
represent a lipid poor adenoma, or a potential malignancy. Similarly, incidentalo-
mas detected on contrast enhanced CT cannot be confidently diagnosed as adrenal
adenomas and hence cause diagnostic dilemma.
CT Adrenal Protocol
This CT protocol is used to investigate whether an indeterminate incidentaloma

represents a lipid poor adenoma. Adenomas enhance following contrast administra-
tion and then classically demonstrate early washout. This adrenal protocol allows us
to quantify the degree of washout and help diagnose a lipid poor adenoma.
CT adrenal protocol usually consists of 3 phases of imaging.

1. Non contrast phase: Unenhanced CT of the upper abdomen
2. Contrast enhanced CT: 100–150 ml IV contrast injected at 2–3 ml/second. CT
upper abdomen is performed after a 60–90 second delay.
3. Delayed CT: A final CT upper abdomen is performed 15 minutes following
initial contrast injection.
We can then measure the Hounsfield units (HU) of the adrenal lesion on all three
phases of imaging. These values are then entered into the below algorithm to quan-
tify absolute washout.
Enhanced CT HU / Delayed CT HU
Absolute washout % 100
Enhanced CT HU / Unenhanced CT HU
Values of ⩾ 60% are considered diagnostic for a lipid poor adenoma and no fur-
ther follow up is required.
Occasionally, a situation may arise whereby an incidentaloma is detected on an
enhanced CT and the patient is still on the CT scanner. In this situation a delayed CT
may be performed, and the relative washout can be calculated. This eliminates the
need for a non-contrast CT. This dual phase protocol to calculate relative washout
may also be used electively to reduce radiation dose.
Enhanced CT HU / Delayed CT HU
Relative washout % 100
Enhanced CT HU
Relative washout values ⩾ 40% are considered diagnostic for a lipid poor ade-
noma and no further follow up is required.
The use of absolute washout or relative washout, using ⩾ 60% and ⩾ 40% thresh-
olds respectively, have been shown to be 98% sensitive and 92% specific for diag-
nosing adrenal adenomas.
Pitfalls
Hyper vascular tumour metastases (e.g. clear cell renal cell carcinoma), phaeochro-
mocytoma and adrenocortical carcinomas may give absolute and relative washout
percentages within the range for an adenoma. Care must be taken whilst reporting
CT adrenals to avoid mistaking these for adrenal adenomas. As a rule, if the overall
enhancement is over 120 HU in the contrast enhanced phase a phaeochromocytoma
or hyper vascular metastasis is more likely than lipid poor adenoma (Fig. 12.2).
12 How to Do a Renal and Adrenal CT 75
Fig. 12.2 Left Adrenal nodule anterior to the left kidney in 3 phases of imaging (non-contrast,
contrast enhanced and delayed phase), with no macroscopic fat, an enhancement of less than 120
HU and an absolute washout value of 75% therefore suggestive of benign lipid poor adrenal ade-
noma. Biochemical correlation however favoured a Phaeochromocytoma
Further Reading
Caoili EM, Korobkin M, Francis IR, et al. Adrenal masses: Characterization with combined unen-
hanced and delayed enhanced CT. Radiology. 2002;222:629–33.
Song JH, Chaudhry FS, Mayo-Smith WW. Incidental adrenal mass on CT: prevalence of adre-
nal disease in 1049 consecutive adrenal masses in patients with no known malignancy. Am J
Roentgenol. 2008;190:1163–8. https://doi.org/10.2214/AJR.07.2799.
Krishna S, Murray CA, McInnes MD et al. CT imaging of solid renal masses: pitfalls and solu-
tions. Clin Radiol. Sep 1, 2017;72(9);708–721.
Chapter 13
How to Do a CT in a Patient
with Presumed Upper Tract Trauma
Anas Hattab and Jonathan Smith
Renal trauma is a urological emergency requiring prompt assessment, imaging and

appropriate management. This chapter discusses the indications for specific imag-
ing modalities and how a CT for suspected renal trauma is performed.
Introduction
Patients with significant blunt abdominal trauma and visible haematuria should be
considered for urgent CT as are those with significant penetrating trauma. Patients
with non-visible haematuria following minor blunt trauma are very unlikely to have
significant urological injury and are therefore not routinely imaged by CT scanning,
unless there is another additional indication (such as cardiovascular instability).
Patients that are difficult to assess clinically such as the unconscious patient, intoxi-
cated patient, the mentally ill patient or the obese patient and patients with penetrat-
ing injuries may require prompt CT in the absence of visible haematuria (Fig. 13.1).
A. Hattab (*)
Manchester Royal Infirmary, Manchester, UK
e-mail: anas.hattab@mft.nhs.uk
J. Smith
St James’s University Hospital, Leeds, UK

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_13
78 A. Hattab and J. Smith
Fig. 13.1 CT portal venous imaging completed to exclude descending colon and kidney injury
following a knife injury to the left loin. The patient had no haematuria but was found to have a
large peri-nephric haematoma with capsular and cortical injury with no acute bleeding or urine
leak following delayed imaging at 5 min (grade III AAST). The injury was successfully treated
conservatively
What Do You Tell the Patient Prior to the Test?
In layman’s terms; ‘We will place you in a large metal doughnut measuring 7 ft in
diameter and following the (intravenous) injection of 150 mls of fluid, that may
make you feel a little hot and flushed, X-rays will be taken to determine the extent
of your injuries. The chance of the CT causing you any harm is very small’.
Are There Any Specific Contraindications to CT?
A patient with a previous serious contrast allergy can have a limited CT scan with-
out IV contrast. CT in pregnancy can be used if ultrasound and/or MRI have been
inconclusive and active bleeding or significant injury requiring immediate treatment
13 How to Do a CT in a Patient with Presumed Upper Tract Trauma 79
is clinically suspected. The health of the mother takes precedence over the health of
the foetus. If a patient has renal failure the radiologist will decide whether to give
contrast depending on the clinical need. CT without I.V. contrast can detect haema-
toma and organs in pieces but cannot identify active bleeding. Thus, unenhanced CT
is, in general, undesirable in severe blunt or penetrating trauma. In the severe trauma
setting there may be no time to check contraindications or if this information cannot
be obtained (such as with the intoxicated or unconscious patient) the trauma team
should be ready to deal with adverse effects if they arise.
A Typical Blunt Trauma Protocol
Initially the patient undergoes a non-contrast brain & C-spine scan to look for blood
& fractures. ‘Bastion Protocol CT Traumagram’ is now widely utilised at most
trauma centres. The protocol consists of biphasic injections:
• 65 ml at 2 ml s−1,
• followed by 95 ml at 3.5 ml s−1
Scan is acquired at 70 s whilst the second bolus is still flowing in. It provides simul-
taneous arterial and venous phases in one scan. Bastion CT reduces the dose of
scan, the dose of contrast and the time of scan. Finally, a delayed study around
5–10 mins is undertaken to identify any urothelial injury.
Targeted CT scan can be carried out in the event of localised penetrating renal
injury. A typical protocol includes unenhanced kidneys, arterial phase at 30 s and
portovenous phase at 70 s. This will identify active contrast extravasation, pseudo-
anueryms and arterio-venous fistulas. In addition it can help in assessing the viabil-
ity of renal parenchyma by evaluating enhancement and uptake of contrast.
If there is clinical concern for bladder injury (normal upper tracts and visible
haematuria) or if there are any secondary signs of bladder injury on CT (abnormal
bladder wall, presence of blood or significant pelvic fractures) then a CT cystogram
needs to be considered to exclude bladder perforation. The preferred CT cystogram
technique involves the instillation of 300 mls of 3% containing contrast under grav-
ity via a urinary catheter since an indirect CT cystogram (using the IV contrast
excreted through the kidneys) can often miss a bladder injury.
Important CT Findings and Impact on Patient Management
Contrast extravasation indicates that the patient is actively bleeding, and this finding
usually requires urgent treatment either by the vascular radiologist or by the sur-
geon. It is important to recognise the level of bleed and whether it is from major or
minor vessels. It is also important to comment on the size of haematoma and
80 A. Hattab and J. Smith
location (such as subcapsular or perinephric). Contrast extravasation following uro-

thelial injury seen on the delayed study, may require therapy by nephrostomy inser-
tion or ureteric stenting, with or without percutaneous drainage of any urinary
collection. Uncommon but severe injuries include renal artery or vein avulsion or
occlusion that usually necessitates immediate intervention (Figs. 13.2 and 13.3)
(Figs. 13.4 and 13.5).
Figs. 13.2 and 13.3 CT scan in delayed Urographic phase demonstrating fracture through a dupli-
cated left kidney. There is a large perinephric haematoma (star). No active bleed was identified on
the prior arterial scan. There is contrast extravasation consistent with renal pelvis rupture (arrow).
Patient underwent selective artery embolisation of the upper moiety and retrograde stent inserted
into a lower moiety calyx
13 How to Do a CT in a Patient with Presumed Upper Tract Trauma 81
Figs. 13.4 and 13.5 CT Urogram 6 months later of the same patient demonstrating atrophy of the
upper moiety (arrow) with no enhancing tissue (star). There is no contrast leak and the haematoma
has nearly resolved
Further Reading
Alonso RC, Nacenta SB, Martinez PD, Guerrero AS and Fuentes CG. Kidney in danger: CT find-
ings of blunt and penetrating renal trauma. Radiographics Nov 2009;29:2033–2053.
Carter NJ, Kirkwood GW, Miles R, et al. The inception of the Bastion Protocol for trauma CT
scanning. J R Nav Med Serv. 2018;104:183–6.
Chapter 14
Principles of Magnetic Resonance Imaging
(MRI)
Richard Hawkins
MRI uses powerful magnets which produce a strong magnetic field that forces pro-
tons to align with that field. When a radiofrequency current is then pulsed through
the patient, the protons are stimulated, and spin out of equilibrium. When the pro-
tons return to their original state they release energy which is picked up by detectors
and converted into an image. Gadolinium is often used to assess contrast
enhancement.
How Does MRI Work?
The patient is placed inside a superconducting magnet producing a very strong mag-
netic field (1.5 or 3.0 Tesla) which is over 32,000 or 64,000 times the strength of the
earth’s core respectively. The hydrogen protons within the patient act like little mag-
nets themselves and line up with the magnetic field. The patient is then exposed to
a series of pulsed alternating radio waves at a specific frequency (the Lamour fre-
quency) to impart energy to them. The protons receive the energy from the radio
waves resulting in a change of their spin state and alignment (the spins align and the
long axis of the protons flip). Following the switching off of the radio waves the
protons relax back to their resting spin state and alignment emitting energy in the
process in the form of radio waves. These radio waves are detected by the coils built
into the MRI scanner and on the surface of the patient. Using this process, complex
pulse sequences encode the spatial position and a particular characteristic of the tis-
sues being interrogated. Complex mathematical algorithms are then used to trans-
form the radio wave data collected into images of the body.
R. Hawkins (*)
Leighton Hospital, Mid Cheshire Hospitals NHS Foundation Trust, Crewe, UK
e-mail: richard.hawkins@mcht.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_14
84 R. Hawkins
Understanding Basic MRI Terminology
T1W and T2W Imaging
The T1 and T2 relaxation times define the time it takes for protons in different tis-
sues to revert to their resting states after the initial radiofrequency pulse aligns their
spins and flips their long axis over by either 90 or 180 degrees. Both T1 and T2
relaxation times are therefore parameters specific to different tissues and when we
‘weight’ images to be either T1W or T2W sequences, certain tissues will display
typical signal intensities according to the weighting. T2 and T1 define the transverse
and longitudinal relaxation times respectively of a proton in tissue.
A T1W image demonstrates fluid as low signal and fat as high signal. The reverse
is true for a T2W image. If the type of image being shown is unknown, then one tip
for determining if it is T1W or T2W is to look at the fluid in the bladder or CSF. If
it is ‘bright’ then it is a T2W image (Figs. 14.1 and 14.2), whereas if it is “dark” it
is a T1W image.
Contrast-Enhanced Imaging
Intravenous gadolinium contrast agents are used as extracellular agents to increase

the visibility of tissues within the body on T1W images, just as iodinated contrast
agents are used in CT. Pathological tissue often demonstrates increased vascularity
Figs. 14.1 and 14.2 Axial T2W (left) and T1W (right) MR images of the bladder. Note the signal
from urine in the bladder is “bright” on the T2W image and “dark” on the T1W image. A right
sided bladder tumour is well visualised on the T2W image
14 Principles of Magnetic Resonance Imaging (MRI) 85
Figs. 14.3 and 14.4 T1W fat saturated pre contrast (left) and post contrast (right) enhanced axial
images through the bladder
and hence increased contrast uptake. Gadolinium speeds up the T1 relaxation time
of protons within tissues. Post contrast imaging is usually T1W with fat saturation
to remove the bright fat signal leaving only the signal from the enhancing tissues.
This is utilised in prostate and bladder MRI (see Fig. 14.3 and 14.4).
Diffusion Weighted Imaging
Diffusion weighted imaging exploits the random motion of water molecules. ‘Free
diffusion’ or ‘Brownian motion’ applies to water molecules in an unrestricted envi-
ronment such as urine in the bladder. Here the water molecules move in random
motion. This free movement of water is restricted in the body by boundaries formed
by cell membranes and the tissue itself. Conditions typically demonstrating
restricted diffusion include cancer, infarction and abscess formation. The amount of
diffusion weighting in an image is governed by the “b value”. The higher the b value
the greater the diffusion weighting. Ultra-high b values of 1400–2000 are used in
prostate imaging. Densely cellular prostate cancer displays restricted diffusion
compared to normal adjacent peripheral zone tissue. Therefore, prostate cancer
appears brighter than the normal peripheral zone on the native diffusion image and
darker than the normal peripheral zone on a calculated image called the apparent
diffusion coefficient (ADC) map (Figs. 14.5 and 14.6).
86 R. Hawkins
Figs. 14.5 and 14.6 Axial ADC map (left) and b2000 DWI image (right) through the prostate
demonstrating prostate cancer within the right peripheral zone in an 8 o’clock position. Diffusion
weighted imaging aids cancer detection and is now incorporated as standard during prostate MRI
Spectroscopy
MR spectroscopy provides metabolic information about prostatic tissue by display-

ing the relative concentrations of chemical compounds within contiguous small vol-
ume of interest (voxel) using chemical shift techniques. In prostate cancer, the
choline level is typically high, secondary to high phospholipid cell membrane turn-
over and the citrate-creatine level reduced. The difference in the choline to citrate-
creatine ratio within voxels allows us to help differentiate cancer from normal tissue.
Current Role of MRI
MRI is the staging investigation of choice for local staging of prostate and penile
cancer. It is routinely used in active surveillance of prostate cancer and may allow
men to safely avoid a prostate biopsy if the MRI shows no evidence of tumour. In
bladder cancer, MRI is better at differentiating between T1 and ≥ T2 disease. Both
MRI and CT achieve similar accuracies in nodal detection. CT rather than MRI is
the technique of choice in detecting lung metastases as it can be acquired quickly
during a single patient breath hold and demonstrates fine spatial resolution. CT
urography is the technique of choice in detecting upper tract tumours. MR urogra-
phy is very useful in the acutely obstructed patient with acute renal failure or in
pregnancy as the point and cause of obstruction can be identified without IV con-
trast or radiation.
14 Principles of Magnetic Resonance Imaging (MRI) 87
MRI-guided Biopsy
Some centres advocate MR-guided biopsies in specific instances to try and diagnose
or exclude prostate cancer. MR-guided biopsies, however, are generally highly
impractical, costly, time consuming and uncomfortable for the patient and are there-
fore not routine practice.
Future Developments
There are continual developments in MR to increase image quality and speed up

image acquisition to make examinations shorter and easier for patients whilst
increasing productivity. New developments in this area include simultaneous mul-
tislice acquisition (allowing 2 slices to be acquired at once halving the acquisition
time), compressed sensing (a complex technique which uses sparse data to greatly
accelerate acquisition times whilst minimally affecting image quality) and most
recently deep learning reconstruction (which uses specially trained neural networks
to transform the raw data instead of conventional methods, allowing reduced acqui-
sition times, improved image quality or both). Also on the horizon is MR finger-
printing which uses unconventional complex acquisition protocols with constantly
changing parameters to create MR “fingerprints” of different conditions which are
then stored in an MR “dictionary”. This was first used in brain imaging but is now
expanding into other areas including prostate imaging.
Further Reading
Jacobs MA, Ibrahim TS, Ouwerkerk R. MR imaging: brief overview and emerging applications.
Radiographics. 2007;July–August 27:1213–29.
Body MRI. Siegelman ES. Elsevier Saunders. Compressed sensing: a paradigm shift in MRI. http://
clinical-mri.com/compressed-sensing-a-paradigm-shift-in-mri/
Panda A, Mehta BB, Coppo S, et al. Magnetic resonance fingerprinting-an overview. Curr Opin
Biomed Eng. 2017;3:56–66. https://doi.org/10.1016/j.cobme.2017.11.001.
Chapter 15
Safety in MR Scanning
Suzanne Phenna
MR utilises 3 magnetic gradient fields to generate an image, each of which pose

risks to patients. It is important as the referrer of MR scans that you understand the
risks and barriers your patient may have to safe scanning. Visiting the radiology
department to speak with the MR manager, to understand what imaging options are
feasible, is advised when doubt exists.
Risks from the MR environment can include injury or death from projectiles/
missiles, heating, RF burns and damage to implanted electrically activated devices.
There are risks to the patient from both the MR environment itself and the agents
used to obtain diagnostic images.
The hazards associated with MR scanning come from:
• The main Magnetic field (B0)
• Time varying radiofrequency fields (B1)
• Time varying gradient magnetic fields (dB/dt)
Magnetic Field B0
MR scanners vary in magnetic field strength which is expressed in Tesla (T). Most
clinical scanners are either 1.5 or 3 T magnetic field strength. A 3 T scanner is
60,000 times stronger than the earth’s magnetic field.
The main risks from the scanner magnetic field include
• Translational force—risk of ferrous objects being attracted to the magnet and
becoming projectiles.
S. Phenna (*)
Northern Care Alliance NHS Foundation Trust, Salford, UK
e-mail: suzanne.phenna@nca.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_15
90 S. Phenna
• Rotational/torque—this is when ferrous objects want to align with static mag-

netic field)
Fatalities have occured from both projectile injuries (ferrous objects colliding with
a patient in the scanner) and from rotational forces (ferrous intracranial aneurysm
clip moving and rupturing a vessel).
The magnetic fringe field is shielded to reduce the overall spread of the magnetic
field, which compresses the magnetic flux field. The changes in magnetic field
strength over distance is described as the maximum gradient spatial field, which is
plotted as a map and is expressed in Tesla per meter (T/m) or Gauss per cm (G/cm).
Each manufacturer produces a spatial gradient map dependent on scanner bore or
open scanner design. Compressed magnetic fields produce steeper gradients with
increased risk of ferromagnetic acceleration closest to the opening of the bore. High
magnetic field strengths can also cause bioeffects such as nausea, dizziness and
small flashes of lights with eyes movement.
Time Varying Radiofrequency Fields B1
Radiofrequency (RF) magnetic fields generate signal for formation of the MR image
via an inherent transmit and receive (TR) body coil within the magnet. Smaller
extremity coils can be deployed to limit the RF field to that region alone which is
useful when electronically activated implants cannot be exposed to RF. Surface
receive only coils detect the signal emitted from the patient and vary in size and
configuration to be as close to the body part being imaged.
Effects of RF B1
Heating
Radiofrequency energy produces tissue heating which is greatest at the isocentre of

the magnet. The degree of heating experienced is influenced by the patients build,
presence of implants, operating mode of the scanner, ambient room temperature,
additional layers of clothing or blankets and the rate of ventilation within the bore
of the scanner. Heating is dissipated by radiation, convection, and conduction.
The scanner has 3 modes of operation:
• Normal mode. This will produce an energy Specific Absorption Rate (SAR) of
up, but no greater than 2 W/kg, resulting in a 0.5 °C body temperature rise
• First level mode. SAR can reach 4 W/kg, resulting in a 1.0 °C rise I body
temperature
• Second level (research only). Up to and greater than 4 W/kg. > 1.0 °C
15 Safety in MR Scanning 91
The MHRA recommends scanning patients in normal operating mode.

Newer scanners also offer a low SAR option, which may be used for achieving
the conditions for SAR by manufacturers of implants.
Burns
There are specific burns that can occur in MR

• Proximity burns. When the patient is too close to the bore of the scanner. 1–2 cm
pads will create a barrier, reducing risk.
• Faraday’s law of induction. The human body can become a conductor if loops
are present in the patient from skin-to-skin contact positioning, resulting in local-
ised heating and burns.
• Antenna/resonant burns: caused by implants/conductive material within, or on,
the patient
• Reflection burns. Heating risk from materials used in medication patches that
have metallic filaments or foil backing, clothing with metallic fibres, or tattoos
Time Varying Gradient Field (dB/dt)
There are 3 sets of gradients which are used to spatially localise the signal during
image formation (x, y and z gradients). The gradients magnetic fields switch on and
off rapidly during scan acquisition which can induce currents within the patient.
The switching gradients can cause:
• Peripheral nerve stimulation PNS (can be uncomfortable)
• Electrical induction (Faraday’s law), which can cause heating around implants
• Stimulation (diaphragm spasm affecting breathing)
• Scanner hardware is limited to prevent cardiac muscle stimulation
This gradient switching is also responsible for the acoustic noise during scanning.
Hearing protection, either earplugs or headphones, are required during the scan.
Gadolinium-based Contrast Agents (GBCA)
Gadolinium is a heavy metal held in a chelating ligand to create a molecule which

has paramagnetic qualities and is excreted by the kidneys. It is used as an MRI con-
trast agent as it shortens the T1 relaxivity of tissues. Allergy to GBCAs are rela-
tively rare, they are less nephrotoxic than iodine-based contrast agents, but should
be avoided during pregnancy.
92 S. Phenna
MR contrast agents have been associated with:

• Nephrogenic Systemic fibrosis (NSF): A disease seen in patients with end-stage
renal impairment who present with tissue inflammation and fibrosis leading to
thickening of the dermis, contractures of limbs or internal organ damage.
Diabetics, hypertensives, those with known kidney disease or > 65 years of age
are at particular risk. Radiographers will administer GCBA under a Patient
Group Directive (PGD) specifying the need for an eGFR in all higher risk
patients. The decision to give contrast to patients with an eGFR of <30 mL/
min/1.73 m2 will be governed by the supervising Radiologist.
• Gadolinium deposition: Gadolinium may be retained in the Globus pallidus and
Dentate nucleus in the brain and within other tissues. Linear GCBAs have a
higher proclivity than macrocyclic agents for this to occur. There is, however,
currently no long-term data to show this has any adverse effect.
MR Safety
Patients, staff, and visitors who will enter the MR environment need to be screened
to ensure they are safe to enter. This will require completion of a safety question-
naire and removal of clothing or objects that can represent a hazard in the scan
room. Most radiology departments will have a specific online or paper referral
which will ask for information on possible contraindications to MR scanning
(Table 15.1). It is also common practice for patients to be sent the safety screening
questionnaire with their appointment letter.
Table 15.1 A standard questionnaire to determine a patient’s safety to have an MR scan

Have you ever had an operation on your Head?
Have you ever had an operation on your Heart?
Do you have a Pacemaker, Cardiac monitoring device or valve replacement?
Do you have an Aneurysm Clip or Coil?
Do you have a Hydrocephalus Shunt or any Programmable Implant?
Do you have any stents in your body?
Do you have any implants or medical devices in or outside your body?
Do you have a Nerve Stimulator?
Do you have a cochlear or brainstem implant?
Have you ever had an accident involving metal fragments penetrating your eyes or body? (E.g.,
Shrapnel, welding/grinding materials, or bullets)
Have you had any operations in the last 2 months?
Do you have any artificial joints or limbs?
Is there any chance of pregnancy? Or are you breastfeeding?
15 Safety in MR Scanning 93
For patients who lack capacity to answer the questionnaire, safety can be ascer-
tained by reviewing the medical notes, obtaining information from a knowledgeable
family member or caregiver or by reviewing recent imaging. If none are available,
then chest, abdominal and lateral skull X-rays should be requested to look for con-
traindications to MR scanning.
MR Item Classification
The (MHRA) recommends that all equipment entering the MR environment is

clearly labelled using with one of the following labels (Table 15.2).
Table 15.2 Definitions of MR item safety from ASTM international standard F2503-13
MR SAFE
‘An item that poses no known hazards resulting from exposure to any MR
environment. MR Safe items are composed of materials that are electrically
nonconductive, non-metallic, and nonmagnetic’
MR CONDITIONAL
‘An item with demonstrated safety in the MR environment within defined
conditions. At a minimum, address the conditions of the static magnetic field,
the switched gradient magnetic field and the radiofrequency fields. Additional
conditions, including specific configurations of the item, may be required.’
MR UNSAFE
‘An item which poses unacceptable risks to the patient, medical staff or other
persons within the MR environment.’
94 S. Phenna
Understanding MR Conditional Labelling
The MR safety of devices commonly encountered in urological practice are shown

in Appendix 2. Implanted medical devices can be classed as passive or active.
Passive implants include joint replacements, vascular stents, aneurysm clips,
orthopaedic plates, and screws. Those fixed into bone are unlikely to undergo deflec-
tion or attractive forces in the magnetic field and can be considered safe to scan
although they can contribute to the heating effects from MR scanning.
Active implanted devices will have moving parts or an internal power supply,
such as internal electronic cardiac devices (IECD), cochlear implants, neurostimu-
lators, programmable hydrocephalus shunts.
There are occasions where a patient may need a scan on either an untested
implant, an MR UNSAFE implant, or a non-conditional implant (when the com-
pany conditions cannot be met). This is considered off-label scanning.
An MR safety multidisciplinary team, comprising of the MR safety expert, MR
responsible person, relevant specialist clinician, radiologist and referring clinician
can perform a risk assessment, looking at the benefits and potential risks of per-
forming a scan or appropriate alternative means of imaging.
Further Reading
International Society for Magnetic Resonance in Medicine: ISMRM Best Practices for Safety
Testing of Experimental RF Hardware 2019. https://www.ismrm.org/safety/RF_Hardware_
Safety_Testing_2022-03.pdf
MHRA: Safety Guidelines for Magnetic Resonance Imaging Equipment in Clinical Use,
February 2021.
MRIsafety.com. http://www.mrisafety.com.
Chapter 16
Urological Applications of MRI Scanning
Magnetic resonance imaging (MRI) techniques are widely used for urological
assessment. In this chapter, we will discuss MRI application for three of the most
common anatomical areas: the kidneys, bladder, and prostate. MRI is also utilised
in diagnostics for the adrenal glands, penile trauma or malignancy.
Introduction
The basics of MRI physics is beyond the scope of this chapter, however familiarity
with different sequences and their value to diagnostic interpretation is essential. The
standard sequences acquired in multiple planes provides evaluation of anatomy and
pathology through differences in the intrinsic properties of adjacent tissues based on
the density and orientation of protons (H+) present in each tissue. Manipulating MR
acquisition parameters applied to a section of the body produces contrast between
tissue types, weighted to these basic intrinsic properties. Standard sequences are
T1-weighted imaging and T2-weighted imaging. Muscle signal is relatively iso-
intense on both these sequences and can be used as a comparison. Basic T2-weighted
images can be recognized by the high signal return (brightness) of water content,
(e.g., looking at the urinary bladder, which appears bright). In a standard T1
weighted sequence, bright areas usually correspond to fat content and water will be
low signal. Proteinaceous or hemorrhagic fluid or tissue can also return high signal
on T1-weighted sequences because of something known as the paramagnetic effect.
Another standard sequence that can help to differentiate blood product and fat is to
acquire fat-suppression images.


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Contrast enhancement with agents that have strong paramagnetic properties (e.g.
gadolinium) are often used to delineate pathology against background normal tissue.
Often, serial images are acquired over time points to observe the dynamic characteristics
of enhancement in a volume of tissue (Dynamic Contrast Enhancement—DCE). The
contrast enhancing properties of different pathologies can vary and are interpreted
against the background contrast enhancement pattern of the normal tissue from where
that pathology has arisen. For example, aggressive malignant tumours often developed
faster than their blood supply, resulting in small leaky vessels (neo-angiogenesis) that
enhance early with contrast and washout early relative to adjacent normal tissue.
A more recent MRI technique established over the last 20 years is diffusion
weighted imaging (DWI). Originally utilised to great success for stroke assessment,
DWI has significantly improved detection of malignancy in a numerous areas. It is
important to recognize that DWI is very sensitive to artefact and movement, there-
fore has limitations depending on the body part being imaged. In urological imaging
for example, it has limited value for the kidneys but at the same time is indispens-
able for prostate imaging (and to a lesser extent bladder imaging). DWI is sensitive
to the movement of water within cells and between cells. It relies on temporal and
spatial acquisition of multiple images, hence the increase in sensitivity to motion
artefact. A simple model to describe DWI, is that tissue with increased cellular den-
sity (tumour) relative to adjacent normal tissue will prevent water molecules from
diffusing freely and randomly over time, via Brownian motion. For each temporal
acquisition, signal return from normal tissue will diminish relative to signal return
for a tumour that is restricting the movement of water. This creates the contrast
necessary for detection. The sensitivity for detection can be increased by either
increasing the strength of the magnetic gradient applied (b-value) or time of acquisi-
tion. The trade-off is overall reduced quality images with poor signal to noise, how-
ever if the area of concern has significant restrictive properties, it will return a “light
bulb” like bright signal against the background contrast of noise.
MRI Kidney
MRI of the kidney is usually performed as a problem-solving tool for the characteri-
sation of renal masses or for evaluation of vessels. A typical set of sequences in an
MRI renal protocol would be T1, T2, T1-fat saturated post contrast in the nephro-
genic, corticomedullary and excretory phases (see CT Urography chapter for detail
regarding these phases). MRI is often considered in younger patients and where
there is expectation of multiple future scans for monitoring (e.g. ADPKD or a com-
plex cyst under follow up).
One of the main advantages of MRI is that it is not subject to pseudo-enhancement.
If a structure enhances on post contrast T1 this can safely be assumed to be true
enhancement. A lesion which shows equivocal enhancement on CT may benefit
from MRI to assess for true and significant enhancement. Similarly, enhancement of
calcified lesions is much better detected on MRI, as calcification appears hypoin-
tense on MRI. On CT the calcification obscures any enhancement.
16 Urological Applications of MRI Scanning 97
A relatively common lesion which causes diagnostic dilemma is an angiomyoli-

poma (AML). 95% of AMLs contain macroscopic fat and hence can be detected
easily on CT with a HU of −20 or by signal drop out on fat suppressed MRI
sequences. However, 5% of AMLs are fat poor and are impossible to accurately
separate from an RCC. Whilst not sensitive or specific enough to secure a diagnosis,
the information from MRI kidney may influence management decisions. Fat poor
AMLs contain microscopic fat which can be detected on MRI.
The main disadvantage of using MRI is often access to MRI scanners, long acqui-
sition times, patient cooperation (claustrophobia, noisy scanner) and contraindications
such as pacemakers. Movement artifact is also a significant consideration. Interpretation
of images can be significantly hampered by movement artifact (Fig. 16.1).
Fig. 16.1 Comparison of CT and MRI in the evaluation of a renal mass. Non contrast CT of the
tumour (top left) shows a homogenous mass of equivocal density (25 HU). In the post contrast
nephrographic study (top right), the lesion remains relatively featureless with equivocal enhance-
ment (35 HU). T2 weighted MRI (bottom left) clearly shows a more complex lesion with areas of low
and high signal. Post contrast (bottom right) confirms real enhancement in the areas that are low on T2
MRI Bladder
This is often indicated for urothelial cancers where there is concern of muscle inva-
sive disease. CT urography is the work horse for detection of urothelial malignancy
however a simple T2 sequence of the bladder will also provide the contrast neces-
sary to detect a cancer. Bladder MRI is most useful for local staging because it can
provide a far superior contrast between layers of the bladder and identify muscle
invasion. A typical scan would include multi-planar T2, dynamic contrast enhance-
ment and DWI. Artefact from bowel gas and peristalsis can be minimised with
antispasmodic agents prior to imaging. Preparation must include optimum bladder
distension prior to imaging, and patients are asked to drink water or avoid passing
urine for a period. T2-weighted imaging will demonstrate sharp contrast between
the low signal muscular layer sandwiched between high signal urine and extrave-
sicular intermediate signal fat. Tumour is identified as of higher signal than the
bladder muscle. When combined with contrast enhancement and DWI, the likeli-
hood of muscle invasive tumour can be assessed using a scoring system (Vesical
Imaging-Reporting And Data System or VI-RADS). Depending on the combination
of findings in each sequence the probability of muscle invasive cancer presence is
given a score (VI-RADS 1 being highly unlikely, and VI-RADS 4/5 being highly
likely +/− extravesicular extension) (Fig. 16.2).
Fig. 16.2 Comparison of CT urography and MRI of the bladder. The CT urography study (top
left) shows a mass arising from the right posterolateral aspect of the bladder filled with urine and
dependent contrast (white). The T2 image (top right) clearly distinguishes between the low signal
muscular layer and the mass. The lesion is bright on DWI (bottom left) and demonstrates enhance-
ment (bottom right) however in both sequences the abnormal signal is linear and smooth. With no
clear disruption of the muscle layer, this would be classified as VI-RADS 2/3
MRI Prostate
Multiparametric MRI (mpMRI) of the prostate has evolved into an established diag-
nostic tool in the current triaging of suspected prostate cancer (PCa), as well as post
diagnostic surveillance for patients where treatment is deferred or avoided.
Integrating mpMRI into the urological management pathway aims to reduce the
number of unnecessary invasive biopsies through appropriate targeting of abnormal
areas in the gland and thereby reducing biopsy related morbidity. The rationale for
mpMRI utility in PCa is to combine all available sequences that are sensitive to
abnormal changes in tissue signal, to increase the diagnostic specificity for detect-
ing clinically significant cancer.
Prostate imaging for PCa is mostly a qualitative assessment of the following
parameters:
• Multi-planar T2-weighted sequences
• Diffusion Weighted Imaging (DWI)—with corresponding Apparent Diffusion
Co-Efficient (ADC value/map)
• Dynamic Contrast Enhancement (DCE) sequences.
A quantitative assessment of the probability of a geographical signal abnormality
representing PCa is given as a score (Prostate Imaging-Reporting And Data System or
PI-RADS score of 1 to 5) based on different combinations of findings from each param-
eter. Alternatively, imaging findings and clinical suspicion (prostate specific antigen
(PSA) levels, examination, family history and risk factors) are combined (Likert score)
to give an overall subjective assessment of the likelihood of PCa. Most prostate cancers
originate in the peripheral zone and for this DWI imaging is the dominant sequence for
predicting the probability of clinically significant cancer, with the other sequences add-
ing weight to an area of suspicion. It is therefore essential to acquire images that con-
form to PI-RADS 2.1 standard for acquisition parameters. As in the bladder,
susceptibility from rectal gas and peristalsis can result in significant artefacts that
reduce the sensitivity of mpMRI. For lesions that appear to arise in the anterior gland
or transition zone, T2-weighted imaging is the dominant sequence with DWI and occa-
sionally DCE adding weight to any suspicious area. mpMRI is also essential for local
staging and is used to help determine whether there is extracapsular disease, seminal
vesicle involvement or T4 disease involving adjacent structures (Fig. 16.3).
Fig. 16.3 Multiparametric Prostate MRI. The top panel from right to left are T2-weighted multipla-
nar sequences through the prostate. The b-1400 DWI sequence (bottom left) returns an area of high
signal abnormality with a corresponding focal area of low ADC (bottom row middle). This is suspi-
cious for a clinically significant cancer and anatomical T2-weighted images show a lesion in this
area. The DCE (bottom right) confirms avid early enhancement. Taken together this lesion scored as
a PI-RADS 4 (high probability for clinically significant cancer) and should be targeted for biopsy
Further Reading
Engels RRM, et al. Multiparametric magnetic resonance imaging for the detection of clini-
cally significant prostate cancer: what urologists need to know. Part 1: acquisition. Eur Urol.
2020;77(4):457–68.
Israël B, et al. Multiparametric magnetic resonance imaging for the detection of clinically sig-
nificant prostate cancer: what urologists need to know. Part 2: interpretation. Eur Urol.
2020;77(4):469–80.
Panebianco V, et al. Multiparametric magnetic resonance imaging for bladder cancer: development
of VI-RADS (vesical imaging-reporting and data system). Eur Urol. 74(3):294–306.
Venderink W, et al. Multiparametric magnetic resonance imaging for the detection of clinically
significant prostate cancer: what urologists need to know. Part 3: targeted biopsy. Eur Urol.
2020;77(4):481–90.
Wang ZJ, Westphalen AC, Zagoria RJ. CT and MRI of small renal masses. Br J Radiol.
2018;Jul;91(1087):20180131. https://doi.org/10.1259/bjr.20180131. Epub 2018 May 10.
PMID: 29668296; PMCID: PMC6221773.
Chapter 17
Vascular Embolisation Techniques
in Urology
Symeon Lechareas
Vascular embolisation is an essential tool in the urologist’s arsenal for a variety of

urological conditions including renal haemorrhage, tumour embolisation and vari-
cocoele. More recently it has been used to treat BPH. It allows minimally invasive
management of bleeding with short recovery times and without the need for major
surgery.
Introduction
Embolisation is a minimally invasive, image guided procedure which aims in the

selective occlusion of target arteries or veins without causing ischemia or necrosis
to the surrounding tissue. It is a well-established tool in the treatment of hemor-
rhagic emergencies in urology with continuously expanding applications following
the development of newer and safer embolic materials.
For a successful outcome, meticulous pre-procedural planning using appropriate
imaging tailored to each clinical setting is essential. For example, renal injuries require
multiphase CT imaging to assess the extent of injury and provide anatomical informa-
tion to the operator which will be used as a roadmap for the embolisation procedure.
The operator must also be aware of the embolic materials available and their safe
delivery methods. Advanced vessel catheterisation skills are essential, along with
excellent knowledge of the angiographic equipment, including guidewires, sheaths,
catheters and micro-catheters.
S. Lechareas (*)
Liverpool University Hospitals, Liverpool, UK
e-mail: symeon.lechareas@sthk.nhs.uk

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https://doi.org/10.1007/978-3-031-26058-2_17
104 S. Lechareas
Vascular Access and Closure
The right common femoral artery is the most common access site used for arterial
interventions including renal artery and prostatic artery embolization. The brachial
and the radial artery are alternatives. For venous procedures, e.g. varicocele emboli-
sation, the right common femoral and the right internal jugular veins are widely used.
The use of ultrasound needle guidance is necessary for safe vascular access.
After the initial puncture, access is established with the introduction of vascular
sheaths over a wire to maintain access through the procedure and prevent access site
injury from multiple exchanges. Most embolization procedures can be performed
with 4–6Fr sheaths depending on the size of the embolic material that needs to be
delivered.
Safe arterial access must be followed by successful closure of the access site to
avoid complications such as pseudo aneurysm and bleeding. For this purpose, the
traditional method of manual compression has been replaced by closure devices
which reduce the mobilisation and hospitalisation time significantly. There are sev-
eral different closure devices on the market using technologies including sutures or
collagen plugs to seal the access site.
Guidewires and Catheters
After sheath introduction, the operator needs to catheterise the target vessel for
delivery of the embolic material with different combinations of guidewires and
catheters. There are three main types of guidewires: access wires, manoeuvre wires
and exchange wires.
Access wires are used through the initial puncture needle to facilitate sheath
placement. Manoeuvre wires are usually hydrophilic and less thrombogenic and are
used for selective catheterisation of the target vessels. Exchange wires are stiffer
and with atraumatic tips and are suitable for exchange of catheters and sheaths.
Catheters are available in a variety of shapes, sizes and lengths and should be
carefully chosen to match the anatomy of the vessels. The most commonly used
catheter in accessing renal vasculature is the Renal Access Cobra Catheter which
has a C-shape tip configuration. This is ideal to negotiate the renal artery and
gonadal veins. Micro-catheters may be used to access more difficult anatomy,
including smaller, distal and tortuous vessels.
Embolic Agents
The choice of the embolic agents needs to be tailored to the need for rapid, tempo-
rary or permanent occlusion. Embolic materials are divided into mechanical (coils
and vascular plugs) and liquids (Polyvinyl Alcohol Particles, Calibrated micro-
spheres, n-butyl cyanoacrylate (n-BCA), Gelfoam and Onyx) (Table 17.1).
17 Vascular Embolisation Techniques in Urology 105
Table 17.1 The properties and applications of embolic agents in urology

Agent Description Target Delivery technique Applications
Coils Platinum / stainless Usually a focal Pushed into Acute focal
steel vessel position by renal / pelvic
Bare/fibered/ Large to small guidewires bleeding
Bioactive arteries and veins The most precise Pre-
agent nephrectomy
Varicocoeles
Vascular Plugs Self-expanding Medium / Large Mounted on Renal bleeding
cylindrical nitinol vessels with high guidewire Pre-
mesh flow Controlled nephrectomy
detachment
Polyvinyl Particles Usually a distal Injected, carried Vascular
Alcohol (PVA) Size range target area by arterial flow. tumours—RCC
Microspheres 50–1200 μm. Medium to small Suspended in / AML
vessels including dilute contrast to
capillaries make it
radiopaque.
n-Butyl Liquid embolic agent Small arteries Injected through Renal Bleeding
cyanoacrylate Polymerisation time Capillaries micro-catheter. Pelvic Bleeding
(n-BCA) controlled with Mixed with AML
glue oxidised oil Lipiodol to act as Pre-
(Lipiodol) a carrier and make nephrectomy
Once polymerised it it radiopaque
becomes solid
Gelfoam Haemostatic sponge Focal vessel or Injected Acute focal
sponge Slurry / Pledgets diffuse pelvic Soaked in dilute renal / pelvic
embolization contrast to make it bleeding.
Medium to small radiopaque.
arteries and
veins.
Mechanical Embolic Materials
Coils are made from platinum or stainless steel. Platinum coils are harder and ideal
for embolisation of large vessels while stainless steel coils are softer and can be
used in smaller vessels. They are available in a variety of diameters (2–15 mm),
shapes (circular, helical) and lengths (2–30 cm) but are packaged straight to enable
easy introduction into the catheter.
They revert to their pre-formed configuration after release from the end of the
catheter. The coils can be bare, fibered or bioactive. Fibered and bioactive coils are
covered with thrombogenic materials to induce rapid clotting. Coils should be sized
20 to 30% larger than the target vessel to prevent migration and non-target
embolisation.
Vascular plugs are ideal for embolisation of medium to large sized vessels. They
can be used as mechanical scaffolds to prevent coil migration in high flow blood
vessels. They are preferably deployed in straight vascular segments. They can be
retrieved and repositioned prior to deployment.
106 S. Lechareas
Liquid Embolic Materials
Polyvinyl Alcohol (PVA) Particles are small and irregular particles which are used
for permanent occlusion of blood vessels. PVA particles adhere to the blood vessel
wall inducing thrombosis and necrosis of the vessel. They are available in sizes
ranging from 50 to 1200 μm. They are mixed with contrast to make them radi-
opaque during injection.
Microspheres are spherical embolic agents made of PVA or more advanced
materials. The main advantage they offer against the other liquid embolic agents is
the strong correlation between the size of the microsphere and the diameter of the
vessel at which occlusion occurs.
Gelatine Sponge (composed of water insoluble gelatine) is the only temporary
embolic agent. It dissolves after 30–45 days. It is used to treat acute bleeding, allow-
ing the damaged endothelium to repair. Depending on the method of preparation it
can be injected as a slurry or pledgets.
n-Butyl Cyanoacrylate (n-BCA) or “glue” is another widely used embolic mate-
rial. It is mixed with Lipiodol which increases its polymerization time and makes it
radiopaque. Once it polymerises it becomes solid, thereby achieving embolisation.
Onyx is an ethylene vinyl alcohol copolymer that provides complete filling and
distal penetration of the peripheral vasculature. It is available in different viscosities
for more controlled deployment.
The Use of Embolization in Clinical Urology
Renal Hemorrhage
Iatrogenic causes are the most common and include partial nephrectomy and
PCNL. The kidney is supplied by end arteries with no collateral supply therefore
tissue loss must be minimised by embolising the target vessel with coils, glue or
gelfoam as distally as possible. This is particularly important in the case of a single
kidney or poor renal function.
Care should be taken in the presence of arteriovenous fistulae following partial
nephrectomy, to avoid non-target embolisation to the pulmonary circulation. To pre-
vent this, large size particles, onyx and coils can be used.
Devascularisation of Renal Tumours
This can be performed to reduce the size of tumours (e.g. AML) or stop acute bleed-
ing (from AML or malignant tumours). The tumor is initially embolised with par-
ticles >300 μm or glue followed by complete devascularisation of the kidney with
proximal coils or vascular plugs in the renal artery, if necessary. Post-embolisation

syndrome may occur if a large volume of tissue has been devascularised. This is
characterized by severe pain, fever and virus type symptoms. Symptoms can last up
to 72 h and mimic infection or abscess formation. A strict protocol of analgesia
should be followed after the procedure as kidney ischemia may induce severe pain.
Varicocele embolisation (Figs. 17.1 and 17.2) can be performed through the
common femoral or internal jugular vein. Indications include chronic testicular pain
and subfertility. It is a safe and minimally invasive procedure with short recovery
Fig. 17.1 Selective left

gonadal venogram prior to
embolization which shows
retrograde filling of the
pampiniform plexus
108 S. Lechareas
Fig. 17.2 Post

embolization venogram of
the left gonadal vein which
shows complete occlusion
of the vessel. Embolization
performed with platinum
coils
time. Selective internal spermatic venography is performed to confirm the presence

of reflux and to assess for collaterals which are a common cause of recurrence. The
catheter tip is advanced to just above the level of the inguinal ligament and a series
of coils deployed from this point up to the level of L3. Bear, fibered or detachable
coils are commonly used.
Post-surgical Pelvic Bleeding
There is an increasing role in the management of arterial haemorrhage following

pelvic surgery. Given the well-developed collateral and anastomotic supplies in the
pelvis, bilateral internal iliac imaging is usually required unless an obvious focal
bleeding point is seen on CT. If haemorrhage is limited to a single vessel, coils or
gelfoam are the treatment of choice. Selective particle embolisation is used for more
diffuse pathology such as bleeding bladder tumours. Rarely, selective bilateral inter-
nal iliac artery embolisation may be required. There is an increased risk of non-
target necrosis in older patients, arteriopaths and those who have undergone
radiotherapy due to collateral disruption.
Prostatic artery embolization (PAE) is a minimally invasive treatment for benign
prostatic hyperplasia (BPH) with the advantages of short hospital stay and repeat-
ability. Indications for prostate artery embolization include those for other surgical
options of bladder outflow obstruction. The procedure is performed through the
right common femoral artery. Arterial rotation CT angiography (cone-beam CT) is
performed to identify the anatomy. Bilateral embolization of the prostate arteries is
targeted. The prostate artery must be super-selectively catheterised with a micro-
catheter and embolised with microspheres with a size of 300–500 μm.
Further Reading
Sheth RA, Sabir S, Krishnamurthy S, et al. Endovascular embolization by transcatheter delivery of

particles: past, present, and future. J Funct Biomater. 2017;8(2):12.
Taslakian B, Ingber R, Aaltonen E, Horn J, Hickey R. Interventional radiology suite: a primer for
trainees. J Clin Med. 2019;8(9):1347. Published 2019 Aug 30.
Part II
Imaging Nuclear Medicine
Chapter 18
Radionuclides and Their Uses in Urology
Matthew Memmott and Richard Lawson
This chapter describes the ideal properties of radiopharmaceuticals and radionu-

clides that are required for nuclear medicine imaging with a gamma camera or a
PET scanner. It shows the radiation dose to the patient from some nuclear medicine
studies used in urology and explains the principles of radiation protection of the
patient.
Nuclear medicine utilises radioactive tracers to assess organ function. These
tracers are called radiopharmaceuticals and many different radiopharmaceuticals
are used depending on the organ or system to be studied. After administration to the
patient, usually by intravenous injection, the amount of radiopharmaceutical appear-
ing in different parts of the body is monitored by detecting the radioactivity. This
can be done with non-imaging tests involving only blood samples (eg GFR, see
Chap. 25), by taking images with a gamma camera (see Chap. 19), or imaging with
a positron emission tomography (PET) scanner (see Chap. 20). Nuclear medicine
images have poor spatial resolution but they demonstrate physiology rather than
anatomy and so are complementary to other imaging modalities.
Radiopharmaceuticals
The radiopharmaceutical has two parts; a pharmaceutical and a radionuclide label.

An ideal radiopharmaceutical should have the properties shown in Box 18.1.
M. Memmott · R. Lawson (*)

e-mail: Richard.Lawson@physics.org

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_18
114 M. Memmott and R. Lawson
Box 18.1 The characteristics of an ideal radiopharmaceutical

• The label should remain bound to the pharmaceutical in-vivo
• The pharmaceutical should concentrate only in the organ under investigation
• Background remaining in rest of the body should be low
• It should not be toxic to the patient and not interfere with the physiological
process under investigation
• Ideally the radionuclide should emit only gamma rays (no alpha or beta
emissions because these are too easily absorbed by the body)
• For imaging with a gamma camera, the gamma rays emitted should have a
suitable energy; more than 100 keV so that they can escape from the patient
and less than about 300 keV so that they can be stopped by the gamma
camera detector.
• For imaging with a PET scanner the radionuclide should emit positrons
with a low energy so that they only travel a short distance in the patient
before combining with an electron to give a pair of 511 keV gamma rays
(see Chap. 20)
• The radionuclide should have a suitable half-life (the time it takes for half
the radioactivity to decay away). In most applications a half-life of a few
hours gives enough time to prepare the radiopharmaceutical and complete
the test.
• It should be cheap and readily available
Radionuclides
A radionuclide is a radioactive form of an atom (Appendix 3). Table 18.1 shows the
properties of some radionuclides that can be used in nuclear medicine.
For the majority of gamma camera imaging studies the preferred radionuclide is
technetium-99 m (99mTc). Tc is the chemical element, ‘99’ is its mass number and
the ‘m’ means that it is a metastable (excited) state. 99mTc has the properties shown
in Box 18.2.
Box 18.2 The properties of technetium-99 m

• It decays by emission of gamma rays only (no alpha or beta emission)
• The gamma ray energy is 140 keV (which is ideal for gamma camera
imaging)
• It has a half-life of 6 hours (which is very convenient)
• It is readily available from a generator which can provide a daily supply of
99m
Tc from the decay of a longer lived parent (99Mo)
18 Radionuclides and Their Uses in Urology 115
Table 18.1 Properties of some radionuclides

Radionuclide Emission Half-life Production method
Technetium-99 m 140 keV gamma ray 6 hr Generator
Fluorine-18 Positron →two 511 keV gammas 110 min Cyclotron
Gallium-68 Positron →two 511 keV gammas 68 min Generator
Carbon-11 Positron →two 511 keV gammas 20 min Cyclotron
Nuclear medicine departments will obtain the radiopharmaceuticals that they

need for their investigations from a nearby radiopharmacy. In the radiopharmacy
99m
Tc is extracted from a 99Mo generator by a process called elution. The eluate is
added to a sterile vial containing the freeze-dried pharmaceutical which must then
be used within a few hours. Most radiopharmacies will have access to a 99Mo gen-
erator, so 99mTc radiopharmaceuticals are widely available.
For PET studies Gallium-68 (68Ga) can be extracted from a generator in a similar
way to 99mTc, but it is much more expensive and not widely available. Carbon-11
(11C) can only be produced in a cyclotron and it has a very short half-life so it is only
available in a few centres that have an on-site cyclotron. Fluorine-18 (18F) is also
produced in a cyclotron, but it has a longer half-life so it can be purchased from a
nearby supplier.
Because these radionuclides are very easily detected, it is possible to administer
very small quantities of pharmaceutical (micrograms or less) so that they do not
disturb the normal functions of the organ or system under investigation. This is
known as the tracer principle.
Radionuclide Dosimetry
The radiation dose to the patient can be kept low by using suitable radionuclides,
since most of the gamma rays escape from the patient (because of the suitable
energy), and the radioactivity doesn’t linger unnecessarily long (because of the
short half-life).
The radiation dose obviously depends directly on the amount of radionuclide
administered. This is measured in units of MBq (MegaBequerels)—1 MBq is a mil-
lion atoms disintegrating every second. The radiation doses from some nuclear
medicine procedures used in urology are shown in Table 18.2.
For comparison, the radiation dose in the UK from natural background averages
2.2 mSv per year. It can be seen that the radiation dose from most gamma camera
studies is less than one year’s natural background whilst PET studies, which are
largely used for malignant conditions, give a higher dose.
116 M. Memmott and R. Lawson
Table 18.2 The radiation dose received from some nuclear medicine studies carried out on
urological patients
Typical administered Radiation dose
Procedure Radio-pharmaceutical activity to the patient
PET scan for tumour imaging 18
F FDG 400 MBq 7.6 mSv
PET scan for prostate cancer 18
F choline 370 MBq 7.4 mSv
F PSMA 280 MBq 5.5 mSv
Ga PSMA 200 MBq 4.6 mSv
C choline 370 MBq 1.6 mSv
PET bone scan 18
F sodium fluoride 250 MBq 4.3 mSv
Gamma camera bone scan 99m
Tc MDP 600 MBq 3.0 mSv
Renogram 99m
Tc DTPA 200 MBq 1.0 mSv
Renogram 99m
Tc MAG3 100 MBq 0.7 mSv
DMSA scan 99m
Tc DMSA 80 MBq 0.7 mSv
GFR determination 99m
Tc DTPA 10 MBq 0.05 mSv
Radiation Protection in Nuclear Medicine
Any risk must be justified by a benefit to the patient and so, just as with X-ray stud-
ies, all nuclear medicine studies in the UK come under the Ionising Radiation
(Medical Exposure) IR(ME)R Regulations. This means that the clinical referrer
must provide the necessary clinical information for the practitioner to justify carry-
ing out the procedure. In nuclear medicine the practitioner is always a consultant
who holds a licence from the Administration of Radioactive Substances Advisory
Committee (ARSAC) authorising them to carry out a specific procedure. Employers
must also hold a licence, listing the practitioners and procedures authorised for each
specific site or installation under their management. Research studies require a sep-
arate ARSAC certificate for each project.
Although patients will themselves remain radioactive for a few hours after these
studies they do not constitute a significant hazard and will not need any special nurs-
ing precautions. Although much of the radiopharmaceutical is excreted in the urine,
normal hygiene precautions (such as plastic apron and gloves) are sufficient to avoid
accidental ingestion of radioactivity by nursing staff. However, it would be sensible
not to do a cystoscopy on the same day as a bone scan or a renogram if this can be
avoided.
Further Reading
Sharp PF, Gemmell HG, Murray AD, editors. Practical nuclear medicine. 3rd ed. Springer; 2005.
Chapter 19
Counting and Imaging in Nuclear
Medicine
Christopher Mathews-Aspinall and Richard Lawson
Nuclear medicine studies require the detection of gamma-emitting radiopharmaceu-

ticals within the patient’s body. This chapter describes equipment for counting the
activity in blood samples and imaging with a gamma camera. The PET scanner,
which is used for imaging positron emitting radionuclides, is described in Chap. 20.
Sample Counting and External Counting
The simplest sort of nuclear medicine test just produces blood samples which need to
be assayed for radioactivity (eg GFR, see Chap. 25). This can easily be done by put-
ting a sample into a well-type counter where it is surrounded by a scintillation crystal
(Fig. 19.1). This crystal emits a flash of light when it is hit by a gamma ray and the
light is detected by a photomultiplier tube, which converts the light into an electronic
pulse and the number of pulses are then counted. Because this type of counter is very
efficient at detecting gamma rays, it is possible to measure extremely small quantities
of radioactivity in this way. This is why very small administered activities can be used
in GFR studies, resulting in a very small radiation dose to the patient.
Studies like the renogram (see Chap. 22) require monitoring of the amount of
radiopharmaceutical in the kidneys with time. In the past this was done by placing
scintillation counters against the patient’s back, over each kidney. Because the coun-
ter is further away from the radiation source, this type of ‘external’ counting is not
as efficient as the well counter and so it requires higher administered radionuclide
doses. The main problem with external counting is that it is not possible to accu-
rately separate activity in the kidney from nearby non-renal background activity.
C. Mathews-Aspinall · R. Lawson (*)

Nuclear Medicine Centre, Manchester University Hospitals, Manchester, UK
e-mail: christopher.mathews@mft.nhs.uk; richard.lawson@physics.org

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_19
118 C. Mathews-Aspinall and R. Lawson
Fig. 19.1 Schematic Radioactive

Sample
diagram of a sample
counter. The sample is
Lead Shielding
surrounded by a scintillator
crystal, where incident
gamma rays create light
Scintillation
Electrical
which is detected by a Photomultiplier
Crystal
Pulse
photomultiplier tube
Gamma Ray
Scintillation
Light
The Gamma Camera and Collimation
The gamma camera is a device that not only detects gamma rays (Appendix 1)
emerging from the patient, but can also determine their position. It can, therefore,
produce an image of the distribution of radiopharmaceutical within the patient. The
gamma camera contains a single large scintillation crystal (typically 500 mm x
350 mm) and an array of many photomultiplier tubes. When a gamma ray hits the
crystal, scintillation light is emitted and collected by all the photomultipliers.
Signals from the photomultipliers are then fed into a computer which calculates the
interaction position from the distribution of light collected.
Gamma rays are, however, emitted from the patient in all directions and so, in
order to produce an image it is necessary to fit a collimator in front of the scintilla-
tion crystal. A collimator is, essentially, a lead plate with tens of thousands of paral-
lel holes in it, each about 2 mm in diameter. The holes restrict the accepted gamma
rays to just those that are travelling close to perpendicular to the face of the collimator.
The spatial resolution of the gamma camera, a measure of its ability to see fine
detail, is determined by the size of the holes in the collimator, which allows a small
range of gamma ray directions to be accepted in practice. This means that resolution
gets worse with distance, so that the image becomes more blurred the further away
the object is from the gamma camera.
Collimator hole size also affects the sensitivity of the gamma camera. Small
holes give good resolution but poor sensitivity, whilst large holes give poor resolu-
tion but better sensitivity. Thus gamma cameras are provided with a range of differ-
ent collimators for different purposes (Fig. 19.2). At a distance of 10 cm the
resolution might be about 7 mm when using a low energy high resolution (LEHR)
collimator, which has small holes, or 9 mm with a low energy general purpose
(LEGP) collimator (medium holes) or 13 mm with a low energy high sensitivity
(LEHS) collimator (larger holes). The sensitivity of the LEGP collimator would be
about twice that of the LEHR and the LEHS four times the LEHR. So choice of
collimator is always a balance of resolution against sensitivity.
Although the collimator is an essential part of forming the image it engenders
inefficiency; it blocks about 99.99% of emitted gamma rays because they aren’t
19 Counting and Imaging in Nuclear Medicine 119
Fig. 19.2 A gamma camera with two detectors, one above the patient couch and the other below
it. A selection of collimators are stored on the carts in the background
travelling in the right direction. Consequently, gamma camera imaging studies

require larger administered activities, and longer imaging times, in order to obtain
sufficient counts for analysis. Even with higher doses and longer counting periods
nuclear medicine images will have only a small number of counts in each image
pixel. This means that the images tend to be ‘noisy’.
For a static study like a DMSA kidney scan (see Chap. 24) the gamma camera
will use a LEHR collimator in order to obtain best possible resolution but will have
to acquire each image for about 5 minutes in order to obtain sufficient counts to see
real activity above the noise. Modern gamma cameras often have two detectors so
that two views can be obtained simultaneously to reduce the scanning time. This can
be particularly helpful for studies such as bone scans (see Chap. 26).
The gamma camera can also be used for dynamic studies, like the renogram (see
Chap. 22), where a series of images are acquired showing how the distribution of
activity changes with time.
SPECT and SPECT-CT
Gamma Cameras can produce 3D images of the activity distribution in the body
using a technique called Single Photon Emission Computed Tomography (SPECT).
This involves taking images at many angles all the way around the patient and
120 C. Mathews-Aspinall and R. Lawson
reconstructing cross sectional slices using a computer. Typical scan times are around
20 minutes.
An issue with SPECT alone is that some gamma rays, emitted from inside the
patient, may be absorbed or scattered by tissue before they reach the gamma cam-
era. This process is referred to as attenuation. Attenuation results in a reduction of
measured counts in deeper tissues, affecting the appearance of SPECT slices and
affecting quantification.
Modern gamma cameras can be combined with a CT scanner. This allows a CT
scan to be acquired with the patient in the same position as they were for the SPECT,
meaning the SPECT and CT images can be fused together. Since CT images repre-
sent varying attenuation of different tissues, an attenuation map can be created.
Attenuation correction can then be applied to the SPECT to improve image quality
and quantification.
Furthermore, SPECT-CT studies have the advantage of combining the functional
information provided in SPECT, with anatomical localisation from the CT. This is
particularly helpful to localise metastases in bone scans (see Chap. 26), where the
SPECT alone may show a region of suspicious uptake that cannot be localised to
specific anatomy until fused with CT.
Data Analysis
Gamma cameras usually have dedicated nuclear medicine computer processing sys-
tems associated with them. These are particularly useful for analysing data from
dynamic studies like the renogram (see Chap. 22). The operator can draw regions of
interest around each kidney on the computer images and generate curves showing
how the activity changes with time. This overcomes the problems of external count-
ing where the kidney location could not be seen and also makes it possible to
exclude non-renal background.
Raw gamma camera images usually need some processing before they are inter-
preted. Therefore the nuclear medicine computer is used to analyse the data and
display a summary of the results. Then a screen capture of the results can be sent to
the hospital Picture Archiving and Communication System (PACS).
Further Reading
Sharp PF, Gemmell HG, Murray AD, editors. Practical Nuclear Medicine. 3rd ed. Springer; 2005.
Cherry SR, Sorenson JA, Phelps ME. Physics in nuclear medicine. 4th ed. Saunders Elsevier; 2012.
Chapter 20
Principles of Positron Emission
Tomography (PET) Scanning
Phei Shan Chuah and Seshadri Nagabhushan
Positron Emission Tomography (PET) is a form of Nuclear Medicine imaging

which uses positron-emitting radionuclides (e.g. carbon, fluorine, gallium).
Positrons react with electrons in tissues of interest to produce two diametrically
opposed gamma photons which are picked up by a ring of detectors in the gantry.
The clinical uses of PET scanning mainly include prostate cancer, but it also plays
a role in metastatic seminoma and urothelial cancer.
Introduction
Positron Emission Tomography (PET) is a form of Nuclear Medicine imaging

which uses positron-emitting radionuclides rather than the gamma-emitting radio-
nuclides used in conventional planar and single photon emission computed tomog-
raphy (SPECT).
PET Radionuclides
There are several radionuclides which are suitable for PET. Many have half-lives of
minutes rather than hours and require production using a cyclotron. For such radio-
nuclides, rapid radiochemistry must be followed by imaging using a PET scanner
on the same site as the cyclotron. However, centres remote from cyclotrons can be
P. S. Chuah · S. Nagabhushan (*)

Department of Nuclear Medicine, Liverpool University Hospitals NHS Foundation Trust,
Liverpool, UK
e-mail: pheishan.chuah@liverpoolft.nhs.uk; nagabhushan.seshadri@liverpoolft.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_20
122 P. S. Chuah and S. Nagabhushan
Table 20.1 Physical properties of positron-emitting radionuclides

Positron-emitting radionuclide Half-life Positron energy (MeV) Production method
Carbon-11 20 mins 0.96 Cyclotron
Nitrogen-13 10 mins 1.19 Cyclotron
Oxygen-15 2 mins 1.74 Cyclotron
Fluorine-18 110 mins 0.63 Cyclotron
Gallium-68 68 mins 1.83 Generator (Ge-68)
Rubidium-82 76 s 3.15 Generator (Sr-82)
supplied with isotopes which have longer half-lives, such as Fluorine-18 (half-
life = 110 mins), or can be eluted from a generator, such as Gallium-68 (half-
life = 68 mins, eluted from a Germanium-68 generator).
The same rationale in selecting an appropriate radionuclide for conventional
nuclear medicine imaging applies to PET radionuclides. One of the advantages of
PET is that the positron-emitting isotopes such as Carbon, Nitrogen, Oxygen and
Fluorine can be directly substituted into molecules that occur naturally in the body
(e.g. Fluorine can replace Hydrogen). This produces PET radiotracers that are exact
positron-emitting analogues of the molecule that is being imaged, and such a radio-
tracer can be reliably assumed to behave in exactly the same way.
PET radiotracers can be used to study a wide range of physiological and patho-
logical processes. The most commonly used radiotracer in clinical practice is
18
F-labelled fluoro-deoxyglucose (18F-FDG). This is an analogue of glucose, which
is trapped within cells following phosphorylation by hexokinase. It is widely used
in oncology imaging as more glucose is required by anaerobic glycolysis within
tumours than aerobic glycolysis in normal tissue, so pronounced FDG uptake is
seen in many tumour types, leading to images with good contrast between malig-
nant and benign structures (Table 20.1).
The Physics of PET Scanning
When a PET radiotracer is injected into the patient, it is absorbed by the body and
accumulates within the tissues of interest. As the radiotracer decays, it emits a posi-
tron, which travels a short distance before annihilating with an electron in the sur-
rounding tissue to produce two back-to-back 511 keV gamma photons. These
gamma rays are then detected by a ring of detectors surrounding the patient in the
PET scanner. This is called ‘in coincidence’ (Fig. 20.1). The positron is assumed to
have met the electron somewhere along the ‘line of response’ defined by the coinci-
dent gamma rays. Millions of these lines of response are recorded in a typical PET
scan and then reconstructed to map out the 3D distribution of the positron-emitting
radionuclide within the body. This process is called ‘annihilation coincidence detec-
tion’ which serves as the basis of PET imaging.
Annihilation coincidence detection significantly increases the sensitivity of PET
compared to conventional SPECT. The spatial resolution of PET is around 5–8 mm
compared to SPECT which is around 8–12 mm.
20 Principles of Positron Emission Tomography (PET) Scanning 123
511 keV gamma
Radioisotope
Positron
Electron Coincidence
Unit
511 keV gamma
Fig. 20.1 Annihilation and coincidence detection
PET Scanners in Clinical Practice
Stand-alone PET scanners have largely been superseded by modern hybrid PET-CT
scanners. The combination of PET and CT scanners in one unit, allows accurate
alignment of functional information from PET and structural information from
CT. Registered PET-CT imaging can precisely identify areas of physiological and
pathological uptake, and thus increase the diagnostic accuracy. CT images are also
used to correct for physical limitations in PET imaging such as attenuation and scat-
ter. A modern PET-CT scanner is shown in Fig. 20.2. The bore of a PET-CT scanner
like this is approximately a metre long which is longer than a CT scanner but shorter
than an MR scanner.
The use of PET-CT in urology is rapidly expanding due to technical advances of
modern PET-CT scanners and development of new positron-emitting radiopharma-
ceuticals such as 18F-NaF, 18F-choline, 18F-Fluciclovine, 68Ga-PSMA and 18F-PSMA,
in addition to 18F-FDG. One of the challenges of PET-CT in urological disorders is
the biodistribution and physiological urinary excretion of most PET tracers which
can reduce the sensitivity to detect pathology within or around the urinary tract.
Despite this challenge, PET-CT is proven to be useful for staging of locoregional
and distant metastasis (Fig. 20.3), detection of recurrence, evaluation of treatment
response and as a prognostic indicator in urological malignancy.
In addition, PET-CT is increasingly becoming an indispensable tool in theranos-
tics. Theranostics are agents that enable both diagnostic imaging and therapy by
utilising the same specific molecular target. PET-CT is used to identify molecular-
targeted receptors, guide molecular-targeted radionuclide therapy and assess
response to treatment. One example is the use of 18F-PSMA PET-CT or 68Ga-PSMA
PET-CT as pre-therapy and post-therapy imaging for 177Lu-PSMA radionuclide
therapy in patients with metastatic castration resistant prostate cancer.
Fig. 20.2 A modern PET-CT scanner
Fig. 20.3 Maximum

intensity projection (MIP)
image of 18F-PSMA
PET-CT in a patient with
prostate cancer and rising
serum PSA level,
demonstrating multiple
PSMA-avid left iliac chain
nodal metastases (red
arrow)
20 Principles of Positron Emission Tomography (PET) Scanning 125
PET-CT Interpretation and Reporting
In clinical practice, visual assessment of PET-CT images is usually the mainstay of

image interpretation. Quantitative measurement of PET is often utilised to provide
a more objective and accurate evaluation of treatment response and prognostication
while minimising inter-observer variability. Various quantitative measures have
been derived from 18F-FDG PET studies.
Standardised uptake value (SUV) is a semiquantitative measure of tracer uptake
in a region of interest which is normalised to the injected activity and patient’s body
weight. In 18F-FDG PET-CT, activity in a lesion is often expressed in the terms of
SUVmax or the value of the most intense pixel in the region of interest. It is used to
aid the differentiation of benign from malignant processes and assessment of tumour
changes in serial scans. However, care must be taken when interpreting SUVs and
similar measurement from PET scans. Such measurements are much less accurate
for small lesions, particularly those <8 mm in diameter, and are also affected by how
the image is acquired, reconstructed and analysed.
Standardised reporting systems are being developed particularly as PSMA-PET
imaging is becoming widely utilised in the assessment of prostate cancer and suit-
ability of PSMA-directed radioligand therapy. One proposal is the use of structured
reporting of PSMA-RADS which is similar to PI-RADS as used in mp-MRI. It is
organised on 5-point scale with higher scores indicating a higher likelihood of pros-
tate cancer.
The use of molecular imaging PSMA scores (miPSMA) and molecular imaging
TNM (miTNM) has also been proposed. miPSMA is a visual scoring scale of PSMA
expression between 0 and 4 in relation to background activity in blood pool, liver
and parotid gland for each region of interest. Higher score correlates to higher level
of PSMA expression. The final staging is then incorporated into molecular imaging
equivalent of tumour, node and metastasis staging framework (miTNM). Further
work is required to validate these promising standardised reporting systems.
Advances in Molecular Imaging
Combined PET and magnetic resonance imaging (PET-MRI) is an emerging tech-

nology in the field of nuclear medicine. PET-MRI offers superior soft tissue contrast
and simultaneous data acquisition while minimising exposure to ionising radiation.
However, its application in clinical practice is still limited due to higher cost, techni-
cal challenges and complexity in interpreting the PET-MRI studies. Early studies
show 68Ga-PSMA PET-MRI increases diagnostic accuracy for primary staging and
detection of biochemical recurrence of prostate cancer compared to mp-MRI and
PET alone but more studies are required to validate this. The ability of PET-MRI to
provide combined anatomical, functional and molecular information could poten-
tially be the ‘one-stop shop’ diagnostic imaging in the work up of patient with
prostate cancer.
Artificial intelligence (AI) is another growing research field in medical imaging.

