MANAGEMENT OF MOHAMED SEID

RENAL TUMORS GSR- III

CONTENTS OF MY TALK

 Introduction
 Benign tumors
 Evaluation of Cystic Renal Lesions
 Incidence , Etiology, Pathology & Clinical presentation of RCC
 Work up
 Clinical assessment
 Laboratory investigations
 Radiologic Evaluation
 Renal biopsy
 TNM Staging
 Management of RCC
History

 Wolcott(1861) - 1st documented Nephrectomy

 Simon(1869)- 1st planned Nephrectomy
 Harris (1882)- reported on 100 extirpations of kidney
 Surgical interventions provided the Clinical information &
Histopathologic insight
Introduction

 RCC includes a number of distinct subtypes derived from the various parts
of the nephron, each with a unique genetic basis and tumor biology

 Other major advances in the past several decades have included the
introduction of RN followed by a trend toward less radical approaches
(NSS, MI-approaches)

 RCC remains primarily a surgical disease

 Renal masses can be Malignant, Benign or Inflammatory

 Radiographic appearance as Simple cystic, Complex cystic, Fatty tumors and

Others with complex cystic to solid components
Benign renal neoplasms

 It constitute a rather large & heterogeneous group of renal

lesions
 account for <4% of all solid renal tumors
 Simple & Complex renal cysts
 AML, Oncocytoma, Cortical & Metanephric adenomas
 Rarer Cystic Nephroma, mixed epithelial-stromal tumor etc
 Inflammatory DDx
 Their age of incidence & symptomatology are similar to RCC
 Mx options vary widely ( Ex. For simple cyst, selective
embolization for larger AML & surgery for solid renal masses
if the DDx includes RCC)
Evaluation of Cystic Renal Lesions

 Renal cysts remain the MC benign renal lesions,

represents >70% of asymptomatic renal masses
 It can be Solitary / Multiple & Unilateral / Bilateral
 Bosniak system is based on imaging features like the
description of septations, calcifications, and enhancement
 The thickness , contour of the wall of the lesion
 The number, contour, and thickness of any septa
 The amount, character, & location of any calcifications
 Density of fluid in the lesion
 Margination of the lesion
 Presence of solid components
 Bosniak classification
 Category I lesions
 uncomplicated, simple cysts that are simple to Dx
with USG, CT, or MRI
 The MC renal cystic lesions, & in the absence of
symptoms, no treatment is necessary
 Category II lesions
 Minimally complex cysts that are generally benign but
have some radiologic findings that cause concern
 These lesions include septated cysts, cysts with wall /
septum calcification , infected cysts, & hyperdense
(high-density) cysts
Bosniak..
 Category IIF lesions
 The risk of radiographic progression is about 15%
 Overall risk of malignancy-3% -10%
 Periodic renal imaging
 Category III lesions
 More complex cysts that cant be confidently distinguished from
RCC
 Imaging features include thickened irregular or smooth walls or
septa
 About 50% likelihood of malignancy
 FNAC of complex cysts is rarely done (sampling error & tumor cell
spillage)
 Require surgery
 Category IV lesions
 Large cystic components; irregular, shaggy margins &
solid enhancing portions
 Almost invariably cystic RCCs that, if localized, require
surgical treatment
Renal cell carcinoma
 MC type of renal malignancy
Risk factors
 2%-3% of all adult Cas
 M:F=3:2  Cigarette smoking
 Peak incidence 50-70 years age  Obesity
 Incidence rates are 10% to
20% higher and 5-year  Hypertension
 survival rates 5% lower in  ESRD,PCKD, familial
African-Americans for unknown syndromes such as
reasons
 Only 2-3% familial the rest
tuberous sclerosis
sporadic  Radiation exposure
 The most lethal of the common
urologic cancers)  Occupational Exposure
Pathology of RCC
 It arises from the renal epithelium of PCT / CD often in the renal
cortex but can arise from almost any component of the nephron
 It occurs:
 equally in either kidneys and is bilateral in 2%
 Multi-centric in as many as 20% of patients
 Occurs in both a sporadic and a hereditary forms
 Based on Morphology and Cytogenetic RCC
 Clear cell (70-80%)
 Papillary ( 10-15%)
 Chromophobe (3-5%)
 Collecting duct( <1%)
 Renal medullary ( rare)
 Unclassified RCC (1-3%)
Pathology..

