THE UROLOGY MASTERCLASS-2019

7th Annual CMC Vellore Postgraduate Course

May 31ST — June 1st, 2019

Department of Urology
Christian Medical College
Vellore

(For Private Circulation only)

Department of Urology, CMC, Vellore i

ii Department of Urology, CMC, Vellore
Message

The aim of this programme is to enhance and improve the understanding of critical issues in
urology. This course is aimed at postgraduate students in their final year of urological training.

The Urology masterclass is designed to include didactic lectures on important topics followed by
multiple case presentations. The best way to approach cases will be demonstrated and the students
and encouraged to actively participate in the case discussions. There will be ample opportunity
to improve communication skills. The candidate requires a sound foundation in basic urology on
which an advanced set of skills can be learned. As earlier,there will be short lectures on various
topics of interest followed by a discussion.

The programme has been accredited by the MGR Medical University for 20 CME credit points.
The Urology masterclass would not have been possible without the help of the invited faculty
who graciously agreed to spare time from their busy schedule. We are extremely grateful to
them. I am obliged also the postgraduate students who have taken the effort to attend the
programme. This programme was sponsored by an educational grant from IPCA Urology. We
thank them for their help.

Nitin Kekre Antony Devasia

Chairman, Organising Committee Chairman, Organising Committee

Dr. Santosh Kumar

Organising Secretary

Department of Urology, CMC, Vellore iii

 THE UROLOGY MASTERCLASS - 2019

Invited faculty Departmental faculty

Amlesh Seth Nitin S Kekre

Aneesh Srivastava Antony Devasia
Ansari MS Santosh Kumar
Anup Kumar J Chandrasingh
Arabind Panda Rajiv Paul Mukha
Arun Chawla Nirmal T J
Dorairajan L Anuj Deep Dangi
Ganesh Gopalakrishnan Arun Jacob Philip George
Krishna Sethia Rajadoss
Mallikarjuna C Cornerstone Wann
Maneesh Sinha Partho Mukherjee
Ninan Chacko Benedict P Samuel
R.B. Sabnis Sasi Kumar C
Shrawan Kumar Singh Ranil Johann Boaz
Shivam Priyadarshi Santhosh N
Sudhir Rawal Sudhindra J
Sivasankar V Selvin Theodore Jayanth
Saravanan K

iv Department of Urology, CMC, Vellore

Contributors
Nitin S Kekre Partho Mukerjee Sumanta Mishra
Professor of Urology Associate Professor of Urology Senior Registrar of Urology
Christian Medical College Vellore Christian Medical College Vellore Christian Medical College Vellore

Antony Devasia Ranil Johann Boaz Abhik Debnath

Professor of Urology Assistant Professor of Urology Senior Registrar of Urology
Christian Medical College Vellore Christian Medical College Vellore Christian Medical College Vellore

Mudasir Farooq
Santosh Kumar Sasi Kumar Chandran Senior Registrar of Urology
Professor of Urology Assistant Professor of Urology Christian Medical College Vellore
Christian Medical College Vellore Christian Medical College Vellore

Rakesh Kumar
Chandrasingh J Santhosh N Senior Registrar of Urology
Professor of Urology Assistant Professor of Urology Christian Medical College Vellore
Christian Medical College Vellore Christian Medical College Vellore

Subash Jat
Rajiv Paul Mukha Sudhindra J Senior Registrar of Urology
Professor of Urology Assistant Professor of Urology Christian Medical College Vellore
Christian Medical College Vellore Christian Medical College Vellore

Ujjwal Kumar
Nirmal TJ Selvin Theodore Jayanth Senior Registrar of Urology
Professor of Urology Assistant Professor of Urology Christian Medical College Vellore
Christian Medical College Vellore Christian Medical College Vellore

Abhilash Cheriayan
Anuj Deep Dangi Senior Registrar of Urology
Associate Professor of Urology Christian Medical College Vellore
Christian Medical College Vellore

Anil Kumar
Arun Jacob Philip George Senior Registrar of Urology
Associate Professor of Urology Christian Medical College Vellore
Christian Medical College Vellore

Sadanala Madhuri Evangeline

Rajadoss P Senior Registrar of Urology
Associate Professor of Urology Christian Medical College Vellore
Christian Medical College Vellore

Rohit Sethi
Benedict Paul Samuel Rajendran Senior Registrar of Urology
Associate Professor of Urology Christian Medical College Vellore
Christian Medical College Vellore

Department of Urology, CMC, Vellore v

 CONTENTS
No. Topic Page No.

FACULTY LECTURES
1) Principles of Optics, light sources and energy sources in Urology: ... 1
A perspective for the urologist in training – Arabind Panda
2) Retrograde urethrogram and Micturating cystourethrogram – Dr. V ivek Venketaramani
3) Computerized tomography – Dr. Sagar Sabharwal
4) Diuretic renography- Principles and practice in Urology – Dr. Nitin Abrol
5) Current indications of anti reflux surgery – J Chandrasingh
6) Flaps in hypospadias surgery – J Chandrasingh
7) How to write an answer – Arabind Panda, Rajiv P Mukha
8) Male urethral stricture – Arabind Panda
9) Neoadjuvant chemotherapy in urothelial carcinoma bladder – Antony Devasia
10) Controversies in management of small renal masses-Are we doing more harm than good – Santosh Kumar
11) Management of urinary leak post renal transplantation – Dr. Rajiv P Mukha
12) The role of cytoreductive nephrectomy in metastatic renal cell carcinoma – Dr. Arun Jacob Philip George
13) Future technologies for BPH - Dr. Rajadoss Pandian
14) Standardizing the initial TURBT – Dr.Ninan Chacko
15) Clinical epidemiology for the Urologist – Dr. Thambu David
16) Therepeutic radiotracers in castration resistant prostate cancer – Dr. Julie Hepsibah

LEARNING POINTS
17) Adrenal disorders ... 50
1) Adrenocortical carcinoma
2) Bilateral pheochromocytoma
3) Adrenal incidentaloma
18) Bladder outlet obstruction ... 55
1) Common definitions
2) Surgical options for a large prostate
3) Surgical options for patient on anticoagulation
4) Emerging minimally invasive treatment options for BPE
5) Treatment algorithm for male LUTS
6) Primary bladder neck obstruction
7) Role of urodynamics in BPE with BOO
8) Post TURP incontinence
9) Female bladder outlet obstruction
19) Carcinoma penis ... 61
1) Risk factors for carcinoma penis
2) Premalignant lesions
3) Poor prognostic factors
4) Lymph nodal anatomy
5) Management of the primary
6) Accuracy of lymph node staging
7) Risk groups for lymph nodal metastasis
8) The clinically node negative groin
9) DSLNB
10) Management of palpable nodes
11) Chemotherapy and targeted therapy
12) Molecular prognostic markers for follow up
20) Carcinoma prostate ... 66
1) ISUP grades
2) EAU risk groups
3) Biomarkers in prostate cancer

vi Department of Urology, CMC, Vellore

 4) Indications for repeat biopsy
5) mpMRI in prostate cancer
6) PSMA PET
7) Active surveillance in prostate cancer
8) Adverse features post RP and management
9) Biochemical recurrence
10) Metastatic hormone sensitive prostate cancer
11) Castrate resistant prostate cancer
12) Bone health in prostate cancer
21) Renal cell carcinoma ... 81
1) RCC with IVC thrombus
2) Metastatic RCC
3) Small renal mass
4) Nephron sparing surgery
5) Bilateral RCC
22) Testicular cancer ... 95
1) Post chemotherapy residual mass
2) Indications of PET
3) Scrotal violation
4) Inguinal lymph node involvement
5) Growing teratoma syndrome
6) Testicular microlithiasis
23) Urothelial carcinoma ... 101
1) Risk factors for progression
2) Role of second TURBT
3) BCG
4) Timely cystectomy
5) Choice of urinary diversion
6) Chemotherapy
7) Trimodality bladder preservation
8) Urethral recurrence post radical cystoprostatectomy
9) Upper tract urothelial carcinoma
10) Perforation during TURBT
11) Adenocarcinoma bladder
24) Infections ... 114
1) Emphysematous pyelonephritis
2) Invasive aspergillosis
3) Xanthogranulomatous pyelonephritis
25) Neurovesical dysfunction ... 116
26) Paediatric Urology ... 119
1) Antenatal hydronephrosis
2) PUV
3) VUR
4) VUR with PUJO
5) Ureterocele
6) Undescended testis
7) DSD
8) Recurrent PUJO
27) Trauma ... 132
1) Renal trauma
2) Paediatric renal trauma
3) Bladder trauma
28) Urolithiasis ... 135
1) 1.5cm lower pole calculus
2) Bilateral staghorn calculi
3) Infected staghorn calculus
4) Child with nephrocalcinosis
Department of Urology, CMC, Vellore vii
 5) Urolithiasis in pregnancy
6) PCNL in spine deformity
7) Open stone surgery
8) Ectopic kidney with stone
9) Horse shoe kidney with stone
10) Forgotten DJ stent
11) Hyperparathyroidism
29) Urinary tuberculosis ... 146
1) Diagnosis
2) Treatment
3) Regimes in MDR and XDR
4) Surgical procedures
5) Follow up
30) Urogenital fistulae ... 150
1) Vesicovaginal fistula
2) Ureterovaginal fistula
31) Urethral stricture ... 154
32) Miscellaneous ... 155
1) Post prostatectomy incontinene
2) Stress urinary incontinence
3) Stones in augmented bladder
4) Cancer in augmented bladder
5) Tuberous sclerosis with bilateral AML
6) Erectile dysfunction
7) Post transplant lymphocele
APPENDIX ... 170
33) Clavien Dindo classification of surgical complications
34) ECOG score
35) Karnofsky score
36) ASA classification
37) Charlson comorbidity index
38) French catheter scale
39) Catheter colour codes
40) Glossary of terms used in statistical analysis
41) Levels of evidence and grades of recommendations
42) Radiation exposure of imaging modalities and properties of commonly used contrast media
43) TNM classification of urological malignancies 8 th edition
44) RECIST criteria
45) Bosniak classification of renal cysts
46) Nephrometry scoring systems
47) Renal protection strategies in nephron sparing surgery
48) Stone scoring systems
49) Stone reference tables
50) Categories of unsuccessful treatment with intravesical BCG and SWOG schedule
51) Xpert TB PCR
52) Grading of prostate volume
53) TURP resection techniques
54) AAST organ injury severity scales
55) Goldmann’s classification of urethral injuries
56) Posterior urethral stricture classification
57) Pelvic fracture urethral distraction defect
58) Landmark BPH trials in brief
59) Chemotherapy regimes in Urology

viii Department of Urology, CMC, Vellore

 The Urology Masterclass, Department of Urology, CMC, Vellore 1

Principles of optics, light sources, guide wires and energy source

units in Urology – A perspective for the urologist in training
Arabind Panda, Senior Consultant Urologist, KIMS, Hyderabad

Urologists have been one of the pioneers in the field of Fig 1. – The patent for Hopkins rod lens
endoscopic surgery. The differentiation of the specialty of
urology from general surgery was driven to a large extent
by the fact that a large bulk of urological practice involved
endoscopic instrumentation.

An understanding of how the implements we use in our

practice work is desirable. I have tried to give a basic
understanding of the foundations of the principal
equipment we use in endosurgery. It is not a treatise and is
not intended to be such.

Endoscope Optics
The basic design of the endoscope used today has remained Fig. 2 – Traditional vs. Hopkins rod lens system
essentially similar to the initial design by Harold Horace
Hopkins (1918 -1994). Hopkins was born in Leicester,
England, the youngest son of a baker. He later was the
Professor of Applied Physical Optics at the University of
Reading, Berkshire. Apart from the rod lens system, he
invented the zoom lens, the flexible fibroscope and the
optics for the laser disc/CD [1].

The traditional cystoscope of those times consisted of a

cylindrical tube of air with a train of thin glass lenses
illuminated by an incandescent bulb. The lenses had to be
mounted in rings and reduced the viewing areas. They were
thick, heavy and had suboptimal image quality. Hopkins
designed a completely new system of rod lenses which was
revolutionary in its time. It resulted in an increase in the Fig. 3 –The eyeshield: Originally designed
optical efficiency by 9 times. For 2 good reasons - first, a for use with the eye, is now used to fit a
lens in the endoscope of lower refractive index (n) than the camera via an optical “coupler”.
spacer leads to an increase in optical efficiency of n2. For
glass n = <1.5; thus, n2= 2.25. Secondly the conventional
system required a rifled inner tube to accurately mount
the lenses, which is not required by the rod lens system.
For a given external diameter of endoscope, the lens
diameter of the rod lens is approximately 1.4 times that of
the conventional system. Light admittance is proportional
to diameter 4- that is (1.4 )4= 3.8. The total improvementis
3.8 X 2.25 = 8.55 (approximately 9) [2]. The British and
American endoscope manufactures of the time dismissed
the initial design as having no commercial value. It
required the foresight of Karl Storz, who coupled this new
system with his own invention of the cold light fountain
(having adapted the principle of Hopkin’s fibroscope to
transmit light) to forever change the face of endoscopic
surgery.

Joseph-Frédéric-Benoît Charrière (1803 -1876) was a Swiss-born French manufacturer of surgical instruments.
Inventor of the Charrière scale
 2 The Urology Masterclass, Department of Urology, CMC, Vellore

TABLE 1: Principal terms

Proximal End
Interface point with the eye or video equipment
Distal End
Furthest point from the proximal end or user’s eye
Insertion Diameter
The diameter quoted as the actual diameter inserted into the anatomy of endoscope sheath.
Expressed in the French scale (after Charrière ) or in millimetres.
Instrument Axis
The axis of the instrument relative to the instrument axis
Optical Axis
The axis of the optical path which is displaced to the instrument axis
Angle of View
The angular value of displacement to the optical axis.
The angle between the axis of the endoscope and the center of the field of view.
Optical Field of View
The area which the conical system covers is as a cone
Fiber Illumination
The area which the fibre illumination covers as a cone and is greater than the optical field of view
Light Post
Input point of the illumination when connected to a light guide and source
Eyeshield
Used as a cup for the eye or a diameter for the attachment of video camera equipment. Diameters
specified is the external or outside diameter

Construction of the endoscope

Definition of the image is further improved by a double layer of antireflective coating at each end of the rod. At the ends
of the endoscope are the lens components. These are fixed into position using lens cement. Though modern endoscopes
has heat resistant cement, close contact of the diathermy loop during trans urethral resection can cause the metal
housing to expand and the cement to crack. The subsequent egress of water into the system can permanently ruin the
scope. Heat induced damage to the distal objective lens occasionally occurs. In the hope of reducing such damage newer
scopes have the distal lens made of synthetic sapphire which is substantially harder and heat resistant than optical
glass. At its superior aspect the endoscopes have illumination fibers which transmit light.

Fig 4: Anatomy of an endoscope

John Hunter – (1728 –1793) was a Scottish surgeon, experimental research on gonorrhea and urethral strictures.
 The Urology Masterclass, Department of Urology, CMC, Vellore
Angle and field of view:
Endoscopes are commonly labeled (and colour coded)
according to the angle of view of the endoscope(Fore
oblique - 0, 5, 12, 25, 30 degrees and retrograde - 70, 120
degrees) (Fig. 5). This is achieved by incorporating the
distal objective lens into a set of prisms. The angle of
total internal reflection from the fused surfaces result in
the angle of view (Fig. 6)
Fig. 5 – Angle and field of view
While the angle of view is adjusted to optimize the vision
for different procedures, the field of view is approximately
70 degrees in laparoscopes and around 90° ( Hopkins 1) to
110 ° ( Hopkins 2) in cystoscopes. This does not vary with
different angles.
Fig. 6 Triple prism arrangement at the distal
objective lens
FLEXIBLE FIBREOPTIC SCOPES
Basil Hirschowitz read about the ‘fibrescope’ of Hopkins
and travelled to meet him. He later along with 2 American
physicists Peters and Curtiss at the University of
Michigan,AnnArbor designed the first flexible gastroscope.
The propagation of images and light through a fiber- optic
cable depends on the propagation of light along thin glass
fibers( called the ‘core’) that has been coated with another
transparent material of lower refractory index (called
‘cladding’).
For the transmission of an image the fibers have to be
‘coherent’ - they have fixed relative positions at each end
and can transmit an optical image. A flexible scope
Hugh Hampton Young (1870 –1945 )–Pioneering American urologist, invented the Young punch for treating BPH,
mercurochrome – an antiseptic and devised radical perineal prostatectomy. Founder editor of the Journal of Urology.
3
generally has three fiber optic bundles—two noncoherent
bundles of fibres that transmit light and a single coherent
bundle of glass fibers that constitutes the imaging bundle
Fig. 7: Arrangement of fibres in a flexible scope
COMPOSITE SCOPES
Recently the rigid shaft construction has been merged with
with flexible optics ( Semirigidureteroscopes). The resulting
“miniscopes” thus possess a small-profile rigid shaft with
either one or two irrigation/instrumentation ports and a
fiberoptic imaging bundle. The use of fiberoptics rather
than the traditional rigid rod-lens design allows for the
smaller shaft diameter and also eliminates the optical
distortion when the shaft of the scope is torqued. These
favorable characteristics more than compensate for any
loss in resolution of the endoscopic image resulting from
the fiberoptic imaging bundle.
DIGITAL ENDOSCOPES
Digital flexible endoscopes contain no viewing lens
component. The traditional lenses being replaced by charge
coupled device (CCD) chips small enough to be mounted at
the distal end of the shaft. Instead of a rod-lens design or
fiberoptic viewing bundles, the CCD chip relays digitized
viewing information via a single fiber back to a distant
processor, which will reconstruct and enhance the image
electronically on a television monitor. The quality of the
image is superior to present-day optics, and suffers no
generational deterioration, as is the case with present-
day analog imaging. The durability of the scope is also
better. At the moment, the profile of these scopes are larger
and thicker than the standard flexible scopes and they have
less tip flexibility. This is however likely to change very
quickly in the future.
Lighting systems
The lighting system consists of three components – the light
source, the light cable and the light fibres within the
endoscope.
A typical light source has a lamp, a heat filter, a fan, a
condensing lens and a manual or automatic intensity
control circuit. Two lamps types, halogen and xenon are
commonly used in modern urological practice.
 4 The Urology Masterclass, Department of Urology, CMC, Vellore
Halogen lamp (tungsten halogen lamp): is an incandescent
lamp with a tungsten filament in an atmosphere of inert
gas to which a small amount of a halogen (iodine or
bromine) is added. Combination of the halogen gas and
the tungsten filament produces a halogen cycle chemical
reaction which redeposits evaporated tungsten back on
the filament, increasing its life and maintaining the clarity
of the envelope. The reversible halogen cycle keeps the
bulb clean and the light output remains almost constant
throughout life. Very high tempretures are produced during
use. The colour tempreture is between 3000 – 3500 Kelvin
resulting in a yellowish tinge. It has a life of approximately
2000 hours.
Xenon arc lamps–They are high intensity discharge bulbs
and have no filament that heats up when the light is turned
on. Rather there is an arc tube, which has two thoriated
tungsten electrodes inside with a small gap between them.
When a high voltage is applied to the current it causes it to
arc across the gap producing light. The tube is filled with
xenon at extremely high pressure — up to 30 atmospheres
(440 psi) — which poses safety concerns. If a lamp is
dropped, it can explode.The colour tempreture is between
5000 – 6000 Kelvin, producing a more whiter light. The
lamp life is approximately 500 – 600 hours.
The light cable: Two forms of light cable are available. The
commoner fiber optic cable – has multiple glass fibers which
do not have to be coherent as they do not transmit an image.
With use, progressive damage to the fibres occurs and the
amount of light transmission falls.
The liquid cable: More expensive, they consist of
apressurized tube with a Teflon cladding, filled with a light
transmissive fluid and plugged at both ends. They are
swaged with quartz at the ends for light transmission. The
quartz ends are very fragile.
GUIDE WIRES:
Guide wires serve 2 purposes. 1) They provide access to a
particular part of the urinary tract. 2) They serve as a guide
over which stents can be passed. These 2 functions require
different guide wire characteristics. Access requires tip
flexibility and low friction; for stent or sheath passage
shaft rigidity is of prime importance.
Structure:
A guide wire has a solid wire core called the mandrel- this
determines the stiffness of the wire. This can be of stainless
steel or of Nitinol. This is covered by a tightly coiled steel
wire or a polyurethane coating. The mandrel is usually
tapered allowing for transition from a stiffer shaft to a
flexible tip- the length and degree of tapering determines
the flexibility of the tip. The outer coiled wire may be round
or flat, the latter giving a smoother surface. Movable core
guidewires are available, where the length of the flexible
portion of the tip can be adjusted by withdrawing or
advancing the mandrel.
To promote low friction the standard guide wires have a
polytetrafluoroethylene (PTFE) coating over the tightly
Joseph McCarthy – Invented the best foroblique cystoscope of his time which when coupled to Sterns resectoscope
resulted in the first successful transurethral resection of the prostate.
coiled wire while the polyurethane is usually coated with
a hydrophilic polymer coating.
Standard floppy tip and super stiff ( Amplaz®) guide wires
differ with regard to the stiffness of the inner mandrel which
is made of stainless steel. Because of the stainless steel
nature of this mandrel, these 2 types of guide wires can
kink permanently if handled roughly. In contrast, the nitinol
alloy core guide wire ( Glide wire, Roadrunner , Zebra wire
®)
consists of a nitinol alloy core. Nitinol or Nickel titanium
is a metal alloy of nickel and titanium. Nitinol alloys have
2 unique properties: shape memory and superelasticity.
Both enable it to recover its original undeformed shape at
a tempreture range above its transformation temperature.
This is a usually a temperature that is within the normal
body temperature. Because of this nitinol has enormous
elasticity, some 10-30 times that of ordinary metal. It makes
it very resistant to kinking. However, it has a memory and,
hence, when forcibly advanced it can coil and then recoil,
propelling a tightly coiled guide wire out of the collecting
system. The hydrophilic coating of the nitinol type guide
wires must also be kept moist.
Guidewires used in urologic procedures range in diameter
from 0.018 inches to 0.038 inches. They are available in
lengths of 60 to 260 cm, usually 150 cm.
A double flexible tipped design ( BiWire“) allows for easy
access and prevents against damage to the working channel
of the flexible ureteroscope when it is advanced in a
“monorail” fashion over the wire.
Most wires have a fixed mandrel that is welded to the outer
covering making it possible to transfer rotary motion, or
torque, in a one-to-one ratio to the tip. Certain
nitinolguidewires have gold ( Terumo“ ) or platinum (
Zebra “) coils at the distal tip and tungsten ( Terumo “)
incorporated into the polyurethane for enhanced
visualization under fluoroscopy (Fig. - 8). Additionaly the
hydrophilic Zebra“--wire has a blue and white striped jacket
for visual feedback.
Fig. 8 - Cross section of a Glide Wire “
Hydrophilic coating
Nitinol alloy core
Resists kinking
O
O Restores shape to manufactured state
Polyurethane jacket
with tungsten
for multiple use
2 cm gold coil at distal tip
O Provides enhanced radiopacity
of tip
Core-to-tip design
O Provides optimal torque control
for navigation
 The Urology Masterclass, Department of Urology, CMC, Vellore
The Electrosurgical Unit (ESU)
Electrosurgery is the application of a high-frequency
electric current to biological tissue as a means to cut,
coagulate, desiccate, or fulgurate tissue. In the early part
of the 20th century, Harvey Cushing was looking for ways
to limit bleeding during neurosurgery. William T. Bovie
along with Cushing developed the first commercial ESU
unit in 1926.
The surgical effect of radiofrequency (RF) currents is the
result of tissue heating. In contrast with true electrocautery,
tissue heating is not produced by conduction from a hot
electrode; instead, heat is produced by passing alternating
currents through the tissue, and as the tissue resists the
flow of current, heat is produced. If heating is rapid and
high temperatures are achieved, intracellular and
extracellular fluids are vaporized, and a cutting action is
produced.
Should heat be produced more slowly, cells are desiccated,
producing a coagulation action. In general, cutting is
produced by high tissue temperatures (> 100° C), whereas
coagulation is produced by tissue heating between 70° and
100° C. Coagulation of blood can be achieved by either
contact desiccation or fulguration. In contact desiccation,
the active electrode is firmly in contact with the tissue. In
fulguration, the electrode is not in contact with the tissue,
but instead long sparks carry the RF current from the
electrode to the tissue over distances of up to 10 mm (spray
mode). This waveform is highly intermittent, with the
generator supplying current only 5% of the activation time
These waveforms are also high voltage(up to 10 kV). This
produces leads to a thin layer of tissue necrosis with little
depth of thermal damage.
Fig. 9 - Applications of different current frequencies
Electrosurgical generators produce a voltage that
alternates sinusoidally between positive and negative
values at frequencies ranging from 500,000 to 3,000,000
cycles per second, (500 kHz and 3 MHz) (Fig. - 9). Each
tissue type has a characteristic resistance(R) that is
measured in ohms (W). The tissue resistance is inversely
proportional to the number of charged particles in the
tissue itself. During electrosurgical action the resistanceof
the tissue at the operative site will vary dramatically; the
initial tissue resistance may be a low value of 200 W/cm ,
Gianpiero D. Palermo, developed the intracytoplasmic sperm injection (ICSI) in 1992 to retrieve single sperm that could
be injected into a woman’s egg to produce an embryo (in-vitro fertilization). It allowed recovery from the epididymides
and even the testes - sperm reservoirs previously deemed unlikely sources of viable sperm from men once thought to be
untreatable.
5
but after several seconds of desiccation, the tissue
resistance will rise to the 1,000 to 3,000 W/cm range (
increased impedance).
With transurethral resection, the demands of the urologist
from the ESU is much more than the general surgeon. The
functions in a fluid medium, of both cutting and
coagulation require greater output power. The power
requirements for underwater cutting range from 125 – 250
W for cutting and 40-75 W for coagulation. Machines are
now universally standardized to a peak output of 400 W.
DIATHERMY FREQUENCY
In order to allow electric current to be applied through the
body without causing physiological effects other than those
necessary the ESU operates at very high frequency (radio
frequency). Lower frequency currents below 100 Khz can
cause nerve and muscle stimulation and represent a shock
hazard.
Fig. 10 – Typical waveforms in the ESU
Significance of the waveform (Fig. 10)
Cut waveform – Pure sine wave, it cuts through tissues but
has little haemostatic effects.
Coagulation waveform – Initially starts off as a sine wave
and is rapidly damped to zero and starts over again.
Blend waveform – Use higher voltages than pure cut
waveforms. It is similar to the cut waveform where the
generator supplies current for less than half the activation
period (50% of the duty cycle). The “off” time allows the
tissue to cool creating some hemostasis. It produces
increased necrosis of the cut surface and purists will
deplore its use in for transurethral resection.
Bipolar waveforms
The wavefroms are usually pure sine waves, analogous to
the monopolar cut waveform. Unlike monopolarcut
waveforms, the bipolar voltages are substantially lower,
usually not > 1,500 V, since tissue impedance is relatively
low due to the proximity of the two electrodes. These low-
voltage sine waves provide excellent contact desiccation,
but are less effective for cutting tissue since adequate
vaporization is difficult to achieve at low voltage.
 6 The Urology Masterclass, Department of Urology, CMC, Vellore
THE GENERATOR
There are two types of electrosurgical generators:
• Ground referenced generators
• Isolated generators
Ground Reference Generators
The current passes through the patient and returns to the
generator, which is linked to ground. The problem is the
current can go to any grounded object other than the pad
(ECG electrodes, OR bed, metal objects) and cause alternate
site burns.
Isolated Generators
Newer models usually have isolated generators. Generators
isolate the current from ground and do not allow significant
current to seek alternate paths to ground. The current must
return through the dispersive pad to the generator.If only a
small portion of the patient’s sticky return pad is in contact,
or if the conductivity of the pad is hampered, pad site burns
can occur.Many of the modern isolated generators also
have return electrode contact quality monitoring (RECQM)
systems that measure the impedance quantity and quality
of between the patient’s skin and the return pad with a
microprocessor.
Fig. 11 - Techniques of delivery –Monopolar and
bipolar
LASERS
The contact of laser energy with tissue results in an effect
depending on the temperature it produces. Thermal effects
– The energy absorbed is transformed into heat, the effects
are similar to that produced with any source of heat; > 40
° - protein denaturation, >60° - protein coagulation, >100°
- vaporization of tissue water, >250° - carbonization, >300°
- tissue vapourization. Mechanical effects- The application
of pulsed laser energy to a stone surface results in
formation of a plasma bubble; the resultant expansion of
which causes the stone to fracture in its stress lines.
Photochemical effect –The selective wavelength of a laser
can cause selective photoactivation of a drug resulting in
its local effect. Tissue welding effect – Application of focused
thermal energy of a particular wavelength can cause in
tissue approximation by to the interdigitation of collagen
with minimal peripheral tissue destruction. At the moment
this is still experimental.
Joseph Murray , (1919 –2012) - American plastic surgeon. Performed the first successful renal transplantation on identical
twins Ronald and Richard Herrick on Dec 23, 1954. He received the Nobel Prize for Medicine in 1990.
On entering a medium that absorbs it, the intensity of the
laser beam decreases exponentially (Lambert- Beer’s
law).This absorbed radiation is converted into heat,
depending on the tempreture results in its effect. The rapid
absorption causes more heat to be produced in immediately
adjacent to the point of contact and not at the deeper layers.
A chromophore is a substance that absorbs the laser energy
producing heat. While the chromophores available in the
human body are melanin, haemoglobin and water, the
substance that will act like one is dependent on the
wavelength of the incident laser light (Fig.10). It is different
for different lasers resulting in their unique tissue effects.
Melanin as a chromophore has no surgical applications
in urology.
The absorption length is the distance at which 63% of the
laser energy is absorbed. The extinction length defines the
optical depth at which 90 % of the energy is absorbed.
There are 2.3 absorption lengths per extinction length. At
the same power level, a laser with a short extinction length
causes superficial vapourization of tissue and a laser with
a long extinction length can cause deep necrosis.
Why is this important?
The absorption spectra of the laser determine its tissue
characteristics. As can be seen from Fig.12 the absorption
spectra of KTP corresponds to haemoglobin as its
chromophore. This means that it is strongly absorbed by
haemoglobin, has short extinction length in vascular
tissue, penetrates vascular tissue only for a few
micrometers and is excellent for haemostasis. However in
water, its extinction length increases dramatically and it
penetrates deeply. The fibers used with KTP are therefore,
side firing, to permit visual control.
On the other hand, Homium:YAG laser is strongly absorbed
by water which is its chromophore. The maximum
penetration in water is only 0.5mm. A steam bubble is
created at the tip of the fibre which separates (cuts)the
tissue. This tearing effect is dominant over vapourization
and therefor the tissue being cut appears fibrous white.
When the laser beam is on incident on a stone, some of the
energy is absorbed which leads to a build p of steam
pressure and fragmentation. During use the time required
Fig. 12
 The Urology Masterclass, Department of Urology, CMC, Vellore 7

for heat to diffuse out is established by the fibre diameter References:

andd the extinction length which corresponds to the thermal 1. Bhatt J, Jones A, Foley S, et al. Harold Horace Hopkins: A
relaxation time. This is approximately 100Ps. This Short Biography. BJU Int. 2010; 106: 1425-1428.
corresponds to the pulse duration (150Ps- 1millisec) of
2. Hopkins H. Handbook of Urological Endoscopy. New
the Ho:YAG laser. The shorter the pulse duration at a given
York, NY: Churchill Livingstone Inc; 1978:20-23.
pulse energy, the higher the pulse peak power leading to
better stone fragmentation. This is to be remembered when 3. Teichmann HO, Thomas R. Herrmann TR, Bach T.
configuring the laser settings for lithotripsy. Technical aspects of lasers in urology. World J Urol
2007; 25:221–225
4. Clayman M1, Uribe CA, Eichel L, Gordon Z, McDougall
Stone fragmentation with Ho:YAG laser: EM, Clayman RV. Comparison of guide wires in urology.
Two mechanisms are involved : Which, when and why? J Urol. 2004 Jun; 171:2146-2150.
The photo-acoustic (or photo-mechanical) effect - There is
the rapid formation of a spherical plasma cavitation
bubble that expands symmetrically to a maximum size and
then collapses violently. Bubble collapse leads to the
generation of a strong shock wave (or acoustic emission).
The photo-thermal mechanism: Involves the direct
absorption of the laser energy by the stone - the stone is
literally “melted”. Vaporization of the water molecules in
the urinary calculus may contribute to the formation of
vapor bubbles within the calculus which, as they expand,
may assist in stone fragmentation.
Urothelial injury is highly unlikely if the distance between
the tip of the fiber and the urothelium is greater than 0.5
mm., since the shock wave produced by cavitation bubble
collapse is small, and much of the photo-thermal effect of
the laser is attenuated by medium between the tip of the
laser fiber and the mucosa.
Moses effect : During the pulse of laser energy, there is a
microscopic air/plasma bubble on the tip of the fiber that
allows the laser energy to travel further than through the
fluid medium directly transmitting the laser energy into
the stone. This “parting of the water” has been termed the
“Moses effect”
Popcorn effect: High-frequency non-contact laser
fragmentation occouring when the stone fragments move
around the laser beam.
Preferred settings for the holmium laser for stone
fragmention are 0.6–0.8 Joules at 6–8 Hz. Studies have
demonstrated that increasing the pulse energy to more
than 1 joule will rapidly degrade the small caliber 200 m
fiber.

A parting word
This is by no means a comprehensive description of optics,
light sources, guide wires or energy sources. It is meant to
convey the basic principles behind the equipment. It is
enough if it is successful in stimulating the post graduate
to greater enquiry.

Claudius Galenus [Galen of Pergamon] (AD 129–c. 200/c. 216) - first among doctors and unique among philosophers;
most accomplished of physicians and surgeons of antiquity
 8 The Urology Masterclass, Department of Urology, CMC, Vellore

Cystourethrography
Vivek Venketaramani, Vellore

Introduction
Since the inception of the field of radiology, techniques
have been devised to study the bladder and the urethra.
Wulff, in 1905, gave the first description of cystographic
techniques via retrograde filling, and Cunningham
subsequently popularized it in 1910.
The development of pediatric urology and the conditions
peculiar to itprovided an impetus to the voiding
urethrographic techniques. Shopfner propagated the use
of voiding cystourethrography in the 1960’s. His
observations exposed many prior fallacies and drastically
altered to approach to the lower urinary tract in children.
Initial studies used silver and barium solutions but they
had many drawbacks, and with the discovery of newer
contrast media they became obsolete.
Today, sonourethrography and magnetic resonance imaging
are beginning to contribute to understanding the structure
and function of the lower urinary tract, however the place
of traditional cystourethrography remains pre-eminent. Figure 1 – Patient positioning for RGU

Common Indications Technique

(A) Retrograde Urethrogram (RGU):
x Trauma
x Stricture disease (anterior urethra)
x Inflammatory conditions
x Urethral neoplasms
(B) MicturatingCystourethrogram (MCU):
x Voiding cystourethrogram:
o Evaluation of UTI in pediatric population –
Traditionally all children who develop a urinary tract
infection were evaluated with an MCU. Today this
paradigm is changing with the development of the
‘top-down’ approach with ultrasound being
performed first, and an MCU only done if
hydro(uretero)nephrosis, scarring, obstructive
uropathy, atypical findings or recurrent UTI are
noted. This claims to detect clinically significant
VUR, reduce radiation exposure to the gonads and
prevent the psychological trauma of an MCU in a
young child (American Academy of Pediatrics
guidelines, National Institute of Clinical Excellence
guidelines)
o Structural and functional bladder outlet obstruction
o Neurovesical dysfunction (alone or as a part of video-
urodynamics)
o Evaluation of male and female urethra
o PFUDD
x Static Cystogram:
o Intravesical pathology
o Bladder diverticulum
o Fistulae between bladder and colon/ vagina
o Hernia involving bladder
o Trauma
(A) RGU:
x Supine position on the fluoroscopy table.
x Rolled up slightly on one hip to approximately 45
degrees with the dependent thigh flexed (Figure 1).
x Oblique view.
x Position is extremely important to avoid foreshortening
and overlap.
x Contrast: 20-30ml of sodium or megluminediatrizoate
(30% in children and 50-60% in adults).
x Prepare the genitalia in a standard fashion.
x Foley’s catheter 16-18F with balloon distended with 1-
2ml of water in the fossa navicularis in adults.
Penis placed laterally over the proximal thigh with
moderate traction.
x Local anesthetic or lubricant not recommended as it
may cause mucosal edema, increased permeability,
vascular stasis or displacement of the balloon.
x Flush catheter and syringe before use.
x Contrast should be filled into the catheter before
entering the urethra.
x Slow gentle pressure may be needed to overcome the
resistance of the external urethral sphincter.
x Better filling may be obtained by clamping the urethra
or occluding the meatus – Clamps – Knutson/ Brodney/
Cunningham/ Henriet spring clip.
(B) MCU:
x No5 feeding tube for infants, No8-10 soft rubber
catheters in older children, and 10-14F catheters in
adults for filling.
 The Urology Masterclass, Department of Urology, CMC, Vellore
x Bladder capacity in children calculated by Koff ’s
formula (look for restlessness or forceful flexion of the
toes).
In adults 300-400ml is instilled, or till the person
appreciates fullness.
x Gravity filling preferred in children – contrast filled
bottle suspended 35-40cm above the table.
x Filling in supine position, voiding in upright position
by tilting the fluoroscopy table.
Both thighs positioned to avoid superimposition of
femurs over urethra.
x Steep oblique to lateral position required because in
the A-P view the bladder is superimposed on the outlet
and proximal urethra.
x Supine position may provide satisfactory images,
especially in females unable to void upright.
x Options for filling – per-urethrally/ excretion MCU/
suprapubic MCU.
x Contrast: Sodium or megluminediatrizoate (15% in
children and 20-30% in adults).
x During filling phase, regular screening to detect VUR,
diverticula or other anomalies.
x After full bladder film, prepare for voiding:
o Children <2yrs of age – steep oblique position with
table in reverse Trendelenburg and camera prepared.
Then catheter is removed.
Be patient – repeated examinations may be required.
Voiding with catheter in situ is an option to facilitate
repetition of the study.
o Older children and adults – catheter removed after
full bladder film. Table and patient placed upright,
another film of full bladder obtained. Patient turned
into steep oblique position and receptacle for
voiding put into place.
x If reflux is present, additional oblique films required
and kidneys filmed in the frontal view to grade the
reflux.
x No study is complete without visualization of the
urethra during voiding.
x Remember MCU is a dynamic procedure and the entire
process can contribute to diagnosis. This is important
in the filling phase, at bladder neck/ EUS relaxation
and during the voiding phase and allows greater
sensitivity in the detection of abnormalities.
(C) Modified techniques:
x Double-contrast/ Penumocystography – Both air and
contrast instilled into bladder to evaluate neoplasms.
Rarely used nowadays.
x Autourethrography – No exposure to operator. Glans
penis taped around the filling catheter in an RGU to
prevent leakage. Patient is taught and injects the
contrast. Patient relaxation with subsequent sphincter
relaxation allows better filling of posterior urethra
according to some studies.
Tungsten Carbide : Christian Diener of Tuttlingen was the first maker to introduce tungsten carbide inserts (greyish alloy with cross
hatched surface) for needle-holders and forceps some thirty years ago. Tungsten carbide products typically have a high resistance
to wear. Its combined hardness and toughness significantly outperform its steel product equivalents.
9
x Double-balloon (positive pressure)urethrography –
Trattner double-balloon catheter used. Investigation of
choice for female urethra especially detection of
diverticuli.
x Opposing urethrogram – Injection via retrograde and
suprapubic pathways simultaneously to assess defect
in pelvic fracture urethral distraction defects.
x Choke cystourethrography – Adult males made to void
against resistance by pinching the penis or using a
Zipser clamp. Enhances visualization of the urethra.
x Pericatheterurethrography – Post-operative cases.
x Stress cystogram– In cases of traumatic bladder rupture,
the bladder is filled little beyond the point at which the
patient has strong sensation or pain.
x Positional instillation of contrast at the ureteric orifice
(PIC cystogram) – Pediatric cystoscope under GA. With
the bladder empty the cystoscope beak is positioned
near the UO and contrast is instilled from the height of
1m. Simultaneous fluoroscopy is performed to detect
VUR. No convincing evidence of its utility at present.
Normal anatomy
(A) Children:
1) Bladder
x Lies above the pubic symphysis in a newborn.
x Descends with age to reach below the pubic symphysis
by 5 years.
x A bladder ‘waist’ seen on a full bladder but disappearing
on voiding is normal, but more pronounced in cystitis.
x Shopfner and Hutch divided it into a vault and base.
x The base of the bladder is flat in the supine position
and becomes cone-shaped when upright.
x Detrusor contraction elevates both halves of the base
plate and progressive narrowing of the angle results in
cone formation.
2) Male urethra
x The vesico-urethral junction is wide open during
voiding.
x Exact location of the external sphincter cannot be
determined on MCU.
x Anterior indentations in the posterior urethra are caused
by pressure from the urogenital diaphragm and
incisuraintermuscularis (proximal urethra).
x Constrictor nudae muscle (extensions of the
bulbocavernosus) produces an anterior or concentric
indentation in the bulbar region (pseudostricture) on
RGU and MCU.
x Cobb’s collar or Moorman’s ring – Muscular or fibrous
narrowing of the bulbar urethra thought to be due to
incomplete dissolution of the urogenital membrane.
x Verumontanum is the only consistent landmark noted
in children and is situated in the posterior wall of the
prostatic urethra.
3) Female urethra
x Short and has an obliquely downward course.
 10 The Urology Masterclass, Department of Urology, CMC, Vellore

x Diameter of the vesico-urethral junction and urethra x Vaginal reflux during voiding is seen only occasionally.
itself are variable and depend on the amount of urine
flowing through it. Complications
• Radiation exposure – Traditional MCU/RGU = 0.3-3mSv
x The incisuraintermuscularis and the meatus do not
expand and the space between them is the fossa Digital fluoroscopy reduces exposure by 50%, and the
navicularis. use of variable rate pulsed fluoroscopy can reduce it
even further.
x Contraction of the transverse fibres of the compressor
• Infection – Avoid performing in the presence of active
urethrae may give rise to an apparent narrowing.
infection.
x Reflux into the vagina can occur in 75% of all female Antibiotic prophylaxis is indicated in patients with risk
children, regardless of position. It may be accentuated factors namely advanced age, immunodeficiency
by hypospadias and labial fusion. disorders, poor nutrition, indwelling catheter, high PVR
(B) Adults: or spinal cord injury.
• Trauma
1) Bladder • Bleeding
x Smooth walled, oval shaped. • Intravasation– Into the venous system can occur
x Descends to a lower level than children when in the secondary to high-pressure injection during RGU. It can
upright position. result in bacteremia or reaction to contrast media
x In males, the base is above the pubic symphysis. • Inadvertent catheterization of vagina or ureter
In females, the base is at the mid-level of the pubic • Autonomic Dysreflexia
symphysis. • Bladder perforation
2) Male urethra (Figure 2) • Intramural extravasation into an unused poorly
x Fossa navicularis is the widest portion of the penile compliant bladder – Self limited and requires no
urethra (1-1.5cm long, and in the glans). treatment
x Penile urethra extends from the meatus to the
penoscrotal junction (bound superiorly by the
suspensory ligament of the penis). It is smooth and
featureless.
x Bulbar urethra extends from the penoscrotal junction
to a horizontal line joining the lower border of both
obturator foramina. Dilated portion of the bulbar
urethra is known as the sump.
Bulbar cone – The bulbar urethra is smooth and assumes
a cone or funnel shape at the bulbo-membranous
junction – key point to note during RGU.
x Membranous urethra is surrounded by the external
sphincter and extends to the verumontanum.
x Prostatic urethra extends to the bladder neck (vesico-
urethral junction).
* - muscularis compressor nudae
x Entire urethra forms a reverse-S bend in the lateral
projection. Fig. 2 - Landmarks of the adult male urethra
x Filling of the prostatic ducts may occur normally but
usually seen in strictures.
x Seminal vesicles and vasa may also be seen due to high-
pressure reflux.
x Cowper ’s glands are situated in the urogenital
diaphragm. Cowper’s ducts are 2cm long and located
posterior and lateral to the membranous urethra. They
open in the bulbar urethral sump. They opacify in case
of distal obstruction.
x Littre’s glands are located peri-urethrally in the anterior
urethra. Most numerous in the dorsal aspect of the
penile urethra and the bulbar urethral sump. Commonly
opacified in acute or chronic urethritis or obstruction.
They rarely may opacify normally.
*- stricture
3) Female urethra
x 4cm long, obliquely downward course and slightly Arrow - verumontanum
curved. Fig. 3 - Bulbar urethral stricture
 The Urology Masterclass, Department of Urology, CMC, Vellore 11

Templates for description Suggested reading:

1) Older RA, Hertz M. Cystourethrography. Clinical
RGU MCU Urography,2nd edition. Philadelphia: Elsevier Health
• Scout film • Scout film Sciences; 2000. p303–355.
• Anterior urethra • Bladder 2) Kawashima A, Sandler CM, Wassermann NF, Leroy AJ,
1. Opacification 1. Shape King Jr BF, Goldman SM. Imaging of urethral disease: A
2. Caliber 2. Size pictorial review. Radiographics 2004; 24:S195–S216.
3. Distensibility 3. Distensibility
4. Symmetry of wall during 3) Peterson CM, Menias CO, Siegel CL. Imaging of the male
4. Normal anatomical urethra. Urethral reconstructive surgery.Totatwa: Humana
landmarks distension / voiding
5. Contour of bladder wall Press (Springer); 2008. p29-42.
• Stricture
– Number, position, – Trabeculations 4) Gallentine ML, Morey AF. Imaging of the male urethra
– Diverticulae for stricture disease. UrolClin N Am2002; 29:361–372.
length, extent of
6. Extrinsic compression 5) Painstil E. Update on recent guidelines for the
spongiofibrosis
– Loaded sigmoid management of urinary tract infections in children: the
• Opacification of colon
periurethral shifting paradigm. CurrOpinPediatr 2013;25:88-94.
– Uterus,
structures – Iliac aneurysm 6) Khouri AE, Bagli DJ. Vesicoureteric reflux. Campbell-
• Filling defects – Ectopic pelvic kidney Walsh Urology, 10 th edition. Philadelphia: Elsevier
– Air bubbles – Dilated and tortuous Saunders; 2012. p3267-3309.
– Foreign bodies ureters 7) Stratton KL, Pope JC, Adams MC, Brock JW, Thomas JC.
– Blood clots 7. Filling defects in bladder Implications of ionizing radiation in the pediatric
– Radiolucent – Ureterocele urology patient. J Urol 2010; 183:2137-2142.
stones – Blood clots, air
– Bezoars bubbles, stones 8) Fulgham PF, Bishoff JT. Urinary tract imaging: Basic
– Condyloma – Tumours Principles. Campbell-Walsh Urology, 10 th edition.
– U r e t h r a l – Intravesically Philadelphia: Elsevier Saunders; 2012. p99-139.
diverticulum enlarged prostate
– Urethral polyp – Foley’s catheter
– Tumours • Bladder neck opening
• Communications • Urethra
– rectum, perineum 1. Posterior urethra
• Posterior urethra – Dilatation /
• P r o c e d u r a l relaxation of EUS
complicationseg. 2. Anterior urethra
– as for RGU
intravasation
• Vesicoureteric reflux
– Laterality
– Degree
– Timing
• Abnormal tracks
connecting with adjacent
organs / areas
• Post void film
 12 The Urology Masterclass, Department of Urology, CMC, Vellore

Uroradiology: CT KUB
Sagar Sabharwal, Vellore
Principle and generations
The basic idea of computer aided tomography: the X-ray
beam moves all around the patient, scanning from hundreds
of different angles

First generation Second generation

Third generation Fourth generation

Most of todays MDCT are based on third generation models

Sven Ivar Seldinger (1921–1998), Swedish radiologist. In 1953, he introduced the Seldinger technique to
obtain safe access to blood vessels and other hollow organs. His technique is used across numerous
specialities, not least minimally invasive urology.
 The Urology Masterclass, Department of Urology, CMC, Vellore 13

Hounsfield scale
Named after Sir Godfrey Newbold Hounsfield
Quantitative scale for describing radiodensity
Tissue density is expressed in different shades of grey in
relation to its Xray absorption

3. Excretory phase:
– 3-5 min after contrast
– Contrast excreted into the collecting system
Phases of renal enhancement 1,2 – Depiction of intraluminal pathology
1. Corticomedullary phase:
– Visible by 25-80 sec
– Cortical capillaries, peritubular capillary spaces
and lumina of proximal cortical tubules start filling
– Cortex distinctly differentiated from unenhanced
medulla
– Advantages
• differentiation of normal variants of renal parenchyma
from renal masses
• better depiction of tumor vascularity

Split bolus MDCT Urography 3

• Proposed by Chai and colleagues
• 2 phase protocol;
– Unenhanced series
– Nephropyelographic phase
• Following initial NCCT, 30cc contrast is infused
• After 10 min delay, 100cc contrast is infused and a CECT
is performed after a delay of 100 sec
• Single acquisition: renal parenchyma (nephrographic
2. Nephrographic phase: phase) and collecting system (pyelographic phase)
assessed
– 90-120 sec
• Reduces the radiation dose to the patient
– Passage of contrast material through the renal
tubule system
– Parenchyma enhances homogeneously
– Optimal for characterization of renal masses
 14 The Urology Masterclass, Department of Urology, CMC, Vellore

4. Bosniak 4
• Nonuniform or enhancing thick wall
• Enhancing or large nodules in the wall
• Clearly solid components in the cystic lesion
5. Macroscopic fat within a noncalcified mass: specific
for benign angiomyolipoma
6. Fat related to malignant neoplasms:
• has been reported
• Generally large tumors that have engulfed
perinephric or renal sinus fat or renal carcinomas
that have areas of osseous metaplasia and small
amounts of fat
7. Oncocytomas
• Cannot be diagnosed based on CT appearance
• Central scar: not specific
8. Small (d”1.5 cm) renal mass: pose problem for CT
imaging
Indeterminate renal masses and CT 4 • MDCT with thin overlapping reconstruction (<3mm)
improves characterization from 29-84% as
• Indeterminate renal mass: cannot be diagnosed
compared to routine 5mm cuts
confidently as benign or malignant at the time it is
discovered Lymph node imaging by CT 5
1. Bosniak 2 • Assessment relies on lymph node anatomy
• Lesion with 1-2 thin (d”1 mm) septations • A normal lymph node
• Thin, fine calcification in walls or septa (wall thickening • Usually measures <1 cm in size
> 1 mm advances the lesion into category III) • Smooth and well-defined border
• Hyperdense benign cyst: • Uniform, homogeneous density
• 3 cm or less in diameter • Most benign nodes have a central fatty hilum
• have one quarter of its wall extending outside the kidney • Based on its anatomic location, the shape of a normal
so the wall can be assessed lymph node may vary
• nonenhancing • Usually normal nodes tend to have an oval or cigar shape
• Sensitivity and specificity based on lymph node size
2. Bosniak 2F
• Group not well defined by Bosniak
CT/MRI
• Consists of lesions that do not neatly fall into category
II/III Region Sensitivity % Specificity %
• Some suspicious features that deserve follow-up to Lung 60/- 77/-
detect any change in character
Pelvis -/67 -/71
• Have one or more of the following abnormalities
• increased number of hairline septa All body regions 54 82
• minimal thickening of cyst wall or septa, which may
demonstrate perceived (not measurable) enhancement
• Lymph node size, though primary yardstick, is not a
• Calcification, which may be thick and nodular reliable parameter for the evaluation of metastatic
• non enhancing soft-tissue components involvement
• totally intrarenal high-attenuation lesions e”3 cm • Other criteria
• Shape: rounded
3. Bosniak 3
• Loss of fatty hilum
• Uniform wall thickening
• Clustering
• Nodularity
• Thick or irregular peripheral calcification CT versus IVU 6,7,8
• Multilocular nature with multiple enhancing septa Worsters meta-analysis: NCCT vs IVU in suspected acute
• Hyperdense lesions that do not fulfill category II urolithiasis
 The Urology Masterclass, Department of Urology, CMC, Vellore 15
– Enhancement pattern
CT IVU
– Necrosis
Sensitivity 0.97 (95% CI = 0.94- 0.69 (95% – Extent
– Planes with surrounding structures
0.99) CI = 0.63–0.75)
• Adrenals
Specificity 0.98 (95% CI = 0.95– 0.95 (95% • Opposite kidney and ureter
1.01) CI = 0.90–0.99) • Bladder Renal vein and IVC
• Lymph nodes
• Lung bases
• CT should be utilized in preference to IVU for patients • Other organs: liver, spleen, pancreas, bowel
with suspected urolithiasis (level 1a evidence) • Bones
• Also gives alternative diagnoses, which occur in one
third of all patients referred with suspected stones
• Do we have the similar kind of evidence, that CT is the References
best modality to treat stones before PNL? 1. Yuh BI et al. Helical CT for detection and characterization
• Only one study till date, comparing 3D CTU with IVU to of renal masses. Semin Ultrasound CT MRI 1997;18:82-
plan a percutaneous access for nephrolithotomy in 90.
stag-horn stones
2. Garant M et al. Enhancement patterns of renal masses
• Did not demonstrate advantage over the IVU
during multiphasic helical CT acquisitions. Abdom
• Perception that CT would be more useful in treating
Imaging 1998;23:431-36.
large stone bulk is not based on any evidence
• However, CT certainly indicated before PCNL in 3. Chai RY et al. Comprehensive evaluation of patients with
• abnormal anatomical situation such as horseshoe hematuria on multislice computed tomography
kidney scanner, protocol design and preliminary observations.
• obesity Australas Radiol 2001;45:536-38.
• bony deformity 4. ACR appropriateness criteria 2010. Indeterminate renal
• Disadvantages of NCCT masses
• Increased radiation dose (IVU: 3.3 mSv, NCCT: 6.5 mSv) 5. Torabi M et al. Current concepts in lymph node imaging.
• Does not give function of the involved kidney J Nuc Med 2004;45:1509-18.
CT KUB description 6. Shine S. Urinary calculus: IVU vs. CT renal stone?A
critically appraised topic. Abdom Imaging 2008;33:41–
Points to mention while reading a CECT KUB 43.
• Mass 7. Aga P, Bansal R. Is intravenous urogram no longer an
– Site imaging of choice for percutaneous nephrolithotomy?
– Size Indian J Urol 2010;26:303-4.
– Shape 8. Liberman SN, Halpern EJ, Sullivan K, Bagley DH. Spiral
– Number computed tomography for stag horn calculi. Urology
– Exophytic/ endophytic 1997;50:519-24.

Tuttlingen, Black forest region, Germany, on the banks of the Danube. Has around 400 factories which are directly involved in the
manufacture of surgical and medical technology products. About 50% of the world’s surgical instruments are manufactured in this
city and the vicinity. Gottfried Jetter began fabricating surgical instruments in 1867, founding Aesculap, the oldest firm. Tuttlingen
subsequently birthed : Karl Storz, Henke-Sass Wolf , Berchtold and KLS Martin among many others.
 16 The Urology Masterclass, Department of Urology, CMC, Vellore

Diuretic Renography
Nitin Abrol, Vellore

Despite recent advances in radiology techniques, nuclear
medicine plays pivotal role in the functional assessment
of urinary tract. Diuretic renogram remains gold standard
in the diagnosis of upper urinary tract obstruction. In this
section, basic physiology and interpretation diuretic
renogram are discussed.
Renal Physiology: Kidneys comprise 3% of body weight and
receive 20% of cardiac output. Renal plasma flow is
approximately 600 ml/min. 20% of plasma is filtered across
the glomerulus in one pass. Out of this 99% is reabsorbed
by tubules. Clearance of a substance from plasma depends
upon its plasma protein binding, molecular weight, and
tubular handling. Ideal agent for measurement of GFR
should have no plasma protein binding, no tubular
handling, and should have exclusive glomerular clearance.
On the other hand ideal substance for measurement of
renal plasma flow should have extraction efficiency equal
to 1. There is no such substance available. PAH is very near
to ideal with extraction efficiency of 0.9.
Radiopharmaceutical Agents: Table below summarizes the
radiopharmaceutical agents currently in use for nuclear
medicine techniques applied in urology.

Renography: It is the dynamic study of renal function using
gamma camera. Each renogram has three distinct phases;
perfusion, concentration, and excretion. In diuretic
renography diuretic is given to induce diuresis. Most
commonly Furosemide is injected at dose of 40 mg in adults.
Pediatric dose is 0.5 mg/kg for children and 1 mg/kg for
infants. Diuresis starts 2-3 minutes after the injection with
maximum diuresis after 15 minutes. However, response of
kidney to diuretic depends on baseline renal function,
baseline hydration, dose, time of injection, renal pelvis
volume, elasticity of pelvis, and degree of ureteric
peristalsis. Therefore following standardized protocol is
very important for correct interpretation of the study.

