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Background: In Japan, since 2014, new treatments such as androgen receptor signaling inhibitors and cabazitaxel have become applicable for metastatic castration-resistant prostate cancer (mCRPC), leading to dramatic changes in treatment options., Objective: This study aims to evaluate the impact of recent advancements in treatment options on the overall survival (OS) of patients diagnosed with de novo metastatic castration-sensitive prostate cancer (mCSPC) in Japan., Methods: A retrospective analysis was conducted on 2450 Japanese men diagnosed with de novo mCSPC between 2008 and 2018. Patients were stratified into two groups based on the period of diagnosis: an earlier period (2008-2013) and a later period (2014-2018). OS was compared between earlier and later periods using Kaplan-Meier analysis in total and propensity score matched subpopulation as well as risk-stratified subgroups., Results: Patients diagnosed in the later period exhibited significantly improved OS compared to those diagnosed in the earlier period. The risk score, calculated based on ISUP grade group, LDH levels, and ALP levels, was a poor prognostic factor. In the later period, compared to the earlier period, there was no improvement in OS in the favorable-risk group, but a significant improvement was observed in the poor-risk group., Conclusion: It was suggested that the introduction of novel androgen receptor signaling inhibitors and chemotherapy treatment regimens since 2014 has led to improved survival outcomes for patients with de novo mCSPC, particularly those with poor-risk profiles. The findings highlight the impact of recent advancements in treatment on the prognosis of patients with metastatic prostate cancer in Japan., Competing Interests: Declarations. Conflict of interest: Masaki Shiota received honoraria from Janssen Pharmaceutical, AstraZeneca, Astellas Pharma, Sanofi, Bayer Yakuhin, and research funding support from Daiichi Sankyo. Naoki Terada received honoraria from Sanofi, Astellas Pharma, and Janssen Pharmaceutical. Takahiro Kimura received honoraria from Astellas Pharma, AstraZeneca, Bayer Yakuhin, Janssen Pharmaceutical, Sanofi, and Takeda Pharmaceutical. Hiroshi Kitamura reports consulting or advisory roles for Astellas Pharma, AstraZeneca, and Janssen Pharmaceutical; honoraria for Astellas Pharma, AstraZeneca, Janssen Pharmaceutical, Nippon Shinyaku, Sanofi, and Takeda Pharmaceutical; research funding for AstraZeneca and Takeda Pharmaceutical. Nobumichi Tanaka is affiliated with an endowed chair funded by Nihon Medi-Physics Co. Shintaro Narita received honoraria from Janssen Pharmaceutical, Astellas Pharma, and Bayer Yakuhin. Masatoshi Eto received honoraria from Ono Pharmaceutical, Takeda Pharmaceutical, Novartis Pharma, Pfizer, Bristol-Myers Squibb, Janssen Pharmaceutical, MSD, Merck Biopharma, AstraZeneca, and Eisai and research funding support from Bayer Yakuhin, Astellas Pharma, Ono Pharmaceutical, and Takeda Pharmaceutical., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

A 50-year-old woman presented to our hospital in May2021 with a fever of approximately39 °C and abdominal pain. A contrast-enhanced computed tomography (CT) scan revealed an 88 mm right renal tumor. Two weeks later, a follow-up CT scan demonstrated rapid tumor growth, with the major axis measuring 100 mm. During this interval, her abdominal pain worsened, and she developed lower leg edema. A contrast-enhanced CT scan conducted 5 days before the scheduled surgery, four weeks after initial presentation, showed further tumor progression, with a diameter of 155 mm. The tumor, which had infiltrated the ascending colon, duodenum, liver, gallbladder, and inferior vena cava (IVC), was surgically removed along with the right kidney. Due to its complexity, the planned wide excision was deemed infeasible. Therefore, a tumor resection was performed macroscopically. Histopathological examination confirmed the diagnosis of undifferentiated pleomorphic sarcoma (UPS). Subsequently, the patient experienced a postoperative tumor recurrence. Although the patient received doxorubicin chemotherapy, she passed away5 weeks after the operation. This case highlights the critical importance of prompt surgical excision with adequate tumor margins in the management of UPS.

Background: Costimulatory blockade-induced allograft tolerance has been achieved in rodent models, but these strategies do not translate well to nonhuman primate and clinical transplants. One confounder that may underlie this discrepancy is the greater ischemic inflammation imposed on the transplants. In mice, cardiac allografts subjected to prolonged cold ischemic storage (CIS) before transplant have increased ischemia-reperfusion injury, which amplifies infiltrating endogenous memory CD8 T-cell activation within hours after transplantation to mediate acute graft inflammation and cytotoxic lymphocyte-associated molecule-4 immunoglobulin-resistant rejection. This study tested strategies inhibiting memory CD8 T-cell activation within such high ischemic allografts to achieve long-term survival., Methods: A/J (H-2 a ) hearts subjected to 0.5 or 8 h of CIS were transplanted to C57BL/6 (H-2 b ) recipients and treatment with peritransplant costimulatory blockade. At 60 d posttransplant, regulatory T cells (Treg) were depleted in recipients of high ischemic allografts with anti-CD25 monoclonal antibody (mAb) or diphtheria toxin., Results: Whereas peritransplant (days 0 and +1) anti-lymphocyte function-associated antigen-1 mAb and anti-CD154 mAb prolonged survival of >60% allografts subjected to minimal CIS for >100 d, only 20% of allografts subjected to prolonged CIS survived beyond day 80 posttransplant and rejection was accompanied by high titers of donor-specific antibody. Peritransplant anti-lymphocyte function-associated antigen-1, anti-tumor necrosis factor-α, and anti-CD154 mAb plus additional anti-CD154 mAb on days 14 and 16 obviated this donor-specific antibody and promoted Treg-mediated tolerance and survival of 60% of high ischemic allografts beyond day 100 posttransplant, but all allografts failed by day 120., Conclusions: These studies indicate a strategy inducing prolonged high ischemic allograft survival through Treg-mediated tolerance that is not sustained indefinitely., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

A 63-year-old woman underwent laparoscopic sacrocolpopexy for pelvic organ prolapse. Four days postoperatively, she underwent an abdominal computed tomography scan because she developed a stomachache, and a strangulated bowel obstruction was suspected. The patient then underwent an emergency laparotomy which revealed strangulation of the small intestine caused by a band formed between the stump of a barbed suture and the mesentery. The strangulation was released by resecting the stump, and intestinal resection was not necessary. Nine days following the re-intervention, the patient was discharged from our hospital. As of four months after the surgery, she has not experienced any recurrence of pelvic organ prolapse or other postoperative complications. We need some ingenuity when using barbed suture in situations where the thread and the intestine come into contact.

