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Purpose: The purpose of this study is to assess the efficacy of laparoendoscopic single-site (LESS) nephrectomy in hemodialysis patients, we compared outcomes between LESS nephrectomy and conventional laparoendoscopic nephrectomy in hemodialysis patients with dialysis-related renal tumors., Material and Methods: A total of 16 hemodialysis patients who underwent LESS nephrectomy (LESS-N; n = 8) or conventional laparoendoscopic nephrectomy (C-N; n = 8) between November 2003 and July 2012 were retrospectively evaluated. Outcomes were compared between the two groups., Results: Patient and tumor characteristics were similar between the LESS-N and C-N groups. The mean operative duration was longer in the LESS-N than in the C-N group (231.0 ± 26.7 min versus 188.6 ± 36.4 min; p = .025). The mean estimated blood loss was lower in the LESS-N compared with the C-N group (26.4 ± 14.4 ml versus 65.6 ± 45.2 ml; p = .047). Postoperative complications were observed in three cases, comprising one case of retroperitoneal hematoma in the LESS-N group and one case each of peritoneal hematoma and retroperitoneal abscess in the C-N group. Surgical scarring was minimal in the LESS-N group., Conclusions: Although there is a little extension of the operating time, LESS nephrectomy in hemodialysis patients is a feasible procedure compared with the conventional method.

We report a case of ALK-positive renal cell carcinoma coincident with Hodgkin lymphoma. The patient was a 19 year-old-girl without sickle cell trait. The right renal tumor was discovered concomitantly with Hodgkin lymphoma (HL). After chemotherapy for HL, right nephrectomy was performed. Microscopically, the tumor showed a solid and focally pseudo-papillary growth pattern studded with tubular structures. Most tumor cells were small bland eosinophilic cells, but rhabdoid cells, vacuolated cells, pleomorphic multinucleated giant cells were also admixed. The variety of growth patterns and cell features led us to speculate a possibility of ALK-positive renal cell carcinoma (ALK + RCC). ALK was immunohistochemically positive, and fluorescence in situ hybridization analysis detected a split signal of the ALK gene. We examined previously reported partner genes (STRN, TPM3, VCL and EML4) by RT-PCR, but fusion gene was not detected. RCC showing solid or cribriform growth patterns with vacuolated cells with intracytoplamic lumina, rhabdoid cells, and mucus production indicates the possibility of ALK + RCC., (© 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Introduction: We previously reported cases of laparoendoscopic single-site nephrectomy performed through an umbilical or pararectal incision. To improve cosmesis and operability, we performed three Pfannenstiel laparoendoscopic reduced-port nephrectomies., Materials and Surgical Technique: In the first case, a GelPOINT access was placed through a 2-cm umbilical incision, and two additional 3-mm trocars were inserted. The specimen was extracted through a 4-cm Pfannenstiel incision. In the second and third cases, a GelPOINT access was placed through a 5-cm Pfannenstiel incision, and two additional 3-mm trocars were inserted. The specimens were extracted without additional skin incisions. In all cases, the endoscope and vessel-sealing device were inserted through the GelPOINT access. We used 3-mm scissors, dissecting forceps, and bipolar forceps., Discussion: The operating time and estimated blood loss were 228, 280, and 155 min and 10, 410, and 5 mL, respectively. There were no intraoperative or postoperative complications. The 3-mm forceps showed similar efficacy as the conventional 5-mm forceps. Therefore, a Pfannenstiel reduced-port nephrectomy using 3-mm working trocars is a safe and feasible procedure with good cosmesis., (© 2016 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.)

Previously, we reported that genomic loss of 14q occurs more frequently in high-grade than in low-grade clear cell renal cell carcinomas (ccRCCs), and has a significant impact on the levels of expression of genes located in this region, suggesting that such genes may be involved in the malignant transformation of ccRCCs. Here, we found that six of the genes located in the minimal common region of 14q loss were significantly downregulated in high-grade ccRCCs due to copy number loss. Using a dataset from The Cancer Genome Atlas Research Network, we found that downregulation of one of these six genes, WDR20, was significantly associated with poorer outcome in patients with ccRCC, suggesting that WDR20 downregulation may be involved in the malignant transformation of ccRCCs. In functional assays, exogenous WDR20 significantly inhibited the growth of RCC cell lines and induced apoptosis. Interestingly, the phosphorylation levels of ERK and protein kinase B/AKT, which reportedly contribute to the malignant phenotype of RCC cells, were clearly reduced by exogenous expression of WDR20. Thus, our data suggest that downregulation of WDR20 due to 14q loss may be involved in the malignant transformation of ccRCCs, in part through activation of the ERK and protein kinase B/AKT pathways., (© 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

