The profile of Renal Cell Carcinomaat DrSoetomo General Hospital January 2006 – December 2010 Sriyono1, L. Hakim1, W.D. Soesanto1, S.H. Wijoto1 1 Department of Urology, Dr. Soetomo Hospital, Airlangga School of Medicine Surabaya Abstract Objectives: To review clinical characteristic of Renal Cell Carcinoma at DrSoetomo General Hospital Methods: A retrospective study of medical records patients suffering Renal Cell Carcinoma recorded at DrSoetomo General Hospital since January 2006 until December 2010. Results: There were collected 29 patients, 18 male in majority (62%), with ratio of 1,6:1 to female. The age range was 30-70 years old, mostly 60-70 years old (24%), at mean of 51 years old. Renal tumor classic triad was seen on 9 patients (31%). Major pathological finding was clear cell in 15 (52%) patients, 34% and 10% of papillary and chromophobe, respectively. According to TNM system 2009, the stage presentation T1 was 1(3%) patient,T2a 7(24%), 2b 10(35%), T3a 6(21%) and T4 5(17%) patients. N0 were 21(73%), N1 5(17%) and N2 3(10%) patients. M0 were 23(79%) and M1 6(21%) patients. StageI was 1 (3%) patient,stage II 15(52%), stage III 3(10%)and stage IV 10(34%). Twenty one (72%) patients were, dominantly, underwent nephrectomy,the other 2(7%) underwent partial nephrectomy; 6 (21%) patients underwent palliative nephrectomy and combined withsunitinib in 4 (14%) patients. On three months follow up post operatively, it was found that 2 (7%) patients died and 7 (24%) developed local recurrence tumor. Conclusion:The Renal Cell Carcinomain our department; majority were male with ratio 1,6; 1. TheT criteria according to TNM 2009patient camein T1 was 1(3%) patient,T2a 7(24%), 2b 10(35%), T3a 6(21%) and T4 5(17%) patients.Stage of the patient according to 2009 TNM staging systemmost of patient were stage II 15(52%) and stage IV in 10(35%) patient. On short follow up post opoperatively, 2 (7%) patients died and 7 (24%) developed local recurrence tumor. Keywords: Renal cell carcinoma, clear cell carcinoma, radical nephrectomy malignancies in adults and role as the most INTRODUCTION Renal cell carcinoma (RCC)accounts for 2 until 3 % of all lethal of urologic cancers. In USA within 2010, approximately 58.240 new RCCdiagnoses were made, and 13.040 died treatment and short outcome RCCwere of RCC. This is primarily a disease of collected form medical record, of Urology elderly patient of 60 – 70 years old. Men department of DrSoetomo hospital. are more often to be affected 1,5 times than RESULTS women. RCCin childhood is uncommon, There about 2.3%-6.6% amongst all renal neoplasms in children. 1,2,3,4. Kidneys are hidden were total 29 patients managed within 5 years of 2006 to 2010 in DrSoetomo hospital Surabaya, 18 (62%) in the were men and 11 (38%) were women. retroperitonealspace which makes renal tumor rarely symptomatic in early stage, Table radiologic diagnostics are used widely, carcinoma based on gender especially USG, the more coincidental The mean age is 51 years old, mostly 30-70 diagnosis are made.4This study’s aim to years old, at peak of aged 60-70 years old. provide a profile of RCC patients managed in dr. Soetomo hospital, Surabaya, East Java, Indonesia within 5 years, January 1. Percentage until growth as big size tumor. The more Distribution of renal cell 30% 20% 10% 0% 2006 until December 2010. < 30 30 - 40 - 50 - 60 - >70 40 50 60 70 Age (year) MATERIAL AND METHODS Figure 1.Age distribution of renal cell This is a retrospective study. The carcinoma samples are all RCC patients who have The most frequent symptoms was admitted to Dr. Soetomoacademic hospital palpable mass in 25 (86%), followed with within 5 years, from January 2006 to flank pain in 17 (59%) and hematuria in December 2010. Data about gender, age, 13(45%). symtoms, laboratory, stage, Triads of renal histology, waspositive in 9 (31%) patients. tumor Percentage 40% 30% 20% 10% 0% T1a T2a T2b T3a T4 Primary Tumor Table 2.Symptoms distribution of renal cell Figure 2.Primary tumor distribution of renal carcinoma Based on laboratory results, 13(45%) patients had hematuria, 3(10%) had anemia, 4(14%) had leukocytosis and 5(17%) had decrease of renal function test. cell carcinoma Based on N Staging tumor, the stage of presentation in N0 was 21(73%), N1 5(17%) and N2 3(10%) patients. 17% 10% N0 N1 73% N2 Table 3.Laboratory results distribution of renal cell carcinoma Figure 3.N staging tumor distribution of Based on primary tumor, the stage renal cell carcinoma of presentation in T1 was 1(3%) patient, Based on M staging tumor, the stage T2a 7(24%), 2b 10(35%), T3a 6(21%) and of presentation in M0 was 23(79%) and M1 T4 5(17%) patient. 