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Introduction Metastases from renal cell carcinoma develop in various organs. However, the breadth of discrepancy in response to immune checkpoint inhibitors across tumor sites within the same individual remains unclear. Patients and methods We reviewed 50 patients with metastatic renal cell carcinoma who had target lesions at multiple sites and received nivolumab monotherapy (n = 36) or nivolumab plus ipilimumab (n = 14). When the best overall response in tumor burden increased at one site but decreased at other sites, the response was defined as a dissociated response. The response was evaluated according to the Response Evaluation Criteria in Solid Tumors 1.1, and patients who met the definition of dissociated response were categorized as dissociated response. The rate of dissociated response and prognosis were evaluated. Results Eight of 36 (22%) and 4 of 14 (29%) patients treated with nivolumab and nivolumab plus ipilimumab were categorized as having dissociated response, respectively. The median overall survival of the patients treated with nivolumab was 20.2 months for those with a partial response, 6.8 months for those with stable disease, and 13.2 months for those with progressive disease, while dissociated response was not reached. There was no significant difference in the median overall survival between patients categorized as having progressive disease and those with dissociates response (P = 0.224). Conclusion A certain proportion of patients with metastatic renal cell carcinoma show dissociated response when treated with immune checkpoint inhibitors. The prognosis of patients with dissociated response and progressive disease was not shown to be significantly different.

The optimal timing of switching from platinum-based chemotherapy to pembrolizumab in patients with advanced urothelial carcinoma (UC) remains unclear.Thirty-four patients who received pembrolizumab as second-line treatment after first-line platinum-based chemotherapy were retrospectively evaluated.According to overall survival (OS) from pembrolizumab, there was a significant difference between ≤4 and4 prior chemotherapy cycles (7.0 and 25.5 months, p=0.034), but not between ≤6 and6 cycles (11.3 and 6.6 months, p=0.658). According to the Cox proportional hazards regression model, the number of chemotherapy cycles was not correlated with better OS in pembrolizumab-treated patients. According to the OS from the first-line treatment, there was a significant difference between ≤4 and4 prior chemotherapy cycles (17.3 and 37.1 months, p0.001), but not between ≤6 and6 cycles (18.6 and 27.3 months, p=0.276).The optimal timing of switching from platinum-base chemotherapy to pembrolizumab in advanced UC is around six cycles.

Introduction: Radiation-associated sarcoma (RAS) is one of the most life-threatening complications associated with the treatment of malignant neoplasms. Because all RAS patients have a history of radiotherapy, there have been no effective treatment options when RAS is not completely resected. Methods: We retrospectively reviewed 20 RAS patients, including 4 unresectable cases treated by carbon ion radiotherapy (CIRT). Results: The primary diseases targeted by radiotherapy included malignant lymphoma (n = 4), cervical cancer (n = 3), pharyngeal cancer (n = 3), breast cancer (n = 2), lung cancer (n = 1), rectal cancer (n = 1), maxillary cancer (n = 1), synovial sarcoma (n = 1), and benign neoplasms (n = 4). The histological diagnoses of RAS included osteosarcoma (n = 8), leiomyosarcoma (n = 3), undifferentiated pleomorphic sarcoma (n = 3), rhabdomyosarcoma (n = 1), angiosarcoma (n = 1), malignant peripheral nerve sheath tumor (n = 1), spindle cell sarcoma NOS (n = 1), and sarcoma not further specified (n = 2). The median survival time from the diagnosis of RAS was 26 months. Eleven patients underwent surgery. Five of these patients achieved a continuous disease free (CDF) status or showed no evidence disease. Four patients underwent CIRT. One of these patients with leiomyosarcoma achieved a CDF status, and the other patient with osteosarcoma achieved a partial response. On the other hand, 2 patients experienced grade 3 toxicities that required surgical treatment. Conclusion: RAS originates from various types of diseases that are treated by radiotherapy and shows diverse pathological features. Complete resection achieves a good prognosis. CIRT can be an effective and feasible option for unresectable RAS.