 RCC can grow large while remaining clinically silent

 They tend to grow into the renal vein (10%) and vena cava &
the tumor thrombi may extend as far as the right atrium
 The most common sites of metastases are:
– Lungs ~ 70%
– LNs / Soft tissues ~ 36%
– Bones ~ 20%
– Liver ~ 18%
– Brain ~ 8%
 Clinical Presentation
INCIDENTAL Symptoms of Obstruction Symptoms of
PRESENTAION -60% localized disease of the IVC systemic disease

At presentation: Hematuria Bilateral Persistent cough

Flank pain lower Bone pain
Localized -45% Abdominal mass extremity Cervical
Locally advanced-25% Perirenal edema lymphadenopathy
Metastatic-30% hematoma Non-reducing Constitutional
or right-sided symptoms
varicocele Weight
loss/fever/malaise
Paraneoplastic
syndromes
Indicators of advanced disease
 The classic triad (too late triad ) of flank pain, gross
hematuria & palpable abdominal mass
 Constitutional symptoms such as weight loss,
fever, & night sweats, PLUS findings such as
palpable cervical LAP , non-reducing varicocele,
and bilateral lower extremity edema
Paraneoplastic
syndrome
 10-20% of patients with
RCC
 RCC once called
internist’s tumor due to
the predominance of
systemic rather than
local manifestations
 Now, a more appropriate
name would be the
radiologist’s tumor,
given the frequency of
incidental detection
PNS..
 HTN & polycythemia are other important PNS s
commonly found in patients with RCC
 One of the more fascinating PNS associated with
RCC is non-metastatic hepatic dysfunction, or
Stauffer syndrome, which has been reported in
3%-20% of cases
 In general, treatment of PNS associated with RCC
has required surgical excision or systemic therapy
& except for hypercalcemia, medical therapies
have not proved helpful
Screening ???
FOR SCREENING
Factors like RCC is still a primarily surgical
disease ,Known R/Fs for RCC
AGAINST SCREENING
 RCC is the relatively low incidence of
RCC in the general population
NOT-COST EFFECTIVE
The focus of screening for RCC must be
on well-defined target populations, such
as patients with ESRD & acquired renal
cystic disease, TSC , and familial RCC
Pre-op Work ups
 Full clinical assessment
 Laboratory investigations
 Mets work up
 Imaging options
 Ultrasound
 CT
 MRI
 Percutaneous biopsy
Preoperative Evaluation and Preparation

 Hx & P/E
 Cardiopulmonary Comorbidities
 Laboratory
 CBC
 OFT, PT/PTT,RBS
 Serum electrolytes including serum ca+2
 LDH,
 Urinalysis , cytology & culture
 ECG
 CXR
 Echo
 Pulmonary function test
 Imaging
Pre-op work up..

Metastatic evaluation
Abdominal CT or MRI
Chest CT
 Abnormal CXR
 Pulmonary symptoms
 IVC involvement
Bone scan
Head CT/ MRI
RADIOGRAPHIC EVALUATION OF RENAL MASSES
 USG
USG
Non-invasive & Cheap
Its able to def cystic Vs solid
Strict USG criteria :
smooth cyst wall with
round/oval shape
No internal echoes complex
Through transmission with
strong acoustic shadows
posteriorly
CT scan
 Gold standard
 Any renal mass that enhances on contrast CT >15 HU should
be considered RCC until proved otherwise
 Solid masses that also have substantial areas of negative CT
attenuation numbers (<−20 HU) indicative of fat are diagnostic
of AML
 In 10%-20% of solid renal masses, CT findings are
indeterminate & additional imaging, biopsy, or surgery is
needed to settle the diagnosis
 On occasion, CT demonstrates an enhancing renal segment
that is iso-dense with the remainder of the kidney, suggestive
of a renal pseudo-tumor
MRI
 Its an alternate standard
imaging modality , CT is
inconclusive , in assessing
( retroperitoneal LNs, IVC )

 Enhancement indicative of
malignancy can also be
assessed by MRI using
gadolinium though its only
qualitative