Objective: To determine the effect of combined androgen blockade with a first-generation anti-androgen on the prognoses of metastatic hormone-sensitive prostate cancer patients stratified by tumor burden., Methods: We retrospectively analyzed the cases of metastatic hormone-sensitive prostate cancer patients who were treated with androgen deprivation therapy in 2008-2017 at 30 institutions in Japan. To compare the overall survival and progression-free survival rates of the patients treated with castration monotherapy and combined androgen blockade, we carried out a Cox proportional hazards regression analysis using both inverse probability of treatment weighting and instrumental variables methods. High-burden disease was defined as the presence of four or more bone metastases and/or visceral metastasis., Results: Of 2048 patients, 702 (34.3%) and 1346 (65.7%) patients were classified as the low- and high-burden groups, respectively. In each group, >80% of the patients were treated with combined androgen blockade. Although there was no significant between-group difference in the overall survival according to the androgen deprivation therapy method, in the high-burden group the progression-free survival of the combined androgen blockade-treated patients was significantly better than that of patients treated with castration monotherapy: inverse probability of treatment weighting method, hazard ratio 0.49, 95% confidence interval 0.34-0.71; instrumental variables method, hazard ratio 0.80, 95% confidence interval 0.60-0.98., Conclusion: In the high-burden group, combined androgen blockade with a first-generation anti-androgen resulted in superior progression-free survival compared with castration monotherapy. For well-selected metastatic hormone-sensitive prostate cancer patients, the use of combined androgen blockade might still have some suitable scenarios., (© 2022 The Japanese Urological Association.)

A 77-year-old man underwent robot-assisted laparoscopic radical cystectomy with pelvic lymph node dissection and ileal conduit for bladder carcinoma. Six months postoperatively, multiple lung metastases and a sacral bone metastasis were detected on computed tomography (CT). The patient then received gemcitabine-carboplatin (G-CBDCA) because he had renal dysfunction, which is a contraindication for cisplatin. After two courses of G-CBDCA, pembrolizumab was started because the lung metastases showed progression. The patient then underwent gemcitabine-paclitaxel (GP) chemotherapy (G : 1,000 mg/m² on days 1, 8, and 15 ; P : 180 mg/m² on day 1 ; every 4 weeks) as third-line treatment because of further progression after two courses of pembrolizumab. The lung metastases showed an almost complete response after two courses of GP. Additionally, after two courses, the lung metastases showed a complete response, and no abnormal fluorodeoxyglucose uptake in the sacral bone metastasis was seen on positron emission tomography-CT. The patient suffered neutropenia and anemia as adverse effects ; however, these disappeared after discontinuing gemcitabine. Chemotherapy was discontinued after the four courses in accordance with the patient's wishes, and he has remained free from recurrence for 2 months after discontinuing therapy.

The metastatic burden is a critical factor for decision-making in the treatment of metastatic hormone-sensitive prostate cancer (HSPC). This study aimed to develop and validate a novel risk model for survival in patients with de novo low- and high-burden metastatic HSPC. The retrospective observational study included men with de novo metastatic prostate cancer who were treated with primary androgen-deprivation therapy at 30 institutions across Japan between 2008 and 2017. We created a risk model for overall survival (OS) in the discovery cohort (n = 1449) stratified by the metastatic burden (low vs high) and validated its predictive ability in a separate cohort (n = 951). Based on multivariate analyses, lower hemoglobin levels, higher Gleason grades, and higher clinical T-stage were associated with poor OS in low-burden disease. Meanwhile, lower hemoglobin levels, higher Gleason grade group, liver metastasis, and higher extent of disease scores in bone were associated with poor OS in patients with high-burden disease. In the discovery and validation cohorts, the risk model using the aforementioned parameters exhibited excellent discriminatory ability for progression-free survival and OS. The predictive ability of this risk model was superior to that of previous risk models. Our novel metastatic burden-stratified risk model exhibited excellent predictive ability for OS, and it is expected to have several clinical uses, such as precise prognostic estimation., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Purpose: To externally validate the utility of the albumin, C-reactive protein and lactate dehydrogenase model to predict the overall survival of previously treated metastatic renal cell carcinoma patients., Patients and Methods: The ability of the albumin, C-reactive protein and lactate dehydrogenase model to predict overall survival was validated and compared with those of other prognostication models using data from 421 metastatic renal cell carcinoma patients receiving second-line axitinib therapy at 36 hospitals belonging to the Japan Urologic Oncology Group., Results: The following factors in this cohort were independently associated with poor overall survival in a multivariate analysis: a low Karnofsky performance status, <1 year from diagnosis to targeted therapy, a high neutrophil count, and low albumin, elevated C-reactive protein, and elevated lactate dehydrogenase, and the Japan Urologic Oncology Group model was newly developed based on the presence/absence of these independent factors. In this cohort, 151 (35.9%), 125 (27.7%) and 145 (34.4%) patients were classified into the favorable, intermediate and poor risk groups, respectively, according to the albumin, C-reactive protein and lactate dehydrogenase model; however, the proportions of patients in the intermediate risk group stratified by the Japan Urologic Oncology Group, Memorial Sloan Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium models were >50%. The superiority of the albumin, C-reactive protein and lactate dehydrogenase model to the Memorial Sloan Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium models, but not the Japan Urologic Oncology Group model, was demonstrated by multiple statistical analyses., Conclusions: The utility of the albumin, C-reactive protein and lactate dehydrogenase model as a simple and objective prognostication tool was successfully validated using data from 421 metastatic renal cell carcinoma patients receiving second-line axitinib., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Metastatic burden is a critical factor for therapy decision-making in metastatic hormone-sensitive prostate cancer. The present study aimed to identify prognostic factors in men with high- or low-metastatic burden treated with primary androgen-deprivation therapy. The study included 2450 men with de novo metastatic prostate cancer who were treated with primary androgen-deprivation therapy at 30 institutions across Japan between 2008 and 2017. We investigated the prognostic value of various clinicopathological parameters for progression-free survival (PFS) and overall survival (OS) in patients stratified by low- or high-metastatic burden. Among the 2450 men, 841 (34.3%) and 1609 (65.7%) were classified as having low- and high-metastatic burden, respectively. Median PFS of the low- and high-burden groups were 44.5 and 16.1 months, respectively, and the median OS was 103.2 and 62.7 months, respectively. Percentage of biopsy-positive core, biopsy Gleason grade group, T-stage, and N-stage were identified to be differentially prognostic. M1a was associated with worse PFS than was M1b in the low-burden group, whereas lung metastasis was associated with better PFS and OS than was M1b in the high-burden group. Differential prognostic factors were identified for patients with low- and high-burden metastatic prostate cancer. These results may assist in decision-making to select the optimal therapeutic strategies for patients with different metastatic burdens., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