Ronald Virag, French vascular surgeon, known for his pioneering work with phentolamine and papaverine for erectile dysfunction.
In 1981, during a surgical procedure on the penis, he discovered that an old medication extracted from poppies, used since the late
19th century to dilate blood vessels, could induce an erection when injected into the penis. He published his observations a year
later in the Lancet.
 The Urology Masterclass, Department of Urology, CMC, Vellore 17

Protocol for diuretic renography: Type 4: (Homsey’s sign): There is transient response to
1. Good hydration: 500ml oral before study diuretic followed by rising curve after about 10 minutes of
diuretic injection. It represents probable intermittent
2. Empty bladder
obstruction and repeat study with F-15 protocol is helpful.
3. Injection of tracer
4. Supine posterior position usually
5. Furosemide injection as per protocol (F+20 or F-15, F0
in children)
6. Pre void image
7. Bladder voiding after scan
8. Post voiding image
9. Abundant fluids after study

Image acquisition and processing: After injection of

radiopharmaceutical agent 1-2 second frames are taken
for 60 seconds (Perfusion) followed by 10 sec frames for
30 min (Uptake and clearance phase). For convenience of
reporting images over 2 minute are condensed into one
image. Field of view should include heart, kidneys, and Tmax: It is time to reach the maximum of the curve. It is
bladder. After subtracting background activity a graph is shorter for tubular agents than for glomerular agents. Tmax
plotted showing variation of radioactive count rate with around 3 minute is normal and more than 20 minute is
time within the organ of interest. This graph is called time very delayed transit.
activity curve. T1/2: Less than 10 minutes represent normal response and
Background subtraction: Gamma camera counts activity in more than 20 minute represents obstructed drainage.
region of kidney. This activity includes true renal activity However, it is not reproducible parameter. It is highly
along with vascular activity (renal + extrarenal), and extra operator dependent and depends upon the positioning of
vascular extra renal activity. These activities need to be ROI and estimation method used.
subtracted from raw renogram curve to obtain background Conclusion: Choice of radiopharmaceutical is not
subtracted true renogram curve. If background subtraction important if measurement of absolute GFR is not
is correct, renogram curve should rise smoothly from zero. consideration. Protocol should be carefully followed for
If both kidneys have equal function then under subtraction generating representative time activity curves. Inspection
does not alter relative renal function. If function is of TAC is most useful parameter for assessment of
asymmetric then incorrect background subtraction can obstruction. Even in well-performed study there is
affect relative function measurement. significant equivocal rate where definitive diagnosis of
Assessment of excretion: Excretory function of kidney is obstruction cannot be made. After excluding modifiers of
assessed with the help of various parameters on diuretic diuretic response , F-15 can reduce equivocal rate.
renogram like time activity curve, Tmax, and T1/2. Inspection
of time activity curve is most important. Upto 1 minute on Suggested Readings:
the curve is the first phase due to arrival of tracer in the 1. Jamar F, Barone R. Renal Imaging. In: Baert AL, Sartor LK
renal vasculature (Perfusion). From 1-3 minute there is eds. Diagnostic Nuclear Medicine: 2nd ed. Heidelberg:
transit through the nephrons (Uptake: glomerular filtration Springer
+ tubular secretion). After 3 minutes is the excretory phase 2. Cosgriff PS. The Urinary Tract. In Sharp PF, Gemmell HG,
due to excretion of contrast in collecting system. 5 types of Murray AD eds. Practical Nuclear Medicine: 3 rd ed.
time activity curves have been described. London: Springer
Type 1: Normal curve with rapid rise and rapid fall.
Type 2: Continuous rise even after diuresis due to urinary
tract obstruction. Before making diagnosis of obstruction
dehydration, full bladder, low GFR of renal unit, and
massive dilatation of renal pelvis need to be excluded.
Type 3a: There is continuous rise but curve dips sharply
after diuretic. This represents non-obstructive pattern due
to dilation related stasis.
Type 3b: There is continuous rise after perfusion phase as
in type 3a. However, after diuretic there is some response
that is not as marked as in type 3a. Once dehydration and
low GFR are excluded repeat study with F-15 protocol can
decrease equivocal rate.
 18 The Urology Masterclass, Department of Urology, CMC, Vellore
Current indications for surgical correction of VUR
J Chandrasingh, Vellore
As our understanding of vesicoureteral reflux (VUR) is
evolving, the role of operative correction of VUR is being
revisited. There are a few situations where operative
intervention is indicated.
It is better to individualize the decision making for any
particular patient, since several of these factors play a
role in management. For patients managed nonoperatively,
chemoprophylaxis is usually continued till the age of five
or reflux resolution, whichever is earlier. Rationale for this
age cut-off is a) Spontaneous resolution, if any, is
completed by this age and for all treatment purposes, if it
is not resolved by then, probability of subsequent
resolution is very low. b) The kidney’s susceptibility to post-
pyelonephritis scarring is inversely related to age and it is
quite low after five years of age.
Though chemoprophylaxis after treating the UTI and
conservative management is sought in most children,
surgical correction of the VUR has a role in some children.
A) Absolute indication :
1. Breakthrough upper urinary tract infections (UTI)
When a child develops pyelonephritis while being on
chemoprophylaxis, surgical correction minimizes the risk
of further episodes of upper tract UTI. The following aspects
need to be addressed before embarking on a change in
plan :
a) To ensure compliance with chemoprophylaxis
Parents may not be administering the antimicrobial, or
the child may not be taking the medication. If the organism
isolated during UTI is sensitive to the medication being
administered, this possibility should be strongly suspected.
b) To verify the dose and sensitivity pattern
As children grow, the dose administered may be less than
what is required. The child might have developed resistance
to the antimicrobial. If any of these are identified, they
need to be corrected.
c) Bowel and bladder dysfunction
It may be difficult to elicit this history, especially for
children who are just toilet trained. If present, treating
these appropriately will reduce the chance of breakthrough
UTIs while on antibiotics.
B) Relative indications :
1. Persistent high grade reflux
Reflux resolution is related to the severity and laterality.
An infant with bilateral high grade reflux may continue to
have persistent high grade reflux and there may be
unwillingness for continued imaging or chemoprophylaxis.
Howard N. Winfield, performed the world’s first laparoscopic partial nephrectomy and Iowa’s first laparoscopic
nephrectomy in 1992 at the University of Iowa
The probability of resolution may be derived from the AUA
VUR guidelines panel graph (Elder et al, 1997). Surgical
correction is an option in these children in view of the low
probability of resolution and non-availability for regular
follow up and prophylaxis.
If a child is detected to have high grade bilateral reflux,
especially if the initial presentation is in late childhood,
the probability of spontaneous resolution is quite low. If
there are no prior episodes of UTI, no scars on DMSA scan
and if one can be assured of prompt diagnosis and
treatment of any subsequent infection, there is a possible
role for non-operative management. However, most children
who present for the first time later in childhood for
evaluation of UTI with high grade reflux have one or more
of the following: Renal cortical scars, doubtful episodes of
UTI which were not diagnosed / treated in the past, non-
availability of prompt pediatric care to diagnose and treat
UTI, compliance issues for prophylaxis and inability to
follow up for renal growth.
2. Associated diverticulae or other congenital
malformations
The probability of spontaneous resolution is low, when
there are large para-ureteric diverticulae. If surgery is
planned for other concomitant defects either involving the
bladder or otherwise (Prune belly syndrome with recurrent
UTI, bladder neck repair for exstrophy etc) ureteric
reimplantation may be concomitantly performed.
3. New scars or retardation of renal growth
Children with VUR on chemoprophylaxis are followed up
with renal ultrasonogram and renal cortical scan.
Persistently retarded renal growth or appearance of new
photopenic areas are used as indications for surgical
correction of the reflux by some. Sonographic measurements
of renal parameters can have variations in one or more
follow up visits. New photopenic areas are known to occur,
even in the absence of clinically obvious pyelonephritis.
Appearance of new scars has been a relative indication
for surgical correction of reflux, though new scars are
known to occur even after successful correction or
spontaneous resolution of reflux.
4. High grade persistent reflux in girls at adolescence
While the persistent reflux in the absence of UTI may be
innocuous in boys, it may be associated with recurrence
of pyelonephritis in girls once they are sexually active.
Furthermore, adverse fetal outcomes may occur due to UTI
during pregnancy. Though there is no robust data to
substantiate reduction in peripartum morbidity by
correction of persistent reflux, surgical correction is offered
to girls with persistent reflux beyond five years.
 The Urology Masterclass, Department of Urology, CMC, Vellore
Flaps in hypospadias surgery
J. Chandrasingh, Vellore
Introduction
Hypospadias is commonly encountered in pediatric
urology, with an incidence of 1 in 300 newborn boys.
Though the milder varieties form the majority of
hypospadias, it is not uncommon to encounter a child with
more challenging anatomy. TIP repair has been popularized
to treat most hypospadias but having the knowledge of
alternate options is essential to choose the best option for
the individual patient. Common indications for local flaps
include: Second layer of closure following TIP repair, Ventral
onlay repair when the urethral plate may be preserved after
orthoplasty but the plate is inadequate for tubularization
or for complete reconstruction of the tube following
transection of the tube.
Vascular supply of penile skin
The penis and anterior scrotal wall are predominantly
supplied by the superficial (superior) and deep (inferior)
external pudendal arteries. These are branches of the first
part of femoral artery. Though the deep external pudendal
is the dominant artery most often, occasionally the
superficial external pudendal is dominant. Theypierce the
deep fascia to run in the membranous layer of the
superficial fascia across the femoral triangle to the base
of the penis. Here they divide into dorsolateral
andventrolateral axial penile branches, which run distally
in the subcutaneous tissue to the glans. At the base of the
penis, the axial arteriesgive off cutaneous branches to form
a subdermal arterial plexus, which extends distallyto the
prepuce. The axial arteries together with interconnecting
branches form a rich subcutaneousarterial network, which
passes distally to the prepuce. Behind the corona, the axial
arteries send perforating branches through Buck’s fascia
to anastomose with the terminal branches of the dorsal
arteries before they end inthe glans. The attenuated
continuation of the arteries passes into the prepuce.
Connections between the subcutaneousarterial plexus and
the subdermal arterial plexus are veryfine, so that the skin
can be dissected off the subcutaneoustissue with little
bleeding.Occasional large connectionsneed to be ligated
and divided to raise the skin. The venae comitantes usually
accompany the arterial divisions.
Perimeatal flaps
Though these flaps (Mathieu) and perimeatal tube
(Mustarde) were popular in the past, the vascularity of the
Barnett Rosenberg, (1926 –2009),a Michigan State University chemist, discovered that platinum analogues inhibited
bacterial growth. Out of this research grew cisplatin, an essential ingredient in many of today’s chemotherapeutic regimens,
including testicular and bladder cancer.
19
perimeatal flap are inferior compared to the dorsal pedicle
based flaps. Hence these are less commonly used now.
Transverse Prepucial Island Flap (TPIF)
Most of the local flaps are based on the vascular anatomy
as described above. The most commonly used flap is the
Transverse prepucial island flap. The width of the flap is
decided based on the required circumference, which in turn,
is based on the available urethral plate. The results are
superior if the flaps are used as onlay, compared to
tubularized flaps.(1) Alternately longitudinal flap based
on similar principle is described, with the reduced
incidence of penile torsion.(2)
Byar’s flap
While the Transverse Island flap requires a fine dissection
of separating the pedicle of the flap from the proximal
penile skin, the Byar’s flap, in addition to raising the flap
from the Buck’s fascia surrounding the penis, the Byar’s
flap requires only the easier of the two dissections –
between the flap and the Buck’s fascia and translocating
the resultant flap ventrally to provide adequate skin plate,
available for a second stage tubularization. Byar’s flap
may be made in addition to TPIF, to cover the ventral penile
skin, though this has a high risk of ischemia to the skin
edges after raising the TPIF flap. Alternately, one half of the
Byar’s may be utilized for tubularized reconstruction of
the distal distal urethra at first stage.(3)
Modified Koyanagi flap
This flap is an option when the reconstruction mandates
division of the urethral plate and a single stage
reconstruction is desired. This flap has a component of
perimeatalflap,A Y-shaped incision is marked out proximal
to the meatus. The “leg” of the Y is in the midline and extends
into the scrotum/perineum incorporating the meatus. Since
this repair incorporates the parameatal skin, the delicate
vascularity of this are needs to be taken care of. In addition,
the decision to perform Koyanagi repair should be taken
prior to degloving the penis, to develop the flap. The arms
of the Y should be directed to each side of the meatus such
that extension of the arms will lead to skin flaps composed
of lateral penile shaft skin of roughly 7 mm in width. The
lateral skin flaps are marked distally and converge onto
the preputial skin. These two strips are then sutured
Fig. 7
together, subsequently reconstructed to construct a neo-
 20 The Urology Masterclass, Department of Urology, CMC, Vellore

urethral tube. As the skin flaps are planned to be roughly

7 mm in width, the resultant urethra will have a 10-12 mm
diameter, approximately 10-12 Fr. Formation of
diverticulum is a known complication. There is a steep
learning curve but good results are reported by several
authors.(4)

Conclusion
Proximal hypospadias is a challenge for reconstructive
pediatric urologists. Staged repair is commonly advocated.
Having an idea of flaps and other reconstructive techniques
will enable offering the most optimal choice based on the
individual anatomy.

References
1. Powell CR, Mcaleer I, Alagiri M, Kaplan GW.Comparison
of flaps versus grafts in proximal hypospadias surgery.J
Urol. 2000 Apr;163(4):1286-8.
2. Chandrasekharam VV. Single stage repair of
hypospadias using longitudinal dorsal island flap:
Single-surgeon experience with 102 cases. Indian J Urol.
2013 Jan;29(1):48-52.
3. Dewan PA, Erdenetsetseg G, Chiang D. Ulaanbaatar
procedure for tubularization of the glans in severe
hypospadias. J Urol. 2004 Mar;171(3):1263-5.
4. Emir H, Jayanthi VR, Nitahara K, Danismend N, Koff
SA.Modification of the Koyanagi technique for the single
stage repair of hypospadias.J Urol. 2000 Sep;164(3 Pt
2):973-5.
 The Urology Masterclass, Department of Urology, CMC, Vellore
How to write an answer
Arabind Panda, Rajiv Mukha
Examinations are formidable even to the best prepared, for
the greatest fool may ask more than the wisest man can
answer - Charles Caleb
The purpose of the all examinations, either for Magister
Chirurgiae or of the Diplomate National Board is to
determine whether candidates have the basic knowledge
required for further training in Urology and are able to use
this knowledge competently. All examinations are a
compromise since the whole curriculum cannot be tested.
This can often put even good candidates at a disadvantage
if the person has not prepared for that particular question.
Two candidates may produce the same answer to a question
but the person who imparts the answer clearly, confidently,
with well-ordered priorities, and is awarded a higher mark.
Writing a good answer is therefore less a matter of chance
and more an art.
Two types of questions find a place in most examination
formats.
Essay questions - are devoted to topics of major importance,
those that have undergone advances or are changing, and
those in which recently instituted or newly evaluated
management has been reported.
Short notes questions – Here the candidate’s knowledge in
a wide range of subjects is examined. It is however to be
remembered that a topic normally set as an essay type
question can be asked as a short note and vice versa. The
examinee then has to cover all points in a succinct and
brief manner and yet stick to time.
Good answers display the ability to comprehend the
question and the reason it was included, select essentials,
arrange facts, discuss complex issues and communicate
lucidly in writing. This can be quite difficult to do in the 3
hours of the examination if not thought out earlier. The
need for pre examination preparation therefore cannot be
overemphasized.
PRE EXAMINATION STRATEGY:
“It is not enough to know, we must apply.”
- Goethe
Start your preparations well in time: This is often a difficult
ask in busy clinical departments, b ut can be the most
important factor between failure and success.
Revise previous years questions: Most of the questions that
are asked in any examination are either direct or indirect
repetitions of previous year topics. It is essential to
compile the important expected questions in each topic
before even starting to prepare. It will be therefore possible
to give adequate importance to these areas during the
initial reading itself. This assumes even greater importance
considering the paucity of time urology registrars have in
most centres.
Joseph McCarthy – Invented the best foroblique cystoscope of his time which when coupled to Sterns resectoscope
resulted in the first successful transurethral resection of the prostate.
21
Flow charts: Prepare a flow chart of management of
important conditions. Flow charts are easy to remember
and enable us to convey a large amount of information in
a very short time. This is best done initially itself and it
can reinforce itself in subsequent readings.
Diagrams: A picture is more valuable than a thousand
words. Examiners often allot separate marks for diagrams.
It is difficult to draw a diagram in the examination hall if
one has not practiced it earlier. It is a good idea to have a
diagram scrapbook with all relevant and important figures
and diagrams in a single place. Having both flow charts
and diagrams for a topic can drastically cut down the
time required for writing an answer.
Look beyond the textbook: The textbook most commonly
read is a reference tome on urology. Bogged down by the
weight of its reputation (and pages), it is not often the best
resource for the postgraduate. Many short monographs
and review articles may explain the topic in a far better
manner. If there are seminal or landmark studies on the
topic it may be an excellent idea to go through the paper.
If possible mention the trial and the author in your answer.
It is greatly appreciated by all examiners.
Take the help of fellow post graduates: If a friend and
colleague is appearing for the same examination, it of
often best to pool resources and efforts. Covering large
and often dry topics is much easier if you have company.
And yes, you recall better if you have discussed it together.
DURING THE EXAMINATION
Read every word of the question carefully, asking yourself,
‘Why was this question asked?’ . If a question has 3
subsections, then each subsection has pre allotted marks.
This is intimated to the examiner in advance and the
marking is done accordingly. Certain boards ask the paper
setter for a key which has to be followed during evaluation.
Make notes but do not start writing the answer until you
are sure how you will arrange it. As you start to write,
remember that examiners can only mark what they can
read. You cannot write all you know so do not waste time
with irrelevant or unimportant facts at the risk of omitting
major points. Remember it is possible to fail even though
everything you have written is correct. The reason you
will have failed is because you have not answered the
question that was asked or because you have failed to
communicate priorities in management. Do not omit
important points because you think they are obvious. It is
safer to mention them. Questions often start with the word
‘discuss’. Identify all the aspects, including the contentious
ones that demand explanation or justification.
Time management: The question that you know best is
the one that often kills you. It is essential to allot equal
time to answer each question. Try to finish each answer 2
 22 The Urology Masterclass, Department of Urology, CMC, Vellore

-3 minutes before the time you have set for it. This is of • advanced donor age,
particular importance in an examination which has 10 • delayed graft function, and
short notes. Here your ability to organise your knowledge
• kidneys with more than two arteries and
is also being tested. Irrelevant points do not get you
additional marks. • infection with polyomavirus (BK virus)
Attempt all questions: This cannot be emphasized enough. producing ureteritis and ureteral stenosis.
Finally, recheck for your sheet for completeness and correct Initial stenting during transplant is not protective for late
any mistakes present. ureteral stricture.
Presentation – Gradual and asymptomatic rise in creatinine
Examples: - 10 marks short note with hydronephrosis on imaging.
Diagnosis: Diuretic renography- May show obstructive
1. Organ sparing treatment of penile carcinoma pattern; antegrade nephrostogram – showing narrowing
Management: Endoscopic – Balloon dilatation/ laser
Ans: Penile preservation aims to minimize physical incision of the stricture followed by stenting. May be
disfigurement and maximize quality of life without successful in 50% of cases. If fails open surgery with
oncological compromise. ureteric reimplantation/ boari flap / anastomosis with the
native ureter.
Patient selection:Low grade low stage disease (stages Tis,
Ta, T1; grades 1 and 2) with low risk for local progression Morris and Knechtle, Kidney transplantation- principles
and/or distant metastatic spread and practice, 6th edition. Page 465
Surgical - involve surgical margins of less than 10mm. ( references are not required in the answer)
i. Mohs micrographic surgery
ii. Laser ablation or excision - CO2, Nd:YAG, KTP 3. Prostate sparing radical cystectomy – pros and cons
iii. Conservative surgery: Ans: Modifications to the classic technique of radical
cystectomy leading to improving postoperative continence
I. Glans-preserving techniques and potency rates. It minimize dissection near the urinary
o Partial glansectomy sphincter and neurovascular bundles through partial or
- with primary closure complete sparing of the prostate, seminal vesicles, and
vasa deferentia.
- with graft reconstruction of the glans
• Patient selection:
• Split-thickness skin grafts
a. Young patients , active sexually
• Full-thickness skin grafts
b. Low risk for occult malignancy in the prostate
• Buccal mucosa
c. No prostatic urethral involvement by tumour
II. Glans-removing techniques: Total Glansectomy with
distal corporectomy and reconstruction with split- • Concerns:
thickness skin grafts a. Oncologic:
Non surgical: i. Occult transitional cell carcinoma in the prostate
i. Topical treatments: 5-Fluoroacil solution, ii. Local and systemic recurrence
Imiquimol cream iii. Occult prostate cancer
ii. Radiotherapy: • Functional results following prostate-sparing
Plesiotherapy cystectomy :
Interstitial brachytherapy i. Continence rates: 94 – 100%
External beam radiotherapy ii. Potency : 80 – 90%
iii. Cryosurgery
iv. Chemotherapy Oncologic benefits: More acceptance of radical surgery by
Until long term results from properly conducted trials are the patient at a time when cure is possible.
available for these techniques, traditional partial and total
penectomy - the gold standard. Kefer J. C, Campbell S. C. Urologic Oncology: Seminars and
Original Investigations 2008; 26:486–493
Ref: Martins F. E, Rodrigues R N, Lopes T. M. Organ-Preserving ( references are not required in the answer)
Surgery for Penile Carcinoma. Advances in Urology 2008
( references are not required in the answer) All the best.
2. Management of post transplant ureteric stricture
Ans: Occurs in 1 – 3% of all renal transplants. The more studying you did for the exam, the less sure you are
as to which answer they want.
Risk factors for late ureteral stricture
- Second Law of Applied Terror
 The Urology Masterclass, Department of Urology, CMC, Vellore
Male urethral stricture
Arabind Panda, Senior Consultant Urologist, KIMS, Hyderabad
Urethral stricture disease is as old as humanity itself.
Dilators and catheters have been described in ancient
Indian and Egyptian medical texts. Their treatment has not
changed much over millennia until the last 50 years.
The anatomy of the male urethra is responsible for the
heterogeneity of urethral stricture. Again urethral stricture
disease must be separated from an isolated urethral
stricture due to trauma. In such a scenario, a “one size fits
all” approach is unlikely to succeed.
It is important to note that most of the evidence for
treatment of urethral strictures comes from case series.
Randomized controlled trials are almost non-existent.
Anatomy
The male urethra originates at the bladder neck and extends
till the external urethral meatus. Regardless of what is
commonly described, it seems practical todivide the
urethra into 2 broad parts- the first consisting of the penile,
bulbar and the membranous and the prostatic. The first
part has the spongy “ spongiosum” covered by a thin
mucosa while the prostatic urethra has prostatic tissue
under the mucosal lining, the transition area being the
prostate- membranous junction (F igure 1).Embryologically,
the prostatic urethra arises from the pelvic part of the
urogenital sinus while the penile and bulbar urethral arise
from the phallic part- the urethral plate. The membranous
part joins the two.
Figure 1
This is important as the response to injury is different in
the two areas. Injuries in the penile, bulbar and the
membranous urethra typically heal with fibrosis-
“spongiofibrosis . The fibrosis is negligible in the prostatic
urethra, therefore the success of transurethral resection of
the prostate.
Urethral strictures Vs. Urethral distraction defects
Urethral strictures occur in the anterior urethra- they may
be inflammatory or traumatic. Distraction defects are due
to the distraction in urethral injuries that are associated
with pelvic fractures. They are situated exclusively in the
transition membranous area between the anterior and
prostatic urethra. Strictly speaking, strictures of the
23
posterior urethra are never primary. They are the result of
failed surgical repair for distraction defects.
Traumatic Vs. inflammatory strictures
Trauma to the urethra causes dense spongiofibrosis that
usually involves a short segment. The rest of the urethra,
both distal and proximal is essentially normal. These
strictures are amenable to excision and primary
anastomosis.
Inflammatory strictures may be due to infective (e.g.
Gonorrhoea) or non-infective causes (e.g. Blalanitis
xerotica obliterans). Regardless of etiology, they usually
have spongiofibrosis that extends well beyond the actual
stricuted segment. The spongiofibrosis is less dense than
traumatic strictures but extends both proximal and distal
to the narrowed segment. Visually, the mucosa over the
diseased segment may be white and metaplastic and the
lumen may have varying degrees of narrowing.
Evaluation
Despite impressive advances in imaging technology, a
combination of retrograde urethrography (RGU) and
voiding cystouretrography(VCUG) remains central to the
assessment of urethral stricture assessment.
For non obliterative strictures, visual inspectionof the
urethra by cystoscopy with a slender scope can provide
information about the extent of narrowingand urethral
metaplasia, providing a marker for the extent of
spongiofibrosis. On occasion, in cases of pelvic fractures
with posterior urethral distraction defect
(PFUDD),antegrade suprapubic tract cystoscopy may be
necessary to evaluate the competence of the bladder neck,
since it is the primary site of continence after urethral
repair.
The role of ultrasonagram (Sonourethrogram) for
delineating the extent of spongiofibrosis has been
investigated but its cumbersomeness and the lack of
objectivity precludes its regular use. Magnetic resonance
imaging can offer information about the degree of
distraction, lateral displacement and the presence of
nearby bone fragments due to the pelvic fracture. However
it is doubtful that it provides any real advantage over RGU/
VCUG for experienced surgeons.
PRINCIPLES OF MANAGEMENT Traumatic lesions
Pelvic fractures with posterior urethral distraction defects
and traumatic bulbar urethral strictures:
The treatment is standardized and least controversial.
Excision of the strictured segment with the surrounding
callus is mandatory with anastomosis of the healthy widely
spatulat ed ends (EPA) usually result s in a successful
outcome. However, though the principles of EPA for PFUDD
and traumatic bulbar urethral strictures are similar, the
nuances of technique are significantly different.
 24 The Urology Masterclass, Department of Urology, CMC, Vellore

Table 1 Steps of EPA for traumatic bulbar urethral strictures

1. Mobilization of the bulbar urethra till the penoscrotal junction

2. Identification and excision of the stricture till healthy urethra proximally and distally
3. Spatulation of both ends
4. Corporal plication ( if required)*
5. Tension free anastomosis with mucosal to mucosal apposition ( 1 or more layers)
* Ganesh Gopalakrishnan

Table 2 Steps of EPA for PFUDD- The stepwise progressive perineal approach( Webster(1)/Ganesh Gopalakrishnan)

1. Mobilization of the bulbar urethra till the penoscrotal junction #

2. Identification of the obliterated segment with urethral division
3. Crural / corporal body separation #
4. Inferior pubectomy # , identification of the proximal end with excision of all callus
5. Prostatic mobilization *
6. Corporal plication *
7. Supracrural rerouting #

#- Webster G (1986) * Ganesh Gopalakrishnan

Figure 2

The steps of corporal body separation, inferior pubectomy Distal urethral mobilization, particularly beyond the
and corporal rerouting , though possible does not help in penoscrotal junction must be balanced by the potential
the repair of traumatic bulbar strictures. The reason is quite for urethral ischemia and chordee. Stripping of the fascial
simple- by definition, this is a bulbo- bulbar anastomosis; layer over the spongiosum has also been postulated to
there is a part of the intact bulbar urethra in the proximal further reduce tension during anastomosis.
segment, particularly during the initial repair. The residual
proximal bulbar urethra retains the curve of the original
anatomic route and tends to pull the distal end outwards
after anastomosis. (F igure 2). However, corporal plication
( Figure 3) and aggressive mobilization of the distal urethra
does help in difficult cases.
 The Urology Masterclass, Department of Urology, CMC, Vellore
Figure 3 – Corporal plication (Ganesh Gopalakrishnan)
The transpubic approach ( Waterhouse/Pierce) was earlier
quite popular, however, the morbidity is much greater. Since
the majority of PFUDD can be managed by an elaborated
perineal approach, the role of the transpubic approach is
limited to very complex cases.
Inflammatory strictures
The maximum controversy exists regarding the idealmethod
of management for inflammatory strictures.
Substitution urethroplasty
Traditionally because oif the longer lengh involved in
inflammatory stricture, augmentation of the luimen of the
diseased urethra with a inlay or onlay segment of flap or
graft has been the preferred approach. This has been
described as substitution urethroplasty, evn though the
entire diseased segment is not substituted.
Flaps Vs. Grafts
Urologists have traditi0onally borrowed reconstructive
techniques from plastic surgeons. Flaps have historically
been the preferred method of reconstruction because of
their reliability(if well done) compared to grafts. The
proximity of hairless skin on the prepuce and the ease of
harvest also made it popular. However, increasingly it is
being recognized that a common cause of complex urethral
inflammatory strictures is balanitis xerotica obliterans (
BXO) which has a tendency to recur on the substituted skin
flap. For this reason in addition to the potential for
increased donor site morbidity and almost equivalent
results when compared to buccal mucosal grafts have
contributed to the decrease in their popularity. Flaps
specially if applied ventrally or as tube tend to form
diverticula over time with associate complications. The
procedure of raising a flap is also more complex than a
graft and remains technically challenging.
25
sc ar. Further, it is hairless and does well in a we t
environment. While it definitely superior to prepuceal skin
in cases of BXO, its advantage in non BXO cases is not
definitely proven.
Staged Vs. single stage repairs
Though an effort should be made for single stage surgery
whenever possible, complex urethral strictures do better
with a staged procedure. It is important to note that 2 stage
procedures actually have 3 stages. The middle “ interval”
stage is important to assess the take of the graft, pliability
of the plate and the patency of the proximal neomeatus
before the 2nd stage tabularization.
Ventral Vs. dorsal placement of the graft
Ventral onlay graft placement is technically easier and has
been reported to have excellent long term results in western
series(4). Dorsal onlay is technically more demanding and
requires more urethral mobilization. Spongioplasty
remains an integral part of the ventralonlay which requires
good quality thick spongiosum . Extensive urethral disease
and the relatively narrower urethra in the Indian
population may not allow for a wide ventral graft after
spongioplasty. It is best reserved for cases with a very short
segment mid to proximal bulbar strictures (in the area
covered by the bulbospongiosus muscle). In all strictures
with longer length, distal extension to the penile urethra,
and a thin bulbar urethra, a dorsal onlay is preferable.
Penile urethral strictures
Short segment penile urethral strictures may be simple to
repair if the rest of the urethra is normal. However in cases
where the entire penisis involved by BXO, it is technically
challenging, Staged substitution procedures is generally
preferred.
Definitive perineal urethrostomy
In cases of multiple failed surgeries- “urethral cripple” in
an older patient, a definitive perineal urethrostomy may
be an excellent option. It is important to place the broad
tip of the perineo-scrotal flap as proximally as possible.
Addition of a dorsal only graft to the ventral perineal flap
may offer greater rates of patency and fewer
reinterventions.
Redo- urethroplasty
Redo- urethroplasty remainschallenging and is best left to
specialist urethral surgeons. The concern in redo
anastomoticurethroplastyis two fold-1. Adequate length of
the residual urethra to permit tension free anastomosis
2. The vascularity and viability of the distal urethral
segment.Complete excision of callus requires extensive
dissection between the prostatic urethra and the rectum. A
more elaborate perineal approach, including inferior
pubectomy is usually required in these cases. Occasionally,
it may not be possible to achieve a tension free
anastomosis with the perineal approach, in which case,
 26 The Urology Masterclass, Department of Urology, CMC, Vellore

intra operative conversion to a transpubic approach

should be done. In inflammatory strictures, a redo
substitution urethroplasty is usually possible, either by a
ventral onlay or dorsal inlay approach.

Urethral rest before urethroplasty

Recent urethral instrumentation (within 30 days) those on
intermittent self-calibration at presentation are deemed
to have unstable strictures. Waiting ( 6- 8 weeks)will allow
for remodelling and permit the exact location and severity
of stricture to be known. A suprapubic cystostomy may be
placed if indicated(5).

Endoscopic internal urethrotomy (EIU) for urethral

strictures:
The long term success rate for endoscopic internal
urethrotomy is poor. It may be used in short segment
urethral strictures with minimal spongiofibrosis.There is
no evidence to suggest that injectionof steroidal and anti-
proliferative agents at the incision site increases the
success rate.
Conclusion
Urethroplasty requires experience and the knowledge of a
wide variety of techniques. There is no single correct
technique and surgery may need to be individualized for
the particular patient. It is best that the surgeon brings a
bouquet of skills to the table and adapt according to the
stricture.
( This is an extremely personal view of a complex subject.
Readers will be best served if they put on their
“reconstructive hats” while reading this.

References:
1. Webster GD, Ramon J. Repair of pelvic fracture posterior
urethral defects using an elaborated perineal
approach: experience with 74 cases. J Urol. 1991
Apr;145(4):744–8.
2. Barbagli G, Sansalone S, Djinovic R, Romano G, Lazzeri
M. Current controversies in reconstructive surgery of the
anterior urethra: a clinical overview. IntBraz J Urol Off J
BrazSoc Urol. 2012 Jun;38(3):307–16; discussion 316.
3. Bürger RA, Müller SC, el-Damanhoury H, Tschakaloff A,
Riedmiller H, Hohenfellner R. The buccal mucosal graft for
urethral reconstruction: a preliminary report. J Urol.
1992 Mar;147(3):662–4.
4. Barbagli G, Montorsi F, Guazzoni G, Larcher A, Fossati N,
Sansalone S, et al. Ve nt ra l o ral muc osal onlay graft
urethroplasty in nontraumatic bulbar urethral
strictures: surgical technique and multivariable analysis
of results in 214 patients. Eur Urol. 2013 Sep;64(3):440–
7.
5. Terlecki RP, Steele MC, Valade z C, More y AF. Ure thral
rest: role and rationale in preparation for anterior
urethroplasty. Urology. 2011 Jun;77(6):1477–81.
 The Urology Masterclass, Department of Urology, CMC, Vellore
Neoadjuvant chemotherapy for urothelial carcinoma bladder
Dr Antony Devasia, Professor, Christian Medical College, Vellore
Rationale for neoadjuvant chemotherapy
Preoperative staging with CT scan is inaccurate, especially
with extra vesical extension and lymph node involvement,
with up to 50% upstaging. (1) The management can be more
effective, if these tumours could be down staged prior to
cystectomy. Neoadjuvant chemotherapy (NC) has been
recommended for muscle invasive bladder cancer with level
1 evidence in several guidelines.
Evidence
The evidence is largely based on four trials conducted over
twenty years ago. In the meta-analysis conducted by the
MRC clinical trials unit and reported by the Advanced
Bladder Cancer meta-analysis collaboration that included
3005 patients from 11 trials, the 5 year overall survival
(OS) benefit was seen to be 5% and a disease free survival
benefit was 9%.(2) An updated meta-analysis that included
3285 patient showed 13% improvement in OS (HR, 0.87;
95% CI, 0.79–0.96; p = 0.004). When Gemcitabine +
Cisplatin/ Carboplatin (GC) was compared with
Methotrexate, V inblastin, Adriamycin and Cisplatin
(MVAC), the OS was better with MVAC (HR, 1.26; 95% CI,
1.01–1.57). After excluding Carboplatin, the difference was
not significant. (3)
The most often quoted trial is the SWOG/ Intergroup study,
where 307 node negative T2-T4 patients were randomised.
153 had MVAC + cystectomy vs 154 cystectomy alone. The
OS between the two were not statistically significant at 77
months vs 46 months (p=0.06) with a greater tendency for
no residual tumour in the final specimen with NC (38% vs.
15%, p<0.001) (4).
Summary of trials
Trial Regimen
MRC BA06/EORTC CMV
30894
SWOG 8710 MVAC
Nordic I Cis + Doxorubicin
+ RT
Nordic II Methotrexate+
Cisplatin
27
The largest study on NC is the International Collaboration
of Trialists (MRC) study that randomized 976 patients with
T2-4aN0M0 disease to local therapy (Cystectomy/ RT) with
(n=485) or without (n=491) NC (3 cycles of Cisplatin,
Methotrexate and V inblastin). At 10 years, there was
improved OS (36% vs. 30%, HR 0.84, p=0.037). However,
CMV is not a standard regime and has not been compared
with MVAC. The 10 year DSS was 27% for NC vs 20% for
immediate treatment (5). These results were used to claim
superiority of NC over cystectomy alone.
The Nordic I trial, 311 patients (pT1 G3, T2-T4aNxM0)
randomly allocated to NC (Cisplatin + Doxorubicin, 2 cycle)
or no chemotherapy arm. All patients received 4 Gy daily
local radiation for 5 days. The 5-year overall survival was
similar in both groups (59% vs 51%, p = 0.1). In the subset
of patients with extravesical disease, the 5-year survival
was significantly better for neoadjuvant chemotherapy
(52% vs 37%, P = 0.03), although this finding is only
hypothesis generating (6). In Nordic II, the treatment arm
received 3 cycles of neoadjuvant Methotrexate + Cisplatin
(n=155) vs. cystectomy alone (n=153) in the control arm.
There was no difference in 5 year OS (53 vs. 46%). However,
a greater percentage had pT0 disease in the NC arm (26.4%
vs. 11.5%, p=0.001). (7)
Criticism of the studies (SWOG and MRC)
In T2 lesions the OS was higher with NC compared to
cystectomy alone pushing the case for NC. However, other
cystectomy only series show much higher survival (6). This
may be attributed to the fact that several of the T2 may
have been understaged with the imaging available in the
eighties. The pT0 who had better OS than the others may
have become T0 with TUR alone, without NC.
Results in terms of survival
6% improvement in absolute survival at 10 yrs
33% lower mortality. Survival 77 vs. 46
months (p=0.06) at 11 yrs
Overall no benefit
15% benefit in survival in T3-4a
No overall benefit (53 vs. 46% OS at 5 yrs)
 28 The Urology Masterclass, Department of Urology, CMC, Vellore
Alternate regimens;
Gemcitabine based
The initial regimens had high toxicity, grade 3 and 4 in
more than a third of patients. The focus therefore shifted
to regimens that were less toxic. The current regimens use
Gemcitabine that is less toxic but its equivalence to MVAC
is extrapolated from retrospective studies in the metastatic
setting (9). Till date, this has not been adequately studied
prospectively to be equivalent, except for one small study
that showed benefit (10). However, another trial showed
gemcitabine regimen to be less effective than MVAC (11).
Dose dense/accelerated regimen (MVAC)
This regimen was designed to reduce the toxicity of the
earlier MVAC regimen, improve efficacy in a reduced time
frame. The cycle was shortened to 2 weeks, increasing the
dose intensity of cisplatin and doxorubicin and reducing
that of vinblastine and methotrexate. The results are
promising. Patients withT2-T4 disease at a follow up of 2
years had pathological response in 49% with a 1 year
disease free survival of 89% in this group (12) The
shortened regimen was found to be as good as the 12 week
regimen with much less toxicity. With level 1 evidence of
superiority of treatment, though marginal, neoadjuvant
chemotherapy is not used being used universally for
various reasons. a)Delay in cystectomy especially if there
is no response to chemo therapy b)In genuine T2 lesions it
may be over treatment c)Perception that there is
perioperative morbidity in the post chemotherapy
scenario. The highly effective dose dense regimen with
lower toxicity with only a short delay in radical cystectomy,
may set the tone for a resurgence in the use of neadjuvant
chemotherapy for muscle invasive bladder cancer
References
1. Tritschler S, Mosler C, Tilki D, Buchner A, Stief C, Graser
A. Interobserver, variability limits exact preoperative
staging by computed tomography in bladder cancer.
Urology 2012;79:1317–21.
2. Advanced Bladder Cancer (ABC) Meta-analysis
Collaboration. Neoadjuvant chemotherapy in invasive
bladder cancer: update of a systematic review and
meta-analysis of individual patient data. Eur Urol
2005;48:202.
3. Y in M, Joshi M, Meijer RP, et al. Neoadjuvant
Chemotherapy for Muscle-Invasive Bladder Cancer: A
Systematic Review and Two-Step Meta-
Analysis. Oncologist. 2016;21(6):708–715. doi:10.1634/
theoncologist.2015-0440
4. Grossman HB, Natale RB, Tangen CM, etal. Neoadjuvant
chemotherapy plus cystectomy compared with
cystectomy alone for locally advanced bladder cancer.
N Engl J Med 2003;349:859–66.
5. International Collaboration of Trialists; Medical
Research Council Advanced Bladder Cancer Working
Party (now the National Cancer Research Institute
Bladder Cancer Clinical Studies Group); European
Organisation for Research and Treatment of Cancer
Genito-Urinary Tract Cancer Group; International phase
III trial assessing neoadjuvant cisplatin, methotrexate,
and vinblastine chemotherapy for muscle-invasive
bladder cancer: long-term results of the BA06 30894
trial. J Clin Oncol. 2011;29(16):2171–2177.
6. Rintala E, Hannisdahl E, Fossa SD, Hellsten S, Sander S.
Neoadjuvant chemotherapy in bladder cancer: a
randomized study. Nordic Cystectomy Trial I. Scand J
Urol Nep. 1993; 27(3):355-62.
7. Amir Sherif, Erkki Rintala, Oddvar Mestad, Jonas Nilsson,
Lars Holmberg, Sten Nilsson & Per-Uno
Malmström (2002) Neoadjuvant Cisplatin-
Methotrexate Chemotherapy for Invasive Bladder
Cancer - Nordic Cystectomy Trial 2, Scandinavian
Journal of Urology and Nephrology, 36:6, 419-425
8. Hautmann RE, de Petriconi RC, Pfeiffer C, Volkmer BG.
Radical cystectomy for urothelial carcinoma of the
bladder without neoadjuvant or adjuvant therapy: long
term results in 1100 patients. Eur Urol 2012;61:1039-
9. Vonder Masse, H,Hansen, SW,Roberts JT etal gemcitabine
and Cisplatin versus methotrexate, vinblastine
doxorubicin and cisplatin in advanced or metastatic
bladder tumor. Results of a large multinational,
multicentre phase III study. J Clin Oncol 2000;18:3068-
3077
10. Herchenhorn D, Dienstmann R, Peixoto FA, et al: Phase
II trial of neoadjuvant gemcitabine and cisplatin in
patients with resectable bladder carcinoma. Int Braz J
Urol, 2007.33:630-638
11. Weight CJ, Garcia JA, Hansel DELack of pathological
downstaging with neoadjuvant chemotherapy for
muscle invasive carcinoma of the bladder. A
contemporary series Cancer :2009;115: 792-799
12. Choueiri TK, Jacobus S, BellmontJ, Qu Aetal.
Neoadjuvant Dose-Dense Methotrexate, Vinblastine,
Doxorubicin, and Cisplatin With Pegfilgrastim Support
in Muscle-Invasive Urothelial Cancer: Pathologic,
Radiologic, and Biomarker Correlates J ClinOncol.
2014;32:1889-94
 The Urology Masterclass, Department of Urology, CMC, Vellore 29

Controversies in the management of SRM- Are we doing more

harm than good?
Dr. Santosh Kumar, Christian Medical College Vellore
Small renal masses (SRM) are defined as enhancing renal desire for cure. Radiofrequency ablation is less effective
masses less than 4 cm in size. The renal adenomas in the than cryoablation. Both of them have significant failure
past have been described as masses less than 3 cm which rates and there is no established protocol for follow-up
looked histologically similar to renal cell carcinoma but after ablation. Enhancement of the mass on follow-up
with a low frequency of metastasis (2.6%) compared to imaging has been the marker for treatment failure. Biopsy
larger tumours. Over the last decade there has been an after ablative therapy is not always performed during
increase in incidence of renal cancer due to detection of follow-up due to which, the true recurrence rates are
SRM, thanks to the generous use of ultrasound and CT scan difficult to comment on. There have been instances of biopsy
for evaluation of unrelated conditions. Most of the tumors proven recurrence even when the imaging shows non
are incidentally detected and the mean tumour size has enhancement. Partial nephrectomy is difficult and likely
decreased from 4.1 to 3.6 cm between 1993 and 2004. to result in nephrectomy if salvage therapy is planned when
Presently the majority of these masses are surgically ablation fails. Surgery is technically difficult in this
treated however, the mortality from renal cancer is still on situation due to dense fibrosis and this has to be kept in
the rise leading to a phenomenon called, ‘Treatment mind when ablative therapy is offered.
disconnect.’ This brings us to the question if we are doing
more harm than good with respect to the evaluation and
Active surveillance is limited to those who are at high
management of SRM.
surgical risk and with decreased life expectancy. Biopsy is
not always included in the surveillance protocols and is
Overall 20% or SRM are malignant and at a risk of likely to identify patients at high risk for the development
progression, 60% are indolent malignant with low risk of of metastases. A risk stratified approach is the need of the
metastasis and 20% are benign. Ironically the imaging hour with regards to management of SRM.
which has led to the increased discovery of SRM is
ridiculously inaccurate in differentiating the benign (fat
poor Angiomyolipoma/ Oncocytoma) from the different
malignant histological variants of renal cancer. The rate
of growth or absence thereof on serial imaging is also a
poor predictor of malignancy. However very rapidly growing
tumours are likely to be aggressive and metastasize. The
incidence of biopsy proven malignancy on histology
increases with the size of the tumour from 54 to 80% for 1
cm to 4 cm tumours respectively as does the histological
grade. It is possible to characterize the pathology for renal
masses by biopsy with a sensitivity of 80 to 92% and a
specificity of 83 to 100%. Biopsy can be performed
accurately and with minimal complications today.
Unfortunately biopsy is seldom performed except before
percutaneous ablation of SRM and rarely before active
surveillance is initiated.

There is a decreasing trend for radical nephrectomy and

an increasing trend for partial nephrectomy in the
treatment of these tumours with an emphasis on renal
preservation. Partial nephrectomy is the treatment of
choice in fit individuals and percutaneous ablation is
reserved for patients with poor performance status but a
 30 The Urology Masterclass, Department of Urology, CMC, Vellore

Management of Urinary Leak Post Renal Transplantation

Dr. Rajiv Paul Mukha, CMC Vellore

Urinary Complications after renal transplantation Renal scintigraphy

• A renogram shows extravasation.
In a large study on laparoscopic donor nephrectomies, (1)
• Most sensitive method to differentiate a urine leak from
ureteral complications occurred in 66/853 patients (7.73%):
lymphoceles and hematomas. (6)
urinary tract infection in 2.81%, anastomosis site stricture
• Presence of radiotracer outside the urinary tract is
in 2.69% and anastomosis site leakage in 1.28%. Other
diagnostic of a urinary leak.
studies showed an incidence of 1.2% to 8.9%
• Hematomas and lymphoceles show an area of low
Incidence and risk factors concentration of radiotracer.
The most common early urological complication is urinary • Cystogram only if a bladder leak is suspected.
leak. Incidence varies from 1.2% to 8.9%. The causes being:
Management
ureteral devascularisation, faulty technique and tunnel
• Needs rapid diagnosis and treatment.
hematoma. (2)(3)(4)
• Commonest site is the ureterovesical anastomosis.
Other risk factors (5) • Early surgery is the preferred approach.
• Donor age • Primary reconstruction is the treatment of choice.
• Delayed graft function
Management (7)
• Ureteric stenting
• New ureteral reimplantation.
Clinical presentation • Bladder flaps if the ureter is short or has necrosis.
• Increased drain output. • Primary reconstruction with the ureter of the recipient.
• Urinary ascites. • DJ stenting with the repair.
• Swelling around the surgical site, scrotum or perineum. • Nephrostomy alone or with the ureteral occlusion if
• Unexplained graft dysfunction. the patient is unstable.
• Pelvic fluid collection.
Conservative approach (8, 9, 10, 11, 12)
• Fever, graft tenderness.
• Only recommended if patient is unstable or a very small
Diagnosis leak.
• Biochemical analysis of drain fluid or fluid from • Prolonged bladder catheterization.
collection. • Percutaneous nephrostomy, drainage of urinoma.
• Lymphoceles have the same creatinine as serum. • Nephrostogram at time of PCN determines site of leak.
• Urinary leaks have raised drain fluid creatinine. • Antegrade stenting once patient stable.
• Ultrasounds, CT and MRI are non specific as they only • Overall success rate of 62% (36% - 87%).
show a fluid collection. • Close monitoring following stent removal necessary
because of the risk of a secondary stricture.

Does the Ureterovesical anastomosis technique matter?

Prevalence of urological complications in all included studies (13)
Ureterovesical anastomotic technique
Complication PL LG U
Leakage 95/3299(2.9%) 116/7104 (1.6%) 40/1187 (3.4%)
Ureteral stricture 106/3278(3.2%) 138/7243 (1.9%) 52/1418 (3.7%)
Vesicoureteral reflux 20/1293(1.5%) 85/3555(2.4%) -
Hematuria 79/1925(4.1%) 52/3040(1.7%) 96/1336(7.2%)

PL Politano-Leadbetter, LG- Lich-Gregoir, U – U stitch

• Extravesical Lich Gregoir had the least incidence of leaks.
 The Urology Masterclass, Department of Urology, CMC, Vellore 31

Impact of prophylactic stenting 10)Swierzewski SJ, Konnak JW, Ellis JH. Treatment of renal
transplant ureteral complications by percutaneous
• A Cochrane review of RCTs and Quasi RCTs (14) including
technique. J Urol1993;149:986e7.
1154 patients showed universal prophylactic stenting
reduces major urinary complications (leaks and 11) Bhagat VJ, Gordon RL, Osorio RW, LaBerge JM, Kerlan Jr
obstruction). RR 0.24, 95% CI 0.07 to 0.77, P = 0.02. The RK, Melzer JS, et al. Ureteral obstructions and leaks
number needed to treat was 13. after renal transplantation: outcome of percutaneous
antegrade ureteral stent placement in 44 patients.
Take home message Radiology 1998;209:159e67.
• Prophylactic stenting helps decrease incidence. 12)Alcaraz A, Bujons A, Pascual X, Juaneda B, Marti J, de la
• At a higher risk of UTI. Torre P, et al. Percutaneous management of transplant
• Short term stenting may mitigate risk. ureteral fistulae is feasible in selected cases. Transplant
Proc 2005;37:2111e4. [34] Favi E, Spagnoletti G, V.
• Lich- Gregoir extravesical is the most favored technique.
13)V ictor P Alberts et al. Ureterovesical anastomotic
• Increased donor age, delayed graft function and
techniques for kidney transplantation: a systematic
vascular compromise to ureter during retrieval are
review and metaanalysis. Transplant
factors to be wary of.
International.March 2014
References: 14)Wilson CH et al. Cochrane review –Routine prophylactic
1) Ureteral complications in Kidney Transplantations: stenting reduces the incidence of major urological
Analysis and Management of 853 Consecutive complications in kidney transplant recepients. June
Laparoscopic Living –Donor Nephrectomies. Transplant 2013
Proc. 2016 Oct; 48(8):2684-2688.
2) Streeter EH, Little DM, Cranston DW, Morris PJ. The
urological complications of renal transplantation: a
series of 1535 patients. BJU Int 2002;90:627e34.
3) Lempine J.Stenman J, Kyllonen L, Salmela K. Surgical
complications following 1670 consecutive adult renal
transplantations: a single center study. Scand J Surg
2015.
4) Nie ZL, Zhang KQ, Li Qs, Jin FS, Zhu FQ, Huo WQ. Treatment
of urinary fistula after kidney transplantation.
Transplant Proc 2009;41:1624e6.
5) Ureteral necrosis after kidney transplantation: risk
factors and impact on graft and patient survival, Karam
G, Maillet F, Parant S, Soulillou JP, Giral-Classe M.
Transplantation. 2004 Sep 15;78(5):725-9.
6) Bretan PN et al. Journal of Radiology 1989
7) Diagnosis and management of ureteral complications
following renal transplantation Brian D. Duty, John M.
Barry. Asian Journal of Urology (2015) 2, 202e207
8) Matalon TA, Thompson MJ, Patel SK, Ramos MV, Jensik
SC, Merkel FK. Percutaneous treatment of urine leaks in
renal transplantation patients. Radiology 1990;174(3
Pt 2):1049e51.
9) Campbell SC, Streem SB, Zelch M, Hodge E, Novick AC.
Percutaneous management of transplant ureteral
fistulas: patient selection and long-term results. J Urol
1993;150: 1115e7.
 32 The Urology Masterclass, Department of Urology, CMC, Vellore

The role of cytoreductive nephrectomy in metastatic renal cell

carcinoma

Dr Arun Jacob Philip George, CMC Vellore

Renal cell carcinoma (RCC) presents with metastases in
30% at the time of diagnosis. Metastatic RCC is one of the
most chemotherapy resistant malignancies (1).
Cytoreductive nephrectomy was demonstrated to improve
survival along with cytokine therapy in two randomized
trials in patients with metastatic RCC who had a good
performance status
The SWOGS8949 trial randomized 246 patients to
nephrectomy with or without adjuvant Interferon alpha.
The nephrectomy arm demonstrated improved overall
survival (OS 11 vs. 8 months, HR 0.74, 95% CI 0.57–0.96
p=0.022). Overall survival was poorer if performance status
was ECOG 1 vs. 0 (HR 1.95, p<0.0001), alkaline phosphatase
was high (HR 1.5, p=0.002) or if there was progression
within 90 days of initiation of therapy (HR 2.1, p<0.001), It
was better with lung metastases (HR 0.73, p=0.028) (2). In
the EORTC study, 85 patients were randomized to
nephrectomy with or without adjuvant Interferon alpha.
The OS was better in the nephrectomy arm (17 vs. 7 months,
HR 0.54 95% CI 0.31-0.94) as was the time to progression
(5 vs. 3 months, HR 0.6 95% CU 0.36-0.97) (3). Combined
analysis of the two trial revealed that cytoreductive
nephrectomy improved survival by a median of 6 months
(13.6 vs. 7.8 months) (4).
However, the role of cytoreductive nephrectomy in the TKI era
has been challenged. Phase 2 trials showed that pre-operative
Sunitinib followed by nephrectomy resulted in a median
survival of 26 months in intermediate risk patients. Those
with progression of disease prior to planned nephrectomy
(HR: 5.34), high Fuhrman grade (HR 3.27), and MSKCC poor
risk at diagnosis (HR 4.75) has poor survival (5).
Two phase III randomized control trials have studied the
role of cytoreductive nephrectomy and its sequencing with
targeted therapy in patients with metastatic RCC and good
performance status. These have been summarized in the
table below:

CARMENA (6) SURTIME (7)

n 450 (226 and 224) 90 (50 and 49)
Intervention vs. control Immediate CN + Sunitinib vs. Immediate CN followed by Sunitinib vs. 3
Sunitinib alone months of Sunitinib followed by CN
Inclusion Asymptomatic primary + Asymptomatic primary + synchronous
synchronous met, ECOG 0/1 met, ECOG 0/1
End points OS and PFS OS and PFS (Revised to 28 week PFS)
Median follow-up 4.2 years 3.3 years
Primary tumour size (mm) 88 (6-200) 94.5 (13-200)
Median age 63 59
Motzer risk group 47% intermediate, 43% poor 87% intermediate, 13% poor
Median number of metastases 2 2
OS (Intervention) 13.9 months (11.8-18.3) 15 months (9.3-29.5)
OS (Control) 18.4 months (14.7-23) 32.4 months (14.5-65.3)
 The Urology Masterclass, Department of Urology, CMC, Vellore 33

SURTIME (Sunitinib Malate in Treating Patients With with metastatic renal cancer: a combined analysis.J
Metastatic Kidney Cancer) aimed to compare the Urol. 2004;171(3): 1071-1076.
sequencing of Sunitinib with cytoreductive nephrectomy. 5. Powles T, Blank C, Chowdhury S, Horenblas S, Peters J,
The planned sample size was 455 with PFS and OS as end Shamash J et al. The outcome of patients treated with
points. However, only 99 patients could be recruited and Sunitinib prior to planned nephrectomy in metastatic
end point was changed to PFS at 28 weeks. Although OS clear cell renal cancer
was greater in the deferred nephrectomy arm (HR 0.57,
6. Méjean A, Ravaud A, Thezenas S, et al. Sunitinib alone or
p=0.03), it was not statistically powered to draw
after nephrectomy in metastatic renal-cell carcinoma.
conclusions.
N Engl J Med. 2018;379(5):417-427
CARMENA (Clinical Trial to Assess the Importance of
7. Bex A, Mulders P, Jewett M, et al. Comparison of immediate
Nephrectomy) also did not complete accrual. But ITT
vs deferred cytoreductive nephrectomy in patients with
analysis was powered to demonstrate non-inferiority in
synchronous metastatic renal cell carcinoma receiving
the Sunitinib only arm (HR 0.89, 95% CI 0.71-1.1). Although
sunitinib: The SURTIME randomized clinical trial. JAMA
the survival among those who did not undergo
Oncol. 2019;5(2):164-170.
nephrectomy was greater (18.4 vs. 13.9 months), it was
not statistically significant. 17% of patients in the
sunitinib-only arm crossed over to receive CN. Poor risk
patients constituted 44% of the intervention and 42% of
control arm. Cytoreductive nephrectomy is usually not
recommended in this group of patients and may confound
results.
Although these RCTs had their limitations, they could help
direct clinical practice. Both highlight the importance of
careful patient selection for nephrectomy and the perils
of immediate cytoreductive nephrectomy (And delay in
initiation of systemic therapy) in poor risk patients. These
results are not generalizable to the current era of
expanding use of immune check point inhibitor therapy
(Nivolumab + ipilimumab, Pembrolizumab/ Avelumab +
Axitinib) and superior survival with the same. Further
trials will be required to answer this question in full.

