Urosurgery 22 Renal Cell Carcinoma

  1. Enumerate the malignant tumors of kidney. Describe the clinical features of renal tumors. [TU 2059]
  2. Etiology of RCC?
    • Cigarette smoking
    • Exposure to asbestos, solvents, and cadmium
    • Hereditary forms of RCC have been described. Von Hippel-Lindau disease (triad of bilateral renal cell tumors, retinal angiomata and cerebellar hemangiomata)
    • Acquired cystic disease of the kidneys
  3. Pathology of RCC?
    RCC is also called as Hypernephroma (Grawitz’s tumour)

    • Gross features-
    • RCCs originate in the cortex and tend to grow out into perinephric tissue, causing the characteristic bulge or mass effect that aids in their detection by diagnostic imaging studies
    • Yellow to orange because of the abundance of lipids, particularly in the clear cell type.
    • RCCs do not have true capsules but may have a pseudocapsule of compressed renal parenchyma, fibrous tissue, and inflammatory cells.

    • Microscopy -
    • Originates from the proximal renal tubular epithelium
    • Histologically, RCC is most often a mixed adenocarcinoma containing clear cells, granular cells, and, occasionally, sarcomatoid-appearing cells
  4. Pathogenesis of RCC?
    • RCCs are vascular tumors that tend to spread either by direct invasion through the renal capsule into perinephric fat and adjacent visceral structures or by direct extension into the renal vein.
    • Approximately 25–30% of patients have evidence of metastatic disease at presentation.
    • The most common site of distant metastases is the lung. Cells enter the circulation and reach the lungs, where they grow to form cannonball secondary deposits
    • However, liver, bone (osteolytic), ipsilateral adjacent lymph nodes and adrenal gland, brain, the opposite kidney, and subcutaneous tissue are frequent sites of disease spread
  5. TNM staging of RCC?

    Describe the various stages of renal cell carcinoma. [TU 2073]
    • T1 Tumor ≤7 cm, limited to the kidney
    • T1a -  ≤4 cm
    • T1b - >4 cm but ≤7 cm 

    • T2 Tumor >7 cm, limited to the kidney
    • T2a -  >7 cm but ≤10 cm 
    • T2b - >10 cm

    • T3 Tumor extends into major veins or perinephric tissues, but not into the ipsilateral adrenal gland and not beyond Gerota's fascia
    • T3a - into the renal vein 
    • T3b -  the vena cava below the diaphragm
    • T3c - the vena cava above the diaphragm 

    T4 Tumor invades beyond Gerota's fascia (including contiguous extension into the ipsilateral adrenal gland)

    N1 -  in regional lymph node(s)

    M1- Distant metastasis
  6. Signs and symptoms of RCC?
    • Triad of gross hematuria, flank pain, and a palpable mass occurs in only 7–10% of patients.
    • Dyspnea, cough, and bone pain that are typically symptoms secondary to metastases
  7. Paraneoplastic syndromes associated with RCC?
    Erythrocytosis - from enhanced production of erythropoietin from the tumor or as a consequence of regional renal hypoxia promoting erythropoietin production from nonneoplastic renal tissue.

    Hypercalcemia - may be due to production of a parathyroid hormone-related peptide that mimics the function of parathyroid hormone

    Hypertension - due to renin production by the neoplasm has been documented in 37%. The excess renin and hypertension associated with RCC are typically refractory to antihypertensive therapy but may respond after nephrectomy.

    Hepatic dysfunction in the absence of hepatic metastases (Stauffer syndrome)