A 66-year-old male with bladder cancer underwent radical cystectomy and ileal conduit construction. The pathological diagnosis was urothelial carcinoma with squamous differentiation (pT3b). Computed tomography (CT) 18 months postoperatively revealed a right external iliac lymph node metastasis. He was treated with systemic chemotherapy after placement of bilateral ureteral stents, but CT following chemotherapy revealed an increase in the size of the metastasis, and the patient was diagnosed with progressive disease. Radiotherapy to the metastasis was selected as local therapy, but the patient was at risk of an uretero-arterial fistula because the right external iliac artery and the right ureter adjacent to the metastasis were involved in the irradiated field. The right external iliac lymph node metastasis was irradiated with a dose of 50 Gy after stent grafting for the right external iliac artery to prevent an ureteroarterial fistula. He had no adverse events, including hematuria after radiotherapy, but died of cancer cachexia 12 months after radiotherapy.

Objectives: To evaluate the association between the use of local radiotherapy (RT) with the survival of patients with de novo metastatic prostate cancer and symptomatic local events (SLEs)., Patients and Methods: Patients were initially diagnosed with metastatic prostate cancer between 2008 and 2017 at 30 institutes in Japan. Prostate-specific antigen (PSA) progression-free survival (PSA-PFS) under initial androgen deprivation therapy and overall survival (OS) was compared between patients receiving local RT (RT group) and no RT (no-RT group) by multivariate Cox proportional hazard analyses. The occurrence rate of grade ≥2 SLEs was compared by multivariate logistic regression analyses. Propensity score matching (PSM) analyses were performed to compare PSA-PFS and OS of the groups in the high and low metastatic burden cohort., Results: Two hundred and five (7%) of 2829 patients received RT before PSA progression. Median PSA-PFS and OS were significantly longer in the RT group than in the no-RT group and the difference was significant in multivariate analyses (HR = 0.44, 95% CI = 0.33-0.57 and HR = 0.40, 95% CI = 0.27-0.60, respectively). The occurrence rate of grade ≥2 SLEs was significantly lower in the RT group (2%) than the no-RT group (9%) and the difference was significant in multivariate analyses (HR = 0.28, 95% CI = 0.10-0.76). Using PSM analyses, PSA-PFS and OS remained significantly different (HR = 0.64, 95% CI = 0.46-0.89 and HR = 0.47, 95% CI = 0.30-0.72, respectively), between the RT (n = 182) and the no-RT (n = 182) groups. The difference in OS was significant in the high metastatic burden cohort (HR = 0.55, 95% CI = 0.37-0.81)., Conclusions: Addition of local RT to standard treatment for de novo metastatic prostate cancer patients tends to have the potential to extend survival, even in patients with high metastatic burden, and to reduce SLEs., Competing Interests: None, (© 2020 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

The present study aimed to evaluate the efficacy of the real-world use of axitinib and to develop a prognostic model for stratifying patients who could derive long-term benefit from axitinib. This was a retrospective, descriptive study evaluating the efficacy of axitinib in patients with metastatic renal cell carcinoma that had been treated with 1 or 2 systemic antiangiogenic therapy regimens at 1 of 36 hospitals belonging to the Japan Urologic Oncology Group between January 2012 and February 2019. The primary outcome was overall survival (OS). Using a split-sample method, candidate variables that exhibited significant relationships with OS were chosen to create a model. The new model was validated using the rest of the cohort. In total, 485 patients were enrolled. The median OS was 34 months in the entire study population, whereas it was not reached, 27 months, and 14 months in the favorable, intermediate, and poor risk groups, respectively, according to the new risk classification model. The following 4 variables were included in the final risk model: the disease stage at diagnosis, number of metastatic sites at the start of axitinib therapy, serum albumin level, and neutrophil : lymphocyte ratio. The adjusted area under the curve values of the new model at 12, 36, and 60 months were 0.77, 0.82, and 0.82, respectively. The efficacy of axitinib in routine practice is comparable or even superior to that reported previously. The patients in the new model's favorable risk group might derive a long-term survival benefit from axitinib treatment., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

A 74-year-old man presented at our hospital with complaints of abdominal pain, nausea, and vomiting. He had undergone laparoscopic radical cystectomy and ileal conduit for urinary bladder cancer 1 month earlier. The patient had abdominal distention, resonant sounds on percussion, and diffuse abdominal tenderness without rebound or guarding. Abdominal CT revealed dilated jejunal loops herniated through a cord-like structure. Based on these findings, emergency surgery was performed, and intestinal dilatation into the space between the ureter, the ileal conduit, and the sacral bone was detected. The loops were released manually and were not resected. To the best of our knowledge, this is the first case report of small bowel obstruction due to internal hernia caused by the ureter after laparoscopic radical cystectomy and ileal conduit. Retroperitonealization and the minimum required mobilization of the ureters may be necessary when urinary diversion is constructed, especially in laparoscopic or robotic surgeries., (© 2018 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.)

