Case Discussion <Brief History> The 35 year-old man has been diagnosed as chronic glomerulonephritis complicated with end stage renal disease (ESRD) and has been on regular hemodialysis for six years. He reported to have no history of hypertension, diabetes or viral hepatitis in the past. His general condition was good and he had a good hemodialysis quality with adequate control of Ca-P product, serum albumin, KT/V. Besides, he had no need of erythropoietin (EPO) injection, and his daily urine output was less than 200 cc after starting hemodialysis. Two months ago, he began to suffer from right flank soreness, but he paid no attention to it. However, painless gross hematuria developed two weeks prior to admission. There were no other symptom such like fever, poor appetite, bowel habit change or weight loss. Initially, he thought the hematuria was due to infection and just took some antibiotics by himself. However, persistent painless hematuria and gradually declined hemoglobin levels were noted. Renal sonography was suggested by his attending physician, which revealed a heterogenous renal mass (Figure 1.) and another suspicious mass (not shown). He was then admitted immediately to the hospital for further evaluation and management. <Laboratory and Image Study> 1. CBC/DC & coagulation profiles: Date WBC  K/μL  RBC  M/μL Hgb g/dL Hct % MCV fL MCH pg  MCHC g/dL Plt K/μL 940511 10.3 3.55 9.6 29.2 82.3 27.0 32.9  489 940520 9.54 3.71 10.1 30.5 82.2 27.2 33.1 423 Date Blast Meta Band Seg Eos Baso Mono  Lym 940511 0 0 0 75.1 1.4 0.2 7.6 15.7 940520 0 0 0 60.0 2.9 0.6 6.4 30.1 2. Biochemistry Date BUN mg/dl Cre mg/dl Na mmol/l K mmol/l Cl mmol/l Ca mmol/l P mmol/l  Mg mmol/l 940511 65 6.43 135.1 4.54 99.0 2.02 4.86 0.89 940520 72 5.86 139.0 4.31           GOT U/l T/D-Bil mg/dl LDH U/l CRP mg/dl 940511 20.0 0.25/ 1437 10.42 940520  17.0 1097 5.54 3. Urine analysis: Date Appearance Sp. gr pH Protein mg/dL Glu g/dL Ketones O.B Urobil EU/dL Bil 940511 R;T 1.020 6.0 >300 - -  4+ 0.1 - 940520 R,T 1.026 6.0 >300 - - 4+ 0.1 - Date Nitrite WBC RBC /HPF  WBC /HPF EpithCell / HPF Cast /LPF  Crystal  Bact 940511 - 30-35 numerous 14 3-5 - - - 940520 - - 30-40 2-5 3-5 - - - <Course and Treatment> Abdominal CT scan with contrast medium revealed two renal tumors which were highly suspected to be renal cell carcinoma (RCC) (Figure 2A.) (Figure 2B.). Series of cancer staging by CT scan showed no definite renal vein or IVC thrombosis, and there was no liver, lung metastasis. Besideds, there was no evidence of bone metastasis on bone scan. The urologist performed a cystoscopy which revealed no tumor mass in the urinary conduit of right kidney. Laparoscopic nephrectomy was performed 3 days after admission and the pathology revealed RCC, clear cell type. The patient recovered well after operation with no more symptoms of gross hematuria. However, EPO injection was required to keep his hemoglobin/hematocrit within optimal range. <Analysis> RCC accounts for approximately 3% of adult malignancies and 90-95% of neoplasms arising from the kidney. It is characterized by a lack of early warning signs, diverse clinical manifestations, resistance to radiation and chemotherapy, and infrequent but reproducible responses to immunotherapy agents such as interferon alpha and interleukin (IL)-2. In the past these tumors were believed to derive from the adrenal gland; therefore, the term hypernephroma often was used. The tissue of origin for RCC is the proximal renal tubular epithelium. The most common histological type of RCC is clear cell. Renal cancer occurs in both a sporadic (nonhereditary) and a hereditary form, and both forms are associated with structural alterations of the short arm of chromosome 3 (3p). RCC is twice as common in men as in women. This condition occurs most commonly in the fourth to sixth decades of life. RCC may remain clinically occult for most of its course. The classic triad of flank pain, hematuria, and flank mass is uncommon (10%) and is indicative of advanced disease. Twenty-five