Metastatic renal cell carcinoma (mRCC) is a tumor entity with poor prognosis due to limited therapy options. Tyrosine kinase inhibitors (TKIs), the novel targeted agents have been used for the treatment of mRCC and have shown efficacy. Interferon (IFN)-α is also one of the most frequently used agents in immunotherapy. However, drug resistance needs to be overcome to achieve a sufficiently positive effect. Interleukin-6 (IL-6), which induce suppressor of cytokine signaling-3 (SOCS3) expression, is one of the factors associated with poor prognosis of patients with renal cell carcinoma (RCC). To analyze the influence of IL-6 in drug resistance of RCC, anti-IL-6 receptor antibody was used in combination with IFN or TKIs. The SOCS3 mRNA expression level was significantly increased by IFNα stimulation in 786-O RCC cells which were resistant to IFN, but not in ACHN cells that were sensitive to IFN. The overexpression of SOCS3 by gene transfection in ACHN significantly inhibited the growthinhibitory effect of IFNα. An in vivo study demonstrated that coadministration of SOCS3-targeted siRNA promoted INFαinduced cell death and growth suppression in 786-O cell xenograft. SOCS3 could be a key component in the resistance to interferon treatment of renal cell carcinoma. Because SOCS3 is rapidly upregulated by IL-6 and a negative regulator of cytokine signaling, IL-6 expression on RCC cells was also analyzed and the 786-O cells showed the high level of IL-6 mRNA expression under the condition of interferon stimulation. IL-6R antibody, tocilizumab, significantly suppressed cell proliferation in 786-O cells by interferon stimulation accompanied with phosphorylation of STAT1 and inhibited SOCS3 expression. The in vivo effects of combination therapy with tocilizumab and interferon showed significant suppression of 786-O tumor growth in a xenograft model. We also hypothesized that TKI resistance and IL-6 secretion are causally connected. And we found that 786-O RCC cells secrete high IL-6 levels after low dose stimulation with the TKIs sorafenib, sunitinib and pazopanib, inducing activation of AKT-mTOR pathway, NFκB, HIF-2α and VEGF expression. Tocilizumab neutralizes the AKT-mTOR pathway activation and results in reduced proliferation. A combination therapy with tocilizumab and TKI suppresses 786-O tumor growth and inhibits angiogenesis in vivo more efficient than TKI alone. Our findings suggest that IL-6 could induce drug resistance on RCC, and combination therapy of IL-6R inhibitors and IFN/TKIs may represent a novel therapeutic approach for RCC treatment.

PurposeWe investigated that preoperative membranous urethral length (MUL) would be associated with the recovery of urinary continence after robot-assisted laparoscopic prostatectomy (RALP).Patients and methodsWe studied 204 patients who underwent RALP between May 2013 and March 2016. All patients underwent pelvic magnetic resonance imaging (MRI) preoperatively to measure MUL. Urinary continence was defined as the use of one pad or less (safety pad). The 204 patients were divided into two groups: continence group, those who achieved recovery of continence at 3, 6, and 12 months after RALP, and incontinence group, those who did not. We retrospectively analyzed the patients in terms of preoperative clinical factors including age, body mass index (BMI), estimated prostate volume, neurovascular bundle salvage, history of preoperative hormonal therapy, and MUL.ResultsThe safety pad use rate was 69.6%, 86.9%, and 91.1% at 3, 6, and 12 months, respectively. On univariate and multivariate analyses, MUL were significant factors in every term of recovery of urinary continence in both groups. According to the receiver operating characteristic (ROC) curve analysis, the preoperative MUL that could best predict early recovery of urinary continence at 3 months after RALP was 12 mm.ConclusionsWe suggest that preoperative MUL > 12 mm would be a predictor of early recovery of urinary continence after RALP.

Squamous cell carcinoma of the prostate is a rare tumor. It has been typically described as an aggressive cancer, with a median survival time of 14 months. We present a case of locally advanced squamous cell carcinoma of the prostate with a regional lymph node metastasis. The patient received a novel combination chemotherapy regimen, docetaxel, cisplatin, and 5-fluorouracil, with radiotherapy to the whole pelvis and prostate. He was subsequently treated with seven courses of docetaxel, cisplatin, and 5-fluorouracil chemotherapy without any severe adverse events. We identified a 60.1 % reduction in the prostatic tumor, and the lymph node metastasis was shrunk after chemotherapy. A needle biopsy of the prostate after chemotherapy revealed no malignancy. No recurrence has been observed for 24 months. A combination of docetaxel, cisplatin, and 5-fluorouracil chemotherapy and radiotherapy might be an effective therapy for squamous cell carcinoma of the prostate.