 Its most useful in patients for

whom iodinated contrast
medium is C / I in severe
allergy , pregnancy & ESRD
Percutaneous Renal biopsy
 For radiologically indeterminate
renal masses; often <3 cm in
size not requiring nephrectomy
 Indicated when suspicion of
renal abscess or RCC must be
differentiated from metastatic
Ca or renal lymphoma
 too High -FN rate for routine
use historically (used to be up
to 18%)
 Alhough about 15 % of Renal Bx
are non-diagnostic, the real
false-negative rate is now <1%
with overall accuracy >80%
Complications appear to be
low (<1%)
 Significant perinephric
bleeding
 Pneumothorax
 Needle track seeding is
exceedingly rare when
centrally located, infiltrative
renal masses are excluded
 Poorly differentiated
urothelial carcinoma is
much higher risk for needle
track seeding than RCC
Staging
 Outcomes in RCC are directly tied to clinical stage at time of
diagnosis
 It includes history, physical examination, and laboratory testing
 Evaluation for renal masses includes imaging of the primary
tumor as well for determining extent of dissemination
 Also, based on clinical suspicion or abnormal results of laboratory
studies, bone and brain imaging is performed
 A key aspect of abdominal CT or MRI is evaluation of the renal vein
and IVC as RCC commonly forms tumor thrombus in these
structures, and this finding is not necessarily correlated with tumor
stage
 Histologic grading is based on the Fuhrman nuclear grading system
on a scale of I to IV
Staging
 History, physical
examination&
 Modified Robson’s lab(CBC, LFT, RFT)
and TNM  Contrast enhanced
 The clinical staging of abdominal CT and/or
renal malignant disease MRI
begins with a thorough  CXR / CT
Clinical evaluation , and
judicious use of
laboratory tests
Modified Robson’s staging

Shortcomings
 Stage III
 The extent of
nodal and
venous
involvement
TNM staging system
Staging of RCC
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor 7 cm or less in greatest dimension, limited to the kidney
T1a Tumor 4 cm or less in greatest dimension, limited to the kidney
T1b Tumor more than 4 cm but not more than 7 cm in greatest dimension, limited to the
kidney
T2 Tumor >7 cm in greatest dimension, limited to the kidney
T2a Tumor >7 cm and ≤10 cm in greatest dimension, limited to the kidney
T2b Tumor >10 cm in greatest dimension, limited to the kidney
T3 Tumor extends into major veins or perinephric tissues but not into the ipsilateral adrenal
gland and not beyond Gerota fascia
T3a Tumor grossly extends into the renal vein or its segmental (muscle-containing)
branches, or tumor invades perirenal and/or renal sinus fat but not beyond Gerota
fascia
T3b Tumor grossly extends into the vena cava below the diaphragm
T3c Tumor grossly extends into the vena cava above the diaphragm or invades the wall
of the vena cava
T4 Tumor invades beyond Gerota fascia (including contiguous extension into the ipsilateral
adrenal gland
 Staging..