References
1. Bex A, Powles T. Selecting patients for cytoreductive
nephrectomy in advanced renal cell carcinoma. Expert
Rev Anticancer Ther. 2012; 12(6):787-797.
2. Lara PN Jr, Tangen CM, Conlon SJ, Flanigan RC, Crawford
ED; Southwest Oncology Group Trial S8949. Predictors
of survival of advanced renal cell carcinoma: long-
term results from Southwest Oncology Group Trial
S8949. J Urol. 2009; 181(2):512–517.
3. Mickisch GH, Garin A, van Poppel H, de Prijck L, Sylvester
R; European Organisation for Research and Treatment
of Cancer (EORTC) Genitourinary Group. Radical
nephrectomy plus interferon-alfa-based
immunotherapy compared with interferon alfa alone
in metastatic renal-cell carcinoma: a randomised trial.
Lancet. 2001;358 (9286):966-970
4. Flanigan RC, Mickisch G, Sylvester R, Tangen C, Van Poppel
H, Crawford ED. Cytoreductive nephrectomy in patients
 34 The Urology Masterclass, Department of Urology, CMC, Vellore
Future technologies for BPH
Dr. Rajadoss Pandian, CMC, Vellore
Benign prostatic enlargement caused by benign
hyperplasia involving both the cellular and stromal content
of the prostate gland, is one of the many factors
contributing to lower urinary tract symptoms. Clinical
presentation could include storage, voiding, and post-
micturition symptoms. Management strategies could
comprise of watchful waiting, dietary and behavioural
modifications, pharmacotherapy, and in not is some
surgical relief of obstruction.
TURP and open prostatectomy, set as the standards for
relief of BPO, have proven clinical outcome, while being
associated with immediate and delayed complications.
Recent research on LUTS, have suggested a multifactorial
aetiology. This has become the basis for development of
newer technologies which are minimally-invasive, day
procedures under local anaesthesia, with minimal
complications. The aim of this discussion is to cover a
brief overview of newer technologies available for lower
urinary tracts symptoms associated with benign prostatic
hyperplasia - including Prostate urethral lift, Transurethral
water vapour therapy – the Rezum system, Aquablation,
Injectable Agents (dehydrated ethanol, botulinum
neurotoxin, NX-1207, PRX302), Histotripsy, and Prostate
Artery Embolization.
Prostatic urethral Lift
Prostatic tissue is compressible, PUL works on the principal
of “mechanical separation of lateral lobes”, without
requiring tissue resection. The system comprises of two
tabs bridged by a non-absorbable suture, which are put in
place using a spring-loaded 19G needle using 20Fr rigid
cystoscope sheath. The outside tab is placed on the prostatic
capsule, attached to the suture, inside tab is placed on the
urethral wall. The lateral lobe is compressed and the suture
is cut at the desired level, which widens the urethral lumen.
Implants are placed on both lateral lobes with an aim is
create a continuous channel between bladder neck and
the veru. Initial pilot study by Woo et al, in 2011 confirmed
improvement (about 40%) of symptoms at 1 year, with
minimal complications(1). Three randomised controlled
trials confirmed improvement of IPSS (40% decrease),
Qmax (50% improvement), QoL (50% improvement), and a
variable change in the post-void residual urine, at 2
years(2–4). A single study showed durable improvement in
measured parameters over a period of 4 year in 79 patients.
Advantages of Urolift includes its low invasiveness,
minimal haematuria, preserved antegrade ejaculation,
outpatient treatment, and durability of symptoms up to 4
years. A new interventional clinical trial to study the
efficacy of this procedure on median lobes is in progress
(NCT02625545)(5).
Aquablation
It is an image guided robot-assisted water-jet ablation of
prostate. Aquablation is done under general anaesthesia
in lithotomy position. High velocity saline stream is used
to ablate prostatic tissue while preserving the capsule.
Prostate gland is mapped using biplanar TRUS probe.
Velocity of saline stream varies on depth, and thickness of
tissue. Longitudinal and rotational movement of probe are
controlled from the console using a robotic handpiece.
Following Aquablation, haemostasis could be aided by
using diathermy or low power laser. Data summarized from
four single-centre, prospective, non-randomised clinical
trials reporting 3-12 follow-up in 54 patients, revealed
improvements ranging from 61-90% for IPSS, 50-101% for
Qmax, 44-88% for QoL and 62-83% for PVR(6). Advantages
of Aquablation include its accuracy, good safety profile
and preservation of antegrade ejaculation. WATER: a
double-blind, randomized controlled trial of Aquablation
Vs TURP confirmed non-inferior symptom relief and lower
risk of sexual dysfunction(7). A multicentre randomised
trial comparing water-jet ablation therapy with TURP is
underway (NCT02505919)(8).
Transurethral water vapour therapy
Convective Radiofrequency water vapour thermal energy
results in protein denaturation and destruction of cells.
Axially deflecting needle with side holes is used to emit
water vapour circumferentially. Typically, 4-6 injections
are required (each lasting 8-10 seconds). Two studies
reported the effect of convective water vapour energy on
prostate, at 12 months follow up: IPSS decreased by 55%,
Qmax increased by 35%, QoL decreased by 55%, with a 4%
decrease in PVR(9,10). Dixon et al, completed a 2 year
follow up, confirming durable symptomatic improvement.
The advantages of Rezum thermal treatment include short
procedure time (average of 5min), office treatment (peri-
prostatic block). One-third of patients had mild-moderate
adverse effects. There were no chronic adverse effects and
no reported erectile or ejaculatory complications. One
prospective, randomised, controlled, single-blind clinical
trial is underway(11).
 The Urology Masterclass, Department of Urology, CMC, Vellore
Injectable agents
Prostatic pseudocapsule prevents injectate from affecting
the surrounding tissues. Easy access to prostate via
transurethral, transrectal and transperineal approaches
and the ability to visualize precise needle deployment
using urethroscopy, TRUS, or MRI has greatly facilitated
the use of intraprostatic injectable agents. Hollow-core,
axially deflecting, nitinol needle was used in the initial
studies. Dehydrated ethanol (EtOH) was the most widely
studied intraprostatic injectable agent. Botulinum
neurotoxin (BoNT) has been evaluated, in addition to these,
two newer agents, NX-1207(pro-apoptotic) and PRX302
(proteolytic) have been tested.
Dehydrated ethanol
Effects have been studied in canine models, complete tissue
ablation was noted at 12 weeks. Conventional enhanced
delivery is new technology using a porous needle
containing small tubule with millions of nanoscale pores,
allowing diffusion through the entire length of catheter.
Two multicentre clinical trials on transurethral EtOH
ablation of prostrate (TEAP) reported significant
improvement in IPSS, QoL and Qmax. 12-month post-
procedure prostate volume decreased by about 15%(12,13).
Bothersome irritative voiding symptoms were noted in
about one-third of patients, about one-fifth of had urinary
retention, haematuria noted in 16-41%, and erectile
dysfunction reported in 2.5-4%. Serious adverse effects
noted in two patients included bladder necrosis and
ureteric stenosis. Li et al, reported a long-term follow in 70
elderly patients who underwent TRUS guided injections.
Flow parameters and PVR improved significantly(14). IPSS
improved by 67% and prostate volume decreased by 16%
by 6 months and remained unchanged. All positive effects
were maintained throughout the follow up period of 2 years.
Two patients had acute cystitis and another 2 patients
developed bladder necrosis. A total injection volume
exceeding 25% of the calculated prostatic volume
increased the risk of injury to periprostatic tissue.
Botulinum neurotoxin
BoNT inhibits neurotransmitter release and causes smooth
muscle relaxation. Therapeutic efficacy in overactive
bladder has formed the basis for effect on prostate. Injected
under TRUS guidance at 3 locations (cranial, middle, caudal)
of transitional zone of each lateral zone using transrectal
or transperineal approach. Systematic review and
metanalysis for BoNT for Lower urinary tract symptoms
showed there were no differences in efficacy when
35
compared with placebo(15). BoNT should be used only in
experimental setting as part for clinical trials.
NX-1207
Proprietary protein with pro-apoptotic properties, led to
40-47% reduction of prostate volume in animal models
(rat and dog). Transrectal ultrasound guided injections are
done using 22G needle. Phase III studies in the US failed to
meet the primary efficacy endpoint.
PRX302
Genetically modified proaerolysin is activated by PSA after
intraprostatic injection. TRUS guided transitional zone
injections are done using transperineal route. A multi-
centre, double-blind, randomized trial showed an
improvement of 3 points on IPSS and 2.2ml/sec on Qmax,
which were sustained at 12 months(16). Mild to moderate
adverse effects in up to one-third of patients, resolved in
72 hours. There was no effect on erectile function.
Histotripsy
Extracorporeal ultrasound energy is delivered
transperineally under TRUS guidance, to cause tissue
homogenisation and intraprostatic cavitation. An abstract
described clinical efficacy and safety in 25 patients, with
6 months follow-up on 24 patients(17). There was 44%
improvement in IPSS, with minimal improvements in
uroflow and PVR. Adverse effects included one anal
abrasion, one microhaematuria, and four urinary retention.
Prostate artery embolization
Prostate arteries are embolised using fine microcatheters
through pelvic arteries under X-ray guidance. Left or right
femoral artery is accessed under local anaesthesia.
Decreased blood supply produces tissue ischaemia
resulting in necrosis and shrinkage. Systematic review
which included two randomised controlled trials and 1
non-randomised controlled trial, 2 case series and 3 case-
reports was reported in 2017(18). It showed a mean
improvement at 36 months in IPSS by 12.1(±8.6), in maximal
urinary flow by 3.2 (±10.3) ml/sec, in QoL score by 1.7(±1.3),
and in prostate volume by 12.6% (±26.9). Adverse effects
included local arterial dissection in 2%, non-target
embolization in 1%, bladder wall ischemia in <1%, acute
urinary retention in 9%, rectal bleeding in 6%, haematuria
in 3%, abnormal ejaculation in 1%, inguinal haematoma
in 2%, urinary tract infection in 3%, sepsis in <1%, and
urethra or bladder neck stricture in 1%. NICE guidelines
advices setting up standard for clinical governance,
 36
consent, and audit, prior to offering this service(19). PAE
patient is selected by Urologist and experienced
interventional radiologist. This procedure should be
performed by an interventional radiologist with specific
training and expertise.
Conclusion
TURP has a remarkable clinical efficacy, while being an
invasive procedure, associated with complications. The
number of elderly patients with significant comorbidities
requiring relief of benign prostatic obstruction has
gradually increased, justifying the development and use
of minimally-invasive modalities of treatment. Most of
these technologies lack long term efficacy data. Urolift
received FDA approval in March 2016, and has the potential
for wider usage. Few highly skilled interventional
radiologists have demonstrated good treatment efficacy
with acceptable safety profile.
Bibliography
1. Woo HH, Chin PT, McNicholas TA, Gill HS, Plante MK,
Bruskewitz RC, et al. Safety and feasibility of the prostatic
urethral lift: a novel, minimally invasive treatment for
lower urinary tract symptoms (LUTS) secondary to
benign prostatic hyperplasia (BPH). BJU Int.
2011;108(1):82–8.
2. Rukstalis D, Rashid P, Bogache WK, Tutrone RF, Barkin J,
Chin PT, et al. 24-month durability after crossover to
the prostatic urethral lift from randomised, blinded
sham. BJU Int. 2016;118(S3):14–22.
3. Gratzke C, Barber N, Speakman MJ, Berges R, Wetterauer
U, Greene D, 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(5):767–75.
4. Roehrborn CG. Prostatic Urethral Lift: A Unique
Minimally Invasive Surgical Treatment of Male Lower
Urinary Tract Symptoms Secondary to Benign Prostatic
Hyperplasia. Urol Clin North Am. 2016 Aug;43(3):357–
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5. Study of Median Lobe Prostatic UroLift Procedure - Full
Text View - ClinicalTrials.gov [Internet]. [cited 2019 May
21]. Available from: https://clinicaltrials.gov/ct2/show/
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6. 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(6):923–9.
The Urology Masterclass, Department of Urology, CMC, Vellore
7. Gilling P, Barber N, Bidair M, Anderson P, Sutton M, Aho
T, et al. WATER: A Double-Blind, Randomized, Controlled
Trial of Aquablation® vs Transurethral Resection of the
Prostate in Benign Prostatic Hyperplasia. J Urol. 2018
May;199(5):1252–61.
8. Waterjet Ablation Therapy for Endoscopic Resection of
Prostate Tissue (WATER) - Full Text V iew -
ClinicalTrials.gov [Internet]. [cited 2019 May 21].
Available from: https://clinicaltrials.gov/ct2/show/
NCT02505919
9. Minimally Invasive Prostate Convective Water Vapor
Energy Ablation: A Multicenter, Randomized, Controlled
Study for the Treatment of Lower Urinary ... - PubMed -
NCBI [Internet]. [cited 2019 May 21]. Available from:
https://www.ncbi.nlm.nih.gov/pubmed/26614889
10.Two-year results after convective radiofrequency water
vapor thermal therapy of symptomatic benign prostatic
hyperplasia. - PubMed - NCBI [Internet]. [cited 2019
May 21]. Available from: https://www.ncbi.nlm.nih.gov/
pubmed/?
11.Rezum FIM Optimization - Full Text V iew -
ClinicalTrials.gov [Internet]. [cited 2019 May 21].
Available from: https://clinicaltrials.gov/ct2/show/
NCT02940392
12.Evaluation of the Transurethral Ethanol Ablation of the
Prostate (TEAP) for Symptomatic Benign Prostatic
Hyperplasia (BPH): A European Multi-Center Evaluation
- European Urology [Internet]. [cited 2019 May 21].
Available from: https://www.europeanurology.com/
article/S0302-2838(04)00279-9/fulltext
13.Phase I/II examination of transurethral ethanol
ablation of the prostate for the treatment of
symptomatic benign prostatic hyperplasia. - PubMed -
NCBI [Internet]. [cited 2019 May 21]. Available from:
h t t p s : / / w w w. n c b i . n l m . n i h. go v / p u b m ed /
?term=Plante+MK%2C+Marks+LS%2C+Anderson+R+et+al.
14.Efficacy and Safety of Ultrasound-guided Transrectal
Ethanol Injection for the Treatment of Benign Prostatic
Hyperplasia in Patients With High-risk Comorbidities:
A Long-term Study at a Single Tertiary Care Institution -
Urology [Internet]. [cited 2019 May 21]. Available from:
h tt ps : / / w w w. g o l d j o u r n a l . n e t /a r t i c l e / S 0 0 9 0 -
4295(13)01554-9/pdf
15.al SS et. Efficacy and safety of botulinum toxin injection
for benign prostatic hyperplasia: a systematic review
and meta-analysis. - PubMed - NCBI [Internet]. [cited
2019 May 22]. Available from: https://
www.ncbi.nlm.nih.gov/pubmed/26560471
16.Elhilali MM, Pommerville P, Yocum RC, Merchant R,
Roehrborn CG, Denmeade SR. Prospective, randomized,
 The Urology Masterclass, Department of Urology, CMC, Vellore 37

double-blind, vehicle controlled, multicenter phase IIb

clinical trial of the pore forming protein PRX302 for
targeted treatment of symptomatic benign prostatic
hyperplasia. J Urol. 2013 Apr;189(4):1421–6.
17.Schuster TG, Wei JT, Hendlin K, Jahnke R, Roberts WW.
Histotripsy Treatment of Benign Prostatic Enlargement
Using the Vortx Rx System: Initial Human Safety and
Efficacy Outcomes. Urology. 2018 Apr;114:184–7.
18.Shim SR, Kanhai KJK, Ko YM, Kim JH. Efficacy and Safety
of Prostatic Arterial Embolization: Systematic Review
with Meta-Analysis and Meta-Regression. J Urol.
2017;197(2):465–79.
19.NICE Guidance - Prostate artery embolisation for lower
urinary tract symptoms caused by benign prostatic
hyperplasia: © NICE (2018) Prostate artery
embolisation for lower urinary tract symptoms caused
by benign prostatic hyperplasia. BJU Int.
2018;122(1):11–2.
 38
Standardizing the Initial TURBT
Dr. Ninan Chacko, Consultant, Square Hospital, Dhaka
A. History of TURBT:
• Endoscopic electrocautery as an alternative to open
suprapubic approach was described in 1910, by Edwin
Beer [JAMA, 54: 1768, 1910.]
• In 1931, Stern and McCarthy described the first cutting
loop resectoscope, for endoscopic diagnosis and
treatment.
• Gibson described TURBT with the McCarty resectoscope
[J Urol 1935 8].
• In 1962 Swinney described in detail the treatment of
Bladder tumours by TUR. [Br J Urol. 1962: 34:215-20]. In
fact in the paper he described nearly everything that
we should be doing.
The cumulative cost of TCC Bladder treatment is high. It
is the second most common Urological cancer. TURBT
is the most common Uro-oncology Procedure. NMIBC
comprise 75% of these.
B. TURBT Goals:
• Identify and map all tumours in the bladder
• Remove all tumours completely
• Ensure each tumour is correctly staged and risk
stratified
• Identify dysplasia or carcinoma in situ (CIS) in the
bladder
• Obtain tissue for pathological staging and risk
stratification
C. Problems with TURBT:
The quality of TURBT is highly variable and depends on
surgeon, centre and training. This is so with Pathological
reporting too. The quality of reporting and treatment
depends on the quality of specimen. This depends on the
resection quality, which also affects recurrence rate.
Refinement and standardization of TUR and reporting has
been slow. It is the weakest link in the treatment chain of
TCC Bladder. It isn’t always taught properly during
residency, as it is difficult to teach and to learn.
TURBT breaks every rule of biopsy. The tumour is
morcellated and disseminated in the bladder. Tissue sent
to the pathologist is disintegrated and full of artefacts.
Muscle is not present in too many specimens, or difficult
to find. Tumour is often not completely removed, and worse
The Urology Masterclass, Department of Urology, CMC, Vellore
not known if so. Re TUR is advocated to overcome these
occurring even in expert hands.
D. Quality of TURBT and residual tumour: Some facts
• Recurrence 25% for experienced vs 39% for less
experienced. [Mariappan P, et al,. Eur Urol 2010; 57:843-
9.]
• Recurrence at 3 months: Faculty 60% vs 72% Residents.
[Jancke G, et al. Scand J Urol Nephrol 2012; 46:343-7.]
• At least 8-mm tumor-free margin around lesion
decreased local recurrence rate from 58% to 19%.
[Jancke G, et al. Scand J Urol Nephrol 2012; 46:343-7.]
• Supervised training in residency 3 months reduced
recurrence from 28% to 16% [Brausi M. Urologia 2013;
80:127-9]
• In Clinical T1, 49% upstaged to T2 on Re-TUR, if no
detrusor muscle in first specimen vs 14% if muscle was
present.
• Even with detrusor muscle, residual tumor in 33% of
patients who underwent a Re-TUR, including 27% with
Ta tumors and 53% of those with T1 tumours. [Grimm
MO, J Urol 2003; 170:433–7.]
E. EAU Guidelines for TURB:
• Guidelines now mention a section on resection of
bladder tumours
1. Perform TURB systematically in individual steps.
2. Bimanual palpation under anaesthesia.
3. Insert resectoscope, under visual control, inspect whole
urethra.
4. Inspection of the whole urothelial lining of the bladder.
5. Biopsy from prostatic urethra (if indicated).
6. Cold-cup bladder biopsies (if indicated).
7. Resection of the tumour;
• [<1 cm Tumour] Resect in one piece including underlying
bladder wall.
• [<1 cm Tumour] Resect in fractions [Three Fractions]
o Exophytic part of tumour
o Tumour base and bladder wall with detrusor
muscle
o Edges of the resection area for tumours
 The Urology Masterclass, Department of Urology, CMC, Vellore 39

• Avoid cauterization to avoid tissue deterioration.
• Take biopsies from abnormal-looking urothelium.
o Biopsy normal-looking mucosa when cytology
positive [Trigone, bladder dome, and right, left,
anterior and posterior bladder walls] .
o Or if high-risk exophytic tumour expected (non-
papillary appearance).
8. Surgical report formulation and precise description of
the specimen for pathology evaluation
9. Endoscopic pictures and diagrams
10.Cystoscopy with 12-degree and 70-degree lens.
11.Bladder volume at 50%-70% of capacity.
12.Systematic approach during cystoscopy. Ureteral
orifices should be identified.
13.Document, draw, Dictate: Tumor size and location
documented using a standard bladder diagram. Utilize
photography + written documentation to document.
[Brausi M. Urologia 2013; 80:127-9, Herr HW. Quality
control in TUR. BJUI 2008;102:1242-6]
With all the above, experienced surgeons lower
recurrence rates.
F. EAU Guidelines: Path report
1. For classification of depth of invasion (staging) use
2009 TNM system.
2. For histological classification, use both 1973 and 2004
WHO grading.
3. Do not use the term “Superficial BC”.
4. When using the term NMIBC, mention the tumour stage
and grade
5. Specify location, grade, depth of invasion, presence of
CIS, about detrusor muscle presence.
6. The report should specify presence of LVI or unusual
(variant) histology.
7. In difficult cases, consider review by an experienced
genitourinary pathologist.
8. Report of En-Block TURBT
• ERBT generally better resection quality with up to 95%
presence of detrusor muscle which can be a surrogate
marker for quality.
• No difference in peri-operative morbidity vs
conventional TURBT.
• No conclusions on impact of ERBT on recurrence [Hermann,
Current Opinion in Urology Vol 27 No. 2 2017 ]
H. Monopolar Vs Bipolar
• Bipolar TURBT not superior to Monopolar with respect
to obturator jerk, bladder perforation and haemostasis.
• Significantly lower incidence of severe cautery artifact
after bipolar resection. [Kekre: J Urol. 2014
Jun;191(6):1703-7 ]
I. Electrical vs. Laser ERBT
• No difference: Operation duration, post-op irrigation,
catheterization time, hospitalization
• Absent Obturator nerve reflex with Laser
• Better haemostasis and precise blood-less cutting Laser
• Tumour @ 3 cm feasible for ERBT [Kramer World J Urol.
2015 Dec;33:1937-43]
• Complications of laser less than TURBT for NMIBC
• Obturator jerk, perforation, irrigation rate, duration of
catheterization, length of hospital stay and 2-year
recurrence-free survival better in laser group Vs TURBT
group [Bai . World J Surg Oncol. 2014 301].
J. Micro-staging of T1
• Possible to stratify T1 High Grade to T1a/b/c, Does it
impact care?
• Recurrence similar all groups.
• Progression rate Higher in T1b & T1c 34% (16/47) Vs
T1a 8% ( 3/38)
• ‘‘If TUR is of good quality and the pathologist is
interested, T1 sub classification is quite possible’’
[Smits, et al. Urology: 1998; 52:1009–13.]
L. Examination under Anesthesia

G. En-Block Resection of bladder tumour ERBT Vs TURBT
ERBT
Lower peri-operative complication
rates
Decrease recurrence rate
Decrease second resection
Improve specimen quality
Ensure muscle in specimen
Limitations: size and location of
the tumor
Can be performed with all Energy
Sources
• NCCN & EAU recommend bimanual palpation at TURBT
TURBT • Palpable mass suggests T2–T3 disease
Pathological artifacts
• Fixed bladder or invasion into the vagina or rectum
Cautery, Thermal Artifact indicates T4 disease.
Crush Artifact
Tangential sections E. Peri-operative Intravesical Chemotherapy
No Spatial Orientation
Where is the muscle • Intravesical Mitomycin/ Epirubicin within 24 hours
after TURBT to reduce recurrence.
 40 The Urology Masterclass, Department of Urology, CMC, Vellore

• EAU / AUA single dose Intravesical therapy after TURBT
for low-grade Ta TCC.
• Reduced odds of recurrence risk: Single 0.66 Vs 0.44 for
multiple tumors. [Sylvester RJ J Urol. 2004: 171:2186-
90]
• Only 20-50% got single dose of Intravesical therapy
after TURBT: [Urological Surgery Quality Collaborative
Study].
M. Re-TURBT: Indications
• Muscle in specimen indicates completeness of TUR &
less under staging. 4.9% of eligible have re-TUR within
60 days
• After incomplete initial TUR (not all visible tumor
removed) if feasible. Exclusion: Muscle invasive, known
incomplete resection.
• If no muscle in Specimen except Ta Low & CIS
• High-risk, H Grade Ta, even with muscle in specimen,
consider Re-TUR of primary site.
• In T1, Re-TUR primary site to include muscle.
• If bladder sparing with variant histology, perform Re-
TUR.
• Retrospective 47 patients after re-TURBT at 4 weeks.
[Urology 75: 365–369, 2010.]
o 33 (70%) initial incomplete resection.
o 10 (30%) macroscopic residual tumor at resection site.
o 23 (48%) at least 1 unresected tumor away from previous
resection site.

N. Procedure Check List: Anderson et al. J Urol 2016: 196, 1014-20

Assessment of prognostic factors Acceptable responses

Procedure Check List
1. Describe number of tumors 1, 2–5, >5, diffuse
2. Describe size of largest tumor End of cutting loop is @ 1 cm wide
3. Describe characteristics of tumors Sessile, nodular, papillary, flat
4. Describe recurrent Vs. primary tumors Recurrent, primary
5. Assess for presence of carcinoma in situ Suspicious, not suspicious
6. Report 2010 AJCC clinical tumor stage cTis, cTa, cT1, cT2, cT3, cT4
Intra-operative processes
7. Bimanual exam under anesthesia Yes, no
8. Visually complete resection Yes, no
9. Visualize detrusor muscle in resection base Yes, no
10. Visual evaluation for perforation Yes, no
Options
11. Photographic documentation of resection bed Yes, no
12. Drawing or description of tumor location Yes, no
13. Separate deep biopsy sent from resection bed Yes, no

O. Do check lists help:

 The Urology Masterclass, Department of Urology, CMC, Vellore 41

P. Check List implications:

• No structure to measure TURBT quality due to lack of
standardization and reporting methods.
• 10-item checklist during TURBT improved reporting of
critical procedural elements.
• No clear impact on inclusion of muscle in specimen.
• Checklist enhances surgeon attention to important
aspects of the procedure

In 1956 the Memorial Hospital pathologist Fred W. Stewart

wrote, “Individuals interested in bladder tumors cannot
help being confused by widely-divergent end-result data
from different sources. This is very largely the fault of the
pathologist who, in confusing himself, confuses the
clinician still more. Many pathologists call bladder
papilloma cancer, leading to a false picture and rosier tint
to bladder cancer results than is real. True bladder cancer
is a highly lethal process.” [Stewart, F. W: Introduction. In:
Bladder Tumors: A Symposium. J. B. Lippincott Co., p. 1, 1956
]
 42 The Urology Masterclass, Department of Urology, CMC, Vellore
Clinical Epidemiology for the Urologist
Dr Thambu David S, CMC, Vellore
Objectives
1. Research questions
2. Making PICO
3. Study designs
4. Descriptive statistics
5. Analytic statistics
Research question
The research question differs from the ordinary question
in that is detailed and specific. E.g.: Ordinary question:
Does Sildenafil work vs. Research question: In patients with
ED, does daily sildenafil taken for 3 months improve erectile
dysfunction as compared to counselling?
Questions to be answered when designing a study with
examples
1. Is disease present: Psychological distress in patients
undergoing surgery for Urological cancer: A single
centre cross-sectional study. Pastore LA et al. Urol Oncol
2017
2. How do you diagnose disease: Transscrotal near infrared
spectroscopy as a diagnostic test for testicular torsion
in pediatric acute scrotum: A prospective comparison
to gold standard diagnostic test study. Schlomer BJ et
al. J Urol 2017.
3. Why do people have disease: Brain white matter changes
associated with Urological chronic pelvic pain
syndrome: Multi-centre imaging from a MAPP case-
control study. Huan L et al. Pain 2016.
4. What happens to people with disease: Local epidemiology
and resistance profiles in acute uncomplicated cystitis
in women: A prospective cohort study in an urban
ambulatory setting. Seitz M et al. BMC Infectious
Diseases 2017.
5. What is the best treatment for a disease: Ejaculation
preserving photoselective vapourization vs. plasma
kinetic vapourization vs. TURP: An RCT (EPPROSTATECT).
ClinicalTrials.gov Identifier: NCT03589196
6. Is it worth the cost: Fast track access to Urologic care for
patients with macroscopic haematuria is efficient and
cost effective: Results from a prospective intervention
study. Liedberg F et al. BJC 2016
PICO
• Patient/ Participant/ Group of people
• Intervention/ new test/ risk factor
• Control/ existing test/ absence of risk factor
• Outcome
Is the disease present: Patient/ Participant/ Group of people
(Among patients with Urological cancer), Intervention
(Undergoing surgery), Control (Nil), Outcome
(Psychological distress)
Why do people have disease: Patient/ Participant/ Group
of people (Among Elderly), Intervention/ new test/ risk
factor (Chronic pelvic pain syndrome), Control/ existing
test/ absence of risk factor (No Chronic pelvic pain
syndrome), Outcome (Risk of brain white matter changes)
What happens to people with disease: Patient/ Participant/
Group of people (Women with acute uncomplicated
cystitis), Intervention/ new test/ risk factor (Treated with
antibiotics), Control/ existing test/ absence of risk factor
(Nil), Outcome (Antibiotic resistance profile)
How do you diagnose: Patient/ Participant/ Group of people
(Paediatric acute scrotum), Intervention/ new test/ risk
factor (Transscrotal infrared spectroscopy), Control/
existing test/ absence of risk factor (Gold standard test),
Outcome (Identification of testicular torsion)
What is the best treatment for a disease: Patient/ Participant/
Group of people (Patients with benign enlargement of
prostate), Intervention/ new test/ risk factor (Transscrotal
infrared spectroscopy), Control/ existing test/ absence of
risk factor (Gold standard test), Outcome (Identification
of testicular torsion)
Study design
Depends on question
Observational studies include cross sectional, cohort, case
control, case series, case report and case control
Reporting guidelines
The Urology Masterclass, Department of Urology, CMC, Vellore 43
44 The Urology Masterclass, Department of Urology, CMC, Vellore

Stard checklist for the reporting of studies of diagnostic accuracy

The Urology Masterclass, Department of Urology, CMC, Vellore 45

CONSORT statement for randomized control trials

46 The Urology Masterclass, Department of Urology, CMC, Vellore

PRISMA guidelines for systematic review or meta-analysis

Section/Topic  ChecklistItem
TITLE  
Title 1. Identifythereportasasystematicreview,metaͲanalysisorboth.

ABSTRACT  
Provide a structured summary including, as applicable; background; objectives; data sources;
Structured study eligibility criteria, participants and interventions; study appraisal and synthesis methods;
2. results; limitations; conclusions and implications of key findings systematic review registration
summary
number.
INTRODUCTION  
Describetherationaleforthereviewinthecontextofwhatisalreadyknown.
Rationale 3.
Provide an explicit statement of question being addressed with reference to participants,
Objectives 4. interventions,comparisons,outcomesandstudydesign.
METHODS  
Indicate if a review protocol exists, if and where it can be accessed [e.g., Web address] and if
Protocoland available,provideregistrationinformationincludingregistrationnumber.
5.
registration
Specify study characteristics [e.g., PICOS, length of followͲup] and report characteristics [e.g.,
Eligibilitycriteria 6. yearsconsidered,language,publicationstatus]usedascriteriaforeligibility,givingrationale.

Information Describe all information sources [e.g., databases with dates of coverage, contact with study
7. authorstoidentifyadditionalstudies]inthesearchanddatalastsearched.
sources
Present fullelectronic searchstrategy for atleastone database,includingany limitsused, such
Search 8. thatitcouldberepeated.
State the process forselectingstudies [i.e., screening,eligibility, includedin systematic review,
Studyselection 9. and,ifapplicable,includedinthemetaͲanalysis).

Describemethodofdataextractionfromreports[e.g.,pilotedforms,independently,induplicate]
Datacollection
10. andanyprocessesforobtainingandconfirmingdatafrominvestigators.
process
List and define all variables for which data were sought [e.g., PICOS, funding sources] and any
Dataitems 11. assumptionandsimplificationsmade.

Describemethods usedforassessing riskofbiasof individual studies[including specificationof

Riskofbiasin
12. whetherthiswasdoneatthestudyoroutcomelevel]andhowthisinformationistobeusedin
individualstudies anydatasynthesis.
Summary Statetheprincipalsummarymeasures[e.g.,riskratio,differenceinmeans].
13.
measures
Synthesisof Describe the methods of handling data and combining results of studies, if done, including
14. measuresofconsistency[e.g.,I2]foreachmetaͲanalysis.
results
Riskofbiasacross Specifyanyassessmentofriskofbiasthatmayaffectthecumulativeevidence[e.g.,publication
15. bias,selectivereporting].
studies
Additional Describemethodsofadditionalanalyses[e.g.,sensitivityorsubgroupanalyses,metaͲregression].
16.
analysis
RESULTS  
Give numbers of studies screened, assessed for eligibility, and included in the review, with
Studyselection 17.
reasonsforexclusionsateachstage,ideallywithaflowdiagram.
Study For each study, present characteristics for which data were extracted [e.g., study size, PICOS,
18.
characteristics followͲupperiod]andprovidethecitations.
Riskofbiaswithin Present dataonrisk ofbias of each studyand, if available,anyoutcome level assessment [see
19.
studies item12].
For all outcomes considered [benefits or harms], present, for each study: [a] simple summary
Resultsof
20. dataforeachinterventiongroup[b]effectestimatesandconfidenceintervals,ideallywitha
individualstudies forestplot.
Synthesisof Present results of each metaͲanalysis done, including confidence intervals and measures of
21.
results consistency.
Riskofbiasacross Presentresultsofanyassessmentofriskofbiasacrossstudies[seeItem15].
22.
studies
Additional Give results of additional analyses, if done [e.g., sensitivity or subgroup analyses, metaͲ
23.
analysis regression[seeItem16]].
DISCUSSION  
Summaryof Summarize the main findings including the strength of evidence for each main outcome:
24. considertheirrelevancetokeygroups[e.g.,healthcareprovides,usersandpolicymakers].
evidence
Discuss limitations at study and outcome level [e.g., risk of bias] and at reviewͲlevel [e.g.,
Limitations 25. incompleteretrievalofidentifiedresearch,reportingbias].

Provideageneralinterpretationoftheresultsinthecontextofotherevidenceandimplications
Conclusions 26. forfutureresearch.
FUNDING  
Describesourcesoffundingforthesystematicreviewandothersupport:roleoffundersforthe
Funding 27.
systematicreview.
 The Urology Masterclass, Department of Urology, CMC, Vellore 47

Descriptive statistics
- Mean, median, mode: These are for continuous data
- Mean: Check if the data is normally distributed. Use
standard deviation to describe width of data. If SD more
than half of mean, DON’T use
- Median is for data that is ‘skewed.’ Use the SD rule from
earlier and use inter-quartile range to describe
- Mode is used to describe the most common/ repetitive
finding. Not used very often

Qualitative data
Uses numbers and percentages.

Hazard
In cohort studies, hazard is the difference in risk between
two groups at a point in time. It takes time into account

Sample size basics

- What is your estimate of prevalence?
- What is your estimate of
– Difference
– Accuracy
– Error allowance-Wrong positive result/ wrong
negative result?
 48 The Urology Masterclass, Department of Urology, CMC, Vellore
Therapeutic radio tracers in castrate resistant prostate cancer
Dr. Julie Hephzibah, CMC Vellore
Prostate cancer (PCa) is one of the most common non-
cutaneous malignancies in men worldwide, and its
incidence has increased substantially in recent
years. Targeted radionuclide therapy involves a radioactive
drug called a radiopharmaceutical that targets cancer
cells.
The following molecular radiotherapies are currently used
to relieve pain and/or treat castration-resistant
prostate cancer that has spread to the bone:
1) Strontium-89 chloride
2) Strontium-153
3) Radium-223 dichloride
In metastatic castration resistant prostate cancer
(mCRPCa), tremendous progress has been made toward
identifying appropriate molecular targets that could enable
efficient targeting for non-invasive imaging and therapy of
mCPRCa.
PSMA and PSMA PET
Prostate specific membrane antigen (PSMA) is highly
overexpressed in prostate cancer cells as a transmembrane
protein. 1 PSMA is a folate hydrolase cell surface
glycoprotein expressed in a number of different tissue types,
including other cancers, but benign processes as well.
Before malignant transformation has occurred, PSMA is
localized to the cytoplasm and apical side of the prostate
epithelium that lines prostatic ducts. The function of
cytoplasmic PSMA is not fully understood; however, as
malignant transformation occurs, PSMA is transferred to
the luminal surface of the prostatic ducts. 2 PSMA
expression has been shown to be widespread in most
prostate tumours even when PSA staining is negative or
weak.3 Increased PSMA expression has also been observed
when the cell becomes castrate-resistant. 4 As a result,
PSMA has emerged as one of the most favourable targets
for PET imaging. Prostate cancer PSMA overexpression has
been shown to be 100- to 1000-fold that of normal tissue
expression; furthermore, PSMA expression may increase
as tumour grade and castrate resistance increases.
Gallium 68 (Ga68)-PSMA PET has a large impact on the
management of patients with prostate cancer. Greater PET
positivity is associated with higher proportion of
management changes. Lutetium -177 (Lu-177) PSMA is used
to treat patients whose PSMA scan with Ga68 is positive.
Lu-177 is a beta emitter. After binding at the tumour cell
surface, radiolabeled PSMA inhibitors are internalized.
Radionuclide treatment with [Lu-177]-PSMA-617 has high
response rates, low toxic effects, and reduction of pain in
men with metastatic castration-resistant prostate cancer
who have progressed after conventional treatments.5
Targeted alpha therapy (TAT)
Targeted alpha therapy with radiolabeled PSMA inhibitors
are another group of promising therapeutic agents. The
short tissue range of alpha-radiation offers the prospect
of targeting tumor cells which are infiltrating bone marrow,
with reduced toxicity compared to beta-emitters. Most
commonly used alpha emitter is Actinium- 225 (Ac-225)
with a half-life of 10 days. A treatment activity of 100 kBq/
kg body weight of Ac-225-PSMA-617 per cycle repeated every
8 weeks has been determined as a reasonable trade-off
between toxicity and biochemical response for advanced-
stage patients. 6 Bismuth-213 (Bi-213) is another alpha
particle emitting nuclide that is being used in clinical
application.
Significant research activity and progress in production
of clinically safe, radionuclidically pure, alpha-emitters,
synthesis of PSMA inhibitors are likely to make this
modality a promising therapeutic option for mCRPCa.
References
1. Leek J, Lench N, Maraj B, et al. Prostate-specific
membrane antigen: Evidence for the existence of a
second related human gene. Br J Cancer. 1995; 72:583-
588.
2. Maurer T, Eiber M, Schwaiger M, Gschwend JE. Current
use of PSMA-PET in prostate cancer management. Nat
Rev Urol. 2016;13: 226-235.
3. Birtle AJ, Freeman A, Masters JR, et al. Tumour markers
for managing men who present with metastatic prostate
cancer and serum prostate-specific antigen levels of
b10 ng/mL. BJU Int. 2005;96:303-307
4. Evans MJ, Smith-Jones PM, Wongvipat J, et al.
Noninvasive measurement of androgen receptor
signaling with a positron-emitting radio
pharmaceutical that targets prostate-specific
membrane antigen. Proc Natl Acad Sci U S A.
2011;108:9578-9582
 The Urology Masterclass, Department of Urology, CMC, Vellore 49

5. [177Lu]-PSMA-617 radionuclide treatment in patients

with metastatic castration-resistant prostate cancer
(LuPSMA trial): a single-centre, single-arm, phase 2
study. John Violet, Rodney J Hicks, Justin Ferdinandus,
Sue Ping Thang, Tim Akhurst, et al Lancet Oncol 2018;
19: 825–33
6. Kratochwil C, Bruchertseifer F, Rathke H, Bronzel M,
Apostolidis C, Weichert W, et al. Targeted alpha therapy
of mCRPC with 225Actinium-PSMA-617: dosimetry
estimate and empirical dose finding. J Nucl Med.
2017;58(10):1624–31
The Urology Masterclass, Department of Urology, CMC, Vellore

LEARNING
POINTS
 50 The Urology Masterclass, Department of Urology, CMC, Vellore

Adrenal Disorders • MRI:

– adrenal carcinomas are noted for heterogeneity, with
I. ADRENOCORTICAL CARCINOMA – FUNCTIONAL intermediate to high signal intensity, on T1-weighted
Differentials for secondary amenorrhea with hirsutism images.
• Exogenous steroids FDG - PET
– Drug history • FDG PET-CT: 100% sensitivity and 87-97% for identifying
• Ovarian tumors malignant adrenal masses.
– High testosterone • Most valuable in detecting distant metastases
– Low 17-ketosteroids (DHEAS, Androstenedione) • The novel PET tracer [11C] metomidate, a marker of 11á-
hydroxylase
• Adrenal tumors
– Assessed in small series of adrenal masses, showing
– High testosterone high uptake in adenomas and carcinomas
– High 17-ketosteroids – Marker differentiates adrenal cortical lesions from
– May show hyper secretion of cortisol, aldosterone pheochromocytomas and metastases, which are
Functional Evaluation uptake negative
• For glucocorticoids: Surgical options
– Low dose dexamethasone suppression test • Surgery offers best chance of cure, control of local and
hormonal symptoms
– Morning 8 AM cortisol
– 24 hour urine cortisol • Open approach : abdominal / retroperitoneal is
commonly employed
• For mineralocorticoids: (If high BP or low potassium
levels) • Laparoscopy is reserved for small, organ confined
disease
– Aldosterone to renin ratio
• Adrenal vein or IVC involvement precludes the
• For androgens: laparoscopic approach
– Testosterone Chemotherapy
– DHEAS Mitotane: adrenolytic drug
– Androstenedione • Mechanisms of action- direct cytotoxicity of cells in
• For catecholamines: the adrenal cortex, oxidative damage through the
– 24 hour urine metanephrines production of free radicals and inhibition of enzymes
involved with steroid synthesis
Weiss classification
• Increase in recurrence-free and overall survival.
Presence of three or more of the Weiss criteria are
associated with malignancy, with a sensitivity of 100% and • Single agent overall response 14 – 36%.
a specificity of 96%. Combination chemotherapy
• High nuclear grade • Mitotane plus either EDP (etoposide, doxorubicin,
• Mitotic rate >5/50 high-power fields cisplatin) or streptozocin
• Atypical mitoses • No significant difference in overall survival.
• Eosinophilic tumor cell cytoplasm (75% of tumor cells) Radiotherapy
• Diffuse architectural pattern (>33% of tumor) with • RT is effective in reducing the high rate of local
fibrous and trabecular bands recurrence in locally advanced ACC.
• Foci of confluent necrosis • 57% response to palliative radiotherapy.
• Venous invasion • Effective in :
• Sinusoidal invasion – management of metastatic ACC
• Capsular invasion – palliating local symptoms
Conventional imaging – preventing complications from large metastases.
• CT: II. BILATERAL PHEOCHROMOCYTOMA
– For carcinomas, the attenuation NCCT > 10 HU. • Up to 30% of pheochromocytomas occur as a component
of hereditary syndromes
– The relative percentage washout of carcinomas is
<40%. • In VHL disease, the incidence of bilateral
pheochromocytomas ranges from 40% to 80%
– Margins are irregular and the contents
inhomogeneous with areas of necrosis, haemorrhage • Overall rate of malignant pheochromocytoma of 3.9%
and calcification. in patients with MEN2 and 3.3% in patients with VHL
• Hereditary cause is predicted by
 The Urology Masterclass, Department of Urology, CMC, Vellore
– bilateral tumors
– multifocal tumors
– extra adrenal location
– young age
– family history of related manifestations of a genetic
syndrome
Genes associated with phaeochromocytoma
• REarranged Transfection protooncogene (RET)
• Von Hippel–Lindau (VHL),
• Neurofibromatosis, Type 1 (NF1),
• Mitochondrial succinate dehydrogenase subunits D and
B genes (SDHD, SDHB).
Preoperative management
Alpha adrenergic blockade –
The purpose is to control hypertension and expand blood
volume. Routinely commenced 10- 14 days preoperatively
but started well before that in case of recent MI, refractory
hypertension, catecholamine induced cardiomyopathy and
vasculitis . Target BP is 120/70 mm of Hg
Beta blockade
After alpha blockade, unopposed beta adrenergic
stimulation can cause tachycardia and arrhythmias
Start after adequate alpha blockade ~10 day, usually 2
days pre-op. Target HR – 80/min
Caution in catecholamine induced cardiomyopathy – acute
pulmonary edema
Beta blockade is always instituted after sufficient alpha
blockade to avoid unopposed alpha-adrenergic receptor
stimulation which can precipitate a hypertensive crisis
Non drug management of ECF volume
Fluids - 4L /day, Supplementary salt - 15gm /day
Start on 2nd or 3rd day of starting alpha blockers
These measures expand contracted blood volume and
prevent orhtostasis
• Caution in heart failure/ renal failure
• Diuretics are contraindicated
Roizen criteria – Four criteria to assess the efficacy of
preoperative alpha blockade
• No in-hospital recording of BP >160/90mmHg for 24
hour prior to operation
• No orthostatic hypotension with BP <80/45mmHg
• No ST /T wave changes for 1 week prior to operation
• No more than 5 premature ventricular contractions /
minute
Treatment
• Treatment strategies include
– synchronous bilateral adrenalectomy
– metachronous adrenalectomy
– subtotal adrenalectomy.
The risk of Addisonian crisis may be as high as 23% to 32%
in patients who undergo bilateral total adrenalectomy
51
Cortical sparing adrenalectomy
• Cortical-sparing adrenalectomy represents a logical
treatment alternative for patients with hereditary
pheochromocytoma. It prevents the need for chronic
corticosteroid replacement, minimizing the risk of
adrenal insufficiency. This strategy is based on the
following rationale:
x metastatic pheochromocytoma rarely occurs in patients
with MEN2, VHL, and other rare inherited
pheochromocytoma-associated syndromes
x Risk of recurrence is acceptably low
• Operative considerations:
- Exposure of the adrenal gland in a bloodless field is
critically important.
- Portion of adrenal gland to be preserved in situ not
be mobilized out of the retroperitoneum
- Cephalad aspect of the adrenal gland, based on the
phrenic circulation, is most suitable for subtotal
adrenal preservation in situ
Long term follow up
• Most cases can stop all BP medications
• HTN free: 5 years 74%, 10 years 45%
• 24 hours urine collection 2 weeks postoperatively
• Annual surveillance- 24 hour urine studies
III. ADRENAL INCIDENTALOMA
Definition: Adrenal massess > 1 cm in diameter identified
on cross sectional imaging performed for unrelated causes.
Incidence : 4.2%.
- Increases with age- 0.5% in 20-30 yrs to 7% in those
> 70yrs
- 20% of adrenal incidentalomas are potential
surgical lesions
- 4-7% of adrenal incidentaloma are
pheochromocytoma
Imaging
x Ultrasound- suboptimal
x Unenhanced CT scan:
- Diagnose adrenal adenoma in>70% of cases
- <10HU – High intracytoplasmic lipid content
- 30% of adrenal adenomas are lipid poor-atypical
- CT washout study (gold standard)
- Lipid poor and lipid rich adenomas – identical
properties regarding rapid wash out of enhancement
after CT contrast load
x Chemical shift MRI
- T1 weighted Chemical-shift MRI exploits the
differences in precessional frequency between lipid
and water protons.
- By assessing differences in signal intensity (SI) when
lipid and water protons are “in phase” versus are
“opposed phase”
- Chemical-shift MRI allows the detection of the
intracytoplasmic lipid
 52 The Urology Masterclass, Department of Urology, CMC, Vellore

- Indication: Indeterminate lesions, lipid poor (Inhomogeneous masses with an irregular border are less
adenoma, to differentiate adenoma from carcinoma/ likely to be benign, especially if the HU reading is more
metastasis/phaeochromocytoma than 20)
Investigations for functioning adrenal lesions Surveillance in adrenal incidentaloma
- MIBG - For masses that appear to be benign (<10 HU;
- Somatostatin-receptor scintigraphy (SRS; washout, >50%), small (<3 cm), and completely
Octreoscan) nonfunctioning imaging and biochemical
- DOTATE-PET reevaluation at 1–2 yr subsequent follow-up for
clinical changes
- FDG-PET
- For more indeterminate lesions repeat evaluation for
Indications: to detect functioning neuroendocrine tumors, growth after 3–12 months
metastatic lesions, paragangliomas
- Subsequent testing earlier for lesions showing
MIBG increasing size
- Radiotracers: I-123 , I- 131(0.5–1.0 mCi)
- Annual follow up for 3-4 yrs is recommended for
- Sensitivity- 60- 80%, Specificity- 95- 100% metabolically silent masses especially for
- Sensitivity of MIBG is poor for extra adrenal masses>3cm diameter
phaeochromocytomas
68
Ga-DOTATATE and 18F-FDG PET/CT
- DOTATATE and FDG are positive at most sites of
disease
- Uptake intensity was significantly higher on DOTATATE
compared to FDG.
- Advantage: Metastatic paragangliomas are better
imaged with DOTATAE/FDG PET vs MIBG( Sensitivity -
15% versus 95-100%)
Characterization of Adrenal Masses by Using FDG PET-
systematic review
- Differentiating between malignant and benign
adrenal disease: 97% sensitivity and 91% specificity
- Qualitative (visual) PET analysis has the best
combined test sensitivity and specificity for PET
characterization of malignant adrenal masses.
- PET compares favorably with CT washout tests for
the characterization of adrenal masses
Summary of functional imaging
- In a well-controlled comparison of four functional
imaging modalities of Pheochromocytoma/
paraganglioma [18F]-DA was the best modality vs CT/
MRI with sensitivity of 76%–82% whereas [123I]-MIBG
lagged behind with sensitivity of 57%–78%.
Role of adrenal biopsy
- Modern imaging has excellent diagnostic ability with
>95% sensitivity
- Histologically adenomas cannot be differentiated
from adrenal carcinomas
- Adrenal biopsy is not without risk and has a very
limited role
Indications of surgery in adrenal incidentaloma
- Functioning tumors
- Size > 4cm(except AML)
- Rate of growth >1cm per year
- Other CT or MRI characteristics may suggest surgery,
regardless of size.
 The Urology Masterclass, Department of Urology, CMC, Vellore 53

Radiological approach to adrenal incidentalomas

Kapoor A et al,CUA guidelines, Can Urol Assoc J 2011;5(4):241-7

54 The Urology Masterclass, Department of Urology, CMC, Vellore

Decisional Algorithm for genetic testing in patient with proven Paraganglioma

Journal of Clinical Endocrinology & Metabolism Volume 99, Issue 6, 1 June 2014, 1915-1942
 The Urology Masterclass, Department of Urology, CMC, Vellore 55

Bladder outlet obstruction

Common definitions related to male LUTS: (Abrams, P., et al. Neurourol Urodyn, 2002.21: 167).
1) Acute retention of urine is defined as a painful, palpable or percussible bladder, when the patient is unable to pass
urine
2) Chronic retention of urine is defined as a non-painful bladder, which remains palpable or percussible after the
patient has passed urine. Such patients may be incontinent.
Surgical options for a large prostate (considered as gland size>80g) –EAU guidelines 2019
1) Open prostatectomy
2) Endoscopic enucleation of prostate
a. HoLEP
b. Bipolar
3) TURP (may be staged)
4) Others – Laser vaporization, Thulium enucleation
HoLEP (Michalak. et al. Am J Clin. Exp Urol.2015)
· Avoids dilutional hyponatremia
· Less intraoperative blood loss, early recovery
· Comparable outcomes with open prostatectomy with lesser hospital stay, catheterization time and transfusion rates
· Overall reintervention rate- 4.3% (bladder neck contracture -0.8%, stricture-1.6%)
· Outcomes depend on experience of the surgeon-there exists a definite learning curve
Surgical options for patient on anticoagulation
· Laser vaporization(preferred option)
· Laser enucleation
· Prostatic artery embolisation (experimental)

Heiman et al, Best practice in the management of BPH in patients requiring anticoagulation, Ther Adv Urol, 2018.
PVP and HoLEP- safest surgical management options for BPH in patients requiring chronic anticoagulation
 56 The Urology Masterclass, Department of Urology, CMC, Vellore

Prostatic artery embolisation

• In patients with moderate to severe LUTS who are not fit for TURP or open prostatectomy.80-300 micron polyvinyl
alcohol particles used to selectively embolize the prostatic arteries. It is performed under local anaesthesia.
• Minimal complication rates( fever, UTI, pelvic pain, urinary retention, puncture site hematoma
• Anatomical obstacles – atherosclerosis, tortuous prostatic arteries and adverse collaterals
• Early prospective non RCTs – efficacy lasts up to 12 months (long term efficacy beyond two years decreases to about
58%). Still experimental
(Shim SR et al metaanalysis J.Urol 2017 197:465 )

Emerging minimally invasive treatment options for BPE (Magistro G, et al.. Eur Urol (2017))

Treatment gAlgorithm

Male LUTS with absolute indications for surgery or non- responders to medical treatment or those who do not want
medical treatment but request active Rx

No High Risk patients? Yes

Yes Can have surgery under No

anaesthesia?
Prostate volume Can stop
Yes anticoagulation/antipla No
telet therapy
<30 ml >80ml
30 - 80 ml

TUIP TURP Open prostratectomy Laser vaporisation PU lift

TURP Laser enucleation HoLEP Laser enucleation Stent
Bipolar enucleation Bipolar enucleation Prostatic artery embolization
Laser vaporisation Laser vaporisation (experimental)
PU lift Thulium enucleation
TURP
EAU
EAU guidelines
id li 2019
2019
 The Urology Masterclass, Department of Urology, CMC, Vellore 57

Primary bladder neck obstruction Treatment options

• Differentials for young males with voiding dysfunction 1) Alpha blockers: variable success and need to continue
after neurological involvement and other anatomical therapy for long duration
and infectious causes of lower tract urinary dysfunction • Response rate 50-70%
have been rule out: • Patients who continue medications at one year·
– Primary bladder neck obstruction Variable 25-80%
– Dysfunctional voiding • The response of alpha blockers was more in patients
– Underactive detrusor with high pressure low flow group and in children
• Few can be weaned off the alpha blocker return to
Definition their pretreatment state and they continue to derive
benefit even after three years. Placebo controlled trial
• Condition where by bladder neck fails to open
available in children shown to be effective.
adequately during voiding resulting in obstruction to
urinary flow in absence of other anatomic obstruction
• Etiology – unknown 2) TUIP: single or bilateral incision.
Theories • Highly effective, but risk of retrograde ejaculation in
young population (~25%).
• Sympathetic nervous system dysfunction
• Risk decreased with single incision (nil).
• Extension of the functional external sphincter to
bladder neck. An unexplained phenomenon of decreased sperm
counts after unilateral incision was noted in one
• Prevalence not known study.
• Diagnosis
– Videourodynamics :
• Bladder neck not opening well
• Delayed opening during voiding phase
– Micturitional urethral pressure profilometry
• Significant pressure drop at or just below the
level of bladder neck
• Nitti et al described three types on videourod
ynamics:
– Type 1: High pressure low flow
– Type 2: Normal pressure low flow with narrowing at
bladder neck.
– Type 3: Delayed opening of bladder neck >10 secs
 58 The Urology Masterclass, Department of Urology, CMC, Vellore
Benign prostatic enlargement with bladder outlet obstruction
– Role of urodynamics
The index patient described in most guidelines on male
lower urinary tract symptoms (MLUTS) is a middle aged/
elderly man (often more than 50 years) with bothersome
dysfunction of storage/voiding/post micturition. The most
common etiology of the bladder outlet obstruction is
prostatic enlargement.
Patient reported bother plays a central role in clinical
decision making.
Urodynamics (UDS) in MLUTS :
1) Degree of bladder outlet obstruction
2) Detrusor contractility
3) Bladdder dysfunction
The above play a role in:
1) Patient selection for invasive/morbid/irreversible
treatment
2) Potentially predict response to individual modalities
3) Help in counseling the patient and setting the
expectations
The American Urological Association/ Society of
Urodynamics Female Pelvic Medicine and Urogenital
Reconstruction (AUA/SUFU) guidelines panel recommend
the following regarding urodynamics in MLUTS:
1) Multichannel filling cystometry – to determine detrusor
overactivity/bladder abnormalities of storage,
particularly when invasive treatment considered –
Expert opinion
2) Pressure flow study – to determine urodynamic
obstruction – Grade B
3) Videourodynamics to localise level of obstruction
particularly for diagnosis of primary bladder outlet
obstruction – Expert opinion
In the algorithm for evaluation of MLUTS according to the
updated AUA guidelines, flow more than 10ml/second
(equivocal poor flow) is an indication for pressure flow
study. However the guidelines state that pressure flow
studies are an optional part of the evaluation, their use as
having the highest level of flexibility with regard to
application of guideline statements.
The other indications for urodynamics in MLUTS include:
1) Elderly - limitations in history taking or possible prior
surgeries or instrumentation
2) Younger range of patients or younger than index
3) Urinary retention and inability to complete
uroflowmetry
4) Non- correlation of symptoms with non invasive
findings
5) Suspicion of neurologic components
6) Confounding condition that could affect bladder
function : diabetes mellitus, previous radiation, pelvic
surgery or previous spine surgery
7) Male LUTS with incontinence
8) Failed prior invasive treatments
Role of UDS in MLUTS:
1) Predictor of success of surgery - greater degree of
obstruction, absence of detrusor overactivity and
absence of detrusor underactivity have better surgical
outcomes
2) Potential cost benefits that may stem from better
diagnostic information
3) UDS with improved counseling could result in more
informed patients with care that meets expectations
Suggested readings:
1. Cox L, Jaffe W. Urodynamics in male LUTS – When are
they necessary and how do we use them? Urol Clin N
Am 41(2014): 399-407
2. www.auanet.org/content/guidelines-and-quality-care/
clinical-guidelines.cfm?sub5bph
3. Winters JC, Dmochowski RR, Goldman HB et al.
Urodynamic studies in adults: AUA/SUFU guideline. J
Urol 2012; 188(Suppl 6) : 2464-72
4. Thomas AW, Cannon A et al. The natural history of lower
urinary tract dysfunction in men: minimum 10-year
urodynamic follow up of transurethral resection of
prostate for bladder outlet obstruction. J Urol 2005;
174(5): 1887-91
5. McVary KT, Roehrborn CG, Avins AL, et al. Update on
AUA guideline on the management of benign prostatic
hyperplasia. J Urol 2011;185(5):1793–803.
 The Urology Masterclass, Department of Urology, CMC, Vellore 59

POST TURP INCONTINENCE FEMALE BLADDER OUTLET OBSTRUCTION

Incidence of urinary incontinence 1% for TURP
Early incontinence: 30–40% Etiology of female BOO
Late iatrogenic stress incontinence: 0.5%
Anatomic
Pathogenesis:-
Extrinsic Pelvic prolapse - cystocele,rectocele,etc
x Bladder dysfunction After incontinence surgery
x Sphincter Incompetence Gynecological-fibroids etc
x Mixed Incontinence Poorly fitting pessary
Aetiology:- Urethral Stricture
Early incontinence – urge incontinence due to fossa healing, Meatal stenosis
associated UTI, detrusor instability caused by long-lasting
Thrombosedcaruncle
BPH.
Fibrosis
Late Incontinence - sphincter incompetence (30%), detrusor
instability (20%), mixed incontinence (30%), residual Diverticulum
adenoma (5%), bladder neck contracture (5%), and urethral Luminal Stone
stricture (5%). Bladder or urethral tumor
Management Ureterocele
x Early Incontinence:- Foreign body
o Time-limited anticholinergic - Toltoridine or FunctionalPBNO
Darifenacin Pseudo dyssynergia
o Anti-inflammatory regimens - Diclofenac. Detrusor-external sphincter dyssynergia
x Late incontinence: If persists > 6 months need
evaluation. Diagnosis
o Ascending urethrogram, x High level of suspicion required.
o Cystourethroscopy, x Most criteria focus on combined pressure–flow criteria
o Urodynamic evaluation (differing from values in men), with or without
fluoroscopic evidence of obstruction
Bladder dysfunction
x AG NUMBER/ BOOI not valid for women with obstruction
x Nonsurgical Management
o Fluid restriction and Urodynamic Definition
o Behavioral modification x Initial formula with good prediction value for
o Medications - anticholinergics obstruction was obtained with Qmax less than 15 mL/
sec + PdetQmax of greater than 20 cm H2O (74.3%
x Pelvic floor exercises sensitivity and 91.1% specificity).
x Neuromodulation x Lemack et al revised this to Qmax = 11 mL/sec and
x Augmentation cystoplasty PdetQmax = 21 cm H2O.
x Urinary diversion. x Currently, highest sensitivity and specificity for
Sphincter incompetence predicting obstruction was obtained with Qmax less
x Conservative treatment :- than 12 mL/sec and PdetQmax greater than 25 cm H2O
o pelvic floor exercise x Nitti et al showed that the addition of fluoroscopic
imaging to urodynamics was helpful in diagnosing
o TRUS-biofeedback and electrostimulation
female BOO.
x Minimally invasive (urethral bulking agents)
x Patients were classified as obstructed if there was
x Paraurethral balloons radiographic evidence of obstruction between the
x Surgical (artificial urinary sphincter or bulbourethral bladder neck and distal urethral in the presence of a
sling). sustained detrusor contraction of any magnitude.
x Urethral resistance ratio has been used in some studies
but definition is not standardized.
 60 The Urology Masterclass, Department of Urology, CMC, Vellore

Treatment
x Treatment of female bladder outlet obstruction is not
yet standardised as data is of poor quality. Study designs
are generally flawed with inadequate sample size,
short duration of treatment and follow-up.
x Many women undergo urethral dilatation, though there
is doubtful evidence to support it. It can improve LUTS
and flow rate but durability is not proven.
x Therefore, individualised treatment is the appropriate
option.

Alpha-blockers
x About half of women with PBNO respond to D-blockers.
o Symptoms improve, flow rates increase and PVR
decrease significantly so alpha blockers can be tried
before invasive therapy.
x Efficacy of D-blocker therapy might suggest a good
response to BNI.
x Many studies show improvement but data unreliable.
x Side effects of dizziness and hypotension may
complicate treatment.
x Do not increase the success of TWOC.
x CIC is an option for those who do not desire an
intervention.

BNI
x No consensus as to where to incise.
o First described by Turner-Warwick at 12 o’clock.
o Conventionally incised at the 5 and 7 o’clock
positions.
o Careful, sufficiently deep incisions at the 2- and 10-
o’clock positions had better efficacy in one study.
o Jin et al showed good subjective and objective
improvement at 5 years with incisions at 12,3,6 and
9 o’clock.
x Good results shown in well-selected cases.
x Potentially serious complications:
o Vesicovaginal fistula (VVF) 3.6%
o Stress urinary incontinence (SUI) 4.7%
o Urethral stricture 3.6%
x Be cautious and certain of diagnosis before performing.

Newer therapies
x Botulinum toxin
o Few trials with small number of subjects show some
efficacy.
o Needs repeat injections every 3-6mo.
o Remains experimental at present.
x Sacral neuromodulation – No reliable data
 The Urology Masterclass, Department of Urology, CMC, Vellore 61

CARCINOMA PENIS

RISK FACTORS TYPES OF PENILE CANCERS

Oddsratio/associationfor NonHPVrelated HPVrelated

Riskfactor
penilecarcinoma
Squamous Basaloid
Phimosis 11Ͳ16
Sarcomatoid Warty
Smoking 5
Pseudoglandular WartyͲbasaloid
RecurrentbalanoͲ
Ͳ Adenosquamous Clearcell
posthitis/BXO
Sporaleneandultraviolet Carcinomacuniculatum
10 (BXOrelated)
A
LowSES Ͳ Verrucous
Multiplesexualpartners Papillary
3Ͳ5
atyoungage
Worst prognosis : Sarcomatoid (75% mortality)
20%inBasaloid,50%in
HumanPapillomaVirus Basaloid and Pseudoglandular (50%)
Basaloidwarty

Grade groups

Grade Mitoses Cellularatypia Bridging/keratinization Border

G1 Rare Mild Prominent Pushing,welldefined

G2 Increased Moderate Lessprominent Infiltrative

G3 Abundant Severe Rare Infiltrative

G4 Abundant Sarcomatoid Absent Infiltrative

Penile premalignant lesions • Mucosal lining of the prepuce or the glans –

• HPV-related Erythroplasia of Queyrat
– Malignant giant condylomata acuminata • Histologically true carcinoma in situ
– Bowenoid papulosis • Both related to HPV 16 and 18 infection
– Bowen’s disease
– erythroplasia de Queyrat Poor prognostic factors
• Higher stage (N most important)
• Chronic inflammation related (5-yr CSS N0: 85–100%,N1: 79–89%,N2: 17–60%,N3: 0–
– Genital Lichen sclerosis (also termed balanitis xerotica 17%)
obliterans ) • Proximal vs. distal urethral involvement
– Penile horn • Higher grade
– Leukoplakia • Lymphovascular invasion (LVI)
– Pseudoepitheliomatous, keratotic and micaceous • Extra capsular extension (ECE) in lymph node
balanitis

Bowen Disease and Erythroplasia of Queyrat

• Same disease with a different clinical presentation
• Penile shaft – Bowen disease
 62 The Urology Masterclass, Department of Urology, CMC, Vellore

Lymph nodal anatomy Non-invasive (CIS, T1a: G1/2)

• Imiquimod/ 5 Fluorouracil (30-40% local
recurrence)
• Nd-YAG, CO2 laser excision (10% recurrence)
• Glans resurfacing (20% invasive on final
biopsy)
Invasive (T1b or higher)
• Circumcision (Confined to prepuce)
• Glansectomy (Confined to glans)
• Partial penectomy (Adequate residual
stump, distal)
• Total/ radical penectomy (Proximal, urethral
involvement)
• RT- External/ brachytherapy (T1/2, <4 cm. 60 Gy)
• Neoadjuvant chemotherapy (T4 tumours)

Leone A. Nat Rev Urol 2017 Risk group for lymph nodal metastasis
• Low risk group <10%: Carcinoma in situ (Tis), verrucous
carcinoma (Ta), Stage T1 G1
Evaluation:
• Intermediate risk group ~10-25%: Stage T1G2
• Clinical examination is reliable for detection of lymph
nodes 82% sensitivity, 79% specificity • High risk group >40%: Venous, perineural or lymphatic
invasion and >/= T1G3
• MRI with artificial erection iffindings are equivocal and
organ conservation needed • pT1a 0-30%
• CT- Obese or prior inguinal surgery to assess nodes • pT1b 30-50%
• Chest X ray/ CT thorax, bone scan when indicated • pT2 50-80%
• >pT3 50-100%
Management of primary tumour • Leone A. Nat Rev Urol 2017
• Surgical amputation gold standard, local recurrence 0- (30% of patients with cN0 harbour micrometastases)
8%. 2 cm margin not necessary
3 mm- G1 Staging of Lymph nodes
5mm- G2 • If nodes are not palpable:
8 mm – G3 • Invasive staging for intermediate and high risk patients
• If nodes are palpable:
• CECT abdomen + pelvis (To identify pelvic nodes/
metastases)
 The Urology Masterclass, Department of Urology, CMC, Vellore 63

The clinically node negative groin

20% of patients with impalpable inguinal nodes harboured occult metastases
CIS/ T1a : Observe if compliant
T1b or higher: Sentinel node biopsy OR

Modified inguinal dissection

Node positive Node negative- Stop

1 node+, no ECE 2/ more nodes/ ECE +

Ipsilateral radical lymph node dissection Ipsilateral radical inguinal + pelvic lymph node dissection

Dynamic SNB
Significant risk factors for pelvic nodal metastasis
• 12-15% false negative rate, Modified DSLNB- 5%
• Number of positive inguinal nodes (cut-off 3)
• ~90% sensitivity
• Diameter of inguinal metastatic nodes (cut-off 30 mm)
• Reduces the need for formal LND in > 70 %, decreases
• Presence of extra nodal extension
morbidity to < 10 %
• Risk Proportion of pelvic LN metastasis: No risk factor
• Modified inguinal LN dissection (mLND)
0%, all 3 risk factors 57.1%
• FNAC: not recommended [does not reliably exclude
micro-metastatic disease]

Modified Dynamic sentinel lymph node biopsy:

• The pooled sensitivity - 88 % (95 % CI: 84-90 %)
• The pooled negative predictive value - 99 % (95% CI:
98-99 %)
 64 The Urology Masterclass, Department of Urology, CMC, Vellore

Palpable inguinal nodes (Mobile, <4 cm)

Bilateral superficial node dissection- Frozen section

Positive Negative

Ipsilateral radical inguinal LN dissection Stop

1 node+, no ECE- Stop 2/ more nodes/ ECE +:

Ipsilateral pelvic LN dissection

Palpable inguinal nodes (Fixed, >4 cm)

Neoadjuvant chemotherapy
(TIP/ TPF)

Response noted, resectable No change/ progression

Salvage lymph node dissection Palliative care

+/- vascular graft/ flap cover

• Chemotherapy
 The Urology Masterclass, Department of Urology, CMC, Vellore 65

Newer Developments: Targeted Therapy

• Anti EGFR Mabs - Panitumumab, Cetuximab
– EGFR is universally expressed in Penile SCC
– Similarity with head and neck SCC
• TKI’s - Sunitinib, Sorafenib
• They are to be considered as single agent treatment in
refractory cases

Local disease recurrence after conservative surgery

• A second conservative procedure is advised if there is
no corpus cavernosum invasion
• If there is a large or deep infiltrating recurrence, partial
or total amputation is inevitable and total phallic
reconstruction should be considered

Molecular prognostic markers:

• p53: an independent predictor of lymph node
metastasis in multivariate analysis (RR 4.8)
• E-cadherin: Not proven in multivariate analysis.
• MMP-9 immunoreactivity: An independent predictor of
disease recurrence (HR 3.2)

Follow up/ surveillance for node negative disease

(EAU 2019)
 66 The Urology Masterclass, Department of Urology, CMC, Vellore

CARCINOMA PROSTATE
1. INTERNATIONAL SOCIETY OF UROLOGICAL PATHOLOGY (ISUP) 2014 GRADES
ISUP grading system was introduced in order to:
a) Align carcinoma prostate grading with the grading of other carcinomas
b) Eliminate the anomaly that the most differentiated carcinoma have a Gleason score of 6
c) To further define the clinically highly significant distinction between Gleason score 7(3+4) and 7(4+3)
Gleason score ISUP grade
2Ͳ6 1
7 (3+4) 2
7 (4+3) 3
8 (4+4 or 3+5 or 5+3) 4
9Ͳ10 5

EAU risk groups for biochemical recurrence of localized and locally advanced prostate cancer
Low risk Intermediate risk High risk
PSA <10ng/ml and PSA 10Ͳ20ng/ml or PSA >20ng/ml or ISUP Any PSA
ISUP grade 1(Gleason ISUP grade 2/3 (Gleason grade 4/5(Gleason score Any ISUP grade
<7) and cT1Ͳ2a score 7) or >7) or cT2c cT3Ͳ4 or cN1
cT2b
Localized Locally advanced

Based on the ISUP grade, Intermediate risk can further be classified as low intermediate risk (ISUP grade 2) and high
intermediate risk (ISUP grade 3) groups with prognostic significance.
 The Urology Masterclass, Department of Urology, CMC, Vellore 67

2. BIOMARKERS IN THE SCREENING AND TREATMENT OF PROSTATE CANCER

(Alford A et al. Rev Urol. 2017; 19(4):221–234)
Summary of available tests and indications
Test Specimen Biomarkers Clinical Target patient Management guidelines
endpoints population
Initial biopsy
PHI (Prostate Blood ͲLevels of tPSA, Risk of HG Men >50 y Score 0Ͳ26.9: 9.8% risk of
Health Index) fPSA,p2PSA cancer on with PSA HG disease
Ͳp2PSA/fPSA x biopsy (score 4Ͳ10 ng/mL Score 27Ͳ35.9: 16.8% risk
(tPSA)1/2 1Ͳ100) and negative of HG disease
DRE result Score 36Ͳ54.9: 33.3% risk
who are of HG disease
considering Score >55: 50.1%
initial biopsy risk of HG disease
Apifiny Blood Circulating levels Risk of HG Men with PSA Score 1Ͳ58: low risk of HG
of 8 PCaͲspecific cancer on >2.5 ng/mL disease
autoantibodies biopsy (score who are Score >59: high risk
1Ͳ100) considering of HG disease
initial biopsy
SelectMDx Urine Expression of Percent risk of Men with Low risk: routine
DLX1 and HOXC6 Gleason >6 elevated PSA followͲup and
disease on value who are screening
biopsy Percent considering High risk: perform
risk of HG initial prostate biopsy
cancer on biopsy
biopsy
Repeat biopsy
PCA3 Urine Ratio of PCA3 Risk of Men age Score 1Ͳ25: low risk
and PSA expression Gleason >6 >50 y who of cancer, safe to
disease on are considering defer biopsy
biopsy (score repeat biopsy Score >26: high risk
1Ͳ100) after initial of cancer, perform
negative biopsy repeat biopsy
ConfirmMDx Biopsy Hypermethylation Risk of PCa Men who Negative: safe to
intensity of tumor on repeat are considering defer biopsy
suppressor genes biopsy a repeat Positive: repeat
GSTP1, RASSF1, biopsy after biopsy
and APC initial negative
biopsy result
Initial or repeat biopsy
4K score Blood Levels of tPSA, Percent risk of Men with an Low risk (1%Ͳ7.5%):
fPSA, intact HG cancer on elevated PSA safe to defer biopsy
PSA, and human biopsy or abnormal with followͲup of
kallikreinͲrelated DRE result who PSA
peptidase 2 are considering High risk (>20%):
initial or rpt perform biopsy
biopsy
MiPS Urine Expression Percent risk of Men with Does not provide
of PCA3 and Gleason elevated PSA lowͲ and highͲrisk cutoffs
TMPRSS2:ERG =6 disease value who are
Combined with on biopsy considering
serum PSA Percent risk of initial biopsy or
HG cancer on rpt biopsy
biopsy after initial
negative result
68 The Urology Masterclass, Department of Urology, CMC, Vellore

After biopsy: Active surveillance vs Intervention

Oncotype Dx Biopsy Expression of 12 Percent likelihood Men with very Does not provide low
PCaͲrelated genes of Gleason lowͲ and low risk and highͲrisk cutoffs
3+3 or 3+4 PCa based Provides pathology
disease on RP on NCCN risk risk
Percent group Men with information (GPS)
likelihood of Gleason 3+3 relative
organͲconfined or 3+4 on to others in the same
disease on RP biopsy NCCN risk group
Promark Biopsy Quantitative Percentage risk Men with Does not provide
levels of 8 Pca of developing Gleason 3+3 lowͲ and highͲrisk
related proteins aggressive or 3+4 on cutoffs
disease biopsy
(Gleason
>4+3, non–organͲ
confined
disease) based
on ProMark
score alone
and when
combined
with NCCN
category
PTEN/ Biopsy Presence or Cancer Men with Negative (intact
TMPRSS2:ERG absence of PTEN aggressiveness Gleason 3+3 PTEN, no ERG
deletion or 3+4 on rearrangement):
Presence or biopsy active
absence of surveillance
TMRPRSS2:ERG Positive (PTEN
fusion deletion and/or ERG
rearrangement):
definitive treatment
Prolaris Biopsy Expression levels Cancer Men with PCa Does not provide
of 31 genes aggressiveness on biopsy lowͲ and highͲrisk
associated (score 1Ͳ10) cutoffs
with cell 10Ͳy PCa specific Provides score
cycle progression mortality risk relative to others in
the same AUA risk
category

Decipher Biopsy Expression levels 5Ͳy metastasis Patients with Does not provide
of 22 genes risk localized lowͲ and highͲrisk
associated with Likelihood of disease on cutoffs
highͲrisk PCa HG disease biopsy Low risk: active
on RP surveillance
10Ͳy PCa specific High risk: consider
mortality risk further treatment
 The Urology Masterclass, Department of Urology, CMC, Vellore 69

After RP : initial biopsy Secondary treatment vs Observation

Prolaris Prostate Expression levels Risk of Men who Does not provide
of 31 genes biochemical have lowͲ and highͲrisk
associated recurrence undergone cutoffs Provides
with cell cycle within 10 y RP score relative to
progression (score 1Ͳ10) others in the same
AUA risk category
Decipher Prostate Expression levels 5Ͳy metastasis Men with Low risk: observe
of 22 genes risk highͲrisk with PSA monitoring,
associated with 10Ͳy PCa specific pathology or RT if PSA value
highͲrisk PCa mortalityrisk highͲrisk clinical Rises High risk:
features adjuvant or early RT
after RP with further
intensification of
treatment as needed

AUA, American Urological Association; DRE, digital rectal examination; GPS, Genomic Prostate Score; HG, high-grade (Gleason>7); fPSA, free
prostate-specific antigen; NCCN, National Comprehensive Cancer Network; p2PSA, [-2]proPSA; PCa, prostate cancer; PHI, Prostate Health
Index; PSA, prostate-specific antigen; RP,radical prostatectomy; tPSA, total prostate-specific antigen.

