Three doctors presented on renal cell carcinoma. Some key points: - Renal cell carcinoma arises from renal tubular cells and is the most common type of kidney cancer. - Presentation may include hematuria, loin pain, and palpable abdominal mass. Metastasis can cause cough or bone pain. - Diagnosis involves imaging like CT scan and lab tests. Surgery is the main treatment but immunotherapy and targeted drugs are also used. - Prognosis depends on stage - early stage has good prognosis but late stage with metastasis has poorer outlook.

1. Presented By: Interns
Dr Jeevan Shrestha
Dr Sanjeev Shrestha
Dr Manish Maharjan
Date: 14th September 2017
RENAL CELL CARCINOMA

2.  I have no conflict of interest or disclosure in
relation to this presentation.

3.  Also known as:
- HyperNephroma
- Grawitz tumour
- Clear cell carcinoma
- Internist tumour
- Renal cell adenocarcinoma
- Renal cell cancer

4.  First described by Konig in 1826
 In 1883, Grawitz, noted the fatty content of
cancer cells similar to that of adrenal cells.
 3% of adult malignancies
 90-95% of neoplasms arising from the kidney
 2 % - 4% increase in incidence per year

5. Adenocarcinoma arising from renal tubular cells.
- Most common site: Proximal Renal Tubules
- Common in males(M:F= 1.6:1)
- More common in 5th -7th decade of life.
- Median age at diagnosis from 2002 to 2006 was 64 years
- Median age of death was 70 years
- This non capsulated tumour is very vascular.
- 30% presents with metastatic disease.
- 10th leading cause of cancer deaths in males in the
United States

6. Phenotypic and Molecular Characteristic :
 Site of Origin
 Proximal Nephron: 1. Clear cell carcinoma(75%)
- VHL mutation
- Hypermethylation
- LOH 3p25
2. Papillary Carcinoma(15%)
-HPRC(type 1) :
Met protooncogene mutation
-HLRCC(type 2):
Fumarate Hydratase mutation
-7q3 Trisomy
 Distal Nephron:
- Oncocytoma
- Chromophobe Carcinoma
- Collecting duct carcinoma
- Undifferentiated carcinoma(<2%)

9. Risk Factors:
- Tobacco Smoking(24-30% cases)
2 fold increase risk for RCC
- Obesity , HTN
- Cystic Kidney disease patient after long term dialysis
- Hormonal : Diethylistillbestrol
- Occupational: Leather tanning, shoe workers,asbestos
 Genetic:
- Von Hippel-Lindau (VHL) syndrome [ 3p25] :
Bilateral
- Hereditary papillary renal carcinoma (HPRC)
- Familial renal oncocytoma (FRO) associated
with Birt-Hogg-Dube syndrome (BHDS)
- Hereditary renal carcinoma (HRC)
- Analgesic(Phenacetin)
- Family History Positive : 2.5 x greater risk
- Dietary: High fat/ Protein

11.  American Cancer Society (Estimation for 2017) :
- 63,990 cases of malignant tumors of the kidney
diagnosed : 40,610 in males
23,380 in females
- 14,400 deaths : 9470 in males
4930 in females
Renal cell carcinoma is expected to account for
80% of this incidence and mortality.

12. Spread
 Local:
- Adrenal Glands
- Renal veins
- Inferior venacava
- Gerota’s fascia(anterior to perinephric space)
- Perinephric Tissue
 Blood:
 Lung(50%), Bone(30%), Liver, Soft tissue, CNS
- Cannon ball secondaries
 Lymphatics:
- Lymph nodes at renal hilum
- Abdominal para-aortic nodes
- Paracaval nodes

13. Case:
 55 year male
 c/o: Swelling in left loin x 9 months
Pain in the left loin x 6 months
Passage of blood in urine x 6 months
- Swelling in the left loin gradually increasing in size
associated with dull aching continuous pain
- Passage of blood in urine, dark red in color,often with
clots, intermittent at interval of 10-15 days and lasts for
about 2-3 days.
- Swelling in left side of scrotum is also present for 2
months.
- Examination: General examinatin normal except
patient is anemic