Research has focused on the use of AI in the optimisation and interpretation of
hybrid molecular imaging such as PET-CT and PET-MRI.
Further Reading
Tarantola G, Zito F, Gerundini P. PET instrumentation and reconstruction algorithms in whole-

body applications. J Nucl Med. 2003;44:756–69.
Lima M, Camacho M, Carvalheira JBC, et al. The current role of PET/CT in urological malignan-
cies. Clin Transl Imaging. 2020;8:313–47.
Ceci F, Oprea-Lager DE, Emmett L, et al. E-PSMA: the EANM standardized reporting guidelines
v1.0 for PSMA-PET. Eur J Nucl Med Mol Imaging. 2021;48(5):1626–38.
Ehman EC, Johnson GB, Villanueva-Meyer JE, et al. PET/MRI: where might it replace PET/CT?
J Magn Reson Imaging. 2017;46(5):1247–62.
Chapter 21
PET-CT Imaging in Prostate Cancer
Seshadri Nagabhushan and Phei Shan Chuah
The emergence of novel PET radiotracers such as choline and PSMA has had a
significant impact on the management of prostate cancer. Its strength lies in the
detection of disease in patients with biochemical relapse, enabling personalised
treatment planning and guiding metastasis-directed therapy. PET-CT is becoming
increasingly indispensable in the management of prostate cancer. These specific
radiotracers have also opened the door for radioligand therapy.
Positron emission tomography (PET-CT) has proven superior to conventional
imaging in the diagnosis and management of many cancers. The emergence of new
radiotracers has positioned PET-CT as a valuable tool in the evaluation of prostate
cancer, both in initial staging and recurrent disease. In addition to the widely used
18
F-FDG, several PET radiotracers are available such as 18F-NaF, 18F-choline,
18
F-Fluciclovine, 68Ga-PSMA and 18F-PSMA (Table 21.1).
S. Nagabhushan (*) · P. S. Chuah

Department of Nuclear Medicine, Liverpool University Hospitals NHS Foundation Trust,
Liverpool, UK
e-mail: nagabhushan.seshadri@liverpoolft.nhs.uk; pheishan.chuah@liverpoolft.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_21
128 S. Nagabhushan and P. S. Chuah
Table 21.1 Common PET tracers used in clinical practice for prostate cancer imaging
PET radiotracer Target Role in prostate cancer
18
F-FDG Glucose metabolism • Limited role
18
F-sodium fluoride Osteoblastic activity • Detection of osteoblastic bone metastases in
prostate cancer
11
C-choline/18F-choline Cell membrane • High risk prostate cancer staging
synthesis • Restaging in biochemical relapse in prostate
cancer at high PSA levels
68
Ga-PSMA/18F-PSMA Prostate-specific • High risk prostate cancer staging
membrane antigen • Restaging in biochemical relapse in prostate
(PSMA) cancer
• Theranostic eligibility prior to PSMA-
targeted radioligand therapy such as
177
Lu-PSMA or 224Ac-PSMA
18
F-Fluciclovine Amino acids • Restaging in biochemical relapse in prostate
cancer
F-Fluorodeoxyglucose (18F-FDG)
18
18
F-FDG is a glucose analogue and is avidly taken up by cells demonstrating up-
regulation of glycolytic pathway e.g. cancer, inflammation. The utility of 18F-FDG
PET-CT in prostate cancer is somewhat limited. There is variable FDG uptake level in
prostate cancers with significant overlap between benign and malignant tissues, however
it is noted that aggressive prostate cancers (Gleason score >7) often display high FDG
uptake. Its utility in the evaluation of prostate cancers in comparison to conventional
imaging techniques has been superseded by the newer prostate-specific radiotracers.
F-Sodium Fluoride (18F-NaF)

18
18
F-NaF is a PET radiotracer used in the evaluation of osteoblastic bone metastasis.
It has a similar mechanism of action with its gamma emitting radiotracer counter-
part, 99mTc-labeled phosphonates (see Chap. 26). It works by chemisorption of fluo-
rine directly into the surface of bone matrix and converting hydroxyapatite to
fluorapatite. 18F-NaF PET-CT is advantageous over 99mTc-labeled bone scintigraphy
with its shorter scanning time, better image quality, higher spatial resolution and
tumour to background ratio. It more sensitive when compared to SPECT tracers for
the evaluation of bone metastasis.
C-Choline and 18F-Choline

11
Choline is an essential component for the synthesis of the phospholipid cell mem-
brane. It is internalised into the cell and undergoes phosphorylation into phospho-
lipid by the enzyme choline kinase. The overexpression of choline kinase enzyme
21 PET-CT Imaging in Prostate Cancer 129
in prostate cancer serves as the basis for choline-labelled PET imaging. Choline
tracer can be labelled with isotopes such as Carbon-11 (11C-Choline) or Fluorine-18
(18F-Fluroethylcholine and 18F-Fluromethylcholine).
Normal biodistribution is in the salivary glands, liver, spleen, pancreas and vari-
able bowel activity. Normal prostate usually exhibits faint activity, but can be seen
more avidly in prostatitis and benign prostatic hyperplasia.
Choline PET imaging plays a role in the detection of biochemical relapse (BCR).
The sensitivity and specificity of choline PET-CT for all sites of recurrence in
patients with BCR are 86–89 and 89–93% respectively. The positivity detection rate
correlates with the PSA level and PSA doubling time when PSA level is at least
>1–2 ng/ml.
Ga-PSMA and 18F-PSMA

68
Prostate-specific membrane antigen (PSMA) is a type II transmembrane protein

which is expressed on the membrane of prostatic epithelial cells. Overexpression of
PSMA in prostate cancer by 100–1000 times more than normal tissue makes PSMA
a desirable tracer. Its expression is associated with higher Gleason score and andro-
gen independence.
It can be labelled with Fluorine-18 (18F-PSMA) or Gallium-68 (68Ga-PSMA).
Although 68Ga-PSMA offers on-site radiopharmaceutical production, 18F-PSMA
shows lower urinary excretion which makes it more favourable in the assessment
lesions close to the urinary tract.
Normal physiological activity is seen in lacrimal and salivary glands, liver,
spleen, kidneys, and intestine. An important pitfall of PSMA PET imaging is the
physiological ganglionic uptake which may be misinterpreted as nodal metastasis.
The clinical application of PSMA PET imaging includes primary staging of high
risk prostate cancer. 68Ga-PSMA PET is more sensitive in detection of nodal and
distant metastasis compared to conventional imaging (CT and bone scan).
PSMA PET imaging is also useful in the identification of metastasis in patients
with BCR when serum PSA level is very low (>0.2 ng/l). The detection rate increases
with serum PSA level. Identification of lymph node metastasis <8 mm and bone
metastasis are feasible on PSMA PET imaging (Figs. 21.1 and 21.2). Both 18F-PSMA
and 68Ga-PSMA have comparable detection rates in patients with BCR disease and
has a positive predictive value of 92 and 87% respectively (Table 21.2). PSMA PET
is superior to other radiotracers such as choline and fluociclovine.
130 S. Nagabhushan and P. S. Chuah
Fig. 21.1 Axial CT and fused PET-CT images of 68Ga-PSMA study in a patient with BCR dem-
onstrating PSMA-avid subcentimetre metastatic nodes in left pelvic wall and right pre-sacral
region (arrow)
Fig. 21.2 Axial CT and fused PET-CT images of Ga68-PSMA study in a patient with BCR dem-
onstrating PSMA-avid bone metastasis in left T2 vertebral body
Table 21.2 Positive Serum PSA level Ga-PSMA (%)

68
F-PSMA (%)
18
detection rate between

0.2–0.49 45 62
68
Ga-PSMA and 18F-PSMA
in relation to PSA 0.5–0.99 59 75
1–1.99 75 91
>2 95 94
21 PET-CT Imaging in Prostate Cancer 131
F-Fluciclovine
18
18
F-Fluciclovine is a radiolabelled synthetic amino acid that is taken up into cells by
transporters (LAT-1 and ASCT2) which are present in high numbers in prostate
cancer cells. The short uptake period for 18F-fluciclovine allows scans to be done
3–5 min after administration, compared with alternative PET tracers, which need
about 1 h for optimal uptake. 18F-Fluciclovine PET-CT can detect recurrence at low
serum PSA levels (<1 ng/ml). Detection rates improve with increasing PSA levels.
18
F-fluciclovine is superior to 11C-choline but inferior to 68Ga-PSMA in detecting
biochemical recurrence.
PSMA-PET Guided Targeted Radioligand Therapy (RLT)
Theranostics is an emerging concept which allows both diagnosis and treatment of

a specific molecular-targeted disease by altering the radioactive isotope. For exam-
ple, 68Ga and 18F are diagnostic positron-emitting radioisotopes. However, these can
be exchanged for therapeutic radioisotopes such as the beta-emitting
Lutetium-177(177Lu), alpha-emitting Actinium-225 (225Ac) and Bismuth-213 (123Bi).
This theranostic concept can be applied to the PSMA molecule. Patients will first
undergo PSMA-labelled PET imaging to ensure adequate uptake of PSMA-ligands,
followed by PSMA-RLT such as 177Lu-PSMA. This has shown improved overall
survival in patients with castrate resistant prostate cancer and offers a new avenue
of treatment for prostate cancer patients.
Further Reading
Mottet N, Conford P, van den Bergh RCN, Briers E, De Santis M, Fanti S, et al. EAU-EANM-
ESTRO-ESUR-SIOG guidelines on prostate cancer. Eur Assoc Urol. 2022;
De Galiza BF, Queiroz MA, Nunes RF, Costa LB, Zaniboni EC, Marin JFG, et al. Nonprostatic dis-
eases on PSMA PET imaging: a spectrum of benign and malignant findings. Cancer Imaging.
2020;20(1):1–23.
Wang R, Shen G, Huang M, Tian R. The diagnostic role of 18F-choline, 18F-Fluciclovine and
18F-PSMA PET/CT in the detection of prostate cancer with biochemical recurrence: a meta-
analysis. Front Oncol. 2021;17:11.
Perera M, Papa N, Roberts M, Williams M, Udovicich C, Vela I, et al. Gallium-68 prostate-specific
membrane antigen positron emission tomography in advanced prostate cancer—updated diag-
nostic utility, sensitivity, specificity, and distribution of prostate-specific membrane antigen-
avid lesions: a systematic review and meta. Eur Urol. 2020;77(4):403–17.
Chapter 22
Understanding the Renogram: How It’s
Done and How to Interpret It
The renogram is a dynamic nuclear medicine study used to investigate kidney perfu-
sion, function and elimination of tracer. This chapter describes how the renogram is
performed and how the result can be interpreted.
Indications
Isotope renography can be used for the assessment of renal perfusion, relative func-
tion, assessment of kidney drainage and as an indicator of the presence of reflux.
99m
Tc DTPA (diethylene-triamine-pentaacetic acid, alternatively known as pentetate).
In the UK the administered activity for an adult can be up to 300 MBq but 200 MBq is
commonly used. DTPA is cleared solely by glomerular filtration and so kidney
uptake is low and blood background remains high. This makes background subtrac-
tion more difficult, particularly in children or patients with poor kidney function.
99m
Tc MAG3 (mercaptoacetyl-triglycine, alternatively known as mertiatide).
In the UK the administered activity for an adult can be up to 100 MBq but 50 MBq
is sufficient to give a good renogram. MAG3 is cleared by a combination of glo-
R. Sajjan · M. Prescott (*)

e-mail: rakesh.sajjan@mft.nhs.uk; mary.prescott@alumni.manchester.ac.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_22
134 R. Sajjan and M. Prescott
merular filtration and tubular secretion, so it has greater kidney uptake leaving
less in the blood background. It is therefore the preferred radiopharmaceutical,
particularly in cases of poor function.
The administered activity of either radiopharmaceutical is reduced according to
age and body weight for children.
Patient Preparation
The patient must be well hydrated. Drinking 300–500 ml of water shortly before the
test is recommended.
Data Acquisition
A gamma camera fitted with a low energy high sensitivity (LEHS) or low energy
general purpose (LEGP) collimator is used to give adequate counts because good
resolution is not needed (see Chap. 19). The patient is positioned either seated with
their back to the camera (to aid normal gravitational drainage) or supine on the
couch with the camera underneath. If the patient has a horseshoe kidney or asym-
metrical positioning of the kidneys, simultaneous acquisition of anterior and poste-
rior supine renograms on a dual headed camera is preferred if possible. The
radiopharmaceutical is injected and immediately the gamma camera starts acquir-
ing a dynamic series of images with one frame every 20 s for 30 to 40 min. If the
kidney has not drained by 40 min, and the renogram was acquired supine, the patient
is asked to stand up and a final static image is acquired. Then the patient empties
their bladder and a post-micturition image is acquired.
If reflux is of concern, at the end of the renogram, instead of the patient leaving
the room to void, an indirect micturating cystogram can be performed by acquiring
a further dynamic study as the patient micturates with their back to the gamma camera.
Computer Data Analysis
On the computer images of the dynamic series, regions of interest are drawn around
each kidney and one or more suitable background regions (Fig. 22.1). Activity-time
curves are created showing how the activity in each region of interest changes with
time. The background curve(s) are used to subtract a background contribution from
each kidney curve. The resulting curve is the renogram. For consistency of display,
it is helpful to scale each kidney curve to percent of administered activity.
22 Understanding the Renogram: How It’s Done and How to Interpret It 135
The relative function of each kidney is calculated from the uptake phase of the
renogram (about 1–3 min). There are several ways of doing this. The Rutland plot
(also known as the Patlak plot) is generally regarded as the most accurate.
However, if the kidneys are asymmetrically positioned, unless simultaneous
anterior and posterior renogram can be acquired with a dual headed camera, a
DMSA scan with geometric mean calculation may be more appropriate for relative
function (see Chap. 24).
Figure 22.1 shows an example of a renogram display showing a sequence of
5 min summed images, the regions of interest used and the derived renogram curves
and calculated relative function.
Analysis of additional regions taken over the periphery of the renal parenchyma
can be used to calculate parenchymal mean transit times. This requires higher
administered activity and care must be taken to exclude analysis of the activity in
the collecting systems, to prevent erroneous results.
5 min 10 min 15 min 20 min
Left Kidney Right Kidney Bladder
15
RF 2min 3min
Left Kidney 80% 6.4% 9.1%
Right Kidney 20% 1.6% 2.3%
10
% dose
0
0 10 20 30 40
minutes
Fig. 22.1 A typical renogram result

Interpretation of the Result
The vascular phase, occurring in the first few seconds after injection, represents a
rapid flow of radiopharmaceutical into the kidney. Most of this is not extracted (par-
ticularly with DTPA) so it remains in the blood within the kidney. Therefore, if
background subtraction is done correctly, this phase should be removed from the
generated renogram curve which should rise smoothly from the origin. From about
1 min onwards the renogram curve rises at a rate proportional to kidney function
and represents the uptake phase.
At any time after about 3 min the renogram curve may reach a peak and begin to
fall in the elimination phase. It is important to realise that this is actually a balance
between uptake and elimination. A rising curve means that uptake exceeds elimina-
tion and a falling curve means that elimination exceeds uptake. A horizontal curve
simply means that uptake and elimination are just balanced. Figure 22.1 shows a
normal renogram for the left kidney (solid blue curve) with normal uptake and nor-
mal elimination. The right kidney (red dashed curve) has less uptake (as indicated
by its less steep rise) and poor elimination (indicated by its continued rise).
Inspection of the dynamic images may indicate whether the parenchyma is drain-
ing into the renal pelvis. If parenchymal transit times are calculated, then a pro-
longed transit time can be used to infer an obstructed system.
Reflux may be seen as a sudden increase in the kidney curve, either during the
renogram or during the micturating cystogram study. However patient movement
must be excluded as a possible cause, which can be done by inspecting a dynamic
display of the images.
The effect of gravity and full bladder on kidney emptying can be determined by
comparing the final static images with those at the end of the dynamic study.
Assessment of Renal Perfusion
If an assessment of renal perfusion is required, then a ‘first pass’ (or first circulation)
study may be incorporated into the renogram. The administered activity is increased
(to 200 MBq 99mTc MAG3 or up to 800 MBq 99mTc DTPA) and the first minute of
the study is acquired at a faster rate of 1 frame per second. Delays in perfusion to
one kidney can be seen by examination of these first pass images. Relative perfusion
can be estimated from the un-subtracted kidney curves during the first minute.
Side Effects of Renography
Anaphylactic reactions to MAG3 have been reported but are extremely rare. Mild
vaso-vagal reactions are possible. Allergic and vaso-vagal reactions to DTPA have
been reported in isolated cases.
22 Understanding the Renogram: How It’s Done and How to Interpret It 137
As with any investigation involving ionising radiation the risk benefit must be
considered. The effective dose from 50 MBq 99mTc MAG 3 is in the region of
0.3 mSv which equates to approximately 2 months of the average natural back-
ground radiation in the UK.
Further Reading
British Nuclear Medicine Society. Dynamic renal radionuclide studies (renography). Clinical
Guidelines. https://www.bnms.org.uk/page/BNMSClinicalGuidelines.
Cook GJR, Maisey MN, Britton KE, Chengazi V, editors. Clinical nuclear medicine. fourth ed.
London: Edward Arnold; 2006.
Chapter 23
The Diuresis Renogram: How It’s Done
and How to Interpret It
The diuresis renogram is just a variant of the standard renogram (see Chap. 22) in
which urine flow rate is increased by administration of a diuretic.
Indications
Diuresis renography is used in the assessment of possible renal drainage impair-

ment and to follow up the outcome from surgical intervention for a previously
obstructed renal system. It can also be used for relative function estimation.
The same radiopharmaceuticals are used as for standard renography (see Chap. 22).
Patient Preparation
The patient must be well hydrated. They should drink 300–500 ml (5–10 ml/kg) of
water prior to the test. They should empty their bladder immediately before the test,
unless the effect of a full bladder and its subsequent emptying is to be assessed.


Switzerland AG 2023
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Data Acquisition
Data is acquired as for a standard renogram (Chap. 22), except that a diuretic is
administered.
If one or both kidneys have not emptied satisfactorily by 20 min after the start of
the renogram, then furosemide may be given IV at a dose of 0.5 mg/kg up to 40 mg
for an adult. This is known as “F + 20”. Data acquisition should continue for at least
another 20 minutes.
If a previous renogram has shown an equivocal response to an F + 20 diuresis,
then a maximum diuretic response can be obtained by the administration of furose-
mide 15 min before the start of the renogram (“F-15”).
The F-15 protocol is used as the primary investigation of a suspected obstructed
system in some centres, although it may be better to start with a standard renogram
in order to assess kidney drainage under normal flow rates before moving on to the
F-15 modification.
If venous access is difficult (for example in children) then furosemide may be
given immediately before the radioactive tracer through the same cannula (“F + 0”).
The data is analysed in the same way as for a standard renogram (Chap. 22).
Interpretation of the Results
If the kidney has a dilated pelvis, then the renogram curve will take a long time to
fall, but on its own this does not distinguish whether the system is a high pressure
(obstructed) system or a low pressure (non-obstructed) one. The response to furose-
mide can help to make the distinction between these two findings.
If an F + 20 renogram is performed and the curve continues to rise, or remains
flat, after furosemide, this represents an obstructed pattern indicative of a high-
pressure system (Fig. 23.1a). If the renogram curve falls rapidly 3 min after furose-
mide, this represents a hypotonic response indicative of a low-pressure,
non-obstructed system (Fig. 23.1b). Should the renogram curve only fall slowly
after furosemide, with loss of concavity in the curve, this represents an equivocal
response (Fig. 23.1c). In this case an F-15 study may be helpful to clarify the result.
If the renogram curve initially starts to fall after furosemide but then begins to rise
again after a few minutes this is known as Homsy’s sign (Fig. 23.1d). It is indicative
of intermittent obstruction which only occurs at high urine flow rates. In these cases
an F-15 renogram will probably appear obstructed.
23 The Diuresis Renogram: How It’s Done and How to Interpret It 141
a
Activity Furosemide b Furosemide
Activity
Obstructed pattern
High pressure system Hypotonic
Low pressure system
0 10 20 30 40 min 0 10 20 30 40 min
c Furosemide d
Furosemide
Activity
Activity
Homsy’ signs
Equivocal response
Obstructed at
Uncertain
high flow
0 10 20 30 40 min 0 10 20 30 40 min
Fig. 23.1 (a to d) The renogram curves that might be seen following furosemide given 20 min
after the radiopharmaceutical
a b
Activity
Activity
Not
Obstructed obstructed
Furosemide Furosemide
at high flow
–15 min 0 10 20 min –15 min 0 10 20 min
Fig. 23.2 (a & b) The renogram curves that might be seen when furosemide was given 15 min
before the radiopharmaceutical
When an F-15 renogram is performed the kidney will have obtained maximum
diuresis by the time the renogram is started. If the renogram continues to rise this
indicates obstruction at high flow (Fig. 23.2a). It gives no indication about how the
kidney handles fluid at normal urine flow. But should the tracer be excreted then the
kidney is not obstructed (Fig. 23.2b).
Limitations
If kidney function is poor the response to furosemide will be impaired, so the ade-
quacy of diuretic response must be judged in relation to uptake. In cases of very
poor function it may not be possible to say whether or not the kidney is obstructed.
Side Effects and Complications
The side effects of MAG 3 and DTPA are the same as for the standard renogram.
The radiation dose is similar.
Contraindications to furosemide, its cautions, side effects and interactions, are
the same as for its clinical use. Amongst these the British National Formulary (BNF)
lists tinnitus and deafness as side effects with unknown frequency after large doses
of furosemide given rapidly. However, it suggests that single doses of up to 80 mg
may be given.
Furosemide can induce renal pain in an obstructed system and this may require
urgent treatment. Equally, there is a theoretical risk of urine leakage from the uri-
nary tract in diuresis renography if the kidney has been operated on recently and is
still obstructed.
If the patient is unable to produce a vasoconstrictive adaptive response due to
other medication, then the rapid loss of fluid as a consequence of diuretic adminis-
tration can induce hypotension, although this is also rare if the patient is well
hydrated as preparation for the study.
The diuresis itself is the effect that troubles the patient the most, especially if
they have any problems with retention, frequency or urgency.
Further Reading1
The SNMMI and EANM procedural guidelines for diuresis renography in infants and children.
https://jnm.snmjournals.org/content/59/10/1636.
British national formulary. https://bnf.nice.org.uk/drugs/furosemide/.
1
See also the further reading suggested in Chap. 22.
Chapter 24
Understanding the DMSA Scan: How It’s
Done and How to Interpret It
A DMSA scan is a static nuclear medicine study that indicates functioning renal
tubular mass. It can be used to detect renal parenchymal abnormalities and to mea-
sure relative kidney function. This chapter describes how the DMSA scan is per-
formed and how the result can be interpreted.
Indications
The principal use of a DMSA scan is for the detection of renal scarring following a
urinary tract infection (UTI) in children. NICE guidelines for urinary tract infec-
tions in infants and children under 16 recommend that scans should not be per-
formed until 4–6 months after the UTI as, in the acute phase, parenchymal defects
may be seen which may heal with time and do not represent true scarring. It can also
be used in the measurement of relative kidney function, particularly when kidneys
may lie at different depths in the patient, such as horseshoe or ectopic kidneys, for
the localisation of a very small poorly functioning kidney and to evaluate functional
capacity following renal trauma or when embolization, or removal, of a kidney is
being considered.


Switzerland AG 2023
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Radiopharmaceutical
99m
Tc DMSA (di-mercapto-succinic acid, alternatively known as succimer) is a
gamma emitting radiopharmaceutical (see Chap. 18) that binds to the proximal con-
voluted tubule. After intravenous injection DMSA accumulates slowly in the renal
cortex and only a small amount is excreted in the urine. The administered activity in
the UK is normally 80 MBq for adults, scaled down appropriately for children.
After administration the patient waits for between 2 and 4 h to allow time for suffi-
cient cortical uptake before imaging.
Data Acquisition
A gamma camera fitted with a Low Energy High resolution (LEHR) collimator is
used to get the best resolution (see Chap. 19) and the patient is positioned supine on
an imaging couch with their back as close as possible to the collimator. Static views
are obtained of the kidneys from posterior, anterior, left posterior oblique and right
posterior oblique projections. Each view should contain 200,000–500,000 counts
which will take about 5 min. The anterior view may be omitted in small children if
they cannot tolerate the gamma camera detector in front of their face.
Single-photon emission computed tomography (SPECT), possibly combined
with CT (SPECT-CT) (see Chap. 19), may be useful in some cases, for example
following trauma or to detect smaller lesions, or to assess function of an area of a
kidney when a partial nephrectomy is contemplated.
On the computer, regions of interest are drawn round each kidney on the posterior
view, together with a nearby background region. The counts in each kidney region
are determined and background counts are subtracted after allowing for differences
in region size. The relative function of each kidney is calculated from the percentage
that it contributes to the total counts. Regions of interest are also drawn on the ante-
rior view and the relative function is calculated in the same way. The geometric
mean of the kidney counts from the posterior and anterior views is calculated, where:
Geometric Mean Count = Posterior Count × Anterior Count
The relative function is calculated using the geometric mean counts for left and
right kidneys. This compensates for any possible differences in kidney depth.
24 Understanding the DMSA Scan: How It’s Done and How to Interpret It 145
Both kidneys should be examined on all views to determine any areas of reduced
uptake, sometimes called ‘photopenic’ areas, indicating cortical loss. The anterior
view will be too far away from the camera, and the resolution too poor, to detect
small focal abnormalities unless the kidneys are mal-positioned or have a horseshoe
configuration. Figure 24.1 shows a DMSA scan showing photopenic (‘cold’) areas
in the upper and lower poles of the right kidney consistent with scarring. This is
most evident on the posterior and oblique images.
If the relative function determined from the posterior and anterior views differ,
this indicates that the two kidneys lie at different depths in the patient. In this situa-
tion the relative function calculated from the geometric mean count gives the best
estimate of the true relative function (see Fig. 24.1). However, in cases of poor
L R R L
Post Ant
L R L R
LPO RPO
Relative Function Left Right
Posterior view 71% 29%
Anterior view 61% 39%
Geometric mean 66% 34%
Fig. 24.1 DMSA scan showing photopenic areas in the upper and lower poles of the right kidney
function it may be difficult to assess the background counts on the anterior image,
so the geometric mean calculation may not be accurate. In such cases it may be
necessary to use the posterior image only for relative renal function calculation.
Side Effects
Allergic reactions to DMSA have been reported but are rare.

considered. The effective dose from 80 MBq 99mTc DMSA is in the region of
0.7 mSv which equates to approximately 4 months of the average natural back-
ground radiation in the UK.
Further Reading
EANM Guidelines on 99mTc DMSA scintigraphy in children. https://eanm.org/publications/

guidelines/gl_paed_dmsa_scin.pdf.
Cook GJR, Maisey MN, Britton KE, Chengazi V, editors. Clinical nuclear medicine. fourth ed.
London: Edward Arnold; 2006.
Chapter 25
How to Do a Radioisotope Glomerular
Filtration Rate Study
Sarah Sargant and Richard Lawson
Glomerular filtration rate can be determined using an injection of 99mTc-DTPA fol-

lowed by multiple blood samples. There is also a method using only a single blood
sample. Both methods are described in this chapter and interpretation of the results
explained.
Glomerular filtration rate (GFR) can be measured by the clearance of any tracer
that passes through the kidneys and is processed solely by glomerular filtration.
Nuclear medicine is ideally suited to this application because it can use minute
tracer quantities of radiopharmaceuticals which do not disturb kidney function and
give a very low radiation dose (see Chap. 18).
Radioisotopic GFR involves blood sampling alone, and samples are usually
taken within 6 h of injection. This is quicker, more reliable, and generally preferable
to a 24 h urine collection required for creatinine clearance measurements. It is also
more accurate than eGFR (estimated GFR) which is based solely on a serum creati-
nine measurement.
There are two methods described in this chapter:
• The slope intercept method, which requires four blood samples to be taken fol-
lowing administration of the radioisotope. This method was previously accepted
as the best way to calculate GFR, and was recommended in the 2004 clinical
guidelines from the British Nuclear Medicine Society (BNMS).
• The single sample method, which has recently been accepted by the nuclear
medicine community as providing a robust measure of GFR with a reduction in
workload for the clinical department providing the test. It is the method currently
recommended for most patients in the BNMS clinical guidelines.
S. Sargant · R. Lawson (*)

e-mail: sarah.woods2@mft.nhs.uk; richard.lawson@physics.org

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_25
148 S. Sargant and R. Lawson
Both slope intercept and single sample methods require very careful and consis-
tent technique which comes from having well trained staff and quality control mea-
sures at each stage of the procedure.
Indications
There are many reasons why an accurate measure of a patient’s renal function is
required.
• Long term monitoring of renal function in patients with kidney disease
• Assessment of live donors for both kidney and liver transplants
• Dose calculation for the delivery of nephrotoxic drugs, for example carboplatin
based chemotherapy
GFR gives a value for total renal clearance, so if individual kidney function is
required for a particular patient, this will require additional imaging using either a
renogram (see Chap. 22) or a DMSA scan (see Chap. 24) to determine relative func-
tion of each kidney.
Radiopharmaceutical
99m
Tc DTPA (diethylne-triamine-pentaacetic acid) is the radiopharmaceutical of
choice for nuclear medicine GFR studies. 99mTc is readily available in nuclear medi-
cine departments, and sample counting equipment is well suited to detect its emis-
sions with high sensitivity (see Chap. 19).
In the UK the usual administered activity of 99mTc DTPA for GFR studies is
10 MBq, with lower activities being prescribed to paediatric patients. The effective
dose to a patient receiving 10 MBq of 99mTc DTPA is 0.05 mSv, which is approxi-
mately equivalent to 1 week of natural background radiation in the UK.
Preparation
The patient should avoid high protein meals, excessive caffeine and strenuous exer-
cise immediately before and during the test. They should maintain normal hydration
during the study. The patient’s height and weight must be recorded.
The arm with the worse venous access (of particular relevance to patients close
to end stage renal failure) should be used for administration of the radiopharmaceu-
tical, leaving the best access for blood samples to be taken throughout the test with-
out any risk of radioactive contamination of the samples.
If the patient has had previous nuclear medicine studies, the likelihood of any
residual activity being present in the blood should be considered prior to starting the
25 How to Do a Radioisotope Glomerular Filtration Rate Study 149
test. A background blood sample may be taken if it seems likely that there will be
measurable activity in the blood.
Procedure
A vial of 99mTc DTPA is prepared in a radiopharmacy. This vial is used to prepare

both a standard (a known activity diluted in a known volume, usually 1000 ml) and
the dose for the patient. The dose is administered through intravenous injection. The
injection site is checked for extravasation, as if the whole dose is not delivered to the
bloodstream the results of the GFR will be incorrect. Blood samples are taken from
the opposite arm to avoid contamination in the samples. The samples are centri-
fuged and the activity in the plasma is measured in a sample counter.
Slope Intercept Method
Blood samples are taken at 2, 3, 4, and 5 h post injection. The clearance of tracer
from plasma follows a bi-exponential decay. After 2 h sufficient time has passed
since the administration to allow tracer to be completely mixed in the extracellular
fluid, so the clearance then approximates closely to a single exponential.
A graph is plotted of plasma counts against time since injection and this is fitted
to an exponential curve. The curve is extrapolated back to time zero and the inter-
cept is compared with the diluted standard counts to determine the initial volume of
dilution in the patient. The slope of the exponential fit gives the rate constant for
clearance of tracer through the kidneys.
Multiplying the rate constant by the volume of dilution gives an estimate of the
GFR based on this single exponential analysis. Then a bi-exponential correction
factor is applied to allow for the fact that because samples are not taken before 2 h
the early exponential is missed.
Single Sample Method
A single blood sample is taken at the appropriate time for the expected result
(between 2 and 6 h post injection). Patients who are anticipated to have a good GFR
will have their samples taken earlier, while patients who are anticipated to have a
poor GFR will have their samples taken later. The concentration of tracer in the
sample is used to determine GFR using a regression equation determined from a
large number of previous patient studies (Table 25.1).
The use of a single sample for GFR calculation has been shown to be robust and
give the same results as the slope intercept method described above, while decreas-
ing the workload for the nuclear medicine department performing the test.
150 S. Sargant and R. Lawson
Table 25.1 Expected result at Expected result (ml/min/1.73m2) Sample time

sample time using the single
Above 100 2h
sample method of GFR
estimation 70–100 3h
50–70 4h
25–50 6h
Below 25 24 h
Choice of Method
The slope intercept method gives more opportunity for consistency checks between
the four samples. The single sample method relies on taking the sample at the opti-
mal time and this requires having a reasonable idea of the expected GFR before-
hand. In patients who have pronounced muscle mass or cachexia the eGFR is likely
to be inaccurate so a slope intercept method is recommended. If a patient’s expected
GFR is completely unknown they will still require the slope intercept method, as the
optimal time for taking the blood sample will also be unknown.
Slope intercept and single sample methods are appropriate for many patients
requiring a GFR, but are not suitable for every case. Patients who have an expected
GFR of less than 25 ml/min/1.73m2 are more suited to the Gref & Karp 24 h single
sample method. Patients who have ascites, oedema, or another extracellular space
are more suited to the Wickham four sample method. More details are available in
the BNMS clinical guidelines [2].
Figure 25.1 shows an example of a typical result. After application of the bi-
exponential correction the normalised GFR corrected for body surface area is 94 ml/
min/1.73m2. This is an accurate measure of the patients normalised GFR which may
be compared with normal values for the patient’s age. Limits on the normalised
GFR exist for determining if it is safe for a particular patient to donate a kidney.
With the bi-exponential correction applied the absolute GFR for this patient is
100 ml/min. This is an accurate measure of the patient’s absolute renal clearance
without normalisation for their size. This figure may be used for chemotherapy dos-
ing schedules. The corrected volume of dilution, 13.6 l in this example, is approxi-
mately the patient’s extra-cellular fluid volume.
For this patient the single sample estimate, based just on the 3 h sample, agrees
with the slope intercept method.
25 How to Do a Radioisotope Glomerular Filtration Rate Study 151
GFR determination by 99m-Tc DTPA clearance

Test Patient Dose and Standard
Date 01/01/2020 Name Dose Standard
DTPA batch ID Weight full 4.8338 4.3690
DTPA activity (MBq) 117 DOB 01/01/1984 Weight empty 3.9918 3.8669
DTPA volume (mI) 8 Sex Male Net weight 0.8420 0.5021
DTPA reference time 06:30 Weight 70 Activity check 8.19 4.89
Counting time (min) 5 Height 170 DS Ratio 1.6770
Standard Dilution 1000 eGFR 70 to 100
Blood samples Date Time Counts Volume Time since Conc. E Time Included
(dd/mm/yyyy) (hh:mm) (cpm) (mI) injection (cpm/ml) (mins) in fit
Background blood 0.0
Injection 01/01/2020 10:02:00
Counted 01/01/2020 16:34:00
Standard 1 201250 2.0 5.3
Average: 215715.9
Standard 2 198700 2.0 10.8
First blood sample 12:02:00 8450 2.0 120 9248.8 16.1 Yes
Second blood sample 13:02:00 5320 2.0 180 5880.2 21.5 Yes
Third blood sample 14:02:00 3500 2.0 240 3905.0 26.8 Yes
Fourth blood sample 15:02:00 2170 2.0 300 2442.3 32.1 Yes
Background 8 8.3 37.4
Fitting Fit probability: 0.15 Good fit

Intercept: 22250 cpm/ml
Half time: 95 mins
100000
10000
Concentration (cpm/ml)
1000
100
10
0 50 100 150 200 250 300 350
Time (min)
Volume of dilution: 16.3 litres Body surface area: 1.83

Corrected volume of dilution: 13.6 litres (Normal is 11.0 to 18.3)
ECV/BSA: 11.6 I./1.73sq.m. (Normal range 10.5 to 16.5)
GFR Normalised for body surface area

Single exponential 119 ml/min 113 ml/min/1.73sq.m.
Bi-exponential 100 ml/min 94 ml/min/1.73sq.m.
Estimated uncertainty +/- 2 ml/min +/- 2 ml/min/1.73sq.m.
Single sample 99 ml/min 94 ml/min/1.73sq.m.
Normal GFR for age 36 years is 103 ml/min/1.73sq.m. (Range 78 to 128)
Fig. 25.1 Example of a GFR result
Further Reading
Fleming JS, Zivanovic MA, Blake GM, Burniston M, Cosgriff PS. Guidelines for the measurement
of glomerular filtration rate using plasma sampling. Nucl Med Commun. 2004;25:759–69.
Burniston M. Clinical guidelines for the measurement of glomerular filtration rate (GFR) using
plasma sampling. British Nuclear Medicine Society; 2018. http://www.bnms.org.uk.
Chapter 26
Understanding the Radionuclide
Bone Scan: How It’s Done and How
To Interpret It
A nuclear medicine bone scan is a useful test for detecting areas of abnormal bone
metabolism. This chapter is about the most common method, using a gamma cam-
era and 99mTc radiopharmaceuticals (see Chap. 19). It is also possible to use a PET
CT scanner with 18F Fluoride for bone imaging (see Chaps. 20 and 21). The PET CT
scan is more sensitive for bone metastases but is not as widely available.
Indications in Urology
Identification of bone metastases in malignancies that are known to metastasise to

bone such as prostate cancer. It is also useful in monitoring progression of bone
metastases and their response to treatment.
99m
Tc MDP (methylene-diphosphonate, also known as medronate) or 99mTc HDP
(hydroxyethylene-diphosphonate, also known as oxidronate) are the most com-
monly used radiopharamaceuticals. The usual administered activity in the UK is
600 MBq for planar imaging; this can be increased to 800 MBq for SPECT (see
Chap. 19). Both radiopharmaceuticals are taken up by areas with osteoblastic activ-
ity, so the distribution shows normal bone as well as areas of abnormal bone


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metabolism which occur around metastases, particularly the sclerotic ones seen in
prostate cancer. They are excreted in the urine so the kidneys and bladder will also
be seen on the images.
Patient Preparation
The patient should be well hydrated and encouraged to void frequently once the
radiopharmaceutical has been administered. This will reduce the radiation dose the
patient is exposed to and also improves image quality. The patient should empty
their bladder before the third phase images.
If pain from metastases is a significant factor, then pain relief should be pre-
scribed and given prior to the scan; the patient will have to lie supine for up to
40 min on the imaging couch.
Multi-Phase Data Acquisition
First phase (optional). A dynamic study may be acquired at 1 image per second for
the first minute following radiopharmaceutical injection in order to demonstrate
blood flow. This is only required when the vascularity of a lesion is to be investi-
gated, and is probably not necessary for identification of bone metastases.
Second phase (optional). A static 1 min image may be acquired immediately
after the first phase images, to demonstrate blood pool. This is also only required
when a lesion’s vascularity is of interest, so it is not usually performed when imag-
ing for the distribution of boney metastases.
Third phase (required). Three hours after injection images showing bone metab-
olism are acquired using one or more of the following techniques:
Whole body image in which the camera slowly moves along the length of the
patient, taking up to 20 minutes to produce a whole-body scan depending on the
capabilities of the camera used. Both anterior and posterior views are usually
produced; with a double headed gamma camera these can be acquired simultane-
ously. These images give an overview of activity in the whole skeleton and can
be useful for identifying metastases.
‘Spot views’ of selected parts of the body. These are static images taking about
5 min each. They will generally be of better quality than the whole-body images
and are useful for giving more detailed information about suspicious areas found
on the whole-body images. They can be taken at different angles.
SPECT (Single Photon Emission Computed Tomography) studies. For a SPECT
study the gamma camera rotates all the way round the patient taking images from
many angles, which takes about 30 min. The computer reconstructs these into
cross sectional images (see Chap. 19). These can be helpful for locating lesions
in three dimensions.
26 Understanding the Radionuclide Bone Scan: How It’s Done and How To Interpret It 155
SPECT-CT. Many modern gamma cameras incorporate a CT scanner in their

design to create a hybrid SPECT-CT system (see Chap. 19). The co-registered
SPECT and CT images can be useful for examining CT findings at sites that are
shown to have abnormal metabolism on the SPECT images. This is especially
useful to distinguish metastases from the degenerative changes often present in
older patients with prostate cancer. It can also help identify smaller areas of
increased uptake and should be performed if the patient has a significant area of
bone pain, even if the planar views show little or no increase.
Late images (optional). If the patient is unable to empty their bladder, so that the
pelvis is obscured by bladder activity, a SPECT scan may be able to resolve this,
but if not a late image (at 24 h) may be helpful.
Areas of increased uptake, ‘hot spots’, indicate increased bone metabolism. These
changes are not specific to metastases and may be seen in fractures, Paget’s disease
and degenerative changes. The pattern of distribution of hot spots may help differ-
entiate malignancy from benign abnormalities as the image in Fig. 26.1 shows. Not
all the lesions are in areas subject to degenerative change and multiple areas of
increased activity in other bones are almost certainly indicative of metastatic dis-
ease in a patient with a history of prostate cancer. However, history is important as
multiple repeated trauma can confuse the picture; fractures can remain active for
many months and even years and other malignancies can show similar patterns.
Fig. 26.1 99mTc MDP

bone scan showing
multiple areas of increased L R R L
radionuclide uptake, highly
suggestive of the presence
of metastases
Posterior Anterior
Fig. 26.2 99mTc MDP

bone SPECT-CT
CT
R L
R L
SPECT
Coronal
Fused
Transaxial
The bone scan is very sensitive to increased bone metabolism and metastases
may show up before they are apparent radiologically. The use of SPECT-CT when
there are fewer lesions or lesions in areas where joint disease can occur, such as the
spine, improves the accuracy of the study by improving localisation of the areas of
increased activity and by comparison to any changes seen on CT. The example in
Fig. 26.2 shows areas of increased activity in the spine and sacro-iliac region on this
coronal SPECT image. In the transaxial sections the fused SPECT and CT image
shows that the lower spine lesion is in the vertebral body and this corresponds to a
sclerotic lesion on the CT image.
Advanced widespread metastases that have spread uniformly throughout the
skeleton (a ‘superscan’) may be mistaken for a normal study if only the relative
counts in different bones are viewed. This can be avoided by considering the abso-
lute number of counts acquired or by comparing bone with other normal areas such
as the kidneys, soft tissues or distal limbs which are usually spared from metastatic
involvement. A “superscan” often shows no renal activity because of avid bone
uptake of the radionuclide which is then not excreted via the kidneys.
Limitations
Because of the limited resolution of the gamma camera, very small lesions may not
be detected. However, lesions with high osteoblastic activity can still show up as
‘hot spots’ on the bone scan even if they are very small. SPECT CT can also help
identify them.
26 Understanding the Radionuclide Bone Scan: How It’s Done and How To Interpret It 157
Very lytic lesions can be missed as the surrounding bone may not be producing
any osteoblastic response. A large lesion is required before it is visible as photope-
nic (“cold”) amongst the surrounding bone uptake.
Bone marrow metastases not yet involving the cortex, as often seen in other uro-
logical malignancies, will be missed unless present in any area also imaged with the
CT component.18F FDG PET scan may be more helpful to determine the presence
of metastases in this circumstance.
Side Effects
MDP and HDP very rarely produce any allergic reaction. If it occurs this is usually
in the form of an urticarial rash which can appear between the first few hours after
administration and the following day. Treatment with antihistamines and steroids
are rarely required. 1 in 200,000 administrations have reported hypersensitivity
reactions including very rare life-threatening anaphylaxis.
considered. The effective dose from 600 MBq 99mTc MDP is about 3 mSv which
equates to approximately 16 months of the average natural background radiation
in the UK.
Further Reading
The EANM practice guidelines for bone scintigraphy. https://www.eanm.org/publications/guide-

lines/EANM_Bone_Scintigraphy_GL_2016.pdf.
Sharp PF, Gemmell HG, Murray AD, editors. Practical Nuclear Medicine. 3rd ed. Springer; 2005.
Chapter 27
Renography of the Transplanted Kidney:
How It’s Done and How to Interpret It
The transplant renogram is a variation of the standard renogram that is optimised for
the transplanted kidney. This chapter explains how it is performed and how to
interpret it.
Indications
A transplant renogram is carried out for the assessment of kidney perfusion post-
transplant and to determine kidney function post-operatively: this can be particu-
larly useful in cases of acute tubular necrosis (ATN) where there is no urine output.
It may also be used to investigate the possibility of urinary leakage from the collect-
ing system or ureter.
Radiopharmaceutical
The radiopharmaceuticals used are the same as for a standard renogram (see Chap.
22) but 99mTc MAG3 is preferred if available. The administered activity of MAG3
for an adult can be as low as 20 MBq to assess kidney function or 200 MBq if kid-
ney perfusion is to be assessed as well. Some departments use the same activity as
their standard renograms.


Switzerland AG 2023
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Patient Preparation
No specific preparation is required. The transplant renogram cannot be performed

during a dialysis session if quantification of function is required. However renal
perfusion can still be assessed during dialysis if a mobile gamma camera is available.
Data Acquisition
The same collimator is used as for standard renography. With the patient lying
supine, the gamma camera is positioned anteriorly over the iliac fossa to view the
transplanted kidney and bladder. The radiopharmaceutical is injected and immedi-
ately a dynamic sequence of images is acquired. For assessment of kidney function
one frame every 20 s for 30 min is adequate. If assessment of perfusion is also
required, the first minute may be acquired at a faster rate of 1 frame every second to
give a ‘first pass’ study. After 30 min a 1 min static image of the bladder and also
images of any catheter bags or drainage tubes are taken.
Should urinary extravasation be suspected, further 5 min static images, at inter-
vals over 2 h, can be useful in identifying any tracer activity outside the urinary tract.
On the computer images of the dynamic series, regions of interest are drawn around
the kidney, together with a background region in the contralateral iliac fossa and a
region around the bladder.
Activity-time curves are created showing how the activity in each region of inter-
est changes with time. The background curve is used to subtract a background con-
tribution from the kidney and bladder curves. Each curve is scaled to percent of
administered activity, making an appropriate allowance for attenuation of gamma
rays in the patient. Using the final static images, activity in the bladder, catheter bag
and any drain bags are quantified as a percent of administered activity. There will be
much less attenuation of gamma rays from the catheter bag than from the bladder or
kidney and a suitable allowance must be made for this.
Kidney perfusion can be assessed qualitatively by inspection of the images from the
first pass study. Activity should appear in the kidney immediately after the iliac
artery. Figure 27.1 shows some images from a first-pass study showing good
27 Renography of the Transplanted Kidney: How It’s Done and How to Interpret It 161
Fig. 27.1 First pass study

of renal transplant R L R L R L R L
0-5 sec 5-10 sec 10-15 sec 15-20 sec
15% Dose
12
9
KIDNEY
3
BLADDER
3 6 9 12 15 18 21 24 27 30
minutes
Fig. 27.2 Typical renogram post cadaveric transplant
perfusion of the transplanted kidney. If activity-time curves are generated there are
several alternative quantitative indexes of kidney perfusion that can be calculated.
Kidney function can be assessed qualitatively by inspection of the dynamic
images or the renogram curve. Figure 27.2 shows a typical MAG 3 renogram show-
ing poor excretion following a cadaveric kidney transplant. A useful quantitative
measure of kidney function with MAG3 is the total of percent administered activity
in the kidney, bladder, catheter bag and any drains added together at 30 minutes.
This figure can be used to track changes in function in serial studies. This is most
useful in identifying potential rejection in a kidney that is still in ATN when serum
results are unhelpful as the patient still requires dialysis.
Urinary leaks can be detected by inspection of late images. Care must be taken
when interpreting the images as a small amount of MAG3 is excreted via the biliary
system and can appear on the these. The presence of reflux up the native ureters
must also be considered. SPECT-CT (Chap. 19) can help with this and may also
help define the site of the extravasation more clearly if required.
Figure 27.3 shows an example of extravasation. The initial image at 5 min shows
a faint photopenic (‘cold’) area suggesting non-active urine in the bladder. At 30 min
there is some excreted activity below the kidney but not in the bladder area. This
could be extravasation or an abnormal bladder/ureteric configuration which is
5 minutes 30 minutes Delayed Sheet & dressing
Fig. 27.3 Demonstration of tracer extravasation during MAG3 renogram
occasionally seen if the ureter was short or there had been previous surgery.
However, the later images clarify the situation; not only is there further tracking of
activity upwards and lateral to the kidney, but also in the wound dressing which had
been removed and imaged separately.
Side Effects
Side effects are the same as for the standard renogram.
Limitations
There is no absolute ‘normal’ for a transplant renogram because every transplanted

kidney is different depending on its history. Therefore, whichever quantification
method is used for monitoring the kidney in ATN, serial studies to show changes are
more useful than a single isolated study.
Figure 27.4 is a schematic representation of serial renography using MAG3 in
the post operative period. The patient required dialysis throughout. The studies
showed improving uptake of MAG3 on days 5 and 7 consistent with recovering
renal function. However, there was a fall on day 10 suggesting a problem which
needs further clinical assessment; likely due to rejection. If there had not been serial
studies on days 5 and 7 this deterioration would have been missed on renography as
the uptake was still better than on day 1, suggesting improving renal function in the
transplanted kidney.
An isolated study can help however in suspected extravasation not seen on ultra-
sound scan and also to confirm, or exclude, absent perfusion of the kidney as a
whole, or to part of the kidney if there is more than one renal artery.
Whilst increasing activity in the bladder as a proportion of total tracer output is
usually a good sign of recovery from ATN, this must be interpreted with caution as
it may depend on the state of hydration, which can vary post-operatively, and
whether or not there has been a post-ischaemic diuresis.
27 Renography of the Transplanted Kidney: How It’s Done and How to Interpret It 163
Fig. 27.4 Changes in the kidney

typical renogram curve in kidney kidney
the first 10 days after kidney
transplantation bladder
Day 3 Day 5 Day 7 Day 10
The assessment of kidney function is more difficult if the recipient still has some
residual function in their own kidneys. Some of the bladder activity may then come
from the native kidneys, and this may also change with changes in fluid balance.
The transplant renogram is not very helpful in diagnosing obstruction in cadav-
eric donor kidneys because the post-ischaemic kidney often shows a rising reno-
gram curve anyway (Fig. 27.2) and doesn’t usually respond rapidly enough to
furosemide for the test to be valid. Rejection can also show a “poor drainage pat-
tern” and so can be difficult to distinguish from obstruction.
Further Reading
Cook GJR, Maisey MN, Britton KE, Chen Gazi V, editors. Clinical nuclear medicine. 4th ed.
Edward Arnold; 2006.
Sharp PF, Gemmell HG, Murray AD, editors. Practical nuclear medicine. 3rd ed. Springer; 2005.
Chapter 28
Dynamic Sentinel Lymph Node Biopsy
in Penile Cancer
Ben Ayres and Nick Watkin
Lymph nodes are markers of the degree of cellular metastasis from most penile
cancers, and accurate detection of the limit of spread has implications for treatment.
The use of a combination of dyes and radionuclides has dramatically helped in the
determination of the nodal staging of this rare genital malignancy.
The term sentinel lymph node refers to the first lymph node, or packet of lymph
nodes, to which tumour cells metastasise from a primary tumour. It is assumed that
the process of micro-metastasis is embolic and that tumour cells are not present in
continuity in the lymphatic channels between the primary site and sentinel lymph
node. It is also, therefore, assumed that if the sentinel lymph node does not have
tumour within it that the remaining nodes in the lymphatic basin are free of tumour.
Penile cancers metastasise almost always via the lymphatic route to the nodes in
either (or both) inguinal basins. The presence and extent of lymph node metastasis
is the single most important prognostic indicator. Around 60–70% of men with
penile cancer present with impalpable inguinal nodes (cN0) and up to 20% of them
will have micro-metastases within those nodes. Staging investigations such as ultra-
sound, CT and MRI have limited sensitivity in detecting them. Accurate staging of
inguinal basins and treatment of nodal disease is vital in achieving a high cancer
specific survival. For patients with a single nodal metastasis 5-year survival
approaches 100%. Inguinal node surveillance, without surgical staging, results in a
much poorer prognosis with 5-year survival rates as low as 35% reported, if a node
subsequently develops. As a result, surgical staging of the inguinal nodes is recom-
mended in men with disease stage T1aG2 penile cancer or higher.
Prophylactic bilateral inguinal node dissection is associated with excellent regional
control rates but has a complication rate of 30–50%, including the risk of permanent
lower limb and/or genital lymphoedema. Moreover, with up to 80% of patients
B. Ayres (*) · N. Watkin

Department of Urology, St George’s University Hospitals NHS Trust, London, UK
e-mail: benjamin.ayres@nhs.net; nick.watkin@nhs.net

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https://doi.org/10.1007/978-3-031-26058-2_28
166 B. Ayres and N. Watkin
having negative nodes, these patients have associated morbidity with no clinical ben-
efit. Inguinal sentinel node sampling is, therefore, a technique that offers accurate
surgical staging of cN0 penile cancer with a reduced, and usually temporary, morbid-
ity of 7–14%.
Finding the Sentinel Nodes
Sentinel lymph node sampling is a staging technique used to accurately evaluate the
nodal status of patients with clinically node-negative penile cancer (cN0).
Cabanas (1977) was the first surgeon to describe the term “sentinel lymph node”
and “sentinel lymph node biopsy” in a cohort of penile cancer patients. Cabanas’
theory and observation was based on anatomical landmarks derived from lymphan-
giogram studies and did not adequately take into account inter-individual variation.
The original procedure involved removal of a single or, more often, a cluster of
lymph nodes medial to the superficial inferior epigastric vein, which is not a suffi-
ciently constant landmark to be reliable. When the technique was adopted by other
surgeons, the false-negative rates were high, and because of this it was largely
abandoned.
In the early 1990’s there was renewed interest in the technique by surgeons man-
aging patients with breast malignancies and melanoma. The use of patent blue-V
dye to map and visualize the lymphatic drainage of sentinel lymph nodes (SLN), in
addition to the preoperative injection of radioactive tracer technetium 99 m-labelled
(99mTc) nanocolloid now forms the basis of the technique we refer to as dynamic
sentinel lymph node biopsy (DSNB). This has resulted in more accurate localisation
of nodes whilst taking into account individual anatomical variations.
From the late 1990’s this modified approach was adopted by a small number of
penile cancer centres. Further improvements in the technique have been made sub-
sequently. These include:
• Extended pathological examination of the sentinel node by serial sectioning and
immuno-histochemical staining.
• Addition of preoperative ultrasonography with fine-needle aspiration cytology to
detect pathologically enlarged nodes, that fail to pick up radioactivity. This has
led to a reliable minimally invasive staging procedure with an associated sensi-
tivity of 92–95% together with low morbidity.
The Technique
The procedure can be performed at the time of surgery for the primary tumour or
delayed until 2–4 weeks later. Before surgery a local anaesthetic spray is applied
around the penile shaft, proximal to the site of the primary tumour. 99mTc-nanocolloid
is then injected intradermally either peri-tumour or just proximal to the tumour and
28 Dynamic Sentinel Lymph Node Biopsy in Penile Cancer 167
dynamic and static images are collected using a dual-head gamma camera. The
SLNs are located using a 57Cobalt-pen and skin markings are made with permanent
ink. The lymphoscintigram helps identify the position and depth of the sentinel
nodes pre-operatively.
10–15 min before surgery, 1 mL of patent blue dye is injected intradermally in
the penile shaft proximal to the site of the tumour. The SLN is located intra-
operatively using a hand-held gamma probe and the blue dye is used to guide dis-
section. The lymph nodes are only removed if they are radioactive and/or blue. Ties
or ligaclips to the lymphatics have been shown to reduce post-operative lymphocele
rates compared to the use of diathermy coagulation. Most sentinel nodes will be
radioactive (close to 100%) but fewer will be blue (around 80%). It is important to
check for background radioactivity levels within the groin to ensure all radioactive
sentinel nodes have been removed.
Due to the extended pathological assessment of the nodes any further treatment
is delayed until full histological results are available. A formal lymph node dissec-
tion is only performed if a sentinel node metastasis is found; there is around a 20%
chance of further nodes being involved with cancer.
A large series of patients in several high-volume (and often centralised) UK and
European penile cancer centres have confirmed the sensitivity of DSNB is approach-
ing 95% with low false negative rates.
Recent innovations in the DSNB technique have been reported using different
tracers and imaging techniques:
• Single photon emission computed tomography/computed tomography (SPECT/
CT) imaging which identifies more sentinel nodes than planar lymphoscintigra-
phy and enables accurate anatomical localisation of nodes.
• A hybrid radioactive and fluorescent tracer using indocyanine green (ICG)—
99m
Tc-nanocolloid. This replaces the injection of patent blue dye but requires an
infra-red camera for fluorescence imaging. A large single-centre study has shown
that fluorescent imaging results in a 39% higher sentinel node detection rate
compared to blue dye alone.
• SentiMag (superparamagnetic iron oxide particles) has shown promising results
in one small study so far, with high levels of concordance with the traditional
DSNB technique.
Further Reading
Leijte JA, Hughes B, Graafland N, Kroon BK, Olmos RA, Nieweg OE, Corbishley C, Heenan S,
Watkin N, Horenblas S. Two-center evaluation of dynamic sentinel node biopsy for squamous
cell carcinoma of the penis. J Clin Oncol. 2009;27:3325–9.
De Vries HM, Brouwer OR, Heijmink S, Horenblas S, Vegt E. Recent developments in penile
cancer imaging. Curr Opin Urol. 2019;29:150–5.
Part III
Technology Diagnostic Technology
Chapter 29
Urinalysis
David G. Ross
Urinalysis is a quick, cheap, and readily available point of care test. The combina-
tion of reagents allows for rapid access testing of urine to screen for indicators that
may require further investigation.
The combination of reagents on a urinalysis dipstick test typically include: (1)
bilirubin, (2) glucose, (3) haemoglobin, (4) ketones, (5) leucocytes, (6) nitrites, (7)
pH, (8) protein, (9) specific gravity, and (10) urobilinogen.
Using a Dipstick
Dipstick tests vary between manufacturers, so users should familiarise themselves

with the product used in their department. To avoid degradation, dipsticks must be
stored in a closed container; a useful check for such changes is a positive glucose
strip pre-testing. Always check the expiry date. The urine sample should be mid-
stream, fresh and collected in a sterile container. Submerge all the pads of the strip
in the sample and remove immediately. Start timing. Read each test at the appropri-
ate time by comparing against the colour reference chart on the bottle.
D. G. Ross (*)
Salford Care Organisation, Northern Care Alliance NHS Foundation Trust, Salford, UK
e-mail: david-ross@doctors.org.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_29
172 D. G. Ross
Urinalysis: Chemistry, Significance, and Errors
Blood/Haemoglobin
How?—Dependent on the peroxidase-like activity of haemoglobin (or myoglobin).

This catalyses the oxidation of a chromogen (3,3′,5,5′-tetramethylbenzidine) by an
organic peroxide (e.g. di-isopropylbenzene di-hydroperoxide). It can detect free
haemoglobin and intact erythrocytes which lyse on the test pad. Free haemoglobin
gives a uniform colour change (orange, green, blue), while intact red blood cells
give a spotted appearance; green spots on yellow/orange background.
Sensitivity = 90% in detecting equivalent of >3 RBCs/hpf; specificity 65–80%.
A trace of haematuria should be considered negative, while ≥1+ is considered
significant. Non-haemolysed and haemolysed are of equal significance.
Who to Investigate—NICE Guidelines [NG12]—Indication for referral on a sus-
pected cancer pathway:
1. Aged 45 years or older and have:
• Unexplained visible haematuria without UTI, or,
• Visible haematuria that persists or recurs after successful treatment of UTI.
2. Aged 60 years or over with unexplained non-visible haematuria, and either:
• dysuria, or,
• a raised WCC on a blood test.
Significance—5–13% of patients with non-visible haematuria (NVH) will have
urological cancer. In patients with NVH, the IDENTIFY Study, found no bladder
cancer in patients aged under 35 years, and, no Upper Tract Urothelial Cancer in
patients aged under 60 years (Tables 29.1 and 29.2).
Table 29.1 Urinary Tract Cancer Urological Cancer Diagnosis % of patients

Detection in patients with non-visible
Bladder cancer 13.1%
haematuria referred on a suspected
cancer pathway [1] Upper tract urothelial cancer 0.36%
Renal cancer 0.5%
Table 29.2 Diagnoses Diagnosis % of patients

of patients investigated
No cause identified 68.2
for microscopic
haematuria [2] UTI 13
Nephrological causes (IgA nephropathy, etc.) 9.4
Bladder cancer 4.8
Stones 4
Prostate cancer 0.3
Kidney cancer 0.2
Upper tract urothelial cancer 0.1
29 Urinalysis 173
Protein
How?—Based on protein error of indicators principle. Tetrabromophenol blue

changes colour in response to the presence of protein in urine. Sticks are very sensi-
tive, and a trace corresponds to 0.15–0.3 g/L, + to 0.3 g/L, ++ to >1 g/L, +++ to
2.5–5 g/L, and ++++ to >10 g/L proteinuria. Normal urinary protein should be less
than 15 mg/dL or <150 mg/24 h.
Significance—Significant proteinuria is a risk factor for renal disease and cardio-
vascular morbidity and mortality. Patients with persistent proteinuria should have it
quantified using either albumin/creatinine or protein/creatinine ratio. ACR has bet-
ter sensitivity than PCR for low levels of proteinuria. Even microalbuminuria
(30–150 mg/24 h) is significant in diabetic patients. Chronic kidney disease (CKD)
is classified G1–5 based on GFR and A1–3 based on ACR; CKD 1 = GFR ≥90 mL/
min and proteinuria A2-A3, and CKD 2 = GFR 60–89 mL/min and proteinuria
A2–3. Both groups require monitoring in primary care. A nephrology referral is
indicated if the urinary ACR > 70/PCR > 100 mg/mmol or the urinary ACR > 30/
PCR > 50 mg/mmol with microscopic haematuria.
Leucocytes
How?—Leucocyte esterase is produced by neutrophils which catalyses the hydro-

lysis of either derivatised pyrrole amino acid ester to liberate 3-hydroxy-5-phenol
pyrrole or indoxyl carbonic acid ester to indoxyl. Pyrrole or indoxyl then reacts with
a diazonium salt to produce a purple product.
Significance—The list of potential causes of persistent pyuria is long; however,
the presence of urinary leucocytes is often used as an indicator of UTI along with
dipstick nitrites. Its performance in this setting is shown in Table 29.3.
Table 29.3 Utility of leucocyte esterase and nitrite urinalysis in the detection of UTI [3]
Dipstick result Pooled sensitivity % Pooled specificity %
LE positive 72 82
Nitrite positive 54 98
LE or nitrite positive 81 77
LE and nitrite positive 43 96
174 D. G. Ross
Nitrites
How?—Nitrite in the urine reacts with ρ-arsanilic acid to form a diazonium com-
pound which couples with 1,2,3,4-tetrahydrobenzo(h)-quinolin-3-ol to produce a
pink colour.
Significance—Nitrites when present in urine are the result of bacteria reducing
urinary nitrates. Around 60% of Gram-negative bacteria are capable of this, which,
together with the requirement of at least 105 bacteria per milliliter for a positive test,
limits the sensitivity of this test in the clinical detection of UTI (Table 29.3).
pH
How?—Double indicator principle, methyl red and bromothymol blue, which pro-
vides a broad range of colours to cover a urinary pH range of 5–8.5 (visually).
Significance—Urinary pH typically reflects plasma pH. An exception is in renal
tubular acidosis where there is an inability to acidify urine in response to an acid
load. Urinary pH is potentially important in urolithiasis. Uric acid stone formation
requires a pH < 5.5, while the actions of urease-splitting organisms provide the
alkaline environment for struvite lithogenesis. Dietary factors can alter pH; high
protein diets lower pH, while citrate supplements will raise it.
Glycosuria
How?—Double sequential enzyme reaction:

1. Glucose oxidase catalyses glucose → glyconic acid + hydrogen peroxide.
2. Peroxidase catalyses hydrogen peroxide + potassium iodide chromo-
gen → coloured oxidised chromogen.
Significance—Occurs when blood sugar is >10 mmol/l, the renal threshold.
Potential Errors When Reading a Dipstick
Potential sources of false positive and negative dipstick test results are shown in
Table 29.4.
29 Urinalysis 175
Table 29.4 Sources of false positive and negative urine dipstick results
Test False positive False negative
Haemoglobin Myoglobin Reducing agents:
Bacterial peroxidases 1. Ascorbic acid
Hypochlorite 2. Captopril
Menstruation
Dehydration
Exercise
Protein – Dilute or alkaline urines
Bence-Jones proteins
Leucocytes Formalin Glycosuria (>3 g/dL)
Vaginal discharge Ascorbic acid
Cephalexin
Imipenem
Meropenem
Clavulanic acid
Tetracycline
Nitrites – Non-nitrate-reducing bacteria
Low nitrate diets
Dilute urine
Urine in the bladder for <4 h
Ascorbic acid
Glucose – Ascorbic acid
References
1. Khadhouri, et al. The IDENTIFY Study; The investigation and detection of urological neopla-
sia in patients referred with suspected urinary tract cancer—a multicentre observational study.
BJU Int. 2021;128:440–50.
2. Khadra MH, et al. A prospective analysis of 1,930 patients with haematuria to evaluate current
diagnostic practice. J Urol. 2000;163(2):524–7.
3. St John A, et al. The use of urinary dipstick tests to exclude urinary tract infection: a systematic
review of the literature. Am J Clin Pathol. 2006;126(3):428–36.
Further Reading
NICE, NICE guideline [NG12]. Published June 2015. Last updated December 2021.
Chapter 30
Principles of Urine Microscopy
and Microbiological Culture
Ffion E. Carlin and Cecilia M. Jukka
In the context of increasing antimicrobial resistance, urine microscopy and culture

are vital tools to aid diagnosis and guide appropriate antibiotic therapy of urinary
tract infection. While this is traditionally performed using a microscope, modern
methods allow automated analysis of urine samples via flow cytometry and particle
recognition systems. Culture is also often automated, using calibrated loop tech-
nique and multipoint technology.
Introduction
Urinary tract infections (UTI) are common resulting in considerable morbidity and
burden on health services. Repeated empirical treatment in the absence of confirmed
infection and without antibiotic susceptibilities can delay appropriate treatment and
promote antibiotic resistance. Empirical prescribing is warranted when a person
presents unwell with obvious urinary symptoms. Indications for both empirical
treatment and investigation differ by patient group based on known risk factors
including pregnant women, women >65 years, men or young children. A large pro-
portion of urine samples tested by microbiology laboratories will show no evidence
of infection on culture or are contaminated and therefore uninterpretable.
F. E. Carlin (*) · C. M. Jukka

Liverpool University Hospitals Foundation Trust, Liverpool, UK
e-mail: cecilia.jukka@liverpoolft.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_30
178 F. E. Carlin and C. M. Jukka
Methods of Urine Collection
If urinary tract infection (UTI) is suspected, a urine sample should ideally be col-
lected prior to initiation of any therapy and sent for microscopy and bacterial culture.
This will be helpful to guide diagnosis and target appropriate antibiotic treatment.
Traditionally, a universal container is used for specimen collection. Specimen con-
tainer lids should be tightly secured to prevent leaks, labelled correctly, and transported
promptly to the laboratory for processing. When delays are expected, containers with
boric acid preservative (bacteriostatic) should be used or samples should be refriger-
ated prior to transport to prevent bacterial overgrowth and false positive culture results.
Early morning urine samples are preferred for testing as the urine is more concen-
trated and it allows bacteria time to multiply overnight. However, in practice, most
cultures are obtained when the patient sees the clinician. Specimen collection should be
a clean catch midstream urine (MSU) and the patient should be instructed in the proper
technique. This involves parting the labia or retracting the prepuce prior to collection;
this helps to minimise contamination of the sample with the commensal bacterial flora
of the genital area, reducing false positive results and the need for repeat sampling.
When it is only possible to obtain a catheter specimen of urine (CSU), the speci-
men should be obtained aseptically from a sample port in the catheter tubing (not be
obtained from the collection bag). Suprapubic aspirate of urine (SPA) is a collection
method which can be used in neonates and infants under 24 months as it is difficult
to obtain a “clean catch” in this group of patients. Though recommended, in practice
this technique is rarely performed as it is invasive. For male infants, or un-
catheterised incontinent adult males, an alternative method of urine specimen col-
lection can be attempted using a reservoir such as a sheath type of convene. Pads for
females and smaller infants are sometimes used, though these methods are associ-
ated with high rates of contamination.
Traditional Microscopy and Non-culture Methods
Investigation of urine samples involves microscopy, used to identify the presence of

white blood cells, red blood cells, casts, epithelial cells, bacteria, and other cellular
components present in the urine. Traditionally this has been done using a micro-
scope and is recommended for all symptomatic patient groups to assist in the inter-
pretation of culture results and diagnosis of UTI.
Modern urine microscopy is now largely done using automated analysers which
can produce objective digital images of the examination results. Their use facilitates
faster turnaround times and reduced laboratory staff workload compared to tradi-
tional methods, consequently reducing costs.
30 Principles of Urine Microscopy and Microbiological Culture 179
Automated urinalysis endeavours to measure or describe the formed elements in

the urine. Three techniques are currently available:
1. Fluorescein flow cytometry with diode laser and hydrodynamic focused conduc-
tometry (IQ Sprint®)
2. Flow cell digital imaging of un-centrifuged urine and automated recognition
software (UF-1000i®)
3. Microscopic urine sediment analysis, digital imaging, and automatic particle
recognition (Sedimax®)
Flow cytometry works by measuring electric impedance (for volume), light scat-
ter (for size) and use of fluorescent dyes (for nuclear and cytoplasmic staining). The
particles are characterised using these measurements and the results are displayed
as scattergrams. In particle recognition systems (e.g. Sedimax®), the urine speci-
men passes through the analyser and a camera captures up to 500 frames per speci-
men. Each image is classified by size, shape, contrast, and texture features. This has
been found to be more reliable for identifying cellular components. Sensitivity of
the automated analysers is high, but with consequently reduced specificity. Skilled
biomedical laboratory assistants are still required to review certain particles (e.g.
Trichomonas vaginalis, yeasts etc.).
Regardless of the screening result, culture is still recommended for all specimens
from children, pregnant women, immunocompromised patients, and those with per-
sistent symptoms but recurrent negative results. For samples not in these categories,
culture is only performed if the number of white blood cells (WBCs) on microscopy
is >40 WBCs per microlitre (μl) of urine.
Pyuria and / or Bacteriuria
Significant pyuria is present in 96% of symptomatic patients with bacteriuria of

>105 colony forming units (cfu) per millilitre (ml) of urine on culture. Sterile pyuria
(pyuria associated with no growth on routine culture media) may be seen after recent
or concurrent treatment with antimicrobial agents or can be associated with calculi,
bladder neoplasms, genital tract infection, infection due to a fastidious organism (i.e
Chlamydia trachomatis, Mycoplasma genitalium, etc) or urogenital tuberculosis. If
Chlamydia or Gonorrhoeal infection is suspected these must be tested separately
and require a first catch urine sample in men; or a vaginal swab in women.
Culture Methods
Commonly used methods for quantification of bacteria in urine include the cali-
brated loop technique and multipoint technology. Examples of culture media used
for inoculation of urine can be seen in Table 30.1.
Culture of urine by multipoint method may be performed using micro-titre trays
containing agar and read manually, or automated with data transferred to the labora-
tory information management system. This technology is the most efficient for a
laboratory handling large number of specimens (Fig. 30.1).
Table 30.1 The advantages and disadvantages of commonly used culture media for inoculation of
urine specimens
Culture Media Advantages Disadvantages
Blood agar Discrimination of gram-positive No inhibition of swarming of
bacteria; enables identification of proteus spp.; poor
proteus spp. by swarming discrimination of different
species of Enterobacteriaceae
Cystine lactose Discrimination of gram-negative Poor growth of some gram-
electrolyte bacteria by lactose fermentation and positive bacteria
deficient(CLED) colony appearance; inhibits swarming
of proteus spp
Chromogenic agar Enables colour identification of Poor growth of some gram-
Escherichia. Coli (pink), enterococci positive bacteria
(blue or green), klebsiella-Enterobacter-
Serratia group (purple), and proteus-
Morganella-Providencia group (brown)
30 Principles of Urine Microscopy and Microbiological Culture 181
Fig. 30.1 Micro-titre trays

Interpretation and Use of Culture Results
Culture results should be correlated with clinical presentation, individual patient

risk factors and presence or absence of pyuria or squamous epithelial cells (which
indicate the degree of contamination). Culture of single pure (or predominant)
organisms ≥105 colony forming units (cfu) /ml with urinary tract symptoms is diag-
nostic of UTI.
Antibiotic treatment should be guided by the identified pathogen susceptibility
pattern and local antibiotic guidelines indicating preferred choices of antibiotics for
different patient groups.
Patients with confirmed recurrent urinary tract infection or challenging resis-
tance patterns may warrant discussion with a microbiologist and investigation for
associated complications.
Further Reading
United Kingdom standards for microbiology investigations (UKSMI)- GOV.UK, B41i18: investi-
gation of urine. Public Health England; published July 2014. Updated January 2019.
Broeren MA, et al. Screening for urinary tract infection with the sysmex uf-1000i urine flow
cytometer. J Clin Microbiol. 2011;49(3):1025–9.
Hay AD, Birnie K, Busby J, et al. The diagnosis of urinary tract infection in young children
(DUTY): a diagnostic prospective observational study to derive and validate a clinical algo-
rithm for the diagnosis of urinary tract infection in children presenting to primary care with an
acute illness. Health Technol Assess. 2016;20(51):1–294.
Chapter 31
Urinary Flow Cytometry
Harry Rudman and Dora Moon
Flow cytometry (FCM) is a process of cumulative cytometric assessment of a popu-

lation of cells in solution. Cytometric characteristics of individual cells are assessed
through measurement of differential light scatter and fluorescence emitted by illu-
minated cells. Urinary flow cytometry (UFC) has appeal as a diagnostic technique
within the field of clinical microbiology due to rapid availability of results by com-
parison to traditional methods such as urine microscopy, culture and sensitivity.
Principles of Flow Cytometry
FCM is an analytical method that provides rapid assessment of cellular characteris-

tics through the measurement of light scattered by illuminated cells. Particles within
a specimen are analysed individually, whilst in flow, producing a cumulative set of
results for a given population.
At the point of analysis, cells are exposed to a light source, typically an arc lamp
or laser. Multiple characteristics of a cell can be assessed according to the subse-
quent light scatter. For example, the amount of light scattered back towards a light
source, or reflected, is indicative of cell size. Conversely, light detected laterally or
beyond the cell is indicative of cellular complexity, or the density of organelles
within the cell. To provide additional information and aid discrimination, cells may
be stained with fluorescent labels known as fluorochromes. Fluorochromes can
attach directly to cellular structures or may be conjugated with intermediaries such
as antibodies.
H. Rudman (*) · D. Moon

Lancashire Teaching Hospitals Trust, Preston, UK
e-mail: harry.rudman@doctors.org.ukb

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_31
184 H. Rudman and D. Moon
Components and Function of a Urinary Flow Cytometer
Urine specimens for analysis by FCM may be centrifuged prior to analysis, although
most contemporary systems accept native samples. Depending on the model of flow
cytometer a volume of ~1-4 ml of urine is required.
Processing and analysis of the specimen has several stages, as follows (Fig. 31.1):
• Following aspiration, specimens are stained using fluorochromes that target cel-
lular nucleic acids as well as the cellular membrane.
• The specimen is passed through a liquid sheath, which generates flow of cells at
a constant velocity, through a narrow window of incident light (hydrodynamic
focusing).
• An optics system focuses incident light on passing cells and collects the scattered
light and fluorescence, passing this to photomultiplier tubes (PMTs). Scattered
light and fluorescence are measured in forward and lateral direction.
• An analogic signal is generated within each PMT for each cell. The pattern of
light signal for each particle is analysed using a series of algorithms to profile the
cellular “fingerprint” and categorise the cell type.
Contemporary flow cytometers, such as the Sysmex UF-5000® (Sysmex
Corporation, Kobe, Japan), are able to identify and quantify numerous types of cells
including erythrocytes, leucocytes, bacteria, epithelial cells and casts. Modern sys-
tems incorporate two separate analysis channels, with one specifically for counting
bacteria, operated at a different temperature and stained with tailored fluorochromes.
PMTs
Side-scattered
light
Liquid Sheath
Fluorescence
Forward-scattered light
Laser
Fig. 31.1 Components of a urinary flow cytometer