This study was conducted to clarify the genomic profiles of metastatic clear cell renal cell carcinomas (ccRCCs) and identify the genes responsible for development of metastasis. We analyzed the genomic profiles of 20 cases of primary ccRCC and their corresponding metastases using array-based comparative genomic hybridization, and identified 32 chromosomal regions in which gene copy number alterations were detected more frequently in metastases than in the primary tumors. Among these 32 regions, 9p24.1-p13.3 loss was the most statistically significant alteration. Furthermore, we found that patients with 9p24.1-p13.3 loss in primary tumors exhibited significantly lower rates of recurrence-free and cancer-specific survival, suggesting that 9p loss in the primary tumor is a potential biomarker predicting early recurrence of metastasis. Interestingly, the genomic profiles of primary tumors with 9p loss resembled those of their corresponding metastases, though 9p loss was accumulated in the metastases derived from the primary tumors without 9p loss. Comparison of the mRNA expression levels revealed that 2 of 58 genes located at 9p24.1-p13.3 were downregulated due to gene copy number loss in ccRCCs. An overexpression study of these two genes in ccRCC cell lines revealed that downregulation of NDUFB6 due to loss at 9p24.1-p13.3 may confer a growth advantage on metastatic ccRCC cells. These results were confirmed by analyzing the data of 405 cases of ccRCC obtained from The Cancer Genome Atlas (TCGA). On the basis of our present data, we propose that NDUFB6 is a possible tumor suppressor of metastatic ccRCCs., (© 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The purpose of the present study was to determine the genomic profile of renal cell carcinoma (RCC) in end-stage renal disease (ESRD) by analyzing genomic copy number aberrations. Seventy-nine tumor samples from 63 patients with RCC-ESRD were analyzed by array comparative genomic hybridization using the Agilent Whole Human Genome 4 × 44K Oligo Micro Array (Agilent Technologies Inc., Palo Alto, CA, USA). Unsupervised hierarchical clustering analysis revealed that the 63 cases could be divided into two groups, Clusters A and B. Cluster A was comprised mainly of clear cell RCC (CCRCC), whereas Cluster B was comprised mainly of papillary RCC (PRCC), acquired cystic disease (ACD)-associated RCC, and clear cell papillary RCC. Analysis of the averaged frequencies revealed that the genomic profiles of Clusters A and B resembled those of sporadic CCRCC and sporadic PRCC, respectively. Although it has been proposed on the basis of histopathology that ACD-associated RCC, clear cell papillary RCC and PRCC-ESRD are distinct subtypes, the present data reveal that the genomic profiles of these types, categorized as Cluster B, resemble one another. Furthermore, the genomic profiles of PRCC, ACD-associated RCC and clear cell papillary RCC admixed in one tissue tended to resemble one another. On the basis of genomic profiling of RCC-ESRD, we conclude that the molecular pathogenesis of CCRCC-ESRD resembles that of sporadic CCRCC. Although various histologic subtypes of non-clear cell RCC-ESRD have been proposed, their genomic profiles resemble those of sporadic PRCC, suggesting that the molecular pathogenesis of non-CCRCC-ESRD may be related to that of sporadic PRCC., (© 2011 Japanese Cancer Association.)