    Other biologically active products that result in clinically significant syndromes,including adrenocorticotropic hormone (Cushing’ssyndrome), enteroglucagon (protein enteropathy), prolactin (galactorrhea), insulin (hypoglycemia), and gonadotropins (gynecomastia and decreased libido; or hirsutism, amenorrhea,and male pattern balding)
  8. Laboratory findings in RCC?
    • Anemia
    • Hematuria
    • Elevated sedimentation rate
  9. USG criteria for simple renal cyst?
    • A well-circumscribed mass without internal echoes
    • Adequate visualization of a strong posterior wall
  10. CECT findings of RCC?
    • A typical finding of RCC on CT is a mass that
    • becomes enhanced with the use of intravenous contrast media.
    • In general, RCC exhibits an overall decreased density
    • in Hounsfield units compared with normal renal parenchyma but shows either a homogeneous or heterogeneous pattern of enhancement (increase in density of >10 Hounsfield units) following contrast administration.
    • CT scanning is also the method of choice in staging the patient by visualizing the renal hilum, perinephric space, renal vein and vena cava, adrenals, regional lymphatics, and adjacent organs.
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  11. Indication of FNAC in RCC?
    Carcinoma kidney is diagnosed on clinical ground and on radiological features. A FNAC is not indicated as it will breach the capsule and may cause seedling of tumor cells along the needle track. Specific indications of FNAC are - 

    • Clinically apparent metastatic disease who may be candidates for nonsurgical therapy.
    • Establishing a diagnosis in patients who are not surgical candidates
    • Differentiating a primary RCC from a renal metastasis in patients with known primary cancers of nonrenal origin.
    • Evaluating some radiographically indeterminate lesions.
  12. Treatment of localized RCC?

    Describe various operative approaches to renal cell carcinoma of the right kindey. [TU 2067/2]
    • ●Radical nephrectomy - most widely used approach and remains the preferred procedure
    • ●Partial nephrectomy (either open or laparoscopic) - patients with tumors <4 cm in size, even in the presence of normal contralateral kidney,  Bilateral RCC, Disease in solitary kidney
    • ●For elderly patients and those with significant comorbid disease - ablative techniques (cryoablation, radiofrequency ablation) are an alternative.
    • ●Active surveillance may be an option for patients with small asymptomatic lesions (<3cm) particularly in elderly patients.
    • ●Following complete resection of a localized RCC, there is no role for adjuvant therapy
  13. Treatment of Disseminated disease?

    How will you manage a case of stage iv renal cell carcinoma? [TU 2073]
    • A) Surgery
    • - cytoreductive nephrectomy (Nephrectomy in the presence of metastatic disease)
    • - Patients presenting with a solitary metastatic site particularly in the lung - combined nephrectomy and removal of the metastatic foci

    B) Radiation therapy – relatively radioresistant, but is effective in metastatic disease in brain, bone and lung.

    C) Biologic response modifiers – recombinant INF-alpha, recombinant IL-2

    • D) Targeted therapy
    • 1. Receptor tyrosine kinase inhibitors
    • a) Bevacizumab - VEGF Inhibitor
    • b) Sorafenib - Raf, VEGF, PDGFR, KIT inhibitor
    • c) Sunitinib - KIT, VEGFR, PDGFR, Flt3 inhibitor
    • d) Pazopanib -  c-KIT, FGFR, PDGFR and VEGFR inhibitor
    • 2. mTOR inhibitors – temsirolimus, everolimus

    • First-line treatment
    • ●For patients who have a good performance status and intact organ function - high-dose interleukin-2 (IL-2) rather than anti-angiogenic targeted therapy

    • Second-line treatment
    • ●For patients who progress after immunotherapy (IL-2) - axitinib rather than sorafenib. 
    • ●For patients who progress after an initial VEGF pathway inhibitor - treatment with nivolumab, cabozantinib, or the combination of lenvatinib plus everolimus rather than single agent everolimus.

    [Note - mTOR is mechanistic target of rapamycin]
  14. Follow up in RCC?
    • Stage T1 disease-  yearly chest x-rays and liver and renal function tests.
    • Stage T2 or T3 - more frequent follow-up of at least 3-month or 6-month intervals in the early postoperative period.
    • Repeat CT scans of the abdomen should also be obtained, especially in those who have undergone partial nephrectomy, to rule out local recurrence.
  15. Radical nephrectomy?
    • Kidney and its enveloping fascia (Gerota’s)
    • Ipsilateral adrenal
    • Proximal one-half of the ureter
    • Lymph nodes up to the area of transection of the renal vessels.

    The vascular pedicle should be ligated before the kidney is mobilised because handling the tumour may cause malignant cells to be released into the circulation.
Card Set
Urosurgery 22 Renal Cell Carcinoma
Renal cell carcinoma