3) Indications for repeat biopsy: (in cases of prior negative

biopsy)
a) Rising and/or persistently elevated PSA
b) Suspicious DRE – 5-30% carcinoma prostate risk
c) Atypical small acinar proliferation (i.e. atypical glands
suspicious for cancer), 31-40% risk of carcinoma
prostate on repeat biopsy
d) Extensive (multiple biopsy sites i.e, >3) high grade
intraepithelial neoplasia (HGPIN), ~30% risk of
carcinoma prostate
e) A few atypical glands immediately adjacent to high
grade prostatic intraepithelial neoplasia (i.e, PINATYP),
50% carcinoma prostate risk
f) Intraductal carcinoma as a solitary finding, >90% risk
of associated high grade carcinoma prostate
g) Positive mpMRI findings
Recently PI-RADS version 2.1 was introduced to further
overcome limitations of PI-RADS v2. This includes
modifications in technical specifications,
interpretation of data, role of DCE, implication of bi-
parametric MRI, changes in prostate volume estimation
and prostate sectoral map for reporting.
PI-RADS category Risk of prostate cancer
1 Very low risk
2 Low risk
3 Intermediate risk
4 High risk
5 Very high risk

Category 5: very high probability of clinically significant

4) mpMRI in prostate cancer carcinoma prostate defined as: Gleason score > 7 and/or
A) PI-RADS (Prostate Imaging Reporting and Data System) volume >0.5ml and/or extraprostatic extension (EPE) .
version 2 was introduced in 2016 to simplify and
standardize reporting. mpMRI (multiparametric MRI)
includes anatomical and functional imaging – three
plane high resolution T2W images, high b-value axial
Diffusion weighted images (DWI) and Apparent
Diffusion Coefficient (ADC) map, axial Dynamic
Contrast Enhancement (DCE) images. Each finding has
a PI-RADS score of 1-5 and final overall PI-RADS score
is given.
 70 The Urology Masterclass, Department of Urology, CMC, Vellore

Algorithm to determine final PI-RADS score

B) mpMRI for staging:

For localized disease mpMRI is better at detecting and targeting anterior lesions than TRUS biopsy alone. For T3 disease
the overall sensitivity is around 60% and for nodal staging the sensitivity is less than 40% like CT scan. These have been
summarized in the following table:

For T3 disease
Sensitivity (95% CI) Specificity (95% CI)
EPE 0.57 (0.49-0.64) 0.91(0.88-0.93)
SVI 0.58 (0.47-0.68) 0.96(0.95-0.97)
Overall 0.61(0.54-0.67) 0.88(0.85-0.91)
N staging
(usual short axis diameter cut off : >8mm for pelvis and >10mm for outside pelvis)
Sensitivity of mpMRI (like CTscan) <40%

Pitfalls and limitations of mpMRI for staging: Post biopsy hemorrhage, artifact due to prostheses, normal periprostatic
venous plexus and neurovascular bundles may overestimate index tumor size or make an incorrect diagnosis of
extraprostatic extension (EPE).

C) mpMRI targeted biopsy:

Studies on radical prostatectomy specimens have shown mpMRI detection rates increase with increase in tumor volume
and ISUP grade.
A NIH study (Siddiqui et al. JAMA 2015) was done on 1003 men with increased PSA or abnormal DRE. mpMRI was followed
by TRUS biopsy only or MRI fusion biopsy only. There was a 30% increased detection of high risk disease and 17%
reduction in the detection of low risk disease. There was thus increased interest in the role of targeted biopsy to avoid
unnecessary biopsies.
 The Urology Masterclass, Department of Urology, CMC, Vellore 71

However as shown in the recent Cochrane metaanalysis, in a biopsy naïve setting systematic biopsy cannot be omitted.
In the repeat biopsy setting targeted biopsy may be an option after explanation to the patient. The detection and miss
rates are summarized in the table below.

Adding MRI targeted biopsy to systematic biopsy

ISUP =2(increases ISUP = 3 (increases
detection up to) detection up to)

In biopsy naive 20% 30%

In biopsy negative 40% 50%
Omitting systematic biopsy
ISUP =2 (misses up to) ISUP =3 (misses up to)
In biopsy naive 16% 18%
In biopsy negative 10% 9%

The EAU 2019 guidelines for mpMRI targeted biopsy are as follows:

5) PSMA PET/CT:
Ga18/F18 PSMA PET CT is being increasingly used in the staging of prostate cancer because of its excellent contrast to noise
ratio and improved detection of lesions. PSMA has high specificity to prostatic tissue even though it may be expressed in
benign bone diseases, sarcoidosis and other malignancies.
For lymph node staging: (Perera et al. metaanalysis Eur Urol. 2016. 70:926)
Sensitivity (95% CI) Specificity (95% CI)
At patient level 86 (37-98) 86 (3-100)
At lesion level 80 (66-89) 97(92-99)

LN’s missed were on an average less than 5mm. Also ISUP grade 1, 2 and 3 (as compared to 4 and 5) and serum PSA <10ng/
ml had higher miss rates. Based on available data PSMA PET has higher sensitivity for LN metastases compared to CT scan
or choline PET/CT.

For bone metastases:

Available evidence shows high variation in the sensitivity (33-99%) with good specificity (82-100%) with most studies
demonstrating increased detection rates compared to conventional imaging(CT and bone scan).
 72 The Urology Masterclass, Department of Urology, CMC, Vellore
The prognosis and ideal management of patients diagnosed
by the more sensitive PSMA PET/CT is unknown. It is unclear
if metastases detectable only with PSMA PET should be
managed using systemic therapies or aggressive local and
metastases directed therapies. Results from ongoing
studies are expected to throw more light in this regard.
For biochemical recurrence:
PSMA PET has shown good potential in patients with
biochemical recurrence. Detection rates of 15-58%, 25-
73%,69-100% and 71-100% have been reported for PSA
ranges of 0.2-0.5ng/ml, 0.5-1ng/ml, 1-2ng/ml and >2ng/ml
respectively. PSMA PET CT is more sensitive to other
conventional modalities at PSA <1ng/ml in biochemical
recurrence. PSMA PET is recommended in both post radical
prostatectomy (if PSA >0.2ng/ml) and post RT biochemical
recurrence if patient is fit and if results will influence
subsequent treatment decisions (Level of evidence 2b – EAU
2019 guidelines).
6) Active surveillance in carcinoma prostate
Active surveillance for low risk localised prostate cancer
reduces risk of overtreatment and morbidity while
retaining the option of curative treatment. Patients should
be counseled about possibility of needing further treatment
in future.
Aim
Selection criteria for active surveillance:
• Varied - Lack of formal RCTs
• Criteria most often used:
– Gleason grade 6 (grade group 1), <2-3 positive cores
(when specified) with <50% cancer involvement in
every positive core
– Gleason grade 3+4=7, grade group 2 if only focal
areas of pattern 4 (<10% area)
– Clinical stage T1c, T2a
– Serum PSA <10ng/dl
– PSA density<0.15ng/ml/cc
Exclusion criteria for active surveillance:
• Additional pathological features that preclude AS
– Predominant ductal carcinoma (including pure
ductal carcinoma)
– Sarcomatoid carcinoma
– Small cell carcinoma
– Extraprostatic extension/lympovascular invasion
– Perineural invasion
• To be used with caution in very young (<55 years), in
more than two positive cores, increased PSA density
and in African Americans
Follow up of active surveillance
• Digital rectal examination annually
• Serum PSA every 3-6 months
• Repeat biopsy (Confirmatory biopsy) at 6-12 months
(to rule out missed high grade disease); changing in the
light of increase use of mpMRI
• Repeat subsequent biopsies (Surveillance biopsy) every
2-5 years
Role of mpMRI in Active surveillance
Cancer upgrading was identified almost three times more
often in men with a positive mpMRI in contrast to a negative
mpMRI during follow up. PI-RADS score >4 and lesion size
>10mm are strongly associated with withdrawal from
active surveillance. mpMRI should be performed before
confirmatory biopsy and combination of targeted (of any
PI-RADS >3 lesion) along with systematic biopsy at
confitmatory biopsy is recommended (EAU 2019
guidelines).
Switching to active treatment
• Pathology : Gleason score more than 6, pattern 4/5;
tumor volume involvement more than 50%
• T-stage progression
• PSA change – doubling time < 3years is a less powerful
indicator to change
• Patient’s request : this occurs in around 10% of patients
on AS
 The Urology Masterclass, Department of Urology, CMC, Vellore 73

Individual life expectancy must be evaluated before Results

considering any active treatment in low risk carcinoma • CSS 98% in all three groups
prostate. For those with up to 10yr individual life
• PFS better in treatment arm (91%) vs AS (78%)
expectancy, active surveillance or watchful waiting are
probably very good options. • Twofold higher metastasis in AS group
ProtecT study: • Similar all cause mortality
Methodology • NNT was 27 (RP)/ 33 (RT) to avoid one pt with metastasis
• RCT that included men with localized (upto T2N0M0) Conclusion
CaP. • In low risk Caucasian males, the three modalities
• Randomized to one of three arms: Active surveillance provided comparable survival
(545), RP (553) or RT (545). • Progression and metastasis rate was higher. Treatment
• Longitudinal follow-up over a 10 yr period. rate was 50% at 10 yrs in AS
Endpoints • First RCT and first study to show comparable outcomes
(AS survival lower in SPCG 4, PIVOT)
• Primary : Cancer specific mortality at 10 yrs
Critique
• Secondary:
• Less than 1% Afro-Carribean patient population
• All cause mortality
• Recruited population may be healthier than CaP in the
• Primary treatment failure (PSA >0.2, 3 m post RP or >2
general population (50-69 yrs, T1c, PSA<20, Gleason
above nadir post RT)
6).
• Metastatic disease (Bony, visceral, or lymph-node on
• PSA based recruitment causing over-representation of
imaging or PSA >100 ng/ml)
low risk cancer.
• Progression (Mets, cT3/4, retention, long term ADT, rectal
• Not all patients in a group adhered to the prescribed
fistulae, ureteric obstruction)
treatment.
Demography
• The trial was conducted over two decades- diagnostic
• Mean age 62 years, 99% Caucasian and therapeutic algorithms evolved (E.g. lap and robotic
• Median PSA 4.8 ng/ml prostatectomy, IMRT).
• Gleason: <7 in 77%, 7 in 20%, >7 in 3% • Longer follow-up (15 yrs) may delineate differences in
• Stage T1c 75% and T2a in 25% survival.
• 80-85% received allotted treatment, 1% loss to f/u

Population Median Risk category Results

follow up
SPCG-4 Pre-PSA era 283 months Low risk and -Cancer specific mortality and overall survival
1989-1999 intermediate was better in the radical prostatectomy group
risk -RR 0.55 (95%CI 0.41-0.74)in favour of RP
-NNT to avert death from any cause 8.4
-At 23 yr, a mean of 2.9 extra years of life was
gained with radical prostatectomy
PIVOT Early years of 152 months Low and -All cause mortality was better in the RP group
PSA testing intermediate (absolute difference 5.5 %points). HR0.85 (95%CI
1994-2002 risk 0.70-1.01;p=0.06)
-Cancer specific mortality also in favour of RP
(absolute difference 4% points). HR0.63 (95%CI
0.30-1.02;p=0.06)
-The all cause mortality and prostate cancer
mortality were not significant than observation
at nearly 20y followup
-Urinary incontinence and erectile and sexual
dysfunction were each greater with surgery than
with observation through 10 years.
-Disease-related or treatment-related limitations
in activities of daily living were greater with
surgery than with observation through 2 years
 74 The Urology Masterclass, Department of Urology, CMC, Vellore
7)ADVERSE BIOPSY FEATURES POST RP AND MANAGEMENT
• Margin positive (HR : 2.4)
• Extracapsular extension (HR:2.0)
• Seminal vesicle involvement (HR:3.8)
• More than 2 lymph node positive with or without
extranodal spread (HR : 2.4)
• Overall biochemical recurrence free survival post RP
for high risk localised carcinoma prostate at 5 and 10
years were 71% and 58% respectively
Adjuvant versus salvage RT (in addition to ADT) in adverse
features post RP
• For patients at increased risk of local relapse, who
present with a PSA level of < 0.1 ng/mL, two options can
be offered in the framework of informed consent.
– Immediate ART to the surgical bed after recovery of
urinary function, during the first six months post
surgery (Adjuvant RT)
– Clinical and biological monitoring followed by
salvage radiotherapy (SRT) before the PSA exceeds
0.5 ng/mL
• Immediate RT
– reduces the risk of recurrence (10yr OS – 74% vs
66%) *
– Increased in 10yr cumulative risk of grade 2 or
higher GU and GI toxicity of 3%
– Accurate patient selection is mandatory (high risk
for relapse)
• Salvage RT
– Evidence from RCTs lacking
Guidelines for imaging in BCR (EAU guidelines 2019)
– Observation followed by SRT at first sign of
recurrence may be associated with durable cancer
control in selected patients
• Dose escalation, novel RT techniques, and the
concomitant use of ADT might improve the long-term
outcomes of postoperative RT
8) Biochemical recurrence
Definition
After RP, the threshold that best predicts further metastases
is a PSA > 0.4 ng/mL and rising. After primary RT, with or
without short-term hormonal manipulation, the RTOG-
ASTRO Phoenix Consensus Conference definition of PSA
failure (with an accuracy of > 80% for clinical failure) is
any PSA increase > 2 ng/mL higher than the PSA nadir value,
regardless of the serum concentration of the nadir.
Risk stratification of biochemical recurrence
EAU low risk BCR:
1) PSADT(doubling time) >1yr AND
2) ISUP grade <4 in RP specimen or biopsy for RT
AND
3) Interval to biochemical failure >18 months
EAU high risk BCR:
1) PSADT <1yr OR
2) ISUP grade 4,5
3) Interval to biochemical failure <18 months
 The Urology Masterclass, Department of Urology, CMC, Vellore 75

Guidelines for treatment of BCR (EAU guidelines 2019)

9) Metastatic hormone sensitive carcinoma prostate

Systemic therapy (docetaxel or abiraterone) in addition to androgen deprivation threrapy (ADT) is presently the standard
of care in men who are fit to receive systemic therapy and have no contraindications for systemic therapy.
Prognostic factors
Definition for volume and risk based on CHAARTED and LATITUDE

Prognostic factors based on SWOG 9346 study

 76 The Urology Masterclass, Department of Urology, CMC, Vellore
Phase 3 RCTs in metastatic hormone sensitive prostate cancer
Some of the salient features of the above studies are:
1) The GETUG AFU 15 was the first RCT to study role of
systemic therapy in metastatic hormone sensitive
prostate cancer. It had a high number of low volume
disease patients (53%). Also up to 80% in the ADT alone
arm received docetaxel when they progressed to mCRPC.
In the long term follow up of GETUG study the high
volume disease subgroup had a 4month non significant
survival advantage with docetaxel.
2) The survival advantage in CHAARTED for docetaxel
addition was more pronounced for the high volume
disease group, with a 17 month survival advantage (HR
0.63 95%CI 0.50-0.79). The low volume group receiving
docetaxel had no significant difference in overall
survival.
3) STAMPEDE is a multistage, multiarm study. The
Docetaxel arm included 61% patients with metastases.
There was no subdivision into high volume and low
volume disease. The metastatic group showed survival
benefit with Docetaxel(HR 0.73 95%CI 0.59-0.89) where
as the non metastatic group did not show any survival
difference with the addition of docetaxel.
4) A metaanalysis of the above three studies (GETUG,
CHAARTED, STAMPEDE docetaxel arm) showed survival
benefit with addition of docetaxel(HR 0.77 95% CI 0.68-
0.87) with absolute improvement in 4yr survival of
9%(95%CI 5-14). The same study showed improved
failure free survival with HR 0.64 (95%CI 0.58-0.70)
translating into a reduction in absolute 4 year failure
rates by 16% (95% CI 12-19).
5) LATITUDE study for addition of Abiraterone to ADT
included all metastatic patients. There was a 38%
improvement in survival (HR 0.62 95%CI 0.51-0.76)
6) STAMPEDE Abiraterone arm showed a similar survival
benefit HR 0.63 (95%CI 0.52-0.76). The survival
advantage was present in both metastatic and non
metastatic groups.
Docetaxel vs Abiraterone
Even though there are no head to head comparisons as yet,
a contemporaneous randomization was done in the
STAMPEDE study (possible because of the multiarm
multistage model).
Even though short term PSA driven outcome measures like
failure free survival, progression free survival and
metastatic progression free survival favoured Abiraterone;
long term clinically meaningful outcome measures such
as cancer specific mortality and overall survival did not
show any difference between docetaxel and abiraterone.
Both had similar grade 4 and 5 toxicities rates. The toxicities
were along expected lines specific to the drugs.(Reference
–Sydes et al. Annals of oncology Feb 2017)
 The Urology Masterclass, Department of Urology, CMC, Vellore 77

The table below summarizes the factors to consider when choosing between abiraterone and docetaxel (reference-Andrew
Hahn et al.ASCO educational book April 2019)

Other factors to consider:

-Pre-existing grade 2-3 hypertension (abiraterone contraindicated) and severe osteoporosis precludes steroid use (and
hence use of abiraterone)
- Pre-existing neuropathy precludes docetaxel use.

Prostate radiotherapy in metastatic hormone sensitive prostate cancer

A recent metaanalysis (STOPCAP) that analysed pooled data from HORRAD and STAMPEDE H arm showed no improvement
in overall survival(HR 0.92 95%CI 0.81-1.04) or progression free survival with addition of prostate radiotherapy. However
there was improvement in biochemical progression and failure free survival.
Subgroup analysis revealed improvement in overall survival (7% improvement in 3 year overall survival) in oligometastatic
disease (less than 5 bone metastases).
It was hence concluded that prostate radiotherapy should be considered in mHSPC with low metastatic burden.
Ongoing trials in mHSPC

10) Castrate resistant prostate cancer (CRPC)

Definition
Castrate serum testosterone < 50 ng/dL or 1.7 nmol/L plus either;
a. Biochemical progression: Three consecutive rises in PSA one week apart resulting in two 50% increases over the nadir,
and a PSA > 2 ng/mL or,
b. Radiological progression: The appearance of new lesions: either two or more new bone lesions on bone scan or a soft
tissue lesion using RECIST (Response Evaluation Criteria in Solid Tumours)
Symptomatic progression alone must be questioned and subject to further investigation. It is not sufficient to diagnose
CRPC.
78 The Urology Masterclass, Department of Urology, CMC, Vellore

Algorithm for management of CRPCAlgorithm for management of CRPC

 The Urology Masterclass, Department of Urology, CMC, Vellore
AUA index patients for CRPC
mCRPC categorized according to symptoms, performance
status and prior docetaxel therapy
• Index patient 1- Asymptomatic CRPC
• Index patient 2- Asymptomatic/Mildly symptomatic -good
performance score no prior docetaxel
• Index patient 3- Symptomatic metastatic CRPC – good
performance score no prior docetaxel
• Index patient 4- Symptomatic metastatic CRPC – poor
performance score no prior docetaxel
• Index patient 5- Symptomatic metastatic CRPC – good
performance score with prior docetaxel
• Index patient 6- Symptomatic metastatic CRPC – poor
performance score with prior docetaxel
14. BONE HEALTH IN CARCINOMA PROSTATE
Introduction
Prevalence of Vitamin D deficiency is 70% and osteoporosis
is 20% in elderly men in South India. Hip fracture secondary
to osteoporosis can result in 25% mortality at 1 year. With
androgen deprivation, the prevalence of osteoporosis
increases to as high as 80% at 10 years. The number needed
to harm (Fracture) was 28 with LHRH agonists and 16 for
orchidectomy.
Risk factors for skeletal related event
One of the following:
• >6 months on ADT
• Previous fractures
• Positive family history for osteoporosis
• Low bodyweight
• Smoking, excessive alcohol consumption
• Corticosteroid use
• Medical comorbidities
• Low vitamin D levels
Baseline assessment
• Bone mineral profile (Ca+, Phosphate, Albumin, 25(OH)
Vitamin D, Alp, creatinine)
• X -RAY spine lateral (To identify sclerotic metastases that
can falsely increase T score)
• Bone turnover markers: NTX (Urine N Telopeptide-
resorption) and P1NP(formation)
• DXA SCAN for BMD. (T score: Patient’s femur neck BMD
vs. healthy young control, same gender)
BMD T-Score
Osteoporosis < minus 2.5
Osteopenia Between minus 1.0 – minus 2.5
Normal > minus 1.0
79
Management of bone health:
Lifestyle modification
Safe weight-bearing, exercise, moderate sun exposure,
discourage alcohol and smoking and a balanced diet
including calcium-rich foods
Calcium supplementation
• Daily requirement: 1000 mg per day
• Diet < 400 mg/ day obtained
• At least one tablet Calcium carbonate(500 mg) needed
daily
• Given with dinner as acid is needed for CaCO3
absorption
• Calcium citrate malate- Costly, but no acid is needed
for absorption
• No Increased risk of renal stones in majority with
calcium supplementation
Vitamin D
• Daily requirement: 800 U/ day
• Optimum serum 25(OH)D level for patients with
osteoporosis and adults >50 yrs is 30 ng/dL
• Vitamin D deficiency: 60,000 U oral weekly for 6 weeks
and monthly for 6 months.
Bone protective agents
• Treatment with bisphosphonates showed a substantial
effect in preventing fractures (RR 0.80; P = 0.005) and
osteoporosis (RR, 0.39; P <0.00001) and should be
recommended in mCaP.
• Always prescribe calcium and V itamin D
supplementation along with these agents Zoledronic
acid
• Nitrogen containing Bisphosphonate that acts by
inhibiting the enzyme Farnesyl pyrophosphate synthase
(FPP) which is required for prenylation of proteins.
• This produces cytoskeletal abnormalities in osteoclasts
and detachment from bone
• It binds to the hydroxyapatite sites on the bone and
when this is taken up by osteoclasts, the formation of
ruffled border is hampered
• It also hampers osteoclast progenitor development and
promotes osteoclast apoptosis
• Zoledronic acid showed the best NNT, compared with
placebo, in relation to osteoporosis and fracture
prevention (NNT = 2.68 and 14.9 respectively). (Neto et
al. Prostate Cancer Prostate Dis. 2012). It also increased
time to first fracture.
• 4 mg IV along with ADT every month in 500 ml NS over
30 minutes
• 70 percent of the absorbed bisphosphonate is cleared
by the kidney, and the remaining 30 percent is taken up
 80 The Urology Masterclass, Department of Urology, CMC, Vellore
by bone. Therefore, normal renal function is required
for Zoledronate.
• ADR:Myalgia, fever, mild increase in creatinine,
osteonecrosis of the jaw (ONJ) in those with poor
dentition
• Other bisphosphonates: Pamidronate, Ibadronate,
Etidronate
Denosumab
• Fully human monoclonal antibody against RANK ligand
• Denosumab acts by inhibition of RANKL (also known as
NF-kB) which inhibits osteoclast activity
• 60-120 mg monthly, subcutaneous
• Does not require renal dose adjustment
• Compared with Zoledronate in a phase III RCT, it showed
lower skeletal resorption (lower NTX and ALP) as well
as increased time to skeletal related event (20.7 vs.
17.1 months, HR 0.82, p=0.008).
• ADR: Fatigue, nausea, hypocalcaemia, hypopho
sphataemia, Osteonecoris of Jaw (ONJ) (2-4%)
Suggested reading and references:
1) Biomarkers in prostate cancer Alford A et al. Rev Urol.
2017; 19(4):221–234
2) mpMRI Furlan et al. Urol Clin N Am 45 (2018) 439–454
3) PIRADS v2.1 Turkbey et al. Eur Urol Feb 2019
4) PSMA PET Perera et al. metaanalysis Eur Urol. 2016.
70:926)
5) ProtecT study Hamdy et al. N Engl J Med 2016;375:1415-
24.
6) SPCG 4 study.Axelsen et al N Engl J Med 2018;379:2319-
29.
7) PIVOT study. Wilt et al. N Engl J Med 2017;377:132-42.
8) Gandaglia etal, Adjuvant and Salvage Radiotherapy
after Radical Prostatectomy in Prostate Cancer Patients,
European Urology, Jan 2017
9) Gravis mHSPC review. Asian Journal of Urology (2019)
6, 162e168
10)Andrew Hahn et al.ASCO educational book April 2019
11)Sarah Budett et al STOPCAP systematic review and
metaanalysis European Urology Feb 2019
12)AUA 2018 guidelines
13)EAU 2019 guidelines
 The Urology Masterclass, Department of Urology, CMC, Vellore 81

RCC with IVC thrombus

Epidemiology
1. Lower extremity oedema
• Overall 4-10% of all RCC
2. Isolated right sided varicocele/ irreducible varicocele
• 5 year survival: 40-60% (T3a), 30-50% (T3b), 20-40% (T3c)
3. Dilated superficial abdominal veins
• Median survival in months: 52 (T3a), 25.8 (T3b), 18 (T3c)
4. Proteinuria
• 45-70% can be cured with aggressive surgery
5. Pulmonary embolism/ right atrial mass
• When to suspect IVC thrombus?
6. Non-function of the involved kidney
Classification

TNM Hinman Novick Neves and

Zincke
Renal vein T3a I I 0
IVC <2 cm from renal vein I
IVC >2 cm from renal vein II II
but below hepatic veins
IVC above hepatic veins, II III III
below diaphragm
IVC above diaphragm T3b III IV IV

Neves and Zincke classification

• Level I: Venous thrombus in the renal vein not reaching IVC.
• Level II: Infra-hepatic IVC thrombus.
• Level III: Thrombi in retrohepatic or suprahepatic IVC not reaching the right atrium
– IIIa (intrahepatic): A thrombus extending into the retrohepatic IVC below the ostia of hepatic veins
– IIIb (hepatic): A thrombus extending into the retrohepatic IVC reaching ostia of the hepatic veins and may cause Budd-
Chiari syndrome.
– IIIc (suprahepatic, infradiaphragmatic): A thrombus extending into the retrohepatic IVC above the hepatic veins but
below the diaphragm.
– IIId (suprahepatic, supradiaphragmatic and infraatrial): A thrombus extending into the supradiaphragmatic,
intrapericardial IVC but not into right atrium.
• Level IV: Right atrial thrombi.

Imaging
• MRI with Gadolinum traditionally preferred:
– Differentiates bland from tumour thrombus (enhancement)
– Invasion of IVC wall better identified
• However, multiplanar CT is equally effective

Venovenous/
Thromb
MRI Cephalad control cardiopulmonary
us level
bypass
May need caudate
I Subhepatic No
mobilization
IVC wall free
II IVC wall Liver mobilization, Pringle’s No
invaded
Sternotomy/
III Atrial thrombus May be needed
transdiaphragmatic
 82 The Urology Masterclass, Department of Urology, CMC, Vellore

Clamping De-clamping
1. Below the thrombus 1. Lower clamp
2. Opposite renal vein 2. Opposite renal vein
3. Above the thrombus 3. Upper clamp

Complications of bypass
• Peri-operative mortality 15%
• Stroke 6.1%, coagulopathy- 25%
• Circumvented with transdiaphragmatic approach under TEE monitoring: 4.5% mortality

Morbidity of surgery for IVC thrombus:

– Air or tumour embolism,
– Renal or liver dysfunction,
– DVT
– Atelectasis, ileus
– Mortality of 2-4%

Hepatic Mobilization and Liver Transplant Techniques
(Ciancio)
• Medial mobilization of the liver involves incising
falciform and round ligaments followed by incision of
the coronary ligaments.
• Hepatoduodenal and hepatogastric ligaments as well
as small hepatic veins draining the caudate lobe can
further be divided for hepatic mobilisation.
• To avoid hepatic congestion or IVC bleeding while a
vascular clamp is placed above the hepatic veins, one
can perform Pringle maneuver, which consists of
temporarily occluding the hepatic artery by clamping
the hepatic pedicle.
• In addition to mobilizing the liver off the vena cava, a
plane between the IVC and the posterior abdominal wall
is important because it permits circumferential
vascular control of the cava.
• These manoeuvres can give access to the
infradiaphragmatic suprahepatic IVC for level III
thrombi.
• Further transdiaphragmatic access to the right atrium
through the pericardium allows clamping of the right
atrium above the thrombus and its removal without
bypass. This requires continuous monitoring with
trans-oesophageal echo
 The Urology Masterclass, Department of Urology, CMC, Vellore 83

Venovenous bypass (VVBP) References

• The technique involves the cannulation of the infrarenal Campbell Walsh Urology 11th edition
IVC or femoral veins in addition to a vein above the IVC Pouliot et al, J Urol 2010
(axillary, subclavian, superior vena caval, internal
jugular, cephalic) or right atrium Guzzo et al, J Urol 2009
• VVBP confers many of the advantages of CPBP like Mandhani et al, IJU 2015
1) Continued venous return to the heart during clamping Ciancio et al Cancer 2001
2) Systemic heparinization may not be required and Ciancio et al J Urol 2002
decreased risk of retroperitoneal haemorrhage Blute et al, BJUI 2004
3) Can be performed for level II, most level III and select Gross-Goupil M et al. Ann Oncol 2018
level IV thrombi with free floating thrombus Nandagopal L et al. Curr Treat Options in Oncol 2018

Adjuvant therapy in high risk localized RCC

• 40% of high risk localized RCC with show relapse.
Adjuvant therapy trials were therefore designed to see
if local recurrence rates could be reduced
• STRAC showed a 20% better DFS.
• ATLAS showed a 36% reduction in risk of a DFS event (HR
0.641; CI 0.468-0.879; p= 0.0051) in the highest risk
subgroup (pT3 with grade 3 or pT4 and/or N+, any T,
any grade). Overall survival data is awaited.
• All other studies were negative
84 The Urology Masterclass, Department of Urology, CMC, Vellore
 The Urology Masterclass, Department of Urology, CMC, Vellore 85

Metastatic RCC
Risk stratification

The Metastatic Renal Cancer Database Consortium (IMDC) criteria

MSKCC/ Motzer criteria

Median survival in months

Category Motzer IMDC

1st line 2nd line
Favourable (0 risk factors) 28.6 43.2 35.3
Intermediate (1-2 risk factors) 14.6 22.5 16.6
Poor (3 or more risk factors) 4.5 7.8 5.4

Targeted therapy - Combination with Bevacizumab showed an improved

Interleukin alpha (18 MU s/c thrice weekly) and
Bevacizumab (10 mg/kg IV every 2 weeks)
- Interferon-á resulted in response rates of 6-15%, a 25%
decrease in tumour progression risk.
Modest survival benefit: median OS of 8 months vs 6 months
(Medroxyprogesterone
Acetate) and 16 months vs 8 months (Vinblastine), both
significant
- Interferon-D may only be effective in some subgroups
(ccRCC, favourable risk criteria, as defined by the
MSKCC and lung metastases only)
response rate up to 30% with a median PFS of 10 months
vs 5 months (IFN alone). However, there was no OS
benefit
-Superceded by TKI and PD-1/CTLA 4 inhibitors
IL-2 (6-7.2 lakh units IV/ kg q8h for 5 days)
- Response rates ranging from 7-27%. Complete response
seen with high-dose bolus IL-2
- Significant toxicity: Vascular leak, hypotension,
respiratory distress & 2-5% mortality. No added benefit
with IFN

Sunitinib ((50 mg OD for 4 weeks-2 weeks gap)

EFFECT trial
STUDY NO.OF OVERALL MEDIAN PFS MEDIAN OS
STUDIES AGENT(S) PHASE POPULATION PATIENTS RESPONSE (mo)* (mo)*
RATE (RECIST)*
Motzer et al Sunitinib vs Randomized 750 31% vs. 6% 11 vs. 5 26.4 vs. 21.8
2007, 2009 IFN-D phase III
 86 The Urology Masterclass, Department of Urology, CMC, Vellore

-ADR: Hypertension, fatigue, diarrhoea, hand foot syndrome, pancytopenia, hypothyroidism

-Approved first line treatment for metastatic clear cell and non-clear cell RCC

Sorafenib (400 mg OD)

-Second line setting, cytokine refractory disease
-Response rate of 10% and median OS 18 vs 14 months (Placebo)- not significant
-Side effects: Hypertension, fatigue, diarrhoea and hand foot syndrome

Pazopanib (800 mg OD)

COMPARZ trial

Motzer et al Pazopanib vs Randomized

phase III 1110 31% vs. 25% 10.5 vs. 10.2 28.4 vs. 29.3
2013c Sunitinib

PISCES: 70% of patients preferred Pazopanib vs 22% who

preferred Sunitinib: Lesser toxicity
All side effects of Sunitinib but milder, higher hepatotoxicity

Axitinib (5 mg BD)
- Selective second-generation inhibitor of VEGFR-1, -2,
and -3. Second-line treatment
- Sunitinib failure- Axitinib was had better PFS than
sorafenib (4.8 vs. 3.4 months
- In a phase III trial of axitinib vs. sorafenib in first-line
treatment-naïve metastatic ccRCC, a difference in
median PFS between the groups was not demonstrated-
Not approved for 1st line
Cabozantinib (60 mg PO OD)
- Oral inhibitor of tyrosine kinase (TK), including MET,
VEGF and AXL
- METEOR trial: Cabozantinib vs Everolimus RCT in VEGF
resistant metastatic clear cell RCC
- The median PFS for Cabozantinib was 7.4 vs. 3.8 months
for Everolimus- 42% improvement (HR: 0.58). The
median PFS for Cabozantinib was 7.4 months vs. 3.8
months for Everolimus.
- The median OS was 21.4 months with Cabozantinib and
16.5 months with Everolimus. (HR was
0.66 (95% CI: 0.53-0.83, p = 0.0003)
- CABOSUN trial: Phase II, Cabozatinib and Sunitinib in
first-line in 157 intermediate- and poor risk patients
favoured cabozantinib for PFS (adjusted HR: 0.66) but
not OS.
- Grade 3 or 4 adverse events were reported in 74% with
cabozantinib and 65% with everolimus.
- Approved 2nd line for clear cell RCC
Everolimus (10 mg PO OD)
- RECORD 1: vs placebo. Better PFS (5 vs 2 months) for
Everolimus. Similar OS in 2nd line setting
- RECORD 2: Bevacizumab + Everolimus vs Bevacizumab
+ IFN in 1st and 2nd line setting
- RECORD 3: Sequencing compared with Sunitinib.
Sunitinib showed better PFS (11 vs 8 months) and OS
(32 vs 22 months) when used as 1st line- Not
recommended as 1st line Nivolumab (PD L1 inhibitor- 3
mg per kilogram of body weight, 60-minute IV every 2
weeks) and Ipilimumab (PD L1 inhibitor- 1 mg per
kilogram of body weight, 60 minute IV every 3 weeks)
- Checkmate 025: Compared Nivolumbac with Everolimus
in RCT, 2nd/3rd line, metastatic ccRCC
- Nivolumab has superior OS to everolimus (HR: 0.73) in
VEGF refractory RCC with a median OS of 25 months for
nivolumab and 19.6 months for everolimus.
- No PFS advantage.
- Fewer grade 3 or 4 toxicity events
- Approved second line for clear cell RCC
- Checkmate 214: Compared Nivolumab + Ipilimumab vs
Sunitinib in first-line treatment of treatment-naïve
advanced or metastatic, intermediate and poor risk
metastatic ccRCC
- Co primary end points: Response rate, PFS and OS
- 28% of the intermediate/poor-risk population with
quantifiable PD-L1 expression were biomarker positive
(> 1% of tumour cell staining for PD-L1)
 The Urology Masterclass, Department of Urology, CMC, Vellore
- Tumours which overexpressed the PD-L1 biomarker at
baseline were associated with a better RR and PFS with
nivolumab plus ipilimumab than sunitinib (PFS HR:
0.48)
- Nivolumab plus ipilimumab was associated with 15%
grade 3-5 toxicity and 1.5% treatment Related deaths
- If treatment stopped due to toxicity- Do not rechallenge.
If Ipilimumab toxicity, single agent Nivolumab for4
cycles
Pembrolizumab (PD-1 inhibitor 200 mg IV every 3 weeks)
and Axitinib (5 mg BD)
- KEYNOTE 426: Phase III RCT Pembrolizumab + Axitinib
vs. Sunitinib in 1st line metastatic ccRCC
- Primary end points were overall and progression-free
survival in intention-to-treat population
- Median follow-up of 12.8 months
- 60% were PD-L1 positive. 69% were IMDC intermediate
and poor risk
- OS at 12 months: 89.9% in the Pembrolizumab-Axitinib
group and 78.3% in the Sunitinib group (HR, 0.53)
- PFS was 15.1 months in the Pembrolizumab–Axitinib
group and 11.1 months in the Sunitinib group (hazard
ratio for disease progression or death, 0.69)
- The objective response rate was 59.3% in the
Pembrolizumab–Axitinib group and 35.7% in the
Sunitinib group (P<0.001)
Sequencing of therapy in metastatic RCC (Modified from EAU 2019)
First line
IMDC favourable risk Sunitinib or Pazopanib
disease
Ipilimumab + Nivolumab
Pembrolizumab + Axitinib
Avelumab + Axitinib
IMDC intermediate and
poor risk disease
Cabozantinib, Sunitinib
or Pazopanib *
Boxed categories
represent strong
recommendations
87
- KEYNOTE 427: Phase II trial, Pembrolizumab in
metastatic cc and non ccRCC
- The primary end point for this study was objective
response rate (ORR) per RECIST v1.1.
- The secondary end points included the duration of
response, PFS, and OS.
- Histology was as follows: Papillary 71% (118),
chromophobe 13% (21), unclassified 16% (26)
- Median follow-up of 11.1 months- 24.8% overall
response (8 patients with complete and 33
With partial response). Papillary (25.4%) and
unclassified (34.6%) and chromophobe (9.5%)
- PFS was 4.1 months and OS 72% at 12 months
Avelumab (PD-L1 inhibitor 10 mg/kg IV every 2 weeks) +
Axitinib
- JAVELIN: Phase III RCT, Avelumab + Axitinib vs Sunitinib
in metastatic ccRCC 1st line
- PFS and OS in PD-L1 positive tumours was primary end
point
- 63.2% PD-L1 positive tumours, 74-81% IMDC
intermediate and poor risk
- Median progression-free survival was 13.8 months with
avelumab plus axitinib, as compared with 7.2 months
with sunitinib (hazard ratio for disease progression or
death, 0.61)
- PD-L1–positive tumors, the objective response rate was
55.2% with avelumab plus axitinib and 25.5% with
sunitinib
- Similar number of deaths at 11 months (37 vs. 44)
Atezolizumab + Bevacizumab (1200 mg IV + 15 mg/kg IV
every 3 weeks)
IMmotion151: Phase III RCT in treatment naive metastatic
RCC of all risk groups. Two arms Atezolizumab+
Bevacizumab and Sunitinib. The PD L1+ group (40%) showed
improved PFS (11.2 vs. 7.7 months, HR 0.74, p=0.02) as did
the overall group of patients (HR 0.83, p=0.002)
Second line Third line
Cabozantinib or Cabozantinib or
nivolumab nivolumab
Cabozantinib or an
Cabozantinib or VEGF -
alternate targeted
targeted therapy
therapy
VEGF - targeted therapy An alternate targeted
or Nivolumab therapy or nivolumab
 88 The Urology Masterclass, Department of Urology, CMC, Vellore

Cytoreductive nephrectomy and Small renal mass

sequencing with Sunitinib - A small renal mass (SRM) is defined as a contrast
enhancing mass with a largest dimension of 4 cm or
CARMENA SURTIME less on abdominal imaging.
n 450 (226 and 224) 90 (50 and 49)
Intervention Immediate CN + Immediate CN +
- The incidental detection of small renal masses (SRMs)
Sunitinib vs. Sunitinib Sunitinib vs. 3 months was 7-13% in 1970’s. This has increased to 48-66% in
alone (Phase III RCT) of Sunitinib folloed by the current literature due to the widespread use of
CN (Phase III RCT) imaging. This increasing incidence has not lead to a
Inclusion Asymptomatic primary Asymptomatic primary
+ synchronous met, + synchronous met,
fall in mortality from renal cancer.
ECOG 0/1 ECOG 0/1 - About half the patients with SRMs are >65 yr of age at
End points OS and PFS OS and PFS diagnosis and many have significant comorbidities.
Primary tumour size 88 (6-200) 94.5 (13-200)
(mm) - Those >75 yr age are more likely to die of cardiovascular
Median age 63 59 and other non-cancer conditions.
Motzer risk group 47% intermediate, 43% 87% intermediate, 13% - It is justified to have active surveillance as the initial
poor poor
Median number of 2 2
option form management in these individuals.
metastases
OS (Intervention) 13.9 months (11.8-18.3) 15 months (9.3-29.5)
OS (Control) 18.4 months (14.7-23) 32.4 months (14.5-65.3)
Natural history of SRM
• Many small renal tumors have a long natural history
Poor risk and are not destined to progress
No cytoreductive nephrectomy • 30% masses < 4 cm benign, 70-80% exhibit indolent
Intermediate risk behaviour
• No Immediate cytoreductive nephrectomy • Average growth- 0.31 cm/ year (0.1-0.35 cm/ year). Up
to 37% may not progress
Asymptomatic synchronous
• Those likely to progress are probably resected too late
• Start targeted therapy despite their localized radiographic appearance
• Delayed cytoreductive nephrectomy
• Progression to metastasis 1-2%. For each 1 cm increase
• Long term benefit if minimal residual metastatic burden in size of primary cancer, the calculated prevalence of
Good performance not requiring systemic therapy metastases increases by 3.5%.
Immediate cytoreductive nephrectomy • The mortality rate of symptomatic and incidentally RCC
Oligometastatic are comparable
Immediate cytoreductive nephrectomy + local treatment of • Autopsy series performed before the widespread use of
metastases imaging show that 67–74% of RCCs remained undetected
until death
Local therapy for palliation of symptoms
• 8.9–20% of undiagnosed RCCs were eventually
• Complete metastatectomy if possible responsible for the patient’s death.
• Bone or brain metastases: Stereotactic radiotherapy for
symptom relief and local control
Factor predicting progression
• Age (75 vs. 66 yrs)
Adrenal metastasis from renal cell carcinoma (RCC)
• Size (4.1 vs. 2.3 cm)
- Ipsilateral 3-5%, contralateral 0.7%
• Initial tumour volume (66.3 vs. 15.1 cc)
- There have been no reports of contralateral adrenal
metastasis from non-clear cell RCC. • Linear growth rate (8 mm vs. 3 mm/yr)
- Isolated contralateral adrenal metastasis: Mostly • Volumetric growth rate of 27 vs. 6.2 cc/yr)
synchronous, may be detected metachronously
Pathology of SRM
References - 46% of SRMs smaller than 1 cm are benign compared to
-EAU guidelines 2019 -Hudes G et al, NEJM 2007 22% between 1-2.9 cm and 20% between 3-3.9 cm.
-Motzer RJ et al NEJM 2007 -Motzer RJ JCO 2012 - Among masses that are malignant, greater size
correlates with higher pathological grade.
-Motzer RJ et al NEJM 2015 -Motzer RJ et al NEJM 2018
- 14 -26% of tumours between 3-4 cm are high grade (3 or
-McDermott JCO 2018 -Rini BI et al NEJM 2019 4) and 12-36% locally invade perinephric fat
-Motzer RJ et al NEJM 2019
(2 articles) -Bex A et al. Eur Urol 2018 Traditional Indications for biopsy
– SRMs that are indeterminate on abdominal imaging
 The Urology Masterclass, Department of Urology, CMC, Vellore
– Possibility of lymphoma
– Renal abscess
– Renal masses that are suspicious for metastatic disease
– Unresectable retroperitoneal tumours involving the
Kidney
– Incidentally diagnosed SRMs in patients who are
potentially candidates for active surveillance or
minimally invasive ablative therapy
– Follow-up of thermal ablation to confirm histologic
success and monitor recurrence
Pros and cons of biopsy
Biopsy procedure
• Imaging that the operator is familiar with
• 18 G needle, Multiple samples (2 or more)
• Avoid central necrosis & cystic masses
• Use of IHC:
– HMB45 (fat poor AML),
– Cytokeratins (oncocytoma vs chromophobe
RCC)
– Carbonic anhydrase IX (clear cell RCC)
Factors predicting poor yield of biopsy
Definitions
• Failure: Insufficient tissue
• Indeterminate: Pathologist cannot reach a diagnosis on
the available tissue
• Inaccurate: Discrepancy between biopsy and final
histology
89
Expanding role of biopsy:
- Renewed interest: – Adoption of modern techniques
including image guidance
– Increasing expertise of interventional radiologists
– Improving expertise of pathologists in interpretation
– Increasing confidence of urologists is using biopsy
results to base treatment decisions
– Small renal masses have a high probability of being
benign- Can avoid surgery in 16-17%
Accuracy of renal mass biopsy (RMB)
• Median diagnostic rate 92%
• Sensitivity 99%, specificity 93%
• False negative 5-25%
• Indeterminate 4-10%
Complications
• Bleeding requiring transfusion 1-2%
• Pneumothorax <1%
• Needle tract seeding 0.01%
Inclusion criteria for Active Surveillance
- Benign lesion on renal tumour biopsy
- Aged and informed patient
- Tumour size <4 cm on cross-sectional imaging, no
aggressive features
- Low-grade, on renal tumour biopsy
- Chromophobe-oncocytic hybrid tumour on renal tumour
biopsy
- Willingness of the patient to undergo regular CT or MRI
scans and repeated biopsies (good compliance)
- Poor surgical risk and limited life expectancy
Exclusion criteria
- Young and healthy patient
- Sarcomatoid features
- Collecting duct or unclassified RCC
- Evidence of T3a disease on cross-sectional imaging
 90 The Urology Masterclass, Department of Urology, CMC, Vellore
- High grade
- Symptomatic lesions
Protocol
• Percutaneous biopsy may be performed first
• CT/MRI at 6 months and annual USG/CT/MRI
• Annual chest X ray if biopsy proven
• Stop if: Diameter 3-4 cm or tumour volume doubling time
<12 months
Other options for SRM if unfit for Surgery
Radio frequency ablation
• Percutaneous/ laparoscopic
• Alternating monopolar current (450-1200 kHz)
• Minimum 70 C required within tumour
• RFS 88-95.2% (5 yrs)
• CSS 97.2-100 % (5 yrs)
Can be recommended if poor surgical risk, SRM
Cryoablation
• Percutaneous/ laparoscopic
• Two freeze thaw cycles, 8-10 min, liquid N2 (-196 C)
• Recurrence free: 87.3-93.2% (5 yrs)
• Cancer specific : 92-100% (5 yrs)
References
Volpe et al, Int J Surg 2016 - Smaldone et al, Cancer 2012
Jewett et al, Eur Urol 2011 - AUA guidelines 2016
Blute et al, Ther Adv Urol 2015 - Marconi, Eur Urol 2016
Lane, J Urol 2008 - Prince, J Urol 2015
Aron et al, J Urol 2010 - Guazzoni et al, Urology 2010
Zagoria et al, Urology 2011 - Psutka et al, Eur Urol 2013
Partial Nephrectomy (PN)/ Nephron sparing surgery (NSS)
Pitfall of radical nephrectomy
• Oncological outcomes are the same whether RN or PN
is performed for renal cortical tumours of less than 4
cm
• Despite adequate imaging, approximately 20% of
clinical T1 renal tumours are benign neoplasms and
60% to 70% are indolent tumours with limited
metastatic potential
• Concerns about late contralateral recurrence following
cure of the index tumour
• Emerging evidence that RN is an independent risk factor
for the development of CKD
• In patients with SRM with normal creatinine and normal
contralateral kidney
– 26% were found to have pre-existing stage 3 chronic
kidney disease (GFR< 60 mL/min/1.73m2)
– 65% of patients treated with RN were found to have
stage 3 chronic kidney disease after surgery vs 20% of
patients managed with PN
• Patients younger than 65 years those treated with RN
for T1a tumours were found to have decrease overall
survival • 12.7% incidence of acute renal failure when
operating on a solitary kidney
• 15.9% developing proteinuria
• 2.7% experiencing chronic renal insufficiency on a long
term basis.
A functioning renal remnant of at least 20% of one
normal kidney is necessary to avoid end-stage renal
failure
Absolute indications
• Patients with bilateral RCC
• RCC involving a solitary functioning kidney -
1. Unilateral renal agenesis
2. Prior removal of the contralateral kidney
3. Irreversible impairment of contralateral renal function
by a benign disorder.
Relative indication
Patients with unilateral carcinoma and a functioning
opposite kidney affected by a condition that might threaten
its future function:
1. Renal artery stenosis
2. Hydronephrosis
3. Chronic pyelonephritis
4. Ureteral reflux
5. Calculus disease
6. Systemic diseases such as diabetes and nephrosclerosis
 The Urology Masterclass, Department of Urology, CMC, Vellore
Elective indication
1. Tumour up to 4 cm with a normal functioning opposite
kidney
• Key concepts include
– Excellent exposure
– Early vascular control
– Wide excision with a negative surgical margin
– Reconstruction of the renal remnant to minimize the
risk of postoperative haemorrhage or urinary fistula
Why do we need cold ischemia?
• Ischaemia diminishes intraoperative renal
haemorrhage
• Improves access to the intrarenal collecting system by
reducing renal tissue turgor.
• It allows better visualisation of the tumour extent.
• It allows complete tumour resection sometimes without
healthy margin.
• It also allows easier closure of the parenchyma.
Mechanism resulting from renal ischaemia
• Primarily at a vascular level
• Multi-inflammatory responses by interleukins lead to
vasoconstriction and vascular spasms.
• A vicious cycle is activated by endothelial injury,
causing the activation of a cytokine cascade that result
in arteriolar vasoconstriction.
• The low renal blood flow releases angiotensin II and
eicosanoids.
• Failure of oxidative phosphorylation and ATP depletion
cause cellular swelling by passive water diffusion into
the cells, leading to ‘‘No reflow’’ phenomenon and
vascular obstruction during renal reperfusion occur.
• Free radicals resulting from ATP degradation cause
further cell damage.
Warm and cold ischemia
• Cellular degeneration begins mainly in the proximal
tubules after 20–30 min of clamping; after >60 min of
WI, complete cellular degeneration of the nephron
occurs.
• Data derived from non-heart beating donors describing
renal tolerance of ischaemia revealed that a WI period
of less than20 min significantly reduced post-
transplant kidney damage.
• Cold ischemia experiments on surface cooling with
medullary temperatures at about 22 C is that CI is not
tolerated for >60–70 min
Perioperative preparation
• De Maeyer et al described the optimal perioperative
preparation to avoid renal injury:
-Pre-ischaemic hydration
91
-Intravenous application of mannitol
-Infiltration of the pedicle with diluted Papaverine solution
Optimal temperature not <15°C was recommended by Ward
after experiments on dog kidneys.
Methods of inducing renal ischemia
• Internal bulldog clamps or exteriorized handheld
Satinsky clamp via a separate port
• Vessel loop for as a tourniquet
• Selective clamping of renal artery has been tried.
• Selective clamping of only the segmental artery
Methods of cooling
Surface cooling
• Laying ice slush/cold saline around the kidney is the
most common technique.
• Similar method of surface cooling have also been
developed for LPN and are recommended if WI is
expected to exceed 20 min.
• After an exposure time of about 10 min by ice slush, the
kidney can be clamped, and a safe CI time for a
maximum of 35 min
Trans-arterial cooling
• By perfusion through the clamped renal artery with
cooled Ringer’s solution.
• Kidney cooling down to 5–10 °C
• Minimises ischemic damage by an abrupt switch of
renal cells from aerobic to anaerobic processes.
• Achieves heterogeneous temperature profile of 5–19 °C
is achieved.
Conclusions on ischemia time
• CI has clear benefits in protecting the kidney during
long ischemic periods but should be used only if
absolutely necessary, that is, if expected clamping time
exceeds 30 min.
• There is no clear evidence of a postoperative benefit in
ischemic periods <30 min, but it is recommended
however, that WI be restricted to a maximum of 20 min
• Only when ischaemia time is expected to exceed 30 min
should CI be used a priori.
Modification in method of clamping
• No clinical study has demonstrated an improvement in
WI time or functional outcome after any modification
of clamping technique (E.g. clamping of the affected
segmental artery vs main artery).
• If only the artery and not the whole pedicle is clamped,
the hypothetical effect of partial oxygenation of
parenchyma caused by retrograde venous backflow
must be weighed against the potentially higher risk of
 92 The Urology Masterclass, Department of Urology, CMC, Vellore
intraoperative venous parenchymal haemorrhage and
consequently, higher blood loss and reduced visibility.
• An influence of pneumoperitoneum on functional
outcome has not been evaluated systematically but is
unlikely under the typical low pressure of
approximately 15 mm Hg.
Strategies to reduce ischemia
• Early unclamping during renorraphy
• Use of bipolar/ ultrasound sealing devices
• Focal radiofrequency ablation
• Induced Hypotension
• Use of parenchymal compression
– HAL PN compression using hand
– Lap PN using Simon renal pole clamp
Pharmacologic reno-protective agents
– Mannitol used as an osmotic diuretic and potential
free radical scavenger
– Furosemide to promote diuresis after unclamping
Zero Ischemia PN
• Selective branch micro-dissection of renal artery and vein
into the renal sinus,
– Branch vascular micro-dissection is performed
wherein the tumour or tumour-bearing segment of the
kidney is specifically supplied by a dedicated
secondary, tertiary, or quaternary branch
• Transient, pharmacologically induced reduction of
blood pressure, timed to precisely coincide with
excision of the deep part of the tumour. – Nadir
hypotension is induced only during excision of the deep
part of the tumour. (For about 1-5 min)
– The doses of inhalational isoflurane (1.5–2.5%) and
nitroglyercin infusion (50–100 mg/min) are increased
to achieve target MAP
• Disadvantages:
– Patients with cardio- and/or cerebrovascular
comorbidities vulnerable to hypotension-related
complications
– Use of electrocautery to incise the renal cortex during
tumour excision creates a variable amount of charring,
primarily along the anterior aspect of the surgical
margin with the potential of compromising pathologic
evaluation of tumour margins
– Some bleeding does occur due to the patent renal artery
and vein. This requires deft suction irrigation and
technical facility with suturing
Haemostasis and PCS suturing
• Utilization of Hem-o-lok clips and Lapra-Ty clips
• Use of barbed suture (Quill or V-Loc)
• Fibrin sealants
– Allow rapid clot formation when applied to a bloodless
surgical field
– Induce fibroblast migration
• Floseal
– Human thrombin and bovine gelatin
– Swells after application providing an additional benefit
of mechanical tamponade
• Polyethylene glycol-based sealants and albumin
gluteraldehyde-based sealants
– Undergo covalent polymerization
– Reduce bleeding and urinary leaks during PN
• Oxidized cellulose
– Mechanical tamponade and surface for platelet adhesion
• C ombination of Floseal with rolled bolster
Comparison between OPN and LPN
• OPN seems to be the safest surgical access with
acceptable postoperative renal function in solitary
kidney.
• Factor influencing postoperative renal function in
solitary kidneys is the time since loss of the
contralateral kidney.
• Patients with congenital solitary kidneys or with loss
of the contralateral kidney 1 yr before surgery have
more favourable postoperative renal function,
explained by the development of a compensatory kidney
hypertrophy that seems to develop within the first year
after surgery
• Higher complication rates after LPN , longer ischaemia
times, even though mean tumour diameters were
smaller.
• Negative aspects of OPN are higher blood loss, longer
operation time, longer hospital stay, and higher
analgesic requirement.
• Renal function after both procedures seems to have been
equivalent in these series
• If a high risk of CKD is expected, OPN should be the
preferred approach because a multivariate analysis
showed a decrease in GFR of of 2.2 ml/min per 1.73m2
for every 5 min of WI.
Laparoscopic Partial Nephrectomy (LPN)
• Open partial nephrectomy remains the standard for NSS
• LPN has emerged as a viable alternative in selected
patients
• Renal function and early oncological outcomes are
equivalent
• Advantages:
– Shorter hospitalization
 The Urology Masterclass, Department of Urology, CMC, Vellore 93

