Critical Evaluation of a microRNA-Based Risk Classifier Predicting Cancer-Specific Survival in Renal Cell Carcinoma with Tumor Thrombus of the Inferior Vena Cava.

(1) Background: Clear cell renal cell carcinoma extending into the inferior vena cava (ccRCCIVC) represents a clinical high-risk setting. However, there is substantial heterogeneity within this patient subgroup regarding survival outcomes. Previously, members of our group developed a microRNA(miR)-based risk classifier-containing miR-21-5p, miR-126-3p and miR-221-3p expression-which significantly predicted the cancer-specific survival (CSS) of ccRCCIVC patients. (2) Methods: Examining a single-center cohort of tumor tissue from n = 56 patients with ccRCCIVC, we measured the expression levels of miR-21, miR-126, and miR-221 using qRT-PCR. The prognostic impact of clinicopathological parameters and miR expression were investigated via single-variable and multivariable Cox regression. Referring to the previously established risk classifier, we performed Kaplan-Meier analyses for single miR expression levels and the combined risk classifier. Cut-off values and weights within the risk classifier were taken from the previous study. (3) Results: miR-21 and miR-126 expression were significantly associated with lymphonodal status at the time of surgery, the development of metastasis during follow-up, and cancer-related death. In Kaplan-Meier analyses, miR-21 and miR-126 significantly impacted CSS in our cohort. Moreover, applying the miR-based risk classifier significantly stratified ccRCCIVC according to CSS. (4) Conclusions: In our retrospective analysis, we successfully validated the miR-based risk classifier within an independent ccRCCIVC cohort.

Frozen section analysis of ureteral margins in patients undergoing radical cystectomy for bladder cancer: differential impact of carcinoma in situ in the bladder on reliability and impact on tumour recurrence in the upper urinary tract.

BACKGROUND: Patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) are at risk for upper urinary tract recurrence (UUTR), especially in case of carcinoma in situ (CIS). Data on the impact of CIS in the urinary bladder on ureteral tumour involvement or UUTR are conflicting. We presently evaluate the accuracy of intraoperative frozen section analysis (FSA) of the ureteral margin, the incidence of ureteral tumour involvement and their impact on UUTR in patients undergoing RC for UCB with versus without CIS of the bladder. MATERIAL AND METHODS: Between 2003 and 2007, 243 patients underwent RC in our department. 176 of these for UCB, either without CIS (n = 117, group I) or solitary/concomitant CIS (n = 59, group II). FSA was performed. Patients were followed up for UUTR. RESULTS: Overall, 403 ureteral margins--including re-resections--were analysed (group I, n = 232; group II, n = 171). One patient (0.85%) in group I and 21 patients (35.6%) in group II had tumour involvement of the ureter (p < 0.0001) at the time of RC. The false-negative rate of FSA compared to final histopathology was 0.4% (1/232) for group I and 2.9% (5/171) for group II, respectively. Mean duration of follow-up was 26 months (1-72). In group II, 2 patients (1.1%) had UUTR in the follow-up; both had initially positive and subsequently false-negative FSA. CONCLUSIONS: Tumour involvement of the ureter is found significantly more often in solitary or concomitant CIS of the bladder. Intraoperative ureteral FSA is accurate and should be recommended in these patients. Ureteral tumour involvement predisposes to UUTR especially with initial positive margins mandating careful follow-up.

Serum carcino-embryonic antigen (CEA) and its possible use as tumor marker for secondary tumors in urinary intestinal reservoirs.

OBJECTIVES: Serum carcino-embryonic antigen (CEA) has become a useful tumor marker in patients with colorectal adenocarcinoma. Patients who undergo uroenteric reconstruction, such as urinary diversion (UD), have an increased risk of developing malignant changes in their UD. We compared serum CEA levels in patients with different types of UD, evaluating long-term CEA changes and assessing its potential for use as a tumor marker of malignant transformation in the UD. MATERIALS AND METHODS: Serum CEA was evaluated 3 to 122 months after surgery in 177 patients with different types of UD and retrospectively analyzed. The normal range for CEA was 0.2-3.4 µg/l. No patient had a history of colorectal cancer. RESULTS: A total of 443 CEA samples from 177 patients were evaluated. CEA was elevated (up to 32 µg/l) in 122 samples (27.5%) from 59 patients (33.3%). Patients with Mainz Pouch II had significantly higher CEA levels (P = 0.037) than patients with other forms of UD. CEA levels increased significantly in the study population during follow-up (P = 0.0000007). Five of the patients (2.8%) developed a secondary neoplasm, 4 of whom had elevated CEA. Three neoplasms (urothelial cancer) were located outside the UD. Only 2 tumors were actually located in the UD: an urothelial cancer at the uretero-colonic anastomosis of the UD with normal CEA levels, and a colonic adenoma at the bottom of the UD with elevated CEA levels. No patient had adenocarcinoma in the UD. CONCLUSION: Elevated serum CEA is a common finding in patients with UD using bowel segments (33.3%), especially in patients with rectal reservoirs. Serum CEA has a tendency to increase over time in patients with UD but is not a valuable marker of secondary neoplasms in these patients.

Testis-sparing surgery versus radical orchiectomy in patients with Leydig cell tumors.

OBJECTIVES: To compare retrospectively the outcome of testis-sparing surgery (TSS) to radical orchiectomy (RO) in patients with Leydig cell tumor (LCT). METHODS: Between 1992 and 2008, 16 patients with LCT of the testis were identified. All but 1 tumor could be detected by ultrasonography. Alpha-fetoprotein and beta-human chorionic gonadotropin levels were normal in all patients. Eight patients underwent RO (mean age at surgery 42 years [27-61]; median tumor size 12.9 mm [10-25]) and the remaining 8 underwent TSS (mean age at surgery 34 years [18-49]; median tumor size 8.6 mm [4-23]). Staging (abdominal computed tomography and chest x-ray or thoracic computed tomography) was negative in all patients. RESULTS: Median follow-up was 77 months (17-186) after RO and 42 months (1-86 months) after TSS. There was no local recurrence or metastasis in patients after RO. A metachronous LCT was removed from the spermatic cord 29 months after TSS of the ipsilateral testis in 1 patient. Another patient underwent surgical exploration of the testis 31 months after ipsilateral TSS because of a suspicious lesion identified in ultrasonography; a tumor was ruled out by histopathology. CONCLUSIONS: In the medium term, TSS is a safe procedure in patients with LCT <25 mm.