RENAL CELL CARCINOMA

RENAL CELL CARCINOMA

1. RENAL CELL CARCINOMA PRESENTOR DR KARAN R RAWAT UNDER THE GUIDANCE OF DR.T.C.SADASUKHI dr h. L gupta

2. Also known as GRAWITZ TUMOUR ,HYPERNEPHROMA

3. STAUFFER’S SYNDROME –REVERSIBLE HEPATIC DYSFUNCTION

4. PARANEOPLASTIC SYNDROMES refers to a constellation of systemic signs and symptoms that are secondary to the presence of a malignancy tumor -related syndromes may be the result of one of several factors: tumor production of humoral substances, or benign tissue production of humoral factors in response to renal malignancy or via the modulation of the immune system . HYPERCALCAEMIA Osseous metastatic RCC lesions appear to elaborate substances that activate osteoclasts , causing the release of calcium from bone. The local secretion of prostaglandins by metastatic RCC lesions has also been implicated in the elevated serum calcium levels seen in these patients. parathyroid hormone (PTH )  binds to the PTH receptor in both bone and renal tissue. This binding leads to increased bone resorption and decreased renal clearance of calcium as well as increased phosphorus excretion

5. Hypertension Potential mechanisms of hypertension in these patients include increased renin secretion, ureteral or parenchymal compression, presence of an arteriovenous fistula, and poly- cythemia . Renin is the active form of the prohormone prorenin , which is secreted by the juxtaglomerular apparatus (JGA) of the nephron . Through its action via the rennin- aldosterone - angiotensin system, renin overproduction may result in hypertension POLYCYTHAEMIA   elevated serum red blood cell concentrations are believed to be mediated by erythropoietin (EPO), a glycoprotein that induces differentiation of erythrocyte colony-forming units in the bone marrow to promote red blood cell production.Under normal physiological conditions, EPO is produced by peritubular renal interstitial cells in response to local tissue hypoxia. However, in RCC, EPO production occurs in the tumor cells themselves

6. NONMETASTATIC HEPATIC REVERSIBLE DYSFUNCTION The syndrome is characterized by elevations in liver enzymes as well as abnormal levels of hepatic synthetic products. Elevations of aspartate aminotransferase , alanine aminotransferase , alkaline phosphatase ], and prothrombin time The cause of Stauffer’s syndrome is poorly understood. Some believe that the tumor itself secretes hepatotoxins or lysosomal enzymes that stimulate hepatic cathepsins or phosphatases , which leads to hepato -cellular injury Clinically , patients may present with hepatosplenomegaly , fever, and weight loss OTHERS : Some are present merely as associated serum findings, such as elevated human chorionic gonadotropin (HCG) or adrenocorticotropic hormone (ACTH). Others, however, manifest themselves as clinical syndromes such as galactorrhea , Cushing’s syndrome, and hyper / hypoglycemia . β- HCG, normally made by the syncytiotrophoblastic cells of the placenta, has been found in elevated levels in patients with RCC.  Elevated levels of this hormone in any adult male or nonpregnant female should suggest malignancy

7. Management of localized RCC SURGERY - Radical nephrectomy Nephron sparing partial nephrectomy OTHER MODALITIES Radiotherapy Chemotherapy Targeted molecular therapy

8. APPROACHES TO RADICAL NEPHRECTOMY -

9. it includes a systematic approach with careful mobilization of Gerota’s fascia and early vascular control. For a flank approach, the posterior peritoneum lateral to the colon is incised along the length of the descending colon (left side) or ascending colon (right side) and reflected medially. For left-sided exposure, the lienorenal ligament is incised to mobilize the spleen cephalad . On the right side, the hepatic flexure of the colon is mobilized. The ureter is identified and encircled with a vessel loop. The gonadal vein is ligated and divided. The plane between the mesentery of the colon and Gerota’s fascia is then developed using a combination of sharp and blunt dissection. On the right side, the vena cava is exposed by Kocherizing the duodenum. Using blunt dissection, the retroperitoneal fat overlying the renal vessels is separated, exposing the renal hilum . It is often helpful to ligate and divide the ureter before this to allow for mobilization and upward displacement of the lower pole of the kidney

