M2 Macrophage Marker Chitinase 3-Like 2 (CHI3L2) Associates With Progression of Conventional Renal Cell Carcinoma.

BACKGROUND/AIM: In spite of early detection, appoximately 15% of the small renal cell carcinomas (RCC) will develop metastasis within 5 years follow-up. The aim of this study was to identify new biomarkers to estimate the postoperative relapse of the most common conventional RCC. PATIENTS AND METHODS: Tissue multi arrays of conventional RCC without metastasis at the time of operation from a cohort of 634 patients were analysed by immunohistochemistry for expression of the chitinase 3-like protein 2 (CHI3L2). Cancer specific survival of patients was estimated with Kaplan-Meier analysis, univariate and multivariate Cox regression models. RESULTS: Kaplan-Meier analysis estimated a shorter cancer-free survival for patients with CHI3L2 positive tumors. In multivariate analysis, the CHI3L2 positivity associated with a 3.5 times higher risk for tumor relapse (p<0.001). CONCLUSION: Expression of CHI3L2 in tumor cells of conventional RCC define a group of patients at high risk for postoperative progression.

Expression of inflammatory lipopolysaccharide binding protein (LBP) predicts the progression of conventional renal cell carcinoma - a short report.

BACKGROUND: The mortality of conventional renal cell carcinoma (RCC) correlates directly with the presence or postoperative development of metastases. The aim of this study was to identify new markers associated with the postoperative progression of conventional RCC. METHODS: Tissue microarrays (TMA) of conventional RCC from a cohort of 414 patients were analysed by immunohistochemistry for expression of the lipopolysaccharide binding protein (LBP), which was identified as a candidate biomarker through Affymetrix U133 Plus 2.0 array analysis. Univariate and multivariate Cox regression models were addressed to cancer-specific survival in association with age, sex, clinicopathological parameters and LBP expression. The survival time of the patients was estimated by Kaplan-Meier analyses, and comparisons of survival curves were made using the Log rank test. RESULTS: Univariate analysis revealed an association of patient survival with all clinicopathological parameters tested and LBP expression. In multivariate analysis only T classification, grade and LBP staining showed a significant association with postoperative cancer-specific survival (p < 0.001). LBP expression was found to be associated with a poor patient survival in Kaplan-Meier analyses. The estimated median survival time for patients with tumours showing LBP expression was 74 months, whereas the overall survival time was 142 months. CONCLUSION: LBP expression in conventional RCC defines a group of patients at a high risk of postoperative progression and may help to direct optimized active surveillance and timely adjuvant therapy.

Cytoplasmic expression of ß-catenin is an independent predictor of progression of conventional renal cell carcinoma: a simple immunostaining score.

AIMS: The aims of this study were to investigate the potential of ß-catenin as a biomarker for predicting cancer-specific survival, and to find a reproducible mode of evaluation of immunohistochemistry. METHODS AND RESULTS: ß-Catenin expression was analysed by immunohistochemistry in a cohort of 488 patients with conventional renal cell carcinoma (RCC) operated on between 2000 and 2010. The association between ß-catenin expression and cancer-specific survival was assessed with univariate and multivariate Cox regression models in relation to conventional clinical pathological prognostic factors, and by Kaplan-Meier survival analysis with the log rank test. The univariate Cox regression model revealed an association of cytoplasmic ß-catenin positivity and pathological variables with cancer-specific death. The multivariate Cox regression model analysis of tumours without metastatic disease at the first presentation identified the T-classification (P < 0.001) and cytoplasmic ß-catenin positivity as risk factors for postoperative tumour progression. Specifically, cytoplasmic ß-catenin expression was an independent factor indicating an unfavourable prognosis, with a four-fold higher risk of cancer-specific death (relative risk 4.017; 95% confidence interval 2.489-6.482; P < 0.001). The median survival time for patients with tumours showing cytoplasmic accumulation of ß-catenin was 48 months, whereas the overall survival time was 166 months. CONCLUSIONS: Cytoplasmic ß-catenin expression is an independent prognostic factor for conventional RCC, and may help to identify patients with a high risk of cancer-specific death and to direct optimized active surveillance or adjuvant therapy.

Lack of TMEM27 expression is associated with postoperative progression of clinically localized conventional renal cell carcinoma.