Nobuki Furubayashi,1 Akinori Minato,2 Takahito Negishi,1 Naotaka Sakamoto,3 Yoohyun Song,4 Yoshifumi Hori,5 Toshihisa Tomoda,6 Shingo Tamura,7 Kentaro Kuroiwa,5 Narihito Seki,4 Naohiro Fujimoto,2 Motonobu Nakamura1 1Department of Urology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan; 2Department of Urology, University of Occupational and Environmental Health, Kitakyushu, Japan; 3Department of Urology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; 4Department of Urology, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan; 5Department of Urology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan; 6Department of Urology, Oita Prefectural Hospital, Oita, Japan; 7Department of Medical Oncology, National Hospital Organization Kyushu Medical Center, Fukuoka, JapanCorrespondence: Nobuki FurubayashiDepartment of Urology, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-ku, Fukuoka, 811-1395, JapanTel +81-92-541-3231Fax +81-92-551-4585Email nobumduro@gmail.comBackground: To evaluate the association of clinical outcomes with posttreatment changes in the relative eosinophil count (REC) and neutrophil-to-eosinophil ratio (NER) in patients with advanced urothelial cancer (UC) treated with pembrolizumab.Materials and Methods: We retrospectively analyzed 105 patients with advanced UC who received pembrolizumab after the failure of platinum-based chemotherapy. The REC and NER before and three weeks after pembrolizumab were recorded. A receiver operating characteristic curve was used to determine the optimal cut-off values for analyzing the risk.Results: There were no significant differences in the overall survival (OS) between the REC ≥ 4.8% and < 4.8% groups and the NER ≥ 13.7 and < 13.7 groups before pembrolizumab (p=0.997 and 0.669, respectively). However, a significant difference in the OS was confirmed between the increased and decreased REC groups and between the decreased and increased NER groups at 3 weeks after pembrolizumab (p< 0.001 and 0.002, respectively). Multivariate analyses revealed that an Eastern Cooperative Oncology Group Performance Status ≥ 2 (P=0.003), albumin < 3.7 g/dl (p=0.002), LDH > 246 U/L (p=0.011), disease site ≥ 3 organs (p=0.019), decreased posttreatment REC (3 weeks later) (p=0.002) and increased posttreatment NER (3 weeks later) (p=0.022) were independent prognostic factors for a worse OS.Conclusion: An increased REC and decreased NER after pembrolizumab may be significant early predictive markers of improved clinical outcomes in patients with advanced UC receiving pembrolizumab.Keywords: urothelial carcinoma, pembrolizumab, eosinophil, neutrophil-to-eosinophil ratio

Nobuki Furubayashi,1 Akinori Minato,2 Takahito Negishi,1 Naotaka Sakamoto,3 Yoohyun Song,4 Yoshifumi Hori,5 Toshihisa Tomoda,6 Mirii Harada,2 Shingo Tamura,7 Hiroki Kobayashi,1 Yamato Wada,1 Kentaro Kuroiwa,5 Narihito Seki,4 Naohiro Fujimoto,2 Motonobu Nakamura1 1Department of Urology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan; 2Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; 3Department of Urology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; 4Department of Urology, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan; 5Department of Urology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan; 6Department of Urology, Oita Prefectural Hospital, Oita, Japan; 7Department of Medical Oncology, National Hospital Organization Kyushu Medical Center, Fukuoka, JapanCorrespondence: Nobuki Furubayashi, Department of Urology, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-ku, Fukuoka, 811-1395, Japan, Tel +81-92-541-3231, Fax +81-92-551-4585, Email nobumduro@gmail.comBackground: To evaluate the eosinophil changes, efficacy and safety of pembrolizumab treatment in advanced urothelial carcinoma patients of older age and those with a poor performance status (PS).Materials and Methods: Consecutive patients with advanced UC who received pembrolizumab after the failure of platinum-based chemotherapy between January 2018 and June 2021 were retrospectively examined.Results: 105 patients (median age, 72 years), 71.4% of whom were men, were enrolled. Patients of ≥ 75 years of age were considered to be older patients (n=40), and patients with PS ≥ 2 were considered to have a poor PS (n=10). The objective response and disease control rates were 42.5% and 52.5%, respectively, in older patients and 0% and 10.0%, respectively, in patients with a poor PS. Overall survival (OS) in the older and younger groups did not differ to a statistically significant extent. However, a poor PS was significantly associated with poor survival. Safety analyses demonstrated no significant difference in the occurrence of any immune-related adverse events (irAEs), including grade ≥ 3, between the older and younger groups. However, a poor PS was significantly associated with the low occurrence of any irAEs. The change of the eosinophil count, the increase of the relative eosinophil count (REC) and the decrease of the neutrophil-to-eosinophil ratio (NER) did not differ to a statistically significant extent between the older and younger groups, but showed significant differences between the poor and good PS (PS 0– 1) groups.Conclusion: Pembrolizumab for advanced UC demonstrated similar changes in the eosinophil count, efficacy and toxicity in both older and younger patients. In patients with a poor PS, although toxicity was significantly lower, survival was significantly worse, and neither an increase in REC nor a decrease in NER were observed, but these values showed significant changes in patients with a good PS.Keywords: urothelial carcinoma, pembrolizumab, age, performance status, immune-related adverse events, relative eosinophil count, neutrophil-to-eosinophil ratio