Background: Clinical outcome of patients with high-grade ccRCC (clear cell renal cell carcinoma) remains still poor despite recent advances in treatment strategies. Molecular mechanism of pathogenesis in developing high-grade ccRCC must be clarified. In the present study, we found that SAV1 was significantly downregulated with copy number loss in high-grade ccRCCs. Therefore, we investigated the SAV1 function on cell proliferation and apoptosis in vitro. Furthermore, we attempted to clarify the downstream signaling which is regulated by SAV1., Methods: We performed array CGH and gene expression analysis of 8 RCC cell lines (786-O, 769-P, KMRC-1, KMRC-2, KMRC-3, KMRC-20, TUHR4TKB, and Caki-2), and expression level of mRNA was confirmed by quantitative RT-PCR (qRT-PCR) analysis. We next re-expressed SAV1 in 786-O cells, and analyzed its colony-forming activity. Then, we transfected siRNAs of SAV1 into the kidney epithelial cell line HK2 and renal proximal tubule epithelial cells (RPTECs), and analyzed their proliferation and apoptosis. Furthermore, the activity of YAP1, which is a downstream molecule of SAV1, was evaluated by western blot analysis, reporter assay and immunohistochemical analysis., Results: We found that SAV1, a component of the Hippo pathway, is frequently downregulated in high-grade ccRCC. SAV1 is located on chromosome 14q22.1, where copy number loss had been observed in 7 of 12 high-grade ccRCCs in our previous study, suggesting that gene copy number loss is responsible for the downregulation of SAV1. Colony-forming activity by 786-O cells, which show homozygous loss of SAV1, was significantly reduced when SAV1 was re-introduced exogenously. Knockdown of SAV1 promoted proliferation of HK2 and RPTEC. Although the phosphorylation level of YAP1 was low in 786-O cells, it was elevated in SAV1-transduced 786-O cells. Furthermore, the transcriptional activity of the YAP1 and TEAD3 complex was inhibited in SAV1-transduced 786-O cells. Immunohistochemistry frequently demonstrated nuclear localization of YAP1 in ccRCC cases with SAV1 downregulation, and it was preferentially detected in high-grade ccRCC., Conclusions: Taken together, downregulation of SAV1 and the consequent YAP1 activation are involved in the pathogenesis of high-grade ccRCC. It is an attractive hypothesis that Hippo signaling could be candidates for new therapeutic target.

MiR-210 is significantly up-regulated in clear cell renal cell carcinoma (CCC), but the mechanism and biological consequences of miR-210 up-regulation are poorly understood. Here, we show that miR-210 is highly expressed in renal carcinoma cell lines and that its expression is clearly correlated with accumulation of hypoxia-inducible factor 1α (HIF1α) under normoxia as well as hypoxia, suggesting that miR-210 up-regulation in renal carcinoma cells is most likely due to accumulation of HIF1α. To reveal the effects of miR-210 up-regulation, the miR-210 precursor was transfected into renal carcinoma cells. After transfection, the cells accumulated at the G2/M phase of the cell cycle and their viability was decreased, suggesting that miR-210 overexpression may trigger an event that hinders normal cell division. Immunocytochemistry demonstrated a multipolar spindle accompanied by centrosome amplification in cells overexpressing miR-210. It has been reported that centrosome amplification induces chromosome mis-segregation, finally leading to chromosome instability and aneuploidy. Indeed, the proportion of aneuploid cells (>4n) was increased in miR-210 overexpressed cells. By using the TargetScan and PicTar algorithms, E2F3 was identified as one of the possible targets of miR-210 and was suppressed at the protein level by miR-210. Moreover, the proportion of aneuploid cells was increased in E2F3 siRNA transfected cells. On the basis of these results, we propose that miR-210 up-regulation due to HIF1α accumulation may induce aneuploidy via E2F3 down-regulation at least in part, and may play a role in tumourigenesis and/or progression of CCC., (Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

A 51 year-old man admitted to our hospital for macroscopic hematuria and right abdominal mass. CT demonstrated a large hypervascular mass and tumor thrombus in the inferior vena cava and right atrium. We diagnosed right renal cancer (stage III), and he underwent radical nephrectomy and resection of tumor thrombus with extracorporeal circulation. Operative time was 9 hours. Time for extracorporeal circulation was 119 minutes, and it took 60 minutes for intraoperative balloon occlusion of descending aorta in order to arrest hemorrhage. Pathological diagnosis was clear cell carcinoma of the kidney (pT3c, N0, M0). Four days after surgery, paraplegia was evident, and a diagnosis of spinal cord infarction was made based on neurologic examination and MRI findings. In cases with such a surgery requiring extracorporeal circulation, preoperative meeting with cardiologists and anesthetists is indispensable in order to fully understand the possible complications. Especially, to keep a careful watch and prepare for spinal cord ischemia is mandatory.