Regional Lymph Nodes (N) Stage Grouping

Stage I T1 N0 M0
NX Regional LNs cannot be assessed
N0 No regional lymph node metastasis Stage II T2 N0 M0
N1 Metastasis in regional LN(s)
Stage III T1 or T2 N1 M0, T3 N0
or N1 M0
Distant Metastasis (M) Stage IV T4 Any N M0
M0 No distant metastasis
M1 Distant metastasis
Management options
The principal treatment options for RCC are as
follows:
 Surgery ( Partial / Radical nephrectomy)
 Radiation therapy
 Ablation therapy
 Immunotherapy
 Molecular-targeted therapy
Ablation therapy
 Thermal ablative therapies
 Cryosurgery
 Radiofrequency
 Indications
 Advanced age
 Comorbidities
 recurrence after previous nephron-sparing surgery
 patients with hereditary renal cancer who present with
multifocal lesions
Surgical Mx..
 Renal surgery has undergone a significant transformation in
the past 10 years, and most renal surgery, both NSS &
radical excision is now performed through either a
laparoscopic or robotically assisted
 Historically, RCC was considered as only a surgical disease &
patients diagnosed with any renal mass underwent RN
 Now, selected patients may undergo renal biopsy & active
surveillance protocols
 Those patients who are appropriate for renal
biopsy are patients considered for either active
surveillance or renal ablation therapy
Mx…
 Surgical resection remains the only known curative
treatment for localized RCC & is used for palliation
in metastatic disease
 For renal tumors that are diagnosed in the absence
of metasases or for those with a solitary metastasis,
surgery is still the standard of care
 Resection of solitary synchronous metastatic
disease is performed when it is technically
feasible
Nephron sparing surgery (NSS/
PN)
 The trend in extirpative surgery is to perform
NSS or PN for most T1 tumors
 PN has equivalent oncologic outcome to RN in this
tumor stage & should be considered for all patients
with a T1a tumor & most with T1b tumors
 Radical nephrectomy for central / hilar-T1& T2
PN/NSS..
 NSS may be straightforward in dealing with
small, well encapsulated, superficial, exophytic
lesions or complex in dealing with larger, central
lesions that involve the renal hilar structures
 For PN , a negative margin should be obtained
with the parenchymal resection & only a few
millimeters of normal parenchyma around the
tumor are considered necessary
PN/NSS..
 The general principles for PN
 negative surgical margin
 Identification & suturing of significant segmental renal vessel
branches
 Collecting system repair when the collecting system is entered
or partially resected
 Techniques helping in controlling bleeding during PN:
 Atraumatic vascular clamping of the renal artery
 Surface cooling of the kidney with iced saline slush
 Tissue sealants
 Hemostatic agents
 Absorbable mesh reconstruction of the kidney
Radical nephrectomy
 For patients with large tumors & those in whom a
PN is not technically feasible like in centrally located
tumors
 Concern for loss of renal function with future risk of
CKD
 In comparison to PN, RN has a lower rate of
post-op complications
 The adrenal gland is no longer removed with RN
except in cases of obvious tumor involvement as
the rate of synchronous involvement is < 10%
RN..
 Typically, RN is performed by either a laparoscopic or
open approach
 Standard incisions
 Anterior subcostal, flank, chevron, & Midline
 Regardless of approach, dissection of the renal pedicle with
ligation of a renal artery must precede vein ligation to
prevent swelling & dangerous bleeding from the kidney
 The entire Gerota fascial envelope, containing the
perinephric fat as a margin around the kidney parenchyma
& tumor, is excised intact
 The ureter is ligated & divided where convenient but in case
of urethelial tumors more distal ligation is recommended
PARTIAL Vs RADICAL-NEPHRECTOMY FOR
LOCALIZED RCC
 PN is preferred for small renal masses (T1a, <4.0cm) when-
ever feasible, because RN represents gross overtreatment
for most such lesions, which tend to have limited
biologic potential
 PN is also strongly preferred whenever preservation of renal
function is potentially important, such as patients with pre-
existing CKD, SICK contralateral kidney, or those with
multifocal or familial RCC
 Larger renal tumors (CS-T1b & T2) have increased
oncologic potential & have often already replaced a
substantial portion of the parenchyma, leaving less to be
saved by PN
 In the setting of a normal contralateral kidney, the relative
merits of PN Vs RN can be debated in this population…
Locally Advanced RCC T3 +T4
 All patients with non-metastatic disease & VTT & an
acceptable performance status should be treated with RN +
Trombectomy

 In the presence of clinically positive LNs (cN+) doing LND

is ???justified

 In patients with non-ressectable disease, embolization can

control symptoms, including gross hematuria or flank pain

 No indication for adjuvant therapy following surgery

 Metastatic RCC
 Options of treatment
 Cytoreductive
nephrectomy
 Immunotherapy
 IFN alpha, interleukin-2
 Targeted therapies
 Sorafenib, sunitinib,
axitinib, pazopanib,
bevacizumab,
temsirolimus,
everolimus,
 Cytoreductive RN combined
with IFN improves survival
in patients with Mets.RCC +
good performance status
 Cytoreductive RN for
patients with simultaneous
complete resection of a
single metastasis or
oligometastases may
improve survival and delay
systemic therapy.
Mets..
 With the exception of brain and possibly bone
metastases, metastasectomy remains by default
the most appropriate local treatment for most sites