14.  Systemic examination:
 Inspection: Normal contour of abdomen with no
scar, distension, engorged vein, or any visible
peristalsis
 Palpation:
- Left kidney is palpable extending from left lumbar to
left hypochondrium.
- Medial, lateral and lower margin is palpable with
irregular surgace, non tender, firm,moving slightly
with respiration.
- Liver and spleen arenot palpable
 Percussion: Dullness in renal angle
 Ausculation: BS +
 Local examination of external genitalia: Normal
except mild degree of varicocele on left side.

15. Clinical Presentaion
 Most are asymptomatic(25%-35%) until development of metastasis
 Incidental
Classical triad(10%cases):
- HEMATURIA(40%)
- LOIN PAIN(40%)
- PALPABLE MASS IN THE FLANK OR ABDOMEN(25%)
Metastasis:
Persisent Cough, Bone pain, Cervical lymphadenopathy, Weight loss, fever,
Malaise
Obstruction of Inferior venacava:
Bilateral lower extremity edema
Right sided varicocele
Left sided varicocele(2% males):
-due to compression of testicular vein
-Irreducible
Constitutional symptoms: Fever/sweating/Malaise/Weight

16. Paraneoplastic syndrome
 Polycythemia(Erythropoietin)
 Hypercalcemia(Parathyroid hormone related peptide)
 Hypertension(Renin)
 Hepatic dysfunction
 Feminisation
 Masculinisation
 Cushing Syndrome(ACTH)
 Eosinophilia
 Leukemoid reaction
 Amyloidosis
 Stauffer syndrome : Non metastatic reversible liver
dysfunction which gets corrected after nephrectomy.

17. Diagnostic tests
 History and physical examination
 Laboratory: CBC,ESR, Serum Calcium,LDH, Renal profile, LFT
 Urine microscopy: Look for RBC
 RADIOLOGICAL:
 USG abdomen: To know size, extension, lymph node involvement,
spread, status of renal veins and inferior venacava
 Intravenous pyelography: Lack of sensitivity and specificity
 Thin slice renal CT scan with and without IV contrast is the best
test for diagnosing renal masses.
-Detects early lesion,function,spread, venous status, lymph node
status, tumour extension.
-CECT : Helps to find out function of opposite kidney.
- Any renal mass that enhances with IV administration of contrast on
CT by more than 15 HU should be considered an RCC until
proved otherwise(Hartman et al, 2004)

18.  Chest Xray: May show calcified cannon ball
secondaries
 MRI:
-Diagnostic to assess the tumour thrombus in IVC.
- To evaluate collecting system
 Renal angiogram: To see vasularity
 Pharmacoangiogram(Inject noradrenaline along with
dye while doing angiogram)
- Tumour blush can be visualised.
- As tumour vessels are autonomous they willnot
constrict.
 Bone scan: To see secondaries
 Inferior venacavogram

20. Robson Modification of the Flocks and
Kadesky system
 Stage I :
Tumor confined within capsule of kidney
 Stage II :
Tumor invading perinephric fat but still
contained
within the Gerota fascia
 Stage III :
Tumor invading
(A) the renal vein or inferior vena cava
(B) Regional lymph node involvement
(C) Both A + B
 Stage IV :
Tumor invading adjacent viscera (excluding
ipsilateral adrenal) or distant metastases

22. AJCC TNM STAGING:
 Primary tumors (T) are defined as the following:
TX : Primary tumor cannot be assessed
T0 : No evidence of primary tumor
T1 : Tumour 7 cm or smaller in greatest dimension, limited
to the kidney
T1a : Tumour is 4 cm or smaller
T1b : Tumour is 4 - 7 cm in greatest dimension
 T2 : Tumour larger than 7 cm in greatest dimension, limited
to the kidney
T2a : Tumour is 7 - 10 cm in greatest dimension
T2b : Tumour is more than 10 cm in greatest dimension