Introduction: The main cause of slightly elevated human chorionic gonadotropin (HCG) after successful treatment of male germ cell tumors is considered to be pituitary-derived HCG. It is well known that pituitary-derived HCG is frequently detected in postmenopausal women. We evaluated the status of serum HCG in men with elevated gonadotropins, which were induced by androgen deprivation therapy, using commercially available assays., Materials and Methods: We enrolled 44 patients with prostate cancer, who underwent luteinizing-hormone releasing hormone agonist treatment. We measured serum follicle-stimulating hormone (FSH), serum luteinizing hormone (LH), serum total HCG, serum free HCG-β subunit, and urine total HCG 3 times per patient, on the day of treatment initiation, the next day, and 3 months after., Results: On the day after treatment initiation, serum and urine HCG was detected in 61% and 73% of patients, respectively. Markedly strong correlations were observed between serum/urine HCG and FSH/LH. In particular, receiver operating characteristic curve analysis indicated excellent area under the curve (0.977, 95% confidence interval 0.951-1.003)) for serum HCG-detectable LH. At the cutoff value of 21.07 mIU/mL for serum HCG-detectable LH, the sensitivity and specificity were 96.7% and 95.3%, respectively. Serum HCG-β was not detectable at any times in any patients., Conclusions: Suggested pituitary-derived HCG can be frequently detected in patients with elevated gonadotropins, and there is a firm association between HCG detection and gonadotropin levels., Competing Interests: Conflict of interest: None declared., (Copyright® by the International Brazilian Journal of Urology.)

A 71-year-old man was admitted to the department of general surgery at our hospital due to constipation. A large bowel endoscopic examination revealed a stenosis of the rectum near the anus. The pathological diagnosis of the biopsy was poorly differentiated adenocarcinoma. After a computed tomography/magnetic resonance imaging examination, rectal cancer infiltrating the prostate was the diagnosis. External beam radiation therapy and chemotherapy were performed. After those neoadjuvant therapies, an abdominoperineal resection of the rectum (Miles) and a retropubic radical prostatectomy were performed. The final pathological diagnosis was prostate cancer infiltrating the rectum. Prostate cancer infiltrating the rectum is rare because of the Denonvillier's fascia barrier. However, it is difficult to distinguish prostate cancer infiltrating the rectum from rectal cancer infiltrating the prostate. Thus, when we see rectal cancer infiltrating the prostate, prostate cancer infiltrating the rectum should be suspected, serum prostate specific antigen (PSA) level should be determined, and PSA immunostaining should be performed.

Objectives: To evaluate the impact of relative dose intensity for gemcitabine-cisplatin chemotherapy in patients with metastatic urothelial carcinoma., Methods: We retrospectively reviewed the medical records of 18 patients with metastatic urothelial carcinoma, who received gemcitabine-cisplatin regimen as the first-line chemotherapy between 2009 and 2015. The doses of gemcitabine and cisplatin were reduced or the intervals between treatment cycles were prolonged according to the treatment efficacy and adverse events during the first and second cycles. The individually optimal relative dose intensity was set as the actual dose per the standard dose in the first and second cycles. From the third course onward, patients received the gemcitabine-cisplatin chemotherapy with the same relative dose intensity. Overall survival was compared with the groups according to the value of relative dose intensity., Results: The median age was 72.5 (range, 56-79) years and 15 men and 3 women were enrolled in the study. The median number of cycles of first-line gemcitabine-cisplatin chemotherapy was 8 (range, 2-17), and the median survival time from initiation of first-line chemotherapy was 20.1 (range, 3.5-32.8) months. The total median relative dose intensity of gemcitabine-cisplatin chemotherapy was 56.1%. The median survival time of 10 patients in the group with the relative dose intensity of less than 60% was significantly longer than that of 8 patients in the group with the relative dose intensity of more than 60% (19.2 and 11.0 months, respectively, p = 0.04)., Conclusion: Individual low relative dose intensity management in the first-line gemcitabine-cisplatin chemotherapy may be an acceptable option for patients with metastatic urothelial carcinoma., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Prolonged cold ischemia storage (CIS) is a leading risk factor for poor transplant outcome. Existing strategies strive to minimize ischemia-reperfusion injury in transplanted organs, yet there is a need for novel approaches to improve outcomes of marginal allografts and expand the pool of donor organs suitable for transplantation. Aquaporins (AQPs) are a family of water channels that facilitate homeostasis, tissue injury, and inflammation. We tested whether inhibition of AQP4 improves the survival of fully MHC-mismatched murine cardiac allografts subjected to 8 hours of CIS. Administration of a small molecule AQP4 inhibitor during donor heart collection and storage and for a short-time posttransplantation improves the viability of donor graft cells, diminishes donor-reactive T cell responses, and extends allograft survival in the absence of other immunosuppression. Furthermore, AQP4 inhibition is synergistic with cytotoxic T lymphocyte-associated antigen 4-Ig in prolonging survival of 8-hour CIS heart allografts. AQP4 blockade markedly reduced T cell proliferation and cytokine production in vitro, suggesting that the improved graft survival is at least in part mediated through direct effects on donor-reactive T cells. These results identify AQPs as a promising target for diminishing donor-specific alloreactivity and improving the survival of high-risk organ transplants., (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)

A 24-year-old woman with a high fever presented at our hospital. She had been diagnosed with Kabuki syndrome at the age of 4 years because she had the typical facial features of the condition ; she had undergone living donor renal transplantation 12 years prior. She was prescribed a course of antibiotics to treat pyelonephritis of the transplanted kidney and the high fever disappeared, but the fever developed again 3 days after the discharge. Abdominal computed tomography revealed a tubular structure of recent onset running from the left dorsal side to the lower part of the bladder. This structure was filled with pus, which we drained. We also performed laparoscopic ureterectomy of the left ureter to achieve a complete cure. No complication was observed after the surgery and the graft renal function did not deteriorate further.