PURPOSE: In spite of early detection of conventional renal cell carcinoma (RCC) by widespread use of abdominal imaging, approximately 10-15 % of patients will die due to disease. The aim of this study was to identify new biomarkers predicting the postoperative progression of conventional RCC. METHODS: Tissue multiarrays (TMA) of conventional RCC from a cohort of 486 patients were analysed by immunohistochemistry for expression of the transmembrane protein TMEM27, which was identified as a candidate biomarker by Affymetrix U133 Plus 2.0 array. Univariate and multivariate Cox regression models were addressed to assess cancer-specific survival in association with clinicopathological variables and TMEM27 expression. Cancer-specific survival time was estimated with Kaplan-Meier analysis, and the comparison of survival curves was made with the log-rank test. RESULTS: The Kaplan-Meier survival analysis indicated a poor disease-specific survival rates for tumours without TMEM27 staining. Univariate analysis revealed an association of patient survival with T stadium, grade, stage and size of tumour and TMEM27 expression in all cases as well as in the cohort of patients with postoperative tumour progression. In multivariate analysis, only T stadium and TMEM27 staining showed a significant association with postoperative cancer-specific death (p < 0.001). CONCLUSIONS: Lack of expression of the TMEM27 in conventional RCC defines a group of patients at high risk for cancer-related death.

Impact of parenchymal loss on renal function after laparoscopic partial nephrectomy under warm ischemia.

PURPOSE: To elucidate the impact of renal parenchymal loss and the ischemic reperfusion injury (RI) on the renal function after laparoscopic partial nephrectomy (LPN) under warm ischemia (WI). METHODS: Thirty-five patients with a single polar renal mass ≤4 cm and normal contralateral kidney underwent LPN. Transperitoneal LPN with WI using en bloc hilar occlusion was performed. The total differential renal function (T-DRF) using 99mTc-dimercaptosuccinic acid was evaluated preoperatively and postoperatively over a period of 1 year. A special region of interest (ROI) was selected on the non-tumorous pole of the involved kidney, and was compared with the same ROI in the contralateral kidney. The latter comparison was defined as partial differential renal function (P-DRF). Any postoperative decline in the P-DRF of the operated kidney was attributed to the RI. Subtraction of the P-DRF decline from the T-DRF decline was attributed to the parenchymal loss caused by the resection of the tumor and suturing of the normal parenchyma. RESULTS: The mean WI time was 22 min, and the mean weight of resected specimen was 18 g. The mean postoperative eGFR declined to 87 ml/min/1.73 m2 from its baseline mean value of 97 ml/min/1.73 m2 (p value = 0.075). Mean postoperative T-DRF and P-DRF of the operated kidney declined by 7 and 3 %, respectively. CONCLUSIONS: After LPN of small renal mass, decline in renal function is primarily attributed to parenchymal loss caused by tumor resection and suturing of the normal parenchyma rather than the RI.

Laparoscopic repair of circumcaval ureter: one-year follow-up of three patients and literature review.

OBJECTIVES: To describe our experience and 1-year follow-up of 3 patients with circumcaval ureter (CU) treated laparoscopically, with the introduction of a new stenting method and review of the published data. Because of its rarity, more reports are needed to advocate more comprehensive knowledge about the preferred surgical technique for the treatment of CU. METHODS: Since November 2005, 3 patients with symptomatic CU have undergone laparoscopic repair of their anomaly at our institutes. In all 3 cases, the ureter was transected and positioned anteriorly with an end-to-end anastomosis. In 2 cases, the retrocavally located ureteral segment was resected. RESULTS: The mean operative time in our series was 210 minutes, without any intraoperative or early postoperative complications. In 1 patient, a slight ureteral stricture was detected that resolved with reinsertion of a double-J stent. Histopathologic examination of the resected ureteral segments revealed sclerosis and muscular hypertrophy. All patients remained symptom free during the 1 year of follow-up. CONCLUSIONS: With all the advantages of a minimally invasive procedure and preserving therapeutic efficacy, the laparoscopic approach should be considered a standard choice for surgical treatment of CU in symptomatic patients. Care should be taken to diagnose and excise the pathologically narrowed ureteral segment.