– Quicker convalescence Augmented Reality Navigation Systems

– Lower narcotic requirement • Fuses the anatomic detail of preoperative 3-D imaging
– Improved cosmesis of CT or MRI with the real-time information of 2-D
intraoperative ultrasound
– Earlier diet resumption
• Synchronous viewing of the real-time ultrasound image
with the corresponding tomogram slice side by side
• Disadvantages:
• Potential to guide the dissection trajectory for safe and
– Technically challenging accurate tumour excision in PN
– Higher rate of intra operative complications • A color-coded zonal navigational system has been
– Longer warm ischemia time developed
– Increased bleeding rate – Surgical target: Red
– Increased urinary leak – <5mm of the target: Yellow
– Steep learning curve – 5–10mm from the target: Green
– > 10mm from the target: Blue
• Newer Developments:
– Hand assisted lap partial nephrectomy Bilateral RCC
o Quicker learning curve Rationale for management
o Allows compression of parenchyma with hand • No difference in cancer-specific survival (CSS) between
o May not need clamping patients with bilateral RCC and patients with unilateral
sporadic RCC
• Bilateral solid renal tumours presents a challenge of
– Robotic partial nephrectomy balancing the need for complete eradication of
o 3-D vision potentially malignant tissue with the goal of maximal
o 540 degree movement preservation of renal function.
o Tremor elimination
Which side first?
– LESS • Suggested protocol:
o Still in infancy • Bilateral NSS to preserve renal reserve
o Loss of triangulation makes it difficult • If the tumour is unfavourable, RN of renal mass
• Option 1: NSS of the more favourable tumour, followed
Pre-operative 3D Image Navigation by NSS or RN of the less favourable contralateral tumour
within 6 weeks
• Based on 0.5-mm-slice thickness computed tomography
scans • It allows the patient to recover from possible acute renal
failure after NSS
• Novel three-dimensional (3D) reconstruction technique
that fuses three key anatomic aspects:
– Surface-rendered tumour • Option 2: RN followed by NSS
– Semi-transparent kidney and • Immediate treatment of the potentially more aggressive
tumour, and allows the prognosis to be assessed from
– Extra- and intrarenal arterial anatomy the pathological features of the unfavourable tumour
• Especially for laparoscopically invisible masses, 3D
image navigation precisely identified tumor specific
arterial branches, facilitating zero-ischemia partial • Option 3: Simultaneous surgery via a laparotomy/
nephrectomy laparoscopy

Intra-operative USG and Doppler Results of treatment

• Delineates tumour, normal parenchyma, collecting
system, and vasculature in an accurate real-time
fashion
• Reduces time to hilar dissection and alters clamping
approach during LPN
• Limited by its dependence on the performance and
interpretation
• CSS 86% at 5 years for bilateral PN.
• Bilateral partial nephrectomy had superior renal
functional preservation.
• Tumour size greater than 7 cm and postoperative CKD
stage III or greater associated with decreased OS due
to non-cancer causes.
• Preservation of renal function had an equivalent, if not
more profound, impact on OS compared to oncological
control.
 94 The Urology Masterclass, Department of Urology, CMC, Vellore

Factors that predispose to postoperative CKD after PN

– Age
– Gender
– WIT
– Tumour size
– Residual parenchyma
– Preoperative renal function

Hyperfiltration injury
• Glomerular hyperfiltration - GFR of more than two SD
above mean of healthy individuals.
• Caused by afferent arteriolar vasodilation and/or by
efferent arteriolar vasoconstriction.
• Glomerular hyperfiltration might directly contribute to
the progression of CKD.
• Long term therapy with angiotensin-converting-enzyme
inhibitors (ACEIs) or angiotensin-receptor blockers
(ARBs) promotes regression of glomerulosclerosis

References
1. Hung AJ et al. Curr Opin Urol 2013
2. Campbell Walsh Urology 11th edition
3. Venkatramani V et al. Indian J Surg Oncol 2017
4. Gschwend JE et al. J Urol 1995
5. Janssen MW et al. WJSO 2018
6. Kijvikai K et al. J Urol 2010
7. Gill et al. J Urol 2003
8. Janteschek G et al. J Urol 2004
9. Eisenberg MS et al. Curr Opin Urol 2011
10. Ng CK. Eur Urol 2012
11. Borofsky MS et al. BJUI 2013
12. Campbell Walsh Urology, 11th ed
 The Urology Masterclass, Department of Urology, CMC, Vellore
TESTICULAR CANCER
CARCINOMA TESTIS
• Only 1–10% of all patients with testicular tumours
present exclusively with symptoms of metastases.
• Extragonadal germ cell tumours (EGCTs) with no
clinically apparent primary testicular tumour are rare.
• Of the patients with metastatic GCT without a testicular
mass:
- 1/3rd has ITGCN in the testis
- 1/3rd has ultrasonographic evidence of a “burned
out” primary tumor
- 1/3rd definitively has a primary extragonadal GCT
• Primary mediastinal non-seminomatous germ cell
tumors are more aggressive than primary testicular
cancer and are more resistant to chemotherapeutic
agents.
• In men with advanced GCT and a normal testicular
examination, scrotal ultrasonography should be
performed to rule out the presence of a small,
impalpable scar or calcification, indicating a “burned
out” primary testicular tumor.
• Non-identification of primary testicular tumor in
presumed extragonadal germ cell tumours carries the
danger of persistent testicular malignancy in up to 50%
of such patients despite systemic chemotherapy.
• Metastatic disease secondary to burned-out lesion has
the same prognosis as a primary testicular malignancy.
• Testicular lymphatic drainage in patients with
horseshoe kidney does not differ from that in normal
individuals except in rare instances of an absent or
duplicated inferior vena cava.
• If such venous anomaly is present, bilateral RPLND is
recommended with upper limit at the level of the
pancreas due to unpredictability of lymphatic drainage.
95
• Division of the isthmus is not necessary and is
contraindicated in the presence of functioning isthmic
parenchyma. This manoeuvre carries risk of
hemorrhage and urinary fistula formation.
Post chemotherapy residual mass in NSGCT
• Post chemotherapy residual disease (PCRD): -
• Retroperitoneum (30%)
• Lungs (27%)
• Mediastinum (15%)
• Neck (4%), liver (2%) bones (1%) and brain (0.5%)
• Following first-line BEP chemotherapy, only 6-10% of
residual masses contain viable cancer, 50% contain
mature teratoma, and 40% contain necrotic-fibrotic
tissue
• 18 FDG-PET; reported up to 40% of false negative rates-
No role
• Surgical excision of PCRD is the standard of care in
metastatic NSGCT if tumour markers levels have fallen
to the normal range
• Residual tumour resection is mandatory in all patients
with a residual mass > 1 cm at cross-sectional CT
imaging
• Presence of residual cancer is a poor prognostic sign
as compared to other histologies of necrosis/fibrosis
or teratoma.
• 10-year survival isf 43% for patients with viable cancer
cells compared with 86% and 84% for patients with
necrosis/fibrosis and mature teratoma respectively
• In persistent larger volume retroperitoneal disease, all
areas of primary metastatic sites must be completely
resected within 4-6 weeks of completion of
chemotherapy
• If technically feasible, a nerve-sparing procedure should
be performed Within 10 days of CT scan and 5 -7 days
of markers
 96 The Urology Masterclass, Department of Urology, CMC, Vellore
Pulmonary resection
• Histologic discordancebetween RPLNDand thoracotomy
in 27 of 93 (29%) patients; 14% with necrosis in
retroperitoneum had teratoma in the chest
• If one side shows only necrosis, the other side may be
followed up
• 3 of 8 patientswith bilateral thoracotomies had
different histology on each side
• Bleomycin associated toxicity – Low FiO2 and judicious
fluids post op
Timing of RPLND
• In persistent larger volume retroperitoneal disease, all
areas of primary metastatic sites must be completely
resected within 4-6 weeks of completion of
chemotherapy. If technically feasible, a nerve-sparing
procedure should be performed
• Within 10 days of CT scan and 5 -7 days of markers
Follow up after post chemotherapy RPLND
• 1st and 2nd year – Physical examination, tumor markers
and CXR threemonthly, Abdominal CT 6monthly, Chest
CT as indicated
• 3– 5 years - Physical examination, tumor markers and
CXR six monthly, Abdominal CT and Chest CT as
Indicated
• After year 5 – Annual Physical examination, tumor
markers and CXR, Abdominal CT and Chest CT as
Indicated EAU guidelines, 2013
Pre operative preparation
• Intent for complete resection
• Pre operative assessment of pulmonary function
• Involvement of Multidisciplinary faculty to plan the
operation
– Vascular surgeons
– Gastrointestinal surgeons
– Urologist
• Secure blood and SICU bed pre operatively
• Complete tumor resection is critical
• provides local control of residual disease
• guide to the necessity for additional chemotherapy
• Resection of seminomatous elements is technically
challenging
• Severe desmoplastic reaction between the regressing
mass and the adjacent vascular and visceral structures.
• Seminomas higher frequency of additional
intraoperative procedures and an increased rate of
postoperative complications.
• Additional nephrectomy and vascular procedures such
as partial or complete resection of the vena cava and
placement of aortic prosthesis
• 38% Seminoma
• 25% NSGCTs
RPLND with Aortic involvement
• Aortic involvement 2%
– Can be extremely difficult when aortic adventitia is
involved.
• Usually possible to skeletonize the aorta - occasional
arterial injury results.
• Magnetic resonance imaging most appropriate imaging
technique
• Difficult to state on CT – Decision often made intra
operatively
• Aortic/iliac artery replacement with a synthetic
prosthesis is easy with modern vascular techniques.
• Aortoenteric fistula
• cover the aortic graft completely with soft tissue
– Greater omentum
– A rectus abdominis pedicle flap
• Additional surgical procedures necessary such as
nephrectomy, small bowel resection and hepatic
resection often necessary RPLND with Vena caval
involvement
• In about 6-10 % cases
• Resection required in about 6.8 %
• More for right testicular primaries
• Should be completely resected about 2/3rd of patients
harbor vital cancer or mature teratoma
• IVC reconstruction
– Polytetrafluoroethylene (PTFE) graft
– Few graft-related complications and
– Relatively good long-term patency,
– Technical excellence required, adds significant time
and complexity to a tumor resection,
– Aggressive graft surveillance is mandatory
– Obliterated vessel and massive collateral venous
drainage makes tumor resection less hazardous
• Complications
– Immediate venous congestion of the lower extremities
– Abdominal ascites
Complications of RPLND
Wound infections,
Paralytic ileus,
Transient hyperamylasemia,
Pneumonitis / atelectasis,
Significant complications (<2%)
Acute renal failure,
Chylous ascites
Obstructive ileus
Post chemotherapy residual mass in Seminoma
• Cisplatin based chemotherapy has >90% cure rate
• 58-80% - residual masses: 50-60% masses
spontaneously resolve
• <10% of them will relapse (majority within 2 years)
• A residual mass of seminoma should NOT be primarily
resected, irrespective of the size, but controlled by
imaging investigations and tumour markers
 The Urology Masterclass, Department of Urology, CMC, Vellore 97

• False positive results are less frequent when scans are RPLND with Aortic involvement
scheduled > 2 months after chemotherapy • Aortic involvement 2%
• In patients with residuals of > 3 cm, FDG-PET should be • Can be extremely difficult when aortic adventitia is
performed in order to gain more information on the involved.
viability of these residuals
• Usually possible to skeletonize the aorta – occasional
• In patients with residuals of < 3 cm, the use of FDG-PET arterial injury results.
is optional
• Magnetic resonance imaging most appropriate imaging
• Viable cancer is seen in: technique
– 12-30% >3 cm • Difficult to state on CT – Decision often made intra-
– 0-10% <3 cm operatively
• In the case of a post-chemotherapy mass that is still • Aortic / iliac artery replacement with a synthetic
positive at reclassification FDG-PET with no volume prosthesis
increase, a second FDG-PET should be performed six • Aorto-enteric fistula
weeks later
— Cover the aortic graft completely with soft tissue
– Greater omentum
Limitations of PET
– Rectus abdominis pedicle flap
• Inflammatory and granulomatous tissues show
• Additional surgical procedures necessary such as
extensive FDG uptake
nephrectomy, small bowel resection and hepatic
• Lesions <1 cm can often go undetected resection often necessary in RPLND with vena caval
• Mature teratoma is indistinguishable from normal and involvement
necrotic tissue —In about 6-10 % cases
• Alternatively, a biopsy should be taken to ascertain —Resection required in about 6.8 %
persistent disease
—More for right testicular primaries
• If this is positive salvage chemotherapy/ RT is indicated
—Should be completely resectable in about 2/3rd of
• In cases in which RPLND is indicated, this should be patients
performed in referral centres, as residuals from
• IVC reconstruction
seminoma may be difficult to remove due to intense
fibrosis (58-74% complete resection rates) – Polytetrafluoroethylene (PTFE) graft
– Few graft-related complications and relatively good
long-term patency,
Pre operative preparation
– Technical excellence required, adds significant time
• Intent for complete resection
and complexity to a tumour resection,
• Pre operative assessment of pulmonary function
– Aggressive graft surveillance is mandatory
• Involvement of Multidisciplinary faculty to plan the
– Obliterated vessel and massive collateral venous
operation
drainage makes tumour resection less hazardous
– Vascular surgeons
• Complications
– Gastrointestinal surgeons
– Immediate venous congestion of the lower extremities
– Urologist
– Abdominal ascites
• Secure blood and ICU bed pre operatively
• Complete tumor resection is critical
Complications of RPLND
• Provides local control of residual disease
Wound infections,
• Guide to the necessity for additional chemotherapy
Paralytic ileus,
• Resection of seminomatous elements is technically
Transient hyperamylasemia,
challenging
Pneumonitis / atelectasis,
• Severe desmoplastic reaction between the regressing
mass and the adjacent vascular and visceral structures.
• Seminomas higher frequency of additional intra- Significant complications (<2%)
operative procedures and an increased rate of post- Acute renal failure,
operative complications. Chylous ascites
• Additional nephrectomy and vascular procedures such Obstructive ileus
as partial or complete resection of the vena cava and
placement of aortic prosthesis: 38% Seminoma, 25%
NSGCTs
 98
Indication for PET
• Both EAU and AUA guidelines recommend PET for all
post-chemo residual masses in seminoma
• RPLND only if PET positive
• PET/CT has not yet been proven superior to PET alone in
this setting
Accuracy of PET
PET CT
Specificity 92% 59%
Sensitivity 80% 63%
PPV 70% 28%
NPV 93% 86%
Limitations of PET
• Inflammatory and granulomatous tissues show
extensive FDG uptake
• Lesions <1 cm can often go undetected
• Mature teratoma is indistinguishable from normal and
necrotic tissue
• Increased pulmonary uptake may be seen in patients
with early BIP
3. SCROTAL VIOLATION
Definition:
Any trans-scrotal approach to the scrotal contents in the
setting of testicular carcinoma, including
• Open testicular biopsy,
• Trans-scrotal orchidectomy and
• Fine needle aspiration.
Incidence:
4 to 17%
Types of scrotal violation:
• Two groups
– With tumor contamination, such as open tumor
biopsy or tumor spillage due to cutting into the
tumordefined as the poor prognosis group
– Without any tumor spillage, contamination, or
positive surgical margins—the good prognosis group.
• Scrotal violation per se is not an exclusion criterion
for the surveillance only policy in patients with Stage I
Non-seminomatous testicular germ cell cancer.
• Scrotal violation was associated with an increased risk
for local recurrence mainly when a residual tumor in
the scrotectomy specimen was found.
• Hemi-scrotectomy is unnecessary in patients who
receive systemic chemotherapy, and in those who elect
surveillance
• No patient treated by chemotherapy had local
recurrence.
For Stage I Seminoma and NSGST
• In the absence of gross tumor spillage, close
observation alone may be adequate management for
scrotal violation
• The role of hemi-scrotectomy to avoid local or systemic
relapse is debatable.
The Urology Masterclass, Department of Urology, CMC, Vellore
• In patients with low stage seminoma the radiation
portals should be extended to include the ipsilateral
groin and scrotum. This may result in an increased risk
of azoospermia
• Recommended follow-up as per schedule in a
surveillance policy: stage I non-seminoma.
• No role of X Ray chest in stage I seminoma surveillance.
4. INGUINAL NODE INVOLVEMENT IN TESTICULAR TUMOR
Risk factor for inguinal nodal involvement:
• Scrotal/ inguinal violation: 2-10%
• May be associated with
– Tumor extension into the epididymis
– Breaching of the tunica vaginalis through to the
scrotal wall
– Extension to the vas deferens
– Secondary retrograde fashion, usually when there
are bulky retroperitoneal metastases
5. GROWING TERATOMA SYNDROME (GTS)
Definition: GTS should be suspected
x Rapid increase in size of metastatic lesions during or
after appropriate systemic chemotherapy
x Normal serum tumor markers
x H/O NSGCT
Presence of teratomatous elements in orchiectomy
specimen highly suspicious
Confirmation of diagnosis
x By the presence of mature teratoma and absence of
malignant germ cells on final HPE of surgical resection
specimen
Etiopathogenesis: Unclear
Three most-quoted theories
1) Preferential destruction of immature malignant cells
by chemotherapy, sparing the mature benign
teratomatous elements
2) Alteration of cell kinetics by chemotherapy resulting in
transformation of totipotent malignant germ cell into
a benign mature teratoma
3) Inherent “Spontaneous differentiation” of malignant
cells into benign tissues
Incidence: 2.2% (1.9-7.6%)
Mostly seen in retroperitoneum, but also described in
x Lung & mediastinum
x Supraclavicular & inguinal lymph nodes
x Mesentery, liver & forearm
Clinical presentation
x Reported early during the chemotherapy to as late as
12 years post chemotherapy
x May also develop after PC-RPLND
x No specific criteria for rate of growth
x Reported median increase in diameter 0.7 cm/month
(12.9 ml/month)
x Clinical behaviour is unpredictable for aggressive local
spread
 The Urology Masterclass, Department of Urology, CMC, Vellore
x Tend to engulf and compress the nearby important
structures
x Potential malignant degeneration
Management
x Chemotherapy & radiation therapy- Not effective
x Total resection is curative
x Rate of recurrence
o 0-4% after complete resections
o 72-83% partial resections
x 5-year overall survival following complete surgery is
89%
x Mortality mainly related to post-operative
complications
Surgical approaches
x Resection of mass only
x Template-type dissection
x Complete bilateral dissection (preferably nerve
sparing)
x Full, bilateral template RPLND (nerve sparing if
possible)- preferred in most patients due to
x Rare chance of residual malignant component in the
post-chemotherapy setting
x Potential malignant degeneration
Outcome - Good outcomes depends on
x Awareness of this condition
x Vigilant imaging on chemotherapy for NSGCTs. Axial
imaging after 2 cycles recommended
x Early recognition of paradoxical response to
chemotherapy (enlarging tumors and normal tumor
markers)
x Early diagnosis
x Prompt and complete surgical resection of tumors
6. TESTICULAR MICROLITHIASIS
What is testicular microlithiasis?
x TML is a condition in which calcium deposits form in
the lumina of seminiferous tubules or arise from the
tubular basement membrane components
x Definition: Five or more microliths per field of view
Epidemiology
x Ultrasonic appearance of testicular microlithiasis in
1987 as “innumerable tiny bright echoes diffusely and
uniformly scattered throughout in the substance of
testes” Using high frequency transducer (10 MHz).
x Autopsy studies –
o testicular microliths in 0.04-11.8% of prepubertal
boys
o 3% of adult males.
x Peterson et al. found the prevalence of testicular
microlithiasis to be 5.6%
Ultrasound diagnostic criteria
x Greater than five calcifications per image field,
x Calcifications less than 2 mm in diameter
99
x Diffuse in nature
x No acoustic shadowing
x No loss of testicular shape or volume.
Grading of testicular microlithiasis
x Minimal/mild (Grade I: 5 to 10 microliths)
x Moderate (Grade II: 10 to 20 microliths)
x Severe (Grade III: >20 microliths)
Depending on the microliths count as seen in any single
view
Significance of Testicular microlithiasis
x Infertility
o Frequency of TML in patients with infertility or
undescended testis : 7-39%
x Fertility potential may be decreased by :
o mechanical obstruction of seminiferous tubules with
microliths
o atrophy of uninvolved tubules with spermatogenic
arrest
o Incidental discovery of TM should not change the
treatment of infertility.
TML and malignancy
x Brazao et al. reported a 40-fold higher prevalence of
CIS in men with bilateral TML compared to those without
TML (20% vs. 0.5%).
x Testicular microlithiasis has been linked to a common
developmental defect of the seminiferous tubules and
defined as part of the “Testicular dysgenesis syndrome”
o testicular cancer, genital abnormalities, sub-fertility
and reduced sperm quality
Indications of biopsy
Biopsy should be done only if detection of CIS will be
followed with treatment.
1. Ipsilateral tumor and TM in the contralateral testis
2. TM with gonadal dysgenesis and other chromosomal
anomalies
3. TM in infertile men and patients with cryptorchidism
or atrophic testis
4. Focal, clumped and unilateral TM without mass
5. Grade IV or V pattern in testicular ultrasonography
6. Classic TM - Grade 3 in microlithiasis count (>20)
Risk factors that warrant follow-up of men with TML
x Previous germ cell tumour
x History of maldescent
x History of orchidopexy
x Atrophy <12 ml(normal 12-30 ml,Mean-18 ml)
x History of germ cell tumor in First deg relative
Guidelines for follow up
x If testicular malignancy is absent in the first evaluation,
TM can be followed up with regular self-examination
of testes.
x Further evaluation and biopsy is indicated only for the
high-risk group.
 100 The Urology Masterclass, Department of Urology, CMC, Vellore

x If any change is noted by the patient, serum markers

may be performed.
x In case of elevation of tumor markers, biopsy can be
done to rule out CIS provided there is intent to treat.
Options in management of CIS/TIN
x Chemotherapy
o Benefit is poor ineradicating TIN.
o The failure rate of 64%
x Radiotherapy
o Solitary testis
o 16-20Gy
x Orchidectomy
o If contralateral testis is normal
x Active surveillance
Active surveillance
o Patients with TML, who are asymptomatic and are
not at high risk of development of CIS and invasive
tumor - regular self-examination and prompt
reporting to the physician in case of appearance of
any new lesions
x TML detected during routine ultrasound evaluation -
does not warrant biopsy
 The Urology Masterclass, Department of Urology, CMC, Vellore 101

UROTHELIAL CARCINOMA
Urothelial carcinoma bladder
• T1G3 - 20% of all bladder cancer – 67,000 cases per EORTC risk factors
year world- wide
• Long-term progression and death rates for high-grade
T1 are about 53% and 34% respectively
• Up to 30% of all high grade T1 will progress even with
intravesical therapy (60% without BCG
High-risk Disease
Factor Risk
Size > 3cm HR = 2.5 for progression
Multifocality (4 or more) HR = 1.7 for progression
HR = 3.4 for progressionHR =
CIS 2.5 for death, 50% progression
at 5yr
Hydronephrosis HR = 2.4 for progression
Each recurrence associated
Prior recurrences
with 5-10% risk of metastases
pT1 on re-staging TURBT HR =6.9 for progression
82% risk of progression if no
BCG refractory
response at 3 months
Early prostatic urethral
20% 5yr survival
recurrence
pT1b tumours 53% risk of progression
Micropapillary, sarcomatoid,
Aggressive variants
small cell. nested

Role of second TURBT

Indication
Any T1; Any G3
Deep muscle not seen on specimen
Rationale
Upstaging to >T2 in 10-20% patients
Residual disease in 33-53% of high grade tumours
Timing
2-6 weeks after initial TURBT
 102 The Urology Masterclass, Department of Urology, CMC, Vellore

Outcomes of BCG in T1HG • Disease specific death rate

• Recurrence rate • Connaught strain prevented recurrence better than Tice
– 33% at 1 year and 57% at 5 years if 4 or more tumours in an RCT (RFS 74% vs. 48%)
initially and more than 1 prior recurrence/yr – 4.8% at 1 year
– 13% at 1 year and 28% at 5 years if < 4 tumours and less – 11.3% at 5 years
than our equal to one prior recurrence/yr Cambier S et al Eur Urol 2016 Jan
• Progression Rentsch Eur Urol 2014
– 11.4% at 1 year Sylvester et al J Urol 2002
– 19.8% at 5 years
(Without BCG, recurrence: 50-80%, progression: 30-60%)

Mechanism of BCG action

Redelman-Sidi et al. Nat Rev Urol 2014

 The Urology Masterclass, Department of Urology, CMC, Vellore
BCG in primary CIS
• Complete response rate in 71-85%
• Five year recurrence free rate among responders – 63-
75%
• In long term follow up initial BCG responders – 25%
will be muscle invasive at 10 years and disease specific
mortality of 15% at 10 years
• Gofrit et al. Urol Oncol 2009 May
• Takenaka et al. Int J Urol 2008
• Losa et al. J Urol, Jan 2000
• Lamm et al, 1992
Risk of recurrence with BCG therapy
• Female gender, HR=1.71
• Recurrent tumours, HR =1.9
• Multiplicity, HR 1.29
• CIS, HR = 1.54
• Tumour size >3cm , HR=1.33
• Maintenance BCG, HR=0.66
• Palou, J., et al. Eur Urol, 2012. 62: 118.
Timely cystectomy
• Radical cystectomy has been traditionally termed early
cystectomy when performed before the traditional
indication of documented muscle invasion.
• Residual disease on second TUR 27-78%
• Risk of understaging in TaT1 tumours 35-62% (Higher if
no muscle in TURB specimen- 14 vs. 49%)
• Cancer-specific survival (CSS)
– 35% at 4 years in those who progress from high-
grade T1
– Vs. 67% in primary T2
– Vs. 80% in timely cystectomy
• Even after 1-3 yrs of BCG in high grade tumours, one-
fifth progress at 5 years
• 1/3rd die despite BCG
103
• For CIS, although the initial response rate to BCG can
be >80%, patients fail treatment have 50% chance of
disease progression and attendant mortality.
• Surveillance is costly and inconvenient
• Timely cystectomy
– CSS of 80% at 5-yr and 76-78% at 10-yr
• Deferred cystectomy
– CSS of 69% at 5 yrs and 51-61% at 10 yrs
• Upstaging after timely cystectomy seen in 10-50%
• Obviates the need for intravesical therapy and
simplifies follow-up
• BCG only delays progression but does not prevent it
• Fritsche, H.M., et al. Eur Urol, 2010.
• Turker, P., et al. BJU Int, 2012. 110: 804.
• Shariat, S.F., et al. Eur Urol, 2007. 51: 137
• Fernandez-Gomez, J., et al. J Urol, 2009. 182: 2195
Candidate for timely cystectomy:
• High-risk group of EORTC (pT1b, LVI, high grade, >3 cm,
multifocal, CIS, recurrent)
• BCG failure
• Prostatic urethral involvement
• Hydronephrosis
• Tumour at sites difficult to resect/ urethral stricture
• Non-compliant for surveillance
• Poor bladder function
• Variant histology
Cons of early cystectomy:
Morbidity of 40% and mortality of 1-2%
TURBT with BCG has acceptable long-term survival (70-
80% at 5yr) in most patients
Over-treatment in one-third of cases
104 The Urology Masterclass, Department of Urology, CMC, Vellore
 Definition of Median 5 yr CSS
Upstaging 5 yr CSS Prognostic
Author N early follow-up N+% (deferred)- p
% (early)- % factors
cystectomy (months) %

Amling (1994) 166 - - 30 7 76 - - Stage

Freeman(1995) 182 - 86 34 8 83.6 - - Stage, LVI
Herr (2001) 90 <24 months 180-240 61 - 75 34 0.001 Stage
Thalmann Recurrent,
56 < 3 months 47 48 16 69 80 0.02
(2004)* multiple
Masood (2004) 30 ‘Immediate’ 57 27 0 88 - - Multiple, CIS
Bianco (2004) 66 - 48 27 9 78 - - CIS
Gupta (2007) 167 - 34 50 18 82 - - CIS
The Urology Masterclass, Department of Urology, CMC, Vellore

Denzinger >3cm,
105 - 65 26 vs 35.3 - 83 67 <0.01
(2008) multiple, CIS
Hautmann Delayed
274 <3 months 58 29 vs 64 9 vs 20 84 75 -
(2009) cystectomy
Age, gender,
Fritsche (2010) 1136 - 48 51 16 82 - -
LVI
More TURTs,
Jager (2011) 278 <4 months 48 34 13 86 72 0.03
stage
Sternberg Residual
150 <3 months 45 14 vs 8 3 vs 5 85 89 -
(2012)* disease
Daneshmand
222 - 172 0 6 81 (RFS) - - LVI
(2013)
105
 106 The Urology Masterclass, Department of Urology, CMC, Vellore

Muscle invasive urothelial carcinoma bladder with urethral

recurrence

Choice of urinary diversion

Does not affect oncological outcome
Ileal conduit still the gold standard.
Factors to be considered

Cancer control General health Technical Quality of life

Risk of local Functioning
Age Compliance
recurrence urethra
Previous pelvic
Previous surgeries Tumor location Sexual function
radiation
Need for adjuvant Renal/hepatic Ability to
Body image
therapy function catheterize
Secondary Medical
Mesentery length Urinary function
malignancies comorbidities
Status of
Urethral or gastrointestinal Bowel condition Family support
bladder neck tract
involvement
Body habitus Operative time Daily maintenance

For Continent diversion

Absolute contraindications
Impaired renal function (creatinine clearance ч50 mL/minute or serum creatinine
ш2.0 mg/dL)
Impaired hepatic function
Physical or mental impairment to perform self-catheterization
Positive apical urethral margin (for neobladder)
Unmotivated patient
Relative contraindications
Associated comorbid conditions
Advanced age
Need for adjuvant chemotherapy
Prior pelvic radiation
Bowel disease
Urethral pathology
Extensive local disease with soft tissue extension and high risk of local recurrence
 The Urology Masterclass, Department of Urology, CMC, Vellore 107

Neoadjuvant chemotherapy MVAC vs GC:

Advantages
• Better tolerated with less toxicity.
• Able to receive full dose and cycles.
– 40% patients will show decline in renal function after
radical cystectomy, precluding cisplatin
• Primary tumor evaluated for response which has
prognostic significance.
• May downstage tumours – Complete response occurs
in 30-40% - better prognosis
• No increase in surgical complications or difficulty in
radical cystectomy
• 5% survival benefit
Disadvantages
• Over-treatment in some cases
• Potential for disease progression in patients with
chemo-resistant disease
• Dynamic contrast-enhanced MRI is promising
• Chemo-related complications, such as infections,
which may potentially delay RC
• MVAC in neo-adjuvant setting has level I evidence.
Although GC lacks prospective phase III randomized
data to support its use.
• Pathological down-staging to pT0
– MVAC 38%
– GC 26%
• Better toxicity profile of GC; grade 3/4 granulocytopenia
– MVAC 57%
– GC 38%
Carboplatin as neo-adjuvant chemotherapy
Substitution of cisplatin with carboplatin in patients with
renal dysfunction - not recommended.
• These patients should forego neoadjuvant
chemotherapy and proceed immediately to definitive
local therapy.
• 8% absolute improvement in survival at 5 years. NNT –
12.5
• Combination regimens provide survival benefit
compared to cisplatin alone
• Similar T0/T1 rates in GC as compared to MVAC
• Yin, M., et al. Oncologist, 2016. 21: 708

Two meta-analysis
• ABC meta-analysis, 2005 – 5% OS benefit at 5 years
• Yin et al 2016 – 8% OS benefit at 5 years

Trial Regimen Results in terms of survival

MRC BA06/EORTC 30894 CMV 6% improvement in

absolute survival at 10y
SWOG 8710 MVAC 14% benefit at 5 yrs

Nordic I Cis + Doxorubicin + RT Overall no benefit – 15%

benefit in survival in T3-4a
Nordic II Mtx+ Cis No overall benefit
 108
Adjuvant chemotherapy
• 30% of patients have a complication severe enough
after radical cystectomy to interfere with administration
of chemotherapy
– One-third will not receive chemotherapy
Extent of lymph node dissection
• What constitutes adequate LN dissection?
– AJCC – At least 12 LN should be removed
– EAU – Minimum 9 LN needed to determine N0 status
• There is no added benefit of extended LND compared to
standard LND in terms of recurrence
§ LEA trial Eur Urol, April 2019
• No added benefit for the super-extended template
compared to extended template
• EAU guidelines provide no guidelines with this regard
• Results of SWOG 1011 trial are awaited
LEA trial
• Phase 3 RCT, 16 centres in Germany
• Efficacy of limited vs extended LND
• T1G3 or T2-T4a
• T4b and neoadjuvant chemo was excluded
• Limited LND – Obturator, internal and external
• Extended LND – Limited LND + LND till IMA
• Designed to show absolute improvement of 15% in 5 yr
recurrence free survival by extended LND
• 5 yr RFS – 64.6% in ELND vs 59.2% in LLND
• 5yr CSS – 75.9% in ELND vs 64.5% in LLND
• 5yr OS – 58.9% in ELND vs 49.7% in LLND
• Median OS – 70.6 mo in ELND vs 52.2 mo in LLND
Trimodality bladder preservation protocol
TURBT + RT(regional control) + Chemo (systemic)
Aim to preserve bladder and QOL without compromising
oncological outcome
Proper selection with T2 lesions with no CIS, no HN,
complete TURBT, good bladder function
Needs strict follow up and motivated patient
Complete response in 60-72% and survival at 5 yrs 50-75%
Can be considered in patients were RC is contraindicated
For CR and near CR – 35% recurrence at 5.9 years
Urethral recurrence
• Can be symptomatic or asymptomatic. Symptoms if
present
• Urethral bleeding of discharge – 80%
• Pain- 32%
• Less common – penile mass, changes in urinary habits
with ONB
The Urology Masterclass, Department of Urology, CMC, Vellore
Urethral recurrence in males:
Rate 4-17% (average 6-7%)
40% recur within the first year, majority by 3 years
Symptomatic recurrence usually suggests an advanced
stage
Median survival 28-53months
5 year survival 35%-43%
The only absolute indication for urethrectomy is a positive
apical urethral margin
• Eur Urol. 2011 Dec;60(6):1266-72
• J Urol 2005 Apr;173(4)
Risk factors
1. Multifocal disease
2. Type of urinary diversion
3. Prostatic urethral involvement
• However a meta-analysis in 2018 showed only male
gender and non orthotopic reconstructions as a risk
factor for urethral recurrence.
• Chan et al. BJUI April 2016
• Fahmy et al. Urol Oncol. Feb 2018
Is prostate biopsy necessary during TURBT?
• Indications for prostatic urethra biopsy in TCC bladder:
– Cytology positive but no tumour on cystoscopy
– Bladder neck involvement
– Multifocal disease
– Prior to consideration of orthotopic neobladder (frozen
section slightly better)
• Procedure
– 5 and 7 o’clock in pre-collicular area with resection loop
Urethral recurrence in females:
Recurrence rate 4.7% -12 %
Traditionally cystectomy in females includes urethrectomy
In orthotopic neobladder, urethrectomy can be avoided in
cases with a negative margin on frozen section
Cancer in the urethra or a T4 tumour involving the anterior
vagina is a contraindication to preservation of the urethra
and orthotopic reconstruction
Urethral surveillance
No recommendations in current guidelines
No definite survival benefit and recurrence rates are too
low to warrant routine surveillance.
Urethral wash cytology – most commonly used for
monitoring urethral recurrence
Management of urethral recurrence
• If cutaneous diversion – urethrectomy and removal of
navicular fossa
 The Urology Masterclass, Department of Urology, CMC, Vellore 109

• In patients with ONB –with low grade, non- invasive • The LND template is likely to have a greater impact on
• TUR patient survival than the number of lymph nodes
removed
• Intraurethral instillations of 5FU
• Lymph node dissection in cases of Ta&T1 disease is not
• BCG treatment
required as lymph node retrieval is only 2.2% T1 versus
• If high grade, invasive 16% pT2-4 tumours.
• Urethrectomy and conversion to cutaneous diversion • The anatomical sites of LND have not yet been clearly
defined however, LND can be achieved according to
Upper tract urothelial carcinoma lymphatic drainage as follows:
• Cystoscopy is mandatory to exclude co-existent bladder • LND medially to the ureter in uretero-pelvic tumour
lesions • Retroperitoneal LND in case of higher ureteral tumour
• RGP with or without cytology and biopsy has 75% and
accuracy in diagnosing UTUC • Tumour of the renal pelvis (i.e., right side: border vena
cava and left side: border aorta)
Cytology
• Cytology of voided specimen less sensitive for UTUC Prognostic factors-Preoperative
than for bladder tumours, even for high-grade lesions • Multifocality
• It should ideally be performed in situ (i.e. ureteral • Grade (biopsy, cytology)
catheterisation and collection of urine or washings) • Advanced age
• Saline washing provides better cell yield and improve • Tobacco consumption
cytology.
• ECOG - PS 1
• Brush biopsy through retrograde catheter or
• Co-morbidity (ASA score)
ureteroscope, has sensitivity & specificity of 90%
• Hydronephrosis
• Urine cytology of the renal pelvis and ureter should be
performed prior to application of contrast agent • Delay surgery > 3 months
because it may deteriorate cytological specimens • BMI > 30
• Neutrophil-to-lymphocyte ratio
CT abdomen and pelvis • African race
• Easier to perform than IVU
• Higher degree of accuracy in determining the presence Prognostic factors-Postoperative
of renal parenchymal lesions. • Stage
• Typical findings on CT: • Grade
– Radiolucent filling defects • Concomitant CIS
– Obstruction or incomplete filling of a part of the upper • Distal ureter management
tract
• Lymphovascular invasion
– Non-visualization of the collecting system
• Lymph node involvement
• Transitional cell cancers have a range of 10 to 70 HU
• Tumour architecture
• CT urography - Imaging technique with the highest
• Surgical margins status
diagnostic accuracy for UTUC
• Tumour necrosis
• Has replaced IVU and ultrasonography as the first-line
imaging test • Molecular marker status
• Sensitivity 67% to 100% and specificity 93 to 99% • Variant histology
• Can also detect wall thickening of the renal pelvis or
ureter, but flat lesions are not detectable Endoscopic Management
• Hydronephrosis in the presence of UTUC is associated Ureteroscopy and ablation
with advanced pathological disease and poorer – Electrocauterization is effective, there is a risk of
oncological outcomes ureteral injury
– LASER- Ho:YAG or Nd:YAG with flexible laser fibers
Role of Lymph node dissection measuring 250 to 365 nm
• Lymph node dissection (LND) associated with RNU is of – Scope deflection d” 120 degrees, to avoid laser fiber
therapeutic interest and allows for optimal staging of breakage
the disease – Ho:YAG laser (0.5 mm depth of penetration) is preferred
energy for treatment of UTUC.
 110 The Urology Masterclass, Department of Urology, CMC, Vellore

• 736 patients with UTUC underwent ureteroscopic Nomograms

treatment follow-up of 14-73 months. Margulis Nomogram (prediction of non-organ confined
• 53% risk of upper tract recurrence and 34% bladder UTUC) had ~77% accuracy
recurrence
– Grade
• Prognostic factors for UTUC recurrence
– Architecture
– tumour size
– Location of the tumour
– grade
– stage
Brein Criteria to identify patients at risk of advanced UTUC
– history of bladder cancer
– Hydronephrosis,
– multifocality
– Ureteroscopic biopsy grade
– Positive cytology
Radical nephroureterectomy
- Lap and open RNU has similar oncological
Bolenz LN density
outcomes and have not changed
• LN density > 30% greater risk of both recurrence and
mortality than LN density <30%.
Distal ureter management in RNU
-Gold standard – Open bladder cuff
Controversies in LND
-Other methods described – endoscopic, extravesical,
• Surgeon is an independent predictor of LND (after
pluck
tumour and patient characteristics are adjusted)
-Not inferior to open bladder cuff with respect to
• Lack of standardization in performing LND
recurrence or survival
• Ontario Cancer Registry (n=422 with UTUC) only 27%
-Factors for intravesical recurrence
had > 1 LN
• Endoscopic ureteral technique
• Scant number of nodes being removed during RNU is
• Lap technique likely the norm worldwide
• Prior bladder cancer
• Higher stage Summary
• CIS • Nodal status is significant predictor of DFS and CSS
• LN involvement (especially pT2–4 disease).
§ E Xylinas et al, Eur Urol Jan 2014 • Potential therapeutic role of LND in UTUC is unclear as
§ WM Li et al, Eur Urol Jun 2010 data is retrospective.
Lymphnode status • Not possible to standardize either the indication or the
extent of LND
At least 8 nodes need to be removed at RNU to achieve
~75% probability of finding >1 positive node.
Bladder recurrence post nephroureterectomy
Cancer-specific survival according to nodal status • Tumour multiplicity independent risk factor (Field
cancerization vs. intraluminal seeding)
Abe et al(2008) n=301
• Positive surgical margins
– pN0 (139) 88
• Tumour necrosis
– pNx (146) 65
• Carcinoma in-situ
– pN+ (27) 22
• Immunosuppression
Lughezzani (2010)n=2842
• Insufficient renal function
– pN0 (1835)81
• Female gender
– pNx (747)78
Single post op dose of MMC
– pN1 (242)34
ODMIT-C trial : Multicenteric RCT
Roscigno et al(200)n=1130
Relative risk reduction of 40% in one year, absolute RR of
– pN0 (412)77
11% and NNT of 9
– pNx (578)69
Single dose THP (Pirarubicin)
– pN+ (140)35
within 48 hours of NU
Phase II RCT, Japan
Absolute RR: 14.9%
 The Urology Masterclass, Department of Urology, CMC, Vellore 111

• T O’Brien et al. Eur Urol. Oct 2011
• Ito et al. J Clin Oncol 2013 Apr
Neoadjuvant chemotherapy
• NACT improves oncological outcomes in locally
advanced UTUC (T3-4 or N+)
• NACT is associated with
– Complete remission(CR) in 9% to 14%, with significant
downstaging
• Post operative reduction in renal function can limit use
of chemotherapy
• Matin SF et al, Cancer 2010
• Liao RS et al, J Urol 2018
Adjuvant chemotherapy
• POUT trial – Phase 3, RCT, largest, Role of adjuvant
chemotherapy post RNU (p T2-T4, N0-3, M0)
• 2 yrs DFS 71% in chemotherapy arm and 51% in
surveillance group. Trial stopped due to efficacy
favouring the chemo arm
• Birtle et al, Journal of Clinical Oncology 2018
• OS benefit in patients receiving adjuvant chemo after
RNU in pT3/T4 and or pN+ UTUC (HR 0.77)
• Seisen et al, Journal of Clinical Oncology 2017
Narrowband imaging (NBI)
• (Herr et al.) NBI à improved the detection of recurrent
NMIBC over standard white-light cystoscopy
• NBI can be used for bladder and upper tract scanning
the bladder on follow up
• Significantly improved visualization upper tract
tumours also
• Optical image enhancement technique enhances the
contrast between mucosal surfaces and microvascular
structures without the use of dyes
• Based on the phenomenon that the depth of light
penetration into the mucosa increases with increasing
wavelength.
• With NBI, the tissue surface is illuminated with light of
narrow bandwidth, with centre wavelengths in the blue
(415 nm) and green (540 nm) spectrum of light.
• Strongly absorbed by haemoglobin, the vascular
structures appear dark brown or green against a pink
or white mucosal background.
• For white light cystoscopy and NBI cystoscopy the
overall sensitivity was 87% and 100% and the overall
specificity 85% and 82%, respectively
• Choice technique – location and experience
– Endoscopic ablation
– Segmental ureterectomy
– Percutaneous access
– Adjuvant topical agents
Segmental ureterectomy
• Adequate pathological specimen
• Definitive grade and stage analysis
• Preserve ipsilateral kidney
• Uretero-ureterostomy Vs Complete distal ureterectomy
+ ureteroneocystostomy
• Area around the tumour should not be invaded
• Failure rate after segmental resection of upper and mid
ureter is higher than distal upper
Antegrade infusion of BCG
BCG protocol
• Normal urine culture, under ultrasound guidance
• Prone position, 10 Fr nephrostomy tube
• Flask with 360mg BCG in 150 ml NS at 20cm above
kidney level of the supine patient
• Rate of infusion 1ml/min
• Six weekly perfusions, PCN removed after 6th dose
(Giannarini G, Studer et al. Eur Urol 2011; 60: 955-60)
Adjuvant topical agents
• Antegrade
– instillation of BCG vaccine or Mitomycin C in the upper
urinary tract
– By PCN via 3 way catheter open at 20 cm after complete
eradication of tumor
• Retrograde - Dangerous
– Through ureteric stent by the help of reflux
– Ureteric obstruction + pyelovenous influx possible
• Medium term results similar to bladder tumor
• Long term results not available

UTUC in solitary functioning kidney

Conservative surgery in UUT TCC
• Low grade UTCC
• Renal insufficiency
• Solitary functioning kidney
 112 The Urology Masterclass, Department of Urology, CMC, Vellore
Perforation during transurethral resection of tumour
(TURT):
• 1.1-58.3%.
• Balance between tumour eradication vs possible
extravesical seeding (T3) & recurrence.
• Predisposing factors:
– Large tumours
– Posterior wall location
– Older age of patient
– Pre-treated bladder
• Overall, low risk of recurrence. One study reports high
recurrence with poor survival after open repair for
bladder perforation during TURT (Skolarikos et al,
Journal of Urology 2004).
Measures to avoid perforation in bladder tumour resection:
• Avoid over-distension, low diathermy settings.
• Follow the contour of the bladder.
• Anaesthetic paralysis/ obturator block.
• Bipolar diathermy.
Management options:
• Small extraperitoneal perforation: Adequate bladder
+/- prevesical space drainage.
• Intra-peritoneal: Risk of sepsis/ mortality.
– Open repair
– Laparoscopic repair
– Radiological intraperitoneal drain + bladder
drainage.
– Cystoscopy through the perforation and guided
placement of intra-peritoneal drain+ bladder drainage.
• Serial, regular follow-up with imaging to document
disease in view of risk of extraperitoneal seeding.
References and suggested readings
1. May F et al. Indian J Urol 2013
2. Venkatramani et al. J Urol 2014
3. Sugihara Toru et al. J Urol 2014
4. Kenneth G Nepple et al. CUAJ, 2009
5. Skolarikos et al. J Urol, 173(6): 1908-11.
6. Balbay MD et al. J Urol 2005
7. Golan et al. BJUI 2011
8. Manikandan R et al. J Endourol.2003
9. Pansadoro et al. Urology 2002
Adenocarcinoma bladder
• Second most common non-urothelial bladder cancer
• Comprising 0.5 to 2% of all bladder cancer cases
• 10% of bladder adenocarcinomas arise from the
urachal remnant
• Types: Glandular, colloid, papillary, signet ring and clear
cell
• Signet ring variant associated with a poorer prognosis
• Local relapse is more common than distant relapse
following cystectomy
• Factors associated with an increased risk of non-
urachal adenocarcinoma include bladder exstrophy
and schistosomiasis
• The survival of patients with non-urachal
adenocarcinoma is poor (5 year overall survival – 35%)
Urachal Adenocarcinoma:
• Primary symptoms
– Haematuria
– Irritative urinary symptoms
– Mucusuria is also common
– Palpable lower abdominal mass
• Younger than those with non-urachal adenocarcinoma
(median age 56 years)
• More common in females
• Distinct natural history from non-urachal
adenocarcinomas
– Less likely to be high grade
– Has a better overall five-year survival
• Radiological features: Supravesical mass with
calcification is highly suggestive of urachal carcinoma
because 50%–70% of urachal carcinoma contain
calcification
• Cystoscopy: Tumors are often papillary or flat
infiltrating lesions with overlying edema. Muscle
invasion is almost always present and diffuse or
circumferential bladder wall thickening is usually seen
Sheldon Staging 1984:
• I - Confined to urachal mucosa
• II - Invasion confined to urachus
• III - Metastatic to regional lymph nodes
– IIIA Extension to bladder
– IIIB Extension to abdominal wall
– IIIC Extension to peritoneum
– IIID Extension to other viscera
• IV - Metastatic to non regional lymph nodes or distant
sites
– IVA Metastatic to lymph nodes
– IVB Metastatic to distant sites
 The Urology Masterclass, Department of Urology, CMC, Vellore 113

Ashley Staging 2006:

I. Confined to urachus and bladder
II. Extension beyond muscularis of urachus or bladder
III. Metastases to regional lymph nodes
IV. Metastases to non-regional lymph nodes or distant sites

Criteria for diagnosis:

• Location in the dome or anterior wall of the bladder
• Sharp demarcation between tumour and normal surface
epithelium
• Lack of an in-situ component
• Adjacent mucosa lacking prominent cystitis glandularis
• Bulk of tumour is in the bladder wall rather than luminal
• Exclusion of primary adenocarcinoma located
elsewhere that has spread secondarily to the bladder
• Enteric type histology
• Absence of urothelial dysplasia

Similarity between urachal and colon adenocarcinoma:

• Histology similar
• Carcinoembryonic antigen and CA 19-9 are commonly
increased in urachal cancer and provide a surrogate
means of monitoring response
• Carcinomatosis and liver involvement are also typical
of advanced urachal and colon cancers

Management of urachal adenocarcinoma:

• Sheldon et al advocated surgical control of the urachal
ligament via en bloc excision of the bladder dome,
urachal ligament, posterior rectus abdominis fascia
and umbilicus
• Majority can be cured with en bloc excision of the
umbilicus, urachus and surrounding soft tissue coupled
with extended partial cystectomy inspite of local
invasion into perivesical tissue
• Urachal tumors that extend into and seed the peritoneal
cavity or invade abdominal organs are rarely cured
even with such aggressive surgery
• There was no significant difference in outcome with
partial versus radical cystectomy
• Negative surgical margins and no lymph node
involvement were favourable prognostic indicators
• No defined role for chemotherapy or radiation in
patients with unresectable or metastatic disease – trial
of 5-FU + Gemcitabine + Cisplatin warramted

References
• Campbell-Walsh Urology, 10th edition
• Ogaya Pinies G et al. Arch Esp Urol 2012
• Siefer-Radtke A. J Urol 1984
• Herr HW. J Urol
114 The Urology Masterclass, Department of Urology, CMC, Vellore

INFECTIONS II. INVASIVE ASPERGILLOSIS

• Rare infection.
I. EMPHYSEMATOUS PYELONEPHRITIS • high index of suspicion esp. in immunocompromised,
DM, AIDS, prolonged steroid use, malignancy, urinary
USG tract instrumentation.
Initial screening • Remove source of infection.
Presence of high-amplitude echoes with low-level posterior • Recommended antifungal agents:
“dirty” acoustic shadowing Liposomal AMB, Voriconazole, Itraconazole,
Caspofungin.
CT Antifungal Agents in general:
Confirms the diagnosis and defines the extent of disease. • Amphotericin B: active against all fungal infections.
Plan management Adverse effects: generalized pain, headache, convulsions,
localized phlebitis, anemia, and thrombocytopenia
Classification Nephrotoxic.
Huang & Tseng Liposomal formulation– same spectrum of activity but less
Class 1: gas in the collecting system only nephrotoxicity.
Class 2: gas in the renal parenchyma without extension Hepatoxic, high cost.
to extra renal space • Fluconazole: Candida & Cryptococcus except C. krusei,
Class 3A: extension of gas or abscess to perinephric space and C. glabrata.
Class 3B: extension of gas or abscess to pararenal space; • Itraconazole:Aspergillus, Blastomyces, Coccidioides, and
and Histoplasma
Class 4: bilateral EPN or solitary kidney with EPN • Voriconazole:similar profile as for Itraconazole,also
active against Zygomycetes and some strains of C.
Prognostic and Risk Factors glabrata and C. krusei that are resistant to the other
Poor prognostic factors azoles.
Thrombocytopenia • Caspofungin: Invasive aspergillosis, refractory to other
approved therapies.
Shock
Altered sensorium
III. XANTHOGRANULOMATOUS
Need for hemodialysis PYELONEPHRITIS
Risk factors for developing EPN Differential diagnosis of fever/ flank pain and mass with
Uncontrolled DM stone history
Ureteral obstruction – Xanthogranulomatous pyelonephritis
Female gender – Pyonephrosis - massive pelvic dilation
– Renal parenchymal malacoplakia - calculi are usually
Organisms not present
Escherichia coli- 70%-90% – Perinephric abcess
Klebsiella, Proteus – Squamous cell carcinoma of kidney
No anaerobes
Imaging for XGP
Management
Percutaneous drainage – Most important
Antibiotics
3rd generation cephalosporins, carbapenems,
Aminoglycosides,

Nephrectomy
Emergency – 4%
Elective – 10% - 20%
 The Urology Masterclass, Department of Urology, CMC, Vellore 115

• Calculi 50-80% • Proteus to be the most common organism in urine

• IVU – 71-82% non-functioning cultures
• RGP – ‘tooth-paste’ or ‘stringy’ appearance • Classic radiological triad of unilateral renal
enlargement with little or no function and a large
• USG:
calculus in the renal pelvis
• Enlarged kidney with shadowing
• Central highly echogenic foci (calculi) Management
• Multiple hypoechoic areas in the parenchyma • Antibiotic therapy may be necessary to stabilize the
separated by apparently normal areas – no flow on patient preoperatively
Doppler • May closely resemble clear cell adenocarcinoma and
• Renal pelvis not markedly dilated can be associated with renal cell carcinoma, papillary
transitional cell carcinoma of the pelvis or bladder,
• Peripelvic fibrosis may obscure shadowing from the
and infiltrating squamous cell carcinoma of the pelvis
calculi
• Nephrectomy with oncological principals
• CT:
• Important to remove the entire inflammatory mass
• Central calculus
• Complication rates of surgery are high as adjacent
• Lack of contrast excretion
organs are often involved3
• Calculi 80%
• Mostly pelvic or staghorn
• ‘Exploded’ – fragmented staghorn
• ‘Suspended’ due to thick pus
• Generalized enlargement of the kidney
• Pelvis contracted around calculus with peripelvic
inflammation and fibrosis
• Numerous low attenuation collections (-15 to +10HU)
• Enhancement of rim of collections due to
neovascularisation
• ‘Bear-paw footprint’ – calyces dilated > pelvis

Malek and Elder’s classification

– Stage I – Nephric – Renal parenchyma only
– Stage II – Nephric and Perinephric
– Stage III – Adjacent structures or retro peritoneum

Evaluation
• Most patients present with flank pain (69%), fever and
chills (69%), and persistent bacteriuria (46%)
116 The Urology Masterclass, Department of Urology, CMC, Vellore

NEUROVESICAL DYSFUNCTION
Neuropathic bowel and bladder dysfunction in children

Classification:
As bladder sphincter dysfunction is poorly correlated with the type and spinal level of the neurological lesion, urodynamic
and functional classifications are much more practical for defining lower urinary tract pathology and planning treatment.
The bladder and sphincter are two units working in harmony to act as a single unit. In neurogenic bladder, the storage and
voiding functions can be disturbed. The bladder and sphincter may function in a overactive or underactive manner
leading to four different combinations. The classification system is based on urodynamic findings:
1) Overactive sphincter and underactive bladder
2) Overactive sphincter and overactive bladder
3) Underactive sphincter and underactive bladder
4) Underactive sphincter and overactive bladder
The same is show in the illustration below. (Verpooten et al. Paed Nephrol 2008)

Goals of treatment
• The primary goal of management is preservation of
renal function.
• Secondary goals of management include urinary and
fecal continence, avoidance of UTI, and facilitation of
sexual function and fertility.
• Preservation of renal function is achieved by
maintaining low bladder pressures and active
management of VUR and avoidance of UTI.
• The ICCS (International Children’s Continence Society)
recommendations for follow-up are based on
developmental stages and the relative risk for
secondary spinal cord tethering.
Principles of bladder management
• Minimally invasive therapies should precede the use
of more invasive therapies to address failure of the
bladder to store or empty.
• Whereas from an etiologic standpoint neurogenic
bladder dysfunction is a heterogeneous group, medical
management will be similar irrespective of the
underlying cause.
 The Urology Masterclass, Department of Urology, CMC, Vellore 117

Strategies to address inadequate bladder storage (Campbell 11th edition)

Cause Minimally invasive option More invasive options

Low compliance CIC
Antimuscarinic therapy
Overnight catheter drainage
Low capacity CIC
Overnight drainage
Overactive bladder CIC
Antimuscarinic therapy
Overnight drainage
Low outlet resistance Sympathomimetic therapy
Intravesical botulinum
Augmentation cystoplasty
Urinary diversion
Intravesical botulinum
Augmentation cystoplasty
Urinary diversion
Intravesical botulinum
Augmentation cystoplasty
Urinary diversion
Bladder neck sling
Bladder neck procedure
Injection of bulking agents to
bladder neck

Strategies to address inadequate bladder emptying

Cause Minimally invasive option
Underactive detrusor CIC
Overnight drainage
Detrusor sphincter CIC
dyssynergia Antimuscarinic therapy
Overnight drainage
More invasive option
Neuromodulation
Intravesical and/or sphincter
botulinum toxin
Urinary diversion
Neuromodulation

Principles of bowel management

• An option for those who are unable to sit on the toilet is manual evacuation of stool.
• In those who are able sit independently, with some anal sphincter activity, a regular postprandial toilet sitting
regimen three times daily after meals has been effective, as it employs the gastrocolic reflex to initiate a bowel
movement.
• When continence is not achieved by defecation, digital stimulation is suggested.
• Retrograde enemas (tap water with irrigation cone) followed by kneading of the abdomen or alternative transanal
irrigation devices are instituted.
• The antegrade continence enema (ACE) is considered the next step in management.