31 Urinary Flow Cytometry 185
pplications of Urinary Flow Cytometry Within

A
Clinical Microbiology
Identification of uropathogens through the traditional, gold-standard method of

urine microscopy and culture typically takes between 18 and 48 hours, meaning
same-day results are unlikely. When you consider that the majority of urine speci-
mens analysed are negative, there is an obvious role for screening of specimens as a
time and cost-saving exercise.
UFC has emerged as an effective screening tool used to rule out urine specimens
that do not require culture and sensitivity. If the bacterial cell count, as measured by
FCM, is not sufficiently high, samples do not proceed to culture. Individual labora-
tories are able to choose their own cut-off values for bacterial count, and may choose
to incorporate the presence of leucocytes, or other cell types, in their decision mak-
ing. This method has been demonstrated to have adequate sensitivity and specificity
in detecting significant bacterial growth when examined alongside paired urine cul-
ture results. Authors report maintaining sensitivity of >95% whilst significantly
reducing the number of samples requiring culture.
Technological advances within the field of UFC mean systems have an increas-
ing ability to characterise pathogens. The third generation Sysmex UF-5000® is
able to flag specimens as gram positive or negative with results reportedly compa-
rable to traditional gram staining. In the future, it may be possible for specific organ-
isms to be identified by FCM alone.
Further Reading
Alvarez-Barrientos A, Arroyo J, Canton R, Nombela C, Sanchez-Perez M. Applications of flow

cytometry to clinical microbiology. Clin Microbiol Rev. 2000;13(2)
Jolkkonen S, Paattiniemi E, Karpanoja P, Sarkkinen H. Screening of urine samples by flow cytom-
etry reduces the need for culture. J Clin Microbiol. 2010;48(9)
Chapter 32
Urine Cytology
Nadira Narine and Durgesh N. Rana
The stage and grade of urothelial carcinoma (UC) are of great importance at diag-
nosis as non muscle-invasive disease (stage I) shows better outcomes then muscle-
invasive disease (stage II-IV). Histology is the gold standard for diagnosis as the
recommendation for detrusor muscle invasion can only be determined with histo-
logical biopsies. Urine cytology plays an important part in the diagnosis and sur-
veillance of high grade urothelial carcinoma, including carcinoma in situ.
Introduction
The stage and grade of urothelial carcinoma (UC) are of great importance at diag-
nosis as non muscle-invasive disease (stage I) shows better outcomes then muscle-
invasive disease (stage II-IV). Histology is the gold standard for diagnosis as the
recommendation for detrusor muscle invasion can only be determined with histo-
logical biopsies.
Cytology has a limited but specific role in the diagnosis of UC. It’s main goal is
in the diagnosis of high-grade urothelial carcinoma (HGUC) including carcinoma-
in-situ (CIS). It is used mainly by clinicians if:
• there are no visible papillary lesions at flexible cystoscopy in the presence of
persistent visible haematuria
• there are red patches at flexible cystoscopy which may represent inflamma-
tion or CIS
N. Narine (*) · D. N. Rana

Cytology Department, Manchester University NHS Foundation Trust, Manchester, UK
e-mail: nadira.narine@mft.nhs.uk; durgesh.rana@mft.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_32
188 N. Narine and D. N. Rana
• lesions that are difficult to visualise e.g. calyceal diverticulae

• patients in whom clinically / radiologically HGUC is suspected but are unable to
have invasive investigations due to co-morbidities.
Because of the anatomical continuity of the renal pelvis, ureter, bladder and ure-
thra, cytology is well suited to guide clinicians to further investigations when cys-
toscopy is indeterminate or negative. A negative cytology has a high negative
predictive value of underlying high-grade disease. Similarly, the sensitivity of urine
cytology is high in HGUC.
Sampling Types
Voided Urine
Although theoretically more cellular, the first morning voided urine is prone to degen-
eration. A full voided sample (i.e. not mid-stream) is collected in a sterile container at
any time of day. A volume between 25–30 mL is adequate. Samples should be trans-
ported to the laboratory as soon as possible after collection to avoid degeneration.
Some centres recommend fixing in an equal volume of an alcohol based fixative.
Catheterised and Ilieal Conduit Urine
Samples taken from a drain bag are not suitable for cytological assessment as they
are very degenerate and contaminated by material from the bag. Instead the catheter
or conduit should be directed into a sterile container for fresh collection.
Aspirated Urine, Washes and Brushes
Urinary samples may be collected from any part of the urinary tract by aspiration,
washing or brushing. As much as possible of the aspirated or washing sample should
be retrieved. In instances of brushings from an obvious lesion, this brush should be
fixed in an alcohol based fixative, to prevent degeneration.
Preparation
Concentration of all types of urinary tract samples by centrifugation with subse-

quent preparation by at least one cytospin or a single megafunnel or Liquid Based
Cytology (LBC) preparation for Papanicolaou (Pap) staining is sufficient for cyto-
logical reporting.
32 Urine Cytology 189
Diagnostic Categories
The Paris System (TPS) for Reporting Urinary Cytology is a standardized reporting
system that includes specific diagnostic categories and cytomorphologic criteria for
the reliable diagnosis of HGUC as well as the risk of high grade malignancy
(ROHM) for each diagnostic category. The main goal of urinary cytology is the
detection of HGUC. The distinction of HGUC from benign changes and low-grade
neoplasms (LGUNs) is central to the clinical utility of urine cytology.
The second edition of the Paris System for Reporting Urinary Cytology (TPS)
proposes five diagnostic categories:
Unsatisfactory: adequacy of urine samples for the diagnosis of HGUC is depen-
dent on collection type, cellularity, volume and cytomorphological findings with the
latter being the most important characteristic as any atypia is reported as such irre-
spective of the other parameters. A urine sample is only deemed unsatisfactory if:
• the sample is acellular or obscured by debris
• any visible cytological features are benign and the sample volume is fewer than
the recommended volume of 25–30 mL
The ROHM in samples reported as unsatisfactory is 0–16%.
Negative for high grade urothelial carcinoma (Fig. 32.1): this refers to those
urinary samples which have cellular features that pose no significant risk for HGUC
Fig. 32.1 Voided urine sample showing scattered single benign urothelial cells together with neu-
trophils. This is negative for high grade urothelial carcinoma. SurePath Pap ×400
and has a ROHM of 8–24%. It includes those samples which comprise cells with the
following features in any combination:
• Benign urothelial cells
• Squamous epithelial cells
• Glandular / columnar cells
• Epithelial cells showing cytopathic effects of human papilloma or herpes sim-
plex virus
• Renal tubular cells +/− renal casts
• Cells with degenerative changes
• Benign urothelial tissue fragments (BUTF) secondary to instrumentation or
infections
• Cells showing iatrogenic changes secondary to BCG, chemotherapy or
radiotherapy
• Low-grade urothelial neoplasia (LGUN)
Atypical Urothelial Cells: to reduce the number of indeterminate/atypical rate of
reports in urinary cytology and provide clarity to clinicians, TPS has defined the Atypical
Urothelial Cells (AUC) category as samples which contain non-basal urothelial cells
with mild to moderate cytological atypia with a nuclear to cytoplasmic ratio ≥0.5. Cells
must be well preserved to raise the concern of AUC and the ROHM is 25–53%.
Suspicious for High Grade Urothelial Carcinoma: According to TPS, the
diagnosis of Suspicious for High-Grade Urothelial Carcinoma (SHGUC) is used
when there are well preserved urothelial cells with severe atypia which quantita-
tively fall short of a diagnosis of HGUC. The ROHM ranges from 59–94%.
High Grade Urothelial Carcinoma (Fig. 32.2): the diagnostic criteria for the
diagnosis of High-Grade Urothelial Carcinoma (HGUC) confers a ROHM of
76–100%. The primary goal of urinary cytology is in the diagnosis of HGUC and
this is aided by the well-defined set of criteria established.
32 Urine Cytology 191
Fig. 32.2 Voided urine sample showing many single malignant urothelial cells with hyperchro-
matic, enlarged nuclei. Red blood cells and necrosis are noted in the background. This is high
grade urothelial carcinoma. SurePath Pap ×400
Summary
Although limited, cytology has a specific and important role in the diagnosis of
HGUC due to excellent sensitivity. It can sample the entire urinary tract and provide
important information to clinicians on further management.
Further Reading
National Institute for health and care excellence. Bladder cancer: diagnosis and management.
NICE; 2015. https://www.nice.org.uk/guidance/ng2.
Sundling KE, Antic T & Pambuccian SE. In: Wojcik EM, Kurtycz DFI & Rosenthal DL, edi-
tors. The Paris system for reporting urinary cytology. 2nd ed. Switzerland: Springer Nature;
2022. p. 1–5.
Rezaee N, Tabatabai ZL, Olson MT. Adequacy of voided urine specimens prepared by ThinPrep
and evaluated using the Paris system for reporting urinary cytology. J Am Soc Cytopathol.
2017;6(4):155–61. https://doi.org/10.1016/j.jasc.2017.04.001.
The Royal College of pathologists. Tissue pathways for diagnostic cytopathology, October 2019.
https://www.rcpath.org/uploads/assets/b328ab3d-f574-40f1-8717c32ccfc4f7d8/G086-Tissue-
pathways-for-diagnostic-cytopathology.pdf.
VandenBussche CJ, Chandra A, Heymann JJ, McCroskey Z, Owens CL, Schubert PT, Wang Y. In:
Wojcik EM, Kurtycz DFI, Rosenthal DL, editors. The Paris system for reporting urinary cytol-
ogy. second ed. Springer Nature: Switzerland; 2022. p. 21–62.
Chapter 33
Histopathological Processing, Staining
and Immuno-Histochemistry
Tegan Miller
Histological examination of biopsy material is imperative to diagnosis. It consists of

three stages before the histological slide can be interpreted: tissue fixation, tissue
processing and staining. Following this, the stained slide is analysed by a histopa-
thologist, who makes a diagnosis depending on factors including morphological
features, as well as the use of further stains such as immuno-histochemistry. There
are many new developments within uropathology, including the use of molecular
techniques in newly defined renal neoplasms, new immunohistochemical stains
and, with respect to prostate cancer, the potential future use of Artificial Intelligence.
Introduction
Histological examination of biopsy material is an important adjunct to diagnosis. It

consists of three stages before the histological slide can be interpreted: tissue fixa-
tion, tissue processing and staining.
Tissue Fixation
Formalin is the standard fixative used in many histopathology departments as it is

compatible with most histological stains, preserving tissues for many months.
Tissue fixation occurs when cross-linking of proteins takes place and this preserves
cellular morphology. Formalin penetrates tissue at approximately 0.5 mm per hour
T. Miller (*)
Department of Histopathology, Manchester Royal Infirmary, Manchester, UK
e-mail: t9mill@doctors.org.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_33
194 T. Miller
so it is important to immerse tissues, particularly large specimens, in adequate vol-

umes of fixative. Poor fixation of tissue can lead to difficulties in assessing morphol-
ogy microscopically.
Processing of Tissue Samples
Tissue may be received as small biopsy fragments, core biopsies, chips or larger
resection specimens. Smaller samples are placed directly into plastic cassettes for
processing. Larger resections are ‘cut up’ into cassette-size pieces approximately
30 × 25 mm, and up to 4 mm in thickness. Techniques using ‘mega’ cassettes, to
enable entire slices of a whole organ to be seen on one slide, are also in standard use
particularly for histological examination of radical prostatectomy specimens.
Tissues placed in cassettes undergo automated processing involving a series of
steps over several hours.
1. Dehydration. Water is removed from the tissue and replaced by graded alcohol.
2. Clearing. The alcohol is then replaced by a clearing agent to help tissue infiltra-
tion by the embedding medium (the most commonly used clearing agent is
xylene).
3. Embedding. Xylene is replaced by paraffin wax in the embedding step to make
the tissues hard enough to cut.
4. Cutting. When cooled, the embedded tissue is cut into very thin sections, nor-
mally 3–4 microns, with a microtome knife.
5. Mounting. These slices are then mounted onto glass slides ready for staining.
Smaller samples such as bladder and prostate core biopsies may have multiple
levels cut through one sample, and sections inbetween the levels saved for
immuno-histochemical staining, if required.
Staining
Haematoxylin and eosin (H&E) staining is the stain most commonly used in histo-
pathology. Haematoxylin stains cell nuclei blue, while eosin stains cytoplasm, con-
nective tissue and other extracellular substances, pink or red. H&E staining can be
used to determine the size and shape of the nucleus in tumour cells and to show the
percentage of tumour cells that are dividing. Recognition of nuclear features such as
nucleoli is important particularly in the diagnosis of prostate carcinoma, and pros-
tatic intra-epithelial neoplasia (PIN) in some cases.
Immuno-histochemical staining can be used in several ways. It may be used to
identify the tissue of origin of metastatic tumours or to identify specific tumour
markers or tumour types. The basis of immuno-histochemistry is an antigen anti-
body reaction, revealed in the tissue by a chromogen complexed with, or activated
33 Histopathological Processing, Staining and Immuno-Histochemistry 195
by, antibody, which is visualised by the pathologist down the microscope. Antibodies
have been specifically developed against particular tissue antigens. A panel of
immuno-histochemical stains, to support a particular diagnosis, and rule out alterna-
tive diagnoses, is generally used.
I mmuno-Histochemical Stains Commonly Used

in Urological Diagnosis
Prostate carcinoma—unless poorly differentiated, these stains can be used to con-

firm cells of a prostatic origin either in primary or metastatic locations:
• prostate specific antigen (PSA)
• prostatic acid phosphatase (PAP)
• NKX3.1
Benign prostate glands usually have a basal layer (which can be identified with
immuno-histochemistry) and malignant prostate glands do not have a basal layer.
The absence of this basal layer can be used to help in the assessment of atypical
small acinar proliferations (ASAP) when trying to differentiate a benign process
from adenocarcinoma. High molecular weight cytokeratins and p63 are commonly
used markers of basal cells in this scenario. Alpha-methylacyl-CoA racemase
(AMACR) is often positive in malignant prostate glands and can be used to support
a morphological diagnosis of prostate cancer.
Urothelial carcinomas generally stain with:
• Cytokeratins (CK) 7 and 20
• GATA-3
• Uroplakin
• CK 34BE12
CK20 and p53 staining patterns can be useful in supporting a diagnosis of carci-
noma in-situ (CIS).
Renal cell carcinomas generally stain with:
• PAX-8
• CD10
• RCC (renal cell carcinoma antibody)
Other antibodies are of use in the differentiation of different types of primary
renal malignancies. CAIX (carbonic anhydrase IX) is useful in the diagnosis of
clear cell renal cell carcinoma (RCC). CK7 can be helpful, for example in the dif-
ferentiation of oncocytoma from chromophobe RCC. CK7 is also positive in papil-
lary RCC. TFE3 (transcription factor gene product) is a marker of translocation
carcinomas.
196 T. Miller
Testicular tumours:
• Testicular germ cell tumours and intra-tubular germ cell neoplasia, depending on
the subtype, stain for a variety of markers, including OCT3/4, CD30, CD117,
PLAP, glypican-3, SALL4, HCG and AFP.
• Inhibin, SF-1, melan A and calretanin can be useful markers of some sex cord
stromal tumours.
New Developments in Pathology
There has been much interest in recent years into the potential future use of Artificial
Intelligence (AI) in histopathology, particularly in diagnosing and grading prostate
cancer in biopsies. Many algorithms use Machine Learning techniques, such as
Deep Learning, to enable the comparison of a scanned image with a large collection
of images previously scanned, with the ability of algorithms to ‘learn’ and develop.
Ongoing studies (at the time of publication) suggest that the highest performing of
these algorithms can achieve, and possibly surpass, the diagnostic accuracy of a
general pathologist. Further development is required in this area before clinical
application.
The classification of renal neoplasms is expanding, with several molecularly
defined entities, which may require immuno-histochemistry (and potentially molec-
ular techniques) for diagnosis, including tumours with abnormalities involving FH,
SBHB, TFEB, TFE3 and ALK genes.
Further Reading
Suvarna SK, Layton C, Bancroft JD. Bancroft’s theory and practice of histological techniques. 8th
ed. Elsevier Health Sciences; 2018.
Nagpal K, Foote D, Liu Y, Chen PHC, Wulczyn E, Tan F, et al. Development and validation of
a deep learning algorithm for improving Gleason scoring of prostate cancer. Npj Digit Med.
2019;2(48) https://doi.org/10.1038/s41746-019-0112-2.
Bulten W, Kartasalo K, Chen PHC, Ström P, Pinckaers H, Nagpal K, et al. Artificial intelligence
for diagnosis and Gleason grading of prostate cancer: the PANDA challenge. Nat Med.
2022;(13):154–63.
Chapter 34
Tumour Markers
Alex Hoyle
The terms ‘tumour marker’ and ‘biomarker’ are often used synonymously when
describing cancer related markers within uro-oncological literature. In the context
of this chapter, a tumour marker is referred to as a biochemically detected indicator,
capable of predicting cancer. A biomarker may be considered a biochemical or his-
topathological marker capable of predicting treatment response or cancer prognosis.
Bladder Cancer
The National Institute for Clinical Excellence (NICE) recommends the use of
tumour markers as adjuncts to cystoscopic bladder evaluation for suspected blad-
der cancer.
Urine cytology is the most well recalled and accurate urinary tumour marker. It
has high sensitivity (80–90%) and specificity (98–100%) for detecting high-grade
urothelial lesions and carcinoma in situ due to high tumour cell shedding. This falls
dramatically to (0–100%) and (6–100%) respectively in the detection of low-grade
disease. Unreliability of cytology in low-grade disease, and false negative rates of
10–20% in high-grade disease cannot reliably avoid cystoscopic bladder evaluation.
Cytology has fallen from routine clinical practice due to diagnostic dilemmas
caused by false positive results. However, many clinicians still use cytology when
assessing upper tract urothelial cancer and monitoring high-grade bladder cancer.
Urine cytology is reported using the Paris system for reporting 2.0 (Table 34.1)
following collection of an entire voided bladder volume. This is typically performed
during the second void of the day, thus avoiding the effects of cellular degradation
A. Hoyle (*)
e-mail: alex.hoyle2@srft.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_34
198 A. Hoyle
seen in stagnant urine voided following sleep. Avoidance should be considered in

patients with recent UTIs to minimise false positive results, or immediately follow-
ing endoscopy which may overly dilute urine.
Novel biomarkers (Table 34.2) boast higher sensitivity than cytology for all blad-
der cancer. Unfortunately, these markers still cannot compete with the reliability of
Table 34.1 The Paris Criteria Outcome

system
1 Nondiagnostic/unsatisfactory
2 Negative for high-grade urothelial carcinoma
3 Atypical urothelial cells
4 Suspicious for high-grade urothelial carcinoma
5 High-grade urothelial carcinoma
6 Low-grade urothelial carcinoma
7 Other primary and secondary malignancy and
miscellaneous lesions
Table 34.2 Novel bladder cancer tumour markers

Brand name/
Tumour marker Manufacturer Mechanism Sensitivity Specificity
Fluorescence in Urovysion Urine test—Detects aneuploidy 42–83% 72% all
situ hybridisation of chromosomes 3, 7 and 17, and pTa–pT1
(FISH) probe set loss of 9p21 loci in malignant 92–100%
urothelial cells ≥pT2
Nuclear Matrix Matritech Urine test—nonchromatin 51–85% 77–96%
protein structure that maintain nuclear
(NMP—22) shape. Released from tumour
cells after lysis
Bladder Tumour Polymedco Urine point of care test 53–89% 54–93%
Antigen (BTA) (qualitative)—monoclonal
STAT antibodies to detect complement
factor H related protein and
complement factor H
Bladder Tumour Polymedco Urine laboratory assay 17–78% 51–95%
Antigen (BTA) (quantative)—as BTA STAT
TRAK
Fluorescent ImmunoCyt/ Urine test—3 fluorescent 53.8–94.1% 61–80.7%
monoclonal uCyt+ monoclonal antibodies directed
antibodies against at urothelial antigens. M344 and
M344, LDQ10 CEA 19A211 found in 71–90%
and 19A211 of pTa and pT1 TCC
Multiplex CertNDx Urine test (DNA)—analyse 92% 51%
immunoassays presence of FGFR3, quantified
matrix metalloproteinase
(MMP-3) and hypermethylation
of TWIST1 and NID2
Reverse CxBladder Urine Test—X5 mRNA markers 82% 85%
transcription (CDC2, HOXA13, MDK,
quantitive IGFBP5, CXCR5)
polymerase chain
reaction
34 Tumour Markers 199
cystoscopic bladder evaluation. Coupled to this, a lower specificity has limited their
uptake within most urology units within the UK.
Prostate Cancer
Prostate specific antigen (PSA) was characterised in 1979 for the monitoring of
prostate cancer. Catalona et al., first reported the outcomes of PSA detectable pros-
tate cancer in localised disease.
PSA is a 34-kDA glycoprotein produced by columnar acinar and ductal prostatic
epithelium with a half-life of 2–3 days. It is a member of the human kallikrein fam-
ily (HK3), (Diagram 34.1). These are serine proteases that cleave protein peptide
bonds, thus resulting in liquifying seminal coagulum to enable fertilisation. It is
typically found in high concentration in sperm but low concentration in blood and
urine. 75% of PSA is bound within blood (complexed) and metabolised in the liver.
Complexed PSA is stable and bound to either α1-antichymotrypsin (ACT) or
α2-macroglobulin (AMG). The remaining 25% is unbound or ‘free’ and is typically
unstable. Examples of unstable PSA include Pro-PSA (transitional zone, cancer)
and benign PSA (transitional zone, BPH).
PSA is used to support detection, risk stratification, staging, surveillance, treat-
ment monitoring and prognosis of prostate cancer. The most controversial role of
PSA is within screening. There is no defined normal PSA level and thus defining an
“abnormal” cut-off remains contentious. Age specific PSA reference ranges recog-
nise the influence of age on PSA value. An abnormal PSA classified as >4.0 ng/mL
balances the trade-offs between sensitivity and specificity. Using this value, a diag-
nostic specificity of 91% and sensitivity of 21% increasing to 51% in high-grade
cases can be quoted. Despite this, the PCPT trial highlighted the limitations of using
this PSA value alone in detecting significant prostate cancer (Table 34.3). Digital
rectal examinations can further influence prostate cancer detection against PSA
alone (Table 34.4). Novel tumour markers have improved sensitivity compared to
PSA (Table 34.5) but are infrequently used following the introduction of multipara-
metric MRI imaging which provides additional staging information with a high
negative predictive value. Detection of clinically significant disease no longer relies
on PSA alone, but a multi-modal stratification.
Diagram 34.1 Relation-

Prostate
ship of PSA to hK family
Active
PrePro-PSA Pro-PSA
complexed PSA
Pro-hK2 HK2
200 A. Hoyle
Table 34.3 Prostate PSA Level Gleason 3 + 3 (%) Gleason ≥ 3 + 4 (%)

Cancer Prevention Trial
0.0–0.5 ng/ml 5.8 0.8
(PCPT), Risk of
significant disease 0.6–1.0 ng/ml 9.1 1.0
with low PSA 1.1–2.0 ng/ml 15 2.0
2.1–3.0 ng/ml 19.3 4.6
3.1–4.0 ng/ml 20.2 6.7
Table 34.4 Risk of PSA Normal DRE (%) Abnormal DRE (%)
prostate cancer based
0.1–1 ng/ml 10 15
upon PSA and DRE [1]
1.1–2.5 ng/ml 17 30
2.6–4.0 ng/ml 23 40
4–10 ng/ml 25 50
>10 ng/ml 50 >75
Table 34.5 Novel prostate cancer tumour markers

Blood
or
urine
Tumour marker test Detect Sensitivity Specificity Facts
SelectMDx Urine HOXC and 76.9% 49.6% Significant
DLX1 mRNA prostate cancer
expression detection
figures. NPP
98%
Engrailed-2 Urine E2 protein by 66% 88.2% First pass urine
ELISA post DRE
Microseminoprotein-B Urine Low levels of 71% 71%
(MSMB) MSMB—
regulated
apoptosis
RT-PCR Blood Detects specific 0–88% N/A
mRNA of
tumour markers,
ie PSA or HK2
PCA3 Urine Detects DD3 84% (PSA 80% (PSA Use alongside
RNA and 4–10) 4–10) PSA and DRE
PSAmRNA in Perform post
urine DRE
Testicular cancer
Three tumour markers have roles in the diagnosis, monitoring, staging and progno-
sis of patients with suspected or confirmed germ cell tumours (GCT). Alpha feto-
protein (AFP), Beta Human Chorionic Gonadotrophin (βHCG) and Lactate
Dehydrogenase (LDH) either in isolation or in combination are raised in 50% of all
patients with testis tumours. These tumour markers have a high specificity but lower
sensitivity. 30% of Seminoma GCTs and 50–60% of non-seminomatous GCTs
present with raised tumour markers. Table 34.6 demonstrates the individual charac-
teristics of each tumour marker. Patterns in marker positivity may support the pre-
diction of final histological subtype. Pure choriocarcinoma and pure seminoma
GCT do not produce AFP. Yolk sac tumours present with raised AFP in >90% of
cases. βHCG is markedly raised in choriocarcinoma and the finding of excessive
βHCG levels (>100,000 mIU/mL) support the role for additional staging to evaluate
the presence of brain metastases. βHCG shares close molecular characteristics to
thyroid stimulating hormone (TSH). An unexplained “thyroid storm” can therefore
be a rare presentation of high metastatic burden βHCG secreting choriocarcinoma.
An appreciation of tumour marker half-life can support the planning of post
operative tumour marker re-sampling. Persistence in post operative tumour markers
should highlight the risk of residual disease either systemically or within the contra-
lateral testicle. Following histological confirmation, the pre-operative tumour
marker profile supports disease staging (Table 34.7) and prognosis (Table 34.8) as
per the IGCCCG guidelines. The assessment of post chemotherapy residual retro-
peritoneal lesions required knowledge of tumour marker dynamics to determine
management. Persistence of which will commonly require salvage chemotherapy
over surgical excision.
Table 34.6 Testicular cancer tumour makers

Tumour Marker Size (Daltons) Normal range Half Life Origins
AFP 70,000 <40 μg/I 3–5 days Trophoblast elements
βHCG 38,000 <5 IU/I 24–36 h Syncytiotrophoblastic elements
LDH 1,34,000 1.5–3.2 IU/I Variable Muscle, liver, kidney and brain
Table 34.7 Testis cancer staging (American joint Committee on Cancer S Staging)
Stage AFP (μg/I) βHCG (IU/I) LDH
S0 Within normal limits Within normal limits Within normal limits
S1 <1000 <5000 <1.5 × normal
S2 1000–10000 5000–50000 1.5–10 × normal
S3 >10000 >50000 >10 × normal
202 A. Hoyle
Table 34.8 Testis cancer prognosis—International Germ Cell Cancer Collaborative (IGCCCG)
Good prognosis
Testis/retroperitoneal primary AND No non-pulmonary Any primary site AND No-non-
visceral metastases AND all of AFP < 1000 ng/ml) pulmonary visceral metastases And
HCG < 5000 IU/L LDH < 1.5 × upper normal limit Normal AFP, any HCG, any LDH
(ULN)
Intermediate Prognosis
Testes/retroperitoneal primary AND no-non-pulmonary Any primary site AND Non-pulmonary
visceral metastases AND any of AFP ≥ 1000 ng/ml visceral metastases AND Normal AFP,
and <10,000 ng/ml) HCG ≥ 5000 IU/L and any HCG, any LDH
<50,000 iu/l LDH ≥ 1.5 × ULN and <10 × ULN
Poor prognosis
Mediastinal primary Or Non-pulmonary visceral No patients classified as poor
metastases Or any of AFP ≥ 10,000 ng/ml prognosis
HCG ≥ 50000 IU/L LDH ≥ 10 × ULN
Renal Cancer and Penile Cancer
There are currently no reliable tumour markers to aid the detection of renal cell
cancer or penile cancer. Several tissue and serum biomarkers exist to help predict
treatment response and prognosis, which fall outside the scope of this chapter.
The Future
Interest is focusing on specific disease related genomic signals identified in com-

mon urological and non-urological cancers. The Galleri test is currently under eval-
uation for clinical application within the NHS. This identifies a series of genetic
signals from DNA within blood that may improve current limitations in sensitivity
seen in existing tumour markers, whilst screening for simultaneous multiple onco-
logical pathologies.
Venous or urine circulating tumour cells (CTC) may negate the need for a tradi-
tional tissue biopsy in favour of a “liquid biopsy,” providing an insight into the biol-
ogy of the disease including tumour type and grade. Combining genomic signalling
and CTC analysis may greatly improve the accuracy and speed of diagnostics,
whilst reducing the invasiveness of traditional investigation.
Reference
1. Catalona WJ, Smith DS, Ratliff TL, et al. Measurement of prostate-specific antigen in serum as
a screening test for prostate cancer. N Engl J Med. 1991;324:1156–61.
Further Reading
NICE, Suspected cancer: recognition and referral. NICE Guideline. 2015. www.nice.org.uk/
guidance/ng12.
Thompson IM, Pauler DK, Goodman PJ, et al. Prevalence of prostate cancer among men with a
prostate-specific antigen level ≤ 4.0 ng per milliliter. N Engl J Med. 2004;350(22):2239–46.
Chapter 35
Measurement of Glomerular Filtration
Rate (GFR)
Stephen Brown
Glomerular Filtration Rate (GFR) is the volume of plasma filtered by the glomeruli
in mls/min. It can be measured as the clearance of any substance that is filtered but
not actively secreted or reabsorbed by the tubules.
Introduction
Glomerular Filtration Rate (GFR) is a measure of the volume of fluid filtered by the
glomerular capillaries expressed in per unit time. Multiple markers can be utilised
in order to measure GFR but these markers ideally should be exclusively filtered by
the kidney and not actively secreted or reabsorbed. The fructose polymer inulin is
the traditional GFR marker which meets these criteria but is not practical for use
clinically. Endogenous markers are used for day-to-day practice but exogenous
markers can be employed if a more accurate measure is required. GFR is propor-
tional to body surface area (BSA) and it is therefore helpful to standardise measure-
ments by expressing in mls/min/1.73m2, the latter being the average adult
BSA. Normal values are generally >90 ml/min/1.73m2.
S. Brown (*)
Stepping Hill Hospital, Stockport, UK
e-mail: stephencwbrown@nhs.net

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_35
206 S. Brown
Endogenous Markers
Creatinine
Creatinine is the commonest marker used to assess renal function. Its metabolic
pathway from the breakdown of phosphocreatine in muscle to renal excretion is
shown in Fig. 35.1. Production is relatively stable and hence its serum concentration
can be used as a surrogate marker to calculate GFR.
Levels are however, affected by muscle bulk and as function falls, tubular secre-
tion and extra renal degradation can increasingly affect the result.
Methods based on serum creatinine become more sensitive as the GFR falls
because of the relationship between serum concentration and clearance (Fig. 35.2).
Several methods are used to derive GFR from the serum concentration:
Tubular secretion blocked by drugs:

Increased by eating Trimethoprim, amiloride, cimetidine
Increased with muscle bulk meat / protein supplements spironolactone, probenecid
eg athletes
MUSCLE SERUM KIDNEY

Produced from the CREATININE
Primarily filtered at the
steady breakd own
Mainly dependent glomeruli with secondary
of phosphocreatine
and creatine on renal clearance secretion in the tubules
Reduced muscle mass Tubular secretion enhanced

eg: women, elderly, malnutrition in renal failure
Fig. 35.1 The metabolic pathways influencing serum creatinine and its renal excretion
120
Creatinine Clearance (ml/min)
100
80
60
20
0
0 100 200 300 400 500 600 700
Serum Creatinine (umol/l)
Fig. 35.2 The relationship between creatinine clearance and serum creatinine concentration
35 Measurement of Glomerular Filtration Rate (GFR) 207
eGFR
eGFR is the most widely used estimate of GFR in clinical practice. It is derived
from the serum creatinine using one of two equations which take into account the
patient’s age, sex and race.
1. The MDRD Equation (from the Modification of Diet in Renal Disease Study)
eGFR = 175 × Serum Creatinine-1.154 × Age-0.203 × [1.212 if black] × [0.742 if
female].
2. The CKD-EPI (Equation (Chronic Kidney Disease Epidemiology Collaboration)
eGFR = 141 × min (Serum Creatinine /κ, 1)α × max(Scr /κ,
1)-1.209
× 0.993Age × 1.018 [if female] × 1.159 [if black].
κ is 0.7 for females and 0.9 for males, α is −0.329 for females and − 0.411 for
males, min indicates the minimum of Scr /κ or 1, and max indicates the maximum of
Scr /κ or 1.
eGFR has been validated for chronic kidney disease (CKD) and shown to be
reasonably accurate in non-hospitalised patients with known CKD regardless of
diagnosis. It is less reliable for obese patients. It is not validated for acute renal
failure, pregnancy or childhood. For children, a version of the Bedside Schwartz
Equation should be used.
Cockraft Gault Equation has largely been replaced by the eGFR. Creatinine
clearance was calculated as follows:
140 − age × lean body weight ( Kg )

CCr =
Cr ( mg / dl ) × 72
24 Hour Creatinine Clearance

A more accurate measure of the GFR is the 24 h creatinine clearance. This can
be obtained by measuring the creatinine concentration in a 24 urine collection
together with the serum concentration during this period and applying the following
formula.
U Cr × V
CCr =
PCr × 24 × 60
PCr is serum concentration.

UCr is urine concentration.
V is urine 24 volume.
The clearance is then corrected for Body Surface Area (BSA).
208 S. Brown
Cystatin C
An alternative endogenous marker is Cystatin C, a low molecular weight protein

(13.3 kilodaltons), which is filtered by the glomerulus, but then completely reab-
sorbed and metabolised by the tubules so does not appear in the urine. It is gener-
ated at a constant rate by all nucleated cells and is therefore less susceptible to
changes in body mass. The eGFR can be calculated for cystatin C in a similar way
to creatinine. In multiple studies cystatin C was more sensitive in identifying mild
reductions in kidney function than serum creatinine. Although reference ranges
have been reported, there is no current standard for cystatin C and testing is only
available in a limited number of laboratories.
Exogenous Markers
Cr-EDTA Clearance
The chelating agent EDTA (Ethylene diamine tetra acetic acid) is filtered by the
kidney but not reabsorbed or secreted. It therefore makes an ideal exogenous marker
for measuring GFR and when labelled with 99mTechnetium, is easy to assay. This
method is discussed in more detail in Chap. 25.
Further Reading
Hallan S, Asberg A, Lindberg M, Johnsen H. Validation of the modification of diet in renal disease
formula for estimating GFR with special emphasis on calibration of the serum creatinine assay.
Am J Kidney Dis [Evaluation Studies Validation Studies]. 2004;44(1):84–93.
Chapter 36
Assessment of Urinary Tract Stones
Robert C. Calvert
The life-time incidence of urinary stone disease is about 13% in the UK. The pri-
mary outcome in the medical management of stones is to reduce future stone forma-
tion, minimize complications and identify underlying metabolic abnormalities.
Introduction
The life-time incidence of urinary stone disease is about 13% in the UK. It is higher
in men and lower in women. There has been significant increase in the number of
hospital episodes and procedures performed for stone disease in recent years, prin-
cipally related to changes in diet. About 50% of people who form a kidney stone
form a further stone within 10 years, increasing to 90% at 30 years.
The primary outcome in the medical management of stones is the desire to influ-
ence the following factors:
• Reduce future stone formation.
• Minimise the risk of stone complications, principally infection and obstruction.
• Identify any underlying metabolic abnormality which predisposes to future stone
formation. The main conditions under consideration here are primary hyperpara-
thyroidism, gout, and cystinuria.
R. C. Calvert (*)
Liverpool University Hospital NHS Foundation Trust, Liverpool, UK

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_36
210 R. C. Calvert
Stone Composition
Calcium oxalate stones are the most common type accounting for 80–90% of stones.
Commonly, there is a component of carbonate apatite in combination with the cal-
cium oxalate. This is an amorphous form of calcium phosphate.
A minority of calcium stones are made of the brushite form of calcium phos-
phate. Patients forming these stones have a higher risk of stone recurrence and a
higher risk of an underlying metabolic abnormality.
Currently, uric acid composition is the second most common stone in both gen-
ders, and is largely related to the current trends in obesity. Patients with type 2 dia-
betes demonstrate insulin resistance with impaired ammonium excretion, resulting
in a reduced urinary pH and a tendency to form uric acid stones. Indeed, up to 50%
of uric acid stone formers have evidence of insulin resistance. Obesity, diabetes,
hypertension (metabolic syndrome in general) are also risk factors for calcium oxa-
late stones and the increased prevalence of these conditions along with poor dietary
habits have driven the increase in stone disease in most Western countries.
Infection related stones (struvite) have declined in frequency over the years, and
this is largely attributable to improved antibiotic management of urinary tract infec-
tion. The decreasing number of staghorn stones in Europe supports this observation
because urinary tract infections are the commonest cause of such large renal calculi.
About 1% of kidney stone formers produce cystine stones. Cystinuria is an auto-
somal recessive condition caused by mutations in SLC3A1 or SLC7A9 genes which
encode the transport proteins which reabsorb the amino acids cystine, ornithine,
arginine and lysine in the proximal tube of the kidney. Cystine is poorly soluble and
patients with homozygous cystinuria normally form multiple stones through
their lives.
Risk Factors of Stone Formation
Co-morbidities which increase stone risk include hypertension, diabetes, obesity,

gout, Crohn’s disease, cystic fibrosis, gastric bypass surgery, hyperparathyroidism
and sarcoidosis.
There are several anatomic risk factors of stone formation (summarised in
Table 36.1).
Many of these risk factors cause some degree of urinary stasis. In addition, infec-
tion is generally considered to be a major promoting influence for lithogenesis.
There are also several metabolic risks for stone formation (summarised in
Table 36.2).
36 Assessment of Urinary Tract Stones 211
Table 36.1 Anatomical and Kidney Calyceal diverticulum

structural risk factors for PUJ obstruction
urinary tract stone formation
Ureter Hydroureter
Bladder Voiding dysfunction including BOO
& neurogenic bladder
Other Urinary tract reconstruction
including ileal conduit & cystoplasty
Foreign bodies Indwelling catheter
JJ/metallic stent
Table 36.2 Metabolic risks for urinary tract stone formation

Calcium based stones Promoters Hypercalciuria
Hyperuricosuria
Hyperoxaluria
Inhibitor deficiency Hypocitraturia
Hypomagnesuria
Urinary characteristics Increasing urinary acidity
Reduced urinary volumes
Non-calcium based stones Promoters Hyperuricosuria
Cystinuria
Inhibitor deficiency Hypocitraturia
Urinary characteristics Increased urinary acidity
Low urine volumes
Urinary tract infection
Basic Evaluation of all Stone Formers
Based upon these risk factors, the usual basic evaluation of a first-time stone former
includes:
• A careful medical history, including family history
• Drug history
• Dietary history
• Stone analysis (If stone is available for analysis, this should be examined by
X-ray diffraction or infrared spectroscopy)
• Serum creatinine, corrected calcium and urate
• Urine dipstick for pH, leucocytes, protein, and nitrites
• Midstream urine for culture
• Consider urine tests for cystine in younger patients
212 R. C. Calvert
Generic Diet and Fluid Advice
Discuss diet and fluid intake with the person (and their family or carers, as appropri-
ate), and advise:
• adults to drink 2.5–3 l of water per day, and children and young people (depend-
ing on their age) 1–2 l
• adding fresh lemon juice to drinking water
• avoiding carbonated drinks
• adults to have a daily salt intake ≤6 g, and children and young people (depending
on their age) 2–6 g
• not restricting daily calcium intake, but maintaining a normal calcium intake of
700–1200 mg for adults, and 350–1000 mg per day for children and young peo-
ple (depending on their age).
• There is epidemiological evidence showing that people with diets high in animal
protein are at increased risk of stone formation and the people with diets high in
fibre, fruit and vegetables have a lower risk of stone formation.
Specialised Evaluation
The basic evaluation is usually all that is required but in certain circumstances a
more intensive assessment is necessary. The centrepiece of this assessment is the
analysis of two 24-h urine collections. Indications for more detailed investigation
include the following groups of patients:
• Early stone recurrence
• “High-risk” first-time stone former (see section on risk factors)
• Strong family history of stone formation
• Significant residual stones post-treatment
• Stone formation at a young age
• Complex or bilateral stone disease
• Brushite or non-calcium based stone
Twenty-Four Hour Urine Collections
At least two specimens should be collected on consecutive days. Collection should

be postponed until at least 4 weeks after stone removal or relief of obstruction.
These studies should not be undertaken in the presence of infected urine or
haematuria.
The collecting bottles should be prepared with 5% thymol in isopropranolol or
stored at a cool temperature (<8 °C) for the period of collection. Urinary pH should
36 Assessment of Urinary Tract Stones 213
be assessed on a fresh specimen. Hydrochloric acid is still used by some laborato-

ries in one of the bottles to reduce calcium precipitation although this does have
some safety risks and studies have shown that it is not necessary if the samples are
processed promptly.
The relevant 24 h urine measurements are:
Saturation determining: volume, pH.
Stone constituents: calcium, oxalate, urate.
Stone inhibitors: citrate, (magnesium).
Dietary indicators: sodium, urea.
Metabolic Treatments
First line management involves changes to diet and fluid. Second line involves phar-
macological measures. High-risk stone formers often have abnormalities in several
of the parameters measured.
The most common abnormalities are:
• Low 24-h fluid volume—patients should be encouraged to drink 2.5–3 l of fluid
per 24 h, mostly water
• High 24-h urine sodium—there is a close relationship between 24-h urine
sodium and the amount of salt consumed in the previous 24 h. High salt intake
drives hypercalciuria and at least half of patients with hypercalciuria will have
this corrected by reducing their salt intake
• High 24-h urine calcium—if this persists despite normalising 24-h urine
sodium, a thiazide diuretic such as bendroflumethiazide or indapamide might be
considered
• Low urine pH—for calcium oxalate or urate stones this is a significant risk fac-
tor. Urine pH can be improved by shifting away from acid-ash food (meats,
breads etc) to foods that increase urine pH (most fruit and vegetables). Avoiding
carbonated drinks may help as can potassium citrate solution.
• High 24-h urate or urea—reducing animal protein intake can improve this,
although allopurinol is sometimes indicated, particularly in association with gout
• Low 24-h urine citrate—this can be increased by consuming more citrus fruits,
adding some fresh lemon to water or with potassium citrate solution
• High 24-h urine oxalate—this is of most relevance in patients with terminal
ileal disease (e.g. Crohn’s disease). Avoiding oxalate in diet is tricky as it is pres-
ent in many food types, but it is worth making sure that the patients isn’t eating
huge amounts of chocolate or nuts. In Crohn’s disease, a calcium supplement
with meals can help bind oxalate in the gut.
The mainstay of metabolic management of patient with urate stones or cystine stone
is dietary and fluid changes (+/− Potassium citrate) to increase the urine pH to
reduce the risk of stone growth.
214 R. C. Calvert
For cystinuria a high fluid intake is also very important (3–4 l/24 h). For struvite
stones associated with infection, the most important factor is to surgically remove
all the stone so that the urine can be eradicated of urease-splitting organisms. A
period of antibiotic prophylaxis after surgery is sometimes used.
Further Reading
Littlejohn TJ, et al. Fluid intake and dietary factors and the risk of incident kidney stones in UK
biobank: a population-based prospective cohort study. Eur Urol Focus. 2020;6:752–61.
Renal and ureteric stones: assessment and management. https://www.nice.org.uk/guidance/ng118.
Skolarikos A, et al. European association of urology guidelines on urolithiasis. 2022. www.
uroweb.org.
Chapter 37
Principles of Pressure Measurement
Ian Pearce
The medical measurement of pressure refers to the height of a column of fluid in a

manometer, relative to atmospheric pressure. It is commonly used to directly mea-
sure the physiology of a cavity such as the bladder. Demonstration of intra-cavity
pressure is dependent upon a transducer and a recording device. The most common
utilisation of this in clinical urology is urodynamic studies.
Measuring Pressure
Pressure transducers relay pressure measurements, using generated electrical sig-

nals, to a urodynamic machine which makes a digital record of the pressure. Two
types of transducer exist which are either external, or internal to the patient. The key
difference between these types of transducer is that the pressure recorded by exter-
nal transducers depends upon the position of the transducer in relation to the cavity,
whilst internal devices transduce pressure dependent upon the position of the trans-
ducer tip relative to the wall of the cavity. Pressure measurement, during any urody-
namic study, is dependent upon three actions: setting a “zero” pressure for the
transducer, calibration and establishment of a pressure reference point.
I. Pearce (*)
Department of Urological Surgery, Manchester Royal Infirmary, Manchester University NHS
e-mail: ian.pearce@mft.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_37
216 I. Pearce
External Pressure Transducers
External strain gauge transducers are the standard transducer used in most urody-
namic studies. They are connected to both bladder and rectal catheters via either
fluid-filled, or air-charged tubing. This tubing is designed to be non-compressible in
order to minimise artifactual pressure fluctuation. Water-filled lines are most com-
monly used but demand ‘zeroing’ at the level of the symphysis pubis and are subject
to a variety of observed artefacts at the level of the transducer (Table 37.1). Air-
charged lines connect the catheter to the diaphragm by a microscopic water droplet
in the transducer housing.
External transducers are constructed of a diaphragm bound with strain sensitive
resistive wire, which has a current passing through it, in a plastic housing (Fig. 37.1).
As the pressure on the connecting tube side of the diaphragm changes, the force
deforms the diaphragm altering the wire’s length and causing a change in its electri-
cal resistance. This results in a voltage surge which is recorded, amplified and trans-
lated into a pressure reading seen on the urodynamic trace. External transducers are
cheap, widely available, accurate and reliable.
Fluid-filled transducers are “zeroed “to atmospheric pressure prior to commenc-
ing the study, with the transducer opened to the atmosphere and closed to the blad-
der. Likewise, for air charged transducers, the transducer is open to the atmosphere
and the machine set to zero prior to the switch being moved to the “charge” position.
Calibration of external transducers is typically performed automatically by the
Table 37.1 Artifactual Cause Effect

pressure registrations seen in Air bubbles within system Dampened pressure signal
fluid-filled, external pressure
Kinking of tubing Dampened pressure signal
transduction systems
Non-urodynamic tubing Dampened pressure signal
Contact between filling and Rhythmic pressure
pressure lines fluctuation
Transducer above reference Erroneously low resting
point pressure
Transducer below reference Erroneously high resting
point pressure
Fig. 37.1 An example of a strain-gauge external transducer system. The diaphragm lies below the
housing (a) which goes to the patient via a water column at connector (b). The transducer dia-
phragm is placed into the housing (c)
37 Principles of Pressure Measurement 217
urodynamic machine but manual calibration may be performed by subjecting the

diaphragm to the pressure exerted by a column of water 0–100 cm high. The classic
pressure reference point, for urodynamic studies, is the top of the symphysis pubis.
The ICS recommends fluid filled external catheters and there is increasing evi-
dence that pressure values are not directly interchangeable between these two sys-
tems. Reference levels widely used were determined by systems utilising fluid filled
external transducers.
Internal Transducers
Internal transducers rely on semi-conductor technology to translate pressure into

voltage changes using a deformable membrane transducer mounted directly on the
tip of a ‘catheter’ (Fig. 37.2). Membrane deformation results in a change in the volt-
age coming down the stem of the wire which connects the transducer to an external
urodynamic recording device. Positioning of the tip of the sensor may result in
artifactual variations in pressure registration (Table 37.2).
Fig. 37.2 A microtip

catheter transducer.
Pressure on the white
membrane results in an
altered potential difference
across the length of the
transducer proportional to
the applied membrane
deformation (image
courtesy of Steve Payne)
Table 37.2 Artifactual Cause Effect

pressure registrations seen Direct contact with Erroneously high bladder pressure
with internal pressure bladder wall
transduction systems
Sensor tip at bladder base Erroneously high bladder pressure
Sensor tip at bladder dome Erroneously low bladder pressure
218 I. Pearce
Catheter tip transducers are ideal for urethral pressure profilometry and ambula-
tory urodynamic studies. They have the advantage of not needing priming, are sub-
ject to minimal artifactual variations, especially patient movement, and allow easy
measurement of resting bladder pressure. Internal transducers are, however expen-
sive, relatively fragile and therefore, not widely used. In addition they behave in an
attenuated fashion, particularly with rapid pressure changes which may be damp-
ened and delayed. Internal catheter tip transducers have factory-set zeroes and are
calibrated either automatically or manually by submerging the tip of the catheter to
a set depth in a column of water. The pressure registration should directly reflect the
depth in the water column, in a linear fashion. The pressure reference point, for
urodynamic studies, is the middle of the bladder.
Further Reading
Lotze PM. A comparison of external transducers and microtransducers in urodynamic studies of

female patients. Curr Urol Rep. 2005;6:326–34.
Schafer W, Abrams P, Liao L, et al. Good urodynamic practice: uroflowmetry, filling cystometry,
and pressure flow studies. Neurourol and Urodyn. 2001;21:261–74.
Gammie A, Clarkson B, Constantinou C, et al. International continence society guidelines on uro-
dynamic equipment performance. Neurourol Urodyn. 2014;33(4):370–9.
Chapter 38
Principles of Measurement of Urinary
Flow
Timothy Napier-Hemy and Richard Napier-Hemy
Urinary flow rate is a volumetric measurement of the quantity of urine excreted in a

specific period of time (ml/min). It is a useful baseline, non-invasive tool in evaluat-
ing patients with voiding dysfunction.
Why Measure Flow?
Patients are notoriously poor at accurately reporting changes in their flow. Flow rate
estimation is an inexpensive and non-invasive objective assessment of voiding
symptoms. It is a first line investigation in male patients with voiding dysfunction
but has a less established role in women. Uroflowmetry measures flow only and
assumptions about detrusor function can only be inferred.
Uroflowmetry should be performed in a private room. Prior, written explanatory
information is advised, this may include a bladder dairy or frequency volume chart.
Patients should be instructed to attend with a comfortably full bladder and void
when they have a “normal desire to do so” in their usual voiding position, avoiding
straining. Men should avoid compressing the penis and prevent their stream from
moving around the funnel.
Following the procedure, it should be recorded whether the patient felt the flow
was representative. Ideally, three flow rates should be performed, but this may be
impractical and is not always required in the presence of a single, normal, represen-
tative void. Voided volume should be above 200 mls and below the maximum
T. Napier-Hemy (*)
Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Salford, UK
R. Napier-Hemy
Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester, UK

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_38
220 T. Napier-Hemy and R. Napier-Hemy
Table 38.1 Types of uroflometer

Type of flow
meter Principle Advantages Disadvantages
Weight Gravimetric principle: weight of Accurate volume Relatively slow
transducer urine collected indicates the volume measurements. response time.
and by differentiation, the flow rate. Relatively simple.
“Wag effect”.
Density of urine
affects results.
Density must be set.
More prone to
“knocking” artifacts.
Rotating- Momentum Flux Principle: urine is Accurate flow rate Interpretation of
disc directed onto a spinning-disc, which measurements traces: artifacts can
spins at constant speed. Flow is Fast response time. arise from “wag
measured by analysis of the power effect”. See below.
needed, from the disc’s motor, to Results are affected
keep the rotation speed constant. by the density of
urine.
Difficult to clean.
Capacitance Bimetallic strip; The electrical Least expensive. Density must be set.
capacitance of a dipstick, mounted in No mechanical Prone to “knocking”
the chamber, changes as the height of parts. artifacts.
the column of urine in a container of
a standard size alters.
voided volume recorded on the patient’s frequency/volume chart. Volumes over

400–500 mls may lead to detrusor overdistension causing reduced contractility. Post
void residual volume should be documented to aid interpretation of the results.
Information gained from uroflowmetry, when combined with clinical history, blad-
der diary and examination can be used to start treatment whilst avoiding or delaying
cystometry.
There are three established means of measuring urinary flow. Each has a funnel
to collect the urine, a calibratable flow measurement device and a data recorder.
Most devices have a printer but more recently wireless/WIFI compatible devices
have allowed for digital data recording and integration with established hospital
information systems. The measuring device principles are given in the Table 38.1.
I nternational Continence Society (ICS) Definitions

and Their Application
• Urine flow rate (Unit: mL/S-UFL) is defined as the volume of fluid expelled
via the urethra per unit time.
• Voided volume (Unit: mL-VV) is the total volume of urine expelled via the
urethra during a single void. It is the area under the flow curve. It can be esti-
mated by appreciating that each square represents a volume of Y mls/s x Xsecs.
The number of complete squares can be counted and multiplied by this. In the
38 Principles of Measurement of Urinary Flow 221
curve below there are 9 complete squares so the voided volume has to be over
450 mls.
• Maximum urine flow rate (Unit: mL/s-Qmax) is the maximum measured
value of the urine flow rate corrected for artefacts. The automated print out gen-
erated by most machines will not identify an artifact and may overestimate
Qmax. Looking at the trace is the best way of working out Qmax.
• Voiding time (Unit: s-VT) is total duration of micturition, including interrup-
tions. When voiding is completed without interruption, voiding time is equal to
flow time.
• Flow time (Unit: s-FT) is the time over which measurable flow actually occurs.
Difference between voiding time and flow time means that there is an intermit-
tent flow. It does not reveal the underlying nature of the intermittency.
• Average urine flow rate (Unit: mL/s-Qave) is voided volume divided by flow
time. The average flow should be interpreted with caution if flow is interrupted
or there is a terminal dribble. Qave can be calculated by timing a void and then
measuring the volume voided. Volume / voiding time = Qave (or VT/V = Qave)
• Time to maximum flow (Unit: s-TQmax) is the elapsed time from onset of
urine flow to maximum urine flow. Automated measurement can be wrong. The
time to Qmax must also be ascertained directly from the trace.
Limitations of Urine Flowmetry
Urinary flow rates reflect the interaction between intra-vesical pressure and urethral
calibre. You can only infer what type of muscle has caused the increase in urinary
flow. Smooth muscle contracts and relaxes slowly and produces the reproducible,
skewed, bell shaped curve shown in Fig 38.1. Striated muscle contraction with
abdominal straining produces more rapid changes in pressure, which are different
Fig. 38.1 A normal urine 50 mL/s flow tate

flow rate curve and its
derived parameters
0 10 20 30 40
Voiding time T100 33 s

Flow time TQ 32 s
Time to max flow TQmax 9 s
Max flow rate Qmax 33.8 mL/s
Average flow rate Qave 18.6 mL/s
Voided volume Vcomp 602 mL
222 T. Napier-Hemy and R. Napier-Hemy
Table 38.2 Artifacts encountered during uroflowmetry and their influence on intra-vesical
pressure, the flow at the external meatus and the observed flow pattern
Effect on Effect on flow
intra-vesical at the external
Artifact pressure urinary meatus Effect on flow trace
Cough Increased Increased Short sharp spike of increased flow.
Valsalva / strain Increased Increased Wider increased flow spike.
Wagging / No increase No increase Sharp spike with decreased flow either side.
cruising Caused by the urinary stream being directed
across the funnel with artifactual variation in
the incident flow recorded by the measuring
transducer.
Manual No increase Reduced flow, Flow interrupted and reduces. Urethra fills
urethral then increased with urine with increased flow on release of
compression urethral compression.
External Possible Small increase, Small increase in flow before it stops.
sphincter small then zero flow
contraction increase
Knocking No increase No increase High spike of flow. Spike so bizarre in
appearance it could not have been caused by
physiological bladder activity.
with each strain. On this basis the investigator may infer whether bladder emptying
is by abdominal strain or detrusor contraction. Uroflowmetry is also subject to arti-
factual variations (Table 38.2).
Future Developments
Software using sound-waves to interpret acoustic flow rates, which can be used on
an app-based platform has been developed. Studies have compared acoustic to con-
ventional uroflowmetry but further investigation regarding reliability and validity is
required.
Further Reading
Caffarel J, Griffiths CJ, Pickard RS, Robson WA, Drinnan MJ. Flow—How far can you go?
Urodinamica. 2006;16:259–69.
D’Ancona C, Haylen B, Oelke M, et al. The International Continence Society (ICS) report on the
terminology for adult male lower urinary tract and pelvic floor symptoms and dysfunction.
Neurourol Urodyn. 2019;38(2):433–77.
Dawidek MT, Singla R, Spooner L, Ho L, Nguan C. Clinical validation of an audio-based uro-
flowmetry application in adult males. Can Urol Assoc J. 2022;16(3):E120–5. https://doi.
org/10.5489/cuaj.7362.
Chapter 39
How to Carry Out a Video
Cystometrogram (VCMG) in an Adult
Magda Kujawa
Videocystometrography (VCMG) is a complex study of urinary tract function and

anatomy, using a contrast medium to fill the bladder, allowing for conventional pres-
sure flow urodynamics with simultaneous imaging of the urinary tract.
Introduction
Performing a good and informative VCMG study is a skilled task and special train-
ing is required to undertake and interrogate the test. To determine best management
for a patient requires studies of the utmost quality. The main indications for the use
of VCMG in the adult population are in the investigation of the following:
• Urinary symptoms seen in neurological disease
• Women who have had previous surgery for stress urinary incontinence (SUI) and
have recurrent symptoms
• Men under 60 years with recalcitrant LUTS e.g. voiding symptoms, chronic
retention or high post void residuals
• Post-prostatectomy incontinence
• Children when anatomical abnormalities are more relevant
• Transplant patients or those with complex previous reconstruction
• Patients who have symptoms that don’t add up and may have had inconclusive
standard UDS.
M. Kujawa (*)
Stepping Hill Hopsital, Stockport NHS Foundation Trust, Stockport, UK
e-mail: magda.kujawa@doctors.org.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_39
224 M. Kujawa
Pre-procedure Checks
The procedure is commonly performed in the X-ray department employing a fixed

X-ray unit and tilt table. Routine antibiotic prophylaxis should be avoided in the
interest of antibiotic stewardship. However, antibiotics should be strongly consid-
ered in the following patients:
• Patients with high post void residuals and neurogenic lower urinary tract
dysfunction
• Children with suspected/confirmed reflux
• Immunosuppressed patients
• Patients using intermittent self-catheterisation or indwelling catheters.
• Patients with recent orthopaedic implantation
Examinations should always be deferred when an untreated UTI is confirmed or
suspected. It is essential to record consent, check pregnancy status and allergies and
to conform with standards of the Ionising Radiation(Medical Exposure) Regulations
IR(ME)R regulations
The study should commence with the patient history and review of a 3 day blad-
der diary to confirm justification of the test and to inform the urodynamic question.
The patient is then asked to void to obtain a free flow rate and check the post void
residual. In order to reproduce patient symptoms, the residual urine should be left
and the bladder filled on top of this, unless the residual is so large dilution of con-
trast would hinder interpretation.
Preparation
The patient is placed in a comfortable position and under aseptic technique, with
lubrication from topical gel anaesthetic, the patient should be catheterised (ure-
thrally or via SPC tract) either using a 6 fr double lumen catheter or with an 8 Fr
filling catheter into which an epidural catheter to measure vesical pressure (16
gauge) can be piggy backed.
Measurement of intra-abdominal pressure is essential as this is subtracted from
intravesical pressure to derive detrusor pressure (pDet = Pves-pAbd). Most com-
monly a rectal catheter is placed. Proprietary catheters are available that protect the
end of the tube with a small balloon that prevents the lumen from blockage and
39 How to Carry Out a Video Cystometrogram (VCMG) in an Adult 225
ensures good contact with the rectal wall. Abdominal pressure can also be measured
high in the vaginal fornix or in a colostomy or ileostomy held in place by the patient
and covering pad. All lines should be secured to the thigh with tape in an arrange-
ment to prevent contact and artefact.
The pressure lines are connected to the solid state pressure transducers on the
urodynamics machine and then flushed with saline to expel all air bubbles ensuring
effective pressure transmission. The pressure transducers are set at the height of the
pubic symphysis and “zeroed” to atmosphere and then closed. It is essential for
quality traces to ensure good subtraction so check this by asking the patient to
cough. There should be an equal deflection on pAbd and pVes with minimal disrup-
tion of pDet and then rapid return to resting pressure with no damping. Lines may
need to be re-flushed to achieve this.
The patient can then be moved into position for the study. This may be supine if
the patient is unable to stand or sit, or a tilt table can be used to move mobile patients
into a standing position. The voiding position should be as close as possible to nor-
mal for the individual.
The Study
The study can then commence with simultaneous recording of intravesical pressure,
rectal pressure, the subtracted detrusor pressure and imaging of the lower urinary
tract. The bladder is filled slowly choosing an appropriate fill rate. The ICS recom-
mends using the maximum voided volume from the bladder diary and dividing by
10 to determine the fill rate. Standard fills rates tend to be 50 mls/min. In patients
with known neurological disease, this should be decreased to 10 ml/min.
During the test the patient should be asked to cough at regular intervals to check
quality control and for provocation of stress urinary incontinence. X ray screening
should also be used to assess bladder anatomy and annotation of the patient’s blad-
der sensation should be noted with filling. When the patient senses a full bladder,
the filling should be ceased. The study moves onto the voiding phase where the
patient should be prompted to void into a flow rate machine whilst performing
simultaneous x-ray screening of the urinary tract. At the end of the study, bladder
emptying should be assessed, again using x-ray (Fig. 39.1).
226 M. Kujawa
Fig. 39.1 This is the Urodynamic trace (pre ICS 2017) from the accompanying video study
(Fig. 39.2) in a patient with stress urinary incontinence. Note the recording of the “zeroing” to
atmosphere at the beginning of the study and the good subtraction of Pabd from Pves to get a rela-
tively flat Pdet line with regular annotation of activity
What is Measures or Observed?
Standard measurements that should be included to ensure a quality study are as

follows:
• Volume at first sensation, normal desire to void, strong sensation and urgency.
• Bladder capacity
• Leak point pressure Valsalva in the assessment of stress incontinence
• Detrusor leak point pressure in those with neurological disease
• Detrusor activity
• Pressure flow studies identifying possible obstruction and bladder contractility
The following information is gained from the imaging system synchronous with the
pressure traces:
• Bladder neck function
• External sphincter function
• Demonstrable incontinence (see Fig. 39.2)
• Bladder anatomy such as trabeculation or diverticula
• Vesico-ureteric reflux
39 How to Carry Out a Video Cystometrogram (VCMG) in an Adult 227
Fig. 39.2 Demonstration of stress incontinence at video urodynamics
Modifications of the video-urodynamic study are possible but in practice are

performed infrequently; these include:
• Electromyography may be applied to the pelvic floor muscles, identifying
sphincteric and bladder neck function. This is not easily performed in children.
• Urethral pressure profilometry using a solid-state catheter-mounted transducer,
withdrawn steadily through the urethra.
Further Reading
Drake M, Hashim H, Gammie A. Abrams’ urodynamics. 4th ed. Wiley Blackwell; 2021.
Working Group of the United Kingdom Continence Society, Abrams P, Eustice S, Gammie A,
Harding C, Kearney R, Rantell A, Reid S, Small D, Toozs-Hobson P, Woodward M. UKCS
minimum standards for urodynamic studies. Neurourol Urodyn. 2019;38:838–56.
Chapter 40
Sphincter Electromyography (EMG)
Emma L. Foster, Katherine E. Burnett, and Christopher D. Betts
Electromyography (EMG) is the study of bioelectrical potentials from striated mus-

cle. Conventional EMG is used to examine individual motor units and to identify
abnormal spontaneous activity. External urethral sphincter activity may be studied
in relation to bladder function, and this is known as kinesiologic EMG.
Electrophysiology
The external striated sphincter is innervated by neurones whose cell bodies lie in
Onuf’s nucleus (S2–S4). A Motor unit (MU) consists of the motoneuron (cell body
in Onufs nucleus) axon and all of the muscle fibres it innervates. An impulse from
the motor neurone passes along the axon to the neuromuscular junction, the action
potential crosses the junction and causes depolarisation in the muscle fibres (muscle
action potential) innervated by the motor neurone. The muscle action potential
releases calcium ions with subsequent muscle fibre contraction. The motor unit
action potential (MUAP) is the sum of the electrical activity resulting from depolari-
sation in a single motor unit. EMG is the study of these action potentials.
EMG can be recorded by surface (skin) electrodes and intramuscular electrodes
(needle). Surface electrodes are highly unreliable in recording urethral sphincter
muscle activity largely because of movement artefacts. The most common type of
needle electrode used for EMG is the concentric needle electrode (CNE); a fine wire
is embedded in a layer of insulation with an outer metal shaft that serves as the
E. L. Foster (*) · K. E. Burnett · C. D. Betts

Department of Urology, Salford Royal Hospital, Salford Care Organisation, Northern Care
Alliance, Salford, UK
e-mail: Emma.foster2@NCA.nhs.uk; emma.foster2@srft.nhs.uk; kate.burnett@nca.nhs.uk;
chris.betts@nca.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_40
230 E. L. Foster et al.
Fig. 40.1 Kinesiologic

urethral sphincter
electromyography with
needle electrode. Electrical
silence in the external
urethral sphincter during
voiding is normal
Fig. 40.2 Recording from

a patient with MS, showing
involuntary increased
sphincter activity occurring
when the detrusor contracts
(detrusor sphincter
dyssynergia (DSD));
voiding only occurs when
the activity in the sphincter
decreases
reference electrode. The exposed tip of the fine inner wire is the active electrode.
The CNE allows for analysis of individual motor units.
In health there is continuous tonic activity in the urethral sphincter which only
becomes silent during voiding (Fig. 40.1). In patients with spinal cord lesions, the
detrusor and the sphincter may be uncoordinated (Fig. 40.2). Combined urodynamic
and EMG studies are highly interesting but the presence of detrusor sphincter dys-
synergia (DSD) in patients with spinal lesions can usually be deduced from the
symptoms, uroflowmetry, residual volumes and video-urodynamic tests.
Detailed EMG of Urethral Sphincter
Detailed EMG analysis of the external striated sphincter is undertaken using a CNE
(see above). In a male patient the needle is inserted through the perineum and
towards the apex of the prostate gland. Some investigators perform a simultaneous
digital rectal examination to help guide needle placement. Sphincter EMG activity
is highly characteristic on the audio output of the EMG machine and an experienced
investigator can readily guide the needle placement while listening to the audio
output. The external striated sphincter is heard in the ‘distance’ and the needle elec-
trode can be advanced towards the tonically firing motor units.
In female patients the needle is inserted just lateral to the external meatus and
guided ‘alongside’ the urethra into the sphincter muscle again guided by the
40 Sphincter Electromyography (EMG) 231
EMG machines audio output. Although the EMG needles are extremely fine a
small amount of anaesthetic gel is usually applied to the area adjacent to the
external meatus.
Motor Unit Action Potentials (MUAP)
Detailed analysis of MUAPs helps to identify normal muscle behaviour from chron-
ically denervated muscle. The duration of individual MUAPS is the most commonly
measured parameter in sphincter EMG; longer duration of MUAPs reflects the rein-
nervation process in the muscle. The changes may be identified several weeks or
months after an acute nerve injury. The MUAPs in reinnervated muscle are often
polyphasic in addition to being prolonged (Fig. 40.4). The duration is the time from
first deflection to the point of return to the baseline; in normal sphincter muscle the
MUAPs are less than 7 msec (Fig. 40.3).
Fig. 40.3 Normal motor

unit recorded with a CNE
from the urethral sphincter
6 ms
232 E. L. Foster et al.
Fig. 40.4 Three motor units shown recorded from a patient with probable Multi System Atrophy.
The MUPs are shown in falling leaf display in the left panels. The units are polyphasic and of
markedly prolonged duration at 17.2 ms, 24.3 ms and 16.5 ms (note different sweep speeds
3 ms/D–10 ms/D)
Clinical Uses of EMG
MSA and IPD
Patients with multi system atrophy (MSA) often first present to urologists with uri-
nary symptoms and/or erectile dysfunction. In MSA, degeneration in Onuf’s nucleus
(ventral part of anterior horn of sacral spinal cord) causes sphincter denervation and
reinnervation whereas in idiopathic Parkinson’s disease (IPD) the sphincters are
normally innervated (Fig. 40.4). Similar reinnervation changes may be found in
patients with recovering from cauda equina syndrome.
There have been historical concerns over high rates of incontinence after bladder
outflow surgery in men with IPD. However, it is now seems likely that many of the
patients who did poorly in the published 1988 study probably had MSA and not
IPD. More recent work has shown that TURP should be offered to men with IPD,
provided that they have been appropriately investigated. Sphincter EMG may help
distinguish between IPD and MSA. Women with MSA do poorly after surgery for
stress incontinence. It is recommended that women with stress incontinence and any
parkinsonism features should have a sphincter EMG before proceeding to surgery.
Particular care is needed in interpreting the sphincter EMG findings in relation
to the clinical situation. In a patient with possible MSA it would be standard prac-
tice to measure the duration of ten motor units from different areas of the sphincter.
The mean duration of ten MUAPs and the proportion of units of greater duration
than 10 ms can be plotted and compared with control data. The reported EMG find-
ings in patients with suspected MSA tend to fall into one of three categories; nor-
mal, equivocal or profoundly abnormal. Repeating the EMG may be helpful in
patients whose initial results are ‘equivocal’. It is important to note that a small
number of prolonged polyphasic units may be found in the sphincters of normal
individuals particularly in the elderly or if there is a history of pelvic surgery or
vaginal delivery.
40 Sphincter Electromyography (EMG) 233
Fowler's Syndrome
Professor Clare Fowler described abnormal spontaneous myotonia-like activity in the

urethral sphincters of premenopausal women with urinary retention. Detailed EMG
analysis has shown that the striking audio outputs are made up of two components:
complex repetitive discharges and decelerating bursts. The disorder may arise from
the abnormal transmission of electrical activity between muscle fibres (ephaptic
transmission). More recently, this myotonia-like activity has also been reported in
young women with normal voiding. Women may have a natural tendency to this activ-
ity in the urethral sphincter muscle and only in certain circumstances does it cause
voiding dysfunction. It is important not to wrongly label a young women with reten-
tion as having Fowlers’ syndrome when other biopsychosocial factors may be
important.
Botulinum Toxin Injection
Using a specialised EMG needle electrode, Botulinum toxin may be injected

through the needle electrode and into the external urethral sphincter in women with
retention. The EMG machines audio output guides needle placement and enables
accurate administration of the Botox.
Further Reading
Malladi P, Simeoni S, Panicker JN. The role of pelvic neurophysiology testing in the assessment
of patients with voiding dysfunction. Curr Bladder Dysfunct Rep. 2020;15:229–39. https://doi.
org/10.1007/s11884-020-00613-0.
Miao Y, Wang K, Han J, Wang Z, Bian Y, Guo Q, Sun C, Wang Q, Song D, Qi X, Qiu
F. Differential value of external anal- and urethral-sphincter electromyography in mul-
tiple system atrophy cerebellar type and spinocerebellar ataxias. J Clin Neurosci. 2020
Oct;80:16–22. https://doi.org/10.1016/j.jocn.2020.07.067. Epub 2020 Aug 15. PMID:
33099340.
Panicker JN, Seth JH, Khan S, Gonzales G, Haslam C, Kessler TM, Fowler CJ. Open-label study
evaluating outpatient urethral sphincter injections of onabotulinumtoxinA to treat women with
urinary retention due to a primary disorder of sphincter relaxation (Fowler’s syndrome). BJU
Int. 2016;117:809–13. https://doi.org/10.1111/bju.13342.
Sakakibara R, Panicker J, Simeoni S, Uchiyama T, Yamamoto T, Tateno F, et al. Bladder dysfunc-
tion as the initial presentation of multiple system atrophy: a prospective cohort study. Clin
Auton Res. 2019;29(6):627–31.
Part IV
Technology Operative
Chapter 41
Operating Theatre Safety
Steve Payne
There are a number of rudiments which are intrinsic to the theatre complex. It
should be a safe, efficient, user-friendly space that is as free from bacterial contami-
nation as possible to minimise the risk of surgical-site infection (SSI); SSI may also
be minimized by the judicious use of antibiotic prophylaxis. The theatre complex
should also be a safe working environment for everybody who is employed there,
utilising appropriate personal protective equipment.
Theatre Design to Minimise Wound Infection
A key principle in theatre design is the concept of a patient flowing from a dirty
area, through a single secure entrance to a clean area, and an aseptic area for their
surgery (Fig. 41.1). The patient is received from the outer, ‘dirty’ zone to a clean
environment between the reception area and the aseptic operative theatre. After sur-
gery, all potentially contaminated materials and instruments, are moved back to the
outer ‘dirty’ zone for disposal or sterilisation. The patient is moved to a clean recov-
ery area before being discharged back to a ward or higher care environment.
Physical characteristics helping to provide a safe aseptic zone in the operating
theatre have been clearly defined, and are shown in Table 41.1.
S. Payne (*)

Switzerland AG 2023
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238 S. Payne
Dirty
zone
Clean
zone
Theatre staff
Aseptic
zone
Patient Ward Reception Theatre Recovery Ward
Equipment
Equipment
Disposal area / TSSU
Fig. 41.1 The patient flow through theatre to optimise patient and staff safety and to reduce infec-
tion risks
Table 41.1 Structural factors to maximise the safety of the physical environment in the aseptic
zone in an operating theatre
Theatre
characteristic Pre-requisite
Floors and These should be durable, impervious, non-slip, anti-static and able to be
surfaces disinfected.
Good This should be provided by vertical, or horizontal, laminar air flow with
ventilation positive pressure air moving from the clean to the dirty environments, thereby
reducing the number of contaminated particles over the patient. The air should
go through high efficiency particulate air (HEPA) filters which remove
particles > 0.3 micron in diameter with an efficiency of 99.97%. 20–40 air
changes/hour are normal but can be increased to 400/hour by a laminar flow
hood. Personal exhaust suits, or the use of plasma air purification (PAP), can
reduce contamination further when prostheses are being inserted.
Ideal A temperature of 20–22 °C, and humidity of 50–55%, is comfortable for
temperature and operating in. Global temperature may need to be increased for prolonged
humidity surgery, children, neonates and the elderly. Warming blankets, warm air blown
over the patient and the heating of intra-venous and irrigation fluids are
standard ways of directly maintaining the patient’s core temperature
intra-operatively. The ambient air temperature in the aseptic zone should be
1 °C lower than the clean zone to further facilitate air movement towards the
outer zone.
41 Operating Theatre Safety 239
Table 41.1 (continued)

Theatre
characteristic Pre-requisite
Good lighting Theatre lighting should be adjustable, bright enough for their intended task
and flexible in use. Luminescence should be 1,000 Lux and colour rendition
85–100 Ra. Focusable headlights may improve illumination further in specific
surgical circumstances and can be battery powered when electricity supply
may be inconsistent or impractical
Appropriate gas Gas services should be piped and available from a boom without trailing
supply and connecting tubing. Waste anaesthetic gases should be scavenged to a
extraction high-volume, low-pressure extraction apparatus. Extraction of the plume
created whilst using electro-cautery is also important to minimise risk of
infective and transmissible malignant risks to the operator.
Safe operating Operating tables and all wheeled peripheral devices should be heavy, have a
tables and stable base yet be moveable to maximise intra-operative flexibility. Ancillary
ancillary positioning equipment needs to be compatible with the table and should
equipment accommodate ancillary devices to reduce DVT risks. The table should have
soft Sorbo-rubber padding to minimise pressure in contact areas, which
should be removable for cleaning, and have a radiolucent area so that
intra-operative X-rays may be taken when required. The electrical safety of
electronic and electrosurgical equipment is paramount to reduce risks of
shock and burns to patients and staff.
actors to Minimise Patient Wound Infection Secondary

F
to Surgical Intervention
The operative site should have gross contamination removed before performing
anti-septic skin preparation and the anti-septic agent should be applied in concentric
circles moving towards the periphery of the operative site. The prepared area must
be large enough to allow extension of the incision, or to create new incisions or
drain sites, if necessary. In addition, there are a number of things that can be done in
the aseptic environment to reduce the risks of wound contamination during surgical
intervention. The evidence of wound contamination being caused by the fomites
encountered during surgery is shown in Table 41.2.
NICE guidance suggests that ‘Antibiotic prophylaxis should not be used rou-
tinely for clean, non-prosthetic, uncomplicated surgery because of the risk of
adverse events, Clostridium difficile-associated disease, resistance and drug hyper-
sensitivity.’ The suggested, ‘acceptable’, reasons for the use of antibiotic prophy-
laxis are shown in Table 41.3. In urology, therefore, the presence of urinary tract
infection, or implantation of some form of prosthesis are really the only indications
for antibiotic prophylaxis.
240 S. Payne
Table 41.2 Factors to prevent surgical wound contamination in the operating room environment
Fomite Effects on wound contamination
Scrub suits No proven benefit
Footwear Strictly, should be kept just in the aseptic operative zone
Caps Reduce shedding of micro-organisms from the hair
Masks These provide temporary protection only but can protect from naso- or oro-
pharyngeal contamination by the operating team
Gowns Prevent shedding of micro-organisms
Drapes Create a barrier between the surgical field and areas of contamination
Theatre Reducing staff numbers and staff movement in and out of the operative zone may
staff be important in minimising the movement of contaminated air
Table 41.3 Reasons to Circumstance

consider prophylactic Clean surgery involving the placement of a prosthesis or
antibiotic therapy implant
Clean-contaminated surgery
Contaminated surgery
Surgery on a dirty or infected wound (requires antibiotic
treatment in addition to prophylaxis).
Factors to Minimise Risks to Surgical Personnel
Few subjects have received as much attention during the 2020 Covid-19 pandemic,
as the efficacy of personal protective equipment (PPE). In particular, the benefits of
masks in protecting both the mask wearer and the person they are facing, has been
extensively scrutinised. Controversy has existed for some time about the benefits to
the patient from the surgical team wearing conventional triple layer surgical masks,
as they have been shown to have time-limited efficacy for the transmission of micro-
organisms to the area of the wound. They are, therefore, probably of more value in
protecting the surgical team from mucosal inoculation via splashes or spills of bio-
logical material during surgery; visor masks, or the combined use of occlusive spec-
tacles and a mask, should be used when that risk is very high. Similarly, surgical
gowns should be water-resistant in appropriate circumstances, yet breathable, flex-
ible and comfortable for the wearer.
Further Reading
Behera BK, Arora H. Surgical gown: a critical review. J Ind Text. 2009;38(3):205–31.
HBN 26. Facilities for surgical procedures: Volume 1. NHS Estates. 2004. https://www.england.
nhs.uk/wp-content/uploads/2021/05/HBN_26.pdf
Surgical site infection. Quality standard (QS 49). NICE. 2013. https://www.nice.org.uk/guidance/
qs49/resources/surgical-site-infection-pdf-2098675107781
Tcharkhtchi A, Abbasnezhad N, Seydani MZ, Zirak N, Farzaneh S, Shirinbayan M. An overview
of filtration efficiency through the masks: Mechanisms of the aerosols penetration. Bioact
Mater. 2021;6(1):106–22.
Chapter 42
Principles of Decontamination
Sotonye K. Tolofari
Decontamination refers to the processes used to remove contaminants such as

micro-organisms or hazardous materials from any particular object or substance.
This term encompasses the processes of cleaning, disinfection and sterilisation.
Introduction
Decontamination of medical devices is an essential process in reducing hospital

acquired infections and adverse events. These processes involve the removal of
materials including proteins, radioactive substances, infectious disease and miscel-
laneous chemicals.
Prior to understanding the methods involved in decontaminating equipment, it is
useful to understand how to determine the level of decontamination required for
particular medical devices or surgical instruments.
This is demonstrated using Spaulding’s classification (Fig. 42.1):
• Critical—Instruments required for procedures that penetrate normally sterile
tissue and/or enter the bloodstream. This would include any open or laparoscopic
surgical equipment, hypodermic needles and intravenous catheters. These instru-
ments would require sterilisation before and after use.
• Semi-critical—Instruments that are in contact with, but do not breach mucous
membranes (e.g. flexible cystoscopes). Again, these instruments would require
high-level disinfection or sterilisation before and after use.
S. K. Tolofari (*)
Salford Care Organisation, Northern Care Alliance NHS Foundation Trust, Salford, UK
e-mail: stolofari@doctors.org.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_42
242 S. K. Tolofari
Fig. 42.1 Spaulding’s

classification
• Non-critical—Instruments in contact with intact skin only (blood pressure cuff/

pulse oximeter, etc.). These instruments require only cleaning or low level disin-
fection before and after use.
Methods of Decontamination
As described above, decontamination refers to a number of different methods that

may be used to remove substances. The three methods include, cleaning, disinfec-
tion and sterilisation.
Cleaning
The physical removal of any contamination on equipment.