6(21%) patients, where 3(50%) patient metastatik was T4, 2(33%) was T3a and one(13%) patient was T2b. 21% M0 79% M1 Figure 4.M staging tumor distribution of Figure 6.Histology distribution of renal cell renal cell carcinoma carcinoma After TNM staging group 2009 Twenty two patients (72 %) were were used, most of renal cell carcinoma underwent radical nephrectomy, 2 (7%) were stage II 15(52%) and stage IV in partial nephrectomy and 6 (21%) palliative 10(35%) and only 1(3%) came in first nephrectomy followed with Sunitib in 4 stage. (14%) patients. 3% 35% 10% 52% stage 1 stage 2 stage 3 stage 4 Figure 7.Surgical treatment distribution of renal cell carcinoma Figure 5.Staging distribution of renal cell carcinoma Based on histologic picture, the most common type is clear cell in 15(52%) followed by papillary in 10 (34%) and chromophobein 2 (7%) patients. After three months evaluation, 2 (7%) patients were passed, and 7 (24%) recurrent. DISCUSSION Within 5 years of 2006 until 2010 in DrSoetomo hospital Surabaya has been managed patient with RCC, itsappear to be more common in men, 18 (62%) with ratio 6:1 to women, in age of 30 to 70 years old, (VHL),hereditary papillary RCC (HPRCC), mostly 60-70 years old (24%) with the hereditary leiomyomatosis (HLRCC) and average rate 51 years old. Similar to the birthogg-dube (BHD).4,5,6 literature which mentioned men and women Macroscopically most of RCC are ratio of 1,5 : 1, aged 60-70 years old. Our surrounded by a pseudo capsule which is datas similiar to the datas of literatur were renal parenchyma that is suppressed by the to be affected 1,5 times of men, mostlyof tumor, rarely infiltrative, unlike transitional 60 – 70 years old. 1,2,3,4. cell carcinoma, except for collecting duct According to WHO there are and sarcomatoidtypes. Clear cell type is subtypes of renal cell carcinoma based on yellow-gold histology which are; clear cell (70% -80%), prognosis papillary (10%-15%), chromophobe(3%- chromophobe. A papillary type has 2 5%), collecting duct (<1%), unclassified subtypes; papillary 2is more aggressive and RCC (1%-3%) and several other rare types appear to have worse prognosis than type 1. such as; multilocular cyst clear cell, Most patients with collecting ducttype are medularyrenalis, found in advance stage and have no mucinous post-neuroblastoma, tubular andspindle cell carcinoma. Clear cell and papillary renal colored and compared to has worse papillary and response to systemic therapy.4,6,7,8 Kidneys are hidden in the cell carcinoma are primarily raised from retroperitonealwhich makes renal tumors proximal tubules of the kidney, while rarely symptomatic, except for big size chromophobeand are tumor. The more radiologic diagnostics are nephron used vastly, especially USG, the more derived from component. collecting more Based on distal duct genetics, the coincidental diagnosis are made.4 Three incidence of RCC also has correlation with risk factors have close influence to the familial factors, such as von hippellindau incidence of RCC, they are tobacco exposure, obesity and hypertension. TNM p53, PTEN (phosphatase and tensin classification of renal cell carcinoma was homolog) (cell cycle), E-cadherin, and made in 2009. Some factors affect the CD44 (cell adhesion) have not shown a prognosis such as anatomical, histological, significance diagnostic value yet.14,15,16. clinical, and molecular factors. Anatomical Based on our data, almost all of the factors are size of the tumor, invasion to the chief complaint were mass 25 (86%) and vein, renal capsule, adrenal gland, lymph flank pain 17(59%) while classic triad of nodes and also distant metastasis. Clinical renal tumor in 9 (31%) patients because the factors advance are performance state, local stage of prior presentation. symptoms, cachexia, anemia and platelet Hematuria was found in 13 (45%) patients count.9,10,11,12,13. of renal cell carcinoma which suggest a suspicion of renal neoplasms besides other urologic cancer.Based on the TNM system 2009,the primary tumor then most of the patients present in T2 (17/58%), T3a in 6(21%), T4 in 5(17%) and only one patient come in T1. Based on N Staging tumor, the stage of presentation in N0 was 21(73%), N1 5(17%) and N2 3(10%) patients. Based Table 4.Renal cell carcinoma (RCC) based on on 2009 TNM system9 presentation in M0 was 23(79%) and M1 Some of molecular markers like M staging tumor, the stage of 6(21%) patients. IX (CaIX), vascular In order to see the prognosis, endothelial