Follow up of child with neurogenic bladder and bowel dysfunction (Campbell 11th edn)
118 The Urology Masterclass, Department of Urology, CMC, Vellore

Algorithm for the management of neurogenic bladder dysfunction in a child

 The Urology Masterclass, Department of Urology, CMC, Vellore 119

Pediatric Urology
Antenatally detected hydronephrosis

• Prenatal diagnosis of urinary tract (UT) dilation occurs in 1-2% of all pregnancies

SFU grading system was most widely used with the best consistency till recently (11/25 studies, meta-analysis)

Demerits-
• Does not include bladder and ureteral anomalies

• Initial postnatal ultrasonography: after 48 h of birth, since infants are relatively dehydrated at birth
• Preferably done between 5-7 days
• The exceptions
– Suspected lower tract obstruction e.g., Posterior urethral valves
– Severe bilateral hydronephrosis with or without hydroureter
– Solitary kidney with hydronephrosis especially if the APD is > 15 mm or it is SFU grade 2 or more in the third trimester
• Repeat study at 4-6 weeks
• Infants with moderate to severe unilateral or bilateral hydronephrosis or ureteric dilatation (SFU grade 3-4, APD >10
mm) who do not show VUR
• 99mTc-mercaptoacetyltriglycine (MAG3), ethylenedi-cysteine (Tc-EC) or Tc-diethylenetriamine-pentaacetic acid (DTPA)
• Performed after 6-8 weeks of age
• Unilateral or bilateral hydronephrosis with renal pelvic APD >10 mm, SFU grade 3-4 or ureteric dilatation, infants
with ANH who develop a urinary tract infection
• The procedure should be done at 4-6 weeks of age
 120 The Urology Masterclass, Department of Urology, CMC, Vellore

• Performed early, within 24-72 hours of life, in patients with suspected lower urinary tract obstruction
• 490 patients (730 renal units)
• All units were regraded using the UTD classification system and compared to the SFU system to assess reliability
• The UTD classification system was reliable in the assessment of hydronephrosis .
• Hydronephrosis resolved in 357 units (49%), and 86 units (12%) were managed by surgical intervention. The remainder
of the renal units demonstrated stable or improved hydronephrosis
• UTD is reliable for evaluation of postnatal hydronephrosis and is valid in predicting surgical intervention
The Urology Masterclass, Department of Urology, CMC, Vellore 121
 122 The Urology Masterclass, Department of Urology, CMC, Vellore
Posterior urethral valve
Prognostic factors
– Ultrasound appearance
• Increased echogenicity , dysplasia – poor prognosis
– Serum creatinine
• Nadir creatinine of 0.8 to 1mg% in first year – good
prognosis
– Presence of reflux
• Mortality- 57%- B/L, 17%- unilateral, and 9% -no reflux
• Reflux associated with dysplasia & high pressures in
kidney
– Age at presentation
• PUV that presented in infancy had poorer prognosis
than that presented in adulthood, but this fact has
changed due to antenatal diagnosis and because most
patients presenting in adulthood have ESRD.
SNOB
• SNOB (Syndrome of nocturnal over distention of the
bladder): HUN and bladder changes developed as a
result of failure to empty the over-distended bladder at
night, in the absence of anatomic bladder outflow
obstruction
• Associated findings:
– Decreasing bladder capacity
– Development or progression of HUN
– Recurrent urinary tract infections
Follow-up
– Worsening incontinence between catheterizations
Pressure Flow Studies
• Persistent daytime urinary incontinence beyond 5 years
• Deterioration in renal function (rising creatinine or drop
in GFR) with no obvious cause like growth spurt.
• Increase in upper tract dilatation in the absence of
outflow obstruction.
• Prior to Renal Transplantation - to ensure a safe,
compliant low-pressure urinary tract.
• To assess the efficacy of treatment or intervention.
• As a research tool to study the evolution or natural
history of developing bladder function in boys with
successfully treated PUV.
Reflux and PUV
• Reflux is very common in PUV (up to 72%) and it is
described bilaterally in up to 32%
• High-grade reflux is mostly associated with a poor
functioning kidney
• Should ensure complete treatment of obstruction and
to rule out unresolved bladder pathology
• Early removal of the renal unit seems to be unnecessary,
as long as it causes no problems
• It may be necessary to augment the bladder and in this
case the ureter may be used
 The Urology Masterclass, Department of Urology, CMC, Vellore 123

Follow-up

(EAU 2019 update) • Poor sensation, high bladder volumes, poor compliance,
high storage pressures, inadequate upper tract
drainage
Valve bladder
• Primary goal is to preserve renal function
• Termed by Mitchell 1982
– Renal failure due to dysplasia + obstructive uropathy
• Peters classification 1992 (urodynamic): myogenic
failure, detrusor hyperreflexia, and decreased • Initial management is – Timed voiding, anticholinergics
compliance/small capacity • á - blockers
• Progression: • Therapy with ACE-I stabilizes and improves renal
– Infants: poor compliance function, retarding pace of renal damage
– In older children: instability from • Clean intermittent catheterisation, 3-4 hourly
hypercontractility • Intermittent catheterisation with nocturnal bladder
– In postpubertal boys: myogenic failure emptying
• Intrinsic bladder dysfunction leads to deterioration of • Augmentation cystoplasty
renal function and upper tract dilatation despite • Renal transplantation
successful valve ablation
 124 The Urology Masterclass, Department of Urology, CMC, Vellore
VUR
Incidence
• Overall reported to be 1 to 2% but it might be higher
• 30 to 50% children present with UTI (depending on age)
• 3 to 19% with hydronephrosis on antenatal USG
• 27.4% in sibling with VUR
• 35.7% in off springs of patients with VUR
Natural history
• Low-grade reflux frequently resolves, high-grade VUR
persists
• 80% of low-grade reflux resolves with medical
management
• Resolution of VUR grades I to III was 50% at 3.5 years
• Grade IV VUR resolved in 50% in children after 11 years
• 20% to 30% will have further infections, but few will
experience long-term renal sequelae
• Sterile reflux does not cause renal damage, but
persistent reflux of infected urine may cause renal
damage
Evaluation
• Urinalysis for proteinuria and bacteriuria
• If the urinalysis indicates infection- urine culture and
sensitivity
• Renal ultrasound to assess the upper urinary tract
• Neither the renal ultrasound nor the DMSA scan is
accurate enough to detect VUR (of all grades)
• Voiding cystourethrography (VCUG) is the gold standard
for the diagnosis of VUR, and the grading of its severity
VUR and bowel dysfunction
• Combination of conditions may be at greater risk of
renal injury due to infection
• With CAP
– Resolution rates 31% (BBD) and 61% (without BBD)
• Endoscopic surgery:
– Resolution rates 50% (BBD) Vs 89% (without BBD)
• Open surgery:
– No alteration of resolution rates, which were 97% in
both groups
RIVUR trial
• Trimethoprim sulfamethaxazole [302] Vs Placebo [305]
• Inclusion criteria: grade I to IV vesicoureteral reflux
• Results
– Recurrence of Febrile UTI:
• Reduced by half in prophylaxis group.
• Interval between enrollment and a 10% incidence of
recurrence: 336 days (prophylaxis) Vs 106 days
(placebo)
• Eight children would have had to be treated for 2 years
to prevent one case of febrile UTI
– Renal Scarring: No significant difference
– Antimicrobial resistance: More common in prophylaxis
group (63% Vs 19 %)
Problems reported with the use of antibiotic prophylaxis
• Bacterial resistance
• Altered gut microbiome (Long term effects unclear)
• Reports of increased weight gain in some studies (RIVUR
secondary analysis- No association)
• Possible association with diabetes, rheumatoid
arthritis, inflammatory bowel disease
Follow-up
• Urinalysis for proteinuria and bacteriuria annually
• Urine culture and sensitivity: if the urinalysis is
suggestive of infection.
• Ultrasonography: every 12 months to monitor renal
growth and any parenchymal scarring.
• Voiding cystography : between 12 and 24 months
(VUR [grades III-V], bladder/bowel dysfunction, and
older age)
• DMSA: When renal ultrasound is abnormal, when there
is a greater concern for scarring (breakthrough UTI)
Definitive management
• Ureteric reimplantation or endoscopic treatment
• Resolution rate per 100 children:
– 98 (reimplantation) Vs 83 (endoscopic therapy)
• Ureteric reimplantation
– Open, laparoscopic or robotic
– Transvesical or extravesical
• Renal ultrasound to assess for obstruction
• Voiding cystography following endoscopic injection of
bulking agents
Follow-up
• Monitoring of blood pressure, height, and weight,
Urinalysis for protein and UTI :
 The Urology Masterclass, Department of Urology, CMC, Vellore
– Annually through adolescence
• If either kidney is abnormal:
– Ultrasound or DMSA scanning.
• Recurrence of febrile UTI:
– Evaluation for bladder/bowel dysfunction or
recurrent VUR is recommended.
VUR with concomitant PUJ obstruction
Historical perspective
- Hutch et al (1962) first suggested that vesicoureteral
reflux could induce symptomatic hydronephrosis that
persists after reflux resolution.
- Williams (1974) described 2 categories of cases
1) Ureteropelvic junction obstruction with incidental low
grade reflux: pyeloplasty was recommended
2) Obstruction assumed to be secondary to massive reflux
with over distension of the renal pelvis. Primary
correction of vesicoureteral reflux is recommended with
the expectation that secondary renal pelvic obstruction
would resolve.
Hollowell classification (1989)
• Group 1: Primary ureteropelvic junction obstruction
and incidental low grade reflux,
• Group 2: Secondary obstruction from high grade reflux.
– Pyeloplasty was recommended for both groups.
• Group 3: Reflux and pseudo ureteropelvic junction
obstruction with dilated upper tracts that were
unobstructed on drainage films or a renal scan.
Etiology of PUJ obstruction in present of reflux
• Over distension of the renal pelvis due to reflux leads
to kinking of the ureteropelvic junction, which then
becomes fixed secondary to inflammation
• Concomitant disease is a primary ureteral abnormality
affecting both ends of the ureter
Use of imaging
• Blane et al showed that sonography is unreliable in
this situation
• Lebowitz and Blickman (1983) demonstrated use of
VCUG with post-void drainage films and in conjunction
with an antegrade study, such as IVU or diuretic renal
scintigraphy with bladder drainage to prevent reflux
• The grading system for primary reflux which is based
on upper tract dilatation is not valid when dilatation
is also due to obstruction.
• A drainage film is crucial whenever upper tract
dilatation is seen on a voiding cystogram.
Role of Renal scintigraphy
• Estimates relative renal function and quantify renal
pelvic drainage.
125
• Serial testing may be necessary to determine
obstruction.
• Accurate test results depends
– Skilled nuclear medicine department staff
– Precise measurement of the area of interest
– Proper timing of diuretic administration.
• In the presence of VUR, bladder drainage is critical
• The accuracy is decreased in massively dilated systems.
• Judged by a prolonged drainage time of radiotracer or
a progressive loss of relative renal function.
Role of IVP
• Rickard and Whitaker described several useful features
of IVP
– Delay in the appearance of contrast material
– Negative pyelogram
– Delay in system emptying
– A rounded renal appearance
– Dilution of contrast medium and uniform cortical loss
indicate obstruction.
• Pitfalls of IVP include intermittent obstruction, poor
renal function and focal cortical scarring, which are
more indicative of reflux nephropathy.
Pyeloplasty first or Ureteric reimplant?
• The natural history of vesicoureteral reflux is resolution.
Improvement is directly related to reflux grade, and
even high grades of reflux may resolve with time.
• Factors favoring observation include
– Lower grades of reflux
– Stable/improving hydronephrosis
Pyeloplasty First
• Several theoretical benefits compared to primary
ureteroneocystotomy
– Prevents the effects of partial obstruction at the
bladder on an upper tract already stressed at the
ureteropelvic junction.
– Sterile reflux is unlikely to cause renal damage which
cannot be said for sterile obstruction.
– After pyeloplasty, less than half of the patients required
ureteral reimplantation, demonstrating the natural
tendency of reflux to improve.
Ureteric reimplant first
• The natural history of vesicoureteral reflux is resolution.
Improvement is directly related to reflux grade, and
even high grades of reflux may resolve with time.
• Obstruction assumed to be secondary to massive reflux
with over distension of the renal pelvis leading to
intermittent PUJ obstruction.
• Primary correction of vesicoureteral reflux is
recommended with the expectation that secondary renal
pelvic obstruction would resolve.
 126 The Urology Masterclass, Department of Urology, CMC, Vellore
Unilateral ureteral duplication with ureterocele
Factors affecting management decisions
a. Function of upper pole
b. Ureterocoele causing outlet obstruction
c. Lower moiety reflux
d. Sepsis
Management options
a. Upper polar hemi-nephrectomy/partial nephrectomy
The practice of automatically removing poorly functioning
or dysplastic kidneys has been challenged. Dysplasia was
absent in 57%, focal in 33% and marked in only 10% of
moieties removed1. The development of hypertension or
malignant degeneration has been unfounded. Injury to the
normal lower moiety vasculature or collecting system and
ureter is known. It may an option in non-functioning
moieties causing recurrent UTIs or sepsis and in ectopia/
duplication without ureterocoeles or reflux where no lower
tract procedure is contemplated.
b. Transurethral incision of ureterocoele only
Simple, endoscopic technique which is useful in a younger
child and as a preliminary procedure, as it may reduce the
degree of ureteral dilatation and make subsequent
reconstruction easier. It may result in reflux and require
additional procedures later. It is occasionally definitive.
c. Uretero-ureterostomy
Increasingly popular and can be done with a minimally
invasive technique or a cosmetically acceptable min
iinguinal incision. It has consistently shown good results
with minimal morbidity and can be done in ectopic ureters
also. It is contraindicated in the presence of lower moiety
reflux and may not be sufficient in large ureterocoeles
causing obstruction. The risks of ‘yo-yo’ reflux or injury/
stenosis of the normal ureter have largely been overstated
d. Excision of ureterocoele, bladder reconstruction, common
sheath reimplantation
These complex procedures are reserved for large
ureterocoeles with/and lower pole moiety reflux
Technique of uretero-ureterostomy
a. Approach – Open: Inguinal, Pfannenstiel for bilateral,
Laparascopic, Robotic
b. End to side, minimal lower pole ureteral dissection,
and generous lower pole ureter spatulation, empty
ureterocoele with feeding tube before ligating lower end
Special points of management and technique
1. Injury to the normal lower pole ureter6 can be avoided
and identifying and incising it is easier if the lower
pole ureter is stented with a ureteric catheter pre-
operatively.
2. Marked upper polar ureteral dilatation may require
tapering techniques.
3. In the presence of infection/sepsis, a lower abdominal
ureterostomy placed near the site of the lateral end of
a Pfannenstiel incision will decompress the system and
can help reconstruction later.
Undescended testis
Embryology of testicular descent
A. The testes appear on the urogenital ridge by the 2nd month
B. The coelomic cavity evaginates into the scrotal swelling
where it forms the processus vaginalis by the middle of
the 3rd month
C. Testes begin descent into the scrotum guided by the
gubernaculum – 7th month
D. The processus vaginalis obliterates spontaneously -
shortly after birth
E. Passage through the inguinal canal -begins in the
28th week of gestation
Factors that assist descent of testes
Mechanical
-Intraabdominal pressure
-Gubernaculum tension
-Processus vaginalis patency
Hormonal
-Testosterone (Inguinoscrotal phase)
Growth factors
-INSL3 – insulin like growth factor (Abdominal phase)
-Calcitonin gene related peptide from genitofemoral nerve
Incidence of undescended testes
- Full term - 1.0 - 4.6% (Most spontaneously descend in
the first 1 month)
- Preterm - 1.1 - 45%
-Nearly 1.0% of all full-term male infants have
undescended testes at one year age
-Bilateral in up to 30% of cases
Suspect disorders of sexual differentiation if…
-Bilateral undescended testes
-Hypospadias
 The Urology Masterclass, Department of Urology, CMC, Vellore 127

Classification

-80% are palpable whereas 20% are not

-Of the non-palpable testes, 50% are intra-abdominal/inguinal/ peeping and 20% are absent and 30% are atrophic

Classification
- Undescended: In the same pathway as descent
- Ectopic: Away from the path of descent. Superficial inguinal pouch (Most common). Femoral, perineal, pubic, penile
or contralateral scrotum.
- Retractile: Can be manipulated back into the scrotum. Overactive cremasteric reflex. 1/3rd can ascend and become
undescended
 128
Evaluation
- Physical examination, sitting with knees drawn up,
warm room and hands
- MRI to identify Mullerian structures if any. USG lacks
sensitivity
Medical treatment
- 9-60% success and 20% recur, not recommended
- GnRH analogues: Buserelin, Gonadorelin (Nasal sprays)
- However, men treated in childhood with buserelin had
better semen analyses compared with men who had
childhood orchidopexy alone or placebo
- Endocrine treatment with GnRH analogues may be
advised for boys with bilateral undescended testes to
preserve the fertility potential
Surgical treatment
- Unlikely to descend past 6 months
- Ideal time of surgery – by 12 to 18 months
- Inguinal approach -Success rate – 92%
- Scrotal approach – 88-100%; low positioned testis
Algorithm
The Urology Masterclass, Department of Urology, CMC, Vellore
Inguinal orchidopexy
- Mobilisation of the testis and spermatic cord -upto
internal inguinal ring, with dissection and division of
all cremasteric fibres
- Patent processus vaginalis - ligate proximally at the
level of the internal ring
- Any additional pathology -removal of an appendix testis
- Size of the testis and dissociation between epididymis
and testis - assess
- Place testis in sub-dartos pouch without any tension
- For length - Prentiss manoeuvre (Tie inferior epigastric
vessels and pass cord medial to the inferior epigastric
vessels
- Fixation sutures - Between the tunica vaginalis and
dartos
- Lymph drainage of a testis - may change from high
retroperitoneal drainage to iliac and inguinal
drainage
Diagnostic laparoscopy
- For non-palpable testes
- 40% abdominal, 40% structures entering deep ring, 10%
peeping, 10% blind ending cord
 The Urology Masterclass, Department of Urology, CMC, Vellore 129

Complications of surgery
-Injury to vas
-Testicular ascent
-Testicular atrophy

Fertility
- Fertility rate- Number of offspring per mating pair
- Paternity rate– Actual potential of fatherhood
- Unilateral UDT – Lower fertility rate, similar paternity
rate as general population
- Bilateral UDT –
Lower fertility rate and paternity rate
• 100% oligospermic, 75% azoospermic
• Post treatment- 75% oligospermic, 42% azoospermic

Risk of malignancy
-Timing of Orchidopexy: < 13 years - 2.2, > 13 years -
5.4

Summary of guidelines (EAU 2019)

• MIS
Disorders of sexual differentiation
– 19p, Type II Receptor gene on 12q
• Hernia uteri inguinalis (HUI)
– Sporadic / X linked or AD
• Characteristics
• Recommended treatment
– 46 XY
– Orchidopexy / Orchidectomy
– Normal male external genitalia (phenotype) - U/L or B/
L UDT – Testicular tumour : UDT
– Internal Müllerian Duct structures - B/L FT/Uterus/ – 3-8% risk of malignancy in retained Müllerian
Upper vagina - draining into prostatic utricle structures ’! Laparoscopic excision
• Normal 17 OH Progesterone • B/L nonpalpable testes OR
• 3 types • U/L nonpalpable testis with hypospadias (specially
proximal) :
– 1. 60-70%: B/L Intra-abdominal testes
DSD UNLESS PROVEN OTHERWISE, WHETHER OR NOT THE
– 2. 20-30%: Classic HUI: One testis in hernial sac / scrotum GENITALIA APPEAR AMBIGUOUS.
& C/L inguinal hernia
– 3. 10%: Both testes in same hernial sac + FT & Uterus
 130 The Urology Masterclass, Department of Urology, CMC, Vellore
Investigations:
– Pelvic USG / MRI - Gonads, Mullerian anatomy, Adrenals
– Karyotype
– S.Electrolytes - CAH
– S.Testosterone / DHT - measure early (may drop quickly)
– 17 - OH Progesterone (21 OHase deficiency) - On Day 3/
4 • Missed anatomical findings at the first intervention
– LH +++ : Anorchia
– hCG Stimulation test
• KKTestosterone/ DHT: 5D reductase deficiency
• Normal response : Androgen insensitivity
• Deficient response: Impaired Testosterone synthesis
- Retrograde contrast studies / Endoscopy at time of
surgery
- Diagnostic Laparoscopy and Gonadal biopsy if
equivocal diagnosis
- Defer ablation till final HPE
Recurrent PUJ obstruction
Definition of pyeloplasty failure
- There are no standardized methods to diagnosed
recurrent PUJO. Usually post pyeloplasty there is
symptomatic resolution (i.e. more than 80% pain relief)
associated with stable or improved renal function and
improved washout from the renal pelvis (i.e. T1/2 < 20
min) on renal scan.
- In asymptomatic children ultrasound is often used more
frequently in follow-up. Renography is reserved for
symptomatic patients or in patient with US showing
progressing hydronephrosis
- The diagnosis of recurrent PUJO is certain if there is
• Inability to improve
– Symptoms,
– Dynamic renographic parameters,
–Renal unit function or hydronephrosis.
Tan et al. defined success as drainage on a diuretic renal
scan (Whittaker test in equivocal cases) and direct
visualization of the PUJ at ureterorenoscopy.
Role of urinary diversion
Anderson and Hynes advised against the use of trans-
anastomotic stenting, as it may predispose to infection
and stricture formation. However the advantage includes,
it ensures urinary diversion, maintain ureteral caliber and
maintain anastomotic alignment. It also provides complete
postoperative urinary drainage and decreases the risk of
urinary leaks. Stenting also ensures no early postoperative
kinking at the anastomotic site. Disadvantage include
urinary infection ,wound infection, haemorrhage and
mechanical ,requires anaesthesia for removal in the
paediatric population.
Reason of failed pyeloplasty
• Young age at initial surgery (less than 6 months),
• Prolonged urinary diversion (dry anastomosis) and
(crossing vessels or long ureteral segment narrowing)
• Lack of RGP before pyeloplasty
• Use of dorsal lumbotomy
• Large redundant renal pelvis if the ureter is not
generously spatulated leading to urinary leakage and
fibrosis
• Poor surgical technique,
• An irreparable pelvi-calyceal system,
• PUJ ischemia with re-stenosis,
• Anastomotic leak with urinoma and fibrosis
• Ureteric stent malfunction and diabetes
Salvage procedure post recurrent PUJO
Endopyelotomy
• It has reduce morbidity, provide a quicker post-operative
recovery and shorter hospital stay
• Introduced by Ramsay et al. in 1984 and further
popularized throughout the 1980s by urologists such
as Badlani et al. who developed the term“endopyelotomy.
• Both retrograde and antegrade approaches are
described
• Retrograde technique includes wire cutting balloon (E.g.
accusize endopyelotomy) and ureteroscopic laser
pyelotomy, usually with the Holmium or
Neodymiumdoped yttrium aluminum garnet laser.
Incisions is usually made in the lateral aspect of the
PUJ
• Percutaneous antegrade endopyelotomy is considered
if there are concomitant pelvi-calyceal stones,
especially >2 cm, which can be managed simultaneously.
• Contraindications :
– Long stenosed segment (>2 cm),
– Uncontrolled coagulopathy and
– Active infection
Laparoscopic re-do pyeloplasty
• Preferred over endopyelotomy in case of crossing
vessels, grades III to IV hydronephrosis or renal
function in the 15% to 25% range. Dismembered
pyeloplasty ,spiral flap procedure Fengerplasty can be
performed It provides larger working space
• It requires often required sharp dissection and
significant mobilization of the entire kidney. Urinary
diversion is must
• Other advantages include identify anterior crossing
vessels,has reduced hospital stay
 The Urology Masterclass, Department of Urology, CMC, Vellore 131

• Disadvantage includes longer operative time, difficulty • Primary PUJO with intra-renal pelvis,
in suturing. Suturing the ureteropelvic junction is the • Secondary PUJO,
most difficult part of performing dismembered
• Complex anatomy and obliterated PUJ/ureter after prior
pyeloplasty.Various other techniques are being devised
surgery.
to facilitate anastomosis. Use of the EndoStitch suturing
device to help save time during the anastomosis.In – Success rates of over 80% are described
addition, use of a running suture for the anastomosis – Good long-term outcomes in children
and LapraTy clips instead of tying knots have also – Approximation of ureteric and calyceal urothelium and
facilitated anastomosis. Others have reported using excision of renal parenchyma
fibrin glue to reinforce the suture. Titanium clips have
also been used (vascular closure staple) to form the • Ileal interposition
ureteral anastomosis in the laboratory but they have – Good long-term kidney function can be seen in up to
not yet been used clinically 25% patients who may require some form of
reintervention i.e. nephrectomy, PCNL (Percutaneous
Open pyeloplasty
nephrolithotomy) or re-anastomosis of proximal ileal
Open pyeloplasty is preferred because of presence of segment. Complications include:
significant peri-ureteric fibrosis, long segment of stenosed
ureter and need for wide mobilization of the proximal ureter – Urinary tract infections
and kidney. Dismembered or flap technique is generally – Metabolic acidosis
utilized. The disadvantage is the increased morbidity
• Auto transplantation
associated with a large incision
– Can typically be combined with a boari flap and pelvi-
Steps of open pyeloplasty vesicostomy.
• RGP or nephrostogram preoperatively is an important
References
initial step in the management of failed pyeloplasty for
precise identification of anatomy preoperatively. Campbell Walsh Urology, 11th edition
• It is important to approach the ureteropelvic junction EAU guidelines 2019
from virgin field. This sometimes necessitates anterior Nguyen HT et al.J Pediat Urol 2010
extension of the flank incision or opening the peritoneal Sidhu G et al. Pediatr Nephrol 2006
cavity. Identification of the ureter below the region of
scarring allowed a carefully planned approach. Nguyen HT et al. J Paed Urol 2014
• Identification of the ureter below the region of scarring Peters CA et al. J Urol 1990
allowed a carefully planned approach. Stephen A et al , J Urol. 2005
• If a fixed retractor is inserted before designing the Desai DY et al. Ind J Urol 2007
pyeloplasty, it can displace the pelvis cephalad or the Holmdahl G et al. J Urol 1996
ureter caudad, leading to redundancy. Koff R et al. J Urol 2002
• A tension-free anastomosis is must Bajpai et al. J Ind Assoc Paed Surg 2013
• Avoid high insertion of the ureter or pelvic redundancy Skoog SJ et al. J Urol 2010
• Drain placement is also important to prevent AUA guidelines on VUR
complications. It should be positioned near the
anastomosis but not on the suture lines, since the The RIVUR trial investigators. NEJM 2014
foreign body may prevent the spontaneous sealing of Storm DW. UCNA 2018
small leaks. Low output via the drain should raise Baily LC, JAMA Paediatrics 2015
suspicion regarding its proper position. Keeney KM, Annual Rev Microbiol 2014
• If inadequate ureteral length or an intrarenal pelvis Langman J. Urogenital System. In: Medical Embryology, 4th
precludes this procedure, ureterocalicostomy is an ed
alternatives
Hutson JM et al Cryptorchidism, Semin Pediatr Surg. 2010
• Postoperatively urine diversion is mandatory. A
nephrostomy tube as well as a trans-anastomotic stent Forest MG et al. Horm Res 1988
is advisable, although a nephrostomy tube alone may Raifer J et al. NEJM 1986
be sufficient in some cases. The stent is removed and a Hagberg S et al. Eur J Paed 1982
low pressure, gravity drip nephrostogram may be Cortes D et al. J Urol 2000
obtained 2 to 3 weeks after the repeat procedure. The
renal pelvis must be emptied at physiological low Cisek LJ et al. J Urol 1998
pressures before removal of the nephrostomy tube. Penson D et al. Paediatrics 2013
Koni A et al. J Urol 2014
Complex reconstruction and auto transplantation
Chua ME et al J Paed Surg 2014
Ureterocalicostomy
Park KH et al. Int J Urol 2007
– Indications:
 132 The Urology Masterclass, Department of Urology, CMC, Vellore

TRAUMA – Flank pain

– Fever – high-grade
I. RENAL TRAUMA – Paralytic Ileus
• Indications for Imaging in Renal Trauma – Cysto + RGP + Stenting / PCN + Antegrade stenting
– Gross Hematuria
– Microscopic Hematuria with shock (systolic • Indications for Exploration
<90mmHg at anytime during evaluation) – Absolute indications:
– Significant associated injuries • Persistent renal bleeding
– Rapid deceleration injuries with clinical suspicion • Expanding perirenal hematoma
or renal injury • Pulsatile perirenal hematoma
– Penetrating trauma even when hemodynamically – Relative indications:
stable • Urinary extravasation
• CT in renal trauma • Nonviable tissue (>20%)
– Gold standard – 96% sensitivity • Delayed diagnosis of arterial injury
– Superior anatomical detail and classification of • Segmental arterial injury
grade of injury • Incomplete staging
– Detects pre-existing anomalies • Combination of above
– Defines contralateral kidney – Exploration for other indication
– Delineates other injuries – Pre-existing renal abnormality like PUJO
• Disadvantages: II. PEDIATRIC RENAL TRAUMA
– Delayed films necessary to detect PCS injury Adult and Pediatric
– Renal vein injuries not well detected • More susceptible to renal injury than adult
• Following up Conservatively Managed Patients – Differences in anatomy
• > 90% of renal injuries can be managed conservatively • Lower than in adult
• Repeat imaging (preferably CT) • Less peri renal fat
– All hospitalised within 2-4 days of significant renal • Relatively large kidney compare to rest of abdominal
injury organs
– All patients with: • Less ossified pediatric thoracic cage
• Fever • More incidence of pre-existing renal disease – PUJO,
• Flank pain megaureter, reflux.
• Falling hematocrit • Hypotension is an unreliable sign – Outpouring of
• Nuclear scintigraphy (DMSA) before discharge to catecholamine maintain the BP even up to 50% blood
document functional status is useful especially in: loss
• All patients with grade 3 injuries associated with • A fall in hemoglobin or PCV is better indicator of blood
devitalized fragments loss
• All patients with grade 4 and 5 renal injuries Indication for imaging
• All patients with persistent post-traumatic hypertension – History – mechanism of injury
should be evaluated with a quantitative radionuclide • Rapid deceleration, fall from >15ft, strike to the flank
scintigraphy with high velocity, i.e. football, cricket bat, etc.
• Ambulate/ Discharge once gross hematuria has resolved – Haematuria- Gross and microscopic (>50/hpf blunt
• Avoid strenuous activity for 6 weeks. trauma and >5/hpf penetrating trauma)
• Follow-up at 3 months – Flank pain
• Examination – Flank echymosis, abrasion
– Urinalysis – Fracture ribs
– Radiological evaluation (individualise) – Abdominal distension/mass/tenderness
– Renal function evaluation When to suspect renal injury
– Monitoring for hypertension – Haematuria
– Management of Urinomas – Flank pain
– 85% resolve spontaneously – Flank echymosis, abrasion
• Indications for intervention: – Fracture ribs
Persistent (>48hours): – Abdominal distension/mass/tenderness
 The Urology Masterclass, Department of Urology, CMC, Vellore 133

– Imaging Modality • Gold standard – 96% sensitivity

• Low threshold in children
Ultrasound with Doppler – reliable first line screening
imaging
– Easy and allow rapid assessment during TRIAGE
– Specificity 95% (but sensitivity 33-89%)
– Detect renal laceration (break in the cortical margin)
– Perinephric collection (Urine or hematoma )
– And follow up patient in the ICU
– Doppler imaging assess vascularity
– Free fluid in the abdomen – Urine or blood?
Disadvantage –
– Do not detect minor retroperitoneal or renal injury
– Highly operator dependent
Contrast enhanced CT
CT is still standard of care- grading and treatment decision
– (EAU 2019)
• Superior anatomical detail and accurate grading
• Detect pre-exist anomalies
• Assessment of contra lateral kidney
• Detect other injuries
Disadvantage
• Delayed images for PCS – 10 to 15 minutes loss if the
patient warrants immediate exploration
• Renal vein not easily diagnosed (Suspect if hematoma
or urinoma seen medially)
Indications
– Hematuria ( microscopic /gross )- definite indication
– Associated abdominal injury regardless of urinalysis
– High velocity/rapid deceleration injury
– Associated rib fractures, spine injury, pelvic fracture
• Follow up CT not recommended. Radiation risk in
children*
Staging renal trauma
AAST (American Association for Surgery of Trauma) 2013

Grade* Description of injury

I Contusion Microscopic or gross hematuria, urologic studies normal
Hematoma Subcapsular, nonexpanding without parenchymal laceration
II Hematoma Nonexpanding perirenal hematma confirmed to renal retroperitoneum
Laceration <1.0 cm parenchymal depth of renal cortex without urinary extravasation
III Laceration <1.0 cm parenchymal depth of renal cortex without collecting system rupture or
urinary extravagation
IV Laceration Parenchymal laceration extending through renal cortex, medulla, and collecting system
Vascular Main renal artery or vein injury with contained hemorrhage
V Laceration Completely shattered kidney
Vascular Avulsion of renal hilum which devascularizes kidney
*Advance one grade for bilateral injuries up to grade III.
‡PUJ disruption is grade 4

Management • Angioembolization – Grade 1-4 injury

• Grade 1-3 Conservative – serial hematocrit, bed rest
for atleast 24 hours
• Grade 4 Conservative if hemodynamically stable, 95%
can be manage conservatively
– Urinoma resolve spontaneously in 85%
– DJ ureteric stents if contrast absent on ipsilateral
ureter
• Grade 5** Hemodynamically stable … conservative in
50%
Intervention
• Children with hemodynamically unstable or penetrating
injury
– When CT now available then Intra operative ‘one shot’
IVU
– 2ml/kg and flouroscopic imaging after 10 minutes
– Document contralateral kidney
– Higher renal preservation rate
– Control hemorrhage and embolization of fistula/
aneurysm
Indication for exploration
– Hemodynamically unstable or low hematocrit (even
after 3 units transfusion )
– Expanding renal hematoma
– Pulsatile hematoma
– Exploration for other causes
– When CT now available then Intra operative ‘one shot’
IVU
– 2ml/kg and flouroscopic imaging after 10 minutes
– Document contralateral kidney
 134 The Urology Masterclass, Department of Urology, CMC, Vellore

BLADDER RUPTURE AAST Bladder Injury scale

Epidemiology Grade* Injury type Description of Injury
RTA : MC cause of blunt bladder trauma
Majority : Extraperitoneal > Intraperitoneal > Combined I Haematoma Contusion, Intramural
Laceration haematoma Partial thickness
INJURY Occurance (%) II Laceration Extraperitoneal < 2cm
Blunt UB trauma + Pelvic # III Laceration Extraperitoneal > 2cm /
(Specially extraperitoneal) 80 - 95 Intraperitoneal < 2cm
Pelvic # + UB injury 5-10 IV Laceration Intraperitoneal > 2cm
+ Other abdo. injuries (atleast 1) 44 V Laceration Intra or Extraperitoneal,
extending into the UB nceck or
+ Urethral injury 10-30 UO (Trigone)
+ Upper tract injury 0.4
Management
Extraperitoneal rupture Conservative (Most extraperitoneal and a few
Mechanism: Pelvic ring distortion intraperitoneal)
x Shearing of the anterolateral UB wall near the UB base x Observation
x “Counter-coup” - bursts opposite the # site x Continuous bladder drainage - 22 F Foley’s
x Occasionally - direct perforation by a sharp bony x A/B prophylaxis - atleast 1 week
fragment Surgical - 2 layer vesicorraphy (absorbable sutures)
Highest risk of UB injury if Indications for Operative Intervention
x Pelvic ring disruption with displacement > 1cm x Intraperitoneal bladder rupture
x Diastasis of pubic symphysis > 1cm x Penetrating non-iatrogenic trauma
x Fracture of the pubic ramus (isolated acetabular injury x Suspected bladder neck injury
unlikely to cause it) x Bony fragments impinging on bladder wall
Diagnosis x Open pelvic fracture
Cardinal sign - GROSS HAEMATURIA x Concomittant rectal / vaginal injury
Absolute indication for imaging : x Entrapment of bladder wall
x pelvic fracture and gross haematuria x Patient undergoing abdominal exploration for other
x penetrating injuries of buttock/pelvis/lower abdomen reasons - to reduce infective complications
with any degree of haematuria Follow - up
Based on clinical scenario in : x Continuous UB drainage
x Gross haematuria without pelvic # x Conservatively managed
x Microhaematuria with pelvic fracture – 1 st cystography 7-14 days after injury (depends on
x Isolated microhaematuria or pelvic # extent of laceration)
Diagnostic modalities – repeat thereafter in case of ongoing leakage
Plain & CT Retrograde (Stress) cystography - – If no contrast extravasation - remove catheter
x comparable sensitivity (90-95%) and speciticity (100%), x After operative repair
CT - Identify other sites of trauma also – Simple injury, healthy patient - Remove catheter after
x retrograde filling of min. 350ml diluted 2 - 4% (6:1 with 7-10 days, no need for control cystography
NS) contrast – Complex injury (Trigone / UB neck involvement /
x 3 films - Scout, Full UB AP, Postdrainage (not required if Ureteric reimplant), Patient factors (CST,
CT) malnourished) - do a control cystography prior to
x Intraperitoneal / Extraperitoneal (Flame shaped) / VVF catheter removal
Excretory phase of CT / IVP - NOT SUFFICIENT
USG - alone - NOT SUFFICIENT
 The Urology Masterclass, Department of Urology, CMC, Vellore 135

UROLITHIASIS ƒ Urinary extravasation

ƒ Higher transfusion rate
1. 1.5cm LOWER CALYCEAL CALCULUS ƒ Longer hospital
1-2cm lower calyceal calculi remain a ‘gray zone’ with Mini-perc:
regards to treatment. The choice between ESWL and invasive
surgery requires careful judgment. • “Peel away sheath”
ESWL: minimally invasive with a low morbidity, short • Tract size <20F (depends on company/instrument)
procedural time and causing minimal convalescence. • Indications:
• Traditional unfavourable factors include: – Useful for children with stone burden < 1.2cm
- Acute infundibulo-pelvic angle – Renal calculi 1-2cm
- Width of infundibulum <5mm • Advantages:
- Length of calyx >10mm ƒ Increased maneuverability
- Shockwave resistant calculi(COM, brushite, or ƒ Decreased blood loss
cystine) ƒ Shorter hospital stay
- Long skin-to-stone distance (> 10 cm) ƒ Possibility of totally tubeless procedure
• Numerous reports show no effect of anatomical factors ƒ Pediatric age
- controversial • Disadvantages:
• Stone free rates: 50-60% – Bleeding hampers visualization
• Cochrane analysis – – Not useful for very large stone burdens
– ESWL had similar success rates compared to RIRS • Results:
with less hospitalization
– 90-100% clearance for 1-2cm renal calculi with
• More cost-effective than RIRS
shorter hospitalization time, reduced blood loss and
• Adjunctive methods like percussion, inversion and pain scores but longer intra-operative duration vs
diuresis can improve stone-free rates standard PCNL
RIRS: – High possibility of tubeless procedure
• Expanding indications with advances in technology and Micro-perc:
technique
• Renal access and PNL are performed in a single step
• Usually require prior stenting and multiple procedures through the “all-seeing optical needle.”
with overall morbidity almost equivalent to PCNL
– 4.85 Fr tract size (needle diameter 1.6mm)
• Stone-free rate better than ESWL and inferior to PCNL
• Micro-optics:
• Expensive but less invasive
– 0.9mm diameter
• Advantages of RIRS over SWL
– 120-degree angle of view
ƒ Use on larger stones
– 10000 pixels resolution
ƒ Obese or pregnant patients
• Procedure:
ƒ Patients with coagulopathy
– Ultrasound/ Fluoroscopic puncture – single-step
PCNL:
– Beveled inner needle removed
• Highest stone free rates – 95-100%
• Success rates need to be balanced against invasiveness – 3-way connector attached to the proximal end of the
of procedure and possible complications sheath
• Preferred in cases of: – Telescope passed through connector side port
ƒ Calyceal anatomy unfavourable for ESWL – Other side port is used for irrigation
ƒ Failed ESWL – Central port is used to pass the laser fiber
(200micron)
ƒ Factors suggesting failure with ESWL:
• Stone free rate 85-90% at 1 month with stone bulk <
ƒ Density >1000HU
2cm
ƒ Skin-stone distance > 10cm
• Use for bladder calculi also reported
ƒ Monohydrate, brushite, cystine stones
Good option for pediatric cases, lower calyceal calculi
x Problems but more studies required
ƒ Invasive • Disadvantages
ƒ Higher risks of complications - Visual clarity
ƒ Bleeding - Use of pressurized irrigation system
ƒ Need for angio-embolization - Lack high quality studies
ƒ Adjacent organ injury - Prolonged duration- experimental
 136 The Urology Masterclass, Department of Urology, CMC, Vellore

• Higher complication rates including haemo/

1.SWL/RIRS
pneumotharax and bleeding with upper calyceal
<10mm 2.PNL punctures
• Inter costal puncture through 11th inter costal space
10-20mm 1.SWL/RIRS
reduces lung/pleural injury, and enables superior pole
Favorable 2.PNL access
factors for SWL
3. INFECTED STAGHORN CALCULUS
Symptomatic 1.RIRS
10-20mm Causes of staghorn calculi:
Lower pole stone 2.SWL
Un-favorable • Struvite
factors for SWL 3.PNL
• Uric acid
1.PNL
• Cystine
>20mm 2.RIRS • Calcium oxalate monohydrate
3.SWL Infection stones:
• Account for 5-15% of stones (F:M=2:1)
• Composed of Magnesium ammonium phosphate and
carbonate apatite
2.BILATERAL STAGHORN CALCULI
• Organisms involved (urease producing): Proteus,
Imaging in staghorn calculi Klebsiella, Pseudomonas and Staphylococcus
• Most accurate method to evaluate a staghorn calculus – Only rare E coli produce urease, but it alters
is CT imaging with three-dimensional reconstruction urokinase and sialidase activity and can cause
– Stone position and burden (stone surface area – can calculi
predict outcome) • Factors predisposing to struvite stone formation:
– Planning access for PNL – Ureteropelvic junction obstruction
– Detects relationship with adjacent organs and – Neurogenic bladder
aberrant anatomy
– Spinal cord injury/paralysis
– Thickness of parenchyma overlying the stone
– Continent urinary diversion
– Detects radiolucent stones
– Ileal conduit
– Less observer dependent
– Foreign body
• 3D CT Urography/Pyelography: invaluable in planning
punctures for complex staghorns or ectopic/horse shoe – Stone disease
kidneys – Indwelling urinary catheter
• Staghorn Morphometry - 3D CTU with 3D software: – Benign prostatic hyperplasia
classifies staghorns into 4 categories based on stone – Bladder diverticulum
burden and unfavourable calyx (1, 2a, 2b and 3). It
– Calyceal diverticulum
predicts success of PCNL and required ancillary
procedures Pre-operative optimization:
GUY’S SCORE • Antibiotics:
• To grade the complexity of PCNL – Sterile urine does not preclude post-operative
bacteriuria (35% risk if antibiotics not used)
• Grade I: solitary stone in mid/lower pole or solitary
stone in the pelvis with simple anatomy – One week of oral ciprofloxacin significantly reduced
post-operative urosepsis in 1 study
• Grade II: solitary stone in upper pole or multiple stones
in a patient with simple anatomy or a solitary stone in – Those with features suggestive of struvite calculi
a patient with abnormal anatomy should receive pre-operative broad spectrum
antibiotics for at least 2 weeks
• Grade III, multiple stones in a patient with abnormal
anatomy or stones in a calyceal diverticulum or partial – Antibiotics also decrease inflammation and bleeding
staghorn calculus • Drainage:
• Grade IV: staghorn calculus or any stone in a patient – Infected hydronephrosis
with spina bifida or spinal injury – Renal function
• It is the only factor that significantly and independently Management:
predicted the stone-free rate (81%, 72%, 35% and 29%
• Until 1970’s it was considered unnecessary to treat
for grade I,II,III and IV respectively)
infection staghorns
Upper vs lower calyceal puncture
– Later morbidity of renal loss, sepsis events and
• Higher success rate with upper calyceal punctures (91% ultimately increased risk of death(30%) was
vs 76%) demonstrated
 The Urology Masterclass, Department of Urology, CMC, Vellore
• Endoscopic procedures (PCNL) are recommended as first
line for staghorn calculi
– Often require staged procedures or adjunctive SWL
– Poorer option is SWL monotherapy +/- hemiacidrin
irrigation
• Complete stone removal is key to preventing recurrence
• Stone and renal pelvic cultures (75-86% concordance)
can guide post-operative antibiotic therapy because
voided culture shows concordance in 0-71% cases
Hemiacidrin irrigation:
• 10% hemiacdrin: pH 3.5-4
• Post-operatively after 4-5days, and once infection and
fever under control
• Started with sterile saline solution and 120ml/hr to
assess tolerability – After 48 hours hemiacidrin
irrigation started and continued for 24-48 hours after
the last visible fragments have been dissolved
• Use at least 2 nephrostomy catheters
• Risk of cardiac arrest due to hypermagnesemia
Preventing recurrence:
• Mean recurrence is 27% at 2.5years
• Radiological and bacteriological follow-up
• Prevention of infection:
– Improved bladder health
– Adequate urinary drainage
– Suppressive antibiotic treatment
• Urinary acidification
– Ammonium chloride/ Ascorbic acid/ Methenamine
hippurate
• Acetohydroxamic acid
– Urease inhibitor: 250mg TID
– Prevents new stones and inhibits growth of stones in
patients with chronic infections with urease +ve
organisms
– 15% risk of DVT – not commonly used
5. CHILD WITH NEPHROCALCINOSIS
Causes of pediatric nephrocalcinosis (Table 1):
MEDULLARY Renal tubular acidosis
Hypercalciuria
Oxalosis
CORTICAL Cortical necrosis
Chronic glomerulonephritis
MIXED Oxalosis
137
Primary hyperoxaluria (PH):
• Inborn errors in metabolism of glyoxylate & oxalate
• PH type 1
– Most common form
– Deficiency of the liver-specific enzyme alanine,
glyoxylate aminotransferase (AGT) results in
overproduction and excessive urinary excretion of
oxalate
– Recurrent urolithiasis and nephrocalcinosis are
hallmark
• Renal biopsy indicated if a high index of suspicion exists
in the absence of radiological features
• Liver biopsy to measure AGT activity essential for
definitive diagnosis of PH1
• Alternative approach: genetic analysis of AGXT gene
for mutations
– supplants the need for liver biopsy
– enables prenatal diagnosis in fetuses
Management: Primary Hyperoxaluria:
• Recommended fluid intake: upto 3 L/m2 per day
• Restriction in oxalate intake of limited usefulness, as
the main source of oxalate is endogenous
• Potassium or sodium citrate at a dose of 100–150 mg/
kg bodyweight recommended
• Pyridoxine (cofactor of AGT) reduces urinary oxalate
by 30% ( Dose : 5 -10mg/kg per day)
6. PREGNANCY WITH URETERIC CALCULUS
• Radiation exposure during various radiological
investigations
– Natural : 3mSv/year
– X-ray Abdomen : 8mSv
– NCCT : 15mSv
– CECT : 30mSv
• Imaging protocol during pregnancy
– X-ray
– USG
• Management protocol
– According to period of gestation
• USG-Primary diagnostic radiological tool
• Non complicated urolithiasis – hydration and
analgesics
• 70-80% of ureteric calculi - pass spontanously
• Relief of obstruction: DJ stenting (< 28Weeks) or PCN(>
28 Weeks)
• URS + intracorporeal laser lithotripsy – best method to
treat ureteric calculus
** Energy source contraindicated– Intra operative
ultrasonic lithotripsy (deafness in unborn child)
• PCNL & ESWL contraindicated
 138 The Urology Masterclass, Department of Urology, CMC, Vellore

7. PCNL AND SPINE DEFORMITIES

Treatment of stone in patients with spinal deformities Percutaneous access
presents a unique challenge Anatomic relationship of ribs, spine and kidneys is
Challenges distorted
- Anesthetic and cardiorespiratory - Patient positioning Aids to plan percutaneous access
- Percutaneous access • CT with contrast with reconstructed images
Anaesthestic & Cardio-respiratory issues • USG-guided fluoroscopic-adjusted puncture
Preoperative evaluation o Direct access to desired calyx
- Pulmonary function test: 47-77% have restricted lung o Avoid visceral injury
ventilation on preoperative PFT o Traverse minimal cortical tissue
- ABG analysis o Achieving multiple tracts by US guidance at the start
- ECHO for ASA-3 of the operation may be helpful
Regional anesthesia is technically challenging due to spine • CT- guided puncture
abnormality and problematic for prone positioning • Laparoscopic assistance
Severe scoliosis • Goumas-Kartalas et al. J Endourol 2010
Altered confirmation of ribs àreduced lung volumes due to
restrictive lung diseaseà atelectasis & V/Q mismatch
PCNL
Difficulty exacerbated by prone position of PCNL, supine
Blood transfusion rate ~20%
may be better.
Stone free rates after PCNL – 63-80%
• Chen et al. Urolithiasis 2013
Higher rates of adjunctive procedures ~50%
• He et al. Int Braz J Urol 2016
ESWL
Inferior to PCNL
Patient positioning
Role in treatment of residual calculi after PCNL
Prone vs Supine and lateral decubitus
Problems
- Maximum area for access with prone position
- Positioning
- Supine/lateral position- reduces area between iliac crest
& ribs, especially if stone is on the concave side of spine - Localizing the stone
Supine vs. Lateral is based on RIRS
- Experience with supine PCNL Limited number of studies. Stone free rates 75-85%
- Ease of access to kidney (side of stone with respect to No blood transfusions and low incidence of complications
the concave side of spine) • Polat et al. J Spinal Cord Med 2017
- Cardio-pulmonary status • Resorlu et al. J Endourol 2012
- Stone burden/need for simultaneous ureteroscopy
Soft padded bolsters & silicone rolls for support- crucial

• Gofrit et al. J Endourol 2004

 The Urology Masterclass, Department of Urology, CMC, Vellore 139

V. STAGHORNS AND OPEN STONE

SURGERIES
Imaging in staghorn calculi
• Most accurate method to evaluate a staghorn calculus
is CT imaging with three-dimensional reconstruction
– Stone position and burden (stone surface area –
can predict outcome)
– Planning access for PNL
– Detects relationship with adjacent organs and
aberrant anatomy
– Thickness of parenchyma overlying the stone
– Detects radiolucent stones Extended pyelolithotomy
– Less observer dependent • Stone in the renal pelvis and multiple extensions into
• 3D CT Urography: invaluable in planning punctures for calyces.
complex staghorns or ectopic/horse shoe kidneys
• Contra-indications:
• Staghorn Morphometry - 3D CTU with a 3D software:
classifies staghorns into 4 categories based on stone – Prior extended pyelolithotomy
burden and unfavourable calyx (1,2a,2b and 3). It – Extremely intra-renal pelvis
predicts success of PCNL and required ancillary – Staghorn calculi in clubbed calyces
procedures • Thin layer of connective tissue extending from the renal
Indications of open surgery capsule into the fat in the renal hilum and then onto
• Anatomical abnormalities - infundibular stenosis, the renal pelvis.
diverticuli, PUJ obstruction, stricture • Incise this layer to gain access to the infundibulum
• Concomitant open surgery/complex stone burden • Subparenchymal dissection exposing the renal pelvis
• Cost considerations and need for single-stage clearance and calyceal infundibula- Gil Vernet
– patient choice • An incision into the renal pelvis and extended in a
• Co-morbid illness, skeletal deformities curved fashion into the necks of the superior and
• Morbid obesity inferior calyces
• Non functioning lower pole, or non functioning kidney
• Ectopic kidney where endoscopic procedures may fail
• Failure of ESWL/PCNL
Operative procedures
• Simple pyelolithotomy
• Extended pyelolithotomy
• Pyelo nephrolithotomy
• Radial nephrolithotomy
• Anatrophic nephrolithotomy
Simple Pyelolithotomy
• For 1-2cm pelvic calculus
• Two stay sutures of 4-0 polyglycolic acid or chromic
catgut.
• U-shaped (Bucket handle) incision in the renal pelvis. Pyelonephrolithotomy
• Incision must not extend through or into the • Large stones in a lower calyceal system
ureteropelvic junction because of the risk of subsequent
scarring. • Continue pyelolithotomy incision into the lower
infundibulum and then onto any involved calyces
• Pelvis should be closed watertight with continuous 4-0
polyglycolic acid or chromic catgut suture. • Leave a stent and close infundibulum and pelvis with a
continuous 4-0 Chromic catgut suture
Radial nephrolithotomy
• For calyceal calculi not amenable to pyelolithotomy
• Small (1 cm) radial incision over the stone, which can
be localized either by palpation with a needle through
the parenchyma or by intraoperative ultrasonography.
 140 The Urology Masterclass, Department of Urology, CMC, Vellore
• Usually combined with simple or extended
pyelolithotomy
Anatrophic nephrolithotomy
• Smith and Boyce, 1968
• The kidney is completely mobilized and renal artery
and vein isolated close to the abdominal aorta
• Renal artery and vein looped and the kidney is cooled
with ice-slush for 10 min
• Traditional technique – Clamp posterior segmental
artery. Inject methylene blue IV and this gives a plane
for incision between blue and blanched tissue
• Nowadays – Hilar and branch dissection avoided – (M.K.
Mansi) and vessels are clamped at origin
• Renal capsule incised longitudinally along the lateral
border and the posterior leaflet mobilized off of the
renal parenchyma for 2–3 cm
• Nephrotomy incision made on the posterior surface 1–
2 cm from the lateral convex border of the kidney
directly into the posterior calyces to remove stones
• Infundibular and calyceal reconstruction is
accomplished.
VI. ECTOPIC KIDNEYS AND STONES
Susceptible to more calculi formation due to stasis
Anterior position of pelvis with malrotation
High insertion of ureter
Aberrant renal vasculature
Challenges
Aberrant vessels
Anatomical distortion
Overlying viscera
Difficult position/space/access
CT scan is a pre-requisite to delineate anatomy and
orientation of the ectopic kidney.
Laparoscopic/robotic pyelolithotomy
When other associated abnormalities like PUJO need to be
treated
Or when PCNL/ESWL are not possible
Stone free rates of ~80%
Robotic pyelolithomy – better optics and easier to close
the pyelotomy
• S. Ramakumar et al. J Endourol, 14 (2000)
ESWL
Limited experience, few series report 60-70% clearance
Higher rates of residual stones, important to exclude
anatomical factors like PUJO
• Tunc L et al. Int J Urol. 2004 Oct; 11(10):831-6.
PCNL
Has to be done supine/transperitoneally
Bowel injury – 13-27%
Transfusion rate – 14-24% in larger stones
Modifications of PCNL for ectopic kidneys
USG guided –For identifying calyces as well as using probe
to deflect bowel
Laparoscopic
 The Urology Masterclass, Department of Urology, CMC, Vellore
Ureteroscopy/RIRS
Stone free rate – upto 80% in some series
Ureter may be tortuous, high insertion –making it
technically difficult.
Extraction of fragments important as drainage may not be
optimal
Consider if Small stones <2cm and availability of small
flexible URS with 270 degree active deflection, holmium
laser and stone baskets
• Jaap D et al, J Urology 2017
• Stein et al, Current Opinion in Urology 2017
USG-guided PCNL
Desai and Jasani reported the use of ultrasound
guidancefor PCNL. Ultrasound guidance can help depict
viscera, and theultrasound probe itself can be used to
deflect bowel away fromthe kidney. However, ultrasound-
guided PCNL may be associatedwith a risk of injury to
overlying collapsed bowel, whichmay not be adequately
visible with ultrasound. Additionally,
ultrasound-guided PCNL is inferior to a laparoscopy-
guidedPCNL in the event a second tract is necessary. The
endoscopicvision provided by laparoscopy can permit a
safer transmesentericpuncture and tract dilatation
compared with ultrasoundimaging, which provides less
clarity and cannot facilitate creation
of an additional tract.
RIRS
It is reserved for cases where ESWL or PCNL not feasible.
Although ureteroscopy hasbeen successful for stones in
pelvic kidneys, additional approachesmay be necessary
to clear all of the fragments.
VII. HORSESHOE KIDNEY AND STONES
Incidence
The horseshoe kidney, with a prevalence of 0.25%, is the
most common renal fusion abnormality. The incidence of
stone formation in horseshoe kidneys is as high as 20%.
Predisposing factors
The malrotation of thefused kidney causes insertion of the
ureters to be superior and lateral (high insertion). In
addition, the ureter is draped over the renal
isthmus,resulting in an anterior deviation in itscourse
several centimetres below the ureteropelvicjunction. These
aberrations often result in impaired urinary drainage and
stasis, which can ultimately predispose to urinary stone
formation.
Compared with a group of stone formerswith normal renal
anatomy, the patients with horseshoe kidneysexhibited a
similar distribution of metabolic derangements, withthe
exception that hypocitraturia was overrepresented.
Low urine volume, hypercalciuria, and hypocitraturia were
the most common derangements identified. These findings
141
suggest that metabolic abnormalities, in addition to
anatomic variations causing urinary stasis, contribute
significantly to the formation of stones in these patients.
Diagnosis
A preoperative contrast enhanced CT scan is needed to look
for various abnormalities associated with horses hoe kidneys.
These abnormalities include a higher incidence of UPJ
obstruction (15%–33%) and aberrant vasculature as the
vesselsenter the isthmus dorsally, precluding
percutaneousaccess there. Another consideration isthe
possibility of a retrorenal colon(Fig.1)(upto 45%) which
wouldaffect access.
Treatment
PCNL: It has become the standard of care for stones greater
than 2 cm in size.The kidney is subcostal and upper calyces
are lateral and dorsal. Access is best achieved via the upper
poleposterior calyx. The access angleis 15o as opposed to the
30o for normal kidneys(Fig. 2)
This access gives direct accesstoward the renal pelvis and
is associated witha low risk of pneumothorax, as the upper
polelies well below the costophrenic angles of
thelung.Lower pole calyces are anterior and difficult to
access with rigid scopes.
ESWL:There have been a number of studies looking at
efficacyof ESWL in horse shoe kidneys with success rates
range from 28% to 80%. Sheir and colleagues documented
a success rate of 79% for stones smaller than 15 mm, which
dropped to 53% once stones were larger than 15 mm.UPJ
obstruction should also be excluded before proceeding. If
the patientis not stone free after ESWL, RIRS or
percutaneous clearance of stones should beconsidered.
RIRS :Its indication is limited to stone burden less than 2
cm. It needs specialized equipment and expertise. It may
require staged procedures.
Laparoscopy: This is a rarely used modality of treatment
forstones in horseshoe kidneys. In the setting of UPJ
obstruction secondary to a crossing vessel, laparoscopy
would be the treatment of choice, as it allows concomitant
treatment of the obstruction.
 142 The Urology Masterclass, Department of Urology, CMC, Vellore

FORGOTTEN DJ STENT – Hydrogel

– Heparin
Forgotten foreign bodies in urinary tract – Silver Nitrate
- Occurs due to poor compliance of the patient or failure – Ofloxacin
of the physician to adequately counsel the patient
– Triclosan - fares significantly better
- Apart from stents, forgotten foreign bodies include
ruptured balloons of catheters, catheter tips, Reduction of stent encrustation
resectoscope beaks and metal tips • Triclosan is a potent, broad-spectrum antimicrobial and
Complications of forgotten stents2 anti inflammatory agent
• Recurrent UTI and sepsis • Glycosaminoglycan-coated stents and catheters have
demonstrated reduced encrustations
• Migration
• Electrified catheters, inflation of balloon retention
• Encrustation and blockage devices with triclosan, intermittent rather than
• Nidus for stone formation continuous drainage through the catheter and
• Fistulization irrigations with Suby G solution
• Fragmentation Prevention of retained stents
Management of forgotten stents • Biodegradable stents - dissolve over time
• NCCT - best imaging modality – Incomplete stent dissolution can result in ureteral
– Shows encrustation and stent condition along the entire obstruction, or become a nidus for urinary tract
length of the ureter infection or encrustation
• Standard options ofmanagement: • Stents with thread which project out of the urethra can
rarely be missed and easily removed by pulling out
– ESWL , high success rates if encrustation minimal
– Low acceptability
– Antegradenephroscopy or ureteroscopy
• Patient education is the key
– PCCL or Cystolitholapaxy
Stent registry
– Ureteroscopy and fragmentation of encrustation
• Various protocols including OT logs, stent log book,
– Open surgery patient cards/pamphlets, etc have been shown to be
•Pre op IV antibiotics and decompression by PCN reduces ineffective as they all suffer from human error
the incidence of sepsis • Computerized stent registry has been shown to reduce
•Multiple procedures and combination of techniques may incidence of forgotten stents to less than 1%.
be required
Risk factors for stent encrustation5
• Poor compliance
• Long indwelling times, sepsis, pyelonephritis, pregnancy
• Chronic renal failure, recurrent or residual stones
• Lithogenic history, metabolic abnormalities congenital
renal anomalies, and malignant ureteral obstruction
• Chemotherapy with hyperuricosuria
• Hydrophilic-coated polyurethane stents encrust faster
Biofilms
•Organic components in the urine crystallize out onto the
surface of biomaterial and become incorporated into a
bacterial biofilm layer.
•Urease produced by the adhered bacteria hydrolyses the
urea to produce ammonia. This elevates urinary pH,
favoring the precipitation of magnesium and calcium
as struvite and hydroxyl apatite.
• Studies confirm that the organic biofilm layer coating
retrieved non-encrusted stents can remarkably enhance
crystal precipitation and aggregation events on the
surface
Reduction of stent encrustation
• Material:Metal stents are more prone to encrustation
• Coating materials:
The Urology Masterclass, Department of Urology, CMC, Vellore 143
 144 The Urology Masterclass, Department of Urology, CMC, Vellore

XI – HYPERPARATHYROIDISM
Signs and symptoms:
Epidemiology of nephrolithiasis in hyperparathyroidism:
• “Stones, Bones, Abdominal Groans and Psychic Moans”
• Primary hyperparathyroidism is the cause of
• Non-specific:
nephrolithiasis in <5% of cases
– Fatigue
• Prevalence of urolithiasis in primary
hyperparathyroidism – Lethargy
– Older studies 40-60% – Depression
– Newer studies – reduced because of detection of – 30-40% are asymptomatic
asymptomatic cases Lab diagnosis:
• Possible risk factors for stone formation: • Repeated serum calcium levels >10.1mg%
– Hypercalciuria, Hyperphosphaturia, Hypocitraturia, – Use ionized calcium in equivocal cases
Hypervitaminosis D
– Randall’s plaques
• Increased urine cAMP levels – historical interest
– Younger age
• Serum chloride:phosphate ratio >33 + serum phosphate
– Previous stone events <2.5mg% raises suspicion
Types of stones: Imaging for hyperparathyroidism:
• Hyperparathyroidism accounts for 2% of oxalate stones • Ultrasound: 35- 75% sensitive (88.5%)
and 10% of apatite stones
• CT: 42- 68% sensitive
Types of hyper-parathyroidism: • MRI: 57- 88% sensitive
• Primary Hyperparathyroidism • Tc99M sestamibi: 70- 91% sensitive
– Parathyroid adenoma (80-85%) • Selective venous cath: up to 80% sensitive
– Parathyroid hyperplasia( 10-15%)
– Parathyroid carcinoma (2-3%)
• Secondary Hyperparathyroidism
• Tertiary Hyperparathyroidism

Composition Hyperparathyroidism Others Idiopathic

Hypercalciuria
Oxalate calculi

Calcium oxalate dihydrate 35.6% 24.8% 49.5%

Calcium oxalate 16.3% 57.4% 30.2%
monohydrate
Phosphate calculi
Carbapatite 32.2% 15% 14.9%
[Ca 10 PO 4(6).CO3 .H 20]

Brushite [CaHPO 4 .2H2 O] 14% 2.2% 4.9%

Other calcium phosphate 1.9% 0.6% 0.4%

 The Urology Masterclass, Department of Urology, CMC, Vellore
Management of hypercalcemia:
• Hypercalcemia above 15mg% can be life-threatening
– Combination of approaches – calcium can be
decreased by 3-9mg% within 24-48hours
• Hydration +/- Diuretics – first-line
– Increase in ECF volume – Increases calcium excretion
by 100-300mg/d
– Increased sodium excretion with loop diuretics
further increases urinary calcium (>500mg/d)
– Life-threatening: 6L isotonic saline/d + Frusemide
100mg every 1-2hr – Urinary calcium increased to
>1g/d and serum calcium reduces by 4mg%/d
• Bisphosphonates – IV Pamidronate or Zolendronic Acid
can lower calcium to normal within 24-48hrs with a
single dose
• Calcitonin – 2-8U/kg IV/SC/IM – rapid action so can be
used in life-threatening hypercalcemia
• Dialysis
CMC STENT REGISTRY
Pops up a message to the clinician, and automatically sends an SMS to the patient
in case his stent removal date is overdue. It also alerts the clinician, and in case the
patient fails to respond to the SMS, a letter is sent at his address
145
Stone management in hyperparathyroidism:
• Stone management:
– As per stone bulk and standard options
– Brushite relatively resistant to SWL
– May need diversion till parathyroidectomy if
obstructed/ infected
• Parathyroidectomy:
– 8.3% risk reduction in renal stone events
– 30% still form stones 5years after parathyroidectomy
– After 10 years, risk returns to that of controls
Suggested readings:
• Mollerup CL et. Risk of renal stone events in primary
hyperparathyroidism before and after parathyroid
surgery: controlled retrospective follow up study.
BMJ 2002;325:807
• Campbell-Walsh Urology, 10th edition
• Berger AD et al. Patients with primary
hyperparathyroidism—why do some form stones? J Urol
2009; 181: 2141-5.
• Bouzidi H et al. Does urinary stone composition and
morphology predict for primary hyperparathyroidism?
Nephrol Dial Transpl 2011; 26: 565-572.
• Harrison’s Principles of Internal Medicine, 16th edition,
2005, McGraw Hill Company.
 146 The Urology Masterclass, Department of Urology, CMC, Vellore