This process will not necessarily remove micro-organisms or bacterial spores. This
process is required prior to sterilisation to reduce the risk of transmission of infec-
tious agents and hazardous chemicals. Cleaning can be manual or automated. Where
possible, an automated cleaning process is preferable to manual. Manual cleaning
can essentially be hand washing with a particular detergent, immersion of the equip-
ment in water and detergent at a temperature specified by the product manufacturers
or manual wiping with an alcohol-based product. Prior to cleaning, it is important
that equipment is dismantled and, in some cases, has a pre-treatment manual clean
in order to remove any gross contamination.
Automated cleaning is performed either by a washer/disinfector or an ultrasonic
cleaner. The recognised phases of a washer/disinfector will include: cool pre-wash
(<35 °C) to prevent protein coagulation, main wash, rinse and thermal
disinfection.
Ultrasonic cleaners can be used as stand-alone cleaners, or in combination with
a washer/disinfector. The instruments are placed into a basket and submerged into a
tank of water and detergent. Ultrasound, at a frequency of 20–40 kHZ, is then used
to agitate water and create bubbles which dislodge and aggregate dirt from the
42 Principles of Decontamination 243
surface of surgical instruments. Ultrasonic cleaning has been shown to remove more
micro-organisms and fine debris from less accessible surfaces on devices than man-
ual wiping alone. The ultrasonic cleaning method is often used as a pre-treatment
clean prior to washer/disinfector automated clean.
Disinfection
Disinfection is the process of removing most viable micro-organisms except

some viruses and bacterial spores.
There are three levels of disinfection: high, intermediate and low. High-level disin-
fection neutralises all micro- organisms, mycobacteria, lipid and non-lipid viruses,
and some, but not all bacterial and fungal spores. Intermediate-level disinfection
kills mycobacteria, most viruses and bacteria. Low-level disinfection kills some
viruses and bacteria.
One method of disinfection is ‘moist heating’. Products can be washed in an
automated washer/disinfector using water and detergent to a heat of 73–90°C. This
will allow for destruction of most micro-organisms.
In some cases, particularly in urology, some instruments (flexible uretero-
scopes/cystoscopes) may not be able to withstand high levels of heat or pressure.
Therefore, some devices may be disinfected by chemical disinfection. The device
must be immersed within the correct chemical concentration and left for a spe-
cific time according to the manufacturer’s directions. This is often performed as
an automated process. In urology, these chemical compounds will include chlo-
rine dioxide (Tristel), glutaraldehyde, orthophthalaldehyde (OPA) or peracetic
acid. These disinfectant substances act as oxidising agents against
micro- organisms.
Sterilisation
The complete destruction of all living micro-organisms including viruses and

bacterial spores.
Sterilisation can be performed by various methods. These may include:
• Porous load sterilisers
This is the process of using heat (steam) and pressure to sterilise instruments
with vacuum assistance to remove air. This is otherwise known as ‘autoclaving’.
The typical stages of a porous load steriliser include air evacuation, 134°C hold
time, for 3 minutes, 121°C hold time for 15 minutes followed by a post-vacuum
or drying stage.
244 S. K. Tolofari
• Bowl and instrument sterilisers

These devices work in a similar way to a porous load steriliser, however there
is no air removal or air-drying cycle. They are not recommended for any device
with a hollow lumen. These devices are not recommended for routine use for
sterilisation in the UK.
• Low temperature gas plasma sterilisers
Some instruments may be heat and moisture sensitive therefore unable to
withstand autoclaving without damage. Hydrogen peroxide and ethylene oxide
gas can be used at low temperatures to sterilise equipment by the process of oxi-
dation. This process creates free radicals that destroy micro-organisms.
Commercially available systems including the STERRAD® system do not typi-
cally exceed 50°C for a cycle of approximately one hour.
Incineration
Incineration is the combustion of any organic substances reducing all living

micro-organisms to ash for disposable items deemed high risk of infectivity. For
example, any equipment used in a patient with Cruetzfeldt Jakob Disease (CJD).
Decontamination of Urological Instruments
Flexible Endoscopes
A flexible cystoscope would be considered as a semi-critical item as per the

Spaulding’s classification (Fig. 42.1). High-level disinfection is considered the min-
imum level of decontamination for a cystoscope. A standard protocol for disinfec-
tion of a flexible cystoscope would include:
1. Disassembly
Deconstruct the key parts, light lead adaptor, suction/irrigation channel, etc.
2. Pre-cleaning
Manual wash or ultrasonic wash to remove gross debris.
3. Leak test
The scope is submerged in water and attached to an air supply to ensure there
is no breach in the covering of the scope which can cause further contamination
of the working elements.
4. Cleaning
Automated washer/disinfector
42 Principles of Decontamination 245
5. High-level disinfection/sterilisation
Many flexible cystoscopes will not be able to withstand high temperatures
required for disinfection. They therefore undergo chemical disinfection with
chlorine dioxide, glutaraldehyde or peracetic acid. Immersion times are variable
between manufacturers.
Rigid Endoscopes
Again, using the Spaulding classification we can identify the rigid endoscope as a
semi-critical instrument that requires high-level disinfection. A standard protocol
for the decontamination of rigid scope would include:
• disassembly
• pre-cleaning
• automated washer/disinfector
• high-level disinfection/sterilisation
As a rigid cystoscope is robust with few delicate moving parts, it can withstand
sterilisation using a porous load steriliser as well as chemical disinfection. The pro-
cesses used for a resectoscope, semi-rigid ureteroscope or urethrotome would be
similar to that of rigid cystoscope.
Laparoscopic and Robotic Surgical Equipment
As per the Spaulding classification, these instruments would be considered critical.

On that basis it is imperative that they undergo sterilisation.
• Disassembly
• Pre-cleaning
• Automated washer/disinfector
• Porous load steriliser/Low temperature gas plasma sterilisers
Open Surgical Equipment (Scalpel Blade, Scissors, Forceps)
The process will be the same as for laparoscopic equipment.

246 S. K. Tolofari
Specific Decontamination Issues
One particular area of concern regarding sterilisation of surgical equipment is

regarding prion related conditions such as Creutzfeldt-Jakob disease (CJD).
Evidence suggests that prions may not be inactivated by routine sterilisation of sur-
gical equipment. Although rarely encountered in urological practice, we must
adhere to NICE guidance suggesting the use of disposable or ‘single use’ instru-
ments for patients deemed high risk, or to follow protocols suggesting quarantine of
reusable equipment with additional sterilisation where necessary.
Further Reading
Beilenhoff U, Biering H, Blum R. Reprocessing of flexible endoscopes and endoscopic acces-

sories used in gastrointestinal endoscopy: Position Statement of the European Society of
Gastrointestinal Endoscopy (ESGE) and European Society of Gastroenterology Nurses and
Associates (ESGENA) Update 2018. Available at: https://www.esge.com/assets/downloads/
pdfs/guidelines/2018_a_0759_1629.pdf
Health Technical Memorandum (HTM) 01–06: Health Technical Memorandum (HTM) 01-01 on
the management and decontamination of surgical instruments (medical devices) used in acute
care. Department of Health & Social Care 2016. Available at: https://www.england.nhs.uk/wp-
content/uploads/2021/05/HTM0101PartA.pdf
Health Technical Memorandum (HTM) 01–06: Management and decontamination of flexible
endoscopes (HTM 01–06). Part C: Decontamination of flexible endoscopes: operational man-
agement. Department of Health & Social Care 2016. Available at: https://www.england.nhs.uk/
wp-content/uploads/2021/05/HTM0106_PartC.pdf
Chapter 43
Patient Safety in the Operating Theatre
Environment
Steve Payne
The safety of the patient is the key consideration in the operating theatre environ-
ment. Whilst this has been recognised for many years, the emphasis on the func-
tional, rather than the physical, surgical environment has changed so that human
factors throughout an operating department’s processes are now recognised as being
more important to the patient’s outcome than the environment in which the surgery
is carried out.
Harm and ‘Never events’
It is understood that almost all of healthcare professionals do not go to work with

the intention of causing harm. However, compromised patient safety resulting in
poor clinical outcomes, ‘medical accidents’, do still occur, often with litigious con-
sequences. These ‘accidents’ are usually as a consequence of simple human errors
or, alternatively are due to a series of circumstances which should not occur, so
called ‘never events’. ‘Never events’ are defined as serious, largely preventable
patient safety incidents that should not occur if the available preventative measures
had been implemented.
The core ‘never events’ occurring in an operating theatre environment, defined
by the National Safety Standards for Invasive Procedures (NSSIP) in 2015, are:
• Wrong site surgery
• Wrong implant/prosthesis
• Retention of a foreign object post-operation
S. Payne (*)

Switzerland AG 2023
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248 S. Payne
Table 43.1 Technical and Technical issues Non-technical issues

non-technical factors that Poor workspace and Poor situational awareness
may contribute to the environment
generation of a never event
(as defined by NSSIP) Poor work design Poor decision-making
Poor organisation and Poor teamwork
culture
Task-related factors Poor leadership
Poor communication Poor stress management
Inadequate policies and
procedures
Analysis of ‘never events’ demonstrates a combination of technical issues and non-

technical factors. Technical issues are generally due to institutional, or individual,
organisational deficiencies whilst non-technical factors are consequent upon fail-
ures in cognitive, social or personal resource skills; these are usually used to com-
plement an individual’s technical skills and contribute to the safe and efficient
performance of a task. A sub-optimal environment, especially as far as achieving an
optimal temperature of 21 °C and humidity of 50%, are key institutional contribu-
tors to the development of error. Technical and non-technical factors that have been
shown to contribute to ‘never events’ are shown in Table 43.1.
uman Factors Generating Error and Which May

H
Compromise Patient Safety
Symptoms of poor individual non-technical performance, human factors, which

may contribute to individual, or team, error, are shown in Table 43.2.
The individual and litigious consequences of error, as well as the professional
harm the institution and surgeon comes to, has resulted in significant introspection
about the safety of the operative process over the last 20 years. Significant changes
in practice have been instituted as a consequence. These have helped define the
organizational responsibilities of the healthcare institution the individual, and the
team within that institution. Provision of an adequate workforce, effective systems
for documentation, scheduling and transfer of information are key organisational
responsibilities of the establishment. Sequential processes, at an individual and
team level, have to be followed, thereafter, to maintain safety during the patient’s
journey through the operating theatre Fig. 43.1). An effective process for the record-
ing of errors, and impartial analysis of those records, must be in place to ensure the
validity of the whole process; this is also an institutional responsibility.
43 Patient Safety in the Operating Theatre Environment 249
Table 43.2 Human factor symptoms that may compromise patient safety
Non-technical issue Symptom
Poor situational • not gathering enough information about the task or process
awareness • overlooking anomalies in the patient process
• not checking ‘mental pictures’ of the task with others
• not recognising increased risk
Poor decision-making • proceeding with the task rather than checking when uncertain
• over-reliance on assumptions rather than facts
Poor teamwork • not defining an optimal team structure
• dominating the team so they can’t contribute
• inadequate exchange of information to ensure a shared understanding
of what has to be done
Poor leadership • not leading by example
• not demonstrating procedural compliance
• not ensuring the whole team shares an awareness of the task
Poor stress • not dealing effectively with work pressures
management • requiring staff to work faster
• requiring staff to work longer
• failing to recognise stress in the team
Safety processes
Organizational Sequential
Governance and audit Procedural verification and site marking

Documentation of invasive procedure Safety briefing
Workforce Sign in
Scheduling and list management Time out
Handover and information transfer Prosthesis verification
Prevention of retained foreign objects
Sign out
Debriefing
Fig. 43.1 The organisational and sequential processes used to reduce peri-operative error during
invasive procedures
Mechanisms to Improve Patient Safety
The key tool to improve operative patient safety has been the World Health
Organisation (WHO) Surgical Safety Checklist. This was developed to reduce the
adverse effects of unsafe healthcare practice and was first published in 2009. It
places nineteen checks into three “phases” during the surgical process (Table 43.3).
250 S. Payne
Table 43.3 Types of VTE prophylaxis

Method Types Mechanism Notes
Early ambulation Walking/mobilising Reduced venous stasis Should be encouraged
as soon as safely
possible
post-operatively
Mechanical Graduated compression Exert pressure on major Contraindicated in
stockings veins, augment muscle patients with peripheral
(e.g. TED™ stockings) pump and improve vascular disease,
lymphatic drainage. known DVT, prolonged
Distal pressure exerted by use, peripheral
stocking is more than neuropathy, limb
proximal. Increases deformity, infected
venous velocity, improves wounds, dermatitis,
venous return and recent skin grafts,
decrease reflux of venous known heart failure
blood
Intermittent pneumatic Lower limb encased in an Generally, well
devices intermittently contracting tolerated but comfort,
(e.g. Flowtrons®) device. Mimics action of fit and compliance can
musculature by producing be an issue
a squeezing effect on
promoting flow and
venous return
Pharmacological Low molecular weight Potentiates antithrombin None have proven
heparin (LMWH) e.g. III, inhibiting thrombin superiority
enoxaparin, dalteparin and factor Xa effected in Consider dose
clotting cascade adjustment in renal
insufficiency and
obesity
Check platelet count
regularly in patients
receiving LMWH—
risk of heparin induced
thrombocytopenia
(HIT)
Low dose Same as LMWH
unfractionated heparin
(UFH)
Fondaparinux Synthetic factor Xa Low dose UFH or
inhibitor fondaparinux can be
used as alternative to
LMWH in renal
impairment or HIT
Oral agents e.g. Direct factor Xa inhibitor, Oral agents are not
rivaroxaban, dabigatran competitive thrombin routinely used. May be
inhibitor part of anticoagulation
strategy in patients
already on therapeutic
anticoagulation
43 Patient Safety in the Operating Theatre Environment 251
The checklist is only effective if all individuals engaging in a series of operations

act as a unified surgical team. A ‘Team Brief’ before commencement of an operat-
ing session, involving the surgeon, anaesthetists, nurses, circulating staff and tech-
nicians is essential to confirm team cohesion; a debrief at the end of the session is
also important to help team morale and so that any issues arising during the session
can be addressed and escalated appropriately.
The WHO checklist has been mandatory in UK hospital’s theatre environments
since 2010 and has led to a culture of pause and reflection before surgical proce-
dures are commenced. It has been said to significantly reduce the incidence of both
complications and 30-day mortality from surgery, especially that carried out as an
emergency. Failure to adopt the checklist is usually due to poor education in the
reasons for, responsibilities during, and the application of its guiding principles in
practice.
Making the Operating Team ‘safe’
It is widely recognised that enhancing clinical performance requires an understand-

ing of the effects on human behaviour of teamwork, tasks, equipment, workspace,
culture and organisation. It is only with application of that knowledge in the clinical
setting that patient safety can be enhanced.
Resource management courses to facilitate effective teamwork in practice, are
increasingly prevalent in staff training. These bring the ethos of ‘prevention’, as a
concept, to patient management during the operative journey. Safety training, espe-
cially as a team activity, the routine use of checklists and the use of high fidelity
simulators to improve familiarity with equipment and techniques have been postu-
lated as the most important factors to reduce the risk of peri-operative patient harm,
than any changes to the physical theatre environment.
The Limitations of Checklists
Experience shows that checklists themselves cannot be fully effective in protecting

patients from adverse incidents; they must be conducted by teams of healthcare
professionals who have trained together and who have received appropriate educa-
tion in the human factors that underpin safe teamwork. Safety is, therefore, not just
about checklists, teamwork or human factors, it is about checklists AND teamwork
AND an understanding of human factors.
252 S. Payne
Further Reading
NHS England. National Safety Standards for Invasive Procedures (NatSSIPs). 2015.
Sevdalis N, Hull L, Birnbach DJ. Improving patient safety in the operating theatre and periop-
erative care: obstacles, interventions, and priorities for accelerating progress. Br J Anaesth.
2012;109(suppl1):i3–16.
Treadwell JR, Lucas S, Tsou AY. Surgical checklists: a systematic review of impacts and imple-
mentation. BMJ Qual Saf. 2014;23(4):299–318.
WHO guidelines for safe surgery 2009. World Health Organization Press. 2009.
Chapter 44
Venous Thromboembolic Prevention
Christian Longley
Venous thromboembolic (VTE) disease remains a significant cause of in-patient

morbidity and mortality. Effective risk stratification and on-going review is essen-
tial for risk reduction, providing health and cost benefits.
Introduction
A blood clot that forms in a deep vein is called a deep vein thrombosis (DVT). If this
travels to the pulmonary vasculature, it is a pulmonary embolism (PE). Collectively
DVT and PE are referred to as venous thromboembolic (VTE) disease. VTE disease
is a common and serious condition, which can be seen in any patient, but are par-
ticularly associated with trauma, surgery, immobilisation and pregnancy.
PE is a frequent and preventable cause of death in post-operative patients. It is
essential to individually assess risk of thrombosis and apply strategies to minimise
the chances of VTE occurring in all patients.
The use of prophylaxis is based on the often clinically silent nature of VTE, high
prevalence in hospitalised patients and the high morbidity and mortality associated
with VTE. There is compelling evidence that prophylaxis reduces adverse outcomes
and health related costs. Individual hospitals will have their own guidelines for
assessing risk, prevention and management of VTE to fulfil their statutory obliga-
tion to patients to ensure compliance to National Institute for Health and Care
Excellence (NICE) guidelines.
C. Longley (*)
e-mail: c.e.longley@doctors.org.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_44
254 C. Longley
Causes of VTE Disease (Table 44.1)
Table 44.1 Causes of VTE disease

Inherited Inherent Acquired
Thrombophilia Oestrogens e.g. Combined Cancer
e.g. Factor V Leiden deficiency, hormonal contraceptives, Critical illness
antiphospholipid syndrome, antithrombin Hormone replacement therapy Obesity
III deficiency, protein C+S deficiencies. Immobilisation
Surgery
Trauma
Pregnancy and
parturiency
44 Venous Thromboembolic Prevention 255
Risk Assessment
Each surgical patient should be assessed and risk stratified according to the proce-
dure and their own patient related factors. Clinicians can use scoring systems to risk
stratify patients based on their mobility, thrombosis risk and bleeding risk (e.g.
Fig. 44.1.)
An assessment of bleeding risk must also be made in those who pharmacological
VTE prophylaxis is considered. Again, this is related to the procedure and the indi-
vidual. Generally, most urological procedures would fall into the lower bleeding
risk category (<2% risk of major bleed). Individual risk factors are multiple but
include, bleeding tendencies, coagulopathies, thrombocytopenia and concurrent
anticoagulation.
VTE risk assessments are fluid and subject to re-evaluation. Most institutions
mandate a review within 48 hours and ideally, VTE should be considered during
each patient review.
256 C. Longley
Fig. 44.1 NICE Clinical Guideline NG89 (2018) Venous thromboembolism in over 16 s: reducing
the risk of hospital-acquired DVT or PE
Primary VTE Prophylaxis
Using risk assessment tools (Fig. 44.1) enables the clinician to combine the risk
category based on the surgery or admission and the individual (Table 44.2).
Most urological patients will require some form of VTE prophylaxis. Only in the
lowest risk patients, who have no individual risk factors and have minor interruption
to their mobility, early and frequent ambulation may suffice as VTE prophylaxis.
Most urological surgery will fall into the low to moderate risk surgical category,
which will require some addition form of prophylaxis. The types of VTE prophy-
laxis are detailed in Table 44.3.
Table 44.2 Risk assessment model for VTE

Risk Individual risk Estimated VTE risk % (in the
category factors absence of prophylaxis) Recommendations
Very low 0 <0.5 Early and frequent
ambulation
Low 1–2 1.5 Mechanical
+/− pharmacological
Moderate 3–4 3.0 Mechanical +
Pharmacological
High >5 6.0 Mechanical +
pharmacological
Table 44.3 Types of VTE prophylaxis

Early Walking/ Reduced venous stasis. Should be encouraged as
ambulation mobilising soon as safely possible
post-operatively.
Mechanical Graduated Exert pressure on major Contraindicated in patients
compression veins, augment muscle with peripheral vascular
stockings (e.g. pump and improve disease, known DVT,
TED™ lymphatic drainage. Distal prolonged use, peripheral
stockings) pressure exerted by neuropathy, limb deformity,
stocking is more than infected wounds, dermatitis,
proximal. Increases venous recent skin grafts, known
velocity, improves venous heart failure.
return and decrease reflux
of venous blood.
Intermittent Lower limb encased in an Generally, well tolerated but
pneumatic intermittently contracting comfort, fit and compliance
devices (e.g. device. Mimics action of can be an issue.
Flowtrons®) musculature by producing
a squeezing effect on
promoting flow and venous
return.
(continued)
258 C. Longley
Table 44.3 (continued)

Pharmacological Low molecular Potentiates antithrombin None have proven
weight heparin III, inhibiting thrombin and superiority
(LMWH) e.g. factor Xa effected in Consider dose adjustment in
enoxaparin, clotting cascade. renal insufficiency and
dalteparin obesity
Check platelet count
regularly in patients
receiving LMWH—risk of
heparin induced
thrombocytopenia (HIT)
Low dose Same as LMWH
unfractionated
heparin (UFH)
Fondaparinux Synthetic factor Xa Low dose UFH or

inhibitor fondaparinux can be used as
alternative to LMWH in
renal impairment or HIT
Oral agents e.g. Direct factor Xa inhibitor, Oral agents are not routinely
rivaroxaban, competitive thrombin used. May be part of
dabigatran inhibitor anticoagulation strategy in
patients already on
therapeutic anticoagulation
Assessment of Bleeding Risk
Some patients may already be anticoagulated for another reason. They will require
bespoke strategies to manage their anticoagulation and VTE prophylaxis in the peri-
operative period. For example, patients who are anticoagulated for atrial fibrillation
(AF) may require this stopping perioperatively, with standard LMWH/mechanical
prophylaxis used until the bleeding risk has minimised enough to restart their usual
anticoagulation. Some patients e.g. mechanical heart valves or recurrent PE may
require bridging treatment regimes, which will require a multi-disciplinary input
from anaesthetic, cardiology and haematology colleagues.
If a patient is considered a high bleeding risk or the consequences of bleeding
may be catastrophic, mechanical methods may be used. Again, ongoing review
should allow for switching to pharmacological methods at the earliest point when
the risk of bleeding becomes acceptably low (e.g. 48–72 hrs post-surgery).
Application of VTE Prophylaxis
The optimal timing is unknown, although mechanical prophylaxis is started the day
before or immediately prior to surgery and pharmacological agents sometime after
surgery. Often six hours post-surgery is used but this can be adjusted by the respon-
sible clinician according to individual patient and surgical factors.
Most VTE prophylaxis will continue until the patient is fully ambulatory or dis-
charged from hospital. The risk of VTE remains high in the post-operative period
even if the patient’s mobility has returned to baseline. Therefore, high risk surgical
patients (e.g. intra-abdominal cancer surgery), will often go home with pharmaco-
logical prophylaxis to continue for 28 days.
Secondary VTE Prophylacis
Rarely, as a temporising manoeuvre, an inferior vena cava (IVC) filter may be sited
pre-operatively in patients who are otherwise contraindicated from taking antico-
agulation or develop recurrent PE whilst anticoagulated.
Further Reading
NICE Clinical Guideline 201. Venous thromboembolism in adults. 2021

Pai M, Douketis JD. Prevention of venous thromboembolic disease in adult nonorthopedic surgical
patients. UpToDate. 2021.
Chapter 45
Anticoagulants and Their Reversal
Gidon Ellis
Anticoagulants are used in the management of thromboembolism and preventing

thrombotic complications in patients with cardiac comorbidities such as AF and
valvular heart disease. They are being increasingly used in an ageing and ever more
co-morbid population. All patients on anticoagulants needs careful consideration
during their perioperative work up.
Warfarin has largely been replaced by a new class of drugs called Direct-Acting
Oral Anticoagulants (DOACs) due to having quicker onset and offset, minimal food
and drug interactions and predictable anticoagulant effect with no need for monitor-
ing. DOACs are associated with lower rates of major and fatal bleeding than warfarin.
Anticoagulant use increases a patient’s peri-operative bleeding risk. Cessation of
anticoagulants increases the risk of thromboembolic events.
Surgeons must consider whether peri-operative anticoagulation cessation is
required and what the correct pre- and post-op intervals are, to ensure successful
surgery and prompt recovery without complication.
To facilitate this an understanding of the coagulation cascade, thrombosis risks,
bleeding risks and mechanisms of reversal are discussed below.
Coagulation Cascade
Thrombi form when fibrin polymers cross-link to form a clot. This can be triggered
by internal damage to a vessel wall (intrinsic pathway) or by external trauma (extrin-
sic pathway). Inactive enzyme precursors are converted into active compounds by a
series of reactions, each of which catalyses the next reaction (Fig. 45.1).
G. Ellis (*)
Royal Free Hospital, London, UK

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_45
262 G. Ellis
Damaged
surface
XII XIIa
Intrinsic pathway
Extrinsic pathway
Trauma
XI XIa
IX IXa VII VIIa
X X
Xa
+Va
Prothrombin Thrombin
Common pathway
Fibrinogen Fibrin
Fibrinogen Fibrin
Cross-linked
fibrin clot
Fig. 45.1 Coagulation cascade
Both the intrinsic and extrinsic pathways culminate in the activation of Factor
Xa, which then binds with Factor Va to form prothrombinase.
• Warfarin is a vitamin K antagonist (VKA) and prevents formation of Factors II,
VII, IX, and X.
• Rivaroxaban, Apixaban and Edoxaban are direct Factor Xa inhibitors.
• Dabigatran binds directly to the enzyme thrombin and inactivates it.
Peri-operative Thrombosis and Bleeding Risks
Many factors need considering in the anticoagulated patient requiring surgery.

These include the underlying disease for which the patient is anticoagulated, the
presence of other, pro-thrombotic risk factors, the background bleeding risk of the
patient as they head into surgery (especially if they are to remain on their anticoagu-
lants) and the bleeding risk involved with the surgery.
45 Anticoagulants and Their Reversal 263
Table 45.1 CHA2DS2-VASc score

Condition Points
C Congestive heart failure/left ventricular systolic dysfunction 1
H Hypertension (>140/90, or treated HTN on medication) 1
A2 Age ≥ 75 years 2
D Diabetes mellitus 1
S2 Stroke (previous CVA, TIA or VTE) 2
V Vascular disease 1
A Age 65–74 years 1
Sc Sex (female sex) 1
Thrombosis Risk
Quantifying a patient’s individual thrombosis risk is challenging. Risk may fluctu-

ate over time (for example, after recent CVA/DVT) and in these cases the surgeon
should consider delaying surgery, if safe.
The CHA2DS2-VASc (Table 45.1) is a tool to help estimate the risk for thrombo-
embolism in individual patients with non-rheumatic atrial fibrillation, based on a
number of distinct parameters. A CHA2DS2-VASc ≥ 2 is thought to confer high risk
of thrombosis in this cohort of patients. Whilst not validated to estimate peri-
operative VTE risk it might be a useful tool with which to consider patient’s risks.
However, a number of other crucial factors, for example known thrombophilia,
mechanical heart valve, renal impairment, active cancer and existing left atrial
thrombus must be considered also.
Bleeding Risk
The risk of bleeding is affected by both patient and procedural factors.

Seven patient factors are considered by the HAS-BLED tool (Table 45.2), giving
a score out of 9. A score of ≥ 3 has been shown to confer higher bleeding risk and
can help decision making.
Urological practice entails a wide range of procedures, each conferring bleeding
risks. Whilst some confer extremely low risk of significant bleeding (e.g. flexible
cystoscopy), others are clearly high risk (e.g. TURP, major extirpative oncological
surgeries). The middle ground can be harder to calculate, and a surgeon must esti-
mate procedural bleeding risk based on their knowledge of the procedures they
perform and their past experiences.
264 G. Ellis
Table 45.2 HAS-BLED score

Condition Points
H Hypertension (uncontrolled, >160 mmHg systolic) 1
A Abnormal renal function (dialysis, transplant, Cr > 200 μmol/L) 1
Abnormal liver function (cirrhosis, bilirubin >2x normal, AST/ALT/ 1
ALP > 3x normal)
S Stroke (history of stroke) 1
B Bleeding (history of major bleeding or bleeding tendencies) 1
L Labile INR 1
E Elderly (age > 65 years) 1
D Medication (DOACs, antiplatelet agents, NSAIDS) 1
Peri-operative Cessation of Anticoagulants
Warfarin is usually stopped 5 days before surgery. As the offset can be unpredictable
patients’ INR should be checked pre-operatively; an INR ≤ 1.5 is usually desirable.
Those with very high thrombosis risk (and low bleeding risk) may be candidates for
peri-operative bridging with low-molecular-weight heparins (LMWH).
Factor Xa inhibitors (Rivaroxaban, Apixaban and Edoxaban) should be stopped
48 hours before any procedure with a high risk of bleeding in all patients. For pro-
cedures with low risk of bleeding these can be stopped 24 hours before, except in
those with significant renal impairment (CrCl 15–29 mL/min), in which an interval
of at least 36 hours should be considered (Table 45.3).
Cessation of Dabigatran is more closely tailored to creatinine clearance; those
with normal function should stop 48 hours and 24 hours before, for high risk and
low bleeding risk procedures, respectively (Table 45.4).
Use of peri-operative bridging with heparins/LMWH is generally not required
for patients on DOACs due to their predictable and prompt offset and onset, which
can therefore be appropriately timed with respect to the procedure.
Full dose DOAC can be resumed 24 hours after low bleeding risk procedures and
from 48–72 hours post high bleeding risk procedures.
45 Anticoagulants and Their Reversal 265
Table 45.3 Peri-operative cessation of Apixaban, Edoxaban and Rivaroxaban [1]

Low risk of bleeding High risk of bleeding
CrCl ≥ 80 mL/min ≥ 24 h ≥ 48 h
CrCl 50–79 mL/min ≥ 24 h ≥ 48 h
CrCl 30–49 mL/min ≥ 24 h ≥ 48 h
CrCl 15–29 mL/min ≥ 36 h ≥ 48 h
CrCl < 15 mL/min Use of DOACs not indicated
Table 45.4 Peri-operative cessation of Dabigatran [1]

Low risk of bleeding High risk of bleeding
CrCl ≥ 80 mL/min ≥ 24 h ≥ 48 h
CrCl 50–79 mL/min ≥ 36 h ≥ 72 h
CrCl 30–49 mL/min ≥ 48 h ≥ 96 h
CrCl < 29 mL/min Use of Dabigatran not indicated
Reversal of Anticoagulants
Bleeding events are the main risk of anticoagulant use, although are less frequent
with DOACs compared to Warfarin. General haemostatic measures should be
employed in these circumstances, as well as prompt management of the bleed-
ing source.
Rapid reversal of anticoagulants in an emergency setting can be achieved by
administration of Prothrombin Concentration Complex (PCC), which contains
highly concentrated coagulation factors (4-factor: II, VII, IX and X, or 3-factor: II,
IX and X) and will reverse anticoagulation within minutes of administration.
Examples of PCC include Beriplex™ and Octaplex™.
If PCC is not available, Warfarin can be reversed by administration of fresh fro-
zen plasma (FFP) or vitamin K. Administration of FFP may take hours due to the
large volumes required and may be associated with fluid overload. Vitamin K effects
may take up to 24 hours for full effect. INR levels must be checked to guide further
therapy.
266 G. Ellis
Andexanet alfa acts by binding to and sequestering Factor Xa inhibitor mole-

cules and is therefore effective at reversing the effects of Apixaban and Rivaroxaban.
Idarucizumab is a humanised monoclonal antibody, which binds to Dabigatran
with high avidity and prevents it binding to thrombin.
There is no approved reversal agent for the reversal of Edoxaban and PCC should
be used in this situation. In these situations, measurement of the DOAC activity may
be useful and it is recommended to consult with a haematologist with expertise in
this area for patient- and scenario-specific advice. Incomplete reversal and thrombo-
sis are complications associated with DOAC reversal and, perhaps due to the under-
lying bleeding condition or patient comorbidity, may be associated with poor
outcomes.
Reference
1. Steffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L, Haeusler KG, Oldgren J,
Reinecke H, Roldan-Schilling V, Rowell N, Sinnaeve P, Collins R, Camm AJ, Heidbüchel H. The
2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist
oral anticoagulants in patients with atrial fibrillation. Eur Heart J. 21 April 2018;39(16):1330–93.
Chapter 46
Haemostatic Agents, Tissue Sealants
and Adhesives
Omer Abdalla and Suresh Venugopal
Bleeding is an occupational hazard for all surgeons. Minimally invasive surgical

techniques have expanded the need for newer methods of achieving haemostasis
beyond manual pressure, suturing and diathermy. Common agents now used include
haemostats (cause blood to clot), sealants (form a barrier between tissues) and adhe-
sives (bind tissues together).
Haemorrhage is a problem encountered by surgeons since the earliest days of
surgery. From pressure and tourniquets, progress was made to use of ligation or
transfixion of blood vessels with sutures. As technology advanced, clips and elec-
trocautery came along to aid haemostasis. With advancing technology enabling
more complex procedures to be carried out minimally invasively, the demand for
achieving haemostasis in unconventional ways has increased.
Injury of a blood vessel stimulates a series of enzymatic reactions which ulti-
mately leads to haemostasis. Haemostasis has four stages: vasoconstriction, platelet
plug formation, coagulation cascade activation, and fibrin clot formation. The pro-
cess of coagulation commences with series of enzymatic reactions within blood ves-
sels (intrinsic pathway) or outside blood vessels (extrinsic pathway). This ultimately
results in the formation of prothrombin activator which converts prothrombin into
thrombin. Thrombin converts fibrinogen to a fibrin monomer. This then polymerises
to form loose fibrin strands. Factor XIII, in presence of calcium, modifies loose fibrin
strands into dense strands which aggregates to form a stable blood clot (Fig. 46.1).
This process can be aided by adjuncts to arrest the bleed such as:
• Haemostats—causes blood to clot
• Sealants—forms a barrier between tissues
• Adhesives—glues the tissues together
O. Abdalla · S. Venugopal (*)

Liverpool University Hospitals, NHS Foundation Trust, Liverpool, UK
e-mail: omer.abdalla@liverpoolft.nhs.uk; suresh.venugopal@liverpoolft.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_46
268 O. Abdalla and S. Venugopal
Resting Contact Cellulose

Collagen
platelets activation Gelatin
Extrinsic pathway
Intrinsic pathway Tissue damage
Platelet Activation of kallikrein,
activation Tissue thromboplastin and
factor XII, factor XI, and
calcium
factor IX
Platelet granule
Activated factor VII Factor VII
Release factors
Factor X Activated factor X
Prothrombin Thrombin
Via factor XIII
Fibrin Fibrin Fibrinogen

polymer monomer
(soluble)
Fibrin glue variants Fibrin clot
Fig. 46.1 The coagulation cascade with principle haemostatic technologies (red boxes)
Haemostatic Agents
Haemostatic agents (haemostats) can be further divided into 4 categories based on

their functional properties: mechanical, active, flowable and fibrin sealants.
(Table 46.1).
Mechanism of Action (see Table 46.1)
Mechanical haemostats act by forming a barrier to the bleeding and constitute a

matrix that expedites clot formation (Gelatines and ORC). Polysaccharide spheres
absorb blood fluid content leading to condensation of red blood cells, platelets and
proteins with formation of haemostatic plug. Collagen-based agents enhance plate-
let aggregation when they adhere to collagen fibrils.
Active haemostats are composed of bovine, porcine or recombinant human
thrombin. They work by converting fibrinogen into fibrin. Flowable agents com-
posed of gelatine matrix combine with thrombin to form a suspended liquid that
upon application cohere to bleeding sites and stop bleeding by converting fibrino-
gen into fibrin and mechanical obstruction to bleeding. Fibrin sealants are an emul-
sion of fibrinogen and thrombin which interact with each other to form fibrin that
expedites coagulation (Table 46.1).
46 Haemostatic Agents, Tissue Sealants and Adhesives 269
Table 46.1 Haemostat mechanisms of action

Haemostat
type Class Products Mechanism of action
Mechanical Porcine gelatine Gelfoam ® Absorbs bleeding (sponges)
Surgifoam ® Creates scaffold that enhance
coagulation and act as barrier to
bleeding
Bovine collagen AviteneTM flour/ Creates matrix that activates
sheets/foam coagulation cascade
Instat ® Enhance platelet aggregation
Oxidized regenerated Surgicel ® Mechanical barrier to bleeding
cellulose (ORC) Contact activation of the clotting
cascade
Acidic environment enhance
coagulation by denaturing proteins
Polysaccharide AristaTM AH Absorb blood fluid contents
sphere Enhance formation of haemostatic
plug
Mechanical barrier
Active Thrombin (Bovine/ Thrombin-JMI ® Thrombin converts fibrinogen into
Porcine) Evithrom fibrin
Recombinant human
thrombin
Flowable Bovine gelatin + HPP FloSeal ® Combination of mechanical and
thrombin SurgifloTM active haemostat mechanisms
Porcine gelatin
+/− thrombin
Fibrin Biological-derived Tisseel Thrombin interacts with fibrinogen to
sealants Evicel ® from fibrin
TachoSil ®
Safety
Mechanical haemostats come in different forms such as powder, sponge, or fibrillar

form. These agents are used as an adjunct to aid control capillary, venous, and arte-
riolar bleeding when conventional methods are either ineffective or impractical.
Risks include infection, foreign body reaction and allergic reaction. Oxidized regen-
erated cellulose (Surgicel®), when left behind, can mimic a gas-containing abscess
on post-operative CT imaging. The radiologist must therefore be aware of it’s use
when requesting post-operative CT imaging to be able to interpret the images cor-
rectly. It can also cause stenosis if applied around anastomoses.
Bovine thrombin is antigenic and can trigger antibody formation against bovine
thrombin (factor II) and bovine factor V which cross-react and neutralise human
factors II & V leading to coagulopathy. The risks associated with flowable agents
and fibrin sealants relates to thrombin, as explained above.
270 O. Abdalla and S. Venugopal
Sealants
These are compounds that act as a barrier to fluid leak (e.g. blood, urine). Sealants
can be used to control bleeding, close suture holes or holes in a hollow viscus. In
urology, they are most commonly used in partial nephrectomy. Tissue sealants are
classified into two categories: biological sealants (e.g. fibrin sealants—discussed
above), and synthetic sealants.
There are three types of synthetic sealants; Polyethylene glycol (PEG) polymers,
Albumin and Glutaraldehyde, and Cyanoacrylate. The synthetic sealants cross-link
with tissue proteins and induce spontaneous bonding with tissues. Synthetic seal-
ants are predominantly used for vascular anastomoses and are rarely used in urology.
Adhesives
In general, tissue adhesives are meant to hold two sides of tissues together and sup-
port wound healing until regenerated tissue has enough mechanical strength. They
are most commonly used to aid skin closure. There are three categories: fibrin seal-
ants (discussed above), cyanoacrylates, and albumin and glutaraldehyde.
Cyanoacrylates such as Dermabond and Indermil polymerizes rapidly when adhere
to water and glue adjacent surfaces. Albumin and glutaraldehyde adhesives such as
Bioglue, interact with tissue proteins and induce sealing of tissue surfaces indepen-
dent to the coagulation pathway.
Further Reading
Boucher BA, Traub O. Achieving hemostasis in the surgical field. Pharmacotherapy. 2009;29:2s–7s.
Burks S, Spotnitz W. Safety and usability of hemostats, sealants, and adhesives. AORN
J. 2014;100:160–76.
LaPelusa A, Dave HD. Physiology, hemostasis. 2021 May 9. In StatPearls [Internet]. Treasure
Island (FL): StatPearls Publishing; 2022 January.
Spotnitz WD, Burks S. State-of-the-art review: hemostats, sealants, and adhesives II: update
as well as how and when to use the components of the surgical toolbox. Clin Appl Thromb
Hemost. 2010;16(5):497–514.
Chapter 47
Transfusion in Urology
Patient Blood Management (PBM) is an internationally recognised concept for the

evidence-based management of transfusion and blood function. This approach pro-
vides the clinician with methods to minimise the use of blood components when
alternatives to transfusion may be associated with better outcomes and more effec-
tive use of resources.
The complications associated with blood transfusion can be severe, and with
constant concerns relating to stock levels of available blood, it is the responsibility
of the clinician to employ adequate PBM principles when caring for their patients.
Complications of Transfusion can be best categorised as “immune-related” or
“non-immune related”.
Immune-related
• Iatrogenic ABO incompatibility: Human error contributes significantly to

transfusion complications. This can include errors during the collection, process-
ing and administration of components and can result in the incorrect blood com-
ponent being transfused. Ultimately this can cause an acute haemolytic reaction.
• Antigen sensitisation: Antigens on the red cell surface of blood when transfused
may initiate antibody formation in the host as it recognises ‘non-self’. Even fol-
lowing correctly performed crossmatching, antigen/antibody reactions can occur
leading to haemolysis (the immune mediated breakdown of red cells).
C. Carroll (*) · H. Lucero

e-mail: craig.carroll@srft.nhs.uk; harriet.lucero@nca.nhs.uk
J. Peters
Manchester Foundation Trust, Manchester, UK
e-mail: jayne.peters@nhsbt.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_47
272 C. Carroll et al.
• Transfusion Related Immunomodulation (TRIM) is another issue to be con-

sidered. This is a dose dependent down regulation of the immune response,
increasing infection risk and potentially increasing rates of tumour recurrence or
metastasis post radical surgery.
• Transfusion Association Lung Injury (TRALI): Can be a form of acute respi-
ratory distress syndrome (ARDS), essentially, a non-cardiogenic pulmonary
oedema following transfusion.
Non-Immune Related
• Transfusion Associated Circulatory Overload (TACO): This remains the

leading cause of transfusion-related death. Care should be taken to assess a
patient’s fluid status and explore alternatives to transfusion to reduce this risk.
• Transfusion Reactions: Non-haemolytic febrile and allergic reactions are the
most common transfusion reactions; these are usually not preventable.
• Coagulopathy: Can occur due to dilutional effect of packed red cells without
platelets or clotting factors.
• Metabolic abnormalities: Common metabolic abnormalities may include hypo-
calcaemia, hypomagnesemia, hyper/hypokalaemia. These effects may be dilu-
tional, due to erythrocyte cell lysis or secondary to higher levels of citrate in
autologous blood.
• Transfusion-transmitted infection (TTI): Although the risk is small due to
donor screening and widescale testing, there remains a risk of acquiring infection
(mainly viral and bacterial) secondary to transfusion. The risk of bacterial trans-
mission is highest with platelets as they are stored at room temperature.
• Hypothermia: Blood products are often cool, or frozen and thawed before
administration. Rapid transfusion can therefore lead to reduced body
temperatures.
For the urology patient the “Three Pillars” of PBM can be applied by the follow-
ing steps.
(1) Pre-operative optimisation of patients
(2) Management of acute losses intra-operatively
(3) Management of post-operative/non operative patients with anaemia
47 Transfusion in Urology 273
(1) Pre-Operative Optimisation

• Management of Pre-Operative Anaemia
Identification, investigation, and treatment of anaemia is key to reducing the
need to consider red cell transfusion. These steps should be undertaken at the
earliest opportunity in the patient’s surgical journey to allow time for diagnosis,
and a response to treatment.
Causes of Anaemia in Urological Patients
Type of anaemia Cause Laboratory investigation

Iron Deficiency Bleeding, diet, malabsorption, Low ferritin and low transferrin
Anaemia (IDA) malignancy saturation
Functional Iron Infection, inflammation (possibly Low transferrin saturation,
Deficiency (FIDA) with iron deficiency) normal or high ferritin
B12/Folate Deficiency Dietary/malnourishment/drugs Low B12/folate
Renal Failure Reduced erythropoiesis, reduced Usually CKD3 & below
red cell survival time
Myeloma Marrow dysfunction, renal failure Abnormal Immunoglobulin
electrophoresis and serum free
light chains
Haemoglobinopathy Reduced manufacture, increased Haemoglobinopathy screen
(trait or disease) fragility (e.g. sickle cell disease
and thalassaemia)
Investigations in Pre-operative Anaemia Screening
Full Blood Count

CRP
Iron studies
Ferritin
B12
Folate
eGFR
Myeloma screen
Haemoglobinopathy screen (where appropriate)
In some instances, the anaemia will be difficult to treat, though IV iron adminis-
tered to patients with iron deficiency can prove highly effective. The response is not
immediate and optimal improvement may take weeks. The response is less marked
and slower to achieve in renal failure. However, the literature suggests that pro-
longed benefits are seen in IDA patients who have received IV iron, though its effect
may not alter peri-operative transfusion. The effect of IV iron in patient with FIDA
is less clear. Erythropoiesis-stimulating agent (ESA) therapy is rarely used in pre-
operative anaemia management and requires expert supervision, being associated
with numerous adverse side effects.
(2) Management of Peri-Operative Losses

The PBM interventions during surgery focus upon surgical technique to
minimise bleeding, ensure normal coagulation by avoidance of excessive hae-
modilution and maintenance of coagulation factors and platelets, use of
tranexamic acid to maintain clot stability and use of cell salvage to reduce the
need for donor red cell transfusion.
Crystalloids, though the traditional means of maintaining circulating volume
during minimal to moderate bleeding, can be detrimental. They have little phys-
iological benefit and most of the volume infused leaves the circulation rapidly.
Dilution of the intravascular compartment causes reduced blood viscosity and
dilutes clotting factors thus reducing initiation and propagation of clot.
Point of Care Testing (POCT) of coagulation using thromboelastography, as
well as traditional laboratory investigations should be considered to guide peri-
operative coagulation therapy. During major haemorrhage (MH), initial blood
component replacement should follow guidelines in the major haemorrhage
protocol. This will advocate red cell—fresh frozen plasma—cryoprecipitate—
platelets at certain ratios. Finessing of coagulation management during MH can
be achieved by POCT.
Tranexamic acid, a lysine analogue, acts by inhibiting activation of plasmin
that breaks down fibrin clot. Although NICE recommendations (NG24, 2015)
advise usage when moderate blood loss is expected (> 500 mls), there are estab-
lished concerns that it may promote clot retention within the urinary tract.
(3) Post-Operative or Non-Operative Management
In the haemodynamically stable patient who is not actively bleeding, avoid-
ance of transfusion is preferable to the administration of donor red cells, thus
restrictive transfusion triggers (70–80 g/L) should be considered. In patients
with significant coronary artery disease, less restrictive triggers are recom-
mended. The NICE guidelines (NG24, 2015) suggest a transfusion trigger of
80 g/L and a post-transfusion haemoglobin target of 80–100 g/L in the context
of acute coronary syndromes. As with pre-operative management, the identifi-
cation of the cause of anaemia is important. Where there has been known bleed-
ing, post-operative IV iron may be of benefit and improve haemoglobin
concentration.
Red Cell Antibodies and Haemolysis
When a patient receives a red cell transfusion, there may be an antigen activation
response that generates a new antibody in the recipient detecting ‘non-self’.
Antibodies may coat red cells highlighting their removal from the circulation by
complement-mediated cell lysis or via the spleen. This can manifest by the patient
having a haemolytic transfusion reaction (signs and symptoms include a fever, rig-
ors, back pain, failure of haemoglobin to increment, jaundice and haemoglobinuria)
or may only be detected when performing subsequent laboratory tests. Haemolysis
47 Transfusion in Urology 275
can be ‘acute’ (within 24 hours) or ‘delayed’ (up to three weeks following transfu-
sion). Severe haemolysis can lead to significant renal impairment and poten-
tially death.
When a ‘group and save’ is performed, the patient’s current antibody status is
confirmed alongside the patient’s ABO and D status. If the antibody screen is posi-
tive, referral to a regional specialist laboratory may be required for identification.
When crossmatching blood, selection of ABO and D compatible blood units which
are antigen negative for known and historical red cell antibodies are selected by the
Hospital Transfusion Laboratory.
It should be noted that “O negative” blood is not immunologically inert, and
when used as un-crossmatched emergency blood for patients, haemolytic transfu-
sion reactions remain a risk.
Further Reading
Muñoz M, Acheson AG, Auerbach M, Besser M, Habler O, Kehlet H, Liumbruno GM, Lasocki
S, Meybohm P, Rao Baikady R, Richards T, Shander A, So-Osman C, Spahn DR, Klein
AA. International consensus statement on the peri-operative management of anaemia and iron
deficiency. Anaesthesia. 2017;72:233–47. https://doi.org/10.1111/anae.13773.
Muñoz M, Acheson AG, Bisbe E, Butcher A, Gómez-Ramírez S, Khalafallah AA, Kehlet H,
Kietaibl S, Liumbruno GM, Meybohm P, Rao Baikady R, Shander A, So-Osman C, Spahn DR,
Klein AA. An international consensus statement on the management of postoperative anae-
mia after major surgical procedures. Anaesthesia. 2018;73:1418–31. https://doi.org/10.1111/
anae.14358.
https://www.transfusionguidelines.org/transfusion-handbook
Chapter 48
Cell Salvage in Urological Surgery
Intraoperative Cell salvage (ICS) is a means of recovering, processing, and preserv-

ing blood lost during surgery.
Whole blood lost during surgery can be recovered during ICS. Red cells within
whole blood are subsequently processed and preserved in a suspension of 0.9% saline
for re-infusion to the patient during (or shortly after) surgery. The red cell substrate is
suctioned from the surgical field or extracted from swabs that have been placed within
the surgical field. Swabs are rinsed in saline which is subsequently suctioned into the
ICS reservoir. ICS should be considered in all cases where blood loss may result in
anaemia or put the patient at risk of donor red cell transfusion (Fig. 48.1).
If a patient is undergoing surgery where blood loss is likely to occur and transfu-
sion may be necessary, the patient should be informed that options exist for red cell
replacement. (Montgomery vs Lanarkshire 2015).
Benefits
Salvaged red cell transfusion has a number of benefits over using allogeneic (donor)
red cells.
• Stored red cells have reduced deformability and depletion of 2,3 DPG (diphos-
phoglycerate). This effectively reduces oxygen availability at capillary beds.
C. Carroll (*) · H. Lucero

e-mail: craig.carroll@srft.nhs.uk; harriet.lucero@nca.nhs.uk
J. Peters
Manchester University, NHS Foundation Trust, Manchester, UK
e-mail: jayne.peters@nhsbt.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_48
• Changes in proteins on the red cell membrane of stored red cells alter immune
function in the recipient, causing Transfusion Related Immunomodulation
(TRIM). The resulting immunosuppression may increase the incidence of post
operative infection (surgical site and other nosocomial infection).
• Packed red cell donor transfusion has been associated with negative oncological
outcomes post-surgery, including increased rates of tumour recurrence and
metastasis.
• Although red cell microbiological screening and cross matching reduces the
risk of infection and antibody incompatibility immensely, antibody sensitisa-
tion can occur, and delayed antibody reactions are also possible (see
Chap. 47).
• Having ICS available allows the anaesthetist to reduce the volume of crystalloid
infusions that are traditionally used to support the circulating volume following
bleeding. This therefore reduces haemodilution with the associated coagulo-
pathic and perfusion related complications.
• ICS may be the only transfusion option in patients who refuse donor blood trans-
fusion. ICS usage can significantly reduce theatre usage of donor red cells, an
important consideration when blood stocks are threatened by demand exceeding
stock levels.
Dirty suction
reservoir Reinfusion
Anti bag of
Coagulation processed Saline
Bag RBC wash
ACDA or
30,000 units
of Heparin in
IV saline
Dual lumen
suction line
Cannula Standard Blood
Giving Set
Filter
PATIENT
Roller
pump
Dual lumen
suction line
Dual lumen
Reservoir
150 µ filter
5,000 units of Heparin Reservoir Centrifuge 5,500

with 1 litre of saline
to 6,000 revs
Swab wash
sterile bowl Cell Salvage Machine Waste
products
collection bag
Smart Suction
Fig. 48.1 Schematic diagram of standard intraoperative set-up for intraoperative cell salvage
48 Cell Salvage in Urological Surgery 279
Indications for Usage
1. Estimated blood loss >500 mls or 10% of circulating volume

2. Patients with low starting haemoglobin or increased risk of bleeding
3. Patients with multiple red cell antibodies or rare blood groups
4. Patients refusing blood products
5. ICS should be considered standard in Major Haemorrhage Protocols.
Absolute Contraindications
1. Untrained staff in patient selection, blood aspiration and processing

2. Patient refusal.
Relative Contraindications and Controversies
ICS in Malignancy
Historically the use of ICS in cancer surgery was controversial on account of suc-
tioned malignant cells being retained in reinfused into the patient, risking malignant
dissemination and metastatic deposits. Some authors have previously advocated irra-
diation of salvaged blood prior to reinfusion. However, there is substantial body of
evidence supporting ICS as a safe practice in cancer surgery. Patients with malignancy
frequently have circulating malignant cells though few are capable of implantation
and generating metastasis. Prudent suction and use of leucocyte depletion filters at
reinfusion can massively reduce the tumour cell load of the red cell suspension. Meta-
analysis of ICS in urological cancer surgery has not demonstrated negative tumour
outcomes compared to donor transfusion or permissive anaemia. The use of ICS is
recommended for cystectomy and radical prostatectomy by the National Institute for
Health and Care Excellence (NICE) and is widely used in nephrectomy surgery.
Sepsis
Sepsis is not an absolute contra-indication to ICS, however aspiration from highly

infected or contaminated blood is to be avoided. The use of leucocyte depletion fil-
ters at reinfusion reduces bacterial load and the standard antibiotic prophylaxis
appears effective in minimising infective complications. It should be noted that sig-

nificant bacterial concentrations have been isolated in ICS product, but this does not
appear to result in post operative sepsis.
Haemoglobinopathy
Theoretical concerns relating to red cell fragility with abnormal red cell morpholo-
gies (eg spherocytosis) exist. In addition, there are concerns that both lysis and
sickling may occur in patients with both sickle disease and trait. The literature is
incomplete in this area and ICS cannot be recommended as a standard in these
patient groups. However, patients who have undergone exchange transfusion for
sickle cell disease prior to their operation, should be discussed with their responsi-
ble haematologist. In situations of life threatening and large volume donor transfu-
sion, ICS may be of benefit.
When ICS is being considered, the WHO surgical checklist processes should be
employed to ensure safe and appropriate practice.
1. Correct patient selection

2. All team members understand their roles for safe collection, processing, and reinfusion
3. IV saline must be used for irrigation
4. A standard waste suction must be set up for aspiration of irrigation, contaminants, pro-
coagulants, tumour rich aspirate.
5. Use a dedicated suction where possible and consider “flooding the wound with saline” to
increase yield and reduce red cell damage”.
Performing ICS
The theatre should be set up to allow the ICS machine to be close to the anaesthetic
team. If swab washing is being performed, a sterile bowl containing appropriate
fluid (IV saline with 5000units per L heparin or ACDA). The ICS suction system
allows the red cell substrate to combine with anticoagulant within the suction tubing
that carries substate to a reservoir. The substrate travels through a coarse filter and
resides in a reservoir until processing. Processing on most systems relies upon cen-
trifugation, where plasma proteins, clotting factors, platelets, particulate matter, free
haemoglobin, aggregates, bacteria, and anticoagulant are spun off and the remain-
ing red cells suspended in normal saline.
The red cell/saline suspension is then delivered to a labelled blood giving bag
and presented for infusion. Infusion occurs through the standard 200 mcg filter,
though additional filters can be used.
48 Cell Salvage in Urological Surgery 281
SAFE SUCTION TECHNIQUES

Avoid aspirating any of the following:
1. Pus
2. Directly from a tumour bed
3. Urine or faeces
4. Bile
5. Betadine, chlorhexidine, or hydrogen peroxide
6. Haemostatic agents
Modification of the ICS Technique
When the ICS substrate is under threat of contamination, remove the ICS sucker
from the surgical site, inform the ICS team (ICSP/ODP) that potential contamina-
tion is possible.
• Do not re-introduce ICS suction until the wound is clear of contaminant.
• Inform the anaesthesia team that you wish to re-commence collection.
Certain substances may be introduced into the operating site e.g. Fibrin Glue, Pro-
coagulant substances. If this occurs
1. Allow the substance to dry, irrigate with 1000 mls IV saline & aspirate this
to waste.
2. Confirm with the anaesthesia team that it is OK to re-commence ICS collection.
Reinfusion of ICS Product
Re-infusion of the red cell suspension should be performed within 6 hours of collec-
tion, in many instances this can occur during surgery. The standard blood giving set
has a 170–200 mcg filter and should be used. In addition, lipid reduction filters and
leucocyte depletion filters may be used. The latter reduces reinfusion of tumour
cells and bacteria, however they require priming, significantly reduce the flow rate
of re-infusion to 40–100 ml per minute and require replacement after 450 mls of
infusion.
Reinfusion hypotension can occur when the product is infused into the patient.
Hypotension can be severe, requiring vasopressor therapy. The cause is unclear,
however it occurs more commonly when LDFs are used.
Further Reading
Carroll C, Young F. Intraoperative cell salvage. BJA Educ. 2021 Mar;3:95–101.

Catling S, Williams S, Freites O, Rees M, Davies C, Hopkins L. Use of a leucocyte filter to remove
tumour cells from intra-operative cell salvage blood. Anaesthesia. 2008;63(12):1332–8.
Hansen E. Is intraoperative blood salvage really safe in cancer surgery? Transfusion.
2012;52(12):2723–4. author reply 4
Kim-Shapiro DB, Lee J, Gladwin MT. Storage lesion: role of red blood cell breakdown.
Transfusion. 2011;51(4):844–51.
Klein AA, Bailey CR, Charlton AJ, Evans E, Guckian-Fisher M, McCrossan R, et al. Association of
anaesthetists guidelines: cell salvage for peri-operative blood conservation 2018. Anaesthesia.
2018;73(9):1141–50.
Chapter 49
Principles of Urological Endoscopes
Hari L. Ratan
Urological endoscopes can fall into one of four categories based on how the image
is transmitted along the telescope:
• Rod lens endoscopes
• Flexible endoscopes
• Semi-rigid endoscopes
• Digital, distal tip chip endoscopes
Rod Lens Endoscopes
These are considered in Chap. 50.
Flexible Endoscopes
Cladded glass rod cores conduct light through the principle of total internal reflec-
tion with little loss of light intensity. A single glass fibre when stretched to 1/100 mm
in diameter and combined with multiple fibres in an, ordered, coherent bundle, can
transmit a complete, but compound, image. A flexible ureterorenoscope has around
4000 fibres in the bundle and can deflect 270° in both directions at the tip.
In addition to this coherent fibre bundle which transmits the image, there is a
separate non-coherent bundle that conducts light into the body cavity, an instrument
channel to allow irrigation and instrumentation and two control wires that are con-
nected to the thumb lever to deflect the distal tip up and down (Fig. 49.1).
H. L. Ratan (*)
Nottingham University Hospitals, Nottingham, UK

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_49
284 H. L. Ratan
Strain relief
Wire fastening Deflection lever
Deflection cables Magnification gear
and lens system
Control wires
Air vent valve

Belt disk
Light post
Fig. 49.1 The control components of a flexible endoscope (image courtesy of Karl Storz)
All of these elements are free to move independently of each other housed in the
vertebrae of the scope as it flexes. An outer cover maintains a water- tight environ-
ment allowing the scope to be effectively cleaned. Any leaks in the outer cover or
inner working channel will allow fluid ingress into the scope which will affect the
view and ultimately seize up the moving parts. It is important to leak test the scope
before every use as fluid ingress is also a potential cross contamination risk.
The benefits of flexible endoscopes are:
• Flexibility, the telescope conforms to the anatomy and not the other way round
• A deflecting tip allows the scope to view and access areas otherwise off limits to
rigid telescopes.
The limits of flexible endoscopy are:
• The image quality is limited by the mechanics and physics of the individual
fibres, and by the total number of fibres in the bundle—the image is not as clear
as the coherent image provided by a similar-sized Hopkins rod lens telescope
and can suffer from the moiré effect.
• Due to the complex nature of the scopes and the fine manufacturing processes,
the scopes are expensive to purchase, and maintain, relative to rod lens instruments.
• The materials used to make the flexible parts will not resist the heat and pro-
cesses involved in steam sterilisation meaning that most flexible endoscopes in
urology are simply decontaminated and not sterile.
Semi-rigid Endoscopes
These instruments use the same coherent image bundle and non-coherent illumina-
tion bundle technology as flexible scopes. but are housed in a semi-rigid metal skin
rather than flexible vertebrae; they do not deflect at the tip.
49 Principles of Urological Endoscopes 285
In the case of a semi-rigid ureteroscope, the design allows a degree of malleabil-

ity whilst maintaining the rigidity needed to advance up a torturous ureter. Semi-
rigid telescopes are often used in paediatric endoscopes where the scope diameters
are between 1–2 mm. It is possible to make rod lens systems this size, but their rela-
tive fragility necessitates a compromise between the optical view and durability.
Digital, Distal-tip Chip Endoscopes
Traditionally, any image made through a flexible endoscope is viewed on a monitor;

this necessitates attaching a camera head to the eyepiece of the scope where it is
converted to a digital format. Regardless of camera quality, the image quality will
be limited by the fibre optic system of the telescope. With the miniaturisation of
charged-couple-device (CCD) and complementary metal–oxide–semiconductor
(CMOS) video chips, it is now possible to mount the chip at the distal tip of the
telescope without increasing the overall size of the telescope. Removing the optical
fibres and placing the chip at the source has dramatically improved the quality of
images available from flexible endoscopes.
Flexible ureterorenoscopes utilise the latest CMOS technology to produce stun-
ning images of the upper urinary tract without compromising the external size,
instrument channel or scope deflection (Fig. 49.2). LED illumination technology is
incorporated into the body of the hand piece and light is transmitted into the patient
by a conventional non-coherent fibre bundle. This eliminates the need for a light
guide cable thus reducing the weight of the instrument and improving its fine
manipulation during surgery. Distal tip chip technology is likely to represent the
future of flexible endoscopy in urology.
Fig. 49.2 Endoscopic

view from a CMOS chip
endoscope (image courtesy
of Karl Storz)
286 H. L. Ratan
Single-Use Endoscopes
A number of single-use (ie disposable) flexible cystoscopes and ureteroscopes have

become available in recent years. The potential benefits of single-use endoscopes
include:
• Single-use ‘scopes are always sterile when opened compared to reusable scopes
which undergo high-level decontamination. Thus, they can be used in patients
who are known to be colonized by multi-resistant organisms without any con-
cern about cross-contamination
• Single-use ‘scope systems are typically more compact, allowing their use outside
of conventional operating room environments, such as in outpatient facilities.
• In high turnover lists (such as one-stop haematuria clinics), time between patients
is minimized as the ‘scopes do not need to be reprocessed.
• Single-use ‘scopes can be used during procedures known to be associated with a
high risk of reusable scope damage, for exampling when treating a stone in a
difficult lower pole renal calyx.
However, the benefits of single use ‘scopes must be carefully considered in the con-
text of the costs and potential environmental impact of this technology.
Chapter 50
Rigid Endoscope Design
James Broome
Rigid endoscopes provide the mainstay of diagnostic and therapeutic interventions

to the lower urinary tract.
Rigid Endoscope Construction
A contemporary rigid endoscope consists of:

• An optical system—comprised of a distal tip objective lens system, a relay sys-
tem in the body of the telescope and a diopter lens which magnifies and brings a
coherent image to the eyepiece. This standard eyepiece allows direct ocular
vision or the connection of a camera head.
• A mechanical sheath that mounts this system and protects it from external influ-
ences. The housing allows the endoscope complex to be effectively sterilised though
steam autoclaving and offers the glass lenses protection from physical damage.
• A non-coherent glass fibre system to transmit light into the patient and illuminate
the cavity under view. The fibre bundle runs through an outer shell of the tele-
scope from the light post to the distal tip and uses the same type of fibres as in a
fibre optic light cable. The “light lead”.
• An instrument/flow channel through which peripheral instrumentation and irrig-
ants can be passed.
This combination of components gives a durable, malleable and endo-surgical sys-
tem with a coherent image that has mechanical strength and can be used to generate
torque. It can be steam or heat sterilized.
J. Broome (*)
Salford Care Organisation, Northern Care Alliance, Manchester, UK
e-mail: james.broome@nca.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_50
288 J. Broome
Fig. 50.1 A simple lens endoscope as first described by Nitze. The lenses are shown in blue
(image courtesy of Karl Storz)
Conventional Optical Systems
In 1877, Maximilian Nitze demonstrated his first conventional thin lens system cys-
toscope (Fig. 50.1). This endoscope, although a landmark in endoscopic surgery,
had its drawbacks. Refraction occurred as light passed through the thin lenses seated
at intervals, which resulted in a dark and distorted image. In addition, the first endo-
scopes used a glowing platinum wire, and later an incandescent light bulb, at their
distal tip as their sole source of illumination. Endoscopic urology as we know it
today was not developed until the problem of thermal tissue injury caused by this
illuminating source was solved.
Rod-lens/Cold Light Optical Systems
In 1959 Prof Harold Hopkins, of Reading University, designed and patented the
Rod Lens System, and in 1960 Dr Karl Storz developed fibre optic cold light illumi-
nation utilising a non-coherent fibre bundle with an externally generated light beam.
In 1966, they collaborated to produce the Hopkins rod lens system in which the rod
lenses are seated at close intervals. This ingenious design, of a glass rod with air
‘lenses’ (Fig. 50.2) and externally generated transmitted light resulted in vastly
improved image brightness, clarity and field of view from a smaller diameter tele-
scope. Light is guided to the tip of the endoscope via a non-coherent fibre-bundle
which starts in the upward projecting ‘light’ pillar. This is attached, via a non-
coherent fibreoptic light guide, to the external light source.
The distal tip objective lens can be angled off the 0° to give an oblique view—the
most commonly used angles in urology are 12°, 30° and 70°. By rotating these
scopes on their axis, a differential field of view can be achieved with minimum
physical trauma to the structure being examined.
In urology today, the rod lens system is incorporated into all adult rigid cysto-
scope, resectoscope, nephroscope and laparoscopic instruments.
50 Rigid Endoscope Design 289
Fig. 50.2 Hopkins rod—lens array endoscope. The lenses are shown in blue (image courtesy of
Karl Storz)
Modified Conformations of the Rod Lens System
In the nephroscope, the requirement for a straight working channel necessitates an

offset parallel or angled offset eyepiece, however the telescope still uses rod lenses
and fibre optic light transmission but with a 6° angle of view.
Telescopes can incorporate instrument and irrigation channels as part of an inte-
grated design. These instruments have the advantage of being generally more dura-
ble but lack the versatility of being able to interchange peripheral instrumentation.
Identifying Problems in a Rod-lens Optical System
Hopkins rod lens telescopes are high performance and precise optical systems which
must be treated with care and cleaned, and maintained, in accordance with the man-
ufacturers’ guidelines. If they are not the following issues may be visible in use:
• Reduced image contrast—caused by fluid ingress into the telescope condensing
on the internal lens surfaces. This not only impedes the surgical view but also
poses a potential contamination issue—if this unidentified fluid can get in, it can
also get out.
• Poor light transmission—caused by damaged to the fibre optic light bundles.
Physical dents on the shaft of the telescope can damage the fibres running along
it resulting in reduced light transmission down the endoscope. The view outside
the patient in a brightly illuminated room is unaffected so such damage is often
missed in cursory checks.
• Partial loss of image field—caused by impact. Chipped lenses often leave the
circular ‘chip’ in view. This is often free to move in the space between the lenses
similar to a kaleidoscope when the telescope is turned. This is easy to visualise
when the distal tip chips. Chips closer to the proximal eyepiece generally give a
blurred image.
• Blurred image—could be due to dull external optical surfaces, cracked lenses or
fluid ingress. Residue can build up on the distal and proximal optical surfaces if
particular attention is not paid to their cleaning. Special telescope cleaning paste
is available to polish the end components of the optical system.
Chapter 51
Light Sources, Light Leads and Camera
Systems
Hari L. Ratan
Good quality light is essential to optimise endoscopic examination, but light can
also be used therapeutically. Endoscopic imaging depends upon effective transmis-
sion of light from the light source, through a light cable and the endoscope’s intrin-
sic light guide. The image is viewed via a coherent fibre-optical or digital system
and displayed on a monitor.
Diagnostic Light Sources
Light sources should, ideally, be matched to the camera system to allow automatic
regulation of output in varying situations. The power of light sources varies from
100 to 300 Watts with light intensity being controlled manually or automatically.
Most light sources have an inbuilt fan cooling system to protect the bulb and the
light should be put on standby when not in use to prolong bulb life. High intensity
light can burn the patient or surgeon or ignite surgical drapes.
Generated light typically comes from a halogen bulb, which gives a softer light,
or xenon bulb, which gives a brighter white light. Narrow band imaging (NBI) is an
optical filter technology that radically improves the visibility of subtle tissue struc-
tures by optimizing the absorbance and scattering characteristics of light. NBI uses
two discrete bands: one blue at 415 nm, and one green at 540 nm. Blue light high-
lights superficial capillary networks, whilst green light emphasizes sub-epithelial
vessels.
H. L. Ratan (*)
Nottingham University Hospitals, Nottingham, UK

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_51
292 H. L. Ratan
Photodynamic Diagnosis (PDD)
PDD relies on the selective emission of fluorescence by cancer cells. This requires
pre-procedure intravesical instillation of a substance such as 5-aminolevulinic acid
(ALA) or hexaminolevulinate (HAL). The drug is usually given 1 hr prior to the
cystoscopy. These substances are taken up by cells within the bladder mucosa and
converted to protoporphyrin IX (PpIX). This conversion varies in activity between
normal and malignant cells. These PpIX molecules can then be detected by illumi-
nating the bladder with “blue light” (wavelength 360–450 nm) during cystoscopy,
theoretically allowing detection of small or subtle malignant lesions which might be
missed during routine “white light” cystoscopy.
Therapeutic Light Sources
For effective photodynamic therapy (PDT) a light source is used to stimulate apop-
tosis in specifically sensitized cancer cells. Red visible light, at a wavelength of
400–1064 nm, penetrates well into tissue and is used to induce production of singlet
oxygen species which induce apoptosis in sensitised tissues. Several types of light
source can be used for PDT including broad-spectrum halogen lamps, light emitting
diodes (LEDs) and lasers. The choice of light source depends upon the light dose
required and the geometry of the area to be illuminated.
Light Leads or Guides
Light guides are non-coherent fibre bundles that link the external light source to the
endoscope. Effective connection from source to ‘scope is key to optimise light
transmission into the organ being examined. One of the most frequently encoun-
tered causes of poor illumination, during endoscopy, is a faulty light cable; this is
usually due to broken fibres in the bundle or build up of ‘film’ on the connectors on
the ends of the guide.
Camera Systems
Modern cameras use charged couple devices (CCD), to obtain good quality images.
The CCD may be mounted in an external, detachable, camera or be integrated at the
end of a video-scope.
In a digital video CCD, the image is projected through a lens onto a two-
dimensional capacitor array (a mono-crystalline layer of silicon, the photoactive
region), causing each capacitor to accumulate an electric charge proportional to the
light intensity at that location. A control circuit causes each capacitor to transfer its
51 Light Sources, Light Leads and Camera Systems 293
contents to its neighbour until the charge is converted into a voltage. In a digital
device, these voltages are then sampled, digitized, and stored in memory and pro-
cessed into a continuous analogue signal which is then fed out to a monitor for
transmission, or for recording or re-processing.
Setting the Camera Up
The light source, guide cable and endoscope should be checked to ensure they are trans-
mitting light correctly and the clarity of the optical system confirmed prior to endoscope
insertion. The camera should be properly connected to the control box, and endoscope,
and the monitor should be switched to the correct channel to display the images from
the camera. Image quality may then be influenced by four generic functions.
White Balance
This is the most important function on the camera and has the greatest impact upon
image quality. It calibrates the camera to white which acts as a baseline from which
all other colours are reproduced. White balance can be set by wrapping a clean
white swab around the distal end of the telescope to form a cone, or funnel, and
activating the ‘white balance’ function on the camera. It is good practice to re-set
the white balance at the start of each endoscopic procedure.
Iris Function
The iris ensures that optimal illumination is provided across the full field of view for
the telescope. There are at least two settings for the iris, “Average” and “Peak”.
Average, when the iris is fully open, is used when looking into large cavities, such
as the bladder and is appropriate for approximately 95% of all laparoscopic proce-
dures in urology. “Peak”, when the iris is closed to reduce glare, is used when the
object of interest is close to the tip of the endoscope, such as calculi during ureteros-
copy. Some modern cameras have a variable control that allows the iris to be set at
any point between these two extremes.
Automatic Gain Control (AGC)
AGC electronically alters illumination should the picture become dark, by increas-
ing the light intensity, without the need to alter the settings on the light source. In
modern cameras, this is activated automatically when the illumination level becomes
low e.g., when the image quality darkens in the presence of blood.
294 H. L. Ratan
Table 51.1 Common problems encountered when setting up an endoscopic monitor

Problem Solution
No Check the camera is connected and that line A or line B channels on the monitor are
Picture receiving the signal
Too Check the iris setting
Bright
Too Dark Check light transmission from source to ‘scope, check AGC
Too Red Incorrect white balance
Too Blue Incorrect white balance against a red background
Digital Enhancement
Digital enhancement makes the picture sharper and is used to bring out fine detail in
the endoscopic image.
Trouble Shooting
Practically, there are 5 possible problems, which may be rectified if an image is sub-
optimal in theatre (Table 51.1).
Further Reading
Chou DS, McDougall EM. Endoscopic imaging and instrumentation. In: Advanced endourology:
The complete clinical guide. New Jersey: Humana; 2006.
Preminger GM, Sur L, Scales CD. Video imaging and documentation. In: Smith’s textbook of
endourology. 2nd ed. Hamilton: BC Decker; 2006.
Chapter 52
Peripherals for Endoscopic Use
Steve Payne
Since the dawn of endoscopy, surgeons have wanted to add more and more instru-
ments to the armamentarium they could deploy to increase the number of proce-
dures they could perform endoscopically. This chapter describes the instruments
that have been developed to allow more endoscopic surgery to be possible.
There are a variety of peripheral devices that can be used for manipulation in the
upper or lower urinary tract. Some of these are inserted via specialized endoscope
sheaths and others, that may be rigid or flexible, are inserted through an access port
Table 52.1.
Specialised endoscopic peripherals are usually rod-lens based and tend to be used
for very specific, and common, procedures, such as transurethral resection, internal
Table 52.1 Peripheral instrumentation used for diagnostic and therapeutic purposes in the
urinary tract
Integrated endoscopic peripheral Port-accessed peripheral
Resectoscope Albarrán lever
Optical urethrotome Biopsy forceps
Optical lithotrites Graspers
Scissors
Injection needles
Stone manipulators
Laser fibres
Stone disrupters
Guidewires and catheters
Diathermy and other thermal sources
S. Payne (*)

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_52
296 S. Payne
urethrotomy and lithotrity of bladder stones. Peripheral devices such as unipolar or

bipolar loops, diathermy balls and endoscopic knife blades can be inserted to the
‘working element’ of these types of endoscope. Mechanical stone destructors work
either by ‘punching’ the stone against the tough metallic outer sheath of the device or
by crushing the stone, visualized endoscopically, between mechanically operated jaws.
Port-accessed instruments are used for diagnostic and therapeutic purposes
through rod lens or fibre-optic instrumentation in both the lower or upper urinary
tracts. The port is usually constructed into a special ‘bridge’ which links the endo-
scope system to the outer sheath of a non-integrated device. Some endoscopes have
all components integrated into the device and contain a port, or ports for the inser-
tion of peripheral instrumentation. The access bridge may have one or two ports;
flow integrity is maintained by the presence of a perforated rubber ‘nipple’ through
which the peripheral can be placed.
The size of appropriate port-accessed devices is dictated by the diameter, or
French gauge, of the working channel of the endoscope, which in rigid endoscopes
is affected by the overall size of the outer sheath. The outer sheath is often 7–10 Fr
for paediatric instrumentation and 17–25 Fr for adult endoscope systems. As most
outer sheaths act as an instrumentation and irrigant flow channel, the presence of the
peripheral decreases irrigant flow and can interfere with vision, especially in the
presence of bleeding. Some port-accessed peripherals are rigid, whilst others are
malleable or entirely flexible. They may be re-usable or disposable, and the choice
of device may depend on the operator’s preference, the peripheral’s durability and
its recycling versus replacement cost.
Peripherals for Rigid Endoscopes
When using a rigid cystoscope, a single or double channel bridge may be used
which may incorporate a deflecting mechanism such as the Albarrán lever Fig. 52.1.
The Albarrán lever allows deflection of less rigid devices such as guidewires,
catheters and stents (Fig. 52.2).
The angle between the port on a non-integrated cystoscope and the instrument/
flow channel of the sheath is usually around 20 degrees (Fig. 52.1) which means that
rigid devices cannot be inserted through this access port without affecting their
efficacy in use.
When a rigid peripheral, such as a lithoclast or grasping forceps, is needed an
offset eyepiece with a straight integrated access port allows the passage of the
device through the working channel (Fig. 52.3). Some ureteroscopes may have
more than one instrument channel so that different implements for stone manipula-
tion can be inserted without risk of them becoming intertwined.
Peripherals used with rigid scopes are generally shorter than those used with
flexible instruments and operate under vision at the tip of the optical system. A
30-degree angle lens is conventionally used for manipulations in the bladder but
52 Peripherals for Endoscopic Use 297
Fig. 52.1 A rod-lens cystoscopy with its outer sheath and an Albarrán lever above. Replacement
of the conventional bridge allows instruments to be inserted into the bladder and deflected by turn-
ing the wheel on the Albarrán lever
Fig. 52.2 An Albarrán

lever being used to deflect
a retrograde catheter
angles between 0–30 degrees may be used in the urethra, ureter or kidney, depen-
dent on the angle of view required to observe the peripheral in action. Peripherals
utilizing a hinge mechanisms, such as alligator forceps (Fig. 52.4) and endoscopic
scissors, need to have whole of the hinge mechanism completely outside the instru-
ment sheath before they can work properly. This means that those peripherals can
only work effectively where there is sufficient space within the body cavity they are
being deployed in to work.
298 S. Payne
Fig. 52.3 An offset

eyepiece endoscope with
straight instrument channel
to facilitate the insertion of
rigid peripherals
Fig. 52.4 The hinge on an

alligator forcep cannot
open fully until it is
completely outside the
working channel or
instrument sheath
Peripherals for Flexible Endoscopes
All flexible endoscopes have an integrated instrument/flow channel within the outer
core which encompasses the fibre bundle and the light guide. The deflectability of
the tip of the endoscope may be limited by the rigidity of the peripheral, and sharp
devices should be inserted to the tip of the endoscope before insertion. This will
help prevent perforation of the instrument channel and instrument damage that
might be caused by advancing a sharp device through the bending section when this
is fully angulated (Fig. 52.5).
52 Peripherals for Endoscopic Use 299
Fig. 52.5 The bending

section of a flexible
ureteroscope with a stone
basket open. The acute
angulation of this section
makes perforation a real
risk when inserting sharp
instruments
Peripherals for Either Flexible or Rigid Endoscopes
All peripherals utilizable via a flexible endoscope’s flow channel can be used down
rigid instrumentation. These devices are, however, often of a smaller diameter, lon-
ger and are both more fragile and more expensive than their re-utilizable alternatives.
Further Reading
Khanna R, Monga M. Instrumentation in endourology. Ther Adv Urol. 2011;3(3):119–26.