While the incidence of antibody-mediated kidney graft rejection has increased, the key cellular and molecular participants underlying this graft injury remain unclear. Rejection of kidney allografts in mice lacking the chemokine receptor CCR5 is dependent on production of donor-specific antibody. Here we determine if cells expressing cytotoxic function contributed to antibody-mediated kidney allograft rejection in these recipients. Wild-type C57BL/6, B6.CCR5(-/-), and B6.CD8(-/-)/CCR5(-/-) mice were transplanted with complete MHC-mismatched A/J kidney grafts, and intragraft inflammatory components were followed to rejection. B6.CCR5(-/-) and B6.CD8(-/-)/CCR5(-/-) recipients rejected kidney allografts by day 35, whereas 65% of allografts in wild-type recipients survived past day 80 post-transplant. Rejected allografts in wild-type C57BL/6, B6.CCR5(-/-), and B6.CD8(-/-)/CCR5(-/-) recipients expressed high levels of VCAM-1 and MMP7 mRNA that was associated with high serum titers of donor-specific antibody. High levels of perforin and granzyme B mRNA expression peaked on day 6 post-transplant in allografts in all recipients, but were absent in isografts. Depletion of natural killer cells in B6.CD8(-/-)/CCR5(-/-) recipients reduced this expression to background levels and promoted the long-term survival of 40% of the kidney allografts. Thus, natural killer cells have a role in increased inflammation during antibody-mediated kidney allograft injury and in rejection of the grafts., (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Objectives: To examine the effects of combined treatment with sulfoquinovosylacylpropanediol and X-ray irradiation on the remodeling of the prostate cancer microenvironment, including angiogenic and hypoxic characteristics., Methods: Human prostate cancer cells (DU145 and PC3) were implanted subcutaneously into the right hind legs of athymic nude mice. After the tumor volume reached 100-300mm(3) , 2mg/kg/day sulfoquinovosylacylpropanediol was given intravenously from day0 to day4, and cells were exposed to 4Gy X-ray irradiation on days0 and 3 (for a total of 8Gy). Tumors were fixed and stained for pathological analyses and immunohistochemical evaluations. To analyze vascular normalization, 60mg/kg pimonidazole dissolved in saline was injected intraperitoneally., Results: Combined treatment with sulfoquinovosylacylpropanediol plus X-ray irradiation enhanced growth inhibition in DU145 xenografts. The tumor vessel density in DU145 cells significantly decreased after the combined treatment. Staining for αsmooth muscle actin in vessels was significantly increased. Pimonidazole staining, showing hypoxic lesions, was negative from 72h, but positive at 6 and 24h after the first combined treatment. In contrast, no enhancement of the microenvironment in PC3 xenografts was observed with sulfoquinovosylacylpropanediol plus X-ray irradiation., Conclusion: Sulfoquinovosylacylpropanediol could be a novel potent radiosensitizing agent targeting angiogenesis in prostate cancer., (© 2015 The Japanese Urological Association.)

Previous studies have reported negative impacts of long-term dialysis on kidney transplantation (KTx) outcomes. However, advances in surgical techniques, immunosuppressive therapies, and post-transplant monitoring have led to an impressive increase in patient and allograft survival. Thus, the number of KTx among patients on long-term dialysis is increasing. We evaluated the influence of dialysis duration on the outcome of living donor KTx. Between January 2000 and October 2011, we performed 1098 first KTx from living donors in adults (>18 years). We divided the patients into six groups, A group: pre-emptive kidney transplantation, B group: <24 months duration of dialysis, C group: 25-60 months duration, D group: 61-120 months duration, E group: 121-240 months duration, and F group: ≥ 241 months duration. The 5-year patient survival rates were 95.7, 98.8, 99.0, 99.0, 97.3, and 100% in groups A-F, respectively. The 5-year graft survival rates were 91.3, 95.6, 94.2, 96.3, 90.7, and 100% in groups A-F, respectively. No significant differences were observed in patient or graft survival among the six groups. Longer dialysis duration was correlated with lower rates of preoperative hypertension and diabetes mellitus. Survivors of long-term dialysis tended to be in good compliance with self-management. If recipients of living KTx have few complications, good prognoses are expectable even if dialysis periods are very long., (© 2014 The Authors. Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis.)

Alloantibodies contribute significantly to renal transplant rejection by activation of complement and various cytokines with a variety of effector cells, and are a major cause of allograft loss. Although there is clinical evidence of antibody- and complement-mediated injury in renal transplantation, the mechanism of antibody-mediated rejection remains largely unknown. In order to understand the sequential production of antibodies and complement components, we presensitized recipient rats by skin transplantation. Anti-donor-specific IgG levels reached a maximum 2 weeks following presensitization after which the rats underwent renal transplantation from the same donor strain. We then evaluated sequential pathological findings based on the Banff classification and several factors related to graft rejection. In this presensitized model, peritubular capillaries were already dilated and stained for C4d. Neutrophil and mononuclear cell infiltration in these capillaries was detected beginning 2 h after transplantation. Donor-specific antibody IgG levels decreased rapidly and anti-IgG antibody stained glomerular and peritubular capillaries in the grafts beginning 2 h after transplantation. Additionally, several cytokines and complement components showed marked changes in the presensitized group. Thus, in the donor-specific presensitized recipient, alloantibodies and complement were activated immediately after transplant. C4d deposition in peritubular capillaries appears to be a key factor for the diagnosis of antibody-associated rejection.