URINARY TUBERCULOSIS

Background
• Longer time than MGIT 960
• 10 million cases in 2017
• Labour-intensive in the handling of vials and
• 0.9 million with HIV maintenance of the instrument
• Among the top 10 causes of death worldwide • Potential risk of cross-contamination of the cultures
— 1.3 million people died from TB (including 0.3 million
with HIV) GeneXpert MTB/RIF PCR
Genitourinary tuberculosis • Cartridge based automated nucleic acid amplification
• 2nd most common form extra pulmonary tuberculosis test
– 30-40 % • WHO endorsed – 2010
• Reactivation of dormant focus • 81 base pair core region of rpoâ gene
• Urinary tract involvement - 80% • Mutations within the RRDR region of the rpoâ gene
• Genital tract involvement - 20 % • Integrates sample processing and real-time PCR
• 18% of infertile women (20-40 years) analysis in a single step
• Rapid < 2 hours
Diagnosis • Automated data analysis and interpretation
Major criteria • Can identify rifampicin resistance
Granulomatous lesion on histopathology
AFB positivity in urine or histopathology TB LAMP
Positive PCR • Loop mediated isothermal Amplification of DNA
Minor criteria • Less infrastructure, biosafety issues, training, visual
flourescence
Changes suggestive of TB on IVU/CT or MRI
• Better sensitivity than smear, less than Xpert (63 vs 77
Haematuria vs 89), same specificity
Raised ESR • Recommended as a replacement for smear if Xpert not
Pulmonary changes available or as an add on test in smear negative – Only
GUTB – Presence of one major and /or 2 minor criteria for pulmonary so far

Advances in Smear microscopy Line probe Assays

• LED
• Fluorescent stains- Auramine O
• 10% more sensitive, equal specificity
• Improvement more pronounced in low bacterial loads
• Time to read slide: 1 min vs 4 min
• No difference between different dyes used
Liquid AFB culture MGIT 960
• 7 ml of Middlebrook 7H9 broth base and an O2 depleted
fluorescent compound embedded in silicone at the
bottom of the tube
• 0.5ml processed specimen inoculated
• Automatic UV reading every hour
• Dextrose, Oleic acid, Albumin and Catalase
• MGIT PANTA
• 7-42 days
BACTEC 460 radiometric assay
• 14
C labelled palmitic acid present in the liquid media of
the culture is metabolized
• 14
CO2 produced is detected
• Requires the use of radioactive reagents
• Role : Rapid detection of multi drug resistance, mainly
Rifampicin and INH
• 6 NRLs and selected IRLs - specialised labs
• Reverse hybridisation of DNA strips
• Sen/Spec – Near 100 for Rif, 84 sens for INH
• Specialised lab, 72 hours
• Genotype MDTBRplus (Hain LifeScience, Germany), INNO-
Lipa Rif.tb (Innogenetics, Belgium)
Role of imaging
• High - dose intravenous urogram accepted as standard-
Being replced by CT Urogram
• Role of RGP
To delineate the length of the stricture at lower ureter
To obtain urine samples for culture from each kidney
• Axial imaging to rule out renal parenchymal masses:
Scarring, autonephrectomy
 The Urology Masterclass, Department of Urology, CMC, Vellore
Mechanism of action of ATT drugs and Drug resistance:
Drug Resistant Tuberculosis
• MDR TB
TB bacteria that a person is infected with are resistant
to isoniazid (INH) and rifampicin (RMP)
• XDR TB
TB that are resistant to at least rifampicin and isoniazid
and resistant to a fluoroquinolone and to at least one
of the three injectable TB drugs, capreomycin,
kanamycin and amikacin
• TDR
TB strains that are resistant to all the first line drugs
as well as all the second line TB drugs
NEWER DRUGS:
Bedaquiline:
• New class diarylquinoline, FDA approved after phase 2
itself
147
• Blocks mycobacterial ATP synthase
• Long half life
• No cross resistance with any 1st or 2nd line drugs For
XDR use only, 6 centres in the country
• 400 mg od for 2 weeks, 200mg thrice weekly for 22
weeks
• Informed consent, QT interval monitoring
Delamanid
• Nitroimidazole
• Inhibit Mycolic acid synthesis
• For MDR Tb only
• 100mg twice daily for 6 months
• Informed consent
• Not to be used with Bedaquiline
 148
Case definition
• Newly diagnosed
Include cases less than 1 month of treatment
Previously treated
- Recurrent TB
- Treatment failure
- Lost to follow up
- Others - Most recent outcome unknown
Treatment
(Km- Kanamycin, Lfx- Levofloxacin, Eto- Ethionamide, Cs- Cycloserine
Cm- Capreomycin, PAS- Para-Amino Salicylate, Mfx- Moxifloxacin, Cfz-
Clofazimine, Lzd- Linezolid, Amx/Clv- Amoxycillin-Clavulanate)
Surgical procedures
• Drainage for hydronephrosis (ureteric stenting or
percutaneous nephrostomy)
• Drainage of abscesses or localized collections
• Definitive local treatment of the affected part of the
kidney (cavernotomy/partial nephrectomy)
• Nephrectomy of the non-functioning tuberculous kidney
(open/laparoscopic/retro-peritoneoscopic techniques)
• Reconstruction of the upper urinary tract
Indications for nephrectomy
• Non-functioning kidney with or without calcification
• Extensive disease involving the whole kidney with
hypertension and PUJ obstruction
• Coexisting renal carcinoma
• Despite sterile urine after chemotherapy 50%
nephrectomy of biopsies still show TB
Indication of partial nephrectomy
- Localized polar lesion containing calcification that has
failed to respond after 6 weeks of intensive
chemotherapy
- An area of calcification that is slowly increasing in
size and is threatening to gradually destroy the whole
kidney
- Partial nephrectomy is not justified in the absence of
calcification
Reconstruction of PUJ
• In intrarenal contracted pelvis the standard method of
Anderson-Hynes (dismembered pyeloplasty) is not
appropriate
The Urology Masterclass, Department of Urology, CMC, Vellore
• Options
-Non-dismembered pyeloplasty
-Calicoureterostomy
-Ureterolysis of the fibrotic segment and stenting
-Intubated ureterotomy (Davis)
-Ileal ureter
Renal salvageability
o Lower ureteric stricture
o Renal units with GFR of >20 ml/min/m2
o Good renal cortical thickness
Ureteral Stricture
• Lower ureteral stricture is seen in 9% of GUTB
• Etiology
– Oedema- Early
– Fibrosis- Late
• Corticosteroids may be given in the initial phase when
there is active disease to decrease inflammation/
oedema and stricture formation
• It is not universally advocated
DJ Stenting
• Early ureteral obstruction could be due to oedema
around orifice.
• Oedema resolves once ATT is started
• May progress to fibrosis
• Preservation of renal function is the goal
• Disease stabilizes in 6 week time.
• No guideline for management of early partial ureteral
obstruction
• Early stenting is better than observation:
– Higher reconstruction rate: 49% Vs 8%
– Lower nephrectomy rate: 34%Vs 73%
– May lead to spontaneous resolution of stricture
Observation
• When no hydronephrosis, flank pain, or sign suggestive
of ureteral obstruction of IVP at time of diagnosis of TB
• Fibrosis can occur after starting ATT
• Interval between starting ATT and appearance of
stricture is not well defined.
• Most strictures occur within 2 months
• Two weekly IVP for at least 3 months is recommended
Duration of stenting
• Stricture should be re assessed after completion of
intensive phase of ATT.
• Definitive reconstructive surgery can be done after
completing 6 weeks of ATT.
• Balloon dilatation has been described
– Results poor than open reconstruction.
– Outcome depends on the function of renal unit
– 25% success in poorly functioning kidneys
 The Urology Masterclass, Department of Urology, CMC, Vellore
Follow up after stent removal
• The recommended follow-up protocol, regardless of the
manifestation of GUTB, is evaluation at 3, 6, and 12
months after the course of chemotherapy
• IVP to ensure patency of ureter
• Post inflammatory fibrosis can continue to progress
after completion of ATT
Central Boari flap in bilateral ureteric stricture
• Reconstruction of bilateral ureteral stricture – Difficult
surgical challenge
• Combined use of bladder flap and TUU – uncommon
technique
• Combined Y-shaped common channel TUU with Boari
flap
– Provides a more blunt-angle anastomosis and a larger
anastomosed-lumen
– Easier urinary drainage from both kidneys and
avoided the risk of ureteroureteral reflux
– Good tension-free repair over the anastomosis
– Efficacious and feasible procedure for long-segment
strictures of both ureters.
Bladder
Aims of the reconstructive surgery
• Enhance the volume of the small urinary bladder thus
enabling the patient to retain urine for a reasonable •
period of time.
• Restoration of function – low pressure (less than 30 cm
of water) reservoir during storage and as a high
pressure • compressor during micturition
• Prevention of incontinence and infection that may
jeopardize upper urinary tract integrity.
• Before any surgical intervention, a minimum of four
weeks of ATT is recommended, which allows
stabilization of the lesion and better planning of
reconstructive surgery
Indications for Augmentation Cystoplasty
• Small capacity contracted bladders where non operative
management protocols have failed.
• Loss of elasticity and compliance, leaving a capacity of
less than 100 ml, in severe disease involvement -
intolerable symptoms like frequency, nocturia, urgency,
pain and haematuria.
Bladder reconstruction
Orthotopic neobladder reconstruction-
• Tubercular thimble bladder with capacity <15 ml and
associated with
Significant lower tract symptoms,
Suprapubic pain
Lower ureteral pathology
• Alternative to augmentation cystoplasty in an attempt
to eliminate the diseased, fibrosed, non-compliant
native bladder
149
• No evidence to suggest that bladder reconstruction was
better than conduit diversion for benign disease.
• Bladder replacement using an ileal segment vs. an
ileocolonic segment is better in terms of lower rates of
nocturnal incontinence.
Renal failure post augmentation cystoplasty
• Deterioration of renal function after augmentation
cystoplasty was strongly associated with preoperative
diagnosis of lower urinary tract dysfunction.
• Impairment of renal function is likely related to primary
pathology rather than augmentation cystoplasty.
• There is no evidence that AC causes renal damage.
• Close follow-up is necessary in patients with poor renal
function to search for remedial and modifiable factors
that lead to renal function deterioration.
Prostatic tuberculosis
• Despite tuberculosis being very common in India,
granulomatous prostatitis associated with
tuberculosis is not common.
• Tubercular prostatitis or prostatic abscess is more
commonly seen in patients with immunocompromised
conditions
• The clinical findings in prostatic tuberculosis are often
nonspeciûc
• In many cases, a diagnosis of tuberculous prostatitis
is made by the pathologist, or the disease is found
incidentally after transurethral resection.
• In mycobacterial prostatitis, granulomas predominate
within the peripheral zone of the prostate, although the
transition or central zone may also be affected
• Tuberculosis of the prostate is usually secondary to
tuberculous infection of the upper urinary tract
• Distinction between prostatic cancer and tuberculosis
is difficult.
• Therefore, suspicion of tuberculous prostatitis requires
a confirmatory biopsy of the prostate
• Transrectal ultrasound-guided needle biopsy of the
prostate can yield a reliable diagnosis
• Complications of tuberculous prostatitis include
involvement of the epididymis, as well as scrotal and
perianal abscesses, anejaculation, infertility
Follow up:
• Clinical follow up monthly – Weight, symptoms
• Smear exam at the end of Intensive phase if positive at
start
• Reconstruction can be undertaken after 4 weeks of ATT/
during Intensive phase
• 6% recurrence at a mean of 5 years for urinary TB, < 1%
if nephrectomy of involved unit
• Surveillance should continue for 10 years following
completion of ATT and should include visits every 6 to
12 months for urine mycobacterial culture and/or urine
polymerase chain reaction as well as ultrasonography.
 150 The Urology Masterclass, Department of Urology, CMC, Vellore

Urogenital Fistulae
I. VESICOVAGINAL FISTULA
Classification
• Simple fistulas: Small in size (<0.5cm), non radiated The VVF Score
-Complex fistulas: Previously failed fistula repairs, large Scarring None 0
(<2.5 cm) , radiotherapy, malignancy, associated Mild 1
rectovaginal fistula, involving continence mechansm
Moderate 2
• Giant vesico-vaginal fistula (Lawson): Combination of
juxta urethral, mid- vaginal and juxta-cervical fistulae. Severe 3
• Intermediate-sized fistulae: between 0.5 and 2.5 cm Urethral status Intact 0
Partial damage 2
Zmerli classification Complete loss 3
• Type I
Simple VVF which doesn’t involve the bladder neck and • 83.5% rate of dryness at discharge for patients with a
the urethra score less that 3, and a 40% rate for those with a score of
3 or higher.
• Type II
Complex VVF which involves the bladder neck or the
urethra
• Type III
Destruction of the pelvic floor
WHO Classification- Criteria based on the degree of anticipated difficulty of the repair
Defining criteria Good prognosis/Simple Complicated/Uncertain

Site Vesico-vaginal(VVF) Recto-vaginal(RGF) mixed VVF/RVF involvement of cervix

Size(diameter) <4cm >4cm
Involvement of the
urethra Absent Present
Scarring of vaginal tissue Absent Present
Circumferential defect * Absent Present
Degree of tissue loss Minimal Extensive
Ureters/bladder Ureters are inside the bladder & Ureters are draining into the vagina
involvement not draining into the vagina & bladder may have stones
Number of attempts at No previous attempt Failed previous attempts of repair
repair
*The complete separation of the urethra from the bladder

Etiology • Avoids exposure to ionizing radiation and contrast

agents
- Congenital
• Not a standard recommendation.
- Acquired: Obstetric, surgical, radiation, malignant, and
miscellaneous causes
- Third world countries: Obstructed labor [90%] Radiation induced VVF
- Industrialized world: (>75 %) injury to the bladder at • Majority of fistulae become apparent 1.5–2 years after
gynecologic or pelvic surgery termination of radiotherapy
Role of MRI • Repair delayed up to 12 months
• Provides excellent tissue contrast. • May require multiple repairs
• Allows demonstration of the level of fistula tracts and • Cystectomy and urinary diversion may be needed in
urine leak clearly. inoperable cases.
 The Urology Masterclass, Department of Urology, CMC, Vellore 151

Urinary Diversion in complex VVF • Delaying surgery until infection has subsided
• With excessive fibrosis in surrounding tissues, multiple advantageous in the case of obstetric fistulae
failed repairs, cystectomy and urinary diversion may • Tissue inflammation, infection needs to clear and
be needed. urinoma or abscess needs to resolve before attempting
• Little objective evidence to determine safety and repair
practicality.
Surgical approaches:
Prognosis • Abdominal route
• Good prognosis or simple fistula – Repaired by surgeons • Vaginal route: Recovery short with less morbidity, blood
competent to undertake loss and post-op bladder irritability
• uncomplicated fistula repairs • Contraindications to vaginal approach
• Uncertain prognosis or complicated fistula– Will -Severely indurated vaginal epithelium around the
require referral and repair by a specialist fistula fistula
surgeon -Prior failed repair
->2 cm, supratrigonal
Diagnosis -Small capacity or poorly compliant bladder
• Elevated creatinine level in either the extravasated fluid -Repair requiring ureteric reimplantation
or the accumulated ascites helps confirm urinary
-Involvement of other pelvic structures
leakage.
-Vaginal stenosis and inability to obtain proper
• CECT with excretory phase diagnoses urinary fistulae
exposure
and shows ureteric integrity, PCS dilatation and
presence of associated urinoma
• MRI, with T2 weighting, provides optimal diagnostic Transabdominal repair
information regarding fistulae and may be preferred • Transvesical or an extravesical (bivalve technique)
for urinary - intestinal fistulae O’Conor
• Laparoscopic and robot-assisted.
Management: • Nezhat et al. were the first to report on the outcomes of
• Spontaneous fistula closure: laparoscopic VVF repairs in 1994
-0.5–2 months of catheterization and anticholinergic • Melamud et al. reported on the first robot assisted VVF
medication [10% cases] repair in 2005.
-Fistula is of small diameter, is detected early, or there • Success rate: 94-100%
is no epithelization of the fistula
• An overall spontaneous closure rate of 13% ± 23% Trans-abdominal repairs:
• Electrocoagulation of the mucosal layer with Technique Principle
catheterization Bladder rotation Large defects and neourethra
• Fibrin sealant has been used as an adjunctive measure flap
following electrocoagulation
Omentalpedicled Greateromentummobilised on the
Peterson in 1979. Gel-like nature of the fibrin patch graft right gastroepiploic artery
sealant that plugs the hole until tissue (TurnerWarwick)
ingrowth occurs from the edges of the fistula O’Conor– Excision of fistulous tract
Timing of intervention Transperitoneal afterdissecting the
• Early (1-3 months) Vs Delayed repair (2-4 months) Mundy - Extra- posterior wall of bladder
-Success of 86 to 100% Vs 88-94%. Psychosocial peritoneal caudally- both organs closed
advantage in two layers
• Delayed repair PeritonealFlap 4x6cmpedicled peritoneal flap
-Undertaken after 3–6 months to allow healing of any (Petri and from paravesical peritonium
inflammation and edema Hohenfellner)
-Delay of 1–2 years - radiation induced VVF Fleischmann Abdominal placement of gracillis
and Picha flap
• Delayed repairs does not appear to result in statistically
superior results and may have significant social and Combined Especially for radiation.
psychological ramifications for the woman and her approach Abdominal closure of
family (Marshall) bladder and vaginal colpocleisis
 152 The Urology Masterclass, Department of Urology, CMC, Vellore

Transvaginal approach Disadvantages:

• Latzko technique • The potential for greater morbidity and complications
• Vaginal flap techniques • Complex procedure compared to transvaginal repair
requiring expensive equipment
• Martius labial fat pad flap/ peritoneal flap
interposition
• Success rates: 82-94% II. URETERO- VAGINAL FISTULA
Etiology:
Trans-vaginal repairs: • 10% of VVF’s may have an associated UVF
Technique Principle • Etiology predominantly gynecological Increasing
numbers of ureteric injuries after the introduction of
Martius flap Labial fat pad +/- bulbospongiosus
laparoscopic surgery – initial reported rates up to 1.4%
muscle
but latest studies show a rate of 0.3% comparable to
Sims and Excision of fistula with double closure open procedures indicating better results as experience
Simon Hribar Latzko + fascia lata patch and with these procedures increases
Histoacryl • Obstetric causes predominantly associated with
Latzko Partial colpocleisis caesarean section
Moir Repair of urethrovaginal fistula with
intact anterior wall by suturing free • Common sites of injury:
edges of vagina over a thin catheter,
Pelvic brim
extending vaginal incision above level
bladder neck and using in-rolling Infundibulopelvic ligament
stitches Cardinal ligament
Ueda Vaginal mucosal flap Tunnel of Wertheim
Lehoczky Island flap of labiummajus fat pad + Lateral pelvic side wall above uterosacral ligament
internal pudendal artery and pudendal
nerve
Prophylactic ureteric stenting
Mraz and sutory Seromuscular ilealflap
• Did not affect the rate of injury
• Does not prevent transmural injury but assist in
Prognostic factors of recurrence after vesico-vaginal fistula immediate recognition
repair
• Multiple fistulas
Ureteric injury:
• Fistula size (>10 mm)
• Intra operative ureteric injury
• Fistula type (Type II)
Transection/Ligation/devascularization/clamping
• Fistula etiology (obstetrical)
• When identified - immediate repair
• Presence of urinary tract infection before the repair
-Ureteroneocystostomy
Prevention of recurrence:
-Psoas hitch
• Adequate exposure, careful dissection and tension free
closure -Boari flap
• Vascularised interposition of flap
• Maintenance of a dry, uninfected suture line • Early post-operative period: Identification and high
index of suspicion of ureteric injury
• CECT/NCCT- Urinoma, collection or sepsis
Laparoscopic and robotic VVF repair:
Advantages:
Early post-operative period:
• Magnification during the procedure
• Cystoscopy, RGP & DJ stenting or PCN when there is
• Better hemostasis obstruction
• Decreased abdominal pain PCN indication-
• Shorter hospital stay • When patient is unfit for anaesthesia
• Quicker recovery and early return to work • Preserve renal function
• Cosmesis • Antegrade DJ stenting later
• Difficulty of pelvic suturing during laparoscopy
overcome by robotic approach
The Urology Masterclass, Department of Urology, CMC, Vellore 153

Delayed identification:
• Intravenous urogram/ CT Urogram
• Delayed identification: Management Ureteroneo
cystostomy with one of the following-
-Psoas hitch
-Boari flap
-Transureteroureterostomy
-Ileal substitution of the ureter
-Renal autotransplantation
 154 The Urology Masterclass, Department of Urology, CMC, Vellore
URETHRAL STRICTURE
Industrialized countries: Iatrogenic or idiopathic
Developing world: Genital lichen sclerosus
Iatrogenic causes : Catheterization, cystourethroscopy,
transurethral resection
Others: Idiopathic, trauma, infection/inflammation, and
lichen sclerosus
Retrograde Urethrogram:
• Conventional Technique
Foley’s catheter
Balloon inflated with 1.0–1.5 mL of saline solution in
navicular fossa
• Clamp Method
balloon less catheter
cushioned clamp placed behind the corona of glans
RGU Technique:
• Retract the foreskin and clean the tip of penis with
Betadine or antiseptic solution
• Position should be oblique to visualize full length of
urethra
• Place Foley’s catheter tip in the navicular fossa and
gently inflate the balloon
• Inject the contrast and image as soon as a major part
of the contrast has been injected, taking spot images
when appropriate
Urethrovenous intravasation:
• Incidence: 1%
• Due to a breach in the urethral mucosa
• Enhanced by inflammation found to accompany most
urethral strictures
• Exposes the patient to hazards like allergic reactions
and pulmonary embolism
• May be accompanied by reflux of pathogenic bacteria
often found in the male urethra and manifests as fever
with chills and rigors and results in septicemia
Reduced by: Injection of the contrast agent at low
pressure, periprocedural antibiotics
Balanitis Xerotica Obliterans
• First described in 1928 by Stuhmer
• Aetiology: poorly understood, could be genetically
determined
• Presents initially on the glans penis or prepuce
• Left untreated affect the entire urethra, penile skin and
scrotum
• Present acutely with erythema and discharge or can
follow a more chronic course, presenting with grey-
white skin discolouration
• Progressive disease may lead to long urethral strictures
• Differential diagnoses
Lichen planus, scleroderma, leukoplakia, vitiligo and
erythroplasia of Queyrat
BXO Treatment options:
Medical
Topical steroid creams in early-stage disease
Limited evidence to support their use in recurrent, severe
or advanced disease.
Relapse rate was lower after tacrolimus, a highly
selective immune modulator, than after the
standard anti-inflammatory therapy
Surgical
Circumcision for disease confined to the foreskins or
glans
BXO involving the meatus or urethra the options include
meatoplasty, urethrotomy, urethral
dilatation or a more definitive procedure such as
urethroplasty
Advantages of a single stage urethroplasty
• Single perineal incision avoiding a penile scar
• Minimally invasive
• Performed in one stage
• Avoids the psychological trauma of 2 (or more)
operations and the need of living for 6 months with
bifid scrotum after staged procedures
Staged procedure:
- Adverse local conditions: Extensive scarring, fistula,
long segment, infection and cancer
-Repeated prior failed urethroplasties
-2-stage urethroplasties using skin had a higher failure
rate than BMG
Buccal mucosa in the first stage versus 2nd stage
Mundy and Barbagli
• 39% graft contraction rate after insertion of buccal graft
in a staged approach
• Needs redo grafting and a 2-stage procedure can be
achieved in 3–4 stages
Kulkarni : Single staged approach for pan anterior stricture
• The proximal urethra is given rest
• Reconstruction is done after 6 months
• Buccal graft is applied during stage II surgery as dorsal
inlay and urethral tubularization
• This avoids graft contracture which is seen if buccal
graft is applied during the first stage
 The Urology Masterclass, Department of Urology, CMC, Vellore
MISCELLANEOUS
I. POST-PROSTATECTOMY
INCONTINENCE:
Definition and incidence:
• No universally accepted definition
• Quoted rates of incontinence are low (<10%)
This usually reflects the rate of severe incontinence or
the rate of surgical intervention.
• After RP, at 18 months minimum follow-up:
8.4% of men were ‘incontinent’ but
only 31.9% had total urinary control
• Surgeons underestimate incontinence by 75%
Risk Factors:
• Patient age
• Stage of disease
• Surgical technique including nerve sparing
• Prior radiation therapy
• Preoperative length of the membranous urethra
• Prior TURP
• Vascular comorbidities
• Preoperative sphincteric insufficiency predicts
postoperative SUI
• Modality of RP: Any effect
• Bladder neck preservation has been reported to improve
continence at 3 months however, no difference was found
at 6 and 12 months
• Nerve sparing has no significant effect
• Incontinence rates are similar between open and
laparoscopic/robotic approaches
Pathophysiology:
• Sphincter incompetence - sole cause in >2/3
• Bladder dysfunction (DO, poor compliance, detrusor
underactivity) in <10%
• Both co-exist in 1/3
• MRI: pre-operative length of the membranous urethra:
Related to the length of continence after surgery.
• Physiotherapy and pelvic floor rehabilitation have been
shown to improve or enhance continence
Work up:
• History, physical examination, urinalysis, and post-void
residual urine. A frequency-volume chart, or bladder
diary
• Pad test quantifies the severity of incontinence. The 24-
hr home test is the most accurate pad test for
quantification and diagnosis and the most reproducible
155
• PVR indicates voiding efficiency
• BUN, creatinine, glucose: only in cases of suspected
renal compromise or polyurea
• Work up
• Cystourethroscopy is useful to verify integrity of the
urethral wall and the status of the bladder
• Imaging:
X ray KUB
USG (KUB)
MCU/ASU
• UDS: To characterize the incontinence and to detect
detrusor overactivity, decreased compliance, and/or
outflow obstruction
• Others: MRI/Transurethral ultrasound: not clear
Timing of surgical intervention:
• Not clear
• 6-12 months of watchful waiting, with pelvic floor
physiotherapy seems reasonable
• Continence may improve even up to 24 months
• Attempts have been made to formulate nomograms to
predict which patients are likely to improve with time:
degree of incontinence, age, type of surgery & pre-
operative sphincter function are considered
• Still under study
Bulking agents:
• Increasing coaptation at the level of the bladder neck
and distal sphincter
• Bovine collagen (Contigen), and silicone macroparticles
(Macroplastique)
• Bovine collagen: 4-20% patients dry, total dryness very
low, multiple injections required
• Predictors of failure: extensive scarring or stricture
formation, previous radiation, and high-grade stress
incontinence (SUI) with low ALPP
Male Slings:
• Provide passive external urethral compression
• Bulbourethral sling: Dacron bolsters under urethra
suspended by sutures to the anterior rectus fascia
Without radiation: cure rate of 42% and mild leakage
rate of 72%
Results much worse in those who had received radiation
• The most common method of sling fixation reported
involves bone anchors.
Polypropylene mesh, allograft dermis, allograft fascia
lata, porcine small intestine submucosal (SIS) graft,
synthetic mesh, and a composite of syntheticand dermis
have also been used.
156 The Urology Masterclass, Department of Urology, CMC, Vellore

• Transobturator slings recently introduced: Algorithm for post-prostatectomy incontinence:

Rely on rotation of the dorsal surface of the proximal
‘•–Ǧ’”‘•–ƒ–‡ –‘›
bulbous urethra and indirect support of the sphincteric ‹ ‘–‹‡ ‡

urethra
• ‘‘Adjustable’’ slings: Ȁ —”ƒ–‡„Žƒ††‡” Ȁ’‘‘”
†‹ƒ”› ‘’Ž‹ƒ ‡
Readjustable sling procedure (REMEEX)
‘‘Argus’ ‘”ƒŽ„Žƒ††‡” ”‡ƒ–
ˆ— –‹‘ ƒ ‘”†‹‰Ž›
• Complications of slings: Erosion, bothersome scrotal
pain & numbness, AUR ‡˜‹‡™Š‹•–‘”›ƒ†
”‡•—Ž–•
• Predictors of failure: Prior AUS placement, radiation &
severe SUI ‘†‡”ƒ–‡–‘•‡˜‡”‡
‹Ž†–‘‘†‡”ƒ–‡
‘”ƒŽ†‡–”—•‘” ‘–”ƒ –‹Ž‹–›
”ƒ˜‹–ƒ–‹‘ƒŽ
• Recommended in those with low to moderate degree of ƒ‹Ž‡†Ȁ•Ž‹‰
‘‘”ƒ—ƒŽ†‡š–‡”‹–›
„‘”ƒŽƒƒ–‘›
incontinence with no prior radiation ”‹‘””ƒ†‹ƒ–‹‘
‡”•‹•–‡– ‡”‹‡ƒŽ•Ž‹‰„ƒ•‡†‘
•’Š‹ –‡”ƒ††‡–”—•‘”
ˆ— –‹‘
Adjustable balloons:
ͺͲͲ
• PROACT (Adjustable Continence Therapy)
‡Ǧ‘’‡”ƒ–‹˜‡•—”‰‡”› ‹”•––‹‡
• Passive compression of the urethra by two balloons ”‹‘”—”‡–Š”‘’Žƒ•–›
—ˆˆƒ–”‘’Š›
located on either side of the urethra
• Perineal incision with transrectal USG ‹‰Ž‡„—Ž„ƒ” —ˆˆ

• Balloons filled with 2ml of isotonic sterile water and

contrast medium
At 1 month and thereafter, the balloons refilled with
1ml increments (maximum filling is 8ml) until
continence is achieved
• 33-70% success rates.
• Complications: Urethral or bladder perforation, AUR,
device expulsion
• Overall: Average results in those with mild to moderate
SUI
Artificial urinary sphincter:
• Most effective long-term surgical treatment for PPI
• Success rates - Continence status of 0–1 pad per day -
59% to 90%
• Satisfaction rates of 87–90%
• Problems: Periodic revisions, explantation due to
mechanical failure, urethral atrophy, infection, and
erosion ( 8-45%)
• Product survival at 5 years: 75%
• Remains the Gold standard for post prostatectomy
incontinence, even for those who had radiation
• The success and high patient satisfaction rates seem to
outweigh the need for periodic revision
‡•‘Ž—–‹‘‘ˆ
‡†— ‡† —ˆˆ•‹œ‡
‡”•‹•–‡–
”ƒ•Ǧ ‘”’‘”ƒŽ†‘—„Ž‡ —ˆˆ  Ž‘•—”‡ƒ†
 —ˆˆ †‹˜‡”•‹‘
‡”•‹•–‡–
Suggested readings:
1. Herschorn S et al. Surgical treatment of stress
incontinence in men. Neuro-urology and Urodynamics
29: 179-190.
2. Winters JC. Male slings in the treatment of sphincteric
incontinence. UCNA 2011; 38: 73-81.
3. Wilson LC et al. Post-prostatectomy urinary
incontinence: A review of surgical treatment options.
BJU Int 2011; 107 (3): 7-10.
4. Campbell-Walsh Urology 10th edition.
5. Lowe BA. Comparison of bladder neck preservation to
bladder neck resection in maintaining postrostatectomy
urinary continence. Urology 1996;48:889–93.
6. Pierorazio PM et al. Preoperative risk
stratificationpredicts likelihood of concurrent PSA-free
survival, continence, and potency (the trifecta analysis)
after radical retropubic prostatectomy. Urology
2007;70:717–22.
7. Poon M et al. Radical retropubic prostatectomy Bladder
neck preservation versus reconstruction. J Urol
2000;163:194–8.
8. Srougi M et al. Urinary continence and pathological
outcome after bladder neck preservation during radical
retropubic prostatectomy: A randomized prospective
trial. J Urol 2001;165:815–8.
 The Urology Masterclass, Department of Urology, CMC, Vellore
9. Steiner MS et al. Impact of anatomical radical
prostatectomy on urinary continence. J Urol
1991;145:512–4.
10.Lepor H et al. The impact of open radical retropubic
prostatectomy on continence and lower urinary tract
symptoms: A prospective assessment using validated
self-administered outcome instruments. J Urol
2004;171:1216–9.
11.Nandipati KC, Raina R, Agarwal A, et al. Nerve-sparing
surgery significantly affects long-term continence after
radical prostatectomy. Urology 2007;70:1127–30.
12.Burkhard FC, Kessler TM, Fleischmann A, et al. Nerve
sparing open radical retropubic prostatectomy—Does
it have an impact on urinary continence? JUrol
2006;176:189–95
157
II. STRESS URINARY INCONTINENCE
1.Supine stress test
• Patient in lithotomy position
• Bladder filled with 200 ml. sterile normal saline solution
by gravity.
• Supine stress test ’! using cough and
Valsalva’smaneuvers
• Efflux from the urethral meatus coinciding with the
cough or Valsalva ’! positive test
• “Negative supine stress test adequately rules out ISD
without the need for formal ALPP or UPP testing. Most
studies suggest that non-invasive means for assessing
intrinsic sphincter function may be adequate in most
patients with uncomplicated non-neurogenic
incontinence
2.Indications of urodynamics in SUI
• Mixed incontinence
• Failed incontinence procedure
• Co-existent neurological diseases
3.Role of UPP
Intended to define urethra’s ability to prevent leakage
• Limitations
• Lack of standardization
• Significant overlap between normal and abnormal
• Variation in interpretation
• Poor predictive value for treatment outcome
4.Role of ALPP
Proposed to assess the sphincteric integrity
• Limitations:
– Symptom severity does not correlate with findings
– Significant overlap between normal and abnormal
– Intrinsic urethral function not the sole factor
– Poor predictive value for treatment outcome
5.Bonney test:
– If the stress provocation test is positive the index finger
of the examiner’s hand is pressed against the anterior
vaginal wall, without pressing on the urethra.
– The stress test is repeated – if no leakage, the Bonney
test is said to be positive
– A positive Bonney test was taken as an indication that
the patient will benefit from surgery
– However, careful studies have shown that this test works
by obstructing the urethra, and that it will be positive
irrespective of incontinence type.
• Bonney test should be discarded in present times
158 The Urology Masterclass, Department of Urology, CMC, Vellore

Algorithm for initial management of urinary incontinence in women

Incontinence Incontinence Incontinenece with

History on physical with mixed urgency/frequency
activity symptoms

Recurrent
-General assessment incontinence

-Urinary symptom assessment(inlcuding urinary volume chart and *Incontinence

questionnare) associated with
-Assess quality of life and desire for treatment -pain,hematuria
-Physical examination:abdominal,pelvic and perineal
-recurrent infection
Clinical -Cough test to demonstrate stress incontinence if appropriate
assessment -voiding symptoms
-Urinalysis+/- urine culture:ifinfected,treat and reassess if appropriate
-Assess estrogen status and treat as appropriate -pelvic irradiation

-Assess voluntary pelvic floor muscle contraction -radical pelvic surgery

-Assess post void residual urine -suspected fistulas

Stress incontinence Mixed incontinence Overactive bladder If other

Presumed presumed due to USI/DOI(Treat most with/without urgency abnormality
Diagnosis sphincteric bothersome incontinence found e.g.
incontinence symptom first) presumed due to
detrusor overactivity -Significant post
void residual

-Significant pelvic
-Lifestyle interventions organ prolapse
-pelvic floor muscle training for SUI/OAB
Management -Pelvic mass
-Bladder retraining for OAB
-Duloxitine(SUI) or Antimuscarinicagents(OAB +/- urgency incontinence)

Other adjuncts such as electrical stimulation

-Vaginal devices,urethral inserts

Failure

Specialised management
 The Urology Masterclass, Department of Urology, CMC, Vellore 159

Algorithm for specialised management

*Recurrent incontinence
Incontinence or
Incontinenc frequency with or *Incontinence associated
e on Incontinence without urge
History with
physical with mixed incontinence
activity symptoms -pain,hematuria

-recurrent infection

-voiding symptoms
Assess for organ mobility/prolapse
-pelvic irradiation
Consider imaging of the urinary tract/pelvic floor
Clinical -radical pelvic surgery
assessment Urodynamics
-suspected fistulas

Mixed
Urodynamic Detrusor Incontinence
incontinence associated with
Diagnosis stress overactivity
incontinence incontinence poor bladder
(Treat most
emptying Consider
bothersome
symptom Urethrocystosccpy
first)
Bladder Detrusor Further imaging
If initial therapy outlet underactivity urodynamics
fails obstruction
If initial therapy
Stress fails:
incontinence
surgery Botulinum toxin Lower urinary tract
Treatment anomaly/pathology
-bulking agents Neuromodulation
Correct
-tapes and slings Bladder anatomical
augmentation bladder Intermittent Correct
-colposuspension neck catheterisation anomaly
obstruction
-artificial urinary -Treat
sphincter pathology

Complications of incontinence surgery

• Immediate (0-24 hours) – Fistulae
– Hemorrhage – Nerve injuries
– Urinary tract and visceral injuries – Ilio inguinal pain
• Short-term (24 hours – 6 weeks) • Long-term (> 6 weeks)
– UTI – De novo detrusor instability
– Infection and erosion – Urogenital prolapse
– Voiding dysfunction – Dyspareunia
160 The Urology Masterclass, Department of Urology, CMC, Vellore

III. STONES IN AUGMENTED BLADDERS
1. Incidence
• Incidence: 10-52%
• Risk of stone formation increases if enterocystoplasty
is combined with an bladder neck surgery / abdominal
wall stoma
• Risk of reservoir calculi higher in those with a stoma
versus native urethra ( 66% vs. 15%)
BOWEL SEGMENT STONE INCIDENCE
Colon 17%
Ileum 8%
Stomach 1.4% ( rare )
1. CAUSES FOR STONE FORMATION IN AUGMENTED
BLADDERS
-Urinary stasis
-Mucous production
-Bacteriuria
-Hypocitraturia
-Foreign bodies ( eg. staples )
2. IMPORTANCE OF IRIGATION PROTOCOL
-Regular irrigation of the reservoir reduces incidence
of bacteriuria, mucus accumulation and reservoir
calculi
-Protocol described:
-Irrigation with 120 - 240 ml saline twice weekly,
along with weekly irrigation using 120- 240 ml
Gentamicin sulphate solution (240 - 480 mg of
Gentamicin/L)
-Position change during irrigation to bathe all aspects
of the bladder
3. MANAGEMENT OF RESERVOIR CALCULI
• Endourological procedures: mainstay of therapy
• Percutaneous access achieved using Amplatz sheaths /
laparoscopic trocars
• Transurethral procedures may be tried if stone burden
is low
• Continent cutaneous diversions: Damage to continence
mechanism and stenosis can occur with excessive
surgical manipulations; Stoma to be used only to fill
the reservoir
REFERENCES
1. DeFoor W, Minevich E, Reddy P, Sekhon D, Polsky E,
Wacksman J, et al. Bladder calculi after augmentation
cystoplasty: risk factors and prevention strategies. J.
Urol. 2004 Nov;172(5 Pt 1):1964–6.
2. Kaefer M, Hendren WH, Bauer SB, Goldenblatt P, Peters
CA, Atala A, et al. Reservoir calculi: a comparison of
reservoirs constructed from stomach and other enteric
segments. J. Urol. 1998 Dec;160(6 Pt 1):2187–90.
3. Clayman RV. Preventing reservoir calculi after
augmentation cystoplasty and continent urinary
diversion: the influence of an irrigation protocol. J. Urol.
2005 Mar;173(3):866–7.
4. Beiko DT, Razvi H. Stones in urinary diversions: update
on medical andsurgical issues. CurrOpinUrol 2002;
12:297–303.
IV. CANCER IN AUGMENTED BLADDER
• 1.5% per decade for ileal/colonic
• 2.8% per decade for gastric bladder augmentations.
• 60%; were >T3 at diagnosis
Risk of cancer over standard norms
• Patients augmented with ileal or colonic segment for a
congenital bladder anomaly have a 7-8 fold increased
risk.
• gastric augments a 14-15 fold increased risk.
Current recommendations for follow up for
enterocystoplasty
• Annual
– Interval medical history
– Renal-bladder ultrasound
– Electrolytes
– Creatinine or Cystatin C (muscle wasting)
– B12
– Urine analysis +/ - urine culture
– Endoscopy – certain criteria
Current Criteria for Endoscopy
1. Four or more symptomatic UTIs per year.*
2. History of gross hematuria and/or urinalysis with
greater than 50 RBC/hpf.†
3. Chronic perineal, pelvic or bladder pain.
4. Abnormal radiographic screening studies.‡
5. Endoscopy of all patients with colon augments at age
50 years or greater, consistent with recommendations
for colonoscopy.
* Symptomatic UTI
Urine culture >105cfu &
1. fever greater than 38.5C, chronic malaise, systemic
fatigue, ûank-pelvic/bladder pain or
2. foul smelling/cloudy urine that fails to clear within 48
hours after increasing hydration and frequency of
catheterization.
 The Urology Masterclass, Department of Urology, CMC, Vellore 161

† Microscopic hematuria of 50 RBC/hpf or less was found V. TUBEROUS SCLEROSIS WITH

on 46% of routine surveillance urinalyses and,
therefore, considered normal in this patient population. BILATERAL AML
In addition, gross hematuria or greater than 50 RBC/
hpf associated with a symptomatic UTI was not Bilateral renal masses
considered positive for further evaluation. 1. Choice of procedure – NSS procedures preferred as
renal functional outcomes are as important to long term
‡ Abnormal radiographic screening studies survival as oncological control
New onset of hydroureteronephrosis, bladder calculi 2. Which side first? – More complex or less complex
or abnormality of bladdermucosa suggestive of a mass The order in which partial nephrectomy and radical
Etiology of cancer in bladder augmentations nephrectomy were conducted did not affect functional
outcomes
1) Chronic bacteriuria inducing nitrosamines and
producing toxic oxygen radicals. Surgical management of bilateral synchronous kidney tumors:
functional and oncological outcomes. Simmons MN, Brandina
2) A direct toxic effect of the urine on the enteric epithelium.
R, Hernandez AV, Gill IS. J Urol. 2010 Sep; 184(3):865-72
3) The removal of the enteric epithelium from a
intraluminal nutritional supplies TSC diagnostic criteria
4) Aberrant intercellular cell signaling mechanisms arising Major criteria Minor criteria
from mesenchymal-epithelial interactions of the 1 Hypomelanotic macules Confetti skin lesions
disparate intestinal and urothelial tissues 2 Ungual fibromas Dental enamel pits >/=3
3 Angiofibromas Intra oral fibromas >/= 2
5) Complications of augmentation colocystoplasty 4 Shagreen patch Retinal achromic patch
1) Metabolic 5 Multiple retinal hamartomas Non renal hamartomas
a. Chloride absorption and acidosis 6 Cortical dysplasias Multiple renal cysts
7 Sub ependymal nodules
b. Patient growth (20% delayed growth) 8 Sub ependymal giant
2) UTI astrocytomas
9 Cardiac rhabdomyomas
a. Treat culture if urea-splitting organism
10 Lymphangiomyomatosis(LAM)
3) Calculus (15%-50%, majority - struvite) 11 Angiomyolipomas (AML)
4) Gastro-intestinal
a. Diarrhoea Definite diagnosis: 2 major (except LAM and AML together)
b. B12 deficiency or 1 major and 2 minor
5) Tumor formation Possible diagnosis: 1 major, 1 major and 1 minor or 2 or
more minor
a. Adenocarcinoma, benign polyps, TCC
b. Latent period 4 years – 26 years Management of AMLs
c. TCC –aggressive, often metastatic 1. Prophylactic surgery to prevent hemorrhage among
patients with renal AMLs larger than 4 cm in diameter,
6) Delayed and spontaneous bladder rupture
particularly those with high vascularity and/or an
a. Upto 5 %, (colonic segment, neurogenic bladder) aneurysm measuring e”5 mm in diameter - The
7) Failure to achieve adequate compliance (5-10%) management of renal angiomyolipoma. Oesterling JE,
Alternatives to Gastrointestinal cystoplasty Fishman EK, Goldman SM, Marshall FF. J Urol. 1986
• Ureterocystoplasty Jun;135(6):1121-4
• Seromuscularenterocystoplasty 2. Conservative management of asymptomatic renal AMLs
4 to 8 cm in diameter if close follow-up (at six months
• Auto-augmentation and then yearly if stable) is feasible - Management of
• Bladder regeneration renal angiomyolipomas associated with tuberous sclerosis
complex. Harabayashi T, Shinohara N, Katano H,
Nonomura K, Shimizu T, Koyanagi T. J Urol.
2004;171(1):102

Role of angio embolisation in AMLs and long term

results
1. First line of treatment for acute symptoms
162 The Urology Masterclass, Department of Urology, CMC, Vellore

2. Long term results – recurrence especially in TSC patients,

need for additional procedures, considerable morbidity
3. Sooriakumaran et al, BJUI June 2009 – 102 patients with
AMLs, 19 patients treated with Selective renal angio-
embolisation Effective in controlling haemorrhage from
AMLs in the acute setting (six)
4 patients required further intervention (four) and there
was a significant complication rate. The reduction in
tumour volume was only modest (28%).
No complications occurred after surgery (median
follow-up 5.5 years) or RFA (median follow-up
9 months)

Indications for mTOR inhibitors in TSC

1. TSC-associated Subependymal giant astrocytomas
requiring intervention but not amenable to surgery –
only FDA approved indication
2. First-line treatment in patients with remaining AML who
previously underwent nephrectomy or embolization as
well as in those with fast growing multiple AMLs
3. Both weekly and daily dosing resulted in a similar 50%
reduction in AML volume – effects stop on discontinuing
drug
 The Urology Masterclass, Department of Urology, CMC, Vellore 163

VI. ERECTILE DYSFUNCTION

• Overall prevalence of 52% ED in men aged 40-70 years. Minimal, moderate, and complete ED: 17.2%, 25.2%, and 9.6%,
respectively.
• Incidence of ED after pelvic fracture alone is approximately 5% to 20%, whereas the incidence in patients with PFUI
increases to as high as 42% to 62%
• ED after pelvic trauma is mostly caused by damage to the autonomic cavernosal supply
• Either by fractures of the sacrum, by extensive pelvic haematomas or by disruption of nerves at the level of the pelvic
floor
• The potential therapeutic benefit of an orally active phosphodiesterase-inhibitor (sildenafil, apomorphine ) seems
limited
• Local measures such as intra-cavernosal injections, intraurethral applications, vacuum
devices or a penile prosthesis should be advised

· Penile Doppler if
-Evaluation of non-responders to PDE5-Inhibitors
-Cancer patients with ED after pelvic surgery due to prostate or rectal cancer
-Patient with pelvic fracture urethral injury
-Marker of silent CAD in men presenting with ED
-Preoperative evaluation for Peyronie’s disease and the quantification of fibrosis
164 The Urology Masterclass, Department of Urology, CMC, Vellore

Penile prosthesis
• Classification:
– Inflatable (2 or 3 piece)
– Semi-rigid devices (malleable, mechanical, soft flexible)
• 3 piece inflatable device provides best rigidity and flaccidity and more natural erection – most preferred
• Regardless of indication penile prosthesis highest satisfaction rate 92-100 % in patients and 91-95 % in partners
• Complications of prosthesis:
-Two main complications: Mechanical failure and infection
-Three piece prosthesis (AMS 700CX/CXR, coloplast Titan Zero degree): < 5 % in 5 yrs
-Infection rate 2-3 % with proper antibiotics and reduced to 1-2 % by using antibiotic
impregnated prosthesis (AMS inhibizone)
 The Urology Masterclass, Department of Urology, CMC, Vellore 165

References
EAU guidelines 2019
Jung D C et al, Ultrasonography 2018;37:16-24
Chung E et al.World J Urol,2013.31:591
Bettochhi C et al.J sex Med,2010.7:304
Carson C C et al.J Urol,2000.164:376
Hellstrom W J et al. J Sex Med,2010.7:501
Mandava et al. J Urol,2012.188:1855
166 The Urology Masterclass, Department of Urology, CMC, Vellore

VII. Post-transplant lymphocoele

• Lymphoceles are the most common peritransplant fluid collections, with a prevalence of 0.5%–20%.
• Symptomatic lymphoceles – 5.6% (1% to 12 %)
• Early complication, occurring within 1–2 months after transplantation
• Causes: Leakage of lymph from surgically disrupted lymphatic channels along the iliac vessels or from the lymphatics
of the transplanted kidney
• Fluid collections usually occur medial to the transplant, between the graft and the bladder

• Risk factors include

-Inadequate ligation of the lymphatic channels across the iliac vessels
-Renal capsular tears,
-Acute rejection
- Delayed graft function
-Lower extremity arteriovenous fistula
-Use of diuretics, anticoagulants, mTOR inhibitors , high dose corticosteroids

• Presentation: Majority of the lymphocele are asymptomatic and do not require any treatment.
• May cause compression of the graft ureter, bladder and the iliac veins and presents with azotemia, graft hydronephrosis,
ipsilateral leg swelling or pain and fever due to infection in the lymphocele.

• Ultrasonography is the most reliable method of diagnosing.

• USG findings of hypoechoic to anechoic masses with through transmission, occasionally with septa and dependant or
scattered debris are suggestive but not specific for the diagnosis.

• Treatment
-Aspiration
-Drain placement (First line treatment)
-Sclerotherapy: Ethanol, Betadine, Fibrin, Tetracycline, Gentamicin or Octreotide
-Laparoscopic deroofing/ fenestration
-Open marsupialization (When lymphocoele does not resolve after drain placement)

Treatment modality Recurrence Complications Follow up

rate (%) (%) (Months)
Aspiration 59 (10-95%) 16 28
Sclerotherapy 31 8 20
Drain placement 50 33 16
Laparosocpic 8 14 28
deroofing/fenestration
Open marsupialisation 16 30 21
 The Urology Masterclass, Department of Urology, CMC, Vellore
References and suggested reading
The standard text book for references
1. Campbell Urology 11th edition
2. European Association of Urology (http://uroweb.org/
guidelines/)
3. National Comprehensive Cancer guidelines https://
www.nccn.org/professionals/
4. AUA Guidelines 2018
1. Urothelial cancer
x Pinto IG Systemic therapy in bladder cancer Indian J
Urol. 2017 Apr-Jun;33(2):118-126.
x BabJuk M et al EAU Guidelines on Non muscle invasive
urothelial carcinoma of the bladder Eur Urol 2017
Mar;71(3);447-461
x Loew JJ et al A systematic review and meta-analysis of
adjuvant and neoadjuvant chemotherapy for upper tract
urothelial carcinoma. Eur Urol. 2014 Sep;66(3):529-41
x Cohen A etal Neoadjuvant and adjuvant chemotherapy
use in upper tract urothelial carcinoma. Urol Oncol.
2017 Jan 5. pii: S1078-1439(16)30406-9.
x Boorijan SA et al. Risk factors and outcomes of urethral
recurrence following radical cystectomy. Eur Urol. 2011
Dec;60(6):1266-72. Epub 2011 Aug 22.
x Huguet J. Diagnosis and treatment of urethral
recurrence after radical cystectomy in the male. Actas
Urol Esp. 2012;36:42-7.
x Bansal A et al Grading of complications of transurethral
resection of bladder tumor using Clavien-Dindo
classification system. Indian J Urol 2016 Jul-Sep
x Urologic clinics of North America Volume 37, Issue 3.
August 2010, Pages 467–474.
x Bus MTJ, de Bruin DM, Faber DJ et al: J Endourol 2015
x Yamany T, van Batavia J, Ahn J et al: Urology 2015.
x Margulis V et al. J Urol 2010
x Brien JC et al. J Urol 2010
x Ogaya Pinies G et al. Urachal adenocarcinoma – case
repor and bibliographic review. Arch Esp Urol 2012;
65(4):498-501.
x Siefer-Radtke A. Urachal adenocarcinoma: A clinician’s
guide for treatment. Semin Oncol 2012; 39(5): 619-624.
2. Renal Cell Carcinoma
x Small Renal Mass, Urologic Clinics of North America
Volume 44, Issue 2, Pages 147-332 (May 2017)
x Simmons MN et al. Kidney tumour measurement using
the C-index method. J Urol 2010; 183: 1708–13.
x Khalifeh A et al. V-hilar suture renorrhaphy during
robotic partial nephrectomy for renal hilar tumours:
Preliminary outcomes of a novel surgical technique.
Urology 2012; 80: 466-471.
167
x Palou J et al. Combined approach of laparoscopic and
open surgery for complex renal lesions. Actas Urol Esp
2013; 37: 120-6.
x Van Poppell H et al. Open partial nephrectomy for
complex tumours and >4cm: Is it still the gold-standard
technique in the minimally invasive era? Arch Esp Urol
2013; 66: 129-38.
x Rogers C et al. Robotic partial nephrectomy: the real
benefit. Curr Opin Urol 2011; 21:60-64.
x Mathew N et al. Surgical Management of Bilateral
Synchronous Kidney Tumors: Functional and
Oncological Outcomes; J Urology 2010.
x Lawindy SM et al. Important considerations in the
surgical management of RCC and IVC tumour thrombus.
BJU Int 2012; 110:926-39.
x Kirkali Z et al. A critical analysis of surgery for kidney
cancer with vena cava invasion. Eur Urol 2007; 52: 658-
62.
3. Urolithiasis
x EUA guidelines 2019
x Lee SW, et al. Comparative effectiveness and safety of
various treatment procedures for lower pole renal
calculi: a systematic review and network meta-
analysis.BJU Int. 2015;116:252–264
x Liu L, et al. Percussion, diuresis and inversion therapy
for the passage of lower pole kidney stones following
shock wave lithotripsy. Cochrane Database Syst
Rev.2013:CD008569
x El-Nahas AR, et al. Flexible ureterorenoscopy versus
extracorporeal shock wave lithotripsy for treatment of
lower pole stones of 10-20 mm. BJU Int.2012;110:898–
902
x Pearle MS, et al. Prospective, randomized trial
comparing shock wave lithotripsy and ureteroscopy for
lower pole caliceal calculi 1 cm or less. J
Urol.2005;173:2005–2009
x Burr J, et al. Is flexible ureterorenoscopy and laser
lithotripsy the new gold standard for lower pole renal
stones when compared to shock wave lithotripsy:
Comparative outcomes from a University hospital over
similar time period. Cent European J Urol. 2015;68:183–
186.
x Jackman SV, et al. The “mini-perc” technique: A less
invasive alternative to percutaneous nephrolithotomy.
World J Urol. 1998;16:371–4.
x Abdelhafez MF, et al. Minimally invasive percutaneous
nephrolithotomy: A comparative study of the
management of small and large renal stones. Urology.
2013;81:241–5
x Kirac M, et al. Comparison of retrograde intrarenal
surgery and mini-percutaneous nephrolithotomy in
168 The Urology Masterclass, Department of Urology, CMC, Vellore
management of lower-pole renal stones with a diameter
of smaller than 15 mm. Urolithiasis. 2013;41:241–246
x Thomas K, Smith NC, Hegarty N, Glass JM. The Guy’s
stone score—grading the complexity of percutaneous
nephrolithotomy procedures. Urology. 2011; 78:277-81.
x Singh et al. Comparative evaluation of upper versus
lower calyceal approach in percutaneous
nephrolithotomy for managing complex renal calculi,
Urol Ann. 2015; 7: 31–35.
x Netto NR, Jr, Ikonomidis J, Ikari O, Claro JA. Comparative
study of percutaneous access for staghorn calculi.
Urology. 2005; 65:659–62.
x Paik ML, et al. Current indications for open stone surgery
in the treatment of renal and ureteral calculi. J
Urol 1998; 159:374–9.
x Mansi MK. Anatrophic nephrolithotomy for complete
staghorn calculi: experience with a simplified
modification of the Smith and Boyce technique. BJUI
2001; 88:803.
4. Urogenital fistulae
x World Health Organization (WHO). Obstetric F istula:
Guiding principles for clinical management and
programme development. World Health Organization;
Geneva: 2006.
x Narayanan P, Nobbenhuis M, Reynolds KM, et al.
Fistulas in malignant gynecologic disease: etiology,
imaging, and management. Radiographics. 2009 Jul-
Aug;29(4):1073-83
x Hilton P. Urogenital fistula in the UK - a personal case
series managed over 25 years. BJU Int. 2012
Jul;110(1):102-10.
x Pshak T, Nikolavsky D, Terlecki R, Flynn BJ. Is tissue
interposition always necessary in transvaginal repair
of benign, recurrent vesicovaginal fistulae? Urology
2013;82:707–12.
x Altaweel WM, Rajih E, Alkhudair W. Interposition flaps
in vesicovaginal fistula repairs can optimize cure rate.
Urol Ann 2013;5:270–2.
x Kumar S et al. Vesicovaginal fistula: An update. Indian
J Urol 2007;23:187-91.
5. Carcinoma prostate
x EAU guidelines 2019
x AUA guidelines 2019
x NCCN guidelines
x Vale et al. Lancet Oncol December 2015 (systematic
review and metaanalysis)
x Gravis Get al. Proc Am Soc Clin Oncol 2015;33 (suppl 7)
x James et al, Lancet 2016; 387: 1163–77
x Sweeney et al. NEJM 2015;373:737-46
x Munsuru et al. J Urol 2015 (Sunnybrook experience)
x Klotz et al. J.Clin.Oncol 2015
x Morash et al. Can Urol Assoc J, 2015. 9: 171
6. Urinary tuberculosis
x Reconstructive surgery for the management of
genitourinary tuberculosis: A single centerexperience.
JUrol 2006;175:2150-4.
x Reconstructive bladder surgery in genitourinary
tuberculosis. Indian J Urol. 2008 Jul-Sep; 24(3): 382–
387.
x Diagnostic accuracy of the Xpert® MTB/RIF assay for
extra-pulmonary tuberculosis: a meta-analysis. The
International Journal of Tuberculosis and Lung Disease,
Volume 19, Number 3, 1 March 2015, pp. 278-284(7).
x Goel A, Goel A, Dalela D. Redefining needs for better
follow-up in urinary tuberculosis. Urol J.
2012;9(4):725–8.
7. Testicular cancer
x Andre F, et al. Eur J Cancer 2000;36:1389.
x Spiess PE, et al. J Urol 2007;177:1330.
x Gorbatiy V, et al. Indian J Urol 2009;25:186
8. Upper tract obstruction
x Eur Urol. 1983; 9(6):321-8. Primary megaureter in
adults. Frohneberg D, Walz PH, Hohenfellner R.
x Arch Ital Urol Androl. 1998 Sep; 70(4):187-93. Our
experience in the conservative surgical treatment of
megaureter in the adult. D’Amico A,
x J Pediatr Surg. 2012 Dec; 47(12):2285-8. doi: 10.1016/
j.jpedsurg.2012.09.020. Laparoscopic pneumovesical
ureteral tapering and reimplantation for megaureter.
Bi Y, Sun Y.
x Ann Urol (Paris). 1996; 30(5):240-3. Ureteral
reimplantation. Aboutaieb R et al
x Hemal AK, Ansari MS, Doddamani D, Gupta NP.
Symptomatic and complicated adult and adolescent
primary obstructive megaureter indications for surgery:
analysis, outcome, and follow-up. Urology 2003 April;
61:703e7.
9. Urethral structure
x On the art of anastomotic posterior urethroplasty: a
27-year experience Mamdouh M. Koraitim , 2005
x Male Urethral Reconstruction and the Management of
Urethral Stricture Disease, Urologic Clinics of North
America; Volume 44, Issue 1, Pages 1-146 (February
2017)
10. Bladder outlet obstruction
x Treatment of Lower Urinary Tract Symptoms and Benign
Prostatic Hyperplasia, Urologic Clinics of North
America, Volume 43, Issue 3, Pages 279-418 (August
2016)
11. Pediatric urology
x H T Nguyen,et al, Multidisciplinary consensus on the
classification of prenatal and postnatal urinary tract
 The Urology Masterclass, Department of Urology, CMC, Vellore 169

dilation (UTD classification system) J Pediatr Urol. 2014 x Altman AL, Haas C, Dinchman KH, et al. Selective
Dec;10(6):982-98 nonoperative management of blunt grade 5 renal injury.
x Koff SA, Mutabagani KH, Jayanthi VR. The valve bladder J Urol 2000 Jul;164(1):27-30
syndrome: Pathophysiology and treatment with x Reis LO, Kim FJ, Moore EE, Hirano ES, Fraga GP,
nocturnal bladder emptying. J Urol. 2002;167:291–7 Nascimento B, Rizoli S.Update in the classification and
x Hennus P.M.L et al. A systematic review of renal and treatment of complex renal injuries. Rev Col Bras Cir.
bladder dysfunction in boys after endoscopic treatment [periódico na Internet] 2013;40(4)
of infravesical obstruction. PLoS One. 2012; 7(9). x Moudouni SM, Hadj Slimen M, Manunta A, et al.
x Kajbafzadeh AM et al. The effects of bladder neck Management of major blunt renal lacerations: is a
incision on urodynamic abnormalities of children with nonoperative approach indicated? Eur Urol 2001
posterior urethral valves. J Urol. 2007 Nov;178(5):2142- Oct;40(4):409-14
7 x Late evaluation of the relationship between
x Antimicrobial Prophylaxis for Children with morphological and functional renal changes and
Vesicoureteral Reflux The RIVUR Trial Investigators, N hypertension after non-operative treatment of high-
Engl J Med 2014; 370:2367-2376 grade renal injuries. Pereira et al, W Jrnl of emerg
surgery.
12. Carcinoma penis
x European Association of Urology Urogenital trauma
x Penile, Urethral, and Scrotal Cancer, Urologic Clinics
guideline. 2019, http://uroweb.org/guideline/
of North America Volume 43, Issue 4, Pages 419-566
urological-trauma/#4_1
(November 2016)
13. Adrenal Disorders
x Bharwani N,, etal. Adrenocortical Carcinoma: The Range
of Appearances on CT and MRI. Am J Roentgenol. 2011
Jun;196(6):W706–W714.
x Fassnacht M, Allolio B. Clinical management of
adrenocortical carcinoma. Best Pract Res Clin
Endocrinol Metab. 2009 Apr;23(2):273–89.
x Terzolo M, et al. Management of adrenal cancer: a 2013
update. J Endocrinol Invest. 2014 Jan 24;
x Fassnacht M, et al. Combination Chemotherapy in
Advanced Adrenocortical Carcinoma. N Engl J Med.
2012;366(23):2189–97.
x Gumbs AA, Gagner M 2006 Laparoscopic
adrenalectomy. Best Pract Res Clin Endocrinol Metab
20:483–499
x Timmers HJ,, et al. Comparison of 18F-fluoro-L-DOPA,
18F-fluoro-deoxyglucose, and 18F-fluorodopamine PET
and 123 I-MIBG scintigraphy in the localization of
pheochromocytoma and paraganglioma. J Clin
Endocrinol Metab. 2009;94:4757–4767.
x Chian A et al,68Ga-DOTATATE and 18F-FDG PET/CT in
Paraganglioma and Pheochromocytoma: utility,
patterns and heterogeneity, Cancer Imaging. 2016; 16:
22.
15. Trauma
x Dugi DD III, Morey AF, Gupta A, et al. American
Association for the Surgery of Trauma grade 4 renal
injury substratification into grades 4a (low risk) and
4b (high risk). J Urol 2010 Feb;183(2):592-7
x Santucci RA, McAninch JM. Grade IV renal injuries:
evaluation, treatment, and outcome. World J Surg 2001
Dec;25(12):1565-72.
 The Urology Masterclass, Department of Urology, CMC, Vellore

APPENDIX
170 The Urology Masterclass, Department of Urology, CMC, Vellore

Clavien-Dindo classification of surgical complications

Ranks a complication in an objective and reproducible manner. It consists of 7 grades (I, II, IIIa, IIIb, IVa, IVb and V). The
introduction of the subclasses a and b allows a contraction of the classification into 5 grades.