Lurvey RB, Canvasser N. Urologic instrumentation: Endoscopes and lasers. In: Urologic prin-
ciples and practice. Cham: Springer; 2020. p. 257–268.
Chapter 53
Peripherals for Laparoscopic Use
Dora Moon
Peripheral instrumentation for laparoscopic surgery is continuously evolving to

increase safety, speed, and efficiency during surgery. Instruments can be used to cut,
cauterise, dissect, retract, staple, clip and retrieve tissue. There is an extensive range
of laparoscopic instruments available, and this chapter is by no means exhaustive, but
aims describe the most encountered instruments in laparoscopic urological surgery.
Dissection, Manipulation, and Retraction
Graspers are a useful tool in laparoscopic surgery for moving structures and per-
forming blunt dissection. There are two main types of graspers: traumatic and
atraumatic. Short fenestrated or Johan graspers are an example of atraumatic grasp-
ers which allow the surgeon to safely hold structures such as bowel and the renal
artery. Maryland graspers are also atraumatic but have a finer curved tip for more
precise dissection and tissue holding. Toothed or crocodile graspers are traumatic
but allow for fixed tissue grasping for example when removing a specimen through
a laparoscopic port or to allow for liver retraction during a right sided nephrectomy.
All laparoscopic graspers come with a rotation wheel allowing for 360 degrees of
movement at the tip and the option of a ratchet or non-ratchet handle. These instruments
vary in diameter from 3–11 mm but the vast majority used in urological surgery are
5 mm. Additionally most of these instruments are modified to allow for the connection
of a monopolar or bipolar diathermy lead to give the further option of haemostasis.
Finally, a fan retractor (Fig 53.1) can be used when retracting larger structures and
assisting in applying appropriate tension during tissue dissection. They tend to be a
larger diameter (up to 10 mm) so need an appropriately sized laparoscopic port for access.
D. Moon (*)
Lancashire Teaching Hospitals NHS Trust, Preston, UK

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_53
302 D. Moon
Fig. 53.1 (a) Closed fan a

retractor. (b) Open fan
retractor
Table 53.1 Tips to minimise thermal injury with monopolar electrosurgical instruments used
laparoscopically
1. Check there is no damage to the insulation on the instrument
2. Only activate the device when the whole of the metal component is in view
3. Only activate the device when it is in direct contact with the intended tissue
4. Use active electrode monitoring (detects a break in insulation resulting in immediate
deactivation)
5. Consider using bipolar surgical devices
Cutting and Haemostasis
To achieve effective tissue cutting with vessel sealing, there are now numerous meth-
ods available to the surgeon. Firstly, there is the option of laparoscopic scissors used
in combination with monopolar diathermy. There are many types of laparoscopic scis-
sors available designed to suit a range of different surgical procedures and techniques.
Another use of monopolar diathermy to achieve tissue cutting is the hook elec-
trode, which allows for fine tissue dissection and simultaneous haemostasis. Safe
use of electrosurgical instruments is essential to minimise thermal injury in both the
field in view and that out of view which may be injured by direct or capacitive cou-
pling—tips for safe use are outlined in Table 53.1.
There is increasing use of newer technologies such as the Harmonic Scalpel and
LigaSure™ systems. The harmonic scalpel works via high frequency ultrasound
energy generated by a piezo-electric crystal, which produces mechanical vibration
at 55,500 Hz at the tips. LigaSure™ uses a bipolar radio-frequency generator and
instrument pressure to seal and divide tissues. It has been designed to detect tissue
impedance in order to appropriately adjust the energy output to match the desired
tissue effects. The advantage of these systems is the ability to simultaneously cut
and seal tissues in addition to grasping and dissection. Both instruments cause mini-
mal energy transfer to surrounding tissues (up to 1 mm).
Retrieval
To safely retrieve a dissected specimen during laparoscopic surgery, the tissue can
be placed into a sac or bag to facilitate extraction, preventing contamination of the
abdominal cavity, and wound, in the process. Most bags are designed with a
53 Peripherals for Laparoscopic Use 303
self-
opening and closing device which allows for a completely laparoscopic
approach to specimen retrieval. Larger bags require larger diameter ports and there-
fore, when placing ports at the beginning of the operation the potential size of the
specimen and its extraction bag needs to be taken into consideration. It is important
to be familiar with the mechanism of deployment, entrapment, closing and removal
of the bag system used.
Suction and Irrigation
The majority of devices for suction and irrigation are disposable and are often in
combination to improve economy of movement. The end of the instrument is usu-
ally blunt and may be used as a dissection tool. The ideal instrument should provide
enough fluid pressure to achieve clot dissolution and a large enough bore to allow
clot suction, without sucking delicate structures into the probe tip.
Suturing, Stapling, and Clipping
Type of sutures, staples and clips are discussed in more detail in Chap. 55. This sec-
tion will briefly cover technologies that have modified these methods for laparo-
scopic use.
Mechanical vessel sealing can be achieved via traditional suturing and whilst this
is a key skill to posses as a laparoscopic surgeon, there are several devices available
to assist in suture placement. Endo Stitch™ is a single use device with a pre-loaded
double-pointed needle and suture that allow easy deployment of both interrupted
and continuous sutures. LAPRA-TY® clips can also be used to deploy absorbable
(vicryl) suture clips laparoscopically. There is no substitute, however, for being able
to place stitches, and tie knots, using a laparoscopic needle holder. There are many
different types of laparoscopic needle holder, and each individual will need to find
a set that is comfortable to them.
There are many stapling devices available, and it is important to be familiar with
the device you use as each is slightly different. Most staplers articulate or reticulate,
come in various sizes and with varying applicators depending on the intended use.
Most deliver multiple rows of staples and have a deployable blade which cuts
between the staple rows. Ensuring that you understand the process of holding,
securing, deploying, cutting, and releasing the staple device is essential to ensure
safe use. Malfunction, such as cutting without stapling, can be catastrophic laparo-
scopically; this is often due to human error.
Metal clips are useful for ligation of small vessels using either single placement
or multi-fire devices. They can however, be easily dislodged especially if coagula-
tion is applied in their vicinity. The Hem-o-lok® polymer ligation clip system allows
304 D. Moon
Fig. 53.2 Hem-o-lok®polymer ligation clip system
for safe and effective management of hilar, and larger vessels (Fig. 53.2). These
clips completely surround the vessel and lock with a satisfying click at the far side
of the vessel. They are not electro-conductive. Laparoscopic clip removers can
safely remove these clips should they be applied incorrectly.
Further Reading
Berguer R. Surgical technology and the ergonomics of laparoscopic instruments. Surg Endosc.
1998;12(5):458–62.
Levine RL, Pasic RP. A practical manual of laparoscopy: a clinical cookbook. London:
Parthenon; 2002.
Rosenblatt A, Bollens R, Cohen BE. Manual of laparoscopic urology. Berlin, Heidelberg: Springer-
Verlag; 2008.
Chapter 54
Peripherals for Mechanical Stone
Manipulation
Ciaran Lynch
Ureteroscopy is one of the mainstays of stone treatment. The advent of nitinol based
technology has been imperative to its success in allowing the urologist to safely
access the urinary tract to allow stone manipulation and retrieval.
Background
Ureteroscopy is one of the mainstays of stone treatment. Stones are most commonly
fragmented with a laser to dust or fragments which are then removed using a device
such as a basket or a grasper. The increased success of ureteroscopic management in
recent years has been due to the miniaturisation of these tools and the development
of nitinol, an alloy of nickel and titanium. Nitinol is elastic and has a ‘memory’ and
is therefore useful as a core material in both guidewires and baskets as it allows it to
retain its original shape, resist kinking and cause minimal loss of deflection.
Guidewire Selection
Guidewires are used as the precursors to almost all endourology. They allow access
and safety for all endoscopic procedures.
Guidewires are available in a range of sizes and designs. The 0.035 and 0.038in.
diameter and the 150 cm length wires are those most commonly used in urology.
Important variable characteristics include tip shape, shaft rigidity, shape memory,
torque (property of the wire that allows movement at one end to be transmitted to
C. Lynch (*)
e-mail: ciaran.lynch@liverpoolft.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_54
306 C. Lynch
the other end providing closer control), and surface resistance. Rigidity, shape
memory, and torque are conferred by the properties of the material used to form the
core of the wire, whilst the degree of surface resistance is dependent on the coating
applied. All guidewires have a flexible, atraumatic tip ranging from 3–15 cm.
A standard guidewire has a stainless-steel core coated with PTFE and a flexible
tip, which may be straight, angled, or J-shaped. An angled tip helps the guidewire
slide pass end-on tissue surfaces, whilst the J-shaped tip reduces the possibility of
tissue perforation. Where there is difficulty in negotiating narrow or tortuous anat-
omy, a more slippery guidewire is commonly employed. A typical example is the
Glidewire® (TerumoTM) made of nitinol with a hydrophilic coating. The hydro-
philic coating reduces friction along its surface when wet, making it very slippery
and easy to pass tight areas such as an impacted ureteric stone. The core of the
Glidewire has less rigidity, meaning a false passage is less likely to be created. It is
also available with a straight or angled tip. The disadvantage of these guidewires is
that they are easily displaced and need to be exchanged for a less slippery and stiffer
guidewire before working within the urinary tract.
Guidewires with a high degree of shaft rigidity are chosen when greater stability
is required when stress is imparted on the wire. These “working” guidewires often
have a nitinol inner core reinforced with a stiffer outer core material. An example is
the Amplatz Super StiffTM that is often used for ureteroscope advancement and tract
dilatation in a PCNL. Some hybrid guidewires, such as the SensorTM guidewire, have
the combination of a floppy hydrophilic-coated tip and a nitinol with PTFE-coated,
kink-resistant body, providing ease of access as well as stability. Some guidewires,
such as the Zebra® wire, have surface markers to demonstrate movement in use.
Ureteral Catheters
4.8–8 Fr open-ended ureteric catheters are placed in the ureter to perform retrograde
pyelography and obtain urine for cytology or culture. They are commonly 70 cm in
length and made of polymer. They are lined with radio-opaque material to allow
visualisation during fluoroscopy.
Ureteral Occlusion Devices
The Dretler Stone Cone TM is a spiral device designed to prevent retropulsion of stone
fragments during intracorporeal lithotripsy. Before it is deployed it is straightened,
allowing placement beyond the stone; when deployed, the distal end coils, occluding the
lumen of the ureter proximally (unless the ureter is significantly dilated). The deployed
coils of the stone cone can then be used to “trawl” stone fragments out of the ureter.
An alternative includes the Cook NTrap ® which consists of a 7 mm umbrella of
woven mesh that is, like the Stone Cone, deployed proximal to the stone to prevent
migration of ureteric fragments.
These are especially useful in cases when there is no access to a flexible uretero-
scope (Figs. 54.1 and 54.2).
54 Peripherals for Mechanical Stone Manipulation 307
Fig. 54.1 Stone Cone

Retrieval coil
Fig. 54.2 Cook NTrap

stone entrapment device
Basket and Grasper Selection
Baskets and graspers can be employed within the urinary tract to manipulate and
retrieve kidney stones. Baskets come in different constructs and the type chosen
depends mainly on the stone size, number, and location. They range in diameter from
1.5–2.2 Fr and are easily deployed down both semi-rigid and flexible ureteroscopes.
For ureteric stones, most modern baskets are made of nitinol. These baskets have
the strength to expand the ureter and open within a narrow lumen. Most have a
straight tip guide, which is placed beyond the stone providing greater stability when
in use. The cage of these baskets is constructed either with wires in a straight or
spiral configuration. The choice between the two is a matter of personal preference,
but in general straight wire cage baskets are better for larger single stones, whilst a
spiral basket is better for capturing multiple smaller stones.
For stones in the calyces, tipless (zero tip) nitinol baskets are preferred as they
can be opened adjacent to tissue surfaces, allowing close stone approximation in a
308 C. Lynch
Fig. 54.3 Stone baskets from left to right: Zero TipTM, NForce® Helical Stone extractor, NGage
stone extractor, Storz 3-prong grasping forceps
limited space while avoiding damage to the calyx. These baskets are more flexible
and have smaller diameters, causing less impairment to scope deflection and irriga-
tion flow when used with a flexible ureteroscope. Other basket types for use in the
kidney include the nitinol NGageTM and Graspit®, which have non-traumatic jaws
that open like forceps providing easier stone capture and release if necessary.
Three-pronged or four-pronged graspers can also be used to retrieve stones in the
ureter. They have the advantage of a low grasping pressure which allows stone
release if it becomes stuck in the ureter. Caution should be used when deploying the
pronged grapsers as there is a risk of causing ureteric injury when deploying the
sharp prongs.
The handles of all modern baskets can be dismantled to allow backward removal
of the ureteroscope whilst the basket remains in place. This is invaluable when the
basket and stone gets trapped in the ureter, permitting removal of the scope and
reinsertion alongside the basket so that the stone can be fragmented further
(Fig. 54.3).
Rigid Instruments
Rigid instruments are often used in PCNL to grab and retrieve stones or fragments.
Alligator forceps have pincer grip handles with various types of jaws whilst the
three-pronged grasper has a U-shaped spring handle that holds onto the stone.
Baskets with a rigid shaft and a U-shaped spring handle such as the NCircle®
can also be used to retrieve stones. This device comes with a basket that either opens
out straight or at an angle. The latter is particularly useful for retrieving stones in
calyces, which cannot be accessed with straight forceps or graspers.
54 Peripherals for Mechanical Stone Manipulation 309
Fig. 54.4 Ureteral access

sheaths
Access Sheaths
Access sheaths for ureteroscopy facilitate the lowering of intra-renal pressure,

improving irrigant flow, better visibility, decreasing operative time and lower rates
of sepsis. They are a 2-piece device with an internal dilator and an outer hydrophilic
sheath. They are preferred in the management of large stones where multiple passes
are required to remove multiple fragments or prolonged ureteroscopic procedures.
They come in a variety of diameters (9.5–14 F internal diameter and 11.5–17.5 F
external diameter) and lengths (20–55 cm). In patients with a previously un-stented
ureter, an access sheath of 9/11 Fr might pass easily, whereas in a previously stented
ureter, a 10/12 sheath might be preferred. They are usually placed in the upper ureter
or pelviureteric junction over a guidewire (Fig. 54.4).
Further Reading
Clayman M, Uribe CA, Eichel L, Gordon Z, McDougall EM, Clayman RV. Comparison of guide
wires in urology. Which, when and why? J Urol. 2004 Jun;171(6 Pt 1):2146–2150. https://doi.
org/10.1097/01.ju.0000124486.78866.a5. PMID: 15126774
Somani BK, Aboumarzouk O, Srivastava A, Traxer O. Flexible ureterorenoscopy: Tips and tricks.
Urol Ann. 2013 Jan;5(1):1–6. https://doi.org/10.4103/0974-7796.106869. PMID: 23662000;
PMCID: PMC3643314.
Stern KL, Monga M. Ureteral access sheaths and irrigation devices. In: Schwartz F, Denstedt J,
editors. Ureteroscopy. Cham: Springer; 2020.
Chapter 55
Sutures and Clips
Bachar Zelhof
Sutures and clips are utilised by surgeons to achieve the two aims of tissue approxi-
mation and/or haemostasis. This chapter describes the common sutures and clips
available and their relative indications for use in certain types of surgical procedures.
Sutures
Suture material must have good knot tying/handling characteristics, be of low tissue
reactivity and have sufficient strength for their purpose. Suture types are grouped
into the following categories:
• Absorbable versus nonabsorbable
• Braided versus non-braided
• Natural versus synthetic
• Smooth versus barbed texture
Absorbable sutures are degraded by processes such as hydrolysis and enzyme
degradation. Absorption time varies from short [40 days] i.e Vicryl rapid, to medium
[50–70 days] i.e Vicryl, or long [200+ days] i.e PDS. Although, many lose half their
tensile strength much sooner. Patient’s factors such as infection or low protein can
increase the absorption rate of a suture and weaken its materials. Non-absorbable
sutures remain until removed such as Polyester and Nylon which provide good ten-
sile strength with low tissue reactivity and less scarring. Although non-absorbable,
they will lose their strength with time.
B. Zelhof (*)

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_55
312 B. Zelhof
Monofilament Sutures are made of a single strand of material which makes them
susceptible to damage from instrumentation like holding the suture with a needle
holder. Monofilament sutures tend to have higher memory which can affect their
handling property and knot security. They cause low inflammatory response and are
less likely to harbour bacteria.
Multifilament sutures can be braided or a twist of smaller strands. They have a
rough surface which causes a high tissue drag but better handling property and knot
security. They cause high inflammatory response and increased tendency to bacte-
rial colonisation.
Sutures can be made of natural materials (such as sheep gut collagen, “catgut” or
silk), synthetic materials or metals.
Smooth surface sutures require knot tying for anchoring into tissue. The knot can
cause tissue inflammation and necrosis and increase susceptibility to infection.
Barbed sutures contain barbs on the surface of their material which hold the
sutures to the tissues. Barbed sutures facilitate suturing in minimally invasive sur-
gery as there is no need to tie a knot. Antibacterial sutures such as Vicryl Plus are
coated with antibacterial agents such as Triclosan to reduce bacterial colonisation
and infection rates. Table 55.1 illustrates the most common sutures used.
Table 55.1 Commonly used surgical suture materials, their absorption times and uses
Brand Absorption
name Material Pattern time Common use/notes
Absorbable sutures
Vicryl Polyglactin Braided 50–70 days Can be dyed [Blue/
purple] or undyed
Vicryl Rapid absorbing Braided 40 days Circumcision
rapida Polyglactin
Monocryl Poliglecaprone Monofilament 90–119 days Subcuticular skin
closure
PDS Polydioxanone Monofilament 180–210 Abdominal closure
days
V-Loc Glycolide, dioxanone, Monofilament 90–110 days Barbed
trimethylene carbonate
Stratafix Polydioxanone Monofilament 90–110 days Barbed
Non-absorbable sutures
Silk Natural Silk Braided Indefinite Secure drains
Nylon Polymers Braided Indefinite Tendon repair
Prolene Polypropylene Monofilament Indefinite Vascular anastomoses
Metal Stainless steel Monofilament Indefinite Chest closure
a
Vicryl Rapid is made of a polymer with a lower molecular weight than standard polyglactin with
a rapid absorption time
55 Sutures and Clips 313
Table 55.2 Suture sizes and their diameter in mm
Suture size Diameter (mm)

11-0 0.01
10-0 0.02
9-0 0.03
8-0 0.04
7-0 0.05
6-0 0.07
5-0 0.1
4-0 0.15
3-0 0.2
2-0 0.3
0 0.35
1 0.4
2 0.5
3 0.6
4 0.6
5 0.7
6 0.8
Suture Size
Sutures were initially manufactured ranging in size from 1 to 6 with 1 being the
smallest. As the surgical techniques evolved the demands for thinner sutures
increased, size 0 was added to the sutures diameter. Subsequently thinner threads
were manufactured and were identified as 00 or 2/0 or 2-0. Table 55.2 summarises
suture codes and their diameters
Needles
Surgical needles are available in over 220 different styles, diameters and curves.
Normally they are made from stainless steel.
Needles have three sections (Fig. 55.1):
• The point, which may be blunt (like in abdominal wall closure to minimize
needle-stick injuries), cutting (pierce fibrous dense tissue), reverse cutting, taper-
cut (used to penetrate tissue that can be damaged with cutting needle),
• The body, straight or curved (1/4, 3/8,1/2, 5/8)
• The swage to which the suture is attached.
314 B. Zelhof
Fig. 55.1 The needle parts
Point Swaged
end
Body
Needles are either traumatic or atraumatic (separate or swaged on to the suture). The
advantage of the atraumatic needle is that the suture is swaged to the eyeless needle
by the manufacturer. This reduces the trauma and friction as the needle passes
through friable tissues. The choice of needles is defined by the tissue being pene-
trated, the available access space, the needle holder and the surgeon’s preference.
Needle/Suture Combinations
However confusing this is initially, most specialties use a very limited range of
suture/needle combinations and the trainee rapidly becomes familiar with them. In
surgery in general, the “anything suture” was historically 2/0 chromic catgut, now
replaced by the ubiquitous 2/0 Vicryl (polyglactin) on a half circle, round bodied
needle (W9136). Catgut has become obsolete because of a vCJD transmission risk.
When performing a laparotomy, the scrub nurse is likely to have various “standard”
sutures and ties immediately available such as 2/0 Vicryl ties and 0 PDS sutures for
abdominal wound closure. In urology, ureteric and renal sutures are usually atrau-
matic 3/0 or 4/0 Vicryl. The bladder is usually closed in two layers of 2/0 Vicryl, the
small bowel anastomosed in one or two layers with the either of these sutures (2,3).
V-lock and Stratafix barbed sutures have become popular in minimally invasive
surgery such as radical prostatectomy or pyeloplasty. Each needle and suture packet
contains 12 items of information (Fig. 55.2).
1. Colour code
2. Life size picture of needle
3. Gauge [size]
4. Company name
5. Type of suture
6. Needle length
Fig 55.2 A suture packet
7. Needle type
8. Length of suture
9. Lot number
10. Expiry date
11. Sterile statement
12. Product code
Stapling Devices
Like sutures, staples have the same two functions of tissue approximation and hae-
mostasis. They can be permanent [usually MRI compatible] or absorbable. They are
made of stainless steel (such as skin clips) or titanium loaded into rechargeable
cartilages. They have been developed to replace hand suturing to improve the speed,
and security, of anastomosis and to be used laparoscopically. They cause minimal
tissue reaction and have low risk of infection. Many different shapes of stapling
applicators have been developed for specific purposes, particularly for bowel anas-
tomoses and vessel sealing (Fig. 55.3) Typical devices include:
• Medtronic/Autosuture
–– Endo GIA, [ie 8.0 cms, 3.8 mm staple, Single], used in ileal conduit creation
and small bowel anastomoses
• Ethicon Endosurgery
–– Proximate ILS [Intra-Luminal Stapler]
• Ethicon skin stapler
316 B. Zelhof
Fig. 55.3 Vascular stapler 35 mm
The US food and drug administration (FDA) has published a letter to the health-
care providers in October 2021 regarding the safe use of surgical staplers (4). The
document outlines the following recommendations:
(1) The choice of staples is appropriate to the tissue type and thickness
(2) Consider other options for oedematous or friable tissue
(3) Be aware iatrogenic injury of the surrounding tissue
(4) Be prepared for stapler failure especially on blood vessels
(5) Ensure that the staples and compatible with the stapler
(6) Avoid crossing of staples line
Stapling techniques for ureteric anastomoses, uretero-ileal anastomoses, neoblad-
der construction and bladder neck—urethral anastomoses in radical prostatectomy
are in development and are not yet commonly used; most anastomoses continue to
be sutured by hand.
Clips
Clips were developed to enable secure “ligation” of vessels or tissue bundles in

laparoscopic surgery as suture tying was perceived as difficult. Many open sur-
geons, however, use clips for the same purpose, particularly in inaccessible areas
such as the depth of the pelvis. Applicators, therefore, exist for both open and lapa-
roscopic clip application. Clips can be either permanent (stainless steel or titanium)
or biodegradable (Magnesium alloy). Clips may be either locking, in which case
they have ‘teeth’ which mesh together or be simply compressive.
Clip applicators can be automatic reloading (multiload) or manual (single load).
Usually they have a 360 degree rotation wheel to allow application in various angles.
Clips can be of different sizes (5 or 10 mm).
Hem-o-locks are routinely used in laparoscopic surgery as a substitute to suture

ligation. They are nonabsorbable polymer locking clips. They are compatible with
Ct and MRI. The presence of teeth in the jaws makes them well secure. The Hem-
o-lock clips are available in 3 sizes mainly XL (Gold), L (purple), medium-large
(green) and medium (blue). The cartilage contains 6 clips. Multiple studies have
confirmed the safety of Hem-o-locks and metal clips in controlling renal vessels
during nephrectomy.
Further Reading
Dennis C, Sethu S, Nayak S, Mohan L, Morsi Y, Manivasagam G. Suture materials—Current and

emerging trends. J Biomed Mater Res Part A. 2016;104A:1544–59.
Israelsson LA, Jonsson T. Suture length to wound length ratio and healing of midline laparotomy
incisions. Br J Surg. 1993;80(10):1284–6.
Seiler CM, Bruckner T, Diener MK, Papyan A, Golcher H, Seidlmayer C, Franck A, Kieser M,
Büchler MW, Knaebel HP. Interrupted or continuous slowly absorbable sutures for closure
of primary elective midline abdominal incisions: a multicenter randomized trial (INSECT:
ISRCTN24023541). Ann Surg. 2009;249(4):576–82.
Simforoosh N, Sarhangnejad R, Basiri A, Amir Mohsen Ziaee S, Sharifiaghdas F, Tabibi A,
Nouralizadeh A, Kashi AH, Moosanejad N. Vascular clips are safe and a great cost-effective
technique for arterial and venous control in laparoscopic nephrectomy: single-center experi-
ence with 1834 laparoscopic nephrectomies. J Endourol. 2012 Aug;26(8):1009–12.
Chapter 56
Contact Lithotripters
The evolution of endoscopic methods of intra-corporeal stone management fuelled

the development of means of disintegrating urinary stones in-situ to minimise
trauma to the collecting system, and to enable large stones to be removed safely in
the pelvi-calyceal system, ureter and bladder.
Contact lithotripters are of three types: pressure disruptors (such as electro-
hydraulic lithotripters) have been superseded by advancements in mechanical dis-
ruptors, which ‘drill’ into the stone such as ultrasonic and ballistic lithotripters, and
laser devices. The benefits and disadvantages of each and their effects on stone will
be considered (Table 56.1).
Table 56.1 How intra-corporeal lithotripters work, their efficacy in stone fragmentation and
potential for thermal injury
Stone Thermal
Lithotripter Mechanism of action contact Resistant stones injury
Electrohydraulic Shock wave generated under No None Yes
(EHL) water through co-axial probe: (<1 mm
micro-explosions away)
Ultrasonic (USL) High-frequency vibration of Yes Calcium oxalate Yes
metal probe; aspiration of monohydrate
fragments
Ballistic Projectile fired onto metal rod Yes None No
by pressurised air
Lasertripsy Photothermal No None Minimal
(Ho:YAG) Photochemical
(Thulium fibre) Cavitation
T. Brophy (*) · S. Payne

e-mail: thomas.brophy@mft.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_56
320 T. Brophy and S. Payne
Electro-Hydraulic Lithotripsy (EHL)
EHL was one of the first methods described for disruption of urinary stones but is
largely obsolete in clinical practice. Like the first extra-corporeal lithotripters, EHL
depends upon the discharge of an ultra-high tension, ultra-short discharge between
insulated coaxial electrodes. A potential difference is created by a generator exter-
nally and passed down a flexible ‘electrode’ into the patient. The spark that is dis-
charged between the two components of the co-axial electrode, under vision,
vaporises the irrigant medium creating a plasma cavitation bubble. The collapse of
the bubble leads to microjets near the stone to be fragmented. The cavitation bubble
size is dependent on the energy used and has significant variability. The bubble can
case distention and damage to the urothelium as a result. Most concerning is the risk
of causing perforation when the probe is activated in direct contact with the tissue.
Retropulsion of the stone can also be a challenge to overcome. Safe use of EHL
necessitates avoiding multiple, rapid shocks in the same area with the least amount
of energy necessary to successfully fragment the stone.
Ultrasonic Lithotripsy (USL)
An ultrasonic lithotripter produces an oscillation down a rigid metal probe, so that

the probe tip, when placed in contact with a calculus, ‘drills’ pieces off the stone
mass. USL generate ultrasound energy by applying electrical current to a peizoc-
eramic crystals which then vibrates at 23–27 KHz. The acoustic wave is ‘chan-
nelled’ from the handpiece down the probe causing the tip to vibrate resulting in
stone fragmentation when the tip is in contact with the stone. The probes are hollow,
coming in a range of diameters from 2.5 F to 6.0 F. Continuous irrigation via the
probe keeps the probe cool, preventing the hand piece overheating, and with the
application of suction, stone fragments and matrix can be evacuated from the uri-
nary tract. (Fig. 56.1).
Hard stones may be resistant to USL and fragments of probe may sheer off. It is
important not to apply excessive pressure on the stone as this may lead to pushing it
through the urothelium. Narrow probes are increasingly being used in mini-PCNL
and may also be used in the ureter; however, they may become easily occluded by
fragments.
56 Contact Lithotripters 321
Fig. 56.1 Ultrasonic

lithotripsy creates multiple
small fragments which are
sucked up through the
hollow probe into the
working channel of the
endoscope. Forward
irrigation, however, may
result in fragment
dissemination
Ballistic Lithotripsy
Ballistic lithotripsy utilizes compressed air (0.35–0.5 MPa) to accelerate a projec-

tile, which hits the probe inside the hand piece. A shockwave is transmitted through
the probe to the calculus, causing mechanical fragmentation. The probe must be in
contact with the stone and ideally pushed against the wall to optimize fragmenta-
tion, prevent of retropulsion and loss of fragments.
The Swiss LithoClast® was the first available pneumatic lithotripsy device. It
can be used to treat ureteric stones through a semi-rigid ureteroscope with the
0.8 mm probe or in combination with an ultrasonic probe to treat renal stones per-
cutaneously. The Cook LMATM StoneBreakerTM is another ballistic lithotripter,
which has the benefit of being portable as it uses self-contained CO2 pressure car-
tridges to deliver the bursts of compressed air. Each cartridge can deliver
80–100 shocks.
Two-Probe Dual-Modality Lithotripsy
Dual-modalilty lithotripsy combines an ultrasonic device with a ballistic probe. The

Swiss Lithoclast® Master utilizes a ballistic probe that is inserted through the hol-
low ultrasonic probe, allowing them to be used in combination or individually. The
CyberWandTM is a coaxial probe; the inner, ultrasonic probe vibrates at 21 KHz
whilst the outer ballistic probe vibrates at 1 KHz.
Single-Probe Dual-Modality Lithotripsy
Advancements in lithotripsy technology has led to next-generation devices that

have both ultrasonic and ballistic lithotripsy in a single probe. The single probe
allows for larger fragment removal resulting in faster stone clearance.
Swiss LithoClast® Trilogy (Boston Scientific) is the next generation LithoClast
(Fig. 56.2a). The single probe design uses ultrasonic alongside an electromagnetic
energy to produce the ballistic energy at an adjustable rate up to 12 Hz.
Fig. 56.2 (a) Swiss Lithoclast® Trilogy generator with handpiece and suction. (Image provided
courtesy of Boston Scientific). (b) ShockPulse-SE lithotripter generator. (Image provided courtesy
of Olympus)
56 Contact Lithotripters 323
ShockPulse-SE (Olympus, Fig. 56.2b) has a unique ultrasonic generator produc-

ing constant ultrasonic wave energy alongside an intermittent ballistic shockwave
energy at a rate of 300 Hz. Unlike other lithotripters the device can be controlled via
the handpiece with high and standard power modes and a variable suction control.
Both lithotripter devices have an expanded range of probes allowing versatility
for PCNL, mini-PCNL, semi-rigid ureteroscopy and bladder stone frgmentation.
Lasertripsy
The most commonly used laser is the holmium-yttrium-aluminium-garnet

(Ho:YAG). It operates at a wavelength of 2,140 nm. Calculi are fragmented by pho-
tothermal vaporisation melting, or photochemical decomposition. There is a smaller
photomechanical effect due to the sudden increase in temperature causing an
expansile gas bubble, which causes cavitation when it collapses.
There are low-power (LP < 35 W) and high-power (HP up to 120 W) generators.
The main difference being the ability of the HP lasers to reach significantly higher
frequencies (80 Hz).
A range of fibre sizes are available (200, 365, 550 μm) allowing use in rigid and
flexible instruments.
Overall complication rates are low; the thermal effects of the laser are restricted
to 0.5–1.0 mm from the fibre tip and the risk of urothelial injury is, thereby,
minimised
Modern laser systems allow manipulation of 3 parameters: Energy, Frequency,
and pulse duration. High energy (1.5–2 J) low frequency (5 Hz) and short pulse
duration settings are used when the strategy is stone fragmentation, whilst low
energy (0.2–0.5 J) high frequency (15–20+ Hz) and long pulse duration is used for
stone dusting.
The dusting technique requires a continuous movement of the laser fibre tip over
the surface of the stone, as if painting it, without direct contact. Fragmentation tech-
nique requires direct contact with the stone focusing the fibre tip on one point.
‘Popcorning’ is a combination of dusting and fragmentation, ideally used for stone
fragments 3–4 mm in a non-dilated calyx. Settings are a long pulse duration, high
energy (1–1.5 J) and high frequency (10–15 Hz). Long pulse duration also reduces
stone retropulsion.
New Thulium fibre lasers have also been developed. Potential benefits over
Ho-YAG lasers include, higher absorption coefficient in water improving their
safety profile, smaller laser fibres (50–150 μm) making them more favourable for
flexible ureteroscopy, lower energy pulse (0.05 J) and a higher pulse frequency
(2000 Hz) resulting in improved stone ablation rates.
Further Reading
Marks AJ, Qiu J, Milner TE, Chan KF, et al. Laser lithotripsy physics. In: Rao PN, Preminger GM,
Kavanagh JP, editors. Urinary tract stone disease. Springer; 2011.
Scotland KB, Kroczak T, Pace KT, et al. Stone technology: intracorporeal lithotripters. World J
Urol. 2017;35(9):1347–51.
Ventimiglia E, Pauchard F, Quadrini F, et al. High-and low-power laser lithotripsy achieves simi-
lar results: a systematic review and meta-analysis of available clinical series. J Endourol.
2021;35(8):1146–52.
Chapter 57
Monopolar Diathermy
Luke Forster
Monopolar diathermy is the application of electrical current to human tissues, via an

active electrode—the circuit is completed by the application of a dispersive elec-
trode elsewhere on the patient’s body. This high frequency electrical current results
in heating of the intervening tissue by synchronous oscillation of intracellular ions,
resulting in tissue effects such as desiccation and vaporisation.
Basics of Electricity
Electrons orbit the nuclei of atoms. Current occurs when electrons flow from one
atom to the orbit of an adjacent atom. The more electrons that are moving the higher
the current. Voltage is the force that moves electrons between atoms. If electrons
encounter resistance, heat can be produced. A complete circuit must be present for
electrons to flow. The power of an electric circuit is measured in watts and depends
on current, voltage, resistance and time.
Current: flow of electrons during a period of time, measured in amperes
Circuit: pathway for uninterrupted flow of electrons
Voltage: force pushing current through the resistance, measured in volts
Resistance/Impedance: obstacle to the flow of current, measured in ohms
Ohms law: Current = voltage/resistance
L. Forster (*)
Frimley NHS Foundation Trust, Frimley Park Hospital, Frimley, UK
e-mail: luke.forster@doctors.org.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_57
326 L. Forster
How Monopolar Works
Monopolar works by producing heat at an active electrode as the electric circuit is

completed. Standard electric current is 60 Hz but an electrosurgical generator takes
this 60 cycle current and increases the frequency to over 200 cycles per second. The
energy is supplied by a high frequency AC generator of 100 KHz to 4 MHz. Lesser
frequencies would cause excessive stimulation to underlying muscles and nerves.
The active electrode has a small surface area for contact with target tissues. This
increased impedance means the heat is focussed. The dispersive electrode is to safely
remove current from the patient. It is a metal plate with large surface area that is placed
on a flat part of the patient e.g. thigh, buttock or back. The plate must be placed away
from any metal implants to avoid the current passing into this and causing heat damage.
Isolated generator technology means the circuit is completed by the generator
rather than the ground. The patient return electrode is the preferred pathway back to
the generator. By removing ground, the isolated generator reduces hazards like cur-
rent division and alternate size burns. Interrogation circuits monitor the quality of
the contact area between the pad and the patient. This protects patients from burns
caused by inadequate contact. The system will deactivate before an injury occurs.
Waveforms
As the waveforms change, so do the corresponding tissue effects. High levels of

heat generated rapidly will cut tissues, whereas low levels of heat generated slowly
will coagulate tissues causing haemostasis.
Electrosurgical generators can produce different waveforms. These have differ-
ent effects on surgical tissue. CUT, COAG and BLEND cause cutting, fulguration
(tissue destruction) and desiccation respectively (Table 57.1).
Dessication: precise coagulation using lower voltages, electrode needs to be in
touch with target tissue
Fulguration: very high voltage with lower current to direct diathermy a few milli-
metres from targeted tissue
Table 57.1 Differences between CUT and COAG

Cut Coagulation
Continuous electric current Duty cycle reduced (ratio of ‘on’ time): Waveform only
waveform on 6% of the time
High current, low voltage Low current, high voltage
Produces heat rapidly Produces less heat, more slowly
Vaporises tissue on contact Coagulum produced
Cells heat up rapidly to point of Cells dry out instead of rupturing
boiling and then rupture
Pure or blend Can be used directly through active electrode or through
conducting device such as forceps
57 Monopolar Diathermy 327
Low Voltage High Voltage
PURE CUT BLEND 1 BLEND 2 BLEND 3 COAG

100% on 50% on 40% on 25% on 6% on
50% off 60% off 75% off 94% off
Typical Example
Fig. 57.1 The relationship between voltage, waveform and tissue effect of pure cut, blend and
coag monopolar diathermy settings
BLEND involves modification of the duty cycle, the ratio of time a circuit is
active or on. As a surgeon progresses from Blend 1 to 3 the duty cycle is progres-
sively reduced, so less heat is produced. Blend 1 is able to vaporise tissues with
minimal haemostasis whereas Blend 3 is less effective at cutting but has greater
haemostatic properties (Fig. 57.1).
Precautions/Safety
• The electrosurgical unit should be inspected along with cables and electrodes
prior to surgery
• Pacemaker/ICD/neurostimulators—devices should be checked or deactivated as
applicable with diathermy plates applied as far away as possible
• Monopolar shouldn’t be used on end-arterial organs e.g. penis, fingers etc. as
main artery thrombosis can result in amputation and necrosis
• Caution should be used if prepping the skin with alcohol-based solutions as this
theoretically could ignite
• The activation sound indicator should be audible during surgery
• The electrosurgical unit should be operated at the lowest effective power setting
to achieve the required effect
• All the metal parts of an instrument should be in view
• The diathermy should only be activated when in direct contact with the tissue
• When not in use the active electrode should be placed in a clean, well-
insulated quiver
• Where possible a smoke evacuation system should be used
328 L. Forster
Further Reading
Monga M, De S, Knudsen BE. Basic energy modalities in urologic surgery. In: Campbell-Walsh
urology. 11th Ed. Elsevier Health Sciences; 2015.
Elkabir J, Anson KM. Energy sources in urology. In: The scientific basis of urology. CRC
Press; 2004.
Chapter 58
Bipolar Diathermy
Luke Forster
Bipolar diathermy is the application of electrical current to human tissues, via two
active electrodes (commonly insulated forceps). This high frequency electrical cur-
rent results in heating of the intervening tissue by synchronous oscillation of intra-
cellular ions.
Background
Electric current flows when electrons pass from one atom to another, with flow
measured in amperes. The greater the current, the larger the number of electrons
that are moving. To allow flow, a circuit must be formed between a positive and
negative electrode with voltage being the force needed to move electrons through
the circuit. If these electrons meet resistance then heat is generated.
Bipolar Electrosurgery
In bipolar electrosurgery the flow and voltage are derived from a generator and the
path of the current only passes through the tissues being treated. Coagulation occurs
when using forceps in which the two halves of the instrument are insulated from
each other so one half is the source of the current and the other half the receiver. No
patient return electrode is required as a result. Bipolar generally uses frequency
between 250 kHz and 1 MHz.
L. Forster (*)
Frimley NHS Foundation Trust, Frimley Park Hospital, Frimley, UK
e-mail: luke.forster@doctors.org.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_58
330 L. Forster
The main advantage of bipolar is that current does not pass through parts of the
body which are not being treated. The precision is useful in laparoscopic surgery
and in operations on the penis. Bipolar is safer in patients with cardiac pacemakers
which could be affected by monopolar current.
Selected Uses in Urology
• Bipolar TURP
This applies bipolar electrosurgical current across a specialised TUR loop, with the
active and return electrodes separated by a ceramic insulator. This technique uses
saline rather than glycine irrigation solution avoiding dilutional hyponatraemia,
TUR syndrome, a potentially life-threatening complication. A European Urology
systematic review reported evidence from 15 good quality RCTs, stating that bipo-
lar resection improves patient outcomes, reduces complications and has potential
cost-savings. A NICE technology guidance review in 2021 reviewed the literature
published and highlighted findings of reduced bleeding, transfusion, length of stay
and readmissions. There was a cost-saving identified when using bipolar rather than
monopolar technology.
• Vessel sealing technology
These specialised instruments seal vessels and tissue bundles for surgical ligation in
laparoscopic and open surgery. The generator measures initial resistance of tissues
before delivering the appropriate energy in a pulsed fashion. They use bipolar
energy in combination with pressure to compress, coagulate and seal vessels up to
7 mm, reducing the need for sutures and clips. The energy cycle stops once the tis-
sue effect is complete. The tissues can be cut once sealed. Thermal spread to sur-
rounding tissues is reduced through using lower energy. There is also less smoke
produced. This technology can contribute to lower levels of blood loss and transfu-
sions, while potentially reducing operative time and length of stay.
• Robotic surgery
There are a range of bipolar instruments used in robotic surgery for tissue dissec-
tion, grasping, haemostasis and transection. These are part of the armamentarium a
robotic surgeon has to optimise patient outcomes while minimising blood loss,
complications and hospital stay. The use of robotic surgery has increased dramati-
cally over the last 10 years with expert opinion championing its benefits. The iROC
trial has recently corroborated these views with findings of shorter hospital stays
and improved recovery in patients undergoing robotic rather that open cystectomy.
58 Bipolar Diathermy 331
Further Reading
Treharne et al., 2018. Economic value of the transurethral resection in saline system for treatment
of benign prostatic hyperplasia in England and Wales: Systematic review, meta-analysis and
cost-consequence model. European Urology Focus.
Shubha De et al. Basic Energy modalities in Urology, Campbell-Walsh Urology 11th Edition
Volume 1.
Symes and Ansen. Energy Sources in Urology, The Scientific Basis of Urology, third edition.
The Plasma system for transurethral resection and haemostasis of the prostate. NICE Medical
technologies guidance, 2021. Accessed online at nice.org.uk May 2022.
Chapter 59
Alternatives to Electrosurgery
Bachar Zelhof
The principles and applications in achieving hemostasis have remained the same
since the introduction of surgical electrocautery in the early twentieth century.
Newer haemostatic technologies have evolved in the era of laparoscopic surgery
to try and improve patient safety by reducing the risks of inadvertent cautery of
local or remote structures, or of explosion. These newer technologies utilise bipo-
lar diathermy and ultrasound technology to achieve their effects.
Background
Whether an individual surgeon chooses to use modern electrosurgical equipment or

alternative energy sources for haemostasis, the choice is ultimately determined by
the type of equipment that the operator feels most comfortable using and the type of
tissue that is being operated upon. Whichever energy form is used, the surgeon must,
however, have a detailed knowledge of the physical concepts required to effect hae-
mostasis and be able to understand the complications that may be created by the
energy, how to avoid them, and how to deal with them if they occur. There are subtle
differences between the different alternative energy sources in how they react with
human tissues, but the clinical outcome often appears to be much the same, depend-
ing more on the skill of the individual surgeon than on the power source employed.
The current alternatives to electrosurgery are:
• The Harmonic scalpel
• The LigaSure™ system
B. Zelhof (*)
Department of Urology, Manchester University NHS Foundation Trust, Manchester Royal
Infirmary, Manchester, UK

Switzerland AG 2023
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334 B. Zelhof
The Harmonic Scalpel
The Harmonic scalpel uses ultrasound energy which is converted to mechanical

energy at the active blades. The Ethicon Harmonic scalpel cuts tissues whilst simul-
taneously sealing the edges of the cut. The system typically comprises of a handheld
ultrasonic transducer, an ultrasonic generator, hand switch, foot pedal, and scalpel
that serves as the cutting instrument. The main mechanism is the active blade which
delivers high frequency frictional force while the inactive upper arm holds tissue in
apposition.
Ultrasonic energy controls bleeding by coaptive coagulation at lower tempera-
tures, typically from 50 °C to 100 °C. Coaption, compression of the vessel walls
together, is followed by sealing with coagulation of a protein coagulum. Coagulation
occurs by denaturing protein when the instrument blade, vibrating at 55,500 Hz,
causes protein in the vessel wall to form a coagulum that then seals the coapted ves-
sels. If the ultrasonic energy application is prolonged, secondary heat is produced
that, in addition, helps to seal larger vessels.
The advanced haemostasis option in Harmonic +7 is more reliable in sealing ves-
sels up to 7 mm diameter (Fig. 59.1).
Fig. 59.1 Advanced harmonic

59 Alternatives to Electrosurgery 335
Comparison with Electrosurgery
Unlike electrosurgery, ultrasonic energy is mechanical in nature and works at much

lower temperatures. Electrosurgery and lasers coagulate by burning at high tem-
peratures causing obliterative coagulation at between 150 °C and 400 °C. Blood and
tissue are thereby desiccated and oxidised, forming a charred eschar that covers and
seals the bleeding area. Rebleeding can occur when the forceps used during electro-
surgery are removed, when they may stick to the cauterised tissue and disrupt
the eschar.
The advantages of the harmonic scalpel are that there is less potential collateral
damage to adjacent structures and the coaptive process minimises smoke and avoids
carbonisation of the tissues (Fig. 59.2). Extensive use during laparoscopic surgery
can, however, result in significant heating of the tip of the blade (up to 100°) and
care must be taken to minimise the risk of thermal injury to adjacent organs, bowel
in particular.
Fig. 59.2 A comparison of Controls lateral spread of

the extent of lateral thermal injury
thermal spread for 7
electrosurgery and 6
ultrasonic energy used in
– Electrosurgery
the harmonic scalpel (3) 5
4
Spread
(mm)
1
– Harmonic scalpel
0
0 1 2 3 4 5 6 7 8 9 10
Time (sec)
336 B. Zelhof
The LigaSure™ System
The Valleylab LigaSure™ system uses a unique combination of pressure and energy
to create vessel fusion. This process uses radiofrequency energy to melt the collagen
and elastin in the vessel walls and reforms it into a permanent, plastic-like, seal. It
does not rely on a proximal thrombus as classic bipolar electrocautery does. A
feedback-controlled response system automatically discontinues energy delivery
when the seal cycle is complete, which minimises the thermal spread to approxi-
mately 2 mm for most LigaSure™ instruments. By utilising a unique energy output,
the result is virtually free of sticking or charring, and the seals can withstand three
times normal systolic blood pressure. This system requires a designated generator
which is often combined, in one unit, with monopolar and bipolar electrosurgery
generators.
The technology is reputed to be able to seal vessels up to 7 mm in diameter and
can be delivered through a variety of instruments for use in both laparoscopic and
open procedures. Many surgeons would, however, recommend clipping vessels of
this size rather than relying on the fusion created by this technology.
Further Reading
Morris AR, Siow A. Basic electrosurgical knowledge among practicing gynecologists: a multina-
tional survey. J Am Assoc Gynecol Laparosc. 2004;11(Suppl 3):S8–21.
Dilip Kumar Dutta. Indranil Dutta. Instrument review. The harmonic scalpel. J Obstet Gynaecol
India. 2016;66(3):209–10. PMID: 27298535
Brill AI. Mapping the thermal gradient of a new radiofrequency bipolar vessel sealing device,
EnSeal, using real-time thermography. J Am Assoc Gynecol Laparosc. 2004;11(Suppl
3):S7–19.
Chapter 60
Operative Tissue Destruction
Matthew Liew
Tissue may be destroyed intra-operatively in a variety of different ways, using some

form of thermal or mechanical energy. For larger specimens the use of morcellation
allows for rapid destruction and subsequent removal through a narrow access route.
Introduction
In current urological practice, operative tissue destruction methods are used following
anatomical endoscopic enucleation of the prostate (AEEP), where different energy
sources can be used to achieve prostate removal including: holmium laser (HoLEP),
Thulium fibre (ThuFLEP), and Bipolar (BipolEP) enucleation of the prostate.
Mechanical Morcellation
HoLEP was the first reported AEEP procedure in 1996. The second part of the
HoLEP operation requires morcellation which can be a rate limiting step for very
large prostates. Mechanical morcellation of prostatic tissue is typically performed
using the device inserted into the bladder though a modified nephroscope. Olympus,
Karl Storz and Richard Wolf have morcellator scopes which are compatible with the
laser resectoscopes to allow a rapid change with the outer sheath remaining in the
patient. The morcellator device is pedal controlled, one for suction to bring the tis-
sue over the blades, and the other is for suction and morcellation. A specimen trap
allows histological examination of the tissue fragments.
M. Liew (*)
Wrightington, Wigan and Leigh NHS Foundation Trust, Wigan, UK

Switzerland AG 2023
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338 M. Liew
Devices for Mechanical Morcellation
Piranha™ (Richard Wolf) (Fig 60.1) and VersaCut™ (Lumenis) (Fig 60.2) devices
are the most widely used morcellators for the removal of prostatic tissue following
laser enucleation.
The VersaCut™ device uses a reusable handpiece and is connected to a com-
bined control box and roller suction pump. A motor in the hand-piece is controlled
by a graduated foot pedal which initiates suction to engage the enucleated prostatic
tissue first towards a slot at the tip of the instrument. The motor then moves a reus-
able hollow slotted reciprocating blade which extends from the tip of the blade with
a guillotine action to morcellate. The pressure sensitive pedals can be used to vary
the speed of the blades and suction. The engaged prostate is ‘chopped’ by the move-
ment of the blade within the sheath by an action not dissimilar to the movement of
the Thompson cold punch.
The Piranha™ device has a side to side oscillating serrated blade with a curved
unexposed tip to reduce inadvertent bladder injury. It is connected to a motor hand
piece, generator, suction pump, disposable tubing /tissue trap, suction canister (3 or
5 L) and a dual foot pedal (for suction and morcellation). The oscillator settings
(default 1500 rpm) can be programmed. It is available both with reusable and dis-
posable blades.
Tissue removal rates are between 4 and 10 g/min which is reduced when the tis-
sue is fibrous and nodular. The latter can cause a so called ‘beach ball effect’
Fig. 60.1 Blade of Piranha Morcellator

60 Operative Tissue Destruction 339
Fig. 60.2 Blade of Versacut morcellator
whereby the tissue jumps without engaging the morcellator. In these instances, the
smooth edges can be ‘roughened’ up with the laser to allow the morcellator blades
to engage. Smaller fragments can be grasped out through the morcellator scope with
forceps or a laparoscopic bag.
Safety Aspects in Mechanical Morcellation
There is clearly a learning curve aspect to morcellation as with particular AEEP

techniques. Urologists want morcellation to be safe and efficient.
The most feared risk during prostate morcellation is bladder perforation which
can occur when the bladder mucosa is sucked into the morcellating slot and the
device activated. This has been reported in 5.2% with the VersaCut™ vs. 1.2% with
the Piranha™ system.
Proponents of AEEP have developed rules for safe morcellation which continue
to reduce the significant bladder perforation risks. These include:
• Ensuring excellent haemostasis before morcellation
• Ensuring full bladder distension at all times using double inflow irrigation, where
outflow is only through the morcellator handpiece, including regularly checking
if the bladder is adequately distended by abdominal palpation
340 M. Liew
• Use only suction to draw tissue of interest to the morcellator blades

• Only morcellate if tissue is clearly visualised over the morcellator blades
• Avoid chasing fragments when in morcellation mode
If the bladder mucosa is sucked into the morcellator blades, the suction pressure
should be released on the generator to allow the tissue to disengage fully.
Further Reading
Morcellation after endoscopic enucleation of the prostate: efficiency and safety of currently
available devices. Franz J et al. Eur Urol Focus 2021; Apr 12; S2405–4569(21). https://doi.
org/10.1016/j.euf.2021.03.021.
Rivera M, Lingeman J, Heinsimer K, York N, Krambeck A. A Survey of Morcellator Preference
and Cost Comparison of the Lumenis VersaCut and Wolf Piranha Morcellators. Urology.
2018;111:54–8.
Chapter 61
Endoscopic Use of Laser Energy
Tev Aho and Omar Al Kadhi
Since 1960 when Theodore Maiman activated the first laser using a synthetic ruby
crystal, Light Amplification by the Stimulated Emission of Radiation (LASER) has
found many, varied applications. Various laser wavelengths have proven safe, pre-
cise and effective for use in endourology.
Laser Physics and Tissue Interaction
Lasers are generally described by their lasing media e.g. holmium-doped yttrium
aluminium garnet (Ho:Y3Al5O12, Ho:YAG), and thulium-doped fibre (thulium fibre
laser) which defines the wavelength and physical characteristics of the laser.
3 steps are required to generate a laser beam from a solid state laser e.g.
Holmium:YAG and Thulium:YAG:
• Energy is infused into the lasing medium, i.e. ion doped YAG crystal, and
absorbed by many of its atoms pushing them into an excited state. These then
emit energy as photons.
• The photons collide with other excited atoms of the lasing medium causing addi-
tional photon emission.
• The emitted photons are amplified by bouncing them between 2 mirrors at either
end of the laser cavity causing energy build up. This energy exits through an
aperture in the front mirror as a very intense, laser, beam
T. Aho (*)
Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
e-mail: tevita.aho@addenbrookes.nhs.uk
O. Al Kadhi
Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK
e-mail: omar.alkadhi@nnuh.nhs.uk

Switzerland AG 2023
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342 T. Aho and O. Al Kadhi
Solid state lasers are often bulky, noisy and require 32 or 64 amp sockets.
The Thulium Fibre Laser (TFL) is a novel fibre laser which is smaller and quieter
than its solid state counterparts and uses a standard electrical socket. A thulium-
doped fibre is used as the medium rather than an ion-doped YAG crystal. Diode
lasers deliver energy through the doped fibre generating photons which exit via an
outgoing fibre. Smaller fibres than are possible with other lasers can be used with
TFL (50–150 microns).
The unique characteristics of laser light are that it is monochromatic, collimated
and coherent. Monochromatic light, of a single colour, is defined by its wavelength.
It can specifically target tissues (the chromophore) that absorb that light wavelength.
Collimated light, travelling in a parallel beam, can be guided through optical fibres
and focussed on a small spot.
Tissue is affected by laser energy by absorbing light and converting it to thermal
energy. When temperatures reach 60–100 C° tissue coagulation occurs with subse-
quent delayed tissue necrosis and debulking. Temperatures exceeding this will lead
to vaporisation with immediate tissue debulking. Laser energy may break stones by
a photo-thermal mechanism, with direct absorption of laser energy causing vapori-
sation of the stone, or by a photo-acoustic effect where a pulsed laser causes forma-
tion of a plasma bubble which expands and collapses generating a shock wave.
Determinants of the Laser: Tissue Interaction
These can be due to characteristics of the laser or the tissue being treated (Table 61.1).
Table 61.1 Factors influencing tissue effect due to the application of laser energy
Laser factors Tissue factors
Wavelength Tissue density
Power: Energy (joules) × rate Water content: If the chromophore is water then
(hertz) = power (Watts) water rich tissues (e.g. prostate, bladder tumours)
Mode of emission: Pulsed vs continuous will be specifically targeted by that wavelength.
Distance from target: Contact or near
contact = incision; close = vaporization;
more distant = coagulation
Pulse width: Short, medium, long
Pulse modulation: e.g. Moses 2.0, virtual
basket
61 Endoscopic Use of Laser Energy 343
Laser Safety
It is mandatory that laser operators receive laser safety training and certification.
Theatre personnel must wear adequate protective eyewear specific to the laser
wavelength, windows should be covered, and a designated member of staff should
operate the laser machine. Laser fibres should be checked for faults prior to activat-
ing the laser machine and this should be switched to standby when not in active use.
Clinical Applications of Lasers in Urology (Table 61.2)
344
Table 61.2 Characteristics of the lasers used, and their applications, in urology
Depth of
tissue
Wavelength penetration
Type of laser (nm) Chromophore (mm) Mode Urological application Fibre type
Nd: YAG 1064 Water and 10 Pulsed or Prostate coagulation Side firing (SF)
haemoglobin continuous TCC ablation End firing (EF)
Holmium:YAG Prostate:
50 W Ablation (HoLAP)
Resection (HoLRP)
Enucleation (HoLEP)
Bladder stones
Ureteric stones
Strictures
Urothelial ca: Ablation/resection
Holmium:YAG 2120 Water 0.4 Pulsed Prostate: SF
100 W Ablation (HoLAP) 550um EF
Resection (HoLRP) 550um EF
Enucleation (HoLEP) 550um EF
Bladder stones 365 or 200 um EF
Ureteric stones 365 um EF
Strictures 365 um EF
T. Aho and O. Al Kadhi
Holmium:YAG Pulsed Prostate:
with pulse Ablation (HoLAP)
modulation Resection (HoLRP)
Enucleation (HoLEP)
Bladder stones
Ureteric stones
Strictures
Greenlight 532 Haemoglobin 0.8 Quasi- Prostate: SF
KTP 80 W continuous Vaporisation (PVP)
HPS LBO 120 W Vapoenucleation
XPS LBO 180 W Anatomical endoscopic enucleation of
61 Endoscopic Use of Laser Energy
the prostate (Greenlep)

Thulium:YAG 2010 Water 0.25 Continuous Prostate: SF
or pulsed Vaporisation EF
Resection (ThuVaRP) EF
Enucleation (ThuLEP) EF
Strictures EF
TCC ablation
Thulium fibre 1940 Water 0.1 Pulsed or Stones EF
continuous Prostate EF
Urothelial carcinoma
Diode 940, 980, 1470 Water and Various Pulsed Prostate: SF
haemoglobin Vaporisation
345
Benign Prostatic Hyperplasia (BPH)
Initial interest in the use of lasers for BPH led to the Nd:YAG procedures such as
Visual Laser Ablation of the Prostate (VLAP) and Contact Laser Ablation of the
Prostate (CLAP). However, low tissue absorption and deep tissue penetration, caus-
ing coagulative necrosis and delayed sloughing of tissue, resulted in high rates of
post-operative retention and dysuria.
The term “laser prostatectomy” is too general to be meaningful and 4 laser tech-
niques are currently used for BPH:
• Vaporisation: The simplest and least efficient method of tissue debulking.
Requires single use side-firing fibres. Tissue morcellation is not required. There
are concerns over durability, particularly in men with prostates >80 cc. No tissue
is available for histology. Particularly well suited to anti-coagulated patients and
for day surgery. Recommended for men with prostates up to 80 cc.(EAU). Most
commonly done using the green light laser but can be done with any laser cur-
rently used for BPH surgery.
• Resection: The laser equivalent of TURP where small chips of prostate are
resected using an end-firing fibre, avoiding the need for a tissue morcellator. Can
be done using any of the lasers currently used for BPH surgery. More efficient
tissue removal than vaporisation and tissue is available for histology. Less effi-
cient than enucleation. Recommended for prostate volumes up to 80 cc.(EAU)
• Anatomical Enucleation: The entire transitional zone of the prostate (BPH ade-
noma) is enucleated using the anatomical plane between the adenoma and the
peripheral zone. Can be done using any of the lasers currently used for BPH
surgery. Anatomical Endoscopic Enucleation of the Prostate (AEEP) is a more
generic term for endoscopic enucleation procedures performed with any energy
source. AEEP is the endoscopic equivalent of Millins prostatectomy with equiva-
lent improvements in urinary symptoms, flow rate and post void residual volume,
and equivalent long term durability. There is no upper prostate size limit in the
hands of experienced surgeons. Tissue is available for histology. Enucleation is
the most effective endoscopic procedure for urinary retention with catheter-free
rates of >98% for both acute and chronic urinary retention.
• Vapo-enucleation: A hybrid technique combining aspects of both enucleation
and vaporisation. The adenoma is enucleated in stages using a side firing fibre,
which is then used to vaporise the enucleated tissue rather than removing it by
morcellation. Similar end result to AEEP but less efficient and therefore limited
to prostates less than around 100 cc. Most commonly done using the green-
light laser.
All laser techniques are possible as daycases, and have been shown to have less
bleeding complications, no TUR syndrome, and shorter catheter times and hospital
stays compared to TURP. All can be done in anticoagulated and medically unfit
patients.
61 Endoscopic Use of Laser Energy 347
Pulse modulated holmium lasers such as “Moses 2.0”, “virtual basket”, “vapor
tunnel” and “bubble blast” optimise the laser-tissue interaction by altering the shape
and characteristics of the vapour bubble generated by the holmium laser with the
aim of improving its enucleating and haemostatic ability which shortens operat-
ing times.
Upper and Lower Tract Stones
Holmium laser lithotripsy has been the treatment of choice for ureteric calculi and
small renal pelvic, or peripheral calyceal, stones of all types, and is increasingly
being used for larger renal calculi via the ureteroscopic route. Holmium laser litho-
tripsy is said to have up to 95% success rates even with harder types of stone with
low risks of urothelial injury due to its high absorption coefficient in water, but can
be slow when a large stone volume requires disintegration.
Pulse modulated holmium reduces stone retropulsion and improves the effi-
ciency of stone dusting and fragmentation.
The recent introduction of the TFL has some potential theoretical advantages in
terms of retropulsion and and efficiency of stone dusting and fragmentation com-
pared to standard Holmium: YAG but is yet to be shown to have any clinically sig-
nificant advantages over pulse modulated Holmium; YAG.
Urothelial Carcinoma (UC)
Laser ablation for bladder UC is restricted to superficial, small (<2.5 cm) lesions
when tissue histology is not required. The advantages are less bleeding and the abil-
ity to use Nd:Yag, holmium and thulium lasers delivered by a flexible cystoscope,
thereby avoiding general anaesthesia. All the commonly used lasers in urology have
been used for en bloc resection of bladder tumours. Ureteroscopic or nephroscopi-
cally delivered lasers allow treatment of upper tract UC in patients unfit for radical
treatment with less bleeding and lower stricture rates in comparison to
electrocautery.
Urethral Stricture Disease
Nd:YAG, KTP, holmium, thulium and diode lasers have all been used for laser ure-
throtomy. Data suggest equivalent results with all modalities but there is a lack of
data comparing laser to optical urethrotomy or urethral dilatation.
Further Reading
Khusid J, Khargi R, Seiden B, Sadiq A, Atallah W, Gupta M. Thulium fibre laser utilisation in urol-
ogy. Investig Clin Urol. 2021;62:136–47.
Traxer O, Keller E. Thulium fiber laser: the new player for kidney stone treatment? A comparison
with holmium:YAG laser. World J Urol. 2020;38:1883–94.
Chapter 62
Double J Stents and Nephrostomy
Drainage of the upper urinary tract by insertion of an open nephrostomy has been
an option for more than a hundred years but the percutaneous approach, with which
we are so familiar, has only been a viable, widely-available, option for the last
50 years. Roughly over the same time period, internalised ‘double J stents’ have
become available for retrograde, antegrade and open drainage, or splinting of the
injured, or reconstructed, ureter and upper urinary tract.
ow Stents and Nephrostomies Drain the Upper