Background/aim Nivolumab monotherapy for advanced/metastatic renal cell carcinoma (RCC) shows a survival benefit. The purpose of this study was to evaluate tumor responses to nivolumab in various metastatic and primary sites in patients with RCC. Patients and methods We retrospectively reviewed 68 patients who underwent nivolumab monotherapy after one or more regimens of targeted therapy for advanced/metastatic RCC. The site-specific response was evaluated and progression-free survival was estimated. Results The site-specific overall response rates (ORRs) were as follows: lung (36%), bone (5%), lymph node (33%), liver (50%), adrenal gland (29%), pancreas (33%), and brain (0%). The ORR of bone metastasis was significantly worse in comparison to lung and liver metastases (p=0.017, 0.008). The site-specific median progression-free survival times were as follows: lung (5.1 months), bone (not reached), lymph node (not reached), and liver (17.5 months). Conclusion Responses to nivolumab may vary depending on metastasized organs.

Nobuki Furubayashi, Takahito Negishi, Akihiro Miura, Nobutaka Nakamura, Motonobu Nakamura Department of Urology, National Hospital Organization Kyushu Cancer Center, Fukuoka, JapanCorrespondence: Nobuki Furubayashi Tel +81-92-541-3231Fax +81-92-551-4585Email furubayashi-jua@umin.ac.jpBackground: To evaluate the organ-specific therapeutic effect of paclitaxel and carboplatin (TC) chemotherapy in patients who failed platinum-based chemotherapy and pembrolizumab for metastatic urothelial carcinoma (UC).Patients and Methods: We retrospectively reviewed the data of patients with metastatic UC who had received TC chemotherapy after the failure of platinum-based chemotherapy and pembrolizumab. The RECIST 1.1 criteria were used to assess the objective response to pembrolizumab and TC chemotherapy at tumor sites.Results: We analyzed 8 patients (male, n=5; female, n=3; median age, 65 years old). All patients except one had visceral metastasis. The median overall survival for TC was 10.9 months (95% confidence interval, 1.0‑12.7 months), and the objective response rate was 25.0% (partial response [PR]: 2 cases). The metastatic organs were the lymph nodes in 5 cases (number of tumor sites: 8), lung in 4 cases (number of tumor sites: 12), liver in 3 cases (number of tumor sites: 14), bone in 3 cases (number of tumor sites: 12), and primary lesion in 3 cases (number of tumor sites: 3). There were no cases of a complete response or progressive disease in any metastatic organs due to TC chemotherapy. A PR was seen in 2 cases of lymph node metastasis (40.0%), 2 cases of lung metastasis (50.0%), and 2 cases of liver metastasis (66.7%). All 3 cases of bone metastasis showed stable disease, as did all 3 cases of primary lesion. Improvement in the therapeutic effect of TC chemotherapy compared with pembrolizumab was observed in 2 cases (40.0%) of lymph node metastasis, 2 cases (50.0%) of lung metastasis, and 1 case (33.3%) of liver metastasis.Conclusion: Lymph node, lung, and liver metastases may respond to TC chemotherapy, even if exacerbated with pembrolizumab after platinum-based chemotherapy in metastatic UC.Keywords: urothelial carcinoma, platinum-based chemotherapy, pembrolizumab, paclitaxel, carboplatin, organ-specific therapeutic effect