We sought to clarify the controversial issue of whether detecting low-level anti-donor-specific HLA antibody (HLA-DSA) by single-antigen flow-bead assay (SAFB) may have a potential role in reducing acute and chronic antibody-mediated rejection (AMR). We retrospectively studied the preoperative serum of ABO-compatible living kidney transplantation recipients transplanted between 2001 and 2004 by SAFB using a Luminex platform. HLA-DSA was detected only by SAFB in 24 patients, although all of them showed negative T-cell and B-cell complement-dependent cytotoxicity (CDC) crossmatches. The HLA-DSA patients went on to have surprisingly high levels of acute and chronic AMR despite being only weakly sensitized (acute AMR, 33.3%; chronic AMR, 41.7%). After 2005, we implemented SAFB routinely and any patient having a positive HLA-DSA was considered to be a desensitization candidate. The 52 patients found to have HLA-DSA underwent kidney transplantation after prior treatment with a single dose of rituximab (RIT) and three or four sessions of double-filtration plasmapheresis (DFPP) in addition to regimens commonly used between 2001 and 2004. After 2005, there was a significant reduction in the occurrence of acute and chronic AMR (acute AMR, 4.7%, P < 0.001; chronic AMR, 4.7%, P < 0.001). The 5-year graft survival rate also improved after implementing SAFB (83.3-98.1%, P = 0.032). The RIT/DFPP-induction protocol may improve graft survival even in patients with low-level DSA., (© 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.)

Recipients of spousal donor transplantation (SDT) have poorer histocompatibility and higher human leukocyte antigen (HLA) sensitization due to pregnancy than those receiving related donor transplantation (RDT). Thus, SDT carries a higher risk of acute rejection (AR). In our department, patients at a high immunological risk, such as those with ABO incompatibility and HLA sensitization, were considered for desensitization by double filtration plasmapheresis and preoperative administration of rituximab. In this study we compared the AR incidence rates between SDT and RDT according to their immunological risk. We performed RDT in 279 and SDT in 100 patients, a total of 379 cases, between 2000 and 2008; 48.7% of RDT and 67.0% of SDT cases were considered to be at a high immunological risk and underwent preoperative desensitization (P=0.002). Even though the AR incident rate of SDT was higher than RDT in the low immunological risk group, in which the patients had undergone transplantation without desensitization (RDT 24.4%, SDT 37.0%, P=0.012), there was no significant difference between the two donor type groups in the high immunological risk group, in which transplantation with desensitization occurred (RDT 21.3%, SDT 31.3%, P>0.05). Preoperative administration of rituximab significantly reduced AR from 37.4% to 10.6% (P<0.001), especially T-cell mediated rejection (36.4% to 20.2%, P=0.01). SDT no longer carries a high risk when appropriate desensitization, including the use of rituximab, is performed. Overall, the five-year graft survival rates were similar between RDT and SDT., (© 2010 The Authors. Therapeutic Apheresis and Dialysis © 2010 International Society for Apheresis.)

In this study, we retrospectively investigated the relationship between the presence/titers of donor-specific (DSA)/nondonor-specific antibody (NDSA) and the rate of graft rejection after transplantation. The subjects comprised 34 recipients who tested positive by FlowPRA(®) Screening. The recipients were divided into two groups; 22 recipients with DSA and 12 recipients with NDSA, as detected using FlowPRA(®) Single Antigen I and II beads. The antibodies were also quantitatively examined using the molecules of equivalent soluble fluorochrome (MESF) method. Nine of the 22 recipients with DSA (9/22, 40%) developed antibody-mediated rejection (AMR), while none of the 12 recipients with NDSA (0/12, 0%) developed AMR (P < 0.01). In a quantitative analysis of the MESF data, patients with DSA with MESF values of over 3000 frequently showed AMR (8/11, 73%). In contrast, one of the patients with DSA with MESF values of <3000 showed AMR (1/11, 9%). One of the 12 patients (1/12, 8%) with NDSA showed cellular rejection (T-cell-mediated rejection), regardless of the MESF values. In patients with DSA, an MESF value of 3000 may be a useful cutoff value for identifying patients at a high risk for AMR., (© 2010 The Authors. Transplant International © 2010 European Society for Organ Transplantation.)

Background and Purpose: Laparoscopic living donor nephrectomy (LLDN) is a standard method of donor nephrectomy. Most cases of LLDN are transperitoneal. Retroperitoneal access, however, implies a direct approach to the retroperitoneal organs without interfering with any of them. Since 2001, we have been trying to establish the technique of retroperitoneoscopic live donor nephrectomy (RPLDN). To assess the safety, feasibility, and usefulness of RPLDN, we reviewed the experience with this technique at our institution., Patients and Methods: From July 2001 to March 2009, 425 patients underwent live donor renal transplantation at our institution with allografts procured by RPLDN. Study variables included operative time, time to retrieval of the kidney, blood loss, warm ischemia time, length of hospital stay, number and length of renal vessels, graft function, and complications., Results: Mean follow-up was 53 months. Donor nephrectomy was performed successfully in all patients. The complication rate was 4.9%. In one case, the procedure was changed to open donor nephrectomy because of severe adhesion in the renal hilum from previous surgery. Ureteral complications occurred in four patients, who were successfully treated with retrograde ureteral stent placement. None of the donors needed readmission. Mean warm ischemia time was 4.8 minutes. Creatinine levels returned to normal in all patients, and long-term allograft function was good. Serum creatinine levels at postoperative days 1, 7, and 14 were 3.7 mg/dL, 1.4 mg/dL, and 1.4 mg/dL on average, respectively. Slow graft function was noted in four (1.1%) cases but returned to the normal level within 2 weeks after surgery. One-year donor survival was 99%, and 1-year graft survival was 98.2%., Conclusions: Excellent donor safety and allograft function were obtained with RPLDN. These results suggest that RPLDN could be an option for LLDN.

Testicular sperm can be obtained from patients with non-obstructive azoospermia. However, there is not enough evidence concerning whether fresh or frozen-thawed sperm is better for successful pregnancy. We retrospectively compared initial treatment results of intracytoplasmic sperm injection using fresh and frozen-thawed testicular sperm in our institution. From August 1997 to May 2006, a total of 27 cases including 18 cases using fresh sperm (269 oocytes) and 9 cases using frozen sperm (97 oocytes) were evaluated. In the fresh and frozen sperm groups 33.4 and 32.9%, respectively, developed good quality embryo. There was no significant difference between the two groups in successful pregnancy and birth rates.