Grades Definition

Grade I Any deviation from the normal postoperative course without the need for
pharmacological treatment or surgical, endoscopic and radiological
interventions.
(Allowed therapeutic regimens are: drugs as antiemetics, antipyretics, analgetics, diuretics and electrolytes and
physiotherapy. This grade also includes wound infections opened at the bedside.)

Grade II Requiring pharmacological treatment with drugs other than such allowed for
grade I complications. Blood transfusions and total parenteral nutrition are
also included.

Grade III Requiring surgical, endoscopic or radiological intervention

Grade III-a Intervention not under general anesthesia

Grade III-b Intervention under general anesthesia

Grade IV Life-threatening complication (including CNS complications) requiring IC/ICU-

management

Grade IV-a Single organ dysfunction (including dialysis)

Grade IV-b Multi organ dysfunction

Grade V:Suffix ‘d’ Death of a patient If the patient suffers from a complication at the time of
discharge, thesuffix “d” (for ‘disability’) is added to the respective grade of
complication. This label indicates the need for a follow-up to fully evaluate the
complication.

Ann Surg 2009; 250: 187 - 196

 The Urology Masterclass, Department of Urology, CMC, Vellore 171

ECOG/WHO/Zubrod score

The Eastern Cooperative Oncology Group(ECOG) score also called the World Health Organization score (WHO) or Zubrod
score (after C. Gordon Zubrod), runs from 0 to 5, with 0 denoting perfect health and 5 deaths. It is used to assess how a
patient’s disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine
appropriate treatment and prognosis.Its advantage over the Karnofsky scale lies in its simplicity.

0 – Asymptomatic (Fully active, able to carry on all predisease activities without restriction)

1 – Symptomatic but completely ambulatory (Restricted in physically strenuous activity but ambulatory and able to carry
out work of a light or sedentary nature. For example, light housework, office work)

2 – Symptomatic, <50% in bed during the day (Ambulatory and capable of all self-care but unable to carry out any work
activities. Up and about more than 50% of waking hours)

3 – Symptomatic, >50% in bed, but not bedbound (Capable of only limited self-care, confined to bed or chair 50% or more
of waking hours)

4 – Bedbound (Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair)

5 – Death

As published in Am. J. Clin. Oncol.:Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T., Carbone, P.P.:
Toxicity And Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649-655, 1982.

Karnofsky Scoring
The Karnofsky scale was developed in the 1940s by David A. Karnofsky and Joseph Burchenal to measure subjective
aspects of the outcome of cancer treatment.It is a clinical estimate of a patient’s physical state, performance, and
prognosis

The Karnofsky score runs from 100 to 0, where 100 is “perfect” health and 0 is death.
100% – normal, no complaints, no signs of disease
90% – capable of normal activity, few symptoms or signs of disease
80% – normal activity with some difficulty, some symptoms or signs
70% – caring for self, not capable of normal activity or work
60% – requiring some help, can take care of most personal requirements
50% – requires help often, requires frequent medical care
40% – disabled, requires special care and help
30% – severely disabled, hospital admission indicated but no risk of death
20% – very ill, urgently requiring admission, requires supportive measures or treatment
10% – moribund, rapidly progressive fatal disease processes
0% – death.
A translation between the ECOG/Zubrod and Karnofsky scales -
ECOG 0-1 equals Karnofsky 80-100
ECOG 2 equals Karnofsky 60-70
ECOG 3-4 equals Karnofsky 10-50
172 The Urology Masterclass, Department of Urology, CMC, Vellore

American Society of Anesthesiologists physical status classification

The American Society of Anesthesiologists (ASA) Physical Status classification system was initially created in 1941 by the
American Society of Anesthetists. The purpose of the grading system is simply to assess the degree of a patient’s
“sickness” or “physical state” prior to selecting the anesthetic or prior to performing surgery. Describing patients
preoperative physical status is used for recordkeeping, for communicating between colleagues, and to create a uniform
system for statistical analysis. The grading system is notintended for use as a measure to predict operative risk.
The modern classification system consists of six categories, as described below

ASA 1: Normal healthy patient.

No organic, physiologic, or psychiatric disturbance; healthy with good exercise tolerance

ASA 2: A patient with mild systemic disease.

No functional limitations; has a well-controlled disease of one body system; controlled hypertension or diabetes
without systemic effects, cigarette smoking without chronic obstructive pulmonary disease (COPD); mild obesity,
pregnancy

ASA 3: A patient with severe systemic disease

Some functional limitation; has a controlled disease of more than one body system or one major system; no
immediate danger of death;

ASA 4: A patient with severe systemic disease that is a constant threat to life.
Has at least one severe disease that is poorly controlled or at end stage; possible risk of death; unstable angina,
symptomatic COPD, symptomatic CHF, hepatorenal failure

ASA 5: A moribund patient who is not expected to survive without the surgery.
Not expected to survive > 24 hours without surgery; imminent risk of death; multiorgan failure, sepsis syndrome
with hemodynamic instability, hypothermia, poorly controlled coagulopathy

ASA 6: A declared brain dead patient whose organs are being removed for donor purposes.

If the surgery is an emergency, the physical status classification is followed by “E” (for emergency). Class 5 is usually an
emergency and is therefore usually “5E”. The class “6E” does not exist and is simply recorded as class “6”, as all organ
retrieval in brain-dead patients is done urgently.

Limitations
Assumes that age of the patient has no relation to physical fitness
A moderate systemic disease cannot be graded according to this system.
A person suffering from more than one systemic disease with different severities cannot be classified with this system.
To predict operative risk the age, obesity, the nature and severity of the operative procedure, selection of anesthetic
techniques, the competency of the surgical team, duration of surgery or anesthesia, etc. are often far more important than
this ASA classification.
 The Urology Masterclass, Department of Urology, CMC, Vellore 173

Charlson co-morbidity index

To calculate estimated 10 year survival based on co-morbidities and age

Variable Definition Points

Myocardial infarction History of definite or probable MI (EKG changes and/or enzyme changes) 1

Congestive heart failure
Peripheral vascular disease
Exertional or paroxysmal nocturnal dyspnea and has responded to digitalis, 1
diuretics, or afterload reducing agents
Intermittent claudication or past bypass for chronic arterial insufficiency, 1
history of gangrene or acute arterial insufficiency, or untreated thoracic or
abdominal aneurysm (=6 cm)

Cerebrovascular accident or
transient ischemic attack
Dementia
Chronic obstructive pulmonary
disease
Connective tissue disease
Peptic ulcer disease
- 1
Chronic cognitive deficit 1
- 1
- 1
Any history of treatment for ulcer disease or history of ulcer bleeding 1

Mild liver disease
Uncomplicated diabetes
Hemiplegia
Moderate to severe chronic
kidney disease
Diabetes with end-organ damage
Mild = chronic hepatitis (or cirrhosis without portal hypertension) 1
- 1
- 2
Severe = on dialysis, status post kidney transplant, uremia, moderate = 2
creatinine >3 mg/dL (0.27 mmol/L)
- 2

Localized solid tumor - 2

Leukemia - 2
Lymphoma - 2
Moderate to severe liver disease Severe = cirrhosis and portal hypertension with variceal bleeding history, 3
moderate = cirrhosis and portal hypertension but no variceal bleeding
history

Metastatic solid tumor - 6

AIDS* - 6

Plus 1 point for every decade age 50 years and over, maximum 4 points.
Note: liver disease and diabetes inputs are mutually exclusive (e.g. do not give points for both “mild liver disease” and
“moderate or severe liver disease”).
*This data is from the original Charlson study in 1987, before the widespread availability of effective antiretroviral therapy.
Charlson ME et al. J.Chronic diseases 1987; 40:373-383
Radovanovic D et al. Heart 2014; 100(4): 288-94
174 The Urology Masterclass, Department of Urology, CMC, Vellore

French catheter scale

The French scale or French gauge system is commonly used to measure the size of a catheter. It is most often abbreviated
as Fr, but can often abbreviated as Fg, FR or F. It may also be abbreviated as CH or Ch (for Charrière, its inventor) in French
speaking countries.
A catheter of 1 French has a diameter of 0.3 mm,[1] and therefore the diameter of a round catheter in millimeters can be
determined by dividing the French size by 3:
D (mm) = Fr/3
or
Fr = D (mm) × 3
For example, if the French size is 9, the diameter is 3 mm.
An increasing French size corresponds to a larger diameter catheter. This is contrary to needle-gauge size, where an
increasing gauge corresponds to a smaller diameter catheter.
The french size is a measure of external diameter of the catheter (not internal drainage channel). So, if a 2 way catheter
of eg. 20 Fr is compared to a 20 Fr 3 way catheter then they both have same external diameter but 2 way catheter will
contain larger drainage channel than 3 way. 3 way catheters accommodate an extra channel for irrigation in the similar
external diameter.
The French gauge was devised by Joseph-Frédéric-Benoît Charrière, a 19th-century Parisian maker of surgical instruments,
who defined the “diameter times 3” relationship.

Colour coding of Foley’s catheters

The proximal inflation/ balloon hub of all Foley’s catheters are colour coded according to its size in the Fr. scale.

Size (in French) Colour of hub

8 Black
10 Grey
12 White
14 Green
16 Orange
18 Red
20 Yellow
22 Purple
24 Blue
 The Urology Masterclass, Department of Urology, CMC, Vellore 175

Glossary of terms used in statistical analysis

Screening
The testing of a asymptomatic population in order to detect cases of a disease at an early stage.

Absolute risk reduction

A measure of the efficacy of a treatment in terms of the absolute number of people saved or lost. For instance, if a
treatment reduces the number of people who die of a disease from 6 to 4 in 1,000, then the absolute risk reduction is 2
in 1,000, or 0.2 percent.

Early detection
Early detection of a disease is the goal of screening for it. Early detection can reduce mortality. Early detection, however,
does not imply mortality reduction. For instance, if there is no effective therapy, then early detection, including treatment,
will not reduce mortality.

Mortality reduction
A measure of the benefit of a treatment in terms of lives saved. The mortality reduction can be represented in many ways,
including relative risk reduction, absolute risk reduction, and increased life expectancy.

Number needed to treat (NNT)

A measure of the efficacy of a treatment. For instance, if biannual mammogram screening eventually saves the life of 1
in 1,000 participating women, the NNT (to save one life) is 1,000. In other words, 999 women do not benefit in terms of
mortality reduction. NNT is also used to measure the harm of a treatment, such as when about 1 in 7,000 women who take
oral contraceptives get thromboembolism, the NNT (with oral contraceptives to cause one case of thromboembolism) is
7,000. In other words, 6,999 do not show this side effect.

Relative risk reduction

A measure of the efficacy of a treatment in terms of the relative number of people saved or lost. For instance, if a
treatment reduces the number of people who die from 6 to 4 in 1,000, then the relative risk reduction is 33.3 percent.
Reporting relative risks is popular because the numbers look larger than the absolute risk reduction (which would be 2
in 1,000 or 0.2 percent). Relative risks do not convey how large the risk is in absolute terms, and as a consequence are
often misunderstood. For instance, if a treatment reduces the number of people who die from 6 to 4 in 10,000, the relative
risk reduction is the same as for 1,000 (33.3 percent), although the absolute risk reduction has decreased to 0.02
percent.

Risk
If the uncertainty associated with an event can be quantified on the basis of empirical observations or causal knowledge,
the uncertainty is called risk. Frequencies and probabilities are ways to express risks. Different from the everyday use
of the term, a risk need not be associated with harm; it can refer to a positive, neutral, or negative event.
176 The Urology Masterclass, Department of Urology, CMC, Vellore

Lead time bias – Overestimation of survival duration by earlier detection due to screening than clinical presentation

Lead time bias

Cancer detected through screening
Perceived survival

Cancer Lead time

onset Death

Cancer detected through symptoms Perceived survival

Length time bias – Overestimation of survival due to relative excess of cases that are detected in the indolent/slowly progressing
phase by screening

Indolent cancer Symptoms and diagnosis Death

begins
Screening

Detectable preclinical phase

Screening
Aggressive cancer begins Symptoms and Death tends to
diagnosis detect more
indolent
cancers

Length time bias

 The Urology Masterclass, Department of Urology, CMC, Vellore 177

Oxford Centre for Evidence-based Medicine Levels of Evidence (March 2009)

(for definitions of terms used see glossary at http://www.cebm.net/?o=1116)

Level Therapy/Prevention, Prognosis Diagnosis Differential Economic and decision

Aetiology/Harm diagnosis/symptom analyses
prevalence study
1a SR (with SR (with homogeneity*) SR (with homogeneity*) SR (with homogeneity*) SR (with homogeneity*)
homogeneity*) of RCTs of inception cohort of Level 1 diagnostic of prospective cohort of Level 1 economic
studies; CDR† validated studies; CDR† with 1b studies studies
in different populations studies from different
clinical centres
1b Individual RCT (with Individual inception Validating** cohort Prospective cohort study Analysis based on
narrow Confidence cohort study with > 80% study with good††† with good followͲup**** clinically sensible costs
Interval‡) follow Ͳup; CDR† reference standards; or or alternatives;
validated in a single CDR† tested within one systematic review(s) of
population clinical centre the evidence; and
including multi Ͳway
sensitivity analyses
1c All or none § All or none caseͲseries Absolute SpPins and All or none caseͲseries Absolute better Ͳvalue or
SnNouts†† worseͲvalue analyses
††††
2a SR (with SR (with homogeneity*) SR (with homogeneity*) SR (with homogeneity*) SR (with homogeneity*)
homogeneity*) of of either retrospective of Level >2 diagnostic of 2b and better studies of Level >2 economic
cohort studies cohort studies or studies studies
untreated control groups
in RCTs
2b Individual cohort study Retrospective cohort Exploratory** cohort Retrospective cohort Analysis based on
(including low quality study or follow Ͳup of study with good††† study, or poor follow Ͳup clinically sensible costs
RCT; e.g., <80% followͲ untreated control reference standards; or alternatives; limited
up) patients in an RCT; CDR† aŌer derivaƟon, review(s) of the
DerivaƟon of CDR† or or validated only on evidence, or single
validated on split Ͳ splitͲsample§§§ or studies; and including
sample§§§ only databases multi Ͳway sensitivity
analyses
2c "Outcomes" Research; "Outcomes" Research Ecological studies Audit or outcomes
Ecological studies research
3a SR (with SR (with homogeneity*) SR (with homogeneity*) SR (with homogeneity*)
homogeneity*) of of 3b and better studies of 3b and better studies of 3b and better studies
caseͲcontrol studies
3b Individual CaseͲControl NonͲconsecutive study; NonͲconsecutive Analysis based on
Study or without consistently cohort study, or very limited alternatives or
applied reference limited population costs, poor quality
standards estimates of data, but
including sensitivity
analyses incorporating
clinically sensible
variations.
4 CaseͲseries (and poor CaseͲseries (and poor CaseͲcontrol study, poor CaseͲseries or Analysis with no
quality cohort and quality prognostic cohort or nonͲindependent superseded reference sensitivity analysis
caseͲcontrol studies §§) studies***) reference standard standards
5 Expert opinion without Expert opinion without Expert opinion without Expert opinion without Expert opinion without
explicit critical explicit critical appraisal, explicit critical appraisal, explicit critical appraisal, explicit critical appraisal,
appraisal, or based on or based on physiology, or based on physiology, or based on physiology, or based on economic
physiology, bench bench research or "first bench research or "first bench research or "first theory or "first
research or "first principles" principles" principles" principles"
principles"

Grades of Recommendation
A consistent level 1 studies
B consistent level 2 or 3 studies or extrapolations from level 1 studies
C level 4 studies or extrapolations from level 2 or 3 studies
D level 5 evidence or troublingly inconsistent or inconclusive studies of any level
“Extrapolations” are where data is used in a situation that has potentially clinically important differences than the
original study situation.
178 The Urology Masterclass, Department of Urology, CMC, Vellore

Radiation exposure of imaging modalities (1- 4)

Method Radiation exposure (mSv)

KUB radiography 0.5-1
IVU 1.3-3.5
Regular-dose NCCT 4.5-5
Low-dose NCCT 0.97-1.9
Enhanced CT 25-35

References:
1. Kluner C, Hein PA, Gralla O, et al. Does ultra-low-dose CT with a radiation dose equivalent to that of KUB suffice to
detect renal and ureteral calculi? J Comput Assist Tomogr 2006 Jan-Feb;30(1):44-50.
2. Caoili EM, Cohan RH, Korobkin M, et al. Urinary tract abnormalities: initial experience with multidetector row CT
urography. Radiology 2002 Feb;222(2):353-60.
3. Van Der Molen AJ, Cowan NC, Mueller-Lisse UG, et al. CT urography: definition, indications and techniques. A guideline
for clinical practice.EurRadiol 2008 Jan;18(1):4-17.
4. Thomson JM, Glocer J, Abbott C, et al. Computed tomography versus intravenous urography in diagnosis of acute flank
pain from urolithiasis: a randomized study comparing imaging costs and radiation dose. AustralasRadiol 2001
Aug;45(3):291-7.

Properties of commonly used contrast media

(JAMA 2006; 295(23):2765–79.)

Jean François Reybard (1795–1863) French surgeon, invented the first self retaining balloon catheter. He described the
catheter as a rubber sound with two channels, one of which was surmounted with an ampul that was distended with water
of air after the sound was introduced into the bladder. This ampul or bulb was made of cat or sheep cecum.
 The Urology Masterclass, Department of Urology, CMC, Vellore 179

The TNM classification of Urological malignancies 8th edition

TNM penile cancer

Clinical classification
T - Primary Tumour
TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
Tis Carcinoma in situ
Ta Non-invasive verrucous carcinoma*
T1 Tumour invades subepithelial connective tissue
T1a Tumour invades subepithelial connective tissue without lymphovascular invasion and is not
poorly differentiated
T1b Tumour invades subepithelial connective tissue with lymphovascular invasion or is poorly
differentiated
T2 Tumour invades corpus spongiosum with or without invasion of the urethra
T3 Tumour invades corpus cavernosum with or without invasion of the urethra
T4 Tumour invades other adjacent structures
N - Regional Lymph Nodes
NX Regional lymph nodes cannot be assessed
N0 No palpable or visibly enlarged inguinal lymph nodes
N1 Palpable mobile unilateral inguinal lymph node
N2 Palpable mobile multiple or bilateral inguinal lymph nodes
N3 Fixed inguinal nodal mass or pelvic lymphadenopathy, unilateral or bilateral
M - Distant Metastasis
M0 No distant metastasis
M1 Distant metastasis
Pathological classification
The pT categories correspond to the clinical T categories.
The pN categories are based upon biopsy or surgical excision
pN - Regional Lymph Nodes
pNX Regional lymph nodes cannot be assessed
pN0 No regional lymph node metastasis
pN1 Metastasis in one or two inguinal lymph nodes
pN2 Metastasis in more than two unilateral inguinal nodes or bilateral inguinal lymph nodes
pN3 Metastasis in pelvic lymph node(s), unilateral or bilateral extranodal or extension of regional lymph
node metastasis
pM - Distant Metastasis
pM1 Distant metastasis microscopically confirmed
G - Histopathological Grading
GX Grade of differentiation cannot be assessed
G1 Well differentiated
G2 Moderately differentiated
G3 Poorly differentiated
G4 Undifferentiated
180 The Urology Masterclass, Department of Urology, CMC, Vellore

TNM prostate cancer

T - Primary Tumour (stage based on digital rectal examination [DRE] only)

TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
T1 Clinically inapparent tumour that is not palpable
T1a Tumour incidental histological finding in 5% or less of tissue resected
T1b Tumour incidental histological finding in more than 5% of tissue resected
T1c Tumour identified by needle biopsy (e.g. because of elevated prostate-specific antigen [PSA])
T2 Tumour that is palpable and confined within the prostate
T2a Tumour involves one half of one lobe or less
T2b Tumour involves more than half of one lobe, but not both lobes
T2c Tumour involves both lobes
T3 Tumour extends through the prostatic capsule
T3a Extracapsular extension (unilateral or bilateral)
T3b Tumour invades seminal vesicle(s)
T4 Tumour is fixed or invades adjacent structures other than seminal vesicles: external sphincter, rectum,
levator muscles, and/or pelvic wall
N - Regional (pelvic) Lymph Nodes1
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
M - Distant Metastasis2
M0 No distant metastasis
M1 Distant metastasis
M1a Non-regional lymph node(s)
M1b Bone(s)
M1c Other site(s)

1Metastasis no larger than 0.2 cm can be designated pNmi.

2 When more than one site of metastasis is present, the most advanced category is used. (p)M1c is the most advanced
category.
Clinical T stage only refers to DRE findings; imaging findings are not considered in the TNM classification. Pathological
staging (pTNM) is based on histopathological tissue assessment and largely parallels the clinical TNM, except for clinical
stage T1c and the T2 substages. All histopathologically confirmed organ-confined PCas after RP are pathological stage T2
and the current Union for International Cancer Control (UICC) no longer recognises pT2 substages

TNM testicular cancer

pT - Primary Tumour1
pTX Primary tumour cannot be assessed (see note 1)
pT0 No evidence of primary tumour (e.g. histological scar in testis)
pTis Intratubular germ cell neoplasia (carcinoma in situ)
pT1 Tumour limited to testis and epididymis without vascular/lymphatic invasion; tumour may invade tunica
albuginea but not tunica vaginalis*
pT2 Tumour limited to testis and epididymis with vascular/lymphatic invasion, or tumour extending through tunica
albuginea with involvement of tunica vaginalis**
pT3 Tumour invades spermatic cord with or without vascular/lymphatic invasion**
pT4 Tumour invades scrotum with or without vascular/lymphatic invasion
 The Urology Masterclass, Department of Urology, CMC, Vellore 181

N - Regional Lymph Nodes – Clinical

NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis with a lymph node mass 2 cm or less in greatest dimension or multiple lymph nodes, none more than
2 cm in greatest dimension
N2 Metastasis with a lymph node mass more than 2 cm but not more than 5 cm in greatest dimension; or more than
5 nodes positive, none more than 5 cm; or greatest dimension; or more than 5 nodes positive, none more than 5
cm; or evidence of extranodal extension of tumour
N3 Metastasis with a lymph node mass more than 5 cm in greatest dimension
pN - Regional Lymph Nodes – Pathological
pNX Regional lymph nodes cannot be assessed
pN0 No regional lymph node metastasis
pN1 Metastasis with a lymph node mass 2 cm or less in greatest dimension and 5 or fewer positive nodes, none more
than 2 cm in greatest dimension pN2 Metastasis with a lymph node mass more than 2 cm but not more than 5 cm
in greatest dimension; or more than 5 nodes positive, none more than 5 cm; or greatest dimension; or more than
5 nodes positive, none more than 5 cm; or extension of tumour evidence or extranodal extension of tumour
pN3 Metastasis with a lymph node mass more than 5 cm in greatest dimension
M - Distant Metastasis
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
M1a Non-regional lymph node(s) or lung metastasis
M1b Distant metastasis other than non-regional lymph nodes and lung
S - Serum Tumour Markers
SX Serum marker studies not available or not performed
S0 Serum marker study levels within normal limits
LDH (U/l) hCG (mIU/mL) AFP (ng/mL)
< 1.5 x N and < 5,000 and < 1,000
1.5-10 x N or 5,000-50,000 or 1,000-10,000
> 10 x N or > 50,000 or > 10,000

Stage grouping
Stage 0 pTis N0 M0 S0
Stage I pT1-T4 N0 M0 SX
Stage IA pT1 N0 M0 S0
Stage IB pT2 - pT4 N0 M0 S0
Stage IS Any patient/TX N0 M0 S1-3
Stage II Any patient/TX N1-N3 M0 SX
Stage IIA Any patient/TX N1 M0 S0
Any patient/TX N1 M0 S1
Stage IIB Any patient/TX N2 M0 S0
Any patient/TX N2 M0 S1
Stage II Any patient/TX N3 M0 S0
Any patient/TX N3 M0 S1
Stage III Any patient/TX Any N M1a SX
Stage IIIA Any patient/TX Any N M1a S0
182 The Urology Masterclass, Department of Urology, CMC, Vellore

Any patient/TX Any N M1a S1

Stage IIIB Any patient/TX N1-N3 M0 S2
Any patient/TX Any N M1a S2
Stage IIIC Any patient/TX N1-N3 M0 S3
Any patient/TX Any N M1a S3
Any patient/TX Any N M1b Any S

TNM renal cell carcinoma

T - Primary Tumour
TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
T1 Tumour < 7 cm or less in greatest dimension, limited to the kidney
T1a Tumour < 4 cm or less
T1b Tumour > 4 cm but < 7 cm
T2 Tumour > 7 cm in greatest dimension, limited to the kidney
T2a Tumour > 7 cm but < 10 cm
T2b Tumours > 10 cm, limited to the kidney
T3 Tumour extends into major veins or perinephric tissues but not into the ipsilateral adrenal gland and not beyond
Gerota fascia
T3a Tumour grossly extends into the renal vein or its segmental (muscle-containing) branches, or tumour
invades perirenal and/or renal sinus fat (peripelvic fat), but not beyond Gerota fascia
T3b Tumour grossly extends into the vena cava below diaphragm
T3c Tumour grossly extends into vena cava above the diaphragm or invades the wall of the vena cava
T4 Tumour invades beyond Gerota fascia (including contiguous extension into the ipsilateral adrenal gland)
N - Regional Lymph Nodes
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in regional lymph node(s)
M - Distant Metastasis
M0 No distant metastasis
M1 Distant metastasis
pTNM stage grouping
Stage I T1 N0 M0
Stage II T2 N0 M0
Stage III T3 N0 M0
T1,T2, T3 N1 M0
Stage IV T4 Any N M0
Any T Any N M1

TNM upper tract urothelial carcinoma

T - Primary tumour
TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
Ta Non-invasive papillary carcinoma
Tis Carcinoma in situ
T1 Tumour invades subepithelial connective tissue
 The Urology Masterclass, Department of Urology, CMC, Vellore 183

T2 Tumour invades muscularis

T3 (Renal pelvis) Tumour invades beyond muscularis into peripelvic fat or renal parenchyma (Ureter) Tumour
invades beyond muscularis into periureteric fat
T4 Tumour invades adjacent organs or through the kidney into perinephric fat
N - Regional lymph nodes
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in a single lymph node 2 cm or less in the greatest dimension
N2 Metastasis in a single lymph node more than 2 cm, or multiple lymph nodes
M - Distant metastasis
M0 No distant metastasis
M1 Distant metastasis

TNM bladder carcinoma

T - Primary tumour
TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
Ta Non-invasive papillary carcinoma
Tis Carcinoma in situ: ‘flat tumour’
T1 Tumour invades subepithelial connective tissue
T2 Tumour invades muscle
T2a Tumour invades superficial muscle (inner half)
T2b Tumour invades deep muscle (outer half)
T3 Tumour invades perivesical tissue
T3a Microscopically
T3b Macroscopically (extravesical mass)
T4 Tumour invades any of the following: prostate stroma, seminal vesicles, uterus, vagina, pelvic wall, abdominal
wall
T4a Tumour invades prostate stroma, seminal vesicles, uterus or vagina
T4b Tumour invades pelvic wall or abdominal wall
N – Regional lymph nodes
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in a single lymph node in the true pelvis (hypogastric, obturator, external iliac, or presacral)
N2 Metastasis in multiple regional lymph nodes in the true pelvis (hypogastric, obturator, external iliac, or presacral)
N3 Metastasis in common iliac lymph node(s)
M - Distant metastasis
M0 No distant metastasis
M1a Non-regional lymph nodes
M1b Other distant metastases

Primary urethral carcinoma

T - Primary Tumour
TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
184 The Urology Masterclass, Department of Urology, CMC, Vellore

Urethra (male and female)

Ta Non-invasive papillary, polypoid, or verrucous carcinoma
Tis Carcinoma in situ
T1 Tumour invades subepithelial connective tissue
T2 Tumour invades any of the following: corpus spongiosum, prostate, periurethral muscle
T3 Tumour invades any of the following: corpus cavernosum, beyond prostatic capsule, anterior vagina, bladder
neck (extraprostatic extension)
T4 Tumour invades other adjacent organs (invasion of the bladder)
Urothelial (transitional cell) carcinoma of the prostate
Tis pu Carcinoma in situ, involvement of prostatic urethra
Tis pd Carcinoma in situ, involvement of prostatic ducts
T1 Tumour invades subepithelial connective tissue (for tumours involving prostatic urethra only)
T2 Tumour invades any of the following: prostatic stroma, corpus sponsiosumspongiosum, periurethral muscle
T3 Tumour invades any of the following: corpus cavernosum, beyond prostatic capsule, bladder neck (extraprostatic
extension)
T4 Tumour invades other adjacent organs (invasion of the bladder or rectum)
N - Regional Lymph Nodes
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in a single lymph node
N2 Metastasis in multiple lymph nodes
M - Distant Metastasis
M0 No distant metastasis
M1 Distant metastasis

Moses Swick, MD (1900 – 1985), injected an organically-bound iodine compound, later named Uroselectan,
into a vein, taking X-rays as the material cleared the body through the urinary tract. Swick’s intravenous pyelogram
heralded a new era in urologic diagnosis.
 The Urology Masterclass, Department of Urology, CMC, Vellore 185

Response Evaluation Criteria in Solid tumors (RECIST)

Evaluation of target lesions
x Complete Response (CR): Disappearance of all target lesions
x Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline
sum longest diameter (LD)
x Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as
reference the smallest sum LD since the treatment started
x Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest
sum LD recorded since the treatment started or the appearance of one or more new lesionsA

Evaluation of non-target lesions

x Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor marker level
x Incomplete Response/ Stable Disease (SD): Persistence of one or more non-target lesion(s) or/and maintenance of
tumor marker level above the normal limits
x Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-
target lesions

Evaluation of best overall response

The best overall response is the best response recorded from the start of the treatment until disease progression/
recurrence (taking as reference for PD the smallest measurements recorded since the treatment started). In general, the
patient’s best response assignment will depend on the achievement of both measurement and confirmation criteria
x Patients with a global deterioration of health status requiring discontinuation of treatment without objective evidence
of disease progression at that time should be classified as having “symptomatic deterioration”. Every effort should be
made to document the objective progression even after discontinuation of treatment.
x In some circumstances it may be difficult to distinguish residual disease from normal tissue. When the evaluation of
complete response depends on this determination, it is recommended that the residual lesion be investigated (fine
needle aspirate/biopsy) to confirm the complete response status.
186 The Urology Masterclass, Department of Urology, CMC, Vellore

Bosniak classification of renal cysts

“Scoots et al. JUrol 2017; 198:12-21”

The Urology Masterclass, Department of Urology, CMC, Vellore 187

Bosniakclassification Prevalenceofmalignancy
I None
II Minimal
IIF(Stable) Lessthan1%
IIF(ReclassificationtoIII/IV–12%) 85%
III 51%
IV
 86%
 Scoots et al. JUrol 2017; 198:12Ͳ21

BosniakIIIcystsubͲclassification Progressionrate
IIIS(septatedenhancingcysts) HR6.16(95%CI2.58Ͳ14.72)
IIIN(cystswithwallorseptationsonlynodularity) HR0.21(95%CI0.05Ͳ0.85)
Pruthi et al. JUrol 2018; 200:1192Ͳ1199 

Scott FB and Bradley WE : Succeeded in implanting a device into the penis that could be pumped with saline to achieve erection.
In 1973 the Scott–Bradley–Timm inflatable prosthesis became the first marketed device designed to allow artificial erectile
tumescence. The history of modern ED surgery began with the development of this prosthesis.
188 The Urology Masterclass, Department of Urology, CMC, Vellore

NEPHROMETRY SCORING SYSTEMS

1. RENAL score (Kutikov and Uzo, J Urol 2009)

-Complexity of renal mass lesion based on size, endophytic component polar location, distance from collecting system
and anterior/ posterior location
Components
 The Urology Masterclass, Department of Urology, CMC, Vellore 189

Utility
- Correlates with approach (radical vs partial/ open vs lap nephrectomy), duration, ischaemia time, blood loss,
complications, renal function post-op, histology and grade
- Objective reporting and comparison of outcomes between groups
Criticism
- High measurement variability noted in some studies (E.g. collecting system anatomy variability in calculation of ‘N’,
poor inter-observer concordance in drawing lines for ‘L’)
- Does not predict post-operative renal function drop in patients with solitary kidney
- SRMs <4 cm may be suited to smaller radius scoring parameters as opposed to <4, 4-7 and >7 cm
- Poor correlation with positive margins.
- Does not reflect complexity with reference to hilar nodal mass, tumour thrombus and local invasion

2. Pre-operative Aspects and Dimensions Used for an Anatomical classification-PADUA (Ficarra V et al. Eur Urol 2006)
Variable HR
Anatomical features* Score
Padua score
Longitudinal (polar) location 6–7 Reference
Superior/inferior 1
8–9 14.535
Middle 2
2:10 30.641
Exophytic rate BMI (<25 vs >25) 0.513
2:50% 1
<50% 2
Endophytic 3

Renal rim
Lateral 1
Medial 2

Renal sinus
Not involved 1
Involved 2

Urinary collecting system

Not involved 1
Dislocated/inûltrated 2

Tumour size (cm)

:::4 1
4.1–7 2
>7 3

* Anterior or posterior face can be indicated with a letter

(‘‘a’’ or ‘‘p’’)
following the score.
190 The Urology Masterclass, Department of Urology, CMC, Vellore
 The Urology Masterclass, Department of Urology, CMC, Vellore 191

DAP nephrometry (Simmons M et al. J Urol 2012)

Predicts kidney volume preservation better, is simpler, less inter-observer variability

Cut-off values more representative for small renal mass
192 The Urology Masterclass, Department of Urology, CMC, Vellore

ABC (Arterial Based Complexity) scoring system (Spaliviero M et al. European Urology, 2016)

Cortical tumour involving interlobular + arcuate: Category 1

Interlobar arteries: Category 2

 The Urology Masterclass, Department of Urology, CMC, Vellore 193

Segmental arteries + collecting system: Category 3S

Hilum/ main vascular pedicle: Category 3S

Centrality/ C index (Simmons M et al. J Urol 2009)

-Reproducible, good prediction of operative difficulty

-Learning curve, lengthy calculation involved, kidney assumed to be uniform ellipse and tumour to be uniform sphere
194 The Urology Masterclass, Department of Urology, CMC, Vellore

C.L.A.M.P nephrometry (Wang Y, Nature Scientific Rep 2018)

Assesses complexity of arterial anatomy supplying tumour where selective clamping is involved
Each arterial branch supplying the tumour is included in calculation
X= Shortest horizontal distance from line tangential to hilum to the planned point of clamping
Y= Shortest vertical distance from horizontal line passing through the middle of hilum to the planned point of clamping
X and Y are assigned a score based on the table below
Score is calculated as a sum of the individual scores of each artery

E.g: If there are three vessels to be clamped for excising one tumour, score will be-
(X+Y)*1 + (X+Y)*1/2 + (X+Y)*1/3
A.M.P refer to the approach to be used for access to the vessel based on tumour- Anterior hemiboundary, M: Multi-
hemiboundary, P: Posterior hemiboundary

Practical advantage is that the complexity is based on the vascular supply of the tumour
The disadvantage is that the same score may theoretically be assigned to central and peripheral tumours just based on
the arterial supply
The Urology Masterclass, Department of Urology, CMC, Vellore 195
196 The Urology Masterclass, Department of Urology, CMC, Vellore

Zonal NePhRO scoring system (Hakky et al. Clin Genitourin Can 2014)

Simpler, easier to use, more predictive of post-op complications, better correlation with stage and complexity of SRM
The Urology Masterclass, Department of Urology, CMC, Vellore 197

Renal protection strategies in Nephron Sparing Surgery

Aim: To minimize ischaemic damage and preserve kidney function

1. No clamping of hilum
2. Manual compression/ Kaufmann clamp compression of parenchyma
3. Use of Mannitol infusion (12.5 gm) and surface cooling the kidney to 15–20 °C by using ice slush for 15 minutes after
clamping of hilum
4. In-situ perfusion with HTK solution (4-8 degrees Celsius at 55-75 cm water) during clamping and resection
5. Nephrectomy followed by extracorporeal perfusion with HTK during bench dissection of complex tumours and
autotransplantation
6. Surface cooling with cold saline irrigation (0.5 C) with pads surrounding the kidney and continuous temperature
monitoring to reach 15 to 25 degree Celsius (Laparoscopic)
7. Laparoscopic ice slush cooling: Endocatch bag placed around the kidney with ice slush after hilar clamping with
continuous temperature monitoring
8. Laparoscopic renal arterial perfusion: Angiocath placed via femoral artery into the renal artery on table followed by
clamping of renal artery close to origin and continuous infusion of iced Ringers lactate at 4 C at a rate of 50 ml per
minute using a pump. Vein not clamped as there is no backflow due to positive pressure. Thermocouple to monitor
renal temperature. Hypothermia- Patient warmed at the end of the procedure
9. Laparoscopic Zero Ischaemia PN: Progressive pharmacologic hypotension during the dissection into the parenchyma
with inhaled isoflurane (1.5–2.5%) and intravenous nitroglycerin (50–100 mg/min), with dosages increased until
MAP of 50–80 mm Hg is achieved. Intrarenal vessels identified and ligated. Once resection is complete, blood
pressure is restored to normal
10.Zero ischaemia PN with vascular microdissection has 4 steps: (1) Pre-op CT reconstruction of renal arterial branch
anatomy, (2) Dissection of tumour-specific tertiary or higher-order renal arterial branches, (3) Neurosurgical aneurysm
microsurgical bulldog clamp(s) for superselective tumor devascularisation (4) Transient, controlled hypotension, if
necessary.
11.Near Infrared Fluorescence and superselective ischaemia: Targeted tertiary tumour-specific branches controlled with
robotic bulldog(s) or neurosurgical aneurysm micro-bulldog(s). Indocyanine green dye injected and NIRF imaging
used to confirm super-selective ischaemia (Defined as darkened tumour/ peri-tumour area with green fluorescence
of remaining kidney) to facilitate accurate resection.

References
1. Hung AJ et al. Curr Opin Urol 2013
2. Campbell Walsh Urology 11th edition
3. Venkatramani V et al. Indian J Surg Oncol 2017
4. Gschwend JE et al. J Urol 1995
5. Janssen MW et al. WJSO 2018
6. Kijvikai K et al. J Urol 2010
7. Gill et al. J Urol 2003
8. Janteschek G et al. J Urol 2004
9. Eisenberg MS et al. Curr Opin Urol 2011
10. Ng CK. Eur Urol 2012
11. Borofsky MS et al. BJUI 2013
198 The Urology Masterclass, Department of Urology, CMC, Vellore

Stone Scoring Systems

Guy’s stone score

(Thomas K et al. Urology 2011; 78:277-281)

The four grades are intended to reflect the anticipated complexity of PCNL. Higher grades correlate with lower post
operative stone free rates.

S.T.O.N.E. nephrolithometry score

Variable Score
1 2 3 4
Stone size(mm2) <400 400-799 800-1599 >1599
Tract length (mm) =100 >100 NA NA
Obstruction No or mild Moderate to NA NA
hydronephrosis severe
hydronephrosis
Involved calyces (n) 1-2 3 Staghorn NA
Stone essence =950 >950 NA NA
(Hounsfield units)
NA – not applicable

Okhunov.Z et al. Urology 2013; 81:1154-1160

The Urology Masterclass, Department of Urology, CMC, Vellore 199

CROES nomogram (Smith A et al. JUrol 2013; 190:149-156)

Based on patient characteristics, stone properties and operator experience. An increasing score predicts increased
probability of treatment success

S-ReSC score (Jeong CW et al. PLoS oNE(2013)8.e65888)

This is based solely on stone distribution within the collecting system. Nine sites of stone location were
identified and one point given for each site. Higher scores correlated with lesser stone free rates and
more complications

S-ReSC scoring system: Sites designated for assessment were:

1) Renal pelvis (#1)
2) Superior and Inferior major calyceal groups (#2-3)
3) Anterior and posterior minor calyceal groups
a. Superior calyx (#4-5)
b. Middle calyx (#6-7)
c. Inferior calyx(#8-9)
200 The Urology Masterclass, Department of Urology, CMC, Vellore

Stone name, shape and composition (EAU 2019, Campbell Walsh 11th ed)

Composition Name Shape Named after

Calcium oxalate monohydrate Whewellite Hourglass William Whewell (19th century
inventor of crystallographic indexing)
Calcium oxalate dihydrate Wheddelite Envelope Named after crystals found at the
bottom of Wheddell sea, Antarctica
Basic calcium phosphate Apatite Hexagonal, Apatein (Greek) for deceitͲ Since it is
prismatic similar to many other minerals
Calcium hydroxyl phosphate Carbonate
apatite
Carbonate apatite phosphate Dahllite Tellef and Johan Martin Dahll
(Norwegian mineralogists)
Tricalcium phosphate Whitlockite Rhombohedral, Herbert Percy Whitlock (American
clear mineralogist and curator of American
Museum of Natural History, NY)
Calcium hydrogen phosphate Brushite Needle George Jarvis Brush (American
mineralogist, 19th century)
Calcium carbonate Aragonite Molina de Aragon in Spain
Anhydrous uric acid Uricite Amorphous shards
Magnesium Ammonium phosphate (MAP) Struvite Coffin lid Heinrich Chistian Gottfried von Struve
(Geologist, 19th century, Hamburg)
MAP monohydrate Dittmarite William Dittmar (Prof of Chemistry,
Glasgow)
MAP trihydrate Newberyite James Cosmo Newbery (Discoverer,
Melbourne)

Basic work-up in stone disease (Skolarikos, Eur Urol 2015)

Clinical Stone history, diet, medication, family history

Imaging USG/ NCCT
Blood Creatinine, calcium (Ionized/ corrected), uric acid
Urinalysis pH, specific gravity, rbc, wbc, protein, nitrite, leucocyte esterase
Urine culture If infection suspected/ invasive intervention planned
Stone analysis Repeat for each episode. Use infrared spectroscopy/ X ray diffraction

High risk stone formers requiring full evaluation (Skolarikos, Eur Urol 2015)

General Child, familial, recurrent, Uric acid/ Brushite, infection stone, solitary kidney, spine trauma
Genetic Cystinuria, Xanthinuria, Primary hyperoxaluria, RTA type 1, Lesch Nyhan syndrome, Cystic fibrosis
Metabolic Hyperparathyroidism, nephrocalcinosis, bariatric surgery/ Crohn’s/ malabsorption, Sarcoidosis
Anatomic Medullary sponge kidney, PUJ obstruction, ureterocoele, calyceal diverticulum, VUR, horseshoe kidney

24 hour urine collection method (EAU 2019, Campbell Walsh 11th ed)
-Two samples collected after 20 stone free days/ 2-3 months after start of medical treatment
-Self determined diet by patient
-Start collection after first void and include the first void of the next day
-Preservative: 5% thymol in isopropanol/ stored at < 8°C/ 10 gm Boric acid added to container
The Urology Masterclass, Department of Urology, CMC, Vellore 201

24 hour urine reference range (Campbell Walsh Urology 11th ed, Kokorowski PJ Ind J Urol 2010)

Component Adult Child

Calcium <200 mg female, <250 mg male <4 mg/kg
Oxalate >40 mg <0.57 mg/kg
Uric acid <800 mg male, <750 mg female <10 mg/kg
Citrate >450 mg male, >550 mg female >6 mg/kg
Magnesium >80 mg >1 mg/kg
pH 5.8-6.2 6-7
Volume >2000 ml >1 ml/kg/hr
Creatinine 20-25 mg/kg weight male, 15-20 mg/kg female

General preventive measures in stone former (EAU 2019)

Fluid intake -2.5-3 lit daily to ensure 2-2.5 lit/ day output, circadian intake, neutral pH beverages
Nutrition -Increased fibre and vegetables -Calcium 1-1.2 gm/ day
-Sodium <4-5 gm/ day -Animal protein 0.8-1 gm/kg weight
Lifestyle -Adequate physical activity for normal BMI

Medical treatment of urinary abnormalities (EAU 2019, Skolarikos, Eur Urol 2015)
Agent Used for Stone type Dose Adverse effects
Alkaline citrate Alkalinisation Calcium oxalate 5-12 gm/ day pH monitoring needed
Prevent CaOx formation Uric acid Children: 0.1-0.15 gm/kg/day Large dose
Hypocitraturia Cystine Ca phosphate stone formation
Allopurinol Hyperuricaemia Uric acid 100-300 mg/day Dose correction in CKD
Hyperuricosuria NH4 urate Children: 1-3 mg/kg/day Pancytopaenia
Ca oxalate Fever, rash, hepatitis
Steven Johnson syndrome
Calcium Enteric hyperoxaluria Ca oxalate 1-1.2 gm/day GI symptoms
Captopril Decrease urine Cystine Cystine 75-150 mg/day Cough
levels (2 nd line drug)
Febuxostat Hyperuricaemia Uric acid 80-120 mg/day Transamnitis, rash, arthralgia
Hyperuricosuria NH4 urate
Ca oxalate
L-Methionine Acidification Infection stones 600-1500 mg/day Systemic acidosis,
Ammonium urate hypercalciuria, osteoporosis
Ca phosphate
Magnesium Enteric hyperoxaluria Ca oxalate 200-400 mg/d Diarrhoea, dose reduction in
Isolated hypomagnesuria Children: 6 mg/kg/d CKD
NaHCO3 Alkalinization Calcium oxalate 1.5 gm/day -
Hypocitraturia Uric acid
Cystine
Pyridoxine Primary hyperoxaluria Calcium oxalate 5-20 mg/kg/day Polyneuropathy
Thiazide Hypercalciuria Calcium oxalate 25–50 mg/day Diabetes, hyperuricaemia, low
Calcium Children: 0.5–1 mg/kg/day blood pressure
phosphate
Tiopronin Cystinuria Cystine 250-2000 mg/day Tachyphylaxis , proteinuria
202 The Urology Masterclass, Department of Urology, CMC, Vellore

Categories of unsuccessful treatment with intravesical BCG (EAU

guidelines 2019)
Definitions Comment

BCG failure Any high grade/CIS/MIBC disease occurrence during or

after BCG = failure

A) Whenever a MIBC is detected during follow-up. -MIBC at anytime during follow up

B) BCG-refractory tumour:
1. If T1G3/HG, non-muscle-invasive papillary tumour is
present at three months
2. If TaG3/HG or CIS (without concomitant papillary -Any high grade recurrence during BCG = Refractory
tumour) is present at both three and six months (after a
second induction course or the first maintenance course
of BCG). If patients with CIS present at three months, an
additional BCG course can achieve a complete response in
> 50% of cases
3. If high-grade tumour appears during BCG therapy.*C) -Any high grade recurrence after BCG despite an initial
High-grade recurrence after BCG. Recurrence of high-grade/ response = Relapsing
grade 3 (WHO 2004/1973) tumour after completion of BCG
maintenance, despite an initial response.
BCG unresponsive Newer updated definition in consultation with FDA to
facilitate trials for treatment of BCG unresponsive
BCG refractory or T1Ta/HG BCG relapse within 6 months or
NMIBC.Includes Refractory + Relapse (HG relapse within 6
development of CIS within 12 months of last BCG exposure
months and CIS within 12 months of last BCG)
BCG intolerance
Severe side effects that prevent further BCG instillation
before completing treatment

* Patients with low-grade recurrence during or after BCG treatment are not considered to be a BCG failure.
Sources for Mycobacterium bovis strains: Connaught, Armand Frappier, Pasteur, Tice, Danish 1331, Tokyo, British

Intravesical BCG schedule according to SWOG study

(Lamm DL et al. J Urol 2000; 163:1124–9.)
Phase BCG schedule Total BCG instillations
Induction phase 6 weekly 6

Maintenance phase At 3months – three weekly 3

At 6 months – three weekly 3
At 12 months – three weekly 3
At 18 months – three weekly 3
At 24 months – three weekly 3
At 30 months – three weekly 3
At 36 months –three weekly 3
TOTAL 27
The Urology Masterclass, Department of Urology, CMC, Vellore 203

TB gene Xpert PCR procedure

Add 2:1 volume reagent to sputum/
urine/ tissue and wait 15 minutes

Liquefaction occurs. Transfer 2 ml to chamber

Sample automatically washed and

filtered to remove inhibitors

Ultrasonic lysis of cells and released DNA

strands mixed with PCR reagents

Amplification of rpoB gene segment

by semi-nested PCR

Molecular beacon binds to wild type rpoB gene

Wild type rpoB gene: Molecular rpoB mutation: Molecular probe does
probe binds to rpoB gene DNA not bind as DNA sequence is altered
segment and fluorescence seen as and little/ no fluorescence seen as
fluorophore separates from quencher quencher is bound to fluorophore
204 The Urology Masterclass, Department of Urology, CMC, Vellore

Methods to grade prostate volume

1. Lodh modification of Romero et al (Health education Journal 2011, JMGIMS 2016)

Grade Weight Surface Median sulcus Depth of lateral sulcus Accesss to entire
prostate
I 20 gm Flat Shallow 1 fingertip Easy
II 40 gm Rounded bilobar Well defined 1-2 fingertips Some difficulty
III 60 gm Rounded Obliterated 2 fingertips Marked difficulty
IV 80 gm Rounded Obliterated >2 fingertips Not possible

2. Reis et al (Adv Urol 2013)

Each fingertip of the surface area corresponds to 10 cc

3. Barnes (Endoscopy 1st edition, 1959)

Clinical grade Degree of encroachment into rectum

Normal <1 cm
I 1-2 cm
II 2-3 cm
III 3-4 cm
IV >4 cm

Cysto
scopic Lateral lobes Prostatic urethra Intravesical
grade
Normal Concave, do not touch in midline 1-2 cm between veru and prostate border Does not cover trigone
I Convex, do not touch 2-3 cm between veru and prostate border Covers <1/2 trigone
II Touch in midline for <2 cm 3-4 cm between veru and prostate border Covers half to full trigone
III Touch in midline for 2-3 cm 4-5 cm between veru and prostate border Extends beyond trigone
IV Touch in midline for >3 cm >5 cm between veru and prostate border Extends upto fundus

Grade Gland to be resected

I <20 gm
II 20-50 gm
III 50-125 gm
IV >125 gm
4. Tsui KH (Urol Sci 2013)
Grade Size Description
I (Mild) <40 gm <2 finger-widths surface area of prostate
II (Moderate) 40-60 gm 2-3 finger-widths surface area of prostate
III (Severe) >60 gm >3 finger-widths surface area of prostate
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5. Grayhack et al (Benign prostatic hyperplasia, 4th edition, 2002)

Grade Size Description Like

0 20 gm Flat, no luminal protrusion into rectum Chestnut
I 25 gm 25% luminal protrusion into rectum Plum
II 50 gm 50% luminal protrusion into rectum Lemon
III 75 gm 75% luminal protrusion into rectum Orange
IV >75 gm >75% luminal protrusion into rectum Grapefruit

6. Aguirre (J Urol 1970)- USG grading

Grade Size
I 21-30 cc
II 31-50 cc
III 51-80 cc
IV >80 cc

7. Chia et al (BJUI Int 2003)- IPP grading on ultrasound

Grade IPP
I <5 mm
II 5-10 mm
III >10 mm
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TURP RESECTION TECHNIQUES

Phases of resection in all methods as per Mauermayer

1. Cone resection: Excision of a tissue cone with its base situated at the internal sphincter

2. Excavation of cavity: The entire prostatic fossa is resected excluding the apex

3. Apical resection: Paracollicular apical tissue is removed

I. Mauermayer technique
1. Groove at 6 O’ clock
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2. Extending groove to 5 and 7 O’ clock

3. Deepening the groove to the capsule

4. Resection of lateral lobes

5. Resection of ventral tissue between 11 and 1 O’ clock

208 The Urology Masterclass, Department of Urology, CMC, Vellore

6. Resection of apical tissue with small cuts and left little finger resting on perineum

7.Resectable apical tissue identified by moving sheath in and out- Mobile (Wobble test)

II. Nesbit technique

1. Ventral cut at the roof starting at 12 o’ clock and moving laterally till the capsule is reached (Intravesical resection)
 The Urology Masterclass, Department of Urology, CMC, Vellore 209

2. Cutting a trench from the roof to 7 and 5 o’ clock to isolate blood supply of lobes

3.Resection of isolated median and lateral lobes (Extravesical resection)

4. Resection upto the capsule

5. Apical resection
210 The Urology Masterclass, Department of Urology, CMC, Vellore

III. Holtgrewe modification of Nesbit technique

-Resection begins at 1 O’ clock instead of 12 o’ clock and proceeds to 6 O’ clock with the
resectoscope tip positioned in the middle of the prostatic fossa.

-This is extended clockwise to the 6-o’clock position and repeated on the opposite side.

-The resectoscope is then repositioned proximal to the veru and tissue is resected in quadrants, beginning with area
between 12-o’clock and the 3-o’clock

-Apical tissue is removed last

IV. Barnes’ technique

1.Excision of median and basal portions of lateral lobes in layers

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2. Excision of lateral lobes from floor to roof one side after other (Extravesical resection)

3. Apical resection

V. Richard Notley method

Resection starts at the floor and proceeds clockwise
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VI. Milner technique

-The Milner technique is started with a deep incision directly into the lateral lobe at the 3 or 9-o’clock position and
proceeds until the surgical capsule is reached.
-Further resection is then performed from this starting point in quadrants.
-Apex is resected last

VII. Alcock and Flocks technique

-A groove is incised on either side at the junction of lower lateral lobe and median lobe, and deepened to expose fibers
of the internal sphincter and divide the principal vessels feeding the median lobe
-The median lobe is then resected
-A trench is made at 3 or 9 O’ clock to the capsule
-The lobes are resected in quadrants
-Apex is resected last

References
1. Transurethral Surgery by Wolfgang Mauermayer
2. Transurethral resection by John P Blandy
3. Transurethral resection of prostate (Medscape) by Stephen W Leslie
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American Association for the Surgery of Trauma Organ Injury

Severity Scale
(Source http://www.aast.org/Library/TraumaTools/InjuryScoringScales.aspx)
Renal trauma

Ureteric trauma
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Bladder trauma

Urethral injury
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216 The Urology Masterclass, Department of Urology, CMC, Vellore

Durrant JJ et al R Army Med Corps 2013;159(Supp I):i32–i39.

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Iatrogenic posterior urethral strictures classification

Pansadaro et al.UROLOGY 53: 784–789, 1999.

Type I – fibrous tissue involves bladder neck only

Type 2 – The stricture is localized to the median

part
of the prostatic fossa

Type 3- The stricture involves the whole prostatic

urethra
218 The Urology Masterclass, Department of Urology, CMC, Vellore

Pelvic fracture urethral distraction defect

Rates of stricture, impotence and urinary incontinence

(Koraitim MM. JUrol.1999; 161: 1433-1441)

Type of procedure Stricture rate Impotence Incontinence

Primary suturing 49% 56% 21%
Primary realignment 53% 36% 5%
Delayed repair 97% 19% 4%

Risk ratio of pelvic fracture type for membranous urethral injury

(Koraitim MM.et al.Br J Urol. 1996; 71: 876)

Type of fracture Odds ratio

Straddle # 3.85
Malgaigne # 3.40
Straddle with sacroiliac joint diastasis 24.02

Bladder neck configuration predicting continence

(Koraitim MM. AJU 2015; 13: 64-67)

Configuration Continence
Open rectangular bladder neck on cystography Incompetent bladder neck suspected
and fixedly open bladder neck on suprapubic
cystoscopy

Funnelling and triangular bladder neck on Competent bladder neck suspected

cystography
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Landmark BPH trials in brief
220 The Urology Masterclass, Department of Urology, CMC, Vellore
Landmark BPH trials in brief
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References:
1) Jacobsen et al. Olmsted county study. J. Urol. 1999; 162:1301-1306
2) Lepor H et al. Veterans affair 359 study. NEJM. 1996; 335: 533-539
3) Kirby et al. PREDICTstudy. Urology. 2003; 61:119-126
4) McConnell et al. PLESS study. NEJM 1998; 338:557-563
5) McConnelll et al. MTOPS study. NEJM 2003; 349(25):2387-98
6) Roehrborn et al. CombAT study. Eur. Urol. 2010; 57(1): 123-38
7) Roehrborn et al. ALTESS study. BJUI 2006; 97:734-41
8) Nickel C et al. ALF-ONE study. BJUI 2005; 95: 571-74
9) McNeil et al. ALAUR study. Urology 2005; 65:83-90
10)Fitzpatrick J. Natural history of BPH. BJUI 2006; 97: Suppl. 2:3-6
11)Roehrborn et al. Review of combination. Rev. Urol. 2005; 7(Suppl.8):S43-S51
 222 The Urology Masterclass, Department of Urology, CMC, Vellore

CHEMOTHERAPY IN UROLOGICAL MALIGNANCIES

Urothelial carcinoma bladder

Neoadjuvant chemotherapy:
Accelerated or dose dense MVAC X 4 cycles followed by reassessment for surgery.
Inj Methotrexate 30 mg/m2 iv push D1,
Inj Vinblastine 3 mg/m2 iv push D1,
Inj Doxorubicin 30 mg/m2 iv in 100 ml NS over 1 hour D1,
Inj Cisplatin 70mg/m2 IV in 500 ml NS over 2 hours D1
Cycle every 2 weeks.
Adjuvant chemotherapy:
Cisplatin + Gemcitabine (Inj Cisplatin 75mg/m2 IV on D1, Gemcitabine 1000 mg/m2 on day 1 and 8)
Gemcitabine + Oxaliplatin (Inj Oxaliplatin 85mg/m2 IV on D1, Gemcitabine 1000 mg/m2 on day 1 and 8)

Prostate cancer
Chemohormonal therapy:
ADT + Inj. Docetaxel 75 mg/m2 every 3 weeks X 6 doses (Chaarted trial protocol).
In CRPC:
Inj. Docetaxel 75 mg/m2 every 3 weeks until disease progression of unacceptable toxicity.
Second line:
Inj. Cabazitaxel 25 mg/m2 every 3 weeks
Tab. Abiraterone 1 gm once daily until disease progression or toxicity.

Carcinoma penis:
Neoadjuvant chemotherapy:
DCF protocol- every 21 days - 3 cycles followed by surgery.
Inj. Docetaxel 75 mg/m2 on day 1.
Inj. Cisplatin 75mg/m2 on D1
Inj. 5 FU 750mg/m2 in 1000ml NS over 24 hrs infusion D1-D5
For patients with borderline performance status:
Inj. Paclitaxel 175 mg/m2 on day 1.
Inj. Cisplatin 75mg/m2 on D1
Cycle every 21 days, 4 cycles

TIP regimen
Inj Paclitaxel 250mg/m2 (D1)
Inj Ifosphamide 1500 mg/m2 (D2-D5)
Inj Cisplatin 25 mg/m2 (D2-D5)
Inj Mesna 600 mg/m2 (D2-D5)
Cycle every 21 days, 4 cycles
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Testicular carcinoma
BEP (Every 3 weeks)