Nobuki Furubayashi,1 Akinori Minato,2 Takahito Negishi,1 Naotaka Sakamoto,3 Yoohyun Song,4 Yoshifumi Hori,5 Toshihisa Tomoda,6 Mirii Harada,2 Shingo Tamura,7 Akihiro Miura,1 Hiroki Komori,1 Kentaro Kuroiwa,5 Narihito Seki,4 Naohiro Fujimoto,2 Motonobu Nakamura1 1Department of Urology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan; 2Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; 3Department of Urology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; 4Department of Urology, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan; 5Department of Urology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan; 6Department of Urology, Oita Prefectural Hospital, Oita, Japan; 7Department of Medical Oncology, National Hospital Organization Kyushu Medical Center, Fukuoka, JapanCorrespondence: Nobuki Furubayashi, Department of Urology, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-ku, Fukuoka, 811-1395, Japan, Tel +81-92-541-3231, Fax +81-92-551-4585, Email nobumduro@gmail.comBackground: To evaluate the association between immune-related adverse events (irAEs) and the clinical outcomes and also between irAEs and the post-treatment changes in the relative eosinophil count (REC) in advanced urothelial carcinoma (UC) patients treated with pembrolizumab.Materials and Methods: This retrospective study analyzed 105 advanced UC patients treated with pembrolizumab after disease progression on platinum-based chemotherapy between January 2018 and June 2021. The association between the occurrence of irAEs and the efficacy of pembrolizumab was investigated. The change in the REC from before the initiation of pembrolizumab therapy, to three weeks after treatment and the incidence of irAEs were determined.Results: Overall irAEs were associated with a significantly higher objective response rate (ORR) (58.8% vs 25.4%, P< 0.001), a longer progression-free survival (PFS) (25.1 months vs 3.1 months, P< 0.001) and overall survival (OS) (31.2 months vs 11.5 months, P< 0.001) compared to patients without irAEs; however, grade ≥ 3 irAEs were not associated with the ORR (36.4% vs 36.2%, P=0.989), PFS (9.5 vs 5.5 months, P=0.249), or OS (not reached vs 13.7 months, P=0.335). Compared to a decreased REC at 3 weeks after pembrolizumab, an increased relative REC at 3 weeks was not associated with the incidence of any-grade irAEs (32.3% vs 32.5%, P=0.984) or of grade ≥ 3 irAEs (10.8% vs 10.0%, P=0.900). Multivariate analyses revealed a female sex (P=0.005), Eastern Cooperative Oncology Group Performance Status ≥ 1 (P=0.024), albumin < 3.7 g/dl (P< 0.001), decreased REC (3 weeks later) (P< 0.001), and the absence of irAEs of any grade (P=0.002) to be independently associated with a worse OS.Conclusion: Patients with irAEs showed a significantly better survival compared to patients without irAEs in advanced UC treated with pembrolizumab. An increased posttreatment REC may be a marker predicting improved clinical outcomes and it had no significant relationship with the incidence of irAEs.Keywords: urothelial carcinoma, pembrolizumab, immune-related adverse events, relative eosinophil count