We report here a case of very late relapse of a nonseminomatous germ cell tumor 21 years after first complete remission. A 42-year-old man, with a clinical history of right testicular cancer, was referred to our hospital with elevated serum alpha-fetoprotein (AFP) level. CT scan demonstrated a 5 x 5 cm retroperitoneal lymph node swelling compressing the inferior vena cava (IVC) extending from the right renal vein down to the bifurcation of the aorta. The patient received a total of four courses of combination chemotherapy consisting of cisplatin, etoposide, paxlitaxel, and ifosfamide. However, the retroperitoneal lymph node metastasis did not respond to chemotherapy, and the serum AFP level increased. Extended bilateral retroperitoneal lymph node dissection with right nephrectomy, partial duodenectomy, and vena cavectomy were performed. The patient has been followed up with no evidence of disease for 48 months after the operation without any further therapy.

Objectives: The incidence of inguinal hernia after radical retropubic prostatectomy (RRP) is high. We speculated that retraction of the vasa deferentia with a retractor might cause stretch injury of the myopectineal orifice and lead to inguinal hernia. In testing this hypothesis, we performed RRP with a modified technique and followed up patients prospectively., Methods: From 1993 to 2002, 171 patients underwent RRP with a retrograde approach, in which the vasa deferentia were cut after the prostate and seminal vesicles were finally exposed. From 2003 to 2005, 150 patients were followed up prospectively who had undergone RRP with a modified technique, in which the bilateral vasa deferentia and surrounding tissues were dissected before placing a retractor so as not to retract them and injure the myopectineal orifice. The incidence rates of inguinal hernia in the two groups were compared. In addition, for the entire group of 321 patients, we determined the risk factors for inguinal hernia after RRP using multivariate analysis., Results: Of the 150 patients in the modified method group, 22 (14.7%) developed an inguinal hernia during follow-up, and 42 (24.6%) of the 171 patients did so in the previous method group. No significant difference was noted between the two groups in terms of the hernia-free rate. Multivariate analysis revealed a body mass index of less than 23 kg/m2 and a history of previous inguinal hernia repair were significant risk factors for postoperative inguinal hernia., Conclusions: We found that retraction of the vasa deferentia with a retractor did not affect the high incidence of postoperative inguinal hernia after RRP.

Objective: The standard protocol of antibiotic prophylaxis in radical prostatectomy remains to be established. We retrospectively compared the occurrence of perioperative infections following radical prostatectomy between two different protocols of antibiotic prophylaxis., Methods: This study included 106 cases of radical retropubic prostatectomy managed on the clinical pathways. Two different protocols of antibiotic prophylaxis were used in otherwise identical pathways. Between January and December 2004, 50 patients received a second generation cephem, cefotiam, for 4 days, beginning 30 min before surgery (4-day group), whilst between December 2004 and July 2005, only two doses of cefotiam were given on the day of operation in 56 patients (1-day group). The incidence of surgical site infection (SSI) and remote infection (RI) was retrospectively investigated., Results: Superficial incisional SSI occurred in one (1.8%) patient in the 1-day group, whereas no patient in the 4-day group developed SSI. No RI was observed in either the 1-day or 4-day group. Intravenous antibiotics were administered besides the pathway in a patient in the 1-day group because unexplained fever more than 38 degrees C continued postoperative day (POD) 2 through POD 4 without signs of SSI or RI. Excluding this case, postoperative more than 38 degrees C was rare and transient after POD 2., Conclusion: The incidence of SSI and RI was low and not significantly different between the 1-day and 4-day groups. Therefore, the 1-day protocol of prophylactic antibiotic treatment seems adequate for preventing perioperative infections in radical prostatectomy.

To enable male patients to undergo uroflowmetry in a private condition without medical supervision, we devised an automatic switching and patient guidance system for the spinning disk uroflowmeter Urodyn 1000, using two commercial electronic devices (an infrared motion sensor tap and a memorizable vacuum fluorescent display). Instead of running the uroflowmeter continuously, which shortens the life of the spinning disk due to mechanical wear, an infrared motion sensor turns on the devices each time a patient enters the room. The patient urinates according to the timely instructions on the visible display and voided urine directly flows into a urinal. The devices are automatically turned off 5 min after the patient leaves the room. With the use of our system, men already acquainted with uroflowmetry could perform self-administered uroflowmetry any time in private. The system was considered useful for improving the quality of patient service.

Transurethral resection is usually performed using an all-in-one drape with a fluid collection pouch, drainage port and hose. Gravity drainage of irrigation fluid through the hose is often hampered, resulting in fluid retention in the pouch. We applied a siphon principle to facilitate fluid drainage by making a U-shaped bend near the distal end of the hose, using an adhesive tape, and hooking the distal end of inverted U shape on the edge of bucket placed on the floor. When the hose is filled with irrigation fluid up to the crest of the siphon, fluid flow driven by atmospheric pressure continues until the pouch is evacuated. Repriming and restarting occur automatically throughout the operation. This simple device has virtually eliminated fluid retention in the pouch and proved to be especially useful in transurethral prostatectomy, which requires a large amount of irrigation fluid.

Aim: Cutaneous ureterostomy is the least invasive method of urinary diversion, but it carries a risk of stomal stenosis. We retrospectively examined the long-term outcome of tubeless cutaneous ureterostomy by the Toyoda method., Methods: Since 1983, the Toyoda cutaneous ureterostomy has been performed in 97 patients (169 renal units) with a minimum follow up of 3 months. The ureteral patency rate was reviewed according to whether the stomal type was single (one ureter, one stoma) or double-barrel (two ureters, one stoma)., Results: After a median follow up of 23 months (range 3 to 169), a tubeless condition was achieved in 102 (82%) of 124 renal units associated with double-barrel stoma and in 35 (78%) of 45 renal units associated with single stoma. Although mild to moderate hydronephrosis was observed in 19% of patients, serum creatinine levels did not change after a minimum of 12 months after surgery (median 35)., Conclusions: A high ureteral patency rate was achieved with cutaneous ureterostomy using the Toyoda method. This procedure, especially double-barrel stomal creation, is a reasonable alternative to other forms of urinary diversion in patients at high risk.