23.  T3 :
Tumour extends into major veins or invades
adrenal gland or perinephric tissues but
not beyond the Gerota fascia
T3a : Tumour invades adrenal gland or
perinephric tissues but not beyond the
Gerota fascia
T3b : Tumour grossly extends into the renal
vein(s)
or venacava below the diaphragm
T3c : Tumour grossly extends into the renal
vein(s)
or venacava above the diaphragm
 T4 : Tumor invading beyond the Gerota fascia

24.  Regional lymph node (N) classification is not
affected by laterality and is defined as follows:
 NX – Regional lymph nodes cannot be assessed
 N0 – No regional lymph node metastasis
 N1 – Metastasis in regional lymph node(s)
 Distant metastasis (M) is defined as the following:
 M0 – No distant metastasis
 M1 – Distant metastasis

28. Prognostic factors:
 Symptomatic presentation
 Weight loss
 Poor performance status
 ESR> 30mm/ hr
 TUMOUR size, positive margins, liver and lung
metastasis
 Anemia
 Elevated ALP
Shuch BM et al 2006

29. Treatment
 Surgery is the treatment of choice
 Partial Nephrectomy
 Radical Nephrectomy
 Chemotherapy (RCC is mostly chemoresistant)
 Angioinfarction
 Immunotherapy
 Adjuvant: Tyrosine kinase Inhibitors(TKI’s)

30.  Partial Nephrectomy
According to the 2009 AUA management guideline, in patients
with a T1 renal mass, complete surgical excision by partial
nephrectomy is a standard of care
Advantage: Avoidance of dialysis and reduced risk of
chronic kidney disease

31. Radical Nephrectomy
 most commonly performed standard surgical procedure today
 Gold standard treatment for localised RCC with contralateral
normal kidney,adequate surgical margin
 Complete removal of the
Gerota fascia and its
contents, including a
resection of kidney,
perirenal fat, and
ipsilateral adrenal
gland, with or without
ipsilateral lymph node
dissection.

32. Molecular-Targeted Agents
 Sunitinib
 Bevacizumab in combination with interferon
 Pazopanib
 Temsirolimus
 Everolimus
 Lenvatinib in combination with everolimus
 Nivolumab
 Cabozantinib
 Sorafenib
 Axitinib

34. Sunitinib
- Multikinase inhibitor
- Receptor inhibited:
- Vascular endothelial growth factor receptors 1,2,
and 3 (VEGFR 1-3), Platelet-derived growth
factor receptor alpha (PDGFR-alpha), and
PDGFR-beta
- Recommended dose for advanced renal cell
carcinoma is one 50 mg oral dose taken once
daily, with or without food, on a schedule of 4
weeks on treatment, followed by 2 weeks off
treatment

35. Chemotherapy
 Floxuridine (5-fluoro 2'-deoxyuridine [FUDR])
 5-fluorouracil (5-FU)
 Vinblastine
 paclitaxel (Taxol)
 carboplatin
 ifosfamide
 gemcitabine
 anthracycline (doxorubicin)
 RCC is refractory to most chemotherapeutic agents
because of multidrug resistance mediated by p-
glycoprotein

36. Experimental Therapeutic Approaches
 Immunomodulatory drugs (eg, lenalidomide)
 Vaccines
 Nonmyeloablative allogeneic peripheral blood
stem-cell transplantation
 Megestrol and antiestrogens

37. Radiation Therapy
 primary therapy for palliation(Painful osseous lesion
or brain metastasis)
 RCC is radioresistant tumor
 radiation treatment of brain metastasis improves
quality of life, local control, and overall survival
duration.
 Symptomatic relied in 64-84% patients
 Renal Artery Embolization:
 Ethanol and gelatin sponge pledgets has been found
effective for palliative treatment
 retrospective study in 8 patients with stage IV disease
found that ethanol ablation controlled hematuria and
flank pain

38. Thank you