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Indoxyl sulfate (IS) is related to the development of cardiovascular disease and total mortality in dialysis patients. High‐performance liquid chromatography (HPLC) is the conventional measurement approach. However, the HPLC method is difficult to perform in real time. Recently, the IS Assay Kit “NIPRO”, which enables the measuring of total IS by the enzyme method, was developed. This new reagent allows the easy and quick measurement of many samples using the automatic biochemical analyzer. Moreover, it was reported that it demonstrated satisfactory analytical performance. If this enzyme method is useful for measuring IS in hemodialysis, we can expect that the mechanism in which the IS effects adversely on a body as uremic toxins will be clarified. However, the enzyme method is more easily influenced by other coexisting substances. In this study, we have assessed on how the uremic toxins and anticoagulation effect on this new reagent and evaluate whether it can be put into practice effectively for hemodialysis patients. For the enzyme method, accuracy, simultaneous repeatability, linearity, limit of detection, influence of coexisting materials, and correlation with the HPLC method were examined. Accuracy and simultaneous repeatability were satisfactory, and linearity was good. The limit of detection was acceptable, and there was no influence of coexisting materials. With regard to the correlation, the regression equation was y = 0.947X + 7.987 and the correlation coefficient (r) was 0.972. This new reagent showed sufficient fundamental performance and had a good correlation with the conventional HPLC method for assessing the plasma of dialysis patients.

Patients who undergo hemodialysis often suffer from cardiovascular disease (CVD), and evaluation of coronary artery calcification is extremely important. These evaluations are typically conducted using a noninvasive method including electron beam computed tomography (CT) or multi-detector CT, and the Agatston method to calculate the coronary artery calcification score (CACS). However, it is difficult to use for patients undergoing dialysis. Because patients undergoing dialysis is too strong in coronary artery calcification, and results become incorrect. Therefore, we were looking for a calcified evaluation place peculiar to a patients undergoing dialysis. We obtained pelvic artery calcification scores (PACS) using a 64-row multi-slice CT to assess the presence of calcification within a triangular space bordered by bordered by osseous structure. We used the Agatston method to calculate PACS. We compared male patients undergoing dialysis with male patients with normal renal function. Patients undergoing hemodialysis had a significantly higher incidence of pelvic artery calcification than normal controls (79.7% vs. 5.5%). In the dialysis group, CACS was 1660.2 (0-9056.1), and PACS was 48.8 (0-2943.1). We found a correlation between PACS and CACS and between PACS and dialysis period. We found penile artery calcification in male patients undergoing hemodialysis was more than normal controls, and it was possible to quantify PACS using the Agatston method. This study suggested the possibility that PACS became the vascular calcification evaluation method of the hemodialysis patient.

Introduction Intraperitoneal urinary bladder perforation due to blunt trauma in intoxicated patients requires quick and accurate diagnosis. However, this is difficult to correctly diagnose in intoxicated patients because their symptoms can be masked. We describe a rare case of intraperitoneal urinary bladder perforation that occurred after blunt trauma. Case presentation A 66‐year‐old intoxicated man stumbled, tripped on a stone step and landed on his lower abdomen, but felt no pain at the time. Two days later, he was diagnosed with intraperitoneal urinary bladder perforation, which was repaired by open surgery. Conclusion Urinary bladder perforation should be considered when patients present with abdominal pain and decrease in urine volume following trauma.

BackgroundReduced port laparoscopic surgery (RPLS) is comparable to conventional multiport laparoscopic surgery and has the potential to provide improved cosmesis and decreased pain; as such, it satisfies a growing demand for less invasive surgical procedures. Moreover, a zigzag incision of the umbilicus results in a less visible scar in plastic surgery. Here we report a series of two cases with bilateral organ tumors treated by single-stage RPLS using a combination of a transumbilical approach and a zigzag incision.Case presentationCase 1: A 63-year-old man was diagnosed with right renal cell carcinoma (RCC) (clear cell carcinoma, pT1a, venous invasion (−)) and a splenic tumor (cavernous hemangioma). Case 2: An 84-year-old woman was diagnosed with concurrent left RCC (clear cell carcinoma, pT1b, 65 × 65 mm, venous invasion (+)) and ascending colon cancer (adenocarcinoma pT3 with no nodal involvement (0/48)). The perioperative course was uneventful in both cases. However, an additional incision was required in Case 2 for specimen excision. Therefore, the scars were more obvious in Case 2 than in Case 1.ConclusionsAlthough more cases are required to evaluate the superiority of this technique, this novel procedure could be considered for patients with bilateral lesions.