H
Urinary Tract
Insertion of a nephrostomy or double J stent into the dilated upper urinary tract will
disobstruct it. External drainage into a no pressure collecting device provides opti-
mal decompression. Insertion of a double J stent into a non-obstructed ureter will
cause a rise in intra-pelvic pressure, ureteric dilatation, vesico-ureteric reflux and
will result in an injury response that influences the efficiency of ureteric peristalsis.
Most urine drains around a double J stent, by preventing coaptive peristalsis, rather
than through the central lumen except at points of complete obstruction when urine
passes through the side holes into the lumen (Fig. 62.1).
T. Brophy (*) · S. Payne

e-mail: thomas.brophy@mft.nhs.uk

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Fig. 62.1 Urine drains by a b

peristalsis around the stent
and, until it becomes
occluded by encrustation,
through the central lumen
(a). The lumen becomes
important at points of
occlusion where urine is
forced in through side
holes until ureteric
peristalsis ‘sucks’ urine out
around the stent below the
occlusion (b)
Pathological Consequences of Stent Insertion
Implanted plastic tubes will cause the production of sialomucins dependent upon
their composition. That injury response will result in mucosal oedema and dilatation
of the ureter. All tubes implanted into the urinary tract will develop a biofilm, and
become encrusted with constituents of the urine. Implanted tubes encrust more rap-
idly in lithogenic urine and should, therefore, remain in-situ for the shortest time
possible in stone-formers. The encrustation process will start within days of implan-
tation and will start to occlude the stent lumen within a week. This may cause irrita-
tion to the patient, make stent removal difficult and stent exchange impossible using
the lumen. Biochemical and biomechanical forces will also have an effect on poly-
mer degradation with potential stent fracture. The rate of deterioration is principally
influenced by the composition of the stent and influences its longevity in-situ.
62 Double J Stents and Nephrostomy 351
Material Science
The construction of nephrostomies and double J stents is identical with a number of

different materials being used, most of which are polymers and many of which are
used as proprietary combinations. The presence of silicone influences the rigidity of
the material, and hence its ease in insertion, comfort to the patient and its longevity
in-situ (Table 62.1).
All polymer stents and nephrostomies require insertion over a guidewire under
radiological control. They usually consist of a radio-opaque 5—8F tapered-tip tube
which has a section with a plastic ‘memory’ that forms a coil once it has deployed
from the guidewire. The coil end of a nephrostomy, and the whole length of a dou-
ble J stent, have small holes in them to facilitate drainage (Fig. 62.2a). These holes
Table 62.1 Common materials used for plastic stents and nephrostomies and their longevity in
situ as double J stents
Composite Base polymers Stent longevity in-vivo
Bardex®, Polyurethane 6 months
Universa® firm Thermally sensitive polyurethane 12 months
C-flex®, (styrene) thermoplastic elastomer 6 months
Sof-flex® Soft polyurethane 6 months
Percuflex® Polyethylene Up to 12 months
Flouro-4™ Silicone Up to 12 months
Inlay optima® Proprietary mix Up to 12 months
Universa® soft Soft polyurethane 6 months
a b
Fig. 62.2 A nephrostomy with preformed pigtail and holes in the coil just in the renal pelvis (a)
together with its Luer connector for an external drainage device. (Image courtesy of Cook Medical)
A multi-length double J stent (b). (Image courtesy of Cook Medical)
may also be used to pass a guidewire through for open stent placement. Percutaneous
nephrostomies often have a fine thread between the tip of the stent and the first side-
hole on the shaft of the tube to ‘lock’ the coil and avoid displacement. Malecot
nephrostomy has a unique wing shaped tip that secures the nephrostomy in position
and allows drainage (Fig. 62.2b). The cutaneous end of the nephrostomy has a Luer
connector for an external collection device.
Double J stents may be between 5—8F diameter and 18—30 cm long with a
preformed coil at each end. Some stents have a ‘multi-length’ coil on either end
which means that the stent uncoils in capacious areas such as the renal pelvis or
bladder (Fig. 62.2b). Multi-length stents have the advantage that fewer lengths of
stent need to be kept in stock.
Choosing the correct stent size is important as longer stents are associated with
increasing LUTS. Worsening stent symptoms have been observed when the distal
end of the stent crosses the midline.
There are a number of pharmacological options for managing stent-related
symptoms. Analgesics are helpful in managing pain but do not improve
LUTS. Alpha-blockers, anticholinergics, and PDE-5 inhibitors have been used on
their own or in combination and been observed to reduce morbidity.
Stents may be coated with hydrophilic Teflon or anti-bacterial/antibiotic coatings
to make insertion easier, or to try and reduce bacterial adherence and encrustation.
Specialised Stents
Specialised stents may be used when standard stents are unable to drain the urinary
tract sufficiently. There are several approaches to managing complex ureteric
obstruction. Tandem JJ stents, inserted in the same technique provide improved
patency rates compared to single JJ stenting.
Metallic stents are increasingly being used in complex, malignancy-associated,
cases. The Resonance® stent (Fig. 62.3a) has an alloy spiral coil that is highly resis-
tant to compressive forces. Resonance® stent has no end holes and requires insertion
through an outer sheath. Memokath™-051 stents (Fig. 62.3b) are thermo-expand-
able and require temperature controlled sterile irrigation fluid for insertion, whilst
the Allium® URS and Uventa™ Ureteral stents are both self-expanding metal
stents. All have high tensile strength preventing compression and are designed to
prevent tumour ingrowth.
Specialised stents may be used to ‘detour’ urine from the kidney via a subcutane-
ous tunnel to the bladder for an extra-anatomic means of draining the upper tract
when the ureter is either absent or unusable.
62 Double J Stents and Nephrostomy 353
a b
Fig. 62.3 Resonance® metallic stent has a coil at both ends keeping it in position (a). (Image
courtesy of Cook Medical) Memokath™-051 stents are positioned across a stricture to allow ret-
rograde flow (b). (Image courtesy of Pnn medical)
Further Reading
JWA R, Payne SR, Gosling PT, et al. The effects of double J stenting on unobstructed ureters. An
experimental and clinical study. Br J Urol. 1985;57:630–4.
Scotland KB, Kroczak T, Pace KT, et al. Stone technology: intracorporeal lithotripters. World J
Urol. 2017;35:1347–51.
Khoo CC, Abboudi H, Cartwright R, El-Husseiny T, Dasgupta R. Metallic ureteric stents in malig-
nant ureteric obstruction: a systematic review. Urology. 2018;118:12–20.
Chapter 63
Urinary Catheters, Design and Usage
Benjamin Starmer
Urinary catheters are tubes used to drain urine away from the bladder or instil fluid
(e.g. medicine, contrast) into the bladder. They are vital tools to urological practice.
Catheters vary in their size, tip shape and material. Knowledge of the different types
of catheters and their properties allows urologists to select the most appropriate
catheter depending on the clinical scenario.
Urinary catheters are perhaps the most frequently used piece of urological tech-
nology. After IV cannulas, they are the most frequently deployed device in an acute
hospital setting. Typically, a fifth of UK in-patients will have a urinary catheter in-
situ at any one time.
Catheters are inserted for 3 main reasons:
1. Drainage (Incontinence (90%), fluid management (7%), urinary retention (2%),
washout blood / clots (1%), bladder injury etc.)
2. Access (for chemo- and immunotherapy in bladder cancer, GAG layer replace-
ment in bladder pain syndrome etc.)
3. Diagnostic studies (e.g. culture, cystogram)
The properties of the ideal catheter include:
1. Good lumen to external diameter ratio—this is better in all-silicone catheters
(see Fig. 63.1.)
2. Low coefficient of friction—it should be slippery to reduce trauma to the ure-
thral epithelium
3. Soft & flexible, but not collapsible
4. Good bio-availability
B. Starmer (*)
e-mail: starmer@doctors.org.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_63
356 B. Starmer
There are various types of catheter and several ways to classify them:
• Size: Catheter diameters are sized by the ‘French’ catheter scale (or Charrière
gauge), which refers to the external circumference in mm. Range from 10Ch
(3.3 mm diameter) to 28Ch (9.3 mm diameter).
• Channels: 1, 2 or 3 channels, one being the balloon retaining mechanism
• Balloon size: 3 to 30mls
• Tip Design: Foley, coude, Tiemann, whistle tip
• Materials: latex, silicone or polyvinyl chloride (PVC)—see Fig. 63.2
• Position/ Use: Indwelling or intermittent/urethral or supra-pubic
Fig. 63.1 Demonstrates

the improved lumen to 4mm 4mm
external diameter ration in
all-silicone catheters,
compared to latex coated
catheters
3mm 3.5mm
Latex coated All silicone
Silicone
PTFF (Teflon) Hydrogel
Silastic
Silicone elastomer
Fig. 63.2 Different catheter materials

63 Urinary Catheters, Design and Usage 357
Latex Catheters
These are the most frequently used in the UK. A coating is required to reduce any
inflammatory response due to the presence of latex.
1. Polytetrafluoroethylene (PTFE)-coated catheters are frequently referred to as
‘medium term’ as they can be left in situ for 28 days. PTFE (also known by the
brand name ‘Teflon’) has a very low coefficient of friction and is very n on-reactive
because of the strength of the carbon-fluoride bonds. They are reasonably cheap.
2. Hydrogel-coated catheters can be left for 3 months and are commonly used in
the UK. Hydrogel refers to a network of polymer chains which are hydrophilic
and because their high water content possess a degree of flexibility. They can be
left in for 3 months.
3. Silicone elastomer (Silastic) coated differ from other polymers in that their back-
bones consist of Si-O-Si units (unlike other polymers that contain carbon back-
bones) and is hydrophobic. Silicone is a highly inert material that is used in
many medical implants. Silicone coated catheters can be left in for 3 months.
Physical Properties of Latex
Latex is a naturally occurring substance that is obtained from cutting the bark of a
Brazilian rubber tree. It is an inherently stretchable and resilient substance. Its con-
stituents comprise polyisoprene (35%), water (62%) and other proteins (3%). It is
these latter proteins that often cause allergy to latex. Similar proteins are found in
walnuts and bananas, explaining why patients are often allergic to multiple agents.
Silicone Catheters
Silicone catheters are well known for their intrinsic biocompatibility, low surface
tension and hydrophobicity though they are also mechanically weak compared to
other substances. These catheters can be used for 3 months and are essential in latex
allergic patients. Silastic™ (a portmanteau of silicone and plastic) is a commonly
used device. All silicone catheters tend to cause less irritation and are available in
various colours.
358 B. Starmer
Rigid Polyvinyl Chloride (PVC) Catheters
Pure PVC polymer is very rigid and plasticizers are added to add flexibility to these
otherwise inert devices. The complexity of these compounds can lead to production
of small amounts of the toxic substances, dioxin and polychlorinated biphenyls
(PCB’s), when disposed of by incineration. PVC catheters are usually rigid 3-way
devices used after endoscopic surgery and are ideal for clot evacuation and bladder
washout. They can be used for at most 5–7 days These catheters are typically 2–3
times the cost of the latex-coated and silicone catheters and should not be used in
latex-allergic patients because they have a latex balloon.
Intermittent Catheters
These may be made of non-silicone materials and are used for intermittent bladder
drainage by the patient or carer; they are designed for disposable use. They may be
coated with several substances including PVP (polyvinylpyrrolidone) and salt
which creates a self-lubricating aqueous layer.
Supra-Pubic Catheters
Many designs of supra-pubic catheter have been used over the years, these are now,
commonly short or long term Foley catheters inserted through a peel-away sheath
inserted into the distended bladder over a trocar. More recently, those products
employing a Seldinger technique have gained popularity because of presumed
improved safety. Supra-pubic catheters should, where possible, be inserted under
ultrasound guidance to minimise the risk of bowel injury.
Catheter Biology
Once a catheter is inserted, it accumulates a film of muco-proteins that are secreted

by the urothelium. Simultaneously, bacteria, originating from the perineum, ascend
the catheter and begin to colonise the urinary tract. These bacteria and the muco-
protein deposits begin to form a biofilm. A biofilm is comprised of an inorganic
scaffold that houses an ever-changing population of living and dying bacteria. For
this reason, a catheter specimen of urine (CSU) will always demonstrate growth,
however this is very often colonisation rather than infection.
63 Urinary Catheters, Design and Usage 359
Antibiotics will never eradicate the bacteria fauna in the biofilm but instead
clone-out antibiotic resistance. Antibiotic stewardship is therefore of paramount
importance when managing catheter-associated urinary tract infection (CAUTI) and
it is important to never treat a patient based on the CSU alone.
The long-term presence of a catheter can induce squamous metaplasia, smaller
bladder capacity and loss of compliance.
Problems with Catheters
Catheter Associated Urinary Tract Infection
The most significant downside to catheterisation is the risk of urosepsis and

CAUTI. Estimates from the US have suggested that there are 7500 deaths in in-
patients every year from CAUTI. Pro-rata this would be almost 2000 in the
UK. Research and quality improvement work demonstrates that this can be substan-
tially reduced by good technique, appropriate management in situ and, particularly,
early removal.
Colonisation with bacteria occurs invariably within 24 hours of placing a cathe-
ter. The rate of bacteriuria can be slowed by impregnating the catheters with silver
oxide / alloys or antimicrobials though they do not stop CAUTI. Typically, these
agents are only used on short term catheters because of long-term increased inflam-
matory responses.
CAUTI can only be diagnosed by symptoms and/ or signs of sepsis in a clinically
unwell patient and a positive culture. CAUTI is difficult to define but the most prag-
matic would be ‘a breach between the colonised bladder and systemic circulation
and that the patient has become clinically unwell’.
Because of the biofilm and potential for seeding further infection, after treatment
of the acute sepsis, the catheter should be changed.
Encrustation/Repeated Blockage
This occurs due to a build-up of debris in the bladder which is comprised of denuded
bladder urothelium, biofilm, semen and bacteria. Some people advocate regular
bladder washouts. Acidic solutions (e.g. citric acid / Suby G) have also been trialled
to break down the encrustation however the evidence base for this is limited. The
patient should be instructed to increase their fluid intake and more frequent catheter
changes may be required.
360 B. Starmer
Bypassing
Catheter blockage and bladder calculi should be ruled out. A flexible cystoscopy is
almost always warranted. Reducing the volume in the retaining balloon should be
the first step. Failing this, anticholinergic medication, β3-adrenoceptor agonists or
even intravesical Botulinum toxin-A can be tried. Consider suprapubic catheter to
avoid trigonal irritation.
Other Problems
Visible haematuria occurs in 30% and is probably best investigated once; ignore
non-visible haematuria. Significant discomfort has been reported in 70% of patients
with catheters which is lower in supra-pubic catheters. Bladder stones, traumatic
hypospadias and urethral strictures are reported in a substantial minority of patients
with long-term urethral catheters, especially neuropaths.
Further Reading
Secret Life of Catheters: An educational programme. https://www.nationalcathetereducationpro-

gramme.org
Schumm K, Lam TB. Types of urethral catheters for management of short-term voiding problems
in hospitalised adults: a short version Cochrane review. Neurourol Urodyn. 2008;27(8):738–46.
Shepherd AJ, Mackay WG, Hagen S. Washout policies in long-term indwelling urinary catheteri-
sation in adults. Cochrane Database Syst Rev. 2017;3(3):CD004012.
Chapter 64
Urological Prosthetics
Ian Eardley
The 3 principal urological prostheses in common use are penile prostheses, the
artificial urinary sphincter and the testicular prosthesis. While the indications, surgi-
cal techniques, outcomes and complications are specific to the different types of pros-
thesis, the overriding concern in all patients who undergo prosthetic surgery is the
avoidance of infection. Prosthetic infection is a devastating complication that almost
always results in removal of that prosthesis and over time peri-operative pathways
have become increasingly refined as surgeons seek to reduce the risk of infection.
Penile Prostheses
Penile prosthesis are indicated for the treatment of end-stage erectile dysfunction,
cases of Peyronie’s disease that are associated with erectile dysfunction, female to
male transgender patients and they have recently become an option in the early
surgical treatment of ischaemic priapism.
The first penile implant was inserted by Nikolai Bogoras in 1936, using human
rib cartilage, but it was not until the 1970s that the first modern prostheses became
available. There are two main types; the semi-rigid prosthesis and the inflatable
prosthesis.
I. Eardley (*)
St. James’s University Hospital, Leeds, UK

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_64
362 I. Eardley
Semi-Rigid Prostheses
Modern semi rigid penile prosthesis have an external silicone covering that encloses
either a malleable metal core (silver or nickel-titanium) or a segmented articulating poly-
ethylene rod. Surgical insertion is undertaken via a sub-coronal (usually) or penoscrotal
incision and surgical complication rates are lower than inflatable devices, while they are
also less prone to mechanical failure. Set against that there are issues around conceal-
ability when the device is not in use and there is no increase in girth for intercourse.
Semis rigid prostheses are available in a variety of diameters and lengths, with
the exact size determined intra-operatively either by cutting the implant to the
required length, or by the addition of “snap-on” rear-tip extenders. Their main role
is in men with limited manual dexterity, in men with severe corporal fibrosis or in
the early surgical treatment of ischaemic priapism.
Inflatable Prostheses (Figs. 64.1 and 64.2)
The first inflatable penile prosthesis became available in 1973 and since then has
undergone a number of technical modifications, although the fundamental princi-
ples of their design have remained unchanged. Modern inflatable penile prosthesis
have three components;
• Two inflatable cylinders that sit within the corpora cavernosa and which are avail-
able in a variety of diameters and lengths. The correct cylinder length for implan-
tation is determined intra-operatively and the addition of “snap-on” rear tip
extenders allows an accurate fit. Some devices have a Parylene polymer applied
to the internal cylinder surfaces to reduce friction during inflation and deflation.
Other devices have an external hydrophilic coating that increases lubricity,
decreases bacterial adherence, and allows for absorption of aqueous antibiotics.
Fig. 64.1 A Coloplast

inflatable penile prosthesis
demonstrating the
cylinders (a), the reservoir
(b) and the pump (c)
c
64 Urological Prosthetics 363
Fig. 64.2 A Boston Scientific inflatable penile prosthesis with the intracorporal cylinders (a), the
reservoir (b) and the scrotal pump (c). The brown colouration reflects the antibiotic coating of the
device with rifampicin and minocycline
• A scrotal pump that is used by the patient to inflate and deflate the device. The
pump has two components; a compressible section that is squeezed repeatedly by
the patient to transfer the fluid from the reservoir to the cylinders and a section (or
button) that is squeezed by the patient in order to allow fluid to passively return to
the reservoir. Some pumps have a lockout valve designed to prevent auto-inflation.
• An intra-abdominal reservoir. The initial prostheses had simple spherical reser-
voirs but subsequent changes include the addition of a lockout valve to decrease
the risk of auto-inflation and the introduction low profile or cloverleaf style res-
ervoirs designed to lie flat when filled to less than full capacity. The commonest
location for the reservoir is the retropubic space, although there is increasing
interest in submuscular (or ectopic) placement behind the rectus muscle. There
has also been recent interest in a subcutaneous reservoir for men with particu-
larly hazardous abdomens.
These components are connected by non-kink tubing such that when the pump is
activated the cylinders inflate with saline from the reservoir. While there are also
one-piece or two-piece inflatable prostheses, their popularity has waned as a conse-
quence of the poor penile rigidity that they provide.
Surgical Outcomes
Surgical insertion is undertaken via a penoscrotal or an infra-pubic incision. The

reservoir can also be inserted by this incision or alternatively by a second groin or
suprapubic incision. When deflated the penis has a good flaccid appearance with
excellent concealment. When inflated the cylinders expand in girth, but not usually
in length, providing a rigid erection with penile girth approximating normal erect
364 I. Eardley
girth and penile length approximating the stretched flaccid penile length. Some
models can expand in length, although there is then a possible increased risk of ero-
sion through the glans penis. The glans penis remains soft following inflation of
each type of device.
Intra and early post-operative complications of penile implantation surgery include
posterior corporal perforation, haematoma, corporal cross-over, distal urethral injury
and bladder, bowel or vascular injury. All these complications are rare. Later compli-
cations include infection, erosion, auto-inflation and mechanical failure. Infection is
the most serious complication and is commoner in diabetics, following radiotherapy,
in revision cases and in cases where a significant haematoma is present post-opera-
tively. In high volume centres the risk of infection is usually reported to be around
1%. Mechanical failure increases with time and reaches around 15–20% at 10 years.
The Artificial Urinary Sphincter (AUS) (Fig. 64.3)
Having been initially introduced in the 1970s, the only model that is currently avail-
able for clinical use is the AMS 800 device. Indications for its use include moderate
and severe stress urinary incontinence that is not amenable to other treatments
including post-prostatectomy incontinence (PPI), end stage sphincter weakness
incontinence in women and neuropathic incontinence. In the latter group of patients
it is important to use the sphincter in conjunction with appropriate management of
the rest of the lower urinary tract.
c a
Fig. 64.3 An artificial urinary sphincter showing the urethral cuff (a), the pressure regulating bal-
loon (b) and the pump (c)
64 Urological Prosthetics 365
The AUS is made from silicone and comprises three components that are con-
nected by kink-proof tubing:
• An inflatable cuff that is placed either around the bulbar urethra or around the
bladder neck. These cuffs are available in a variety of sizes.
• A pump that is placed in the scrotum or the labia majora
• A pressure regulating balloon that is placed usually in the retropubic space or
extra-peritoneally behind the inguinal canal. There are a variety of balloon pres-
sures available.
Surgical insertion in men is via a perineal incision for a bulbar urethral cuff or via
an abdominal incision for a bladder neck cuff. The former approach is typically
used for post-prostatectomy incontinence and the latter approach is used for neuro-
pathic incontinence. In women a sphincter can be placed either by a retropubic
approach or via an anterior vaginal incision. There is increasing interest in transperi-
toneal robotic insertion of the AUS in women.
The principle of the device is that the pressure regulating balloon maintains cuff
inflation and urethral closure, such that when the patient needs to pass urine (or to
insert a catheter) they need to squeeze the pump in order to deflate the cuff. Following
the passage of urine the cuff spontaneously reinflates, typically over 1–2 minutes.
Because the cuff provides a constant closure pressure, it remains possible to leak
urine when there is a raised intra-abdominal pressure such as occurs during
coughing.
Following surgical insertion, the device is initially left with the cuff deflated. The
device is ‘activated’ around 6 weeks after implantation by pressure on a button on
the pump such that the cuff inflates and closes the urethra. Complete continence or
significant improvement is achieved in around 80% of patients.
Intra-operative complications include urethral injury, rectal injury (in bladder
neck cuff insertion) while the major late complications include infection and ero-
sion (which usually occur together), urethral atrophy and mechanical failure. In
post-prostatectomy incontinence the frequency of these complications has been
reported to be around 8%, 8% and 6% respectively.
Testicular Prostheses
Testicular prostheses are either silicone or a saline-filled silicone shell. They are
best placed via an inguinal, not scrotal, approach after puberty with the associated
full development of the contralateral scrotum. They are available in a range of sizes
which allows size matching against the contralateral testis. An anchor strap or but-
ton at the inferior pole of the prosthesis is sutured to the deep surface of dartos to
stop upward migration of the prosthesis. The principle complications from testicu-
lar prostheses are pain, scarring around the implant, shifting of the prosthesis out of
position, rupture of the core contents, due to trauma, or dissatisfaction with the
cosmetic appearance of the implanted scrotum. Due to their simplicity, correctly
inserted and without infection, testicular prostheses should last a lifetime.
366 I. Eardley
Table 64.1 Peri-operative measures to decrease the risk of developing prosthetic infection
Pre-operative Screening for urinary infection
Checking for infective skin lesions
Optimal diabetic control
Preoperative chlorhexidine/betadine shower/bath
Preoperative anti-staphylococcal nasal ointment
Putting implant cases first on the operating list
Admission on the day of surgery
Prophylactic antibiotics
Intra- Use of a laminar flow operating theatre
operative A 10-minute preoperative antiseptic scrub
Skin shave in theatre
Reduction of theatre traffic
Waterproof gowns and double gloving
Impregnated drapes
“No touch” surgical technique
Rapid surgery
Use of antibiotic coated implants where availablea
Avoidance of haematoma
Intra-operative antibiotic irrigation
Post-operative Prophylactic antibiotics (AUA recommends continuation for 24 hours
postoperatively)
Pressure dressings, where appropriate
Short duration suction drain, where appropriate
Short hospital stay
a
One major penile prosthesis manufacturer (Boston Scientific) coats its implants with rifampicin
and minocycline, while the other major manufacturer (Coloplast) uses an external hydrophilic
coating that allows absorption of antibiotic irritants
Prevention of Prosthetic Infection
The measures required to minimise the risk of prosthetic infection can be divided
into those employed at the pre-operative, intra-operative and post-operative parts of
the surgical process (Table 64.1).
Further Reading
Barnard JT, Cakir OO, Ralph D. Yafi FA Technological advances in penile implant surgery Journal
Sexual Medicine. 2021;18:1158–66.
Van der Aa F, Drake MJ, Kasyan GR, Petrolekas A. Cornu JN the artificial urinary sphincter after a
quarter of a century critical systematic review of its use in male non-neurogenic incontinence.
Eur Urol. 2013;63:681–9.
Chapter 65
Mesh in Urological Surgery
Niyukta Thakare and Chris Harding
The synthetic sling was first introduced for women with SUI in mid 1990s and the
number of procedures peaked in the second decade of the twenty-first century.
Although initial results were extremely promising, complications including chronic
pain, loss of mobility and reduction in sexual function were becoming evident.
Currently, the use of vaginally inserted mesh for SUI has been paused in the UK and
can only be carried out in exceptional circumstances.
Synthetic Mesh
The main purpose of a mesh is to provide reinforcement and support to tissues that
are weak and require support. Ideal, and undesirable, mesh properties are shown in
Table 65.1.
Table 65.1 Desirable and undesirable characteristics of meshes used surgically
Desirable characteristic Undesirable characteristic

Integrates into native tissues Excites hypersensitivity
Non-toxic Cytotoxic
Generates minimal tissue reaction Genotoxic
Biocompatibility Carcinogenic
Has tensile strength Promotes bacterial growth
Is elastic Structurally degrades
pH stable Shrinks
Thermostable
N. Thakare (*)
Freeman Hospital, Newcastle upon Tyne, UK
N. Harding (*)
Department of Urology, Freeman Hospital, High Heaton, Newcastle upon Tyne, UK

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_65
368 N. Thakare and C. Harding
All implant materials must undergo rigorous tests for biocompatibility prior to
approval by regulatory bodies including the Food and Drug Administration (FDA)
and the Medicines and Healthcare products Regulatory Agency (MHRA).
Synthetic meshes are made of polymers, which can either be non-absorbable or
biodegradable. Biomaterials are devices that interact with biological systems and
can be combined to produce a composite or hybrid implant. Synthetic materials can
be monofilament or multifilament, knitted or woven, and these features contribute
to elasticity and porosity of the mesh. The Amid classification describes four types
of synthetic meshes for abdominal hernia repair as follows:
• Type I: Macroporous, containing pores larger than 75 microns, which is the
required pore size for admission of macrophages, fibroblasts (fibroplasia), blood
vessels (angiogenesis) and collagen fibres into the pores.
• Type II: Microporous, containing pores that are less than 10 microns in at least
one of their three dimensions.
• Type III: Macroporous with multifilament or microporous components.
• Type IV: Biomaterials with submicronic pore size.
The majority of meshes used for SUI are type I.
Synthetic Non-absorbable Materials
Polymers used for manufacturing synthetic non-absorbable slings and mesh prod-
ucts are:
I. Polypropylene (PP) Type I
Thermoplastic polymer, with optimal properties including tensile strength of
31–41 mPa and melting point of >160 °C. Monofilament and multifilament
macroporous products can be produced with better biocompatibility. Gynecare
TVT™ tension-free vaginal tape, TVT-O™, UraTape®, ObTape®, MonArc™
Sling, Altis, Ajust and Gynemesh™ (Pelvic Organ Prolpase (POP) repair) are
all made from this material. The AdVance XP, I-STOP TOMS and VIRTUE
male slings are also made from PP.
II. Polytetrafluoroethylene (PTFE) Type II
Expanded PTFE has been used to design microporous mesh, called Gore-
Tex®. It rapidly integrated into tissue causing less inflammatory response and
fewer adhesions. However, it had high complication rates in the form of erosion
and need for removal.
III. Polyethylene (PE) & polyethylene terephthalate (PET) Type III
Mesh may be multifilament, knitted or woven. The pubovaginal sling
Mersilene®, made from PET, has been used for colpo-suspension.
IV. Silicone Type IV
Silastic slings made of woven PET and silicone have been found to cause
swelling and deformation, they have poor mechanical strength and high immu-
nogenicity, that leads to an increased rate of complications. The ARGUS adjust-
able sling for male incontinence is made from silicone.
65 Mesh in Urological Surgery 369
V. Polyvinylidene difluoride (PVDF)

PVDF is marketed as Dynamesh®, which has been used for POP repair. It
has reduced bacterial adherence making it a favourable material for bioengi-
neering applications and has been used for sacro-colpopexy.
Synthetic Biodegradable Materials
Biodegradable materials are used to decrease erosion and low biocompatibility

associated with non-absorbable synthetic materials.
I. Polylactic acid (PLA)
PLA is hydrolysed to lactic acid in the body and metabolised. PLA has better
biocompatibility than PP, however it is brittle, and the mechanical properties are
rather inferior, a characteristic drawback of absorbable materials.
II. Polycaprolactone (PCL)
PCL is metabolised via the tricarboxylic acid cycle. As its degradation rate
is slow it is most suitable for long-term use.
III. Poly D, L-lactic-co-glycolic acid (PLGA)
PLGA degrades by hydrolysis into lactic and glycolic acid. Depending on
the ratio of lactic and glycolic acid, it has a varied composition and physical
properties.
IV. Poly glycolide-co-lactide acid blended-poly caprolactone (PGLA/PCL)
A combination product using fibres with varying characteristics.
Biological Mesh
The limitations of synthetic materials has led to the development of products gener-
ated from naturally derived tissue or cell components. Biological meshes can be
produced by producing extracellular matrices by decellularization of xenografts and
allografts, combining synthetic scaffolds with biological components or developing
tissue engineered constructs.
Extracellular Matrix (ECM)
Collagen I and III, and Elastin are vital constituents of the pelvic floor in women
providing strength and support to tissues. Use of collagen-rich animal derived or
cadaveric ECM appears to be a rational approach to produce biological grafts. Post-
implantation, tissue remodelling, and vascular ingrowth occurs, which are vital for
integration with host tissue. Newer, off the shelf, products are completely acellular.
Porcine small intestinal submucosa (SIS), urinary bladder matrix (UBM), bovine
and porcine dermis (B&PD) and human cadaveric dermis have all been used as
ECM sources. Commonly used products are Surgsis™ (Porcine SIS) Permacol™
(cross-linked porcine acellular dermal matrix), Strattice™ (non-cross-linked por-
cine acellular dermal matrix), Matri Stem Surgical Matrix PSMX© (porcine UBM)
meshes, and Pelvicol™ (porcine dermal acellular xenograft) pubovaginal sling. The
main drawback of ECM implants is reduced mechanical strength due to the process-
ing techniques used and this may limit durability in the long-term.
Cell-Seeded Synthetic Implants
Synthetic meshes can be impregnated or coated with the patient’s own cells or allo-
geneic cells from a different source. This immunomodulates the foreign body
response to the synthetic material allowing collagen ingrowth and neovasculariza-
tion, whilst retaining the mechanical properties of the synthetic material. PDVF,
PLA, PCL and PLGA have all been used whilst PLA has been found to have proper-
ties closest to native tissues. Adipose derived stem cells (ADSCs) have been widely
investigated in SUI/POP meshes. Recently an oestradiol-releasing biodegradable
PLA mesh seeded with ADSCs has been investigated.
Non-synthetic Bioengineered Mesh
An implant which biologically resembles native tissues is most likely to have func-
tional properties and host-implant relationship similar to the natural environment.
Natural scaffolds including ECMs and composites of collagen with PLA for exam-
ple are seeded with cells including ADSCs, bone marrow MSCs, and fibroblasts
derived from human, rabbit, and rat sources. Although initial studies show promis-
ing results, longevity and durability of these grafts are still a long way from being
established.
Outcomes
Clinical outcomes of surgery utilising implanted mesh have been evaluated in sev-
eral meta-analyses and trials as outlined in Table 65.2 below:
65 Mesh in Urological Surgery 371
Table 65.2 Evidence about the best way of using meshes in comparison to other ways of providing
support for other causes of male and female incontinence
Meta-analysis/Trial Application Evidence
ESTER network Female SUI Evidence that mid-urethral and traditional slings are
meta-analysis effective in treating incontinence symptoms in the
short-term, and mid-urethral slings are less costly;
however the safety profile of both has yet to be fully
documented.
TOMUS trial Female SUI Higher success in retropubic group than trans-obturator
insertion at 2 and 5 years
SIMS trial (Ajust Female SUI Single-incision mini-slings were non-inferior to standard
and Altis vs synthetic mid-urethral slings with respect to patient-reported
sub-urethral slings) success at 15 months, and the percentage of patients
reporting success remained similar in the two groups at
the 36-month follow-up.
PROSPECT trial Female POP Mesh or graft material used for augmentation of POP
(Surgisis BD) repair did not improve outcomes.
MASTER trial Male Baseline severity of incontinence did not influence
(AdVance vs AUS) incontinence outcomes in either group. Improvement in symptoms and
quality of life was high in both groups, however patient
satisfaction was higher in the AUS cohort.
SUI = Stress urinary incontinence. POP = pelvic organ prolapse. AUS = Artificial urinary sphincter
Complications
Factors contributing to potential complications from implanted mesh include acute

and chronic inflammation, infection, and a foreign body response, and the main
symptoms are pain and erosion or extrusion leading to sexual dysfunction, de novo
LUTS, recurrent UTIs and rarely systemic symptoms such as chronic fatigue, skin
problems, hair loss and cognitive impairment.
The Cumberledge review, ‘First Do no Harm’ published in 2020, was inspired by
patient campaigns against mesh implantation. One of its recommendations was to
set up networks of mesh centres to provide specialist management for those affected
by the complications of mesh implantation. Currently patients and health care pro-
fessionals are encouraged to report mesh-related complications through the ‘Yellow
card’ scheme.
Further Reading
Gomelsky A, Dmochowski RR. Biocompatibility assessment of synthetic sling materials for

female stress urinary incontinence. J Urol. 2007;178(4):1171–81.
MacCraith E, O’Brien FJ, Davis NF. Biodegradable materials for surgical management of stress
urinary incontinence: a narrative review. European Journal of Obstetrics & Gynecology and
Reproductive Biology. 2021;259:153–60.
Chapple CR, Osman NI, Mangera A, Hillary C, Roman S, Bullock A, Macneil S. Application of
tissue engineering to pelvic organ prolapse and stress urinary incontinence. Low Urin Tract
Symptoms. 2015;7(2):63–70.
Farmer Z, Domínguez-Robles J, Mancinelli C, Larrañeta E, Lamprou D. Urogynecological surgi-
cal mesh implants: new trends in materials, manufacturing and therapeutic approaches. Int J
Pharm. 2020;585:119512.
Cumberledge J. First do no harm. The report of the Independent Medicines and Medical Devices
Safety Review Available at: https://www.immdsreview.org.uk/downloads/IMMDSReview_
Web.pdf.
Chapter 66
Irrigation Fluids and Their Hazards
Matthew Liew
Irrigant fluids are utilised in endoscopy and endoscopic surgery to enable distension
of a viscous and clearance of blood and particulate, to improve the surgeon’s view.
Different fluids can be employed to achieve this and the relative indications and
risks are discussion in this chapter.
Introduction
Fluid is infused into the urinary tract during endoscopic urology surgery for a range
of procedures on both the upper and lower urinary tract. All bladder irrigants should
be pyrogen free and used as close to body temperature as possible to minimise heat
loss during surgery. The commonest irrigation fluid used in the UK is saline (0.9%),
but for monopolar prostatic resection a non-ionic liquid that does not conduct elec-
tricity is required. A variety of solutions can be used including water, glycine, sor-
bitol and mannitol. Apart from water, all are weakly hypotonic thereby reducing the
risk of intra-vascular haemolysis. Water is, however, the irrigant of choice in trans-
urethral bladder tumour laser ablation (TULA) for better vision and tumour cell
lysis. There are proven safety and efficiency benefits of bipolar systems using saline
including facilitating day case TURP surgery as standard. However, monopolar
TURP with glycine 1.5% is still widely used, primarily for economic reasons and
low allergenicity. There are hazards with glycine infusion, most notably intravascu-
lar absorption with the development of the so-called TUR syndrome. Here, we dis-
cuss the known and potential hazards of glycine and saline use in urological surgery.
M. Liew (*)
Wrightington, Wigan and Leigh Teaching Hospitals NHS Foundation Trust, Wigan, UK

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_66
374 M. Liew
Table 66.1 Symptoms commonly associated with dilutional hyponatraemia
Nausea Confusion
Vomiting Anxiety
Bradycardia Paraesthesia
Hypotension Visual disturbance
Chest pain Seizures
TUR Syndrome
TUR syndrome is primarily a dilutional hyponatraemia that occurs when fluid is

absorbed through venous channels commonly opened during prostatic resection. It
is characterised by a serum sodium of <125 mmol/L and two or more associated
clinical symptoms (Table 66.1). It can lead to death if untreated. TUR syndrome
utilising saline irrigation fluid is rare but cases have been reported.
Incidence and Risk Factors for Developing TUR Syndrome
Significant fluid absorption occurs in approximately 10% of cases undergoing

TURP although the prevalence of the full syndrome is much lower. There are sev-
eral risks factors including operator experience, gland size, duration of the surgery,
height of the irrigant column and intra-prostatic fossa pressure. Prostatic capsule or
bladder perforation may lead to absorption via peri-prostatic venous, intra-peritoneal
or peri-vesical routes.
Intravascular Volume Shifts
Intra-vascular volume expansion by up to 200 ml/min of irrigant can cause initial

hypertension. Later, hyponatraemia and hypertension will lead to fluid shifts from
the intravascular space along osmotic and hydrostatic pressure gradients resulting in
hypotension, pulmonary oedema and, if untreated, hypovolaemic shock. Factors
that can aggravate the hypotension include a direct toxic effect of glycine on the
myocardium, the sympathetic blockade that accompanies a regional block as well as
endotoxaemia that may occur during endoscopic surgery.
66 Irrigation Fluids and Their Hazards 375
Plasma Solute Effects
The changes in plasma solutes in TUR syndrome can be varied and complex. Hypo-
osmolality rather than hyponatraemia is probably the main cause of neurological
signs since the blood brain barrier pore size is impermeable to sodium but freely
permeable to water. Cerebral oedema caused by acute hypo-osmolality increases
intra-cranial pressure, resulting in bradycardia and hypertension via the
Cushing reflex.
Hyperammonaemia
Glycine is 90% liver metabolised (10% renal) by oxidative deamination to form

glyoxylic acid and ammonia. Ammonia can alter CNS function although the exact
mechanism is unclear.
Hyperglycinaemia
Glycine is itself an inhibitory neurotransmitter and may have a role in the develop-
ment of visual changes, encephalopathy and seizures. While the exact mechanism is
not completely understood, its action may involve N-methyl-D-aspartate (NMDA),
(which is an excitatory neurotransmitter) since NMDA receptor activity is potenti-
ated by glycine. It is also thought that glycine causes visual changes via its action as
a neurotransmitter within the retina although these changes typically return to nor-
mal within 24 hours as glycine levels normalise.
Management of TUR Syndrome
Prevention (such as limiting surgery to <90 mins using continuous irrigation cysto-
scope) and early recognition is key. The presence of symptoms and signs, sugges-
tive of hyponatraemia, is the single most important factor in determining morbidity
and mortality. Spinal anaesthesia is useful in detecting the early signs of TURP
syndrome.
376 M. Liew
Intensive monitoring and supportive HDU/ICU care is central to the manage-

ment of these patients. Hypertonic saline (3%) can be used to treat severe hypona-
tramia and hypo-osmolality but may aggravate the hypervolaemic manifestations.
Osmolality should be corrected aggressively (sodium correction 2 mmol/L/h) until
symptoms resolve then more slowly at about 1.5 mmol/L/h. The most serious com-
plication of rapid correction of hyponatraemia is central pontine myelinosis (CPM)
a demyelinating condition with poor prognosis.
Diuretic use is recommended only with acute pulmonary oedema, as mannitol
and furosemide can cause further sodium loss and worsen the situation.
Other Issues with Irrigation Fluid in Urology
Retrograde Intra renal surgery (RIRS) has had huge uptake with the exponential rise
in technology in recent years. It has become apparent that high intrarenal pressure
from irrigation fluid especially during prolonged surgery is associated with renal
injury. Measures employed include avoiding continuous pressurised irrigation, use
of access sheaths and single use flexible ureteroscopes with in-built real time pres-
sure recording monitors (Boston Scientific LithoVue™ Elite System). It is likely
that pressure and temperature sensors incorporated into scopes will be the standard
of care for RIRS in the future.
Further Reading
Cheung GY, Tempany S, Chu MHM. Complications associated with intraoperative use of irriga-
tion fluid for endoscopic procedures. Update in Anaesthesia. 2020:49–53.
Hawary A, Mukhtar K, Sinclair A, Pearce I. Transurethral resection of the prostate syndrome:
almost gone but not forgotten. J Endourol. 2009;23:2013–20.
Yousef A, Suliman GA, Elashry OM, Elsharaby MD, Elgamasy AEK. A randomized comparison
between three types of irrigating fluids during transurethral resection in benign prostatic hyper-
plasia. BMC anaesthesiology. 2010;10:7.
Chapter 67
Insufflants and Their Hazards
Yuhao Zhang and Stephen Bromage
Laparoscopic and robotic surgery require the formation of a pneumoperitoneum

which is achieved via the introduction of a gaseous insufflant into the abdominal
cavity. Carbon dioxide is the most commonly used gas insufflant. It is important to
understand the cardio-respiratory effects of a CO2 pneumoperitoneum as they can
result in severe and even fatal complications.
Types of Insufflants
A range of insufflation gasses have been used for laparoscopy. An ideal insufflation
gas should be physiologically inert, colourless, highly soluble in blood, chemically
stable, widely available and inexpensive. CO2 has emerged as the predominant
choice due to its high solubility, lack of colour and low risk of combustion. The
advantages and disadvantages of various insufflants are shown in Table 67.1.
Y. Zhang (*)
Stockport NHS Foundation Trust, Stockport, UK
e-mail: yuhao.zhang@doctors.org.uk
S. Bromage
Stepping Hill Hospital, Stockport, UK
e-mail: sjbromage@doctors.org.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_67
378 Y. Zhang and S. Bromage
Table 67.1 Advantages and disadvantages of various gaseous insufflants

Gas Advantages Disadvantages
Carbon dioxide High solubility, low combustibility, Hypercapnia
(CO2) rapid elimination Peritoneal irritation (abdominal and
shoulder tip pain)
Nitrous oxide Anaesthesic properties, no acidosis, Combustion, sedating properties on
(N2O) high solubility surgeons
Air Inexpensive, no acidosis or Poor solubility (air embolus),
hypercapnia combustion
Helium Inert, non-combustible Poor solubility (air embolism),
expensive
Use of CO2 in Laparoscopic Urological Surgery
Stored CO2 is at high pressure whilst contained in a cylinder (760 mm Hg or 200 bar)
and is reduced to the required inflation pressure by a reduction valve. The CO2
insufflator pressure is usually set at 12–15 mm/Hg; this can be increased to 20 mm/
Hg when required to reduce bleeding; this increases the risk of complications asso-
ciated with higher pressure insufflation. The initial gas flow is normally 1 L/min;
this is increased when it is clear that the peritoneal cavity has been entered follow-
ing initial percutaneous puncture. A low flow rate is important to reduce the chance
of bradycardia and if this occurs gas can be quickly released.
The normal temperature of CO2 is 21 °C and although this can cause problems
with fogging of the laparoscope, increasing the temperature has no other significant
benefits and therefore is not usually performed.
Risks and Side Effects of CO2 Insufflation
Subcutaneous Insufflation
Subcutaneous emphysema is more common in extra-peritoneal procedures due to

the larger surface area available for absorption. It is also more common in the elderly
due to decreased tissue resistance. Gas may be pushed into the subcutaneous tis-
sues, because the insufflation trochar is not in the correct cavity or because gas
escapes from the cavity being insufflated. This can result in spreading subcutaneous
emphysema. This is not a particularly dangerous complication and the tissues will
absorb the CO2 over a period of days. A small amount of localised subcutaneous
insufflation occurs commonly and goes unnoticed, and larger amounts of leakage
occur rarely (<1%); this can extend down to the scrotum, and thighs, or up to the
chest and neck. This complication can be minimized by the following:
• correct port positioning
• keeping pressures low
• observing the high end-tidal CO2 (this may be the first sign of significant gaseous
extravasation)
67 Insufflants and Their Hazards 379
Metabolic Consequences of CO2 as an Insufflant
As CO2 is readily absorbed, this results in hypercarbia and acidosis. This effect may
be increased by impairment of ventilation by the raised intra-abdominal pressure,
which can reduce the elimination of CO2. Hypercarbia and acidosis can cause vaso-
dilatation and decrease cardiac contractility. It also stimulates the sympathetic ner-
vous system resulting in tachycardia and vasoconstriction. These effects are most
pronounced in patients with pre-existing respiratory disease.
Desufflation of the pneumoperitoneum at the end of surgery does not lead to an
immediate return to physiological baseline. Significant volumes of CO2 can be
absorbed by the body during surgery. The anaesthetist may have to mechanically
ventilate the patient and delay extubation until adequate CO2 is removed.
CO2 and Air Embolus
The risk of CO2 emboli is low due to its rapid absorption in the blood and the ability
of blood to transport high levels of it. The lethal volume of CO2 that is likely to have
an embolic effect is around 200 ml - five times the volume of air that would have an
embolic effect. Gaseous emboli may occur in laparoscopic surgery after entry in
injured vessels or via direct intravascular insufflation (often due to a misplaced trocar).
Although a clinically evident CO2, or air embolus is rare in laparoscopic surgery,
it is important to recognise clinical signs that embolisation has occurred. Gas entry
into the systemic circulation can cause occlusion of small vessels and ischaemia. In
the anaesthetised patient, the main signs are:
• cardiac arrhythmias
• hypotension
• myocardial ischaemia
• increased central venous pressure
• pulmonary hypertension
Gas locks created by the emboli can lead to life-threatening right heart failure and
subsequent cardiovascular collapse. Immediate treatment consists of administering
100% FiO2 and release of the pneumoperitoneum. The patient is then positioned
head-down and into left lateral decubitus to allow gas bubbles to rise to the apex of
the right atrium, preventing entry into the pulmonary circulation and towards the
head. Aggressive fluid resuscitation can also increase central venous pressure to
discourage emboli from entering the systemic circulation.
Physiological Effects of a Prolonged Pneumo-Peritoneum
The establishment of a pneumo-peritoneum itself has several physiological conse-

quences that are more pronounced with a prolonged procedure (Table 67.2). In
healthy individuals these effects usually have little significance, however, in patients
380 Y. Zhang and S. Bromage
Table 67.2 Common physiological effects of a pneumo-peritoneum at 15 mm/Hg
Physiological factor Effect

Venous return ↓
MAP ↑
SVR ↑
Heart rate ↑
Partial pressure CO2 ↓
Functional residual capacity ↓
End tidal CO2 ↑
Urine output/ GFR ↓
with a pre-existing cardiovascular or respiratory co-morbidity they can result in

significant problems by influencing cardio-pulmonary physiology.
In most cases intra-abdominal pressure during laparoscopy reduces the venous
return (pre-load) and subsequently cardiac output. In response, systemic vascular
resistance (SVR) increases (after-load) as does heart rate, mean arterial pressure
(MAP) and pulmonary resistance. Central venous pressure (CVP) will be artificially
high and care must be taken when interpreting CVP readings. Arrhythmias may
occur due to hypercapnia however, bradycardias can also be observed due to vagal
stimulation from peritoneal stretching. If the patient is in a hypervolaemic state,
then atrial pressures and therefore vena-caval pressures, may be high resisting the
pneumo-peritoneal pressure and increasing venous return.
Respiratory effects occur mainly due to diaphragmatic displacement and reduc-
tion in movement. The vital capacity and functional residual capacity are reduced,
pulmonary compliance drops and airway resistance increases. Average peak airway
pressure is increased to maintain tidal volume. The use of CO2 will also raise the
partial pressure of CO2 in the blood, which may need to be eliminated by increasing
either the ventilated respiratory rate or tidal volume. A head-down Trendelenburg
position increases the pressure placed onto the diaphragm, decreasing lung compli-
ance and increasing peak airway pressures. However, there is also an increase in the
venous return to the heart which can increase the cardiac output. These shifts in
physiological pressures must be taken into account when positioning a patient.
Renal, splanchnic and hepatic perfusion is reduced by a pneumo-peritoneum and
there is activation of the renin-angiotensin system resulting in generalised vasocon-
striction. Urine output is reduced due to a decreased glomerular filtration rate (GFR)
and mesenteric blood flow is also reduced which may, rarely, cause a mesenteric
thrombosis. Using an inflation pressure of less than 15 mm/Hg avoids many of these
potential complications.
Post-Operative Pain Due to Insufflants
Although laparoscopic surgery is associated with lower levels of post-operative pain

than open surgery, pain relating to insufflants is a unique feature. CO2 retention in the
abdomen irritates the diaphragm and the phrenic nerve. Pain is therefore referred to
67 Insufflants and Their Hazards 381
the C5 dermatome at the shoulder. Some methods of removing excess CO2 have been
proposed such as the pulmonary recruitment manoeuvre and intraperitoneal normal
saline infusion which have been shown to reduce post-operative shoulder tip pain.
Robotic Surgery
Robotic-assisted laparoscopic procedures come with many of the same pitfalls as

traditional laparoscopic surgery when it comes to insufflants. More specifically,
robotic-assisted radical prostatectomy (RARP) requires an extreme head-down
Trendelenburg position of 30–400 and higher insufflation pressures (15 mmHg) in
the peritoneal cavity as compared to the traditional extra-peritoneal Retzius laparo-
scopic approach. Both of these factors exacerbate the cardio-respiratory sequalae
mentioned above. Furthermore, most of the lung is below the left atrium in this
position which can lead to ventilation-perfusion mismatch, atelectasis, and pulmo-
nary oedema.
Reducing Risks of Pneumoperitoneum
There are clear hazards associated with insufflants and laparoscopic surgery but
these can be mitigated against by careful planning and monitoring. All patients
should undergo a thorough pre-operative anaesthetic review to identify any underly-
ing cardio-respiratory conditions which can be optimised pre-operatively. In par-
ticular, patients with morbid obesity, congestive heart failure, valvular heart disease,
ischaemic heart disease, and obstructive pulmonary disease are particularly at risk.
Intraoperatively, care must be taken to minimise the insufflation pressures and oper-
ating time by the surgeon. Vigilant monitoring of vitals and early correction of hae-
modynamic and metabolic disturbances is also essential.
More recently, valveless insufflation devices such as Airseal™ have been shown
to better maintain a stable insufflation pressure and decrease overall theatre time.
Importantly, it operates at a lower pressure and can reduce CO2 absorption, leading
to lower rates of post-operative abdominal and shoulder tip pain.
Further Reading
Bishoff J, Kavoussi L. Atlas of laparoscopic and robotic urological surgery. 3rd ed. Elsevier; 2016.
Cardiovascular and Ventilatory Consequences of Laparoscopic Surgery.” Atkinson T et al.
Circulation vol. 135,7 (2017): 700–710.
Chapter 68
Laparoscopic Ports
Euan Green
Laparoscopy requires insertion of several (or a single) port(s) to gain access into the
abdomen for visualisation and manipulation of intra-corporeal structures. They are
best classified by size, trocar type and entry technique.
Port Types and Sizes
Laparoscopic ports consist of a sheath and trocar used to gain access to a body cav-
ity for endoscopic surgery. Many competing products are available. Most laparo-
scopic ports have a bladed or sharp trocar to allow ease of dissection into the
peritoneum. The trocar tip may differ between a conical or pyramidal shape. Blunt
tip trocars are also available for open access techniques. Some initial ports will have
inflatable ‘balloons’ attached to allow the creation of space for the operative field.
This is of particular use in retroperitoneal or extra-peritoneal surgery. For example,
a retroperitoneal approach to a laparoscopic nephrectomy.
Ports are available in several sizes from 3 mm to 15 mm. Most commonly, the
laparoscope is inserted through a 10 or 12 mm port (the ‘camera port’), with smaller
5 mm ports for secondary instrumentation. A 12 mm or 15 mm port is often used for
organ retrieval. For example, a kidney in an “Endocatch” bag.
Optical ports, for example, the Visiport™, combine the smaller incision of a
closed access approach with direct visualization of the tissue layers during port
placement, thereby reducing the opportunity for inadvertent visceral injury.
Typically, a 00 laparoscope is inserted into an optical trocar for insertion. This is
known as the closed visual entry technique.
E. Green (*)
e-mail: euan.green@srft.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_68
384 E. Green
Expandable ports, such as the STEP™ system allow an expandable mesh sheath
to be inserted with minimal tissue trauma over a Veress-type needle. Once inserted
to the appropriate depth, a trocar replaces the needle and hence mechanically dilates
the sheath, expanding the port to the required diameter. The Veress needle technique
refers to the closed entry technique whereby the needle blindly punctures layers of
the abdominal wall to achieve pneumoperitoneum.
Some ports also include an inflatable balloon to help with port stabilization
intra-operatively.
Ports for use with robotic surgery systems include a mounting for securing the
robotic arm to the port so that the port and instrument move in synchronisation with
each other. Robotic ports are also reusable for the most part.
Principles of Port Placement
A primary port is used to establish pneumoperitoneum for endoscopy. Primary port

placement can be undertaken in one of three ways with either an open or closed
technique. A Veress needle has a blunt spring-loaded obturator which advances
once the needle reaches the cavity. Despite this, there is potential for injury to
underlying viscera, particularly when adhesions are present. As such, many sur-
geons favour an open or ‘Hasson’ approach whereby the cavity is accessed through
an open cutdown. A blunt tipped trocar (Fig. 68.1) can then be inserted which may
require securing with sutures to the muscular aponeurosis. A disadvantage of this
technique is that a slightly longer incision is required. The final technique is the
closed visual entry technique using the Visiport™ as described above.
Fig. 68.1 Blunt-tipped trocar and port used for Hasson (open) primary access
68 Laparoscopic Ports 385
The number, size and position of secondary ports depends on the procedure
being performed. Although 5 mm ports allow passage of most instruments, a
10/12 mm port is required for the passage of most suture needles, linear staplers and
for specimen retrieval. A typical configuration of ports for laparoscopic radical
nephrectomy is shown in Fig. 68.2. Ports should be directed towards the target site,
and positioned such that a clashing of instruments, or laparoscope, is minimized.
Figure 68.3 shows a typical configuration for robotic renal surgery. Ports are often
placed in a straight line with newer DaVinci XI systems. Secondary ports are
inserted under laparoscopic guidance to avoid injury to viscera or abdominal wall
vasculature. Similarly, during removal, the site should be observed to avoid bleed-
ing or bowel herniation.
Fig. 68.2 Typical port placement for laparoscopic radical nephrectomy: A: primary access port
(10–12 mm), B and C: secondary instrument ports (5 or 10–12 mm)
R
8
8 12
12-C
R A
C
Fig. 68.3 Typical port placement for robotic assisted radical/partial nephrectomy: A or C: primary
access port (10–12 mm), R robotic 8 mm port
386 E. Green
Single Port Access
In an effort to even further reduce the morbidity associated with laparoscopic sur-
gery, single port access (SPA) technology has evolved, whereby procedures are per-
formed using multiple instruments through a single access point shared with the
laparoscope. This approach is also known as laparo-endoscopic single site surgery
(LESS) and single incision laparoscopic surgery (SILS). Inevitably, using a single
access point is extremely challenging technically, with limited freedom of move-
ment and loss of triangulation. Due to the increasing popularity of robotic assisted
laparoscopic surgery (SPA) is not seen commonly in practice in the UK.
Natural Orifice Transluminal Endoscopic Surgery (NOTES)
NOTES experience is limited to small case series and has an undefined role in urol-
ogy. This technology is designed to access the peritoneal cavity and target organ
through an endoscopic incision in a neighbouring luminal structure, for example the
stomach, vagina, bladder or colon. In the absence of any external incisions, it is
hoped that it will offer significant advantages in terms of cosmesis, and reduce
wound related problems such as infection, herniation, and post-operative pain.
NOTES uptake has been limited for similar reasons to SPA surgery.
Further Reading
Stolzenburg JU, Kallidonis P, Hellawell G, et al. Technique of laparoscopic-endoscopic single site

surgery radical nephrectomy. Eur Urol. 2009;56(4):644–50.
Symes A., Raynes, A. J Urological applications of single-site laparoscopic surgery. Minim Access
Surg 201; 7(1): 90-95.
Chapter 69
Principles of Robotic Surgery
Robin Weston
Over 90% of radical prostatectomies are now performed robotically in the

UK. Robotic surgical systems consist of 3 parts: surgeon console, patient cart(s) and
monitor. It offers significant advantages over laparoscopy, including 3D vision,
wristed movements, scaled movements and elimination of tremor.
Introduction
Robotic surgery is somewhat a misnomer as what we commonly refer to as robotic

surgery is a master slave device. The history of robotic surgical systems in general
has been well documented.
From a urology perspective, there were a few rudimentary ‘surgical robots’ although
these were really camera holding or retraction devices. The global monopoly for the
current generation has been the Intuitive da Vinci system which has stepwise pro-
gressed from the Standard, Si, X to the Xi. Competitor platforms have emerged onto
the market and although features may vary the principals of the systems remain similar.
During the initial development of robotic surgery, the concept of performing
operations with the surgeon remote from the patient by many miles on another con-
tinent or even in space was entertained. In 2001, a transatlantic cholecystectomy
was carried out in Strasbourg with the surgeon in New York over 7000 km away.
At present, operating over great distances is not a priority for most surgeons. The
technical considerations and potential medicolegal issues mean that surgeons,
although operating remote from the patient via a console, prefer to be in the same
operating theatre. A legacy of this evolution is the microphones and speakers are
R. Weston (*)
Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
e-mail: robinweston@nhs.net

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_69
388 R. Weston
installed on the console and operating cart of all the da Vinci systems to facilitate
communication between console surgeon and bedside team. The basic principle of
teamwork is that reliable communication exists between all members. A key point
which is often lost on patients and the media, is that currently there is no degree of
autonomous control with any of the systems.
Robotic Systems and Setup
At present the daVinci Xi system consists of a surgeon console, a patient cart con-
sisting of 4 robot arms attached to a boom and the visual cart containing much of the
computer processing along with a high-definition monitor and integrated energy
generator (Fig. 69.1). The Versius (Fig. 69.2) and Hugo robots from CMR surgical
SURGEON CONSOLE PATIENT CART VISION CART
Fig. 69.1 The da Vinci XI surgical system
Fig. 69.2 Versius modular system with open console

69 Principles of Robotic Surgery 389
and Medtronic respectively, are similar except instead of a single patient cart with
arms attached they have modular individual surgical arms which can be configured
independently around the patient. Furthermore, they have an open surgeon console
requiring 3D glasses to be worn instead of an enclosed console.
The movement of the surgeons’ hands at the console are replicated by the robotic
arms inside the patient. Lateral movements are scaled i.e. large movements with the
hands translate into finer movements inside the patient with a ratio of around 1:1.5
to 1:3. Rotational movement is not scaled with the da Vinci system, although can be
with the Hugo system. Along with the 3D magnified image, this allows the surgeon
to intuitively manipulate the surgical instruments as if they were an extension of
their own hands (Fig. 69.3).
Foot pedals and finger switches are utilised to control camera movement and to
use energy devices, typically bipolar and monopolar diathermy. The interchange-
ability of instruments on these systems gives access to stapling devices, clip appliers
and vessel sealers.
Ports are placed through the abdominal wall after the establishment of a pneu-
moperitoneum, and these are ‘docked’ to the robot with specially designed 8mm
ports (in the case of the daVinci Xi). The advantage of this system is that the instru-
ments and camera are designed to fit an 8mm port allowing the camera and working
arms to be interchangeable which can be particularly useful in operations such as
nephro-ureterectomy. Only the CMR system has the advantage of using standard
5 mm laparoscopic ports. However, the camera and instruments are not currently
interchangeable.
In the early days with relatively shorter instruments more bulky robot arms and
single quadrant operating, accurate port placement was essential and unforgiving.
With the stepwise evolution of the da Vinci system this process has become easier
and more flexible improving access for multi-quadrant operating.
Fig. 69.3 Wristed

instruments for the da
Vinci system
390 R. Weston
Advantages of Robotic Surgery
The advantages of robotic surgery compared to standard laparoscopy are easy to

describe. The current robotic systems all deliver 3D magnified vision, wristed
interchangeable instruments, ergonomic position for the surgeon and energy
devices. 3D vision and wrist movement certainly assist suturing. Although these
features have been applied to more conventional laparoscopic surgery they are not
performed as intuitively and therefore laparoscopic adoption has been less
widespread.
Advantages of minimally invasive surgery
• Reduced incision length and scarring
• Reduction in post-operative pain
• Less blood loss
• Quicker return to normal activity
Advantages of robotic surgery over standard laparoscopy
• 3D vision
• Wristed instruments with greater degree of movement than human wrist
• Scaled movements and elimination of tremor
• Ergonomic surgeon position
Although perhaps less publicised, the ergonomic benefit of operating at a console
with the ability to ‘clutch’ the controls so that the surgeon can be always comfort-
able during the operation is invaluable. Any surgeon who has performed laparo-
scopic prostatectomy and then converted to robotic will be acutely aware of this and
may feel far more comfortable doing 2–3 prostates a day rather than 1–2.
The daVinci robot can utilise immunofluorescence to enhance visualisation of
vascular structures and tumour identification through variability in vascularisation.
This is performed by injecting intravenous indocyanine green (ICG) and utilising
the inbuilt laser via the scope at a frequency of 803nm which causes excitation of
the albumin bound ICG and shows fluorescence within vascular structures. This has
uses in urology particularly in renal surgery where it can help identify hilar vascular
anatomy and renal tumour demarcation.
Another advantage is the ability to view real time ultrasound images within
the console. This relies on third party USS equipment with flexible probes
which allow manipulation of the probe by the surgeon via the console whilst
seeing the USS image in the console; again, particularly useful for identifying
renal tumours.
These examples of enhanced visualisation are not exclusive but are particularly
suited to robotic surgery. There is currently significant investment in the develop-
ment for more advanced features particularly dynamic overlay of anatomy extrapo-
lated from cross sectional imaging. The concept is simple however reliable
reproducibility is technically difficult, and remains a challenge.
69 Principles of Robotic Surgery 391
Robotic Surgical Training
Training is a key consideration when introducing new technology, and this is par-
ticularly relevant to robotic surgery. Video recording of surgical procedures has
been available for laparoscopic and endoscopic surgery for many years. Almost
universally robotic surgeons will have spent many hours studying robotic proce-
dures and will have experience of recording their own operations for personal edu-
cation purposes. Most training fellowships now use this as an effective way to
enhance and improve training.
Telestration is a technological innovation that compensates for the inability of a
trainer to point out anatomy or give visual direction whilst the trainee is operating
within a console. It allows the trainer to draw on the screen at the patient cart and
the graphic to be visible within the console. With the addition of dual console sup-
port this has been enhanced and allows the trainer to use a pointer within a 3D field
to guide the trainee. Dual console operating has the additional benefit for allowing
the trainer to give and take control of the surgical arms.
Patient Considerations
Clinicians can be distracted by technology, and it is essential that the most impor-
tant factor, the patient, is not overlooked. Perioperative issues pertinent but not
exclusive to robotic surgery include:
• Positioning—the patient may be relatively inaccessible during the procedure
therefore reliable venous access and monitoring are important.
• Complexity of procedures often results in long anaesthetic times which is exac-
erbated by the learning curve.
• Protection of pressure areas is vital including the potential risk of robot arms
touching patient.
• A steep head down position is utilised during pelvic surgery and an appropriate
interface between the patient and the operating table such as specifically designed
foam mats, strapping or shoulder supports to prevent slipping is essential.
• Eye protection to prevent reflux of gastric contents damaging eyes.
• Ensuring that the patient is paralysed during the entire robotic procedure as any
movement whilst robot is ‘docked’ to the patient can cause life-threatening injury.
Physiological Considerations
• Pneumoperitoneum can result in reduced venous return, thereby decreasing car-

diac output; arrhythmia (particularly bradycardia); increase in systemic vascular
resistance; increased airway pressure and V-Q mismatch.
392 R. Weston
• Head down can further exacerbate cardiovascular issues by increasing airway

pressures and systemic vascular resistance but does improve cardiac return.
• Carbon dioxide insufflation can cause carbon dioxide embolus and over long
periods result in hypercarbia.
• Pre-existing cardiovascular pathology is important and must be considered when
deciding on suitability for robotic surgery.
Contraindications to robotic surgery include raised intracranial pressure and haemo-
dynamic instability. Previous surgery and adhesions are relative contraindications
and depend on experience of the surgeon. Peripheral vascular disease is another
concern as it can result in decreased perfusion and critical limb ischaemia during the
steep head down position associated with pelvic surgery. This may preclude com-
partment syndrome and potential leg amputation.
Further Reading
Ashrafian H, Clancy O, Grover V. The evolution of robotic surgery: surgical and anaesthetic
aspects. Br J Anaesth. 2017;119(1):i72–84.
Atkinson TM, Giraud GD, Togioka BM. Cardiovascular and ventilatory consequences of laparo-
scopic surgery. Circulation. 2017;135(7):700–10.
Chapter 70
Setting Up Robotic Surgery
Robin Weston
The purchase, implementation and sustainability of a robotic surgical program

requires thoughtful planning and preparation. Setting up robotic surgery offers sig-
nificant challenges including financial planning, surgical robotic training and devel-
oping a robotic theatre team.
Introduction
Key questions to ask when implementing new technology are “who is going to ben-
efit?”, and “what is the cost?” The expectation is delivering clinical improvements
for the patient such as better functional outcome, reduced blood loss, quicker recov-
ery, the ability to perform more cases and reduce complications. Some or all these
parameters may be achievable in the short-term or in some cases only be aspira-
tional. It is therefore imperative to have a fully worked up business case with realis-
tic patient numbers and expected improvements in outcome such as length of stay.
It must also be remembered that the bottom line in healthcare is not always absolute
cost, and if clinical outcomes can be improved then the business case should be able
to estimate the additional cost per case and justify it accordingly. The financial out-
lay may be quickly mitigated by the reduced cost implications from shorter length
of stay and reduced transfusion rate. Furthermore, economies of scale also can help
to reduce cost per procedure, when considering capital outlay and maintenance con-
tracts. Various calculations have looked at case volume and finances, and below 150
cases a year it is very difficult to mitigate against capital costs.
R. Weston (*)
Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
e-mail: robinweston@nhs.net

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_70
394 R. Weston
Which surgeons will use a newly acquired robotic system will need to be decided
so theatre planning and realistic case volume can be determined. Hospitals often
find that demand can outstrip capacity and business cases for second systems need
to be considered.
Most units setting up a robotic service already perform the surgical procedure
either with laparoscopic or open surgery. Clearly this is advantageous as a great
deal of the pre-requisite support such as available theatres, pathology services,
ward space, referral population etc. is already in place. When this is not the case,
thought must be given to whether there is sufficient patient volume and if suit-
able infrastructure and clinical support exists to deliver a safe and efficient pro-
gram. Surgery is only a part of the patient management and specialist nurse
support, counselling services, physiotherapy other specialist input must be con-
sidered if creating a business case for performing new procedures, particularly
cancer surgery.
The index procedure in urology is radical prostatectomy with over 90% of pros-
tatectomies being performed by this technique in the United Kingdom. Partial
nephrectomy, radical cystectomy and pyeloplasty are also routinely performed in
most robotic units. There has been a paucity of randomised controlled trials in sur-
gery and the massive expansion in robotic surgery preceded conclusive data sup-
porting it. The first randomised controlled trial for open versus robotic radical
prostatectomy in 2016 demonstrated a reduced length of stay and less blood loss
however the functional primary endpoints were similar. Since then evidence sup-
porting robotic surgery has continued to accumulate particularly in urology, with a
recent multicentre randomised trial demonstrating superiority of robotic over open
cystectomy.
Robotic Surgical Training
Human factors are clearly essential to the successful implementation of a robotic

program and this is invariably led by the surgeon. Specific robotic fellowship train-
ing is the usual format for junior surgeons wishing to acquire proficiency in robotic
surgery. Clearly being capable of independently performing the procedure is prefer-
ential but it is commonplace for units to start robotic programs with robot naïve
surgeons. In this circumstance, it is essential that mentors/proctors are identified
who will be able to support the surgeon. Depending on experience, the amount of
support will vary. For example, an experienced laparoscopic prostate surgeon may
translate very quickly to robotic technique where many of the same steps are repli-
cated. Conversely an open renal surgeon may find minimally invasive surgery chal-
lenging and transition to robotic partial nephrectomy may require considerable time.
Much of the training pathway experience is based around the daVinci platform. Over
the past couple of decades there has been continued development and formalisation
of both fellowship training and consultant proctoring. Modular training programs
for specific steps of complex procedures have been promoted by organisations such
as BAUS and can be extremely helpful in safely training robotic surgeon (Fig. 70.1).
70 Setting Up Robotic Surgery 395
1. Insertion ports 7. Dissection vas and seminal vesicles

2. Robot setup/bladder detachment 8. Posterior prostatic dissection
3. Pelvic node dissection 9. Apical dissection
4. Endopelvic fascia dissection 10.Urethro-vesical anastomosis
5. Ligation DVC 11.Full procedure
6. Bladder neck dissection
Fig. 70.1 An example of a modular training pathway for robotic prostatectomy
Robotic Theatre Team
Dedicated robotic surgical assistants have also become indispensable for many
units. A robotic assistant is required in addition to the scrub nurse for almost all
cases and therefore in simple terms of manpower a robotic assistant negates the
requirement for a second surgeon to be required at the bedside. This has benefits in
terms of training, allowing trainees / surgeons to concentrate on the console and
furthermore can facilitate safer and quicker surgery through consistency within
the team.
The rest of the theatre team including scrub nurses, ODP’s and anaesthetists are
also essential in maintaining a safe environment in theatre. Training needs to have
taken place so that correct positioning, robot docking, adequate clearance of arms
from the patient and emergency undocking are all understood by the whole team.
Practical Steps in Setting up a Robotic Service
In units planning to commence their first robotic procedure, some important steps
are required:
• Identification and training of surgeon: ideally a single surgeon should start a
program so that the learning curve is not prolonged. In many instances, however
a pair of surgeons working together alternating between assisting and being at
the console has proved effective.
• Visit an established unit performing the procedure so that patient positioning,
ports and sutures used along with patient warming, suction, calf compression etc.
is fitted around the operating table and how the anaesthetist performs eye protec-
tion can all be directly observed.
• The core team should ideally attend training days in a dry lab or preferably an
animal lab shortly before the first case.
• Having a dry run in the specific theatre a day or two prior to the first case to
ensure position of robot, operating table, anaesthetic machine etc. is worked out.
The anaesthetist and ODP are essential here. Furthermore, during the dry run all
cables, ports etc. can be confirmed.
396 R. Weston
• Patient selection is key. The patient should have simple anatomy, BMI <30, a
virgin abdomen, minimal co-morbidity and fully consented to the situation.
• An experienced mentor should be present who has approved the case and has the
ability of performing the case if necessary. The mentor should also make time
constraints clear, what to do if there is failure to progress (i.e. will they take over
the case or convert to open). Furthermore, have a senior colleague who can
objectively observe patient safety.
Investing in, identifying a team and training them are paramount to the rapid suc-
cessful initiation of a robotic program. The main aim of this endeavour is to bring
improvement to the patients while minimising risk. In the early days of the learning
curve this may mean equivalence in outcomes and so it is essential that all efforts
are taken to accelerate the learning curve. Comprehensive data collection must also
occur, so that outcomes such as length of stay and complications are recorded,
allowing swift action to be taken if required. The National Prostate Cancer Audit in
the UK has proven essential for benchmarking units around the country and has a
successful track record for positively intervening where units fall outside expected
parameters.
Dual console operating is feature that can assist in training surgeons in a similar
way to dual control pedals in a car where the instructor can take over controls. The
technology allows the mentor to take or give control of various arms during the
procedure and allows two surgeons to operate concurrently.
Further Reading
Hughes D, Camp C, O’Hara J, Adshead J. Health resource use after robot-assisted surgery vs open
and conventional laparoscopic techniques in oncology: analysis of English secondary care data
for radical prostatectomy and partial nephrectomy. BJU Int. 2016;117(6):940–7.
Yaxley J, Coughlin G, Chambers S. Robot-assisted laparoscopic prostatectomy versus open radical
retropubic prostatectomy: early outcomes from a randomised controlled phase 3 study. Lancet.
2016;388:1057–66.
Challacombe B, Ahmed K, Soomro N et al. BAUS robotic surgery curriculum – guidelines for
training https://www.baus.org.uk/_userfiles/pages/files/Publications/Robotic%20Surgery%20
Curriculum.pdf
Chapter 71
Principles of Tissue Transfer for Urologists
Patrick Gordon, Wai Gin Lee, and David Ralph
In urology, several operations use the principles of tissue transfer, from superficial skin
grafts to cover genitals to entire free flaps to reconstruct the genitalia. Tissue transfer
is also widely used in the majority of reconstructive procedures involving the urethra.
Grafts
Skin grafting (SG) involves harvesting of a free segment of skin from a donor site
and transplanting it to a distant recipient site (Fig. 71.1a). Grafts rely on their nutri-
ents and blood supply from the host tissue, so do not require vascular anastomosis.
As such they are limited in size and surface area due to their metabolic requirements.
The graft must lie within 1–2 mm of the recipient blood supply to gain the nutri-
tional support that is needed to become incorporated into its new location. The recip-
ient bed therefore must be healthy, free of infection and have a good blood supply.
Graft ‘take’ consists in four stages:
1. Adherence: strong fibrin crosslinks form between graft and recipient bed.
2. Plasmatic Imbibition: 0–72 h graft draws nutrition by capillary action through
graft bed. Can look oedematous and pale
3. Inosculation: 48–73 h vessels begin to anastomose and graft take colour.
4. Remodeling: Graft takes host site characteristics developing new vessels and
sweat glands.
P. Gordon (*)
St. James’s University Hospital, Leeds, UK
e-mail: patrick.gordon3@nhs.net
W. G. Lee · D. Ralph
University College Hospital, London, UK
e-mail: waigin.lee@nhs.net; david@andrology.co.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_71
398 P. Gordon et al.
b c
Fig. 71.1 above show (a) FTSG used on the penile shaft, with meshed SSG used on the scrotum.
Also shown are (b) the air dermatome and (c) the meshing device
71 Principles of Tissue Transfer for Urologists 399
Split Skin Grafts
Split skin grafts (SSG) are harvested using an air dermatome (Fig. 71.1b) in various
thickness (0.012–0.024 inches) and comprises entire epidermis and portion dermis.
The graft may be ‘meshed’, providing a lattice of graft material to cover larger areas
(Fig. 71.1c). The donor site is then dressed for 7–10 days. The graft is secured in
place with sutures and a compression dressings applied for 5–10 days to ensure
close contact with the host bed. The use of quilting sutures throughout the graft
promotes close contact to the graft bed and minimizes the development of underly-
ing haematoma that may lift the graft away from the host site.
Full Thickness Skin Grafts
Full thickness skin grafts (FTSG) are excised with a scalpel and contain all skin
components (epidermis, dermis, hair follicles, sebaceous glands) and are applied
using the same principles as SSG (Table 71.1).
Table 71.1 The advantages and disadvantages of split and full thickness skin grafts
Advantages Disadvantages
SSG Fast uniform take, can be meshed to cover large Contracture, structurally weak,
area, donor site heals fast and can be re-used maintains donor site pigmentation
FTSG Less contracture, growth potential, take on host Donor site defect, requires well
site characteristics. vascularised host bed.
Flaps
Flaps are larger areas of tissue with a higher metabolic demand than a skin graft.
They can be transferred with pedicle intact or as a free flap requiring an artery and
vein to be anastomosed. In urology, the main example of a free flap is the radial
forearm free flap (RAP) used in phalloplasty. Here the skin and subcutaneous tissue
is transferred on its pedicle (Fig. 71.2) for the artery to be anastomosed to the infe-
rior epigastric and veins to branches of saphenous using microsurgery to its new site
to form a phallus. The donor site is then closed with either SSG or FTSG from the
buttocks.
Flaps can be described in the following ways:
• Island flaps: There is no skin continuity at the base of the flap such that the donor
tissue is like an “island” on the end of a vascular pedicle.
• Peninsular flaps: There is skin continuity at the base of the flap and these flaps
are used for advancement, rotation or transposition.
• Random flaps: There is no identifiable vascular pedicle and are therefore
restricted in size and shape by the length to width ratio
• Axial flaps: There is a defined vascular pedicle, which result in the possibility of
creating a larger flap.
Fig. 71.2 A free RAP being elevated to demonstrate the vasculature required to facilitate anasto-
mosis onto a donor arterial supply and to provide venour drainage from the flap
71 Principles of Tissue Transfer for Urologists 401
Urethral Reconstruction
The urethra can be reconstructed by augmenting a stricture using free buccal or

lingual mucosa grafts (BMG & LMG), free grafts of full-thickness preputial skin,
other mucosae or pedicled flaps using prepuce, or locally-available penile or scro-
tal skin.
Mucosal grafting uses a measured strip of mucosa, approximating to the length
of the graft required, which is taken from the oral cavity or the undersurface of the
tongue leaving the underlying muscular tissue exposed. This tissue has thick epithe-
lium that is easily handled and sutured in place. The resulting oral wound can then
be left open, closed or partially closed, incurring minimal donor site morbidity. Fat
has to be stripped from the graft, reducing metabolic demand to improve graft
‘take’, and the B/LMG sutured in place with the same principles as for skin grafts.
As compression dressings cannot be applied when the graft is applied at a single
stage reconstruction, the graft has to be stitched to the host site, ‘quilted’, with
absorbable sutures to prevent separation of the graft from the underlying host tissue.
Single or multi-stage reconstruction is largely dependent upon the size of graft
required and the vascularity of the host graft bed site. Oral mucosal grafts, to all
intents and purposes, act in the same way as a FTSG and have the advantage over
free preputial grafts and skin flaps of being hairless, waterproof, structurally strong
and easy to handle. The donor site also regenerates so can be used on multiple occa-
sions, if necessary.
Grafts of bladder and bowel mucosa, and even tunica vaginalis, have been used
to reconstruct the urethra but are difficult to handle, have variable graft take as a
consequence of their ‘fragility’, and incur significant donor-site morbidity as a con-
sequence of their harvesting. They are only considered when preferable material is
unavailable for reconstruction.
With local flaps the blood supply lies within the thin subcutaneous layer imme-
diately under the skin, whilst there is also a deeper fascial layer, the “Dartos” layer,
which provides supporting vascularity. The development of an axial fascio-
cutaneous island flap, encompassing the superficial and deeper layers, and utilizing
locally available skin means that vascularized material can be mobilized and used to
augment the opened up urethra (Table 71.2). These types of flap are preferred when
anaesthesia is restricted to the use of regional techniques, when oral mucosa cannot
be used, or when the graft bed’s vascularity is compromised for any reason. The
principle disadvantage of flaps is that hair continues to grow in penile shaft or scro-
tal skin; this may become a nidus for stone formation, within the reconstructed
urethra, in the longer term.
Table 71.2 Skin flap types used urologically