growth factor (VEGF), hypoxia categorizing are done into tumor staging inducible factor (HIF), Ki67 (proliferation), where 15 patients are stage II (52%), carbonic anhydrase 10(34%) are stage IV and only 1(3%) is embolization before nephrectomy. For unfit stage I. This is possible because of patients who are not possible for surgery, community’s lack of awareness of the embolization may reduce pain and gross importance hematuria.16,17,18,19. of renal tumor’s early treatment, they don’t come for help when it’s early. Radical nephrectomy is the chosen option for local renal cell carcinoma which From pathological results, for as is not possible to do partial nephrectomy. many as 15 patients (52%) the most seen Laparoscopy type was clear celltype, followed by comparable cancer free rates after long papillary cellin 10 patients (34%) and period of time, with minimal blood loss and 2(10%) In shorter length of stay. Ideal indication for clear laparoscopy partial nephrectomy is small celltype is the majority type of RCC for peripheral tumor. Nephrectomy is curative about 70-80% followed by papillary 10- treatment only as long as all tumors are 15% and chromophobe3-5%. We didn’t resectable. find any other type at Dr. Soetomo hospital. nephrectomy is palliative, only performed if werechromophobetype. accordance with the literature, Partial resection for local renal cell and In open surgery metastatic have disease, it is possible. 20,21,22,23,24,25,26 carcinoma shows a similar outcome to Due to growth of proximal tubule radical nephrectomy. Adrenalectomy is not of the kidney, RCC is now showing performed if the adrenal gland is normal on resistance to some protein drugs, P- CT or MRI, and found no nodule during glycoprotein surgery without any seen invasion to the metastatic RCC, immunotherapy such as upper pole. Lymph node dissection during alpha-Interferon (IFN-α) and Interleukin-2 nephrectomy is proven to give better (IL2) prognosis and life expectancy, as well as 20%.Interleukin-2 is more toxic than alpha- show and chemotherapy. response about In 15- IFN and only clear cell type give response showing worse prognosis. Surgery is the to immunotherapy. 27,28,29. first choice for local recurrence without Some targeted therapy which inhibit the vascular endothelial growth factor (VEGF); sunitinib, distant metastasis. If there is any metastasis, we may give systemic therapy. 36,37,38 sorafenib, Based on our data, 21(72%) patients bevacizumabmaupunpazofenibandmammali were an target of rapamycin (mTOR) pathways; 2(7%) patients partial nephrectomy, and temsirolimus and also everolimus, give 6(21%) patients better outcome than immunotherapy with radical nephrectomy, more treatment of Sunitibin 4(14%). Radical tolerable Biphosponator complications. Zoledronic acid performed radical nephrectomy, underwent palliative followed with are nephrectomy was performed in almost all recommended for ones with hyperkalemia patients who were possible for surgery with with normal kidney function, which are good performance state, because RCC is given 4 mg every 4 weeks intravenously. radio and chemo resistance, so that there 4,30,31,32,33,34,35 would be no further treatment after surgery. Surveillance is for follow up of By resecting the kidney along with fascia possibility of recurrence and metastasis. Gerota and perirenal fat, we expect no Recurrence mostly occurs after 3 years of metastasis and recurrence. operation, 43% occur in the first year, 70% Two patients were performed partial in the second year, 80% in the third year nephrectomy because the tumors were and 93% in the fifth year. Metastasis is localized in lower pole of the kidney. While common to the lung, bone, liver, brain and patients who already had metastasis were local areas. Local recurrence after still underwent palliative nephrectomy. The nephrectomy occurs in with purpose is reducing huge mass effect, and contralateral recurrence about 1,2% and stops the growth of the primary tumor. Four 2.9%, of them who were performed palliative IV in 10(35%) patient. On short follow up nephrectomy, were given Sunitib; which is post opoperatively, 2 (7%) patients died and a targeted therapy treatments to inhibit 7 (24%) developed local recurrence tumor. vascular endothelial growth factor (VEGF) Campaign is needed for general then followed further for the hope of better practitioners and radiologist to become outcome. aware of renal tumor, so that more RCC Three months of evaluation we will be found at earlier stage. 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