10. The dissection is then carried cephalad along the vena cava (right side) or aorta (left side). On the right side, the right renal vein is identified entering into the vena cava, isolated, and clamped After identification of the renal artery (exposure may be enhanced by the use of a vein retractor on the renal vein), the artery is dissected free and cleaned for a distance of approximately 2 to 3 cm and clamped with right angle clamp. The sutures are then separated and tied, allowing a safe distance for division of the artery. A small hemoclip or suture ligature may be placed on the proximal aspect of the artery before division. A right-angle clamp is placed under the artery to be divided and gently elevated, and the artery is cut with either a knife Metzenbaum scissors. The right renal vein is then ligated in a similar fashion

11. On the left, the  renal vein  is isolated as it courses over the aorta. The left adrenal and gonadal veins are identified emanating from the left renal vein, and, if present, a posteriorly directed lumbar venous tributary is noted. A right-angle clamp is passed around the renal vein, followed by a silk suture proximal to the tributaries, and tagged. The venous tributaries are then individually ligated and divided with silk and small hemoclips where necessary, leaving the silk suture on the main renal vein tagged. The left renal artery and vein are then ligated similarly to the technique described above for the right side.

12. Gerota’s fascia is then mobilized posteriorly and superiorly using a combination of sharp and blunt dissection. Hemoclips along the superior and medial border are useful to control any potential bleeding during this portion of the procedure. The adrenal hilum is then dissected from caudal to cranial with the aid of either hemoclips or straight clamps and ties. On the right side, the short posteriorly located right adrenal vein should be anticipated as it exits directly from the vena cava. When encountered, the right adrenal vein is isolated, ligated , and divided. The specimen is then delivered, and meticulous hemostasis is achieved

13. Complications for radical nephrectomy Bleeding Infection Post operative pneumonia INJURY T0 ADJACENT ORGAN –DUODENUM,INTESTINE,IVC

14. Advantages of laproscopic surgery Shorter recovery time Shorter hospital stay Smaller incision Few post operative complications

15. TYPES – POLAR NEPHRECTOMY WEDGE RESECTION ENUCLEATION

16. Recent advances – prognostic biomarkers for RCC [ INDIAN JOURNAL OF UROLOGY FEB-MAR 2013 ] Hypoxia-inducible factor 1 α (HIF-1 α) Lidgren   et al. demonstrated that patients with conventional RCC having a high HIF-1α level survived significantly longer than those with low HIF-1α. Carbonic anhydrase IX (CAIX) Carbonic anhydrase IX is one of the most validated prognostic biomarkers of RCC. Bui  et al. performed immunohistochemical analysis for CAIX expression on tissue microarrays from patients with conventional RCC. They demonstrated that 94% of the RCC tissues expressed CAIX and that decreased expression predicted a worse outcome for patients with locally advanced RCC and was an independent predictor of poor survival in patients with metastatic RCC.

17. IMMUNOLOGIC MARKERS Tumor -infiltrating lymphocytes (TILs) there is a paradoxical relation between increased levels of TILs and diminished cancer-specific survival.[ 34 ] Tumor -infiltrating lymphocytes were shown to be functionally defective, incompletely activated, depleted or anergic Cózar   et al. , evaluated TILs of RCCs and found substantial numbers of natural killer (NK) cells and polarized Th1 CD4 +  cells. Moreover, significantly fewer NK cells in peripheral blood, a lower proportion of CCR5/CXCR3/CD4 +  cells and a higher proportion of CCR4/CD4 +  cells were observed in patients with metastatic RCC in the study

18. POST OPERATIVE SURVELLIANCE IN PARTIAL OR RADICAL NEPHRECTOMY PATIENTS LAB INVESTIGATIONS -- CBC,LFT,S.CALCIUM,BUN,S.ELECTROLYTES.