to thirty percent of patients are asymptomatic, and their RCC are found on incidental radiologic study. The most common presentations in order are hematuria (40%), flank pain (40%), weight loss (33%), and palpable mass in the flank or abdomen (25%). Approximately 30% of patients with RCC present with metastatic disease. Organs involved include: lung (75%), soft tissues (36%), bone (20%), liver (18%), cutaneous sites (8%), and CNS (8%). The risk of RCC is increased with the following: abuse of phenacetin-containing analgesics, acquired cystic kidney disease associated with chronic renal insufficiency, dialysis, tuberous sclerosis, renal transplantation, VHL disease. In patients with ESRD who have high hemoglobin level without the need of EPO injection, renal malignancy, acute hepatitis, cystic kidey disease were often mentioned. Surgical resection remains the only known effective treatment for localized renal cell carcinoma, and it also is used for palliation in metastatic disease. More than 50% of patients with renal cell carcinoma are cured in early stages, but outcome for stage IV disease is poor. The probability of cure is related directly to the stage or degree of tumor dissemination, so the approach is curative for early stage disease. Selected patients with metastatic disease respond to immunotherapy, but many patients can be offered only palliative therapy for advanced disease. <Reference> Chemotherapy for renal cell carcinoma. Semin Oncol 2000 Apr; 27(2): 177-86 Genetic and clinical aspects of familial renal neoplasms. Semin Oncol 2000 Apr; 27(2): 138-49 Epidemiologic aspects of renal cell cancer. Semin Oncol 2000 Apr; 27(2): 115-23 Renal-cell carcinoma. N Engl J Med 1996 Sep 19; 335(12): 865-75 Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 1999 Aug; 17(8): 2530-40 Renal cell carcinoma: presentation, staging, and surgical treatment. Semin Oncol 2000 Apr; 27(2): 160-76 Kidney cancer. Lancet 1998 Nov 21; 352(9141): 1691-6 EMedicine, Renal Cell Carcinoma. January 20, 2005 繼續教育考題 1. (D) RCC表現的triad不包括何者？ A Flank pain B Flank mass C Hematuria D Anemia 2. (B) 在 Von Hippel Lindau disease的病患中，腎臟最易發生的惡性腫瘤為何？ A  Angiomyolipoma B  Renal cell carcinoma C Transitional cell carcinoma D  Squamous cell carcinoma 3. (B) RCC起源自腎臟何處？ A Glomerulus B Proximal tubule C Distal tubule D Collecting duct 4. (A) RCC最常見之臨床表現為？ A Hematuria B Flank pain C Flank mass D Anemia 5. (E) 何者是產生RCC的危險因子？ A  Renal transplantation B Cystic renal disease C Abusive analgesic usage D Chronic dialysis E All of above 6. (B) 何者是RCC病患最主要的腎外轉移處？ A  Liver B  Lung C Another kidney D  CNS 7. (E) 任何病患出現血尿時，何者可能性需要考慮？ A Urinary tract infection B Ruptured renal cyst C . Renal cell carcinoma D Urolithiasis E All of above 8. (D) RCC最常見之細胞形態？ A Chromophilic type B Chromophobic type C Oncocytoma type D Clear cell type 9. (D) ESRD的病患若產生高Hemoglobin，要考慮那些underlying disease? A Cystic renal disease B Acute hepatitis C  Renal malignancy D All of above 10. (B) RCC的免疫療法多採用何種製劑? A  Interferon beta B Interleukin (IL)-2 C Tumor necrotic factor-alpha D Interleukin (IL)-6 答案解說 (D) Triad of flank pain, hematuria, and flank mass is uncommon (10%) (B) Von Hippel Lindau disease的病患中，腎臟最易發生的惡性腫瘤Renal cell carcinoma (B) RCC起源自腎臟proximal tubule (A ) RCC最常見之臨床表現為hematuria (E ) Abuse of phenacetin-containing analgesics, acquired cystic kidney disease associated with chronic renal insufficiency, dialysis, tuberous sclerosis, renal transplantation, VHL disease. (B )Organs involved include: lung (75%), soft tissues (36%), bone (20%), liver (18%), cutaneous sites (8%), and CNS (8%). (E) 病患出現血尿時，要區分是microscopic or gross hematuria, painful or painless, age older or younger than 50. 因此Urinary tract infection, ruptured renal cyst, renal cell carcinoma, urolithiasis皆要考慮 (D )The most common histological type of RCC is clear cell. (D) In patient with ESRD has high hemoglobin without the need of EPO injection, renal malignancy, acute hepatitis, cystic kidey disease were often mentioned. (B) Interferon alpha and interleukin (IL)-2