 Radiotherapy to bone and brain metastases from

RCC can induce significant relief from local
symptoms (e.g. pain).
Recurrent RCC
 Locally recurrent disease can occur either after PR,
RN & after thermal ablation
 local recurrence after nephrectomy is a recurrent
disease in the already operated renal fossa
 Repeated ablation or surgical resection is
recommended
REGIONAL LYMPH NODE
DISSECTION
 Its often performed with a RN , although, on the
basis of most evidence, it is more helpful as a
staging / prognostic procedure than as a
therapeutic one
 For patients with locally advanced or metastatic
disease, immunotherapy & targeted therapy are
used in a neo-adjuvant or adjuvant fashion with
palliative RN
Active Surveillance
 Active surveillance is defined as the initial
monitoring of tumour size by serial abdominal
imaging (US, CT, or MRI) with delayed intervention
reserved for tumours showing clinical progression
during follow-up
 Indication
 In elderly or poor surgical risk patients
 Small(<3cm), solid, enhancing, well-marginated, homogeneous
asymptomatic renal lesions
 Serial renal imaging at 6-month or 1-year intervals
 Prognosis
Tumor Related
• Stage Patient Related Laboratory
• Performance • Anemia
• Grade status • Thrombocytosis
• Symptomatic
• Size presentation • Hypercalcemia
• Histologic subtype • Constitutional • Elevated ESR
symptoms • Elevated
• Sarcomatoid • Paraneoplastic alkaline
histology syndromes phosphatase
• Metastasis-free level
• Tumor necrosis interval • CA-9 expression

• Sites of metastasis
• Burden of metastasis
Fuhrman’s System for Nuclear Grade in RCC

In the original report, the 5-year survival rates for grades 1 to

4 were 64%, 34%, 31%, and 10%, respectively, and nuclear
grade proved to be the most significant prognostic factor for
organ-confined tumors in this series
Prognosis
Stage Grouping 5yr survival( %)

Stage I T1 N0 M0 80- 100%

Stage II T2 N0 M0 50-80%

Stage III T1 or T2 N1 M0 0-20%

T3 Any N M0

Stage IV T4 Any N M0 0-10%

Any T Any N M1
Operative technique
 Radical nephrectomy
 Partial nephrectomy
Radical nephrectomy
Extent

Boundaries of a left radical nephrectomy. Dotted line represents both the surgical
margin and Gerota’s fascia.
Radical nephrectomy
Incision
 Mobilization to expose the kidney

After entering the peritoneal cavity, the colon is reflected medially to

expose the left (A) or right (B) kidney and great vessels .
Ligation and division of renal pedicle
Extent of lymphadenectomy
 From the crura of the diaphragm just
below the origin of the SMA to the
origin of IMA.
 Four levels of Venacaval involvement of RCC

Classification of inferior vena caval tumor thrombus from renal cell carcinoma,
according to the distal extend of the thrombus, as perirenal, subhepatic, intrahepatic,
and suprahepatic.
Radical Nephrectomy With Infrahepatic Vena Caval
removal
Radical Nephrectomy With Intrahepatic
or Suprahepatic Vena Caval thrombus Removal

 Bilateral subcostal incision + Median sternotomy

 It requires cardiopulmonary bypass with deep
hypothermic circulatory arrest

Technique of veno-venous bypass for removal

of supradiaphragmatic vena caval tumor
thrombus
Partial Nephrectomy
 It includes
 polar segmental nephrectomy
 Simple enucleation,
 wedge resection, and
 transverse resection
Basic principles
 Mobilization of the kidney with early vascular
control,
 Avoidance of ischemic renal damage,
 Complete tumor excision with free margins,
 Precise closure of the collecting system,
 Careful hemostasis, and Closure or coverage of the
renal defect with adjacent fat, fascia, peritoneum
Complications
 Renal insufficiency
 Urine leak
 Injury to adjacent organs
 Hemorrhage
 Local recurrence
 Postoperative urinary fistula following NSS
Fuhrman’s System for Nuclear Grade in RCC

GRADE NUCLEAR SIZE NUCLEAR NUCLEOLI

OUTLINE
1 10 μm Round, uniform Absent or inconspicuous

2 15 μm Irregular Small (visible at 400×

magnification)

3 20μm Irregular Prominent

4 >20 μm Bizarre ,often Prominent, heavy
multi-lobulated chromatin clumps present

 The system uses 4 grades based on nuclear size

,irregularity and nuclear prominence
 Its most effective in predicting metastasis (50% of high-
grade tumors within 5 years)
THANK
YOU
References
 European association of Urology, 2015.
 CAMPBELL – WALSH Urology, 11th edition
 SMITH’S GENERAL UROLOGY, 17th edition
 Operative Urology at the Cleveland Clinic
 Uptodate 21.2