We describe 2 cases of obstructive azoospermia associated with situs inversus and sinopulmonary infection due to ciliary defects. Electron microscopy of testicular sperm flagella demonstrated normal morphology with nine peripheral doublets surrounding a central pair and complete sets of inner and outer dynein arms. Electron microscopy of the nasal mucosa revealed partial defects of the dynein arms of cilia, although the "9+2" morphology was preserved. Our cases were considered unique variants of Young's syndrome but also had characteristic features of Kartagener syndrome, and thus support the hypothesis that Young's syndrome has a genetic etiology similar to that of Kartagener syndrome.

Objectives: To retrospectively correlate the magnetic resonance imaging (MRI) diagnosis with the surgical findings and/or clinical outcomes in patients presenting with an acute scrotum., Methods: From January 1997 to June 2004, 39 selected patients presenting with an acute scrotum underwent dynamic contrast-enhanced subtraction MRI as a 24-hour stand-by examination. The MRI diagnosis was based solely on the presence or absence of testicular contrast enhancement, without respect to the clinical history or physical examination findings., Results: Contrast enhancement of the affected and normal testes could be accurately compared in all cases. The MRI diagnosis was testicular torsion (no testicular contrast enhancement, n = 13), nonspecific (reduced to normal enhancement, n = 10), appendiceal torsion (n = 3), and epididymitis (n = 13). The surgical findings and/or subsequent clinical outcomes showed that MRI diagnosis of testicular torsion was accurate in all 13 cases. Furthermore, exploration revealed testicular torsion in 1 case with very little enhancement. The sensitivity and specificity of MRI in the diagnosis of testicular torsion was 93% (13 of 14) and 100% (25 of 25), respectively. Although MRI detected testicular perfusion, 5 of the 6 patients with clinical suspicion of intermittent torsion underwent surgical exploration., Conclusions: MRI is a highly accurate imaging modality for the diagnosis of testicular torsion. However, it could not be used to rule out intermittent torsion and the clinical use of negative findings for an MRI torsion test was less than 100% specificity. Because this was a preliminary retrospective study, the true clinical value of MRI should be evaluated by prospective studies.

Objective: To examine an unusual case of Klinefelter's syndrome., Design: Case report., Setting: An infertility clinic at a private hospital., Patient(s): A patient with nonmosaic Klinefelter's syndrome who had had a child with his ex-wife without artificial reproductive technologies., Intervention(s): Karyotyping with peripheral blood lymphocytes, microdissection testicular sperm extraction, and intracytoplasmic sperm injection (ICSI)., Main Outcome Measure(s): Sperm count and testicular histopathology., Result(s): Semen analysis revealed severe oligoasthenozoospermia. Intracytoplasmic sperm injection using ejaculated spermatozoa was performed, and successful pregnancy and delivery were achieved. Two years later, multiple semen analyses revealed azoospermia. Microdissection testicular sperm extraction was performed, and motile sperm were successfully retrieved. Unfortunately, the first cycle of ICSI using testicular sperm failed. Testicular histopathology was compatible with decreased spermatogenesis., Conclusion(s): This is a case of a man with nonmosaic Klinefelter's syndrome who exhibited progressive decline of spermatogenesis. This case suggests the merit of early sperm retrieval and cryopreservation for future management of infertility in Klinefelter's syndrome.

We present the case of a patient with Klinefelter syndrome and priapism after testosterone administration. The patient underwent testicular sperm extraction for interventional fertilization, but no sperm were found. Because he had given up trying to father a child and his testosterone level had been low, testosterone replacement therapy was started with testosterone enanthate. After the third injection, he presented with low-flow priapism. Conservative management was successful, and no recurrence developed during the next 15 months. Testosterone replacement therapy carries some risk of priapism even for patients with Klinefelter syndrome.

Objectives: To evaluate the efficacy and safety of acute normovolemic hemodilution (ANH) in patients undergoing radical prostatectomy. Preoperative autologous blood donation (PAD) is widely accepted as a means of reducing the need for allogeneic blood transfusion in radical prostatectomy. ANH is an alternative method for obtaining autologous blood., Methods: On the basis of our previous report that showed the equivalence of PAD and ANH, we prospectively replaced PAD with ANH as a standard practice for radical prostatectomy after September 1999. Of 174 radical prostatectomy patients between September 1999 and June 2004, 153 underwent ANH alone, 15 chose to receive both PAD and ANH, and ANH was contraindicated in 15 because of comorbidities., Results: For the 153 patients undergoing ANH alone, 1032 +/- 201 mL of autologous blood was collected. With an intraoperative blood loss of 1602 +/- 926 mL, 14 patients (9.2%) received allogeneic blood transfusion. The preoperative, intraoperative nadir, and postoperative hematocrit value was 43.6% +/- 3.4%, 25.8% +/- 3.8%, and 31.9% +/- 4.3%, respectively. No patient experienced a perioperative adverse event related to hemodilution or blood transfusion., Conclusions: Our continued experience has shown that ANH is a safe and effective means of autologous blood procurement. Given its advantages, including lower cost, lower risk, and simplicity, we conclude that ANH can replace conventional PAD for use in radical prostatectomy, although the true value of ANH should be determined by future randomized studies including a no-treatment control group.

Selective transcatheter embolization using an interlocking detachable coil was performed in two cases with renal artery aneurysms. Case 1, a 73-year-old male, was referred to our department complaining of macrohematuria persisting for three days. Case 2, a 52-year-old female, visited our department because calcifications in both renal pedicle areas were found in a health check up. Drip infusion pyelography (DIP) and computerized tomography (CT) revealed in case 1 an aneurysm which was 11 x 10 cm in diameter with nearly circumferential calcification in the right renal pedicle area and in case 2 two aneurysms, one 12 x 10 cm in the right and one 22 x 20 cm in the left with imperfect calcification. Enhanced CT confirmed blood flow in the aneurysms. Because abdominal surgery, was considered to be a highrisks in both cases 1 and 2 the coil embolization was performed. The patients have been followed up after the embolization without any particular complications or changes in the coil location.