Type Type Vascular pedicle Use
Pedicled Island Axial Dartos fascial flap based on Urethral
foreskin flap fascio- two dorso-laterally placed reconstruction
cutaneous vascular pedicles
Orandi flap Island Axial Dartos fascial flap Urethral
fascio- reconstruction
cutaneous
Scrotal flap Island Axial Dartos fascial flap Urethral
fascio- reconstruction
cutaneous
Intestinal Island Axial Various Augmentation and
flap substitution
cystoplasty
Ureteric replacement
Omental Peninsular Axial Right gastroepiploic vessels Fistula repair and
flap prevention
Martius flap Peninsular Axial Posterior labial vessels Fistula repair, urethral
support
Boari Peninsular Random NA Ureteric
bladder flap reconstruction
Further Reading
Grafts, local and regional flaps. JW Granzow, JB Boyd. In: M.Z. Siemionow and M. Eisenmann-
Klein (eds.), Plastic and reconstructive surgery, Springer specialist surgery series, Springer-
Verlag London Limited 2010.
Patino G, Zheng MY, Breyer BN, Cohen AJ. Skin grafting applications in urology. Reviews in
urology. 2019;21(1):8.
Part V
Technology Interventional
Chapter 72
Neuromodulation by Sacral Nerve
Stimulation
Katherine E. Burnett, Christopher D. Betts, and Emma L. Foster
Sacral neuromodulation (SNM) is a NICE approved treatment for urinary tract dys-
function, which uses low level electrical stimulation of the sacral spinal cord via an
electrode placed in the S3 foramen. The mechanism of action of SNM is not fully
understood, but evidence suggests it interferes with the afferent input to the sacral
spinal cord, inhibiting detrusor overactivity.
Background
The mechanism of action of SNM remains unclear despite over 20 years of use,
however it is thought to modulate spinal cord reflexes and brain involvement via
afferent signalling modulating bladder efferent activity at spinal or supraspinal lev-
els rather than a direct stimulation of the detrusor or sphincter muscles. It has been
long established from animal work that an increase in pelvic nerve afferent activity
can inhibit detrusor muscle activity.
In Fowlers’ (high tone non relaxing sphincter) syndrome, SNM may block the inhib-
itory effect of sphincter overactivity on the detrusor and enable voiding by inhibiting
the guarding reflex. On the basis of PET studies in women with retention, Fowler has
proposed that SNM may restore voiding by “resetting brainstem function.” Currently,
SNM is indicated in the treatment of refractory idiopathic detrusor overactivity and
non-obstructive urinary retention in women. There is developing evidence for its use in
some patients with neurogenic bladder dysfunction and painful bladder disorders.
K. E. Burnett · C. D. Betts · E. L. Foster (*)

Department of Urology, Salford Royal Hospital, Northern Care Alliance NHS Foundation
Trust, Salford, UK
e-mail: kate.burnett@nca.nhs.uk; chris.betts@nca.nhs.uk; Emma.foster2@nca.nhs

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_72
406 K. E. Burnett et al.
Test Implantation Procedure
At present, the test phase or percutaneous nerve evaluation (PNE) is the best means of
selecting patients most likely to gain from long-term SNM. In the test phase, a foramen
needle is passed into the S3 foramen traditionally under a general anaesthetic looking
for a motor response of large toe flexion and a characteristic contraction of the pelvic
floor, an ‘anal bellow’. More recent practice is to perform this stage under a local anaes-
thetic with the patients reporting a sensory response. The foramen is located with the
aid of surface markings and or boney landmarks with fluoroscopy if locally available.
A temporary electrode is passed through the foramen needle and connected to an
external pulse generator (EPG). The patient can adjust the strength of stimulation,
and they should complete frequency/volume charts and relevant symptoms score
questionnaires. The limitations of PNE include lead migration, discomfort from the
securing dressings, and the short testing period of 5–14 days.
Permanent Implantation Procedure
Long-term SNM involves the percutaneous insertion a self-anchoring tined lead

(Figs. 72.1 and 72.2) through the S3 foramen.
The motor responses are checked and fluoroscopy is used to guide the insertion
of the lead. The lead has four individual electrodes, and three should appear outside
the foramen. The lead is tunnelled to a pocket in the outer gluteal region and con-
nected to an internal pulse generator (IPG). Only bipolar diathermy can be used in
the presence of the tined lead and IPG.
Fig. 72.1 The tined lead

for percutaneous insertion
into a sacral foramen. Note
the four individual
electrodes at the distal end
of the lead
72 Neuromodulation by Sacral Nerve Stimulation 407
Fig. 72.2 Intraoperative

lateral sacral fluoroscopy
showing tined lead in
sacral foramen and
position of the four
electrodes
The physician sets the stimulation parameters within certain limits. In all sys-
tems the patient can adjust the IPG within the set limits using their handheld device.
The polarity of the four electrodes can be changed by the physician to produce dif-
ferent electrical fields. It may be necessary to try different programmes (combina-
tions of electrodes) to gain maximum symptomatic benefit.
A “two-stage” implantation procedure is sometimes employed if the PNE was
inadequate or difficult to site the test lead, this allows the test phase to be extended
to 4 weeks, and if successful only a small procedure is required to connect lead
to an IPG.
The battery life of the IPG depends on the stimulation parameters and is usually
5–8 years in a non-recharge battery. In recent years there has been the development
of recharge systems that requires the patients to recharge the battery wirelessly once
every 2–3 weeks, but allows a smaller implant IPG and a longer life of the device
(15 years) (Fig. 72.3).
Patients with SNM devices cannot have magnetic resonance imaging if they have
an older device implanted, however newer devices (generally implanted after 2019),
are MRI conditional, meaning that if the device is intact and the MRI department
are aware of the device it is likely safe. The Local MRI department can contact
implant centres and manufacturers for MRI information. All patients with devices
should not pass through the standard security gates or whole body scanners at bor-
der controls. If the patient walks close to a radio-frequency security antenna as used
in shops, then the stimulation parameters of some of the IPGs can be temporarily
changed.
408 K. E. Burnett et al.
Fig. 72.3 The Axonics

rechargeable IPG and
Patient handset (left) and
Medtronic non
rechargeable and
rechargeable IPGs and
Smart phone Handset
Complications of SNM include infection, lead breakage, lead migration, leg

pain, discomfort at the site of the IPG, and loss of efficacy. Explantation of the tined
lead may be complicated by lead breakage and retained lead fragments (which
would have implication for future MRI ability). Revision rates are up to 40% and
usually involve replacing the tined lead. SNM is free of the complications associ-
ated with major intra-abdominal surgery, does not require self catheterisation, and
can be readily reversed.
Results
About 50% of patients respond well to the PNE and go on to long-term SNM. Data
from controlled trials and case series indicate that approximately 80% of patients
who receive SNM for detrusor overactivity had improvement in their main symp-
toms at 3–5 years post implantation. There is a need for longer term outcome and
quality-of-life data. In one series of female retention, 70% of the women were void-
ing spontaneously at a mean follow-up of 7 years.
Further Reading
Bolton JF, Harrison SC. Neuromodulation 10 years on: how widely should we use this technique
in bladder dysfunction? Curr Opin Urol. 2009;19(4):375–9.
Paniker J, DasGupta R, Elneil S, Fowler CJ. Urinary retention. In: Fowler CJ, Panicker JN,
Emmanuel A, editors. Pelvic organ dysfunction in neurological disease. Cambridge: Cambridge
University Press; 2010. p. 293–306.
Siegel S, Noblett K, Mangel J, Griebling TL, Sutherland SE, Bird ET, Comiter C, Culkin D, Bennett
J, Zylstra S, Kan F, Thiery E. Three-year follow-up results of a prospective, Multicenter study
in overactive bladder subjects treated with sacral neuromodulation. Urology. 2016;94:57–63.
https://doi.org/10.1016/j.urology.2016.04.024. Epub 2016 Apr 27
Chapter 73
Principles of Extracorporeal Shockwave
Lithotripsy (ESWL)
Robert C. Calvert
ESWL uses acoustic energy to achieve stone fragmentation. All lithotripters have
three elements to exert their clinical effect: a shockwave generator which produces
and focuses the shock, a means of coupling the shockwave to the patient, and an
imaging modality to target the shockwave onto the stone.
Introduction
All lithotripters have three elements to exert their clinical effect: a shockwave gen-
erator which produces and focuses the shock, a means of coupling the shockwave to
the patient, and an imaging modality to target the shockwave onto the stone.
Physics of Lithotripsy
Lithotripsy depends upon the transmission of sound energy. Sound has compressive
and tensile phases, and in liquid, it affects the density, pressure, and particle velocity
of the fluid it is in. The velocity of the wave influences its energy, and dissipation of
the acoustic energy is dependent upon the acoustic impedance of any structures it
comes into contact with. The ideal shockwave for lithotripsy has a rapid peak pres-
sure rise, followed by a slower negative pressure. A typical time-against-pressure
curve is shown in Fig. 73.1 with the pressure wave lasting <10 μs and producing a
peak pressure of 30–199 mPa.
R. C. Calvert (*)

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_73
410 R. C. Calvert
Fig. 73.1 An Pmax

extracorporeal lithotripsy
shockwave. The physical
Pressure
characteristics of the
shockwave used, clinically
in lithotripsy. Pmax is the
maximum pressure, Pr is
the negative peak pressure,
and ∆t the pressure
rise time Time
∆t Pr
All lithotripters have a focusing mechanism to concentrate the acoustic energy

into a focal zone in which we aim to keep the stone in for as long as possible. This
reduces damaging effects on the surrounding tissues. A small focal zone increases
the energy but makes targeting more difficult as renal and upper ureteric stone move
by several cms with every respiratory cycle. In clinical lithotripsy, this zone can be
from a few millimeters to centimeters in size and is normally ellipsoidal in shape
with its longest dimension along the axis of the shock wave. Some lithotripsy
machines allow you to vary the size of the focal zone.
Theoretical Mechanisms of Stone Fragmentation
A variety of mechanisms may cause shattering of a stone during lithotripsy. The

major factors influencing fragmentation will depend on the constitution of the stone,
its surrounding medium, and the type of lithotripter used. The hypotheses of litho-
tripting effects are shown in Table 73.1.
73 Principles of Extracorporeal Shockwave Lithotripsy (ESWL) 411
Table 73.1 The hypotheses of stone fragmentation (Rassweiler et al. 2011)

Hypothesis of
stone
fragmentation Proposed mechanism Prerequisites Type of action Comments
Tear and shear Pressure gradients Shock wave Hammer-like Only relevant
forces resulting from smaller in space action resulting in for small focal
(super- impedance changes extension than a crater-like zones
focusing) at the front of the the stone fragmentation at
stone and the distal both ends of the
surface with pressure stone
inversion
Cavitation Negative pressure Low viscosity of Microexplosive More
waves induce a surrounding erosion, principally important
collapsing cavitation medium at the proximal end during stone
bubble at the stone’s of the stone comminution
front surface
Spallation Reflected tensile Shockwave Breaking the stone Only relevant
wave at distal surface smaller in space from the inside for small focal
of the stone with extension than similar to freezing zones
maximum tension the stone water in brittle
there material
Quasistatic Pressure gradient Shockwave is Nutcracker-like Only relevant
squeezing between broader than the action for large focal
circumferential and stone shockwave zones
longitudinal waves velocity is lower
results in squeezing in the water than
of the stone in the stone.
Dynamic Shear waves initiated Parallel travelling Nutcracker-like Best theory to
squeezing at the corner of the of longitudinal action which explain
stone are reinforced waves shockwave “splits” the stone lithotripsy
by squeezing waves velocity is lower
along the stone’s in the water than
length in the stone
Shockwave Generators
Three types of shockwave generator have been used clinically.

1. Electrohydraulic shockwave generators have a storage capacitor which dis-
charges an ultra high tension and ultra short potential difference, across a gap
separating a submerged anode/cathode complex. This discharge causes a spark
that generates a bubble pulse and leads to an expanding underwater shockwave.
The shock is produced at a first focal zone (F1) and focused, by a hemi-ellipsoid
reflecting parabola, onto a second focal zone (the F2). Electroconductive shock-
wave generators are a modification of this principle but employ a highly conduc-
tive electrolytic solution during shockwave generation.
412 R. C. Calvert
2. Electromagnetic shockwave generators work on the same principle as an acous-

tic speaker. The generator is made of two metal plates separated by an insulator
and backed by a ceramic base. A storage capacitor discharges, causing an ultra
short magnetic repulsion between the two plates with resultant shockwave away
from the ceramic base. A flat shockwave, of an intensity proportional to the
applied current, travels at the speed of sound and is focused by a convex acoustic
lens onto a focal point (F1). A common variant is where the electromagnetic coil
is placed in a long cylinder firing the shock waves horizontally and which are
then reflected to the focal point. This configuration allows in-line monitoring of
the stone with an ultrasound probe.
3. Piezoelectric shockwaves are generated by the mechanical force resulting from
an electrical field being applied to a quartz crystal. Multiple piezoelectric crys-
tals are caused to deform synchronously to produce many different frequencies
of sound energy. As the crystals are arranged in a “dish-like array,” inclined
inwards, the summation of the different wave forms focuses the lithotripsy
energy at the point at which all the wave forms coalesce (the F1 of the dish).
Coupling
The shockwave energy can be substantially degraded if there is not good coupling
of the shockwave probe to the skin avoiding air-bubbles. The original HM-3 litho-
tripter required the patient to be emersed in a bath of water. In some lithotripsy
machines, degassed water is still used a the conductive medium (albeit with emer-
sion) but ultrasound gel is more commonly used. Avoiding placing probes on skin
folds and shaving hairy backs and reducing unnecessary patient movement can help
improve coupling.
Imaging
Accurate targeting of the shockwave on the stone is essential for effective lithotripsy.
Both X-ray screening with a C-arm or ultrasound guidance may be used and some
operators use a combination of both. When using X-ray, the stone will need to be
located in 2 planes to ensure that the shock waves are delivered at the correct depth.
Respiratory movement makes targeting challenging, and lithotripters with larger focal
zones may produce better results as fewer shocks are wasted. Periodic monitoring of
positioning is important to ensure that the patient has not moved. This can be achieved
with X-ray screening or either in-line or off-line ultrasound. Some operators use the
duplex function on their ultrasound to give audible feedback of when the shockwaves
are hitting the stone. Some lithotripsy machines have virtual reality localization func-
tions to help assess position both for X-ray and ultrasound. Ultrasound has the advan-
tage of not using radiation but some ureteric stones can be difficult to visualise.
73 Principles of Extracorporeal Shockwave Lithotripsy (ESWL) 413
Factors Influencing the Efficacy of ESWL
Patient selection is key. Patients with a skin to stone distance >15 cm (i.e. obesity)
have lower stone clearance. Anatomical considerations should also be considered,
especially in lower pole stones, such as infundibular height, width and infundibulo-
pelvic angle. As these factors increase, the efficacy of ESWL reduces.
Further Reading
Cleveland RO, McAteer JA. The physics of shock wave lithotripsy. In: chapter 38 in Smiths text-
book of endourology. Hamilton: BC Decker Inc.; 2007.
Rassweiler JJ, Knoll T, Köhrmann K-U, McAteer JA, Lingeman JE, Cleveland RO, Bailey MR,
Chaussy C. Shock wave technology and application: an update. Eur Urol. 2011;59:784–96.
Chapter 74
How to Carry Out Shockwave Lithotripsy
(SWL)
Robert C. Calvert
Shockwave lithotripsy (SWL) is an effective and noninvasive modality for the

treatment of urolithiasis. Stone-free rates vary between 50% and 95%. The key steps
to success are appropriate patient selection and careful treatment delivery.
Introduction
Extracorporeal shockwave lithotripsy (SWL) is an effective and non-invasive modal-

ity for the treatment of urolithiasis. Stone-free rates vary between 50% and 95%. The
key steps to success are appropriate patient selection and careful treatment delivery.
Patient Selection: Which Modality of Treatment?
The decision-making process for managing any patient with urolithiasis is based on con-
sideration of stone, patient / clinical (including patient choice), renal and service factors.
SWL is an effective treatment for ureteric and renal stones under 10 mm. Having
hot lithotripsy available (ideally in less than 48 hours) for ureteric stones that are
unlikely to pass reduces the number of patients needing a general anaesthetic emer-
gency ureteroscopy and reduces the risk of patients going home with ureteric stents.
(NICE guidelines on Renal and Ureteric stones 2019).
SWL is also an option to be considered for 10–20 mm renal and ureteric stones
although the success rates are lower compared with ureteroscopy. Lithotripsy would
R. C. Calvert (*)

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_74
416 R. C. Calvert
not be a standard treatment choice for stones >20 mm where percutaneous nephro-
lithotomy (PCNL) should be considered.
SWL is contraindicated in pregnancy, untreated coagulopathy, untreated urinary
tract infection, abdominal aortic or renal artery aneurysms in the shockwave’s path,
or severe skeletal malformations.
There are several key additional factors which influence the efficiency of SWL:
stone density, stone location, renal anatomy, and body habitus. The density of a
stone, on non-contrast CT, may help predict its susceptibility to SWL. Densities of
>1000 HU have lower clearance rates in some series. About 50% of renal stones are
located in the lower pole. Stone fragments are less likely to clear if there is a long
narrow infundibulum to the calyx that the stone is sitting in or if there is a very acute
infundibulo-pelvic angle. There are some reports of lower clearance rates in obese
patients. Stone localization can become difficult, and the skin-to-stone distance may
exceed the focal length of the lithotripter. Inserting a double J stent does not improve
overall stone clearance rates but may reduce the risk of steinstrasse where litho-
tripsy is being used for a large renal stone.
dvice in Specific Situations and Potential Complications

A
of Treatment
Specific advice should be given prior to treatment regarding antiplatelet drugs (dis-
continue 7–10 days pre-treatment), oral anticoagulants (stop and give low molecu-
lar weight heparin in selected patients), implanted defibrillators, pacemakers, or
neurostimulators when specialist input is required.
Complications may be common—bleeding, infection, pain, skin bruising, need
for repeat treatments, treatment failure, or occasional fragments causing obstruction
potentially requiring intervention, and severe infection. Renal haematoma is a less
common but potentially more serious complication.
Day of Treatment: Pre-treatment Protocol
Patients should be managed using an ESWL-specific pathway to minimise the poten-

tial for errors and oversights. Consent must be confirmed along with the site and side
of the stone being treated, antiplatelet / anticoagulant cessation (including INR where
appropriate), and allergy status. Baseline observations are recorded and a urine dip-
stick performed. Patients must be questioned regarding symptomatic urinary infec-
tion, which may determine the need for either antibiotic cover or treatment deferral.
Antibiotic cover should be considered if the urine dipstick is positive for leucocytes
and nitrites in an asymptomatic patient or in patients at a high risk of infection.
Analgesia improves treatment efficacy by reducing pain-induced movements and
excessive respiratory excursions. Typically, 100 mg of diclofenac is given per
74 How to Carry Out Shockwave Lithotripsy (SWL) 417
rectum 30 minutes before treatment along with an opiate. Intravenous alfentanil

boluses 200–400mcg boluses are often used however this requires close medical
monitoring. Many units manage most patients without IV analgesia: fentanyl loz-
enges are used in some units. Younger children would normally have SWL carried
out under general anaesthesia.
SWL Delivery
Outcomes from SWL are operator dependent. The key factors influencing outcome
are related to positioning / localisation, coupling and shock delivery.
Positioning depends on the machine used with most renal and ureteric stones
being treatable supine. The prone position may be used for lower ureteric stones,
preferably with some urine in the bladder, to displace gaseous bowel loops. Some
operators use a supine trans-gluteal approach for distal ureteric stones.
Stone localisation may be achieved using fluoroscopy or ultrasound, depending
upon local expertise and stone position. Fluoroscopic localisation is usually in three
planes with the use of appropriate radiation protection measures. Real-time ultra-
sound reduces radiation dose and enables localisation throughout treatment. X-ray
and ultrasound localisation may be difficult due to body habitus, anatomy, the pres-
ence of bowel gas, and excessive respiratory movement.
Coupling of the lithotripter to the patient is achieved using ultrasound gel or
water. When gel is used, it should be warmed and applied with a spatula to avoid
bubbles which reduce shockwave transmission.
Prior to, and during, lithotripsy, patient monitoring must be instituted. Shock
delivery protocols vary. Treatment should be commenced at low power (∼25% of
maximum) for the first few minutes. Many operators then have a short pause and
then resume gradually ramping up the power. The voltage ramping and pausing
have been shown on animal models to cause renal vasoconstriction and reduce the
risk of renal injury. The objective is to deliver a fixed amount of energy to the stone,
typically 1000 J for renal stones and 1400 J for ureteric stones. Shock frequency can
also be optimised. Reducing the frequency improves clearance, yet this benefit must
be balanced against the resulting longer treatment. Previously shocks were deliv-
ered at 2 Hz, however now 1 Hz is considered optimal.
SWL should be discontinued when there is persistent hypertension, uncontrolled
pain, localisation failure, or complete fragmentation is observed.
Post-treatment Management
Post-SWL, a standard protocol should be followed. Patients are generally observed

for a least 30 minutes, although this will be longer if IV opiates, sedation or general
anaesthesia have been used.
418 R. C. Calvert
Patients are discharged home when they feel well with advice regarding what to
expect, when to seek medical advice, and who to contact. They are given appropri-
ate analgesia and antibiotics where indicated. A follow-up appointment should be
arranged, typically in 1–2 weeks for renal stones, allowing for retreatment follow-
ing a 4-week interval. Ureteric stones can be retreated at shorter intervals; thus, it is
advisable to schedule their next session directly where it is felt necessary.
Further Reading
Renal and ureteric stones: assessment and management, https://www.nice.org.uk/guidance/ng118.

Skolarikos A, et al. European Association of Urology Guidelines on Urolithiasis, www.uroweb.
org. 2022;
Madaan S, Joyce AD. Limitations of extracorporeal shock wave lithotripsy. Curr Opin Urol.
2007;17(2):109–13.
Srisubat A, et al. Extracorporeal shock wave lithotripsy versus percutaneous nephrolithot-
omy versus retrograde intrarenal surgery for kidney stones. Cochrane Database Syst Rev.
2009;7(4):CD007044.
Chapter 75
Novel Technologies for BPH
Craig Jones
TURP has remained the gold standard approach in the surgical management of
bladder outflow surgery in men. However, in recent years, there has been an increas-
ing popularity of novel minimally invasive surgical techniques (MIST), amongst
other surgical techniques, aiming to reduce complications and morbidity in BPH
surgery with demonstrable improvements in flow rates and symptom scores.
Prostate Enucleation
A number of technologies can be applied to the endoscopic removal of prostate tis-

sue by enucleation. The most common technique utilises holmium laser (HoLEP),
however use of thulium laser (ThuLEP) and bipolar diathermy (BiPolEP) have
been reported. HoLEP typically uses a 60–100 W holmium laser (wavelength
2140 nm) with power settings 2–2.4 J at 25–50 Hz. Tissue coagulation and necrosis
is limited to 3–4 mm, enough to obtain adequate haemostasis.
The most common technique for enucleation of the prostate is using the Gilling
technique; three longitudinal incisions with systematic removal of the median lobe
and the two lateral lobes in a retrograde fashion.
Further Reading: Gilling, P.J. et al. Randomized trial comparing HoLEP
vs TURP.
C. Jones (*)
e-mail: craig.m.jones@doctors.org.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_75
420 C. Jones
Photo-Selective Vaporisation of the Prostate (PVP)
LASER technology can also be utilised to vaporise prostate tissue widening the
channel for urine flow. Its use is often limited to prostates that are mild to moder-
ately enlarged however experienced centres have reported treating larger prostates.
Potassium-titanyl-phosphate (KTP) generates a laser frequency with a wavelength
of 532 nm which is in the green electromagnetic spectrum and commonly referred
to as “Greenlight laser”. The energy with a penetration depth of only 0.8 mm is
selectively absorbed by haemoglobin and not at all by water, resulting in vaporisa-
tion of tissue with minimal charring.
Further Reading: GOLIATH Study.
Prostate Artery Embolisation
Prostate artery embolisation (PAE) is a minimally invasive treatment performed

under local anaesthetic. Under fluoroscopic guidance vascular access typically
through the right or left femoral artery permits catheterisation of small prostatic
arteries. Thus, facilitating super-selective embolisation using agents such as polyvi-
nyl alcohol (PVA) containing microparticles with the aim to reduce blood supply to
the prostate gland leading to necrosis and volume reduction.
Further Reading: ROPE Study.
Minimally Invasive Techniques
A number of novel minimally invasive surgical techniques have demonstrated effi-

cacy in the treatment of benign prostatic hypertrophy (BPH). In carefully selected
patients these can provide an improvement in flow rate and symptom scores with the
advantage that some can be administered under local anaesthetic and with more
favourable side effects, particularly in relation to sexual function.
The novel technologies outlined include Urolift® (Teleflex), Rezum™ (Boston
Scientific), iTind (Olympus) and AQUABEAM® (PROCEPT BioRobotics Inc).
Prostatic Urethral Lift—Urolift®
Teleflex
Prostatic Urethral Lift (PUL) can be performed under local or general anaesthetic.
The lateral lobes of the prostate are compressed by small suture-based implants
which are inserted under cystoscopic guidance. This results in widening of the pros-
tatic urethral opening which improves the flow of urine.
75 Novel Technologies for BPH 421
Fig. 75.1 UroLift Implant
Urethral
End-Piece
PET Suture
Capsular Tab
The implant consists of three components: a nitinol capsular tab, a polyethylene

terephthalate (PET) monofilament suture and a stainless-steel urethral end-piece.
See Fig. 75.1. The implants should be placed 1.5 cm distal to bladder neck at 1 cm
intervals at the 2–3 o’clock or 9–10 o’clock positions. Typically, 4 to 6 implants are
required per treatment to open the anterior channel from the bladder to the pros-
tatic apex.
Further Reading: BPH6 Study, L.I.F.T Stdy.
Convective Water Vapour Energy Ablation—Rezum™
Boston Scientific
Convective water vapor therapy delivered directly into the transitional zone of the
prostate under general or local anaesthetic leading to cell death and a reduced pros-
tate volume.
Under direct vision, a narrow sheath is inserted via the urethra. A needle is
deployed at the tip of the scope through the urethral urothelium into the prostate
parenchyma. Water vapour (steam) at a temperature of 103 °C generated through
application of a radiofrequency current against an inductive coil in the hand-
piece, is injected via the needle through multiple emitter holes for 9 seconds
supplying convective heat into the prostate tissue. Cell membranes are dena-
tured leading to immediate cell death and necrosis with a subsequent reduction
in tissue volume (Fig. 75.2).
Further Reading: McVary et al. Randomised controlled double-blind trial.
422 C. Jones
Fig. 75.2 Rezum™ device
Temporarily Implanted Nitinol device—iTind
Olympus
The device is placed into the prostatic urethra in a folded configuration and held in
position by the anchoring leaflet. This can be done using either a rigid or a flexible
cystoscope under local anaesthetic. During the treatment (between 5–7 days) the
device expands, exerting gentle pressure at three points (5,7 and 12 o’clock) leading
to localised ischaemia thus widening the bladder opening and allowing urine to flow
more freely. After the treatment the device is then completely removed.
Unlike other treatments it does not involve any the heating or removal of pros-
tatic tissue, and there is no permanent implant (Fig. 75.3).
Further Reading: MT-02 Study.
d e
b
Fig. 75.3 iTind device. (iTind device: a—iTind device (expanded configuration shown); b—
Anchoring leaflet; c—Guidewire; d—Introducer sheath; e—Retrieval snare)
Aquablation—AquaBeam Robotic System
PROCEPT BioRobotics Inc.
This technique involves an USS-guided, robotically executed water jet to the surgi-
cal plan that precisely ablates prostatic tissue. A bi-planar transrectal ultrasound
(TRUS) probe is positioned rectally and the prostate tissue to be ablated mapped.
The mapping software allows for changes in depth of up to 24.3 mm and angle of
resection up to 225 degrees, with inbuilt safety mechanisms to only ablate the
mapped tissue and protect the external sphincter. Real-time TRUS allows monitor-
ing whilst the transurethral robotic handpiece produces a high velocity stream of
saline which automatically adjusts the flowrate according to the depth of penetra-
tion required. With a procedural time of approximately 4 minutes, the robotic tech-
nology facilitates fast, consistent and reproducible resections. Following dissection,
haemostasis is achieved endoscopically using electrocautery or with gentle catheter
balloon traction.
The below table summarises the available MIST options (Table 75.1).
Further Reading: Gilling P et al. Initial clinical experience of Aquablation.
424 C. Jones
Table 75.1 Summary of novel minimally invasive surgical techniques (MIST)

Treatment UroLift Rezum iTind AQUABEAM
Indications Symptomatic BPH Symptomatic Symptomatic Symptomatic
Men >45 BPH BPH BPH
PV <100 cc Men >50y Men >50y Men >45y
PV 30–80 cc PV <75 cc PV 30-80 cc
Contraindications Active urinary tract Active urinary Active urinary Active urinary
infection tract infection tract infection tract infection
Urethral conditions Artificial urinary Artificial urinary Neurogenic
that may prevent sphincter sphincter or bladder
insertion of Penile prosthesis other urethral Urethral
delivery system implant stricture
into bladder Previous
Urinary prostatic surgery
incontinence due to Obstructive
incompetent median lobe
sphincter Post void
Current visible residual
haematuria >250mls
Anaesthetic LA / GA / spinal LA / GA / spinal LA GA / spinal
Catheterisation rate 20% 90% <1% 100%
catheter duration 0.9–1.2 days 3.4 days NA 1–4 days
Side effects Dysuria 35.7% Dysuria 17% Dysuria 23% Dysuria 10%
Haematuria 27.1% Haematuria 12% Haematuria 14% Haematuria
Pelvic pain 18.6% Frequency 6% Blood
Urgency 10.0% transfusion
Incontinence 8.9% <1%
Retention 5.7% UTI 7%
Nocturia 5.0% Retention 5%
Stricture <2%
Incontinence
5%
Ejaculatory or None Haematospermia None Ejaculatory
erectile 6% dysfunction
dysfunction 10%
Retreatment rate 13.6% after 4.4% after 4 years 8.6% after 6% after
5 years11 3 years 5 years
BPH, benign prostatic hyperplasia; PV, Prostate Volume; LA, local anaesthetic; GA, general anaes-
thetic; NA, not available
Further Reading
Gilling PJ, et al. Long-term results of a randomized trial comparing holmium laser enucle-
ation of the prostate and transurethral resection of the prostate: results at 7 years. BJU Int.
2012;109:408–11.
Thomas JA, et al. A Multicenter randomized noninferiority trial comparing GreenLight-XPS laser
vaporization of the prostate and transurethral resection of the prostate for the treatment of benign
prostatic obstruction: two-yr outcomes of the GOLIATH study. Eur Urol. 2016;69:94–102.
Ray AF, et al. Efficacy and safety of prostate artery embolization for benign prostatic hyperplasia:
an observational study and propensity-matched comparison with transurethral resection of the
prostate (the UK-ROPE study). BJU Int. 2018;122:270–82.
Gratzke C, et al. Prostatic urethral lift vs transurethral resection of the prostate: 2-year results of the
BPH6 prospective, multicentre, randomized study. BJU Int. 2017;119:767–75.
Roehrborn CG, et al. Five year results of the prospective randomized controlled prostatic urethral
L.I.F.T. study. Can J Urol. 2017;24:8802–13.
McVary KT, et al. Minimally invasive prostate convective water vapor energy ablation: a
Multicenter, randomized, controlled study for the treatment of lower urinary tract symptoms
secondary to benign prostatic hyperplasia. J Urol. 2016;195:1529–38.
Kadner G, et al. Second generation of temporary implantable nitinol device (iTind) in men with
LUTS: 2 year results of the MT-02-study. World J Urol. 2020;38:3235–44.
Gilling P, Reuther R, Kahokehr A, Fraundorfer M. Aquablation – image-guided robot-assisted
waterjet ablation of the prostate: initial clinical experience. BJU Int. 2016;117:923–9.
Chapter 76
Ablative Therapies
Nikhil Mayor and Taimur T. Shah
Ablative therapies consist of high intensity focused ultrasound, cryotherapy, radio-

frequency ablation, irreversible electroporation and laser. They aim to treat urologi-
cal cancers effectively while minimising side effects compared to those of radical
surgery. However, long-term data on their oncological efficacy is lacking.
High-Intensity Focused Ultrasound (HIFU)
HIFU waves at frequencies of 1 to 3.5 MHz are emitted from a high-powered trans-
ducer producing temperatures of 90 °C at the focal point but leave intervening tis-
sues unharmed. Tissue ablation occurs through two mechanisms: thermal energy
and acoustic cavitation. Thermal energy, from friction between oscillating cellular
components, leads to protein denaturisation at temperatures >43 °C. Acoustic cavi-
tation causes cell necrosis via high-amplitude pressure oscillations generating gas
bubbles which oscillate and collapse rapidly resulting in coagulative necrosis.
Prostate cancer can be treated per rectum using a trans-rectal transducer to pro-
duce an array of ellipsoid-shaped target lesions covering the whole of the prostate.
The therapy is controlled by real time ultrasound with both the ultrasound and HIFU
transducers built into a single trans-rectal probe. Trans-urethral devices also exist
but are not commonly used. The treatment is delivered as a day case procedure, tak-
ing up to 2–3 h to complete. It can be used to treat primary or recurrent prostate
cancer in either a whole-gland or, more commonly, in a focal manner. Complications
N. Mayor · T. T. Shah (*)

Imperial College London (ICL), Charing Cross Hospital, Imperial College Healthcare NHS
Trust, London, UK
e-mail: nikhil.mayor@nhs.net; taimur.shah@doctors.org.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_76
428 N. Mayor and T. T. Shah
Fig. 76.1 High Intensity Focussed ultrasound (HIFU)—Intra-operative ultrasound image with
superimposed shape of HIFU pulse
include urinary tract infection (<5%) and retention (<1%). Urosepsis and rectoure-
thral fistulae are recognised complication but with modern techniques are very rare
sequelae (Fig. 76.1).
Cryotherapy
Third-generation cryotherapy, uses the Joule-Thomson effect to cause freezing to

achieve the therapeutic effect, usually via a dual-gas system with argon and helium, in
“freeze-thaw” cycles. High-pressured argon is circulated to a cryoprobe tip at −186 °C,
followed by rapidly expanding helium producing the thawing mechanism. Fourth-
generation systems omit the helium and use a heating element built into the needles.
Cell death is multifactorial consisting of freezing of intracellular fluid, dehydra-
tion, direct shearing forces from ice crystal formation, bursting of cells during rapid
thawing, and a cryo-immunological effect. Histological analysis shows central
necrosis with a surrounding ice rim. Cryotherapy is most effective at temperatures
below −40 °C and when at least two freeze-thaw cycles are implemented.
Like HIFU, cryotherapy can be used in prostate cancer in a focal or whole-gland
manner and both in primary and recurrent disease. A transperineal approach under
Trans-Rectal Ultrasound (TRUS) guidance is used for the insertion of the cryo-
probes. Thermocouples (needles with temperature sensors) are placed to monitor
temperatures within the target lesion and avoid damage to critical structures such as
the rectum. A benefit of cryotherapy is that the growing ice-ball can be seen on the
live TRUS images. Good medium-term oncological and functional outcomes have
been reported in focal therapy cohorts. Rectourethral fistulae are rare.
Cryotherapy also offers an effective alternative to partial nephrectomy in those
with small renal masses, particularly in the elderly/comorbid. Two to eight probes
are inserted via a percutaneous CT-guided or laparoscopic approach. The ice ball
should cover the entire tumour with an additional 5–10 mm margin as the leading
edge of the ice is not cytotoxic. The technique is limited by the time taken to
76 Ablative Therapies 429
Fig. 76.2 Cryotherapy—Top—images of various lengths of iceball’s; Bottom—Live images of

renal cryotherapy. (Images courtesy of Galil medical)
produce an adequate sized ice ball and the need for multiple punctures sites. The
main complication is bleeding, correlating with number of puncture sites, tumour
size, and age (Fig. 76.2).
Radio-Frequency Ablation (RFA)
RFA involves delivery of alternating electrical current into tumour at the lower end
of the radiofrequency range (400–600 kHz). Ionic agitation results in frictional
heating of tissue in the immediate vicinity of the electrodes. Temperatures of
60–90 °C lead to irreversible protein denaturation and coagulation necrosis.
RFA is also used for small renal masses in those unfit for surgery. Oncological
outcomes are similar to partial nephrectomy. Immediate post-ablation CT is per-
formed. Most common complications are nerve and urothelial injury, with ure-
teric/calyceal injuries more likely in centrally-located tumours. Others include
pain and paraesthesia reported in <5% of patients. Urine leak, bowel and liver
injury are rare.
430 N. Mayor and T. T. Shah
Interstitial radiofrequency ablation needles can be passed transurethrally into the

lateral lobes of the prostate to treat benign prostatic hyperplasia (BPH). A high
recurrence rate of transurethral needle ablation (TUNA) and the rise of more effec-
tive minimally-invasive approaches to BPH management has led to its decrease in
popularity and it is no longer recommended.
Irreversible Electroporation (IRE)
IRE works by formation of nanopores in the cell membrane leading to increased

permeability, disruption of osmotic balance, and consequently apoptosis. High volt-
age (1200–3000 V) pulses target a tumour through needle electrodes placed in the
surrounding tissue. Unlike RFA and HIFU, the technique allows predominantly
nonthermal ablation.
In prostate cancer, the target lesion is identified with TRUS and 19G monopolar
IRE electrode needles are inserted transperineally. Electrical pulses can trigger
muscle contraction therefore deep muscle relaxants are required. An initial pulse
test is performed to test for muscle paralysis followed by eight sets of ten pulses
lasting 70 ms at a current of 20–40A. Mild haematuria, dysuria, urinary tract infec-
tions, urgency, and temporary incontinence are common. Retrospective and early-
phase studies indicate acceptable short-term functional and oncological outcomes.
IRE remains investigational for renal masses. The procedure may be performed
intraoperatively, laparoscopically, or percutaneously under the control of CT or
ultrasound.
Its nonthermal nature means it may be advantageous in tumours close to the renal
hilum but experience is limited.
Laser-Targeted Therapies for Prostate Cancer
Laser Interstitial Thermotherapy (LITT)
This thermal ablation technique is applied with a laser fibre and by raising the tem-
perature > 60 °C results in direct focused cell death. One or two laser fibres are
placed transperineally with a brachytherapy template, with thermocouple probes at
the ablation boundary and near critical structures. Long-term evidence is lacking
(Fig. 76.3).
76 Ablative Therapies 431
Radial Laser Applicator Diffuser Laser Applicator
Fig. 76.3 Radial and Diffuse laser applicator (Courtesy of Clinical Laserthermia Systems AB)
Photodynamic Therapy (PDT)
Low-power laser or LED fibres in plastic catheters are inserted into the prostate vascu-
lature under TRUS or MRI guidance, minutes after administration of an intravenous
photosensitiser. Tissue ablation occurs in the presence of endogenous oxygen through
photosensitised generation of reactive oxygen species leading to apoptosis and necrosis.
The complex interaction between tissue, light, oxygen, and the photosensitiser means
dosimetry can be imprecise. Penetration of light through tissues is also limited and has
inter-patient variability. Evidence has shown acceptable results in low-risk disease.
Further Reading
1. Reddy D, Peters M, Shah TT, et al. Cancer control outcomes following focal therapy using
high-intensity focused ultrasound in 1379 men with nonmetastatic prostate cancer: a multi-
institute 15-year experience. Eur Urol. 2022;81(4):407–13.
2. Valerio M, Cerantola Y, Eggener SE, et al. New and established Technology in Focal Ablation
of the prostate: a systematic review. Eur Urol. 2017;71(1):17–34.
3. Salagierski M, Wojciechowska A, Zając K, et al. The role of ablation and minimally invasive
techniques in the Management of Small Renal Masses. Eur Urol Oncol. 2018;1(5):395–402.
Chapter 77
Principles of Radiotherapy
Martin Swinton and Andrew Hudson
Radiotherapy is a key pillar in the management of cancer, with over half of all can-
cer patients receiving it as part of their cancer treatment. It is used as organ-preserv-
ing treatment in curative settings, as an adjunct to surgery, and in palliative settings
to relieve symptoms.
Introduction
All radiotherapy works on the basis that DNA damage from ionising radiation
causes mitotic catastrophe to kill dividing cancer cells and cause tumour regression.
Radiation-induced mitotic catastrophe also damages normal cells, so a crucial com-
ponent of radiotherapy delivery is limiting the radiation dose (measured in Gy) to
normal tissue whilst maintaining a tumouricidal dose to the cancer. In addition,
biological differences between tumour and normal tissue are exploited to maximise
the therapeutic ratio between normal and tumour tissues.
Radiotherapy Regimens and Fractionation
Without modern technology to direct radiation fields, the simplest approach to

reduce normal tissue damage is to split the total radiation dose into smaller daily
treatments given over several weeks (fractionation). This harnesses normal tissue’s
enhanced ability to repair DNA damage compared to cancer cells, so that higher
total doses can be tolerated. Therefore ‘traditional’ radiotherapy doses per treatment
(per fraction) are low and established around 2Gy.
M. Swinton · A. Hudson (*)

Christie Hospital NHS Foundation Trust, Manchester, UK
e-mail: martin.swinton@nhs.net; andrew.hudson8@nhs.net

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_77
434 M. Swinton and A. Hudson
Technological advances in the last two decades have allowed better normal tissue
avoidance and the use of higher doses per fraction (hypofractionated regimens) in
which radical treatments are given in fewer fractions (eg. 4 rather than 7 weeks) of
higher doses per fraction. Current trials are investigating Stereotactic Ablative Body
Radiotherapy (SABR) in prostate cancer which utilise even higher doses (>7 Gy)
per fraction delivered in 5 or fewer fractions. Hypofractionation is more convenient
for patients, cost-effective, and often more biologically effective. Palliative radio-
therapy requires a lower total radiation dose for its effect and so is usually given
with 5 treatments across 1 week or as a single treatment.
External Beam Radiotherapy
Modern radiotherapy machines contain a linear accelerator, which produces high

energy electrons and collides them into a tungsten target producing a beam of high
energy photons (gamma radiation). The photon beam emerges from a head in the
mobile portion of the machine called the gantry. The patient lies on a flat couch around
which the gantry can rotate allowing treatment delivery from any angle. Lead leaves
are positioned within the gantry head to absorb the radiation in complex shapes to
shield normal tissue areas. As technology has improved, these lead leaves have become
thinner with better resolution to allow finer control of the intensity of the beam allow-
ing more complex conformal shapes and intensity-modulated radiotherapy (IMRT).
Radiotherapy Treatment Planning
To shape beams to avoid normal tissue, computer models use 3D patient images to
generate radiotherapy treatment plans. Clinicians use the imaging scans to define
both the tumour region requiring treatment and the position of nearby organs to
avoid as much as possible. Margins are created around the tumour and organs to
account for organ motion and positioning discrepancies between the initial scan and
subsequent treatments.
Planning software allows modelling of the radiation dose distribution in the
patient that the treatment beams will deliver. The effects of adding beams, changing
beam shape or position can be simulated until an optimal plan is produced that
delivers homogenous dose to the tumour and minimises dose to critical organs.
Image Guided Radiotherapy
Changes in size or position of the tumour or other organs can occur both between
treatments (inter-fraction) and during a treatment (intra-fraction), as a result of
changes in bladder or rectal filling, patient positioning on the couch, or shrinkage of
tumour during the treatment course.
77 Principles of Radiotherapy 435
a b
Fig. 77.1 Images acquired from MR Linac for a patient in the treatment position with a T2cN0M0
Gleason 3 + 4 prostate cancer. (a) The treating oncologist uses the MR images to contours organs
at risk (OARs) rectum (brown) and bladder (green). The prostate and base of seminal vesicles are
contoured and, following a standard protocol, expanded to create planning target volumes that
receive 36.25 Gy (light blue) and 30Gy (orange) across 5# treatment fractions (SABR). (b) is a
colour map of dose contours showing a conformal dose around the prostate, sparing adjacent
OARs such as the rectum
Imaging prior to treatment allows verification that treatments are being delivered
accurately. CT images can be acquired which are excellent for identifying and
matching to bony landmarks, but soft tissue differentiation is more limited. Linear
Accelerators with an inbuilt MR scanner (MR Linac) are now in use at a small num-
ber of tertiary cancer centres and allow a significant advance in verification of organ
and tumour position on daily imaging (Fig. 77.1).
Proton Therapy
Whilst conventional external beam radiotherapy is delivered using high energy pho-
tons, radiation dose can also be delivered using larger subatomic particles such as
protons. A physical benefit with proton therapy is that delivered energy can be more
accurately deposited to tumours. However, there is a lack of evidence of clinical
effectiveness for this technology in the common urological cancers and these treat-
ments remain experimental.
Radiosensitisers
Radiosensitisers are designed to increase tumour cell death per unit dose of radia-
tion and to be clinically beneficial must sensitise cancer cells more than normal
cells. Oxygen is required to fix radiation damage in cells and due to erratic vascula-
ture, many tumours are hypoxic compared to surrounding normal tissue, causing
radioresistance. A hypoxia modification strategy using inhaled oxygen and
436 M. Swinton and A. Hudson
nicotinamide (BCON) has demonstrated increase overall survival in bladder cancer

patients. Radiosensitising chemotherapeutics can also be given concurrently with
radiotherapy (such as gemcitabine) with the hypothesis that tumours are differen-
tially sensitised compared to normal tissue.
Brachytherapy
Brachytherapy spatially limits radiation dose to normal tissue using a radioactive

source directly inserted into the tumour via the transperineal route. The advantage
is the rapid dose fall off around the source (via the inverse square rule) allows a
large differential between the dose received by the tumour and surrounding nor-
mal tissue.
In low dose rate brachytherapy, seeds iodine-125 are permanently implanted into
the prostate and left to deliver radiation over an extended period of weeks to months.
In high-dose rate brachytherapy treatments (Fig. 77.2), transperineal catheters allow
placement of a high-activity radioactive source within the prostate for a shorter
period (e.g. a few minutes) before removal.
Fig. 77.2 Axial image from a brachytherapy planning system with the needle catheter positions
(orange circles) and the isodose map achieved with the needle positions
77 Principles of Radiotherapy 437
Systemic Use of Radioisotopes
Radioisotopes are chemical elements that emit ionising radiation and are given sys-
temically to be taken up by tumour cells. Radium-223 is licensed for patients with
prostate cancer and bone metastases. Mimicking calcium at sites of new bone for-
mation, it preferentially locates to bone metastases. Its effect is primarily through
production of alpha radiation that causes short range damage (around 100 μm) to
adjacent cells.
Alternatively, radioisotopes can be attached to antibodies to specifically target
tumour regions and deliver radiation dose. Lutetium-PSMA is one such treatment
currently in clinical trials for metastatic prostate cancer.
Further Reading
National Radiotherapy Dataset (RTDS) (ncin.org.uk).

Hoskin, P. J. (2012). Radiotherapy in practice: external beam therapy. In Radiotherapy in prac-
tice, 2 ed.
Song YP, Mistry H, Irlam J, Valentine H, Yang L, Lane B, West C, Choudhury A, Hoskin PJ. Long-
term outcomes of radical radiation therapy with hypoxia modification with biomarker discov-
ery for stratification: 10-year update of the BCON (bladder carbogen nicotinamide) phase 3
randomized trial (ISRCTN45938399). Int J Radiat Oncol Biol Phys. 2021;110(5) https://doi.
org/10.1016/j.ijrobp.2021.03.001.
Chapter 78
Brachytherapy for Prostate Cancer
Mariam Obeid and Maria Serra
‘Brachy’ is derived from the Greek word for ‘short’. Brachytherapy is a treatment
modality where radiation is delivered directly into or adjacent to a tumour. It allows
the delivery of high dose radiation to the tumour, while minimising radiation dose
to the surrounding normal tissues.
The origin of prostate brachytherapy dates back 1911 when Octave Pasteu, a
urologist from Paris, treated prostate cancer by temporarily administering radium
via a urethral catheter. It was not until the 1980s, with the introduction of a transrec-
tal ultrasound (TRUS) based procedure, that prostate brachytherapy was routinely
used in the treatment of prostate cancer.
Overview of Brachytherapy
Brachytherapy is a radical treatment option for prostate cancer. It can be used as a

monotherapy or in combination with external beam radiotherapy (EBRT). Prostate
radiotherapy can be delivered with low dose rate (LDR) or high dose rate (HDR)
treatments.
LDR brachytherapy, also known as seed implant, is a procedure where a radioac-
tive source is implanted permanently into the prostate. It uses a radiation source
with a dose-rate of less than 2 Gy per hour. The implants consist of either loose
seeds, stranded seeds, or a combination of both.
M. Obeid · M. Serra (*)

The Christie NHS Foundation Trust, Manchester, UK
e-mail: mariam.obeid@nhs.net; maria.serra@nhs.net

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_78
440 M. Obeid and M. Serra
HDR brachytherapy, on the other hand, involves radiation sources with higher
activity temporarily inserted into the prostate using catheter needles introduced
transperineally with TRUS guidance. The dose is delivered at a rate of more than
12 Gy per hour. Treatment is given in 1–3 implants, with catheters left within the
patient to deliver between 1–6 fractions. The full radiation dose is divided into mul-
tiple smaller doses called fractions.
Most patients who have brachytherapy (LDR or HDR) are treated to the whole
prostate. However, it is also possible to use brachytherapy to treat focally or the
hemi-gland. The rationale behind the 2 latter options is to reduce treatment toxicity.
Patient Selection
The indications for LDR and HDR brachytherapy are different and will be dis-
cussed further down in this chapter. However, there are contraindications that are
common to both techniques, summarised in Table 78.1.
Table 78.1 Contraindications to prostate brachytherapy

Relative contraindications or logistical
Absolute contraindications challenges
Metastasis or tumour infiltration of nearby Inflammatory bowel disease
structures
Active infection in the area intended for treatment High risk of bleeding
Anatomical defects such as rectal fistulae, absence Moderate-to-severe urinary symptoms or
of a rectum and significant TURP defects poor urinary function, defined as:
• International Prostate Symptom
Score > 20
• Peak flow rate < 10 cm3/second
• Post-void residual volume > 100 cm3
Ataxia telangiectasia Life expectancy less than 10 years
High perioperative risk Large prostate size (usually above 60 cm3)
or large median lobes
Pubic arch anatomy impeding optimal
procedural technique
Previous pelvic radiotherapy
78 Brachytherapy for Prostate Cancer 441
Prostate Brachytherapy as Monotherapy
LDR Prostate Brachytherapy
Indications
LDR prostate brachytherapy monotherapy can be offered to patients with low and
favourable intermediate-risk prostate cancer (in summary: Gleason 3+3 with
PSA < 20 ng/ml or Gleason 3+4 with PSA < 10 ng/ml). Patients also need to meet
the criteria mentioned above for prostate size and urinary function.
Isotopes
There are 3 different radioisotopes used in LDR brachytherapy as summarised

below in Table 78.2. However, in the United Kingdom and Europe only Iodine-125
is used in clinical practice.
Technical Aspects
Patients are usually placed in the lithotomy position, with the legs separated, flexed,
and supported with stirrups. Under general, regional, or local anaesthesia and using
a sterile approach, a transrectal ultrasound probe is inserted to assess the prostate
volume and shape, and to guide seed insertion accuracy. A total of 70 to 150 radio-
active seeds (number of seeds depends on prostate volume and seed activity) are
implanted transperineally using needle catheters inserted through a template, a grid-
like device with defined coordinates. A radiation therapy planning software is then
used to model the prostate coverage and calculate the dose.
Table 78.2 Properties of Radioisotope Half-Life (days) Preferred Dose (Gy)

radioisotopes used in Iodine-125 59.4 145
brachytherapy
Palladium-103 17.0 125
Caesium-131 9.7 115
Treatment Planning and Dosimetry
Treatment planning can be done prior to implantation (usually called pre-planning)

or intraoperatively (live planning) using TRUS guidance. Intraoperative planning is
often considered superior, as it allows for the adjustment of seed deposition and
dose coverage in real time.
The mainstay of any radiotherapy treatment is to deliver high doses of radiation
to the target while limiting dose to normal tissues (organs at risk) to reduce the risk
of toxicity. Dosimetry follows the recommendations made by the radiation oncol-
ogy societies. The specific dosing parameters for the prostate volume are sum-
marised in the Table 78.3 below. Organs at risk, the urethra and rectum, require
specific dose constraints. However, there is no consensus regarding dose constraints
to other organs, including those involved in erectile function.
Radiation Protection
Patients must be advised to observe some precautions following seed implantation

while the sources are active. They are advised to avoid prolonged contact with
young children and pregnant women for the first 2 months. Sexual intercourse
should be avoided in the first few weeks, and following that, barrier contraception
must be used in the first 5 occasions of intercourse as a seed may be expelled on
ejaculation. Patients may trigger airport security systems (or similar) so they should
carry a document stating that they have had LDR prostate brachytherapy. The
International Commission on Radiological Protection (ICRP) recommends that cre-
mation is avoided if death occurs within 20 months of iodine seed implant.
HDR Prostate Brachytherapy
Indications
HDR brachytherapy monotherapy can be used in select patients with low and inter-
mediate risk prostate cancer with favourable features. Patient selection criteria are
similar to those previously mentioned for LDR brachytherapy.
Table 78.3 Some examples of quality planning constraints in prostate brachytherapy

Prostate (CTV) Urethra Rectum
D90 > 100% V100 > 95% V150 < 50% D10 < 150% D 2 cc ≤ 145 Gy
D30 < 130% D 0.1 cc ≤ 200 Gy
CTV, Clinical Target Volume; D90, dose that covers 90% volume of CTV; V100, volume of CTV
receiving 100% of the dose; V150, volume of CTV receiving 150% of the dose
Technical Aspects
Patient positioning and anaesthetic support is similar to LDR brachytherapy. Up to

eighteen hollow metal needles are inserted into the prostate with TRUS guidance
and a treatment plan is then developed.
Treatment Planning and Dosimetry
No single dose has been established for HDR, and multiple fraction combinations
are possible. Latest clinical trial evidence shows that a single fraction of HDR is
suboptimal with unacceptable levels of local failure. It is recommended that patients
have multiple treatments known as fractions. Treatment fractions must be separated
by at least 6 hours to allow for normal cell repair and the capture of proliferating
cancer cells in different stages of mitosis.
The CTV V100 in HDR monotherapy should be more than 95%. HDR offers the
ability to enhance dose distribution to the tumour while decreasing damage to sur-
rounding organs by varying the amount of time the radioactive source stays in particu-
lar positions within each needle. “Hotspots”, or volumes outside the planned target
volume (PTV) receiving more than 100% of prescribed dose are often smaller in HDR
brachytherapy than in LDR brachytherapy. Hence, HDR is thought to be superior to
LDR in terms of dosimetry. In theory, this should reduce normal tissue toxicities.
Prostate Brachytherapy as a Boost
Indications
Several phase III randomized studies published in the beginning of the 2000s dem-
onstrated the relationship between dose escalation and biochemical control in pros-
tate cancer. Dose escalation in the management of prostate cancer can be achieved
with modern external beam radiotherapy techniques like IMRT (intensity modu-
lated radiotherapy) and/or prostate brachytherapy boost.
Hoskin et al.’s phase III randomised study compared outcomes of EBRT alone to
EBRT with HDR boost. The study found that adding HDR boost significantly
improved relapse-free survival in comparison to EBRT alone, resulting in a 31%
reduction in the risk of recurrence. The adverse effect profile was found to be com-
parable in both trial arms.
More recently, ASCENDE-RT trial demonstrated a significant improvement in
the rates of biochemical relapse for patients treated with LDR brachytherapy boost.
However, the LDR and EBRT combination revealed a greater likelihood of grade
3–4 genitourinary and gastrointestinal toxicities.
Table 78.4 Brachytherapy Brachytherapy technique Preferred dose (Gy)

boost doses LDR (Iodine-125) 110–115 Gy
HDR (Iridium-192) 15 Gy
Current guidelines have therefore adapted to reflect the results above and the
recommendation has evolved into offering brachytherapy boost to intermediate or
high-risk prostate cancer patients who are suitable for brachytherapy. Due to the
more favourable profile of toxicities HDR is the preferred technique. However,
HDR boost patient selection must be considered with care, since certain traits like
older age and co-morbidities have been linked to higher rates of late toxicities
(Table 78.4).
Salvage Brachytherapy
Indications
Salvage brachytherapy (using LDR or HDR monotherapy) is an option for patients

with local recurrence of prostate cancer after EBRT or prostate brachytherapy. This
treatment may be considered if patients have a recurrence limited to the prostate
documented by multiparametric MRI and prostate biopsy. Distant or loco-regional
metastases should be excluded.
This is considered a second radical treatment with re-irradiation. The potential
benefit of this treatment needs to be balanced against the risk of increased toxicity
(genitourinary and gastrointestinal) and the patient’s expected survival. Generally,
salvage brachytherapy is considered for patients who have had a good disease-free
interval of at least 2 years, minimal late toxicities from previous radiotherapy-based
treatment and a PSA doubling time over 12 months.
The data supporting the use of salvage brachytherapy comes from a phase II and
retrospective cohort studies.
Further Reading
Crook JM, et al. A prospective phase 2 trial of transperineal ultrasound-guided brachytherapy

for locally recurrent prostate cancer after external beam radiation therapy (NRG Oncology/
RTOG-0526). Int J Radiat Oncol Biol Phys. 2019;103(2):335–43. https://doi.org/10.1016/j.
ijrobp.2018.09.039.
Fischer-Valuck BW, et al. A brief review of low-dose rate (LDR) and high-dose rate (HDR) brachy-
therapy boost for high-risk prostate. Front Oncol. 10 Dec 2019;9:1378. https://doi.org/10.3389/
fonc.2019.01378.
Hoskin PJ, et al. Randomised trial of external beam radiotherapy alone or combined with high-dose-
rate brachytherapy boost for localised prostate cancer. Radiother Oncol. 2012;103(2):217–22.
https://doi.org/10.1016/j.radonc.2012.01.007.
Morris WJ, et al. Androgen Suppression combined with elective nodal and dose escalated radia-
tion therapy (the ASCENDE-RT Trial): an analysis of survival endpoints for a randomized trial
comparing a low-dose-rate brachytherapy boost to a dose-escalated external beam boost for
high- and intermediate-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2017;98(2):275–85.
https://doi.org/10.1016/j.ijrobp.2016.11.026.
Zaorsky NG, et al. The evolution of brachytherapy for prostate cancer. Nat Rev Urol.
2017;14(7):415–39. https://doi.org/10.1038/nrurol.2017.76.
Chapter 79
Augmented Intravesical Drug
Administration
Benjamin Starmer and Henry Lazarowicz
Intravesical drug administration has traditionally relied on passive diffusion of a

drug across the urothelium. Efforts have been made to augment drug absorption and
clinical efficacy, using methods such as electromotive drug administration and
chemohyperthermia.
Introduction
Intravesical drug administration has been a cornerstone of urological practice in the

management of non-muscle invasive bladder cancer, recurrent UTI/bladder pain
syndrome and overactive bladder for many years.
The intravesical route relies on passive diffusion of the drug across the relatively
impermeable urothelium. This can result in unpredictable pharmacokinetic responses,
as molecules will need to be water soluble to dissolve in the urine and lipophilic to
cross the urothelial plasma membrane to enter the cell. Furthermore, the initial
administered drug concentration will be governed by the presence and volume of
urine within the bladder. Further dilution arises from the continuous production of
urine during the treatment dwell time. Hydration status is therefore an important fac-
tor that will influence this. The dwell time of the drug can also be adversely affected
by premature drainage or expulsion of urine by inadvertent voiding.
Many of the drugs administered into the bladder will become ionised in urine
and their solubility, efficacy and overall polar charge will be governed by the uri-
nary pH, which will vary between patients. For instance, lidocaine, is most active in
its un-ionised form, as this is most able to cross the phospholipid membrane.
B. Starmer (*) · H. Lazarowicz

e-mail: starmer@doctors.org.uk; henry.lazarowicz@nhs.net

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_79
448 B. Starmer and H. Lazarowicz
However, in urine of increasing acidity, it will increasingly be in an ionised state,

and therefore biologically inactive. This explains why bicarbonate is often added as
a buffer to intravesical drug preparations for bladder pain syndrome: to improve
drug penetration.
Beyond the factors outlined above, which can be difficult to individually control,
the two most notable methods employed to improve intravesical drug penetration and
bioavailability are electromotive drug administration (EMDA) and chemohyperther-
mia (CHT). More recently, there has been an increased interest in the use of slow-
release devices deployed within the bladder that are designed to enhance dwell time.
Interest in these methods has been stimulated by recent intravesical BCG short-
ages, which have left patients with high-risk non-muscle invasive bladder cancer
with limited alternative bladder-preserving options.
Electromotive Drug Administration (EMDA)
This involves passing an electrical current between 2 electrodes, one placed within
the bladder and the other outside of it, usually applied as a large surface area plate
in direct contact with the skin (thereby diminishing the current density at this inter-
face). EMDA improves drug delivery across the urothelium through two distinct
mechanisms:
1 Enhanced drug migration, via the process of iontophoresis, which collectively
comprises of electrophoresis and electro-osmosis and
2 Enhanced barrier permeability at a cellular level, via the process of
electroporation.
Electrophoresis is the transport of a charged substance across a transport medium
(in this case urine or drug diluent) arising from the application of an electrical field
across it, thereby causing the charged molecule (e.g. lidocaine) to migrate because
of the electrorepulsive forces that arise. The direction of travel will be governed by
the polarity of the applied electrical field and the overall charge of the molecule.
Positively charged molecules (cations) will migrate towards the negatively charged
anode and negatively charged molecules (anions) will migrate towards the cathode.
All other factors being equal, the rate of migration of these charged particles will be
directly proportional to their charge and inversely proportional to their size.
Electro-osmosis is the process by which non-ionised polar molecules, e.g.
Mitomycin C, migrate when there is a convective flow of water that arises in asso-
ciation with ion gradients generated in the transport medium.
Electroporation is the process by which an applied electrical field increases
plasma cell membrane permeability and electrical conductivity at a cellular level,
thereby making the cell more receptive to the passage of small molecules across the
plasma membrane. In the context of augmented bladder drug delivery, this is likely
to have the least effect, as high voltages are required to disrupt the polarity and per-
meability of the plasma membranes and these are not achieved with the equipment
settings used.
79 Augmented Intravesical Drug Administration 449
A typical EMDA set up involves the use of a current generator that delivers a
pulsed direct electric current of 0–30 mA at 0–55 V to the bladder through a spe-
cially designed catheter with a silver spiral integrated into the tip (Fig. 79.1). The
electrical circuit is closed by the placement of 2 ‘return’ electrodes that are placed
on the lower abdominal wall skin (Fig. 79.2). The polarity of these electrodes can be
changed according to the charge of the desired drug being administered.
Fig. 79.1 Picture of an EMDA urinary catheter
a b
Abdominal patch electrodes
Generator
– – – -
2 2
Electric 2
current Bladder
electrode
1
Bladder
Catheter
Fig. 79.2 Diagram of intravesical EMDA set-up. Diagram of electrodes (a). Diagram of patient
set up (b)
A variety of medications have been trialled using EMDA, including:

• Mitomycin C (MMC) in non-muscle invasive bladder cancer (NMIBC)
• Oxybutynin/lidocaine/botulinum toxin A for overactive bladder (OAB)
• Lidocaine for bladder pain syndrome, radiation cystitis and as an anaesthetic
for TURBT
• Bethanechol for detrusor acontractility
Treatment time depends on the medication and condition. For EMDA MMC deploy-
ment in non-muscle invasive bladder cancer, this is typically 30 minutes and the
current is gradually increased as the treatment progresses. Side effects from EMDA
are mild, self-limiting and comparable to those experienced with MMC via passive
diffusion.
Chemohyerthermia (CHT)
CHT is the application of heat to the bladder (typically 40–44 °C) in combination
with chemotherapy e.g. Mitomycin C.
Suggested mechanisms of action include:
• Improved drug delivery through vasodilatation and increased blood flow in the
lamina propria
• Direct malignant cell killing—hyperthermia is directly cytotoxic by damaging
DNA and altering cellular metabolism
• Improved sensitisation of malignant cells to chemotherapy—Multiple cyto-
toxic agents have shown improved efficacy when administered to heated tumour
cells in vitro.
• Triggering a heightened immune response—hyperthermia causes cytokine
release and increases tumour-infiltrating leukocytes
Generally, the heat can be delivered internally or externally and the heat source may
be direct or indirect.
Internal Devices
These devices typically use a catheter to introduce the hyperthermia to the bladder.
This can either be delivered indirectly using conductive hyperthermia, where the
fluid is heated externally and is circulated into the bladder to and from the heat
source via a 3-way catheter. These devices have the advantage of being the smallest,
most portable and cheapest systems on offer and apart from set-up and device
removal, require minimal supervision during use. Examples of this system include
the Combat Bladder Recirculating System and UniThermia.
79 Augmented Intravesical Drug Administration 451
Fig. 79.3 Diagram of Synergo SB-TS 101 system during treatment
Microwave radiofrequency-emitting intravesical catheters provide an alternative

direct heat source for the bladder (Fig. 79.3). These operate at a frequency of
915 MHz, and the resulting vibration of the water molecules results in the direct
generation of heat within the bladder. As microwave heat generation tends not to be
uniform, the bladder temperature is continuously measured using thermocouples
integrated into the 20 Fr 3-way catheter and the urethra is continuously cooled to
avoid injury while the irrigation fluid is continuously recirculated (Fig. 79.3).
Synergo is most common example of a system that utilises microwave technology.
Internal devices have the advantage of a more uniform temperature across the
whole urothelium, however there remains a temperature gradient across the bladder
wall and whilst this is unlikely to be significant for NMIBC, it may have important
implications for muscle invasive disease.
External Devices
These are less commonly used, as they require a radiofrequency shielded room and
involvement of the medical physics team to ensure correct deployment of the radio-
frequency energy, thereby increasing the complexity and costs of the system. As
such, they are not amenable to the outpatient clinic settings where these treatments
are usually delivered.
One type of external heating uses deep regional radiofrequency, using an array of
electromagnetic radiofrequency emitters to focus heat on a region of the body at a
frequency of 100+/−2 MHz (e.g. BSD-2000 device). Intravesical temperature is
monitored through the placement of a urinary catheter probe, to ensure a tempera-
ture of 40–44 °C is achieved and additional temperature probes are placed in the
bladder and rectum/vagina to monitor their internal temperatures and avoid collat-
eral thermal injury. A water-filled applicator is also applied to the lower abdomen to
cool the skin during treatment.
Like radiotherapy, a radiofrequency planning scan is also required to direct
treatment.
Clinical Application of CHT
An emerging role has been the deployment of CHT in BCG unresponsive/intolerant

patients who are not candidates for radical cystectomy. Generally, the treatment is
well tolerated and data shows acceptable rates of progression, although large-series
RCTs with long-term outcome data are presently not available.
Future Developments
Many of the devices in development are now aiming to improve the dwell time of
the intravesical drug in the bladder. These include the use of intravesical drug deliv-
ery systems, where a device is inserted into the bladder and left in situ for an
extended period. The device is then removed via flexible cystoscopy at a later date.
Other developments also include the development of chemotherapy-containing
hydrogels and mucoadhesives that coat and adhere to the urothelium. The drug is
then slowly released from the gel, increasing dwell times anywhere up to 6–8 hours.
Further Reading
Douglass L, Schoenberg M. The future of intravesical drug delivery for non-muscle invasive blad-
der cancer. Bl Cancer. 2016;2(3):285–92.
Hashemi S, Sahai A, Malde S. Applications of electromotive drug administration in urology. Urol
Ann. 2020;12(4):301–8.
Tan WP, Longo TA, Inman BA. Heated intravesical chemotherapy: biology and clinical utility.
Urol Clin North Am. 2020;47(1):55–72.
Part VI
Technology of Renal Failure
Chapter 80
Principles of Renal Replacement Therapy
(RRT)
Mumtaz Patel
“Chronic” implies long term and irrecoverable; cf “acute” which implies the rela-
tively sudden onset of renal impairment. In most situations, acute renal failure is
something that has a potentially recoverable component unless there has been bilat-
eral renal infarction or total nephrectomy. “Renal failure,” in the context of chronic
kidney disease (CKD), should be regarded more as “renal impairment” rather than
failure and does not necessarily imply the need for renal replacement therapy (RRT),
at least in the short term.
Chronic Kidney Disease (CKD)
“Chronic” implies long term and irrecoverable; cf “acute” which implies the rela-
tively sudden onset of renal impairment. In most situations, acute renal failure is
something that has a potentially recoverable component unless there has been bilat-
eral renal infarction or total nephrectomy. “Renal failure,” in the context of CKD,
should be regarded more as “renal impairment” rather than failure and does not
necessarily imply the need for RRT, at least in the short term.
Currently, the concept, and nomenclature, of chronic kidney disease (CKD) has
been developed which has the advantage of enumeration in the presence of abnor-
mal urinary findings and/or structural, or genetic, traits suggesting renal disease
(Table 80.1).
CKD is defined and staged using estimated glomerular filtration rate (eGFR) and
indicators of kidney damage such as albuminuria. CKD is recognized as a leading
M. Patel (*)
Department of Nephrology, Manchester University Hospitals NHS Foundation Trust,
Manchester, UK
e-mail: mumtaz.patel@mft.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_80
456 M. Patel
Table 80.1 The Kidney Disease Outcomes Quality Initiative (KDOQI) chronic kidney disease
(CKD) classification (NKF-KDOQI 2011)
CKD grade Descriptor of type of renal dysfunction eGFR mL/min
CKD 1 Kidney damage (e.g., proteinuria) but with normal >90
GFR
CKD 2 Kidney damage with mildly reduced GFR 60–89
CKD 3 Moderately reduced GFR 30–59
CKD 4 Severely reduced GFR 15–29
CKD 5 Kidney failure <15
global health problem with estimated prevalence at 13.4% (11.7–15.1%). Patients

with end-stage kidney disease (ESKD) needing renal replacement therapy (RRT) is
estimated between 4.9 and 7.1 million with a significant burden on healthcare sys-
tems worldwide.
Stage 5 CKD is also known as End-stage kidney disease (ESKD). This is a term
usually used to imply that the patient is in imminent need of renal replacement
therapy (RRT) or indeed already established on it. The ambiguity of this term is best
avoided by the use of the phrases “dialysis dependant” or “renal transplant recipi-
ent” when describing the patient’s condition.
Renal Replacement Therapy (RRT)
RRT is used to treat established CKD 5 and encompasses:

• Chronic peritoneal dialysis
–– Chronic ambulatory peritoneal dialysis (CAPD)
–– Automated peritoneal dialysis (APD)
• Haemodialysis
• Renal transplantation
Acute peritoneal dialysis and haemofiltration, whilst technically RRT, are not
undertaken on a long-term basis but merely to address acute renal insufficiency.
RRT, like acute dialysis, is used to normalise, as much as possible, the internal
milieu in the absence of sufficient native renal function and aims to:
• Maintain normal serum electrolyte composition (sodium, potassium, bicarbon-
ate, calcium, etc.)
• Remove waste products of metabolism (urea, creatinine, and the “middle
molecules”)
• Ensure removal of excess water to prevent fluid overload
RRT also includes replacing the hormonal components of renal function, where
indicated, of Erythropoietin and Vitamin D analogues such as alfacalcidol. These
help maintain haemoglobin and provide substrate for conversion to 1,25 dihydroxy-
cholecalciferol, respectively, to reduce bone demineralisation.
80 Principles of Renal Replacement Therapy (RRT) 457
Table 80.2 The relative costs of the different forms of renal replacement therapy in the UK (2021)
Type of RRT Cost
In-centre haemodialysis £35,023 pa
Satellite haemodialysis £32,669 pa
APD £21,665 pa
CAPD £15,570 pa
Home haemodialysis £20,764 pa
Renal transplantation £30,000 pa
Post-transplantation management £10,000 pa
Common problems such as hypertension, hypercholestrolaemia, and hyperphos-

phataemia are intrinsic components of RRT as is patient education about the need
for strict adherence to fluid, dietary, lifestyle, and medication modifications.
The Economics of RRT
There is still a great deal of controversy as to the exact costs of providing RRT, and
it varies substantially according to modality of treatment. Various authorities, how-
ever, give the following approximate costs per annum (Table 80.2).
Whatever the true expenditure, which varies from centre to centre, most authori-
ties agree that in-centre dialysis is significantly more expensive than home therapies.
Efficacy of RRT
Patient survival, and graft survival for renal transplants, is not linear and depends on
variables such as patient age and comorbidity. Survival on dialysis is usually calcu-
lated after the first 90 days because a significant mortality is associated with the
30% or so of patients who initially present needing acute replacements. Five-year
survival is 85% in a patient of 25 years but drops to 50% for a 50-year-old irrespec-
tive of whether or not they are transplanted. Variables, such as the tissue match,
whether or not the patient receives a live donor transplant (usually, but not exclu-
sively, from a relative), and if the transplant takes place prior to the need for dialysis,
influence these figures. 5-year transplant survival rates are at 93% for living donors
and 87% for deceased donors. Overall, survival rates at 1, 5, and 10 years in the UK
on RRT are in the order of 95%, 80%, and 60%, respectively.
458 M. Patel
Benefits of Transplantation
Renal transplantation, for the vast majority of patients, is the most suitable form of
RRT unless:
• It is technically impossible
• It is medically inappropriate, having considered the patient’s comorbidities or
life expectancy
• They have chosen a conservative path and opted not to have RRT in any form
• There is a personal preference specifically not to undertake transplantation for
whatever reason
Survival benefit from transplantation, as opposed to remaining on dialysis, is evi-
dent well within the first year due to the relief from the discipline and hazards of
dialysis and the patient’s greater sense of well-being. It does, however, demand the
other disciplines of maintaining a healthy lifestyle, strict adherence to the prescribed
immunosuppressive regimen, and the rigid use of other medications. There are asso-
ciated longer-term disadvantages of immunosuppression such as symptomatic
CMV disease, pneumocystis, and tuberculosis. Immunosuppression also brings a
significant increase in the incidence of skin malignancies, predominantly squamous
cell carcinoma, and other virally mediated cancers including carcinoma of the cer-
vix and post-transplant lymphoproliferative disease (PTLD).
Further Reading
23rd Annual Report of the Renal Association, UK Renal Registry 2019. https://ukkidney.org/
audit-research/annual-report
KDOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and strat-
ification. The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF
KDOQI™). New York. 2011. http://www.kidney.org/professionals/KDOQI/guidelines_ckd/
toc.htm.
Chapter 81
Principles of Peritoneal Dialysis
Dimitrios Poulikakos and David Lewis
Peritoneal dialysis (PD) is a type of renal replacement therapy, with similar survival
rates and lower cost compared to haemodialysis. PD offers flexibility and promotes
patient empowerment through effective education, support, and partnership with the
multidisciplinary PD community team.
Principles of PD
The main principles behind the use of PD for treatment of renal failure are that
uraemic toxins (eg urea, creatinine) and solutes (eg sodium, potassium) within the
blood compartment will diffuse from the peritoneal micro-circulation across the
peritoneal membrane into the dialysis fluid (dialysate) within the peritoneal cavity
either down a concentration gradient or by convection. After a given period of time
the fluid (effluent) is then drained out, to be replaced by fresh dialysate. The connec-
tion between the patient and the dialysate drainage system must be kept sterile at all
times. By varying the concentration of the dialysate different volumes of water can
be removed (ultra-filtration) with each dialysis exchange, as a result of osmosis.
Peritoneal dialysis will only usually be successful for < 6 years because of sev-
eral factors, including:
• Complications of therapy, recurrent peritonitis, encapsulating peritoneal sclero-
sis (EPS) or peritoneal membrane failure.
• Loss of residual renal function—the success of peritoneal dialysis relies upon
most patients having some residual renal function (ie patients start dialysis when
D. Poulikakos (*) · D. Lewis

Salford Care Organisation, Northern Care Alliance Foundation Trust, Salford, UK
e-mail: dimitrios.poulikakos@nca.nhs.uk; david.lewis@nca.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_81
460 D. Poulikakos and D. Lewis
their GFR is 7–10 ml/min). In patients with relatively increased metabolic

demands, the absence of residual function means dialysis is unable to provide
sufficient clearance of waste products and water.
Types of PD
CAPD
The most commonly used form of peritoneal dialysis is continuous ambulatory peri-
toneal dialysis (CAPD). A typical regime would involve 4 self-administered
exchanges of 1.5 to 2.5 litres of dialysate depending on the size of the patient in a
24-hour period. Such a regime might be expected to provide a 60–65 Kg-sized
patient with a clearance of toxins equivalent to a GFR of 5–7 ml/min.
APD
Automated PD (APD) uses a machine to automatically perform the drain in/drain

out functions during the night without the need for patient involvement. Typically,
APD would provide 5–6 overnight exchanges whilst the patient sleeps; there is a
need to connect the patient’s dialysis catheter to the APD machine in a sterile man-
ner and to disconnect it at the end of the session. In most of the programmes in UK
trained staff can support patients unable to perform connection and disconnection
(assisted APD).
Patient Selection
Ideally all patients facing renal replacement therapy should be given a choice
regarding their preferred treatment modality. Their dexterity, general capability,
motivation and the amount of space available in the home (for storage of dialysate)
will influence that choice; PD should only be undertaken in a clean environment.
The following would exclude patients from commencing PD:
• previous major abdominal surgery; especially where there is reduced peritoneal
membrane surface area available, stomas
• Morbid obesity
• Anuric patients with high metabolic demands
• Anticipated need for placement of PEG feeding tube. Placement of a PEG while
on PD is contraindicated. PEG placement prior to commencement PD is safe
however is associated with frequent infective complications.
81 Principles of Peritoneal Dialysis 461
A typical CAPD candidate should, therefore, be relatively fit, have some residual
renal function and a need for home therapy or for flexibility with their dialy-
sis regime.
PD Catheters and Placement
PD catheters utilised for peritoneal access are usually silicon catheters with 3 seg-
ments: intraperitoneal (perforated) segment, tunnelled segment with 2 Dacron cuffs
at the ends to anchor the catheter and prevent bacterial migration, and extraperito-
neal segment.
PD catheters can be inserted percutaneously (Seldinger technique) via an inci-
sion in the midline below the umbilicus under local anaesthesia or surgically (lapa-
roscopically) under general anaesthesia.
The catheter tip is placed in the pelvis and the proximal catheter is tunnelled,
subcutaneously, to an exit site several centimetres from the midline (Fig. 81.1).
a
Outer
skin
Peritoneal cavity
Subcutaneous Peritoneal
cuff cuff
b
Outer
skin
Peritoneal cavity
Subcutaneous Peritoneal
cuff cuff
Fig. 81.1 Double-cuffed Tenckhoff catheters (a) straight (b) curled

Prescribing PD
Dialysis solutions are sterile, buffered with bicarbonate, and are available in several
different glucose concentrations of differing osmotic strengths (1.5% to 4.25%) to
facilitate ultra-filtration. The amount of ultra-filtration obtained with a given strength
of dialysate varies from person to person. Some patients are high transporters of
glucose, which means that the osmotic effect of the dialysate rapidly dissipates and
fluid removal is poor; in this group polymer-based dialysates, such as icodextrin,
may be used.
Complications Associated with PD
Infectious complications:
• Peritonitis—usually presents with abdominal pain, cloudy peritoneal effluent,
fever and the diagnosis is confirmed with increased peritoneal leukocyte count
(>100 million cells/L). No organism is grown from the peritoneal effluent in
approximately 20% of cases. PD peritonitis should be < 0.5 episodes per year at
risk. Infecting organisms include coagulase −ve staphylococci, staphylococcus
aureus and gram −ve bacilli. Most cases respond promptly (2–3 days) to intra-
peritoneal antibiotics. Treatment usually starts with intraperitoneal Vancomycin
and Gentamycin and is adjusted according to fluid culture result. In cases who do
not respond to antibiotic treatment within 4–5 days and/or show signs of progres-
sive sepsis the catheter should be removed. Repeated infections may be associ-
ated with microbial adhesions and biofilm bacterial growth requiring catheter
replacement or can lead to development of resistant infections (eg yeasts) requir-
ing catheter removal. Recurrent infections can lead to peritoneal membrane fail-
ure and to encapsulating peritoneal sclerosis.
• Exit site infection, this usually responds to oral antibiotics. If infection extends
to the tunnel the catheter may need to be removed
Non-infectious complications:
• Catheter malfunctioning. Problems with catheter flows are common due to con-
stipation that can also be complicated by catheter migration (eg catheter tip
moves out of the pelvis). Most cases respond to treatment with laxatives.
Catheters can also be blocked by fibrin or trapped between adhesions.
• Hernias. Development of incisional hernia is common however any other abdom-
inal hernia may develop due to increased intrabdominal pressure particularly
with high volumes of dialysate during the day. Patent processus vaginalis can
manifest with scrotal swelling at PD initiation. Pre-existing hernias should be
corrected prior to initiation of PD. PD prescription should be adjusted to reduce
intrabdominal pressure (low volume APD) at the time of diagnosis of new her-
nias in PD patients.
81 Principles of Peritoneal Dialysis 463
• Leaks. Fluid leaks can be either through the catheter exit site immediately after
catheter insertion or, through the subcutaneous tissue when the exit site is sealed.
Leak can also manifest as abdominal and scrotal swelling. Exit site leaks are usu-
ally managed with PD discontinuation for 2–3 weeks and subsequent re-initiation
with low volumes. This is usually possible without needing bridging with hae-
modialysis treatment due to adequate residual renal function at the time of PD
catheter insertion. If there is also scrotal swelling imaging with ultrasound or CT
should be performed to investigate for possible underlying hernias.
Pleuroperitoneal leaks present as pleural effusion increasing in size with PD
treatment.
• Ultra-filtration failure—due to repeated peritonitis, and after several years of
exposure of the peritoneal membrane to the dialysis solutions.
• Encapsulating peritoneal sclerosis (EPS)—a thickening of the peritoneal mem-
brane, with reduced function and encasement of intra-abdominal organs
(Fig. 81.2). The incidence of EPS increases with duration of peritoneal dialysis
(eg 2% of patients after 4 years of therapy). Symptoms include abdominal pain
and malnutrition, and bowel obstruction and perforation can occur with more
advanced cases. Surgery is life-saving in some cases.
Fig. 81.2 Abdominal CT

scan with oral contrast
showing irregular, nodular
peritoneal thickening
(arrow) and no peritoneal
calcification. There is no
bowel wall thickening or
any dilated small-bowel
loops. There is diffuse
vascular calcification. The
arrowhead shows an
incidental calcified left
renal cyst
Imaging in PD
Abdominal X -Ray is commonly used to detect the position of the catheter and
assess for faecal loading. X- Ray screening following infusion of dialysate via the
PD catheter containing contrast material can be used to detect loculation within the
peritoneal cavity. CT peritoneogram following infusion of dialysate containing con-
trast material can detect loculation or leaks. Ultrasound scan is used to identify
hernias or collections.
Care of PD Patient
Patients on PD are followed up by a multidisciplinary team managing the whole

spectrum of complications of end stage renal disease. The majority of patients are
receiving erythropoietin stimulating agents and intravenous iron treatment for treat-
ment of anaemia, Vitamin D analogues and oral phosphate binders for treatment of
secondary hyperparathyroidism and renal bone disease, and renin angiotensin sys-
tem blockers and high dose of loop diuretics aiming at preserving their residual
urine output. All patients are assessed for suitability for kidney transplantation and
undergo relevant investigations and pre transplant interventions.
Surgical Support for PD
The relative frequency of laparoscopic surgical insertion vs percutaneous insertion

of PD catheters depends on the expertise of different renal centres. Complex patients
with possible adhesions are usually referred for surgical insertion. Surgical removal
of PD catheter should be considered in all surgically inserted catheters and in the
presence of PD peritonitis with suspected underlying bowel pathology based on
fluid culture. Caution should be exercised to ensure the subcutaneous Dacron cuffs
are removed because these can become infected in the future if left in situ. Close
relationship between surgical and renal team is important to establish local path-
ways for common PD complications (hernias, patent processus vaginalis).
Further Reading
International Society of Peritoneal Dialysis guidelines. ISPD Guidelines—International Society

for Peritoneal Dialysis.
Levy J, Brown E, Lawrence A. Oxford handbook of dialysis. 4th ed. Oxford University Press; 2016.
Chapter 82
Haemodialysis
Mumtaz Patel
Hemodialysis is a treatment in which blood is passed through an external device and

then returned to the body to replace normal renal function. Within the dialyzer, the
artificial kidney, the solute constituents of the blood are altered by exposing it to
dialysis fluid across a semipermeable membrane.
Principles of Haemodialysis
Haemodialysis is a treatment in which blood is passed through an artificial kidney

(dialyser) and then returned to the body. Within the dialyser, the solute constituents
of the blood are altered by exposing it to dialysis fluid across a semipermeable mem-
brane. Most dialysers are around 20–30 cm long and contain hundreds of tiny tubes
arranged side by side, made from a semipermeable membrane (Fig. 82.1). Blood
flows through the tubes providing a large surface area to allow passage of fluid and
diffusion of electrolytes. The tubes are bathed by dialysis fluid running in the oppo-
site direction providing a countercurrent system to maximise the concentration gra-
dient across the membrane. Conceptually, the membrane can be thought of as a sheet
containing holes or pores. Water molecules and low molecular weight solutes such
as urea, creatinine, and electrolytes can pass through the pores, but high molecular
weight solutes such as plasma proteins and some drugs cannot. Blood flows through
the dialyser at 300–400 mL/min and is anticoagulated with low molecular weight
heparin or unfractionated heparin to prevent clotting within the dialysis circuit. The
dialysis treatment can be altered by changing the electrolyte composition of the
dialysis fluid, the rate of fluid removal (ultrafiltration) and the duration of treatment.
M. Patel (*)
Department of Nephrology, Manchester University Hospitals, NHS Foundation Trust,
Manchester, UK
e-mail: mumtaz.patel@mft.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_82
466 M. Patel
Venous pressure monitor

Air trap and air detector
Clean blood
Saline solution
Fresh dialysate
Dialyser
Patient
Used dialysate
Inflow pressure
monitor
Blood pump
Heparin pump Arterial pressure Removed blood

(to prevent clotting) monitor for cleaning
Fig. 82.1 A haemodialysis circuit
A patient’s “dry weight” is their body weight without any excess fluid. Patients
are weighed before each treatment to determine how much ultrafiltration is needed
to return them to their dry weight. Most patients need to comply with a diet low in
salt, potassium, and phosphate as well as a fluid restriction of <1 l per day. Most
patients on long-term haemodialysis require >4 h of treatment three times weekly,
although evidence suggests their quality of life is improved if they dialyse for >12 h
per week. This may be delivered either by more frequent sessions or longer hours,
even overnight in some cases. Home haemodialysis is encouraged where possible to
facilitate this whilst maximising quality of life.
Initiation of Haemodialysis
Haemodialysis is usually the dialysis type of choice in acute kidney injury in adults
as it is easy to initiate via a central venous catheter. It has predictable efficacy and few
problems in the short term as long as the systolic blood pressure is >100 mmHg. In a
chronic setting, haemodialysis is usually initiated when the eGFR is between 8 and
10 mL/min and/or when the patient is symptomatic. It is initiated earlier if dietary
and medical therapies have failed to control fluid overload and serum potassium levels.
82 Haemodialysis 467
Vascular Access for Haemodialysis
Temporary access may be provided with a double-lumen central venous cannula.

Long term, the safest form of vascular access is an arteriovenous (AV) fistula, which
provides the maximum blood flow with the lowest risk of infection or thrombosis.
AV fistulas have been shown to have much better outcomes for dialysis patients. The
ideal site is the non-dominant wrist, creating an anastomosis between the radial
artery and the cephalic vein to form a “radio-cephalic” fistula. If this is not possible,
fistulas can be created at the elbow (brachiocephalic or transposed brachiobasilic)
or in the dominant arm (Fig. 82.2).
Once created, the fistula usually takes at least 8 weeks to mature before it is ready
for use. Patients with inadequate veins for fistula creation may have an AV graft,
either in the arm or in the thigh, but this is more prone to infection and thrombosis.
Some patients require several operations to secure a functioning AV fistula, and for
this reason, patients are usually referred for AV fistula creation when the eGFR is
Fig. 82.2 Arteriovenous

(AV) fistula
Artery
Vein
Blood from
dialysis
machine
Blood to
dialysis
machine
AV fistula
468 M. Patel
around 15 mL/min. Pre-dialysis, patients should use the hand, not arm veins, for can-
nulation and blood sampling to preserve the arm veins for fistula creation in the future.
Complications of Haemodialysis
Many problems relating to haemodialysis are related to functioning vascular access.

AV fistulas may last for many years, but complications include sudden thrombosis,
requiring urgent thrombolysis; gradual development of stenosis, requiring fistulo-
plasty, stenting, or revision surgery and steal syndrome leading to digital ischaemia.
If a fistula fails, a central venous catheter is required to continue dialysis treatment
until another fistula can be created. Complications of large-bore venous catheters
include air embolism, bacteraemia, endocarditis, discitis, catheter thrombosis, and
central vein stenosis/thrombosis leading to symptoms of SVC obstruction. Other
complications of dialysis include reactions to the dialyser, cardiac arrhythmias, and
poor tolerance of fluid removal leading to hypotension.
Long-term complications of end-stage renal failure are many and include mark-
edly increased risk of cardiovascular disease and heart failure, infections, anaemia
resistant to erythropoietin, hyperparathyroidism, calciphylaxis, malnutrition, and
psychosocial problems. Some patients choose to withdraw from dialysis either
because they no longer tolerate it or because of poor quality of life.
ractical Points Relating to the Management of Surgical

P
Patients on Haemodialysis
• Do not act on results of blood tests taken immediately after dialysis as they
change rapidly, e.g., potassium is often below the normal range but will rapidly
rebound.
• Haemodialysis patients undergoing surgery will usually require haemodialysis
on the day before and the day after surgery to minimise perioperative risk.
• Anticoagulation is usually used during dialysis but can be avoided in the periop-
erative period by using short-duration dialysis.
• Many drugs are removed by dialysis so should usually be given at the end of
dialysis, e.g., intravenous (IV) antibiotics.
• There is a higher risk of adverse drug reactions in patients with renal failure, so
if in doubt, consult the renal team regarding drug dosing.
Further Reading
Currie A. Renal drug handbook. 3rd ed. Abingdon: Radcliffe Medical Press; 2008.
Daugirdas JT, Blake PG, Ing TS. Handbook of dialysis. 5th ed. Philadelphia: Lippincott Williams
& Wilkins; 2014.
Chapter 83
Principles of Renal Transplantation
David Van Dellen and Jennifer Kingston
The first successful renal transplantation was undertaken in Boston, Massachusetts,

in 1954 in monozygotic twins. There have subsequently been numerous scientific
and surgical advances made to improve renal transplantation outcomes, with the
most successful developments being in the advent of adequate immunosuppression.
This chapter summarises the key areas of kidney transplantation in terms of indica-
tions, patient selection, risks and survival benefit.
Indications
Renal transplantation should, ideally, be the principle renal replacement interven-

tion for patients with established stage 5/end stage renal failure (ESRF), provided
they are deemed fit for major surgery and lifelong immunosuppression. It provides
financial benefit to the healthcare service and offers improved survival and greater
quality of life when compared to maintaining a patient on dialysis. Patients who are
transplanted prior to commencing dialysis (pre-emptive) have further improved
overall survival and graft survival. Both the British Transplant Society (BTS) and
UK Renal Association recommend that transplantation should preferentially occur
prior to commencement of dialysis. Transplant discussion should therefore occur in
the event of progressive decline in renal function, when glomerular filtration rate
(GFR) falls below 20 mL/min/1.73 m2. Only around 50% of patients with end stage
renal failure are deemed to be fit for transplant surgery.
The median waiting time for a kidney transplant in the UK is currently just over
1.5 years. Although the waiting time has improved over the last decade there
D. Van Dellen (*) · J. Kingston

e-mail: david.vandellen@mft.nhs.uk; jennifer.kingston@mft.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_83
470 D. Van Dellen and J. Kingston
continues to be a shortfall between the number of patients requiring kidney trans-

plantation and the number of grafts available, exacerbated by an ageing population
and the COVID-19 pandemic.
Contraindications
There are several absolute contraindications to renal transplantation, as follows:

• active and recent malignancy
• active sepsis or infection
• active renal disease (Goodpastures syndrome, vasculitis)
• short life expectancy (< 2 years)
• positive flow-cytometric or cytotoxic crossmatch
A caveat to infection is the presence of chronic viral illnesses which do not result
in end organ failure and can be pharmacologically controlled, including human
immunodeficiency virus (HIV) and hepatitis B and C. There are also a number of
relative contraindications to consider during patient assessment for kidney
transplantation:
• advanced age (increasing frequency of age-related comorbidity)
• body mass index (BMI)
• previous recurrence of renal disease (Focal segmental glomerulosclerosis, IgA
nephropathy)
• urological reconstruction or abnormalities
• history of poor treatment compliance
• age <2 years or weight less than 10 kg
• significant peripheral arterial disease
When taking the above factors into account, there is no universal consensus and
decisions will vary between transplant centres. Individualised decisions regarding
level of risk should be made in an appropriate MDT and after consultation with the
patient. Age is not considered an absolute contraindication, but age-related co-
morbidity may contribute to decision making, particularly if there is poor cardiac or
respiratory function. BMI is another variable not standardised across the UK,
although evidence suggests that increased BMI increases the risk of primary non-
function, delayed graft function, as well as recipient cardiorespiratory and wound
complications. Many transplant centres refuse renal transplant in patients with BMI
> 35 kg/m2. Neurological or anatomical bladder abnormalities do not contraindicate
transplantation, although they may require pre-emptive management (ISC or ileal
conduit formation).
The presence of alloantibodies secondary to prior blood transfusion, pregnancy,
or previous transplantation do not contraindicate transplantation however they do
make matching more problematic. Living related donor transplantation can now be
done across the ABO barrier.
83 Principles of Renal Transplantation 471
Types of Renal Transplant
Renal transplantation can occur following either living or deceased kidney dona-
tion. Living donor transplantation is the treatment of preference due to its superior
patient and graft survival. Living donor transplantation may occur via a genetically
related, or non-genetically related individual, an altruistic donor or from the national
paired/pooled scheme. Deceased or cadaveric kidney donation can be the result of
donation after brain stem death (DBD) or donation after circulatory death (DCD),
the latter of which constitutes the largest pool of donated kidneys in the UK. DBD
donors fulfil legal brain stem death criteria testing, whilst the latter do not meet
these criteria but further treatment is agreed to be futile. Procurement of organs in
these cases is therefore undertaken once cardiac output and circulation has ceased.
The National Waiting List Allocation
Data from NHS Blood and Transplant (NHSBT) in 2020 shows there were around
5000 patients in the UK waiting, on average 2–3 years, for a kidney transplant. In
the UK, all kidneys from deceased donors are allocated via the national offering
scheme, managed by NHSBT. All kidneys are allocated via an evidence-based com-
puter algorithm, unless the donor is over 70 or classed as high risk. Allocation is
based on two ranked tiers of potential recipients. Tier A patients are those with:
• a matchability score of 10 (top 10% of hard to match recipients),
• 100% calculated reaction frequency (cRF) which reflects antibody profile com-
pared to the general population, or
• patients whom have accrued 7 years of waiting time
Tier A patients are prioritised according to matchability score and waiting time.
Tier B are all other potential eligible recipients and are prioritised on a points-based
system which incorporates blood group matching, HLA mismatch, age difference,
location and waiting time. All kidneys are allocated preferentially to paediatric
recipients.
Surgical Technique of Kidney Transplantation
The surgery of transplantation has not changed significantly since the initial trans-
plant performed in the 1950’s. In most adults, the transplant is placed extra-
peritoneally in the iliac fossa, anastomosing the renal vein end-to-side to the external
iliac vein, and with the renal artery either end-to-side, or end-to-end with the exter-
nal or internal iliac arteries. Use of the internal iliac artery is less common in an
ageing recipient. Most transplant surgeons will make an extra-vesical stented ure-
teroneocystostomy of the Lich-Gregoir type.
Immunosuppression
Immunosuppression for kidney transplantation is required both at induction and for

lifelong maintenance in order to reduce the incidence of rejection and to prolong graft
survival. Induction therapy is an intensive immunosuppression regimen used for up
to two weeks at the time of transplant. There are no agreed national “standard” immu-
nosuppressive protocols and as such there are variations in regimens dependent upon
transplant centre, donor and recipient variables and patient tolerability of side effects.
Most protocols will include an induction agent such as a monoclonal interleukin-2
receptor blocker and a maintenance regime of a calcineurin inhibitor (CNI), an anti-
proliferative agent with short or long-term steroids (Fig. 83.1). There are important
potential side effects to be considered with long term immunosuppression including:
Immunosuppressant Class of Drug Comment

Drug
Basiliximab (Simulect) Monoclonal anbody Inducon agent for the prophylaxis of acute organ
rejecon. Administered in two intravenous doses 4
days apart. Acts as an interleukin-2 receptor
antagonist.
Alemtuzumab Monoclonal anbody directed against CD52

(expressed on the surface of immune cells).
Effecve as an inducon agent in reducing
rejecon in paents with high immunological risk.
Has a higher risk of opportunisc
infecons and PTLD.
Concentrated an- Used either as an inducon agent (although not
Rabbitan-human humanT-lymphocyte currently approved by NICE) or to treat acute
thymocyte immunoglobulin anbody mediated rejecon. Possible higher
immunoglobulin(r-ATG) risk of PTLD. Other side effects include
leucopenia and cytokine release syndrome.
Tacrolimus Calcineurin inhibitors Tacrolimus is the CNI of choice and

recommended by NICE.
Ciclosporin
Mycophenolate mofel An-proliferave Can result in myelosuppression.

agents Mycophenolate may result in gastrointesnal side
effects but is associated with improved gra and
Mycophenolicacid paent survival when compared to azathioprine.
(Myforc)
Azathioprine
Oral Prednisolone Steroids Oen short term use only in the immediate post-
operave period. Long term use results in diabetes,
hypertension, osteoporosis and hyperlipidaemia.
Methylprednisolone Used at inducon and for treatment of acute

rejecon.
Fig. 83.1 Common immunosuppression medications for renal transplant

83 Principles of Renal Transplantation 473
• increased cardiovascular risk

• susceptibility to opportunistic infections
• increased risk of malignancy (e.g. post-transplant lymphoproliferative disorder)
CNI related toxicity includes electrolyte imbalance, tremor, gingival hyperpla-
sia, hirsutism, hypertension, dyslipidaemia and new onset or worsening of diabetes.
Women of childbearing age should be counselled with regard to the teratogenic
effects of mycophenolate mofetil. Advice currently is to delay conception until 12
months post-transplant and convert mycophenolate to azathioprine 3 months prior
to attempting conception.
Complications of Kidney Transplantation
Transplant complications can be most easily categorised as early or late (Fig. 83.2).
Early complications are mostly related to the surgery of graft placement of which
arterial or venous thrombosis is the most devastating. Significant risk factors include
deceased donor, extremes of donor or recipient age, peri or post-operative haemo-
dynamic instability, peritoneal dialysis, diabetic nephropathy, previous thrombosis
or prolonged cold ischaemic time of the donor kidney.
Late complications are often related to anti-rejection therapy, and this should be
reduced wherever possible, to the lowest effective dose whilst maintain the equilib-
rium of preventing rejection. The majority of malignancies related to immunosup-
pression will be actinic basal cell or squamous cell carcinomas, which are potentially
curable. Post-transplant lymphoproliferative disorder (PTLD) occurs in 1–2% of
transplanted patients but has a potential 50% mortality rate. Interstitial fibrosis and
Early Complicaons < 30 days Late Complicaons >30 days
Mortality New Onset Diabetes
Renal Artery Stenosis
Vascular Complicaons Haemorrhage Opportunisc Infecons

(pneumocyss pneumonia, cytomegalovirus, BK
Thrombosis virus)
Aneurysm
Dissecon
Lymphocele Malignancy
Urinary leak PTLD
Rejecon Intersal Fibrosis and Tubular Atrophy (IFTA)
Ureteric Stricture/Stenosis
Fig. 83.2 Early and late complications of renal transplant

tubular atrophy (IFTA) is almost universal with time in those taking CNIs, with an
incidence of 100% at 10 years, resulting in slow and progressive graft loss. Other
late complications include incisional hernia (occurring in around 3% of recipients)
and renal artery stenosis.
Outcome from Renal Transplantation
Median graft survival from a from a living donor is approximately 20 years, whilst
from a deceased donor transplant this value falls to around 12 years. Overall, sur-
vival in patients following renal transplantation is significantly higher than in
patients remaining on dialysis.
Further Reading
British Transplant Society: Transplantation from deceased donors after circulatory death. https://
bts.org.uk/wp-content/uploads/2016/09/15_BTS_Donors_DCD-1.pdf
Shrestha B, Haylor J, Raftery A. Historical perspectives in kidney transplantation: an updated
review. Prog Transplant. 2015;25(1):64–76.
UK Renal Registry 24th Annual Report 2018. https://ukkidney.org/sites/renal.org/files/publica-
tion/file-attachments/24th_UKRR_ANNUAL_REPORT.pdf
Part VII
Assessment of Technology
Chapter 84
Key Concepts in the Design of Randomised
Controlled Trials
Kieran J. O’Flynn
An RCT is a prospective research study in which the participants are divided, ran-
domly, into separate groups that compare different treatments or interventions.
Introduction
The Dutch trials of Paludrine in Malaria and the Medical Research Council’s first
trial of streptomycin in pulmonary tuberculosis, both published in the late 1940s,
are usually cited as the first publications of randomised controlled trials (RCT). An
RCT is a prospective research study in which the participants are divided, randomly,
into separate groups that compare different treatments or interventions. Questions
regarding benefits (and harms) of an intervention are best answered with a well
conducted RCT, whereas questions regarding risk factors for disease or progression
are best answered with prospective cohort studies (see Fig. 84.1). The experimental
group has the intervention being tested, and the other (the comparison or control
group) has an alternative intervention, a dummy intervention (placebo) or no inter-
vention at all. The groups are followed up to see how effective the experimental
intervention was. Outcomes are measured at specific times and any difference in
response between the groups is assessed statistically. This method is primarily used
to reduce bias in its various forms, with can affect other types of research studies.
K. J. O’Flynn (*)
e-mail: kieran.oflynn@srft.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_84
478 K. J. O’Flynn
Level I Evidence from a systemac review or meta-analysis of all

relevant RCTs (randomized controlled trial) or evidence-based clinical pracce
guidelines based on systemac reviews of RCTs or 3 or more RCTs of good
quality that have similar results.
Level II Evidence obtained from at least one well designed RCT (eg large mul-site RCT).
Level III Evidence obtained from well-designed controlled trials without randomizaon
(ie quasi-experimental).
Level IV Evidence from well-designed case-control or cohort studies.
Level V Evidence from systemac reviews of descripve and qualitave studies

(meta-synthesis).
Level VI Evidence from a single descripve or qualitave study.
Level VII Evidence from the opinion of authories and/or reports of expert commiees
Fig. 84.1 Levels of evidence
Key Concepts in Trial Design Planning
Clinical Equipoise
A number of criteria must be met for the proper conduct of an RCT; clinical equi-
poise (the researcher needs to be genuinely uncertain as to whether there is a real
difference between the treatments), no foreknowledge, no bias in patient manage-
ment, no bias in the outcome assessment of the patient, and an intention to treat
analysis of the data, with no post randomisation exclusions.
Null Hypothesis and p Values
When a researcher decides to test a hypothesis in a trial setting, he or she would like
to know if it’s true. Unfortunately, the absolute truthfulness of general hypotheses
cannot be answered using empirical techniques. The null hypothesis (often denoted
H0) postulates that there is usually no significant difference between specified popu-
lations, with any observed difference being due to sampling or experimental error.
Researchers make inferences from quantitative analyses, typically derived from
samples of a given population and statistical modelling; it is hoped (and generally
efforts are made to ensure) that the study group reflects the population as a whole.
84 Key Concepts in the Design of Randomised Controlled Trials 479
The Truth
Treatment A is better Treatment A is no better

than treatment B than treatment B
Type I error
Treatment A is better Correct
(risk of making this
than treatment B (1-β= power)
error = α = the P value)
Conclusions drawn from
a clinical trial
Treatment A is no better Type II error Correct
than treatment B (risk of making this error = β)
Fig. 84.2 Type 1 or alpha error. For any hypothesis, the value of alpha, false positive, is usually
determined in advance, usually at 5%. A false positive should then occur in less than 1 in 20 studies
In a clinical study, the p value is the risk of a false positive conclusion that a treat-
ment is effective, when in truth it is not (see Fig. 84.2). In essence the p value tells
you how often the results would have occurred by chance if the experimental treat-
ment was no different from the control. Authors are often asked to report exact
p-values (often together with 95% confidence intervals of the estimates of effect
sizes) as well as to perform hypothesis tests, that is, separating the main results into
being statistically significant or not, given a pre-set level of rejection.
If, for example the experimental therapy produces a relative risk reduction of
25% (itself uncommon in modern clinical practice) and the P value is 0.06, this
means that if there was really no difference between the treatment and control arm
and if you repeated the trial 100 times, results as a more extreme than those observed
(i.e a relative risk reduction of 25% or more) would have happened 6 times in a
hundred by chance alone. Put another way, the p value is a measure of the effect of
chance within a study of getting a particular result, (i.e p < 0.05 or < 1 in 20).
By convention, a p < 0.05 is considered ‘statistically significant’ and a trial gen-
erating a relative risk reduction of 25% with a P value of < 0.05 is positive and has
established that the experimental and control treatments really are different. Low
p-values are typically used as evidential measures to support research findings in
published medical research. However, this assumption may be misguided as a p
value only measures the probability of the observed results being a chance phenom-
enon and hence p values tell us nothing about the size of a difference or even the
direction of the difference. The clinical significance of the p value must be inferred
by a thorough understanding of the study’s question, design, and conduct.
Power in Randomised Controlled Trials
The probability of drawing a true positive conclusion is called the ‘Power’ of the
study. In planning a trial, investigators should decide how great a risk they are will-
ing to run to drawing the wrong conclusion.
480 K. J. O’Flynn
Fig. 84.3 The 5 key • α error risk of a false positive

elements in planning • β error risk of a false negative
an RCT • The clinical significant difference worth detecting
• The rate of event treatment in the control patients
• The number of patients in each group
In doing so they often decide on a 5% risk of getting a false positive outcome

from the trial referred to as an alpha error or type I error (Fig. 84.3). Typically, they
may also decide to run a risk of a false negative outcome and to run a 20% risk of
concluding that the experimental treatment and conventional treatments do not pro-
duce different clinical outcomes when in fact they do. This is termed a false nega-
tive, Type II or Beta (β) error. If β is 0.20, then the power of the study is 1-0.2 or
80%. In essence if the experimental and conventional therapy do produce different
outcomes, the study has an 80% chance of finding it and labelling it statistically
significant. Most authors decide a false positive risk α of 0.05 and a false negative
risk β of 0.2, sometimes referred to as ‘conventional levels of statistically
significance’.
In other clinical situations, the clinicians may want to establish that the new
treatment is not better than, but as good as a standard treatment (termed a non-
inferiority trial): the false negative risk may be set lower. In setting out to do a clini-
cal trial, the trialists need to use their judgement about what the expected outcome
in patients assigned to conventional treatment and the degree of difference between
those assigned the experimental treatment that would be considered clinically
significant.
These five elements (Fig. 84.3), α, β, the clinically significant difference, the rate
of event treatment in the control patients and the number of patients in each group
are interrelated. If investigators set α and β, and the clinically significant difference
they wish to detect, knowing the rate of events that occurs with conventional ther-
apy, they can then calculate the number of patients required for the trial. Trialists
need to balance the precision of the trial with the extra effort and expense to recruit
larger number of patients.
Conducting an RCT
Types of RCTs
Explanatory RCTs test efficacy in a research setting with highly selected partici-
pants and under highly controlled conditions. In contrast, pragmatic RCTs test
effectiveness in everyday practice with relatively unselected participants and under
flexible conditions. RCTs can also be classified as “superiority trials,” “non inferior-
ity trials,” and “equivalence trials,” which differ in methodology and reporting.
Other study designs include the following
84 Key Concepts in the Design of Randomised Controlled Trials 481
• Parallel group—each participant is randomly assigned to a specific group, either

receiving the new intervention or acting as a control.
• Crossover—over time, each participant receives (or does not receive) an inter-
vention in a random sequence
• Cluster—pre-existing groups of participants (e.g., villages, schools) are ran-
domly selected to receive (or not receive) an intervention.
• Factorial—each participant is randomly assigned to a group that receives a par-
ticular combination of interventions or non-interventions e.g. Stampede.
Randomisation Procedures
After randomisation, two (or more) groups of subjects are followed up in exactly the
same way, the only differences being the therapeutic intervention they receive. The
most important advantage of proper randomisation is that it minimises allocation
bias, balancing recognised known and unknown factors, in the assignment of treat-
ments. An ideal randomisation procedure achieves the following goals:
• Equal group sizes for adequate statistical power, especially in subgroup analysis.
• Low selection bias. The procedure should not allow an investigator to predict
the next subject’s group assignment
• Low probability of confounding i.e., a low probability of “accidental bias”
No single randomisation procedure meets those goals in every circumstance, so
researchers must select a procedure for a given study based on its advantages and
disadvantages. Simple randomisation (akin to tossing a coin) may result in imbal-
anced group sizes in small RCTs and is no longer used. To balance group size
’restricted randomisation’ is frequently used. In blocked randomisation, a “block
size” and “allocation ratio” (number of subjects in one group versus the other group)
are specified, and subjects are allocated randomly within each block. This type of
randomisation can be combined with ‘stratified randomisation’, to ensure good
balance of participant characteristics in each group. Integral to the process is ‘allo-
cation concealment’, defined as the procedure for protecting the randomisation
process so that the treatment to be allocated is not known before the patient is
entered into the study. Most large RCTs use some form of central randomisation. An
RCT may be ‘blinded’, a procedure that prevent study participants, caregivers, or
outcome assessors from knowing which intervention was received. In pragmatic
trials, (e.g surgery and some therapeutic trials), although the participants and pro-
viders are often unblinded, it may be desirable to blind the assessor or obtain an
objective source of data for evaluation of outcomes. RCTs may be stopped early if
an intervention produces ‘larger than expected benefits or harm’. These boundaries
may be set by an overseeing ethics committee.
482 K. J. O’Flynn
Further Reading
Centre for Evidence Based Medicine. http://www.cebm.net CEBM. Oxford

Sackett DL, Haynes RB, Guyatt GH, Tugwell P. Clinical epidemiology: a basic science for clinical
medicine. 2nd ed. Little Brown; 1991. ISBN 0-316-76599-6.
Sedgwick P. Understanding statistical hypothesis testing. BMJ. 2014;348:g3557. https://doi.
org/10.1136/bmj.g3557.
Chapter 85
Reporting and Interpreting Data
from RCTs
Kieran J. O’Flynn
In order to critically appraise research, and make informed decisions about pre-
sented evidence, one must understand a trial’s design, conduct, analysis and inter-
pretation, to accurately assess the validity of its results.
Basic Principles
The types of statistical methods used in RCTs depend on the characteristics of the
individual trial. Important considerations in the analysis of RCT data include:
• The CONSORT statement (Fig. 85.1) comprising a 25-point check list and a
flow diagram, is an evidence-based, minimum set of recommendations for
reporting randomised trials. It offers a standard way for authors to prepare reports
of trial findings, facilitating their complete and transparent reporting, aiding their
critical appraisal and interpretation. It is designed to enable readers understand a
trial’s design, conduct, analysis, and interpretation, and to assess the validity of
its results. The CONSORT statement is endorsed by many prominent general and
specialty medical journals.
• Internal and external validity. Because RCTs reduce spurious causality and
bias, they are considered by most to be the most reliable form of scientific evi-
dence in the hierarchy of evidence and in combination with meta-analysis form
the bedrock of many clinical practice guidelines in urological practice.
Disadvantages of RCTs include their cost and external validity (i.e. its applica-
bility in a ‘real world setting’). Factors include:
K. J. O’Flynn (*)
e-mail: kieran.oflynn@srft.nhs.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_85
484 K. J. O’Flynn
Fig. 85.1 CONSORT 2010 checklist of information to include when reporting a randomised trial
–– Where and how the RCT was performed; what works in one healthcare setting
may not work in another and patients in RCTs are recognised to do better than
standard care as they have more interaction with clinicians
–– Characteristics of the patients; RCTs often exclude the elderly, and those with
common co-existing medical conditions and may therefore not be applicable
to some patients
–– Outcome measures: RCTs may use composite measures infrequently used in
clinical practice
–– Limited study duration may result in incomplete reporting of adverse effects
of interventions
85 Reporting and Interpreting Data from RCTs 485
• Intention to treat analysis. This enables a real-world view of the efficacy of the
trial in which all participants are evaluated in the group to which they were
assigned, irrespective of whether they received the allocated treatment or not.
• Subgroup analysis. These should be specified at the outset of the study and be
biologically plausible. Multiple comparisons of groups may produce false posi-
tive findings that cannot be confirmed by other studies.
Confidence Intervals (CI)
While authors are often asked to report exact p values (see Chap. 84), an alternative
approach is that instead of being informed that some degree of relative risk reduc-
tion is likely to occur by chance (e.g less than 5%, p < 0.05 or less than 1%, p <
0.01), authors can say that the true that the true risk of reduction is likely to lie most
(e.g 90% or 95%) of the time; this is termed the confidence interval.
P values and CIs refer to two different, yet complementary approaches to statisti-
cal analysis: hypothesis testing and estimation. In the hypothesis testing framework,
the p value describes the probability that the observed result is due to chance if, in
fact, there is no true difference between the groups. A very small p value suggests
that the null hypothesis is highly unlikely to be true, and thus suggests that the
observed effect is real.
In contrast, the estimation approach seeks to quantify the effect of interest and
provide a measure of the associated degree of uncertainty by means of a CI. The CI
represents a range of values on either side of the estimate between which we can be
95% sure that the true values falls. A CI therefore communicates the degree of
uncertainty of the study result as an estimate of the ‘true’ population value. The
width of the confidence interval is determined by the sample size (larger samples
will give more precise results with a narrower CI) and the variability of the charac-
teristic being measured (between subjects, within subjects, measurement error etc.).
elative Risk Reduction, Absolute Risk Reduction

R
and Numbers Needed to Treat (NNT)
Published studies aim to express the benefits of a particular treatment in terms of

clinical significance. A common technique is to calculate the percentage reduction
in the risk of target complications (e.g. death, disease recurrence) through active
treatment by comparing the difference in complication rates between placebo and
active patients with what would have occurred with no treatment (i.e. the complica-
tion rate seen in placebo/no or standard intervention patients). This calculation is
called the relative risk reduction (RRR), and its derivation is shown in figure below
(Fig. 85.2). Applying this yardstick, relative risk reductions of ≥ 50% almost always
486 K. J. O’Flynn
Relative risk reduction, absolute risk reduction and

numbers needed to treat
No Experimental event rate (EER) = A

Outcome
Outcome A+B
Control event rate (CER) - C

C+D
Exposed A B Total
Relative risk - EER

CER
Not Exposed
C D Total
Relative risk reduction - EER - CER expressed as a percentage
CER
Absolute risk reduction = EER - CER
Number need to treat (NNT) = 1

ARR
Fig. 85.2 How relative risk reduction, absolute risk reduction and number need to treat are
calculated
and of ≥25% often are considered to be clinically significant. However, the relative
risk reduction discards the measure of the risk of no treatment, as it does not account
for the absolute risk of the event taking place. The absolute difference in the poten-
tial risk of death or disease recurrence shows the absolute gains from treating the
therapy group and captures the clinical significance of the difference. It therefore
provides more information than the relative risk reduction, but not in a form that can
readily be used in clinical decision making with patients.
The number need to treat (NNT) was developed to improve a clinician’s ability
to communicate the consequences of a therapy. The NNT is calculated from a
dichotomous outcome (i.e. dead/alive, metastasis/no metastasis). It is the reciprocal
of the absolute risk difference between the groups in a clinical trial. One divided by
the absolute risk difference equals the NNT. It represents the number of patients, on
average, that must be treated to result in one additional outcome. If the NNT is
large, many patients would need to be treated to gain a benefit. If the NNT is small,
few patients need to be subjected to therapy to observe a benefit.
Kaplan Meier Curves and Hazard Ratio
A Kaplan Meier (KM) curve is a nonparametric statistical technique using a graphi-

cal way of describing the timing of dichotomous events (e.g. death, recurrence of
cancer, stone passage etc) in a group of patients at different times from a defined
starting point. The survival curve usually describes the probability of a patient being
event-free (along the Y axis) and the time past after entry into the study (along the
X axis).
85 Reporting and Interpreting Data from RCTs 487
The median survival time is of particular importance when describing time to

event data. It is the duration of follow-up at which the Kaplan-Meier probability is
0.5 and it represents the average survival time. The median survival time until death
is derived by drawing a horizontal line across from the probability of 0.5, and it is
the time point at which this line crosses the curve for a treatment group.
The numbers of patients in each group that were at risk of the ‘event’ during
follow-up are shown under the Kaplan-Meier survival plot. Typically, towards the
end of the study these numbers drop. Therefore, the Kaplan-Meier survival proba-
bilities will often decrease in accuracy because they are based on decreasing num-
bers of participants. For most Kaplan-Meier plots, the curves on the right-hand
flattens as fewer participants experience the event. Consequently, caution is gener-
ally needed not to over interpret this part of the plot unless a reasonable number of
subjects are still at risk.
The hazard ratio, sometimes called a relative hazard, is typically used to com-
pare time to event data between two treatment groups and is derived as the ratio of
the hazard of death for the intervention group to the hazard of death for the placebo
group across the study period. A hazard ratio above 1 indicates a raised hazard for
the treatment group, below 1 a decreased hazard, while a value equal to 1 would
indicate that the hazard of death for the was equal for both groups.
RCTs in Surgery
Half of all trials are never published, and positive trials are twice as likely to be
published as results from negative trials. The ISRCTN registry is a primary clinical
trial registry recognised by WHO. Its key purpose is to ensure that all healthcare
decisions are informed by the available evidence, thus aspiring to overcome publi-
cation bias and selective reporting. A growing number of medical journals now
insist on registration of clinical trials before they consider the submission of a paper.
Although improving, there remains a relative paucity of high quality RCTs in the
surgical literature relating to surgical management. RCTs in surgery pose particular
problems. At its core is the fact that surgeons invest a great deal of time and effort
in acquiring operative skills and may be reluctant to trial a new technique that truly
assesses its efficacy once they have mastered the procedures intricacies. In urology,
robotic surgery has become the norm for radical prostatectomy and partial nephrec-
tomy, untroubled by an evidence base attesting to its superiority over conventional
surgery.
As the evidence base increases, (much derived from cohort studies and follow-up
databases, rather than RCTs), surgeons’ attitudes evolve. Our greater understanding
of the natural history of low-grade prostate cancer has led to a reduction in the num-
ber of radical prostatectomies being performed. Ideally new technology should be
carefully assessed and validated prior to its introduction into health care. Whereas
well conducted RCTs remain the best source of evidence in the efficacy of treatment
we remain likely to be guided by well-designed cohort studies and surgical
‘influencers.’
488 K. J. O’Flynn
Further Reading
Consort Transparent Reporting of Clinical Trials. http://www.consort-statement.org/consort-2010

ISRCTN registry http://www.isrctn.com
Sackett DL, Haynes RB, Guyatt GH, Tugwell P. Clinical epidemiology. a basic science for Clinical
medicine. 2nd ed. Little Brown; 1991. ISBN 0-316-76599-6.
Chapter 86
Health Technology Assessment (HTA)
Luke Vale, Diarmuid Coughlan, and Michael Drinnan
Health technology assessment (HTA) is a multidisciplinary process that uses explicit

methods to determine the value of a health technology at different points in its life-
cycle. The purpose is to inform decision-making to promote an equitable, efficient,
and high-quality health system.
What is the Process?
The process is formal, systematic, and transparent and uses state-of-the-art methods
to consider the best available evidence. This synthesis is then used, often within an
economic evaluation, to determine whether the technology should be adopted. The
HTA process is linked to national and international decision-making bodies that
approve health technologies for routine clinical use.
HTA encompasses all interventions, be it a test, device, medicine, vaccine, pro-
cedure or program that seek to contribute to the prevention, diagnosis, treatment,
and rehabilitation of health problems. The underlying aim is for all existing and new
health care interventions to undergo stringent assessment. This assessment can vary
depending on the intervention but essentially considers safety and clinical benefits
alongside the cost analysis.
L. Vale (*) · D. Coughlan

Newcastle University, Newcastle upon Tyne, UK
e-mail: luke.vale@ncl.ac.uk; diarmuid.coughlan@newcastle.ac.uk
M. Drinnan
Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
e-mail: michael.drinnan@ncl.ac.uk

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2_86
490 L. Vale et al.
What Does it Involve?
The HTA process provides evidence statements concerning the technology under
assessment by addressing a number of interrelated questions (Box 86.1).
Box 86.1 Evidence domains for HTA

• Does it fulfil a need?—health care gap
• Can it be described?—specification
• Is it safe?—safety
• Does it work?—reliability
• Does it do what it is supposed to do?—validity
• Does it improve outcome under ideal conditions—efficacy
• Does it improve outcome under routine conditions?—effectiveness
• Is it appropriate within the chosen setting?—acceptability
• Is it widely adoptable?—generalisability
• Does it provide value for money?—cost effectiveness
• Is it better than existing technologies?—implementation
To answer these questions evidence must be collected by conducting preliminary

testing and proof of principle research. Once there is approval for human testing,
clinical studies are performed which vary in scope according to the technology but
generally the pattern used for new drug assessment (Box 86.2). This evidence is
then reviewed, synthesised, and used to model longer-term implications of
implementation.
Box 86.2 Phases of clinical study required for HTA

Primary research
Phase 1 Confirmation of safety in humans
Phase 2 Demonstration of probable benefit
Phase 3 Controlled study against comparator
Phase 4 Pragmatic studies against standard care
Secondary research
Systematic review and meta-analysis of existing evidence
Mathematical modeling of effectiveness and cost-effectiveness
The National Institute for Health Research (NIHR) fund researchers to conduct
HTA reports in the UK. An example in in urology imaging is the use of
Multiparametric MRI to improve detection of prostate cancer compared with tran-
srectal ultrasound-guided prostate biopsy alone: the PROMIS study.
86 Health Technology Assessment (HTA) 491
Specification
The first stage is for the innovator to accurately describe the technology and receive
regulatory approval. For a device, this involves completion of a technical file speci-
fying its components and how they are put together for functionality and is related
to intellectual property (IP) protection and conformity assessment. For a new care
pathway, it will involve description of all steps in terms of who does what, when
and where.
Safety
Except for medicines, there is little uniformity of safety approvals required for new
health technologies. In the United Kingdom (UK), the Medicines and Healthcare
Products Regulatory Agency (MRHA) categorises devices into one of four classes
according to perceived risk, and then assessed for relevant safety standards for use
in humans. In contrast, introduction of new surgical procedures relies predomi-
nantly on the ethical framework of clinician innovators.
Reliability and Validity
It is crucial that any new technology does what is meant to do; validity and does it
in a reliable way; encompassing technical reliability and functional repeatability
within acceptable margins of error. Demonstration of validity and reliability requires
well-designed studies using appropriate methodology and analysed to inform use-
fulness of the technology in its chosen setting.
Efficacy and Effectiveness
Efficacy describes whether a technology works in the intended way and is assessed
by measuring a change in an appropriate outcome under carefully controlled condi-
tions by its developers. This is usually done by a comparative study against an exist-
ing standard intervention or a placebo/no intervention arm. The primary outcome
must be carefully chosen to best reflect the improvement in health care envisaged
and which allows wider comparison of its worth. The next step is to see if the benefit
is transferable to conditions of standard care, effectiveness. Ideally, this should be
done using a pragmatic randomised trial design controlled against routine practice.
These studies also determine whether the technology is acceptable for its chosen
health care setting often using qualitative methods and whether it is generalisable
across settings.
492 L. Vale et al.
Adoption
Having demonstrated that a new technology is safe, and more effective than existing
options a decision must be made whether it should be implemented, guided by an
interaction between providers, funders and consumers. In centrally funded health
care systems, such as the NHS, there is more of a focus on maximising the benefits
that can be obtained from the finite resources allocated to health care. This requires
a more rigorous comparative evaluation to ensure that scarce resources are used to
fund technologies that give most benefit. In England, a key part of this role is under-
taken by the National Institute for Health and Care Excellence (NICE) (similar
organisations exist for the other UK nations and in many other countries worldwide).
NICE relies on HTA reports produced by independent groups contracted to do
this work. These reports synthesise available evidence to estimate, with specified
margins of uncertainty, relative clinical effectiveness, and cost-effectiveness. The
available evidence includes published and unpublished information and often
detailed critiques of evidence synthesis and economic evaluations submitted by
Industry to NICE. The HTA guides and gives quantifiable justification to the deci-
sion of policy makers as to whether a technology should or should not be adopted.
This is increasingly governed by estimates of the cumulative difference in costs and
benefits from using the technology compared with an alternative over a period of
time. The time period used depends on how long any difference in outcomes is
expected to last; for treatments, the patient’s lifetime is typically used, whilst for
devices the lifetime of the technology is more appropriate.
The decision whether to adopt is usually governed by funding constraints (bud-
get impact) since most new technologies will involve an increase in expenditure
that, given that funds are limited, has to be saved elsewhere (opportunity cost). This
decision can be related to estimates of the expenditure needed to gain the benefit of
the new technology, or more commonly to the cost of increasing well-being amongst
users measured, for example, by quality-adjusted life years (QALYs). NICE typi-
cally recommends that a technology is suitable for use within the NHS if the cost
per QALY gained is less than £20,000.
Further Reading
Brown LC, Ahmed HU, Faria R, El-Shater Bosaily A, Gabe R, Kaplan RS, et al. Multiparametric
MRI to improve detection of prostate cancer compared with transrectal ultrasound-guided
prostate biopsy alone: the PROMIS study. Health Technol Assess. 2018;22(39):1–176.
Goodman CS. HTA 101: Introduction to Health Technology Assessment. 2014. Web-based document
freely accessible at: https://www.nlm.nih.gov/nichsr/hta101/HTA_101_FINAL_7-23-14.pdf
National Institute for Health and Care Excellence. The Guidelines Manual. London:
National Institute for Health and Clinical Excellence. January 2022. Available from:
https://www.nice.org.uk/process/pmg36/chapter/introduction-t o-h ealth-t echnology-
evaluation#medical-technologies-evaluation-programme
O’Rourke B, Oortwijn W, Schuller T. The new definition of health technology assessment: a mile-
stone in international collaboration. Int J Technol Assess Health Care 2020;36: 1–4. Available
from: https://www.inahta.org/2020/05/announcing-the-new-definition-of-hta/
Appendices
Appendix 1: The Electromagnetic Spectrum
Ionising radiation consists of particles, or electromagnetic waves, that are energetic

enough to detach electrons from atoms, or molecules, causing ionisation. Ionisation
produces free radicals, which are atoms, or molecules, containing unpaired elec-
trons that tend to be especially chemically reactive due to their electronic structure.
Free radicals have damaging effects on tissue.
The ability of an electromagnetic wave to ionize an atom, or molecule, depends
on its frequency, which determines the energy of its associated particle, the photon.
Roughly speaking, particles or photons with energies above about 10 electron volts
(10 eV) are needed to cause ionisation. This corresponds to radiation with a wave-
length less than about 100 nm. Therefore radiation from the short-wavelength end
of the electromagnetic spectrum, high frequency ultra-violet, X-rays, and gamma
rays, is ionizing and can be harmful. But lower energy radiation, such as visible
light, infra-red, micro-waves, and radio waves, are non-ionizing and are thought to
be essentially biologically harmless below the levels that cause tissue heating.
© The Editor(s) (if applicable) and The Author(s), under exclusive license to 493
Springer Nature Switzerland AG 2023
https://doi.org/10.1007/978-3-031-26058-2
494 Appendices
Frequency (Hz)
Wavelength
Gamma-rays 0.1 Å
1019
1Å
0.1 nm
1018
X-rays
1 nm
400 nm
1017
10 nm
1016
Ultraviolet 500 nm
100 nm
1015
Visible
1000 nm
Near IR
1 µm 600 nm
1014
Infra-red 10 µm
1013
700 nm
Thermal IR 100 µm
1012
Far IR 1000 µm
1000 MHz 1 mm
1011
UHF 1 cm
Microwaves
500 MHz 1010
Radar
10 cm
109
VHF 1m
7–13 108 Radio, TV
100 MHz FM 10 m
VHF 107
2–6
50 MHz 100 m
106 AM
1000 m
Long-waves
Appendices 495
Appendix 2. MR Conditional List: Urological Device Safety
MR SAFE
‘An item that poses no known hazards resulting from exposure to any MR
environment. MR Safe items are composed of materials that are electrically
nonconductive, non-metallic, and nonmagnetic’
MR CONDITIONAL
‘An item with demonstrated safety in the MR environment within defined
conditions. At a minimum, address the conditions of the static magnetic
field, the switched gradient magnetic field and the radiofrequency fields.
Additional conditions, including specific configurations of the item,
may be required.’
MR UNSAFE
‘An item which poses unacceptable risks to the patient, medical staff or
other persons within the MR environment.’
Head only
using
Whole transmit/
Generator model Lead model body receive
number number label eligible coil 3T 1.5
Sacral neuromodulation systems
Axonics Sacral Model 1101 Tined Lead yes yes yes
neuromodulation (Model
system 1201/2201),
Medtronic 3058 (if serial no yes
Interstim II number begins
with NJYES)
Medtronic 3058 978B1 yes yes
Interstim II
Medtronic 3203 (depends Any no yes
Interstim on serial Interstim
number) lead
Medtronic 427T no no
Interstim Twin
Medtronic 97810 978A1 yes yes
Interstim micro
Penile implants
AMS pumps AMS Malleable yes yes yes
600/600M
AMS 700 Ultrex yes
plus
AMS 700 CX S 1.5T yes
inflatable
AMS penile AMS 700 yes
prosthesis CX/700
CXM/700
CXR/700
LGX/700/
Ambicor penile
prosthesis
496 Appendices
Head only
using
Whole transmit/
Spectra/spectra yes
concealable
penile prosthesis
AMS 700 yes
inflate/deflated
pump
AMS 700 series yes
3-piece inflatable
pump
AMS 700 yes
Ultrex/700
Ultrex Plus
Prosthesis
AMS 700 Ultrex yes
AMS Dynaflex yes
AMS Hydroflex yes
AMS malleable yes

600/600M
AMS Malleable yes
650
AMS Tactile yes
pump
AMS DURA II yes
penile prosthesis
AMS Duraphase
Surgitek Flex-Rod II yes
Flexi-Flate yes
Flexi-Rod yes
(standard)
Appendices 497
Head only
using
Whole transmit/
Jonas Dacomed Penile implant yes
Corp
Omniphase
Mentor Corp Mentor flexible yes
Mentor inflatable yes
Osmond Osmond external yes
Coloplast Corp Excel inflatable yes

penile prosthesis
90–95XXSC
Genesis yes
Malleable penile
implant
Titan inflatable yes
Penile prosthesis
Rigicon Rigi10 malleable yes yes
penile prosthesis
Infla10
Nephrostomy/ The majority are MR safe. Below are some that are conditional (and 1 that
stents is MR unsafe)
Cook resonance
ureter stent
Applied medical
Silhouette ureter
stent
Urovision- Magnetic Black
Urotech Star stent
Prostatic stents
Endocare Horizon yes
prostatic stent
SRS medical Spanner
Prostatic stent
Allium Medical Triangular
prostatic stent
Bulbar ureteric
stent
498 Appendices
Head only
using
Whole transmit/
Miscellaneous urological devices
NeoTract Inc UroLift Implant
Boston Scientific/ AMS 800

AMS Urinaryes
control system
Uromedica Adjustable
Continence
therapy ProACT/
ACT
AMI ATOMS system
Promedon Victo/
Victo Victo + artificial
sphincter
Zephyr Surgical ZSI 375 artificial
Implants sphincter
Incontinence
sling systems
Appendices 499
Appendix 3: Radionuclides Used in Urology
Radionuclide Half life Use(s) in urology

Carbon-11 20 mins Positron emitter used in Choline PSMA PET for prostate
cancer.
Caesium-131 9.7 days Used for LDR brachytherapy, emits soft X-rays.
Chromium 51 28 days Gamme emitter used in radioisotope measurement of GFR
with EDTA
Fluorine-18 110 mins Used as FLT (Fluorothymidine), F-miso
(Fluoromisonidazole), 18F-choline: used as tracer with
PET, for imaging malignant tumours
Gallium-68 68 mins Positron emitter used in PSMA PET-CT. Derived from
germanium-68 in a generator.
Germanium-68 271 days Used as the ‘parent’ in a generator to produce Ga-68.
Iodine-125 60 days Used in LDR brachytherapy also diagnostically to evaluate
the GFR of kidneys. Iodine-125 does not emit a photon of
sufficient energy to be useful for renal imaging
Iridium-192 74 days Supplied in wire form for use as an internal radiotherapy
source for HDR brachytherapy for prostate cancer (used
then removed). Strong beta emitter.
Lutetium-177 6.7 days Lu-177 is increasingly important as it emits just enough
gamma for imaging while the beta radiation does the
therapy on metastatic prostate cancer. It is usually
produced by neutron activation of natural or enriched
lutetium-176 targets or indirectly by neutron irradiation of
Yb-176.
Molybdenum-99 66 hours Used as the ‘parent’ in a generator to produce
technetium-99m.
Palladium-103 17 days Used to make permanent implant seeds for LDR
brachytherapy for prostate cancer. Emits soft x-rays.
Radium-223 11.4 d Used for bone pain in metastatic prostate cancer. Lodges in
bone, emits soft X-rays.
Strontium-89 50 days Very effective in reducing the bone pain of metastatic
prostate cancer. Beta emitter.
Technetium-99m 6 hours Used in to image the skeleton and kidney (structure and
filtration rate). Produced from Mo-99 in a generator. The
most common radioisotope for diagnosis, accounting for
over 80% of scans.
Ytterbium-177 1.9 hours Progenitor of Lu-177, through neutron irradiation of
Yb-176.
500 Appendices
Appendix 4: Expected Laboratory Values
Test Abbreviation Lower limit Upper limit SI Unit

Blood
Haematology
Haemoglobina Hb 12 18 g/dL
White cell count WCC 4.5 × 109 1.1 × 1010 /L
Mean corpuscular volumea MCV 78 102 fL
Mean cellular haemoglobin MCHC 310 370 g/L
concentration
Haematocrita 0.36 0.49 %RBCs
Platelets 130 × 109 400 × 109 /L
Serum
Basic biochemistry
Glucose 3.9 6.1 mmol/L
Glycated haemoglobin HBA1c 42 48 mmol/mol
Creatininea Cr 52 119 μmol/L
Urea 2.9 8.9 mmol/L
Sodium Na++ 135 145 mmol/L
Potassium K+ 3.4 5 mmol/L
Bicarbonate HCO3− 22 29 mEq/L
Chloride Cl−− 95 108 mmol/L
Magnesium Mg++ 1.6 2.5 mg/dL
Calcium Ca++ 2.1 2.6 mmol/L
Phosphate PO3− 0.81 1.45 mmol/L
Parathyroid hormone PTH 10 55 pg/mL
Uric acid 0.5 1.5 mg/dL
Total Protein 6 8 g/dL
Albumin 31 43 g/L
Bilirubin (direct) 0 7 ug/dL
Alanine aminotransferasea ALT 0.12 0.92 μkat/L
Aspartate aminotransferasea AST 0.15 0,67 μkat/L
Gamma glutamyl transferasea γGT 0 65 u/L
Alkaline phosphatasea ALP 0.5 0.92 μkat/L
Amylase 0.88 2.05 nkat/L
Andrology
Follicle stimulating hormonea FSH 1.5 12.4 mIU/ml
Luteinising hormonea LH 1.4 15.4 IU/L
Testosterone (male)b 9.36 37.1 nmol/L
(female) 0.21 2.98 nmol/L
Appendices 501
Test Abbreviation Lower limit Upper limit SI Unit

Sex hormone binding globulina SHBG 10 57 nmol/L
Prolactina <550 μg/L
Anti-Mullerian Hormonec AMH 14.3 48.5 pmol/L
Tumour markers
Beta HCG (male) βHCG <2 mIU/ml
Placental alkaline phosphatase PLAP <100 mIU/L
(male)
Alpha fetoprotein (male) αFP 10 20 ng/mL
Total prostate specific antigen PSA <4 ng/ml
Free:Total PSA ratio >20 %
a
Male to female variation
b
Varies dependent upon timing of sample
c
Female only test
Test Lower limit Upper limit Unit

Urine
Volume 0.8 2 L/24 hrs
pH 5 7
Specific gravity 1.001 1.035
Osmolality 38 140 mOsm/kg H2O
Calcium 0 7.5 mmol/24 hrs
Phosphate 0.97 1.345 mmol/L
Citrate 40 60 mEq/24 hrs
Oxalate 0.11 0.46 mmol/24 hrs
Protein <100 mg/24 hrs
Urea 428.4 714 mmol/24 hrs
Uric acid 250 750 mg/24 hrs
Cystine <240 mg/L
Semen
Volume 1.5 7.6 mls
pH 7.2 7.8
Concentration 15 259 ×106/ml
Sperm per ejaculation 20 150 ×106/ml
Motility − excellent 32 75 %
Motility − excellent + sluggish 40 81 %
Morphology >4 48 %
DNA fragmentation 25 <15 %
502 Appendices
Appendix 5: Levels of Evidence for Therapeutic Studiesa
Levels of
evidence Therapy/Prevention/Aetiology/Harm
1a Systematic review with homogeneity of randomised controlled trials (RCTs)
1b Individual RCT with narrow confidence interval
1c All or none. Met when all the patients died before the treatment became available,
but some now survive on it, or when some patients died before the treatment
became available, but now none die of it.
2a Systematic review (with homogeneity) of cohort studies
2b Individual cohort study (including low quality RCT; (e.g. follow-up <80%)
3a Systematic review (with homogeneity) of case-controlled study
3b Individual case- control study
4 Case series (and poor-quality cohort and case control studies)
5 Expert opinion without explicit critical appraisal or based on physiology, bench
research or ‘first principles’
Adapted from the Oxford Centre for Evidence Based Medicine—Levels of
a
Evidence, available at www.cebm.org.uk

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Imaging and

Imaging and Technology

Benjamin Starmer Steve Payne

Springer-Verlag London 2012

ISBN 978-3-031-26057-5 ISBN 978-3-031-26058-2 (eBook)

Part I Imaging Radiology

Part II Imaging Nuclear Medicine

Part III Technology Diagnostic Technology

Part IV Technology Operative

44 Venous Thromboembolic Prevention ���������������������������������������������������� 253

Part V Technology Interventional

79 Augmented Intravesical Drug Administration�������������������������������������� 447

Part VI Technology of Renal Failure

Part VII Assessment of Technology

Omer Abdalla Liverpool University Hospitals NHS Foundation Trust,

Michael Drinnan Newcastle upon Tyne Hospitals NHS Foundation Trust,

Christian Longley Liverpool University Hospitals, Liverpool, UK

Dimitrios Poulikakos Salford Care Organisation, Northern Care Alliance

Robin Weston Liverpool University Hospitals NHS Foundation Trust,

Plain radiography, intra-venous urography, computed tomography (CT), and fluo-

Principles of X-Ray Production

© The Author(s), under exclusive license to Springer Nature 3

106 103 10 10–3 10–6 10–9 10–12 10–15

Fig. 1.1 X-Rays place in the electromagnetic spectrum

Collimator X-Ray beam

Glass Envelope Lead housing

Tungsten Anode Heated Cathode

Bremsstrahlung or Breaking Radiation

This is produced by the sudden deceleration of electrons as they pass close to an

Table 1.1 Thresholds for Lens cataracts >2.0 Sv

Most significantly these include carcinogenesis and mutagenesis. These have no

Ionising Radiations Regulations 2017

Ionising Radiation (Medical Exposure) Regulations 2017

These concern protection of patients and identify responsibilities for employers,

Table 1.2 Typical radiation Chest X-ray 0.02 mSv

Diagnostic reference levels (DRLs) exist which act as a guide to appropriate

How to Perform a Clinical Radiograph

Before undertaking any radiographic examination, appropriate checks must be

© The Author(s), under exclusive license to Springer Nature 9

How to Use a C-arm

Image intensification systems are used to provide images during fluoroscopy

9. Wear adequate protective garments, including thyroid shields.

Contrast agents are a heterogeneous group of pharmaceuticals used during radio-

© The Author(s), under exclusive license to Springer Nature 13

• high concentration agents (high radio-opacity and viscosity)—used for IV

Table 3.1 Recognised Common Rare

Gadolinium Based Contrast Agents (GBCAs)

Micro-bubble particles are used in Contrast-enhanced ultrasound (CEUS) to iden-

Guidance on gadolinium-based contrast agent administration to adult patients. Royal College of

Nicholas Faure Walker and Richard Whitehouse

DXA is a radiological investigation for the measurement of the mineral content of

How Does It Work?

As a simple approximation, the body is composed of three materials:

© The Author(s), under exclusive license to Springer Nature 19

Table 4.1 Factors influencing DXA measurements

Patient Preparation for and DXA Scanning

How Are the Results Expressed?

Z- and T-Scores—What Is the Difference and Why Use Them?

Part I Imaging Radiology

Part II Imaging Nuclear Medicine

Part III Technology Diagnostic Technology

Part IV Technology Operative

44 Venous Thromboembolic Prevention �� 253

Part V Technology Interventional

79 Augmented Intravesical Drug Administration�� 447

Part VI Technology of Renal Failure

Part VII Assessment of Technology

Principles of X-Ray Production

Bremsstrahlung or Breaking Radiation

Ionising Radiations Regulations 2017

Ionising Radiation (Medical Exposure) Regulations 2017

How to Perform a Clinical Radiograph

How to Use a C-arm

Gadolinium Based Contrast Agents (GBCAs)

How Does It Work?

Patient Preparation for and DXA Scanning

How Are the Results Expressed?

Z- and T-Scores—What Is the Difference and Why Use Them?

Why Diagnose Osteoporosis in Someone with No Fractures?

What Else Can a DXA Scanner Do?

Production and Propagation of the Sound Wave

An ultrasound wave is produced by the application of a voltage across a piezo-

Colour Flow Doppler

Range Gated Doppler

Scan Technique and Pathology

Pseudotumours (Benign Variant Anatomy)

The Painful Testicle

The Testicular Mass

Indications for Trans-perineal Biopsy of the Prostate

Principles of Ultrasound and Probe Selection

Positioning and Patient Preparation

Template and Fusion Biopsy

Factors to Consider When Deciding on Clinical Management

PATIENT – Comorbidities & performance status

Interaction with Matter

Physics of Computed Tomography