Papillary renal cell carcinoma: analysis of germline mutations in the MET proto-oncogene in a clinic-based population.

Approximately 10% of all renal cell carcinomas (RCCs) present a distinctive papillary histology. Familial papillary RCC (PRCC) has been described, but the majority of cases appear to be sporadic. Recently, germline mutations in the MET proto-oncogene on chromosome 7 have been identified in families with hereditary PRCC. We evaluated 59 patients with PRCC for the frequency of MET germline mutations to determine the value of genetic screening of this patient population. Between 1976 and 1997, 165 patients were identified with PRCC by retrospective chart review. Fifty-nine of 133 surviving patients agreed to provide a family history, a blood specimen, and informed consent for genetic research. DNA was isolated from peripheral blood leukocytes. Denaturing high-performance liquid chromatography (DHPLC) followed by genomic sequencing was performed on eight exons of the MET proto-oncogene, including exons 5-7 of the extracellular domain, exon 14, and exons 16-19 of the tyrosine kinase domain. The 59 patients in this study included 49 men and 10 women with a mean age at diagnosis of 61 years. Bilateral and/or multifocal disease was present in 13 cases (22%). No germline mutations were detected in the studied exons of the MET proto-oncogene (exons previously reported to contain deleterious mutations in familial PRCC). No pathological MET proto-oncogene germline mutations were identified in 59 patients with PRCC. The germline mutation rate in this clinic-based population of individuals with PRCC approaches 0% (CI = 0-6.18). MET proto-oncogene germline mutation screening does not appear to be clinically indicated in patients with PRCC without additional evidence for a genetic predisposition (positive family history, unusual age at onset, bilateral disease).

Laparoscopic transureteroureterostomy: demonstration of its feasibility in swine.

PURPOSE: To evaluate the feasibility of laparoscopic transureteroureterostomy (TUU) in a porcine model. MATERIALS AND METHODS: Nine female pigs had bilateral ureteral stents placed 3 weeks prior to surgery. At surgery, a left-to-right laparoscopic TUU was performed. Ureteral stents were placed across the anastomosis in seven cases. Six weeks after surgery, the stents were removed. After an additional 3 weeks, an excretory urogram, retrograde ureteropyelogram, and ureteroscopic examination of the anastomosis were performed. Serum creatinine assay and urine cultures were performed at regular intervals. Antibiotic prophylaxis was used for 1 week after each procedure. RESULTS: Of the nine animals, eight underwent successful laparoscopic TUU. Excretory urograms revealed prompt function and washout in all these cases. One animal developed an anastomotic stricture; in this animal, the ureters had remained nondilated after initial stent placement. Serum creatinine values remained within the normal range for all animals undergoing successful surgery. Additional complications included one urinary tract infection and one postoperative ileus, which were treated without difficulty. The operative time ranged from 2.5 to 6 hours, with shorter procedures later in the series. CONCLUSIONS: Laparoscopic TUU is practical in the porcine model. It may prove to be an alternative to an open TUU in patients with lower ureteral lesions when ureteroneocystostomy is not feasible.

Prospective analysis of intraoperative frozen needle biopsy of solid renal masses in adults.

PURPOSE: We prospectively determined the accuracy of intraoperative needle biopsy of solid renal masses. MATERIALS AND METHODS: A total of 103 patients diagnosed with a solid renal mass and scheduled for surgery were prospectively evaluated. Radical or partial nephrectomy was performed, and biopsy of the surgical specimen was done twice through the tumor using an 18 gauge biopsy gun. Biopsy specimens of 106 tumors were sent for frozen sectioning, stained with hematoxylin and eosin, and reviewed by 2 independent pathologists blinded to each other and whole tissue specimens. Biopsy results were compared to whole tissue specimens. RESULTS: Specimens were obtained from 60 radical and 46 partial nephrectomy cases. Malignant neoplasms were present in 91 cases (86%). Overall, 15 cases (14%) were benign, of which 11 were oncocytomas. If lesions 4 cm. or less only were included in analysis, the incidence of benign lesions increased to 22%. Overall accuracy of the 2 pathologists was 76 and 80%. Nondiagnostic rates were 11 and 17%. Both observers incorrectly diagnosed 4 malignant lesions (5%) as benign, and incorrectly diagnosed 3 and 5 benign lesions (21 and 36%), respectively, as malignant. Analysis of values for both observers yielded a sensitivity of 77 and 84%, specificity 60 and 73%, positive predictive value 94 and 96%, and negative predictive value 69 and 73%. CONCLUSIONS: Overall frozen needle biopsy was accurate in more than 75% of cases and showed an excellent positive predictive value for carcinoma of more than 94%. Unfortunately, there was a large degree of inaccuracy for benign lesions and we do not recommend the routine use of intraoperative frozen needle biopsy to guide surgical decision making.

Renal oncocytoma: multifocality, bilateralism, metachronous tumor development and coexistent renal cell carcinoma.

PURPOSE: We analyzed a large series of cases of renal oncocytoma to define the incidence of coexistent renal cell carcinoma, multifocality, bilateralism and metachronous tumor development. MATERIALS AND METHODS: Between 1980 and 1997, 100 men and 38 women with a mean age of 68 years with oncocytoma, were treated surgically at our institution. We analyzed tumor characteristics and reviewed specimens for coexistent renal cell carcinoma. RESULTS: Tumors were discovered incidentally in 58% of the cases. Specimens were obtained from 84 radical and 70 partial nephrectomies. Tumor size ranged from 0.3 to 14.5 cm. (median 3.2). Oncocytoma was unilateral in 131 cases (95%) and bilateral in 7 (5%), while there were multiple oncocytomas in 8 (6%). Mean followup was 41 months (range 0 to 200). The disease specific survival rate was 100% and no patient had metastasis. In 6 patients (4%) metachronous oncocytoma developed during followup. No patient had locally recurrent oncocytoma after partial nephrectomy for a solitary renal oncocytoma. Renal cell carcinoma and oncocytoma were found in 14 patients (10%), including unilateral synchronous disease in 9 and bilateral synchronous disease in 5. CONCLUSIONS: Our data support the benign nature of renal oncocytoma. Multifocality, bilateralism and metachronous tumor develop in approximately 4 to 6% of all cases. Renal cell carcinoma coexisted in 10% of oncocytoma cases.