Background: Since December 2017, pembrolizumab has been approved in Japan as a second-line treatment for radical unresectable urothelial carcinoma (UC) that has become exacerbated after chemotherapy by the international randomized phase 3 trial, KEYNOTE-045. The aim of this study was to evaluate the oncological efficacy and safety of pembrolizumab after failure of platinum-based chemotherapy in Japanese patients with advanced UC in real-world clinical practice. Methods: A total of 34 patients who received pembrolizumab after the failure of platinum-based chemotherapy for advanced urothelial carcinoma at four institutions between January 2018 and August 2019 were retrospectively evaluated. In all patients, UC was histopathologically diagnosed, and disease progression after platinum-based chemotherapy was radiologically confirmed. Results: The median follow-up period was 7.7 months. The objective response rate, median progression-free survival, and median overall survival were 20.6%, 3.3 months, and 11.7 months, respectively. Regarding the toxicities associated with pembrolizumab, adverse events (AEs) of any grade occurred in 61.8%, and grade 3 AEs occurred in 23.5%; grade ? 4 AEs did not occur in any patients. Univariate analyses revealed that the Eastern Cooperative Oncology Group Performance Status, neutrophil/lymphocyte ratio, liver metastases, and time from previous chemotherapy were prognostic variables. Multivariate analyses revealed that liver metastases (positive: hazard ratio, 4.23; 95% confidence interval, 1.48 - 12.08; P < 0.01) and time from previous chemotherapy (? 3 months: hazard ratio, 5.06; 95% confidence interval, 1.43 - 17.91; P = 0.01) were independent prognostic factors. Conclusions: In this real-world clinical study, these findings concerning the efficacy and safety of pembrolizumab for advanced UC in Japanese patients were comparable to those of the open-label, international, phase 3 trial KEYNOTE-045. Liver metastases and time from previous chemotherapy were independent prognostic factors in the present study. J Clin Med Res. 2020;12(5):300-306 doi: https://doi.org/10.14740/jocmr4162

Although variant urothelial carcinoma (VUC, defined here as urothelial carcinoma with any histological variant) is a clinically aggressive disease, the efficacy of pembrolizumab against VUC is not well characterized. This study assessed the therapeutic response and survival outcomes in patients with advanced VUC treated with pembrolizumab for unresectable recurrent or metastatic disease.We retrospectively evaluated 103 patients with advanced bladder and upper urinary tract cancer who received pembrolizumab after failure of platinum-based chemotherapy at 6 institutions between January 2018 and June 2021. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were compared between patients with pure urothelial carcinoma (PUC) and those with VUC.We identified 81 and 22 patients with PUC and VUC, respectively. Squamous differentiation (n = 14) was the most common variant element, followed by glandular differentiation (n = 3) and micropapillary variant (n = 3). Baseline characteristics were comparable between the groups. Patients with VUC showed significantly better ORR (59.1% vs. 29.6%, P = .014) and comparable DCR (68.2% vs. 49.4%, P = .150) compared to those with PUC. There were no significant differences between the PUC and VUC groups with respect to PFS (median 5.0 months vs. 10.4 months, P = .222) or OS (median 13.5 months vs. 23.8 months, P = .497).Response of VUC to pembrolizumab was not inferior to that of PUC in patients with advanced-stage bladder and upper urinary tract cancer.

Background/Aim: Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare subtype of renal cell carcinoma and generally considered a low-grade renal epithelial neoplasm. However, MTSCC with distant metastases often shows a poor prognosis. This is the first reported case of cytoreductive nephrectomy after nivolumab plus ipilimumab combination treatment. Case Report: A 26-year-old man had a 72-mm tumor at the left kidney with multiple osteolytic bone metastases. A biopsy of the renal tumor and bone metastases resulted in the diagnosis of MTSCC of the kidney with bone metastases. After nivolumab plus ipilimumab combined treatment, he underwent cytoreductive nephrectomy. The excised specimen showed higher PD-L1 expression in the spindle components than in the tubular components, but CD4- and CD8-positve T-cells showed greater infiltration in the tubular components than the spindle components. Conclusion: Combination immunotherapy of nivolumab and ipilimumab may be an effective treatment option for metastatic MTSCC of the kidney.

Background/aim Despite the presence of a mixed response (MR) in patients with urothelial carcinoma (UC) who receive immune checkpoint inhibitors, the clinical outcome of these patient has not been reported. We evaluated the clinical outcome of MR to pembrolizumab for advanced UC. Patients and methods Advanced UC patients who received pembrolizumab after platinum-based chemotherapy failure with measurable disease in multiple organs were retrospectively analyzed. Results Among 31 patients, MR [including progressive disease (PD)+complete response (CR) or partial response (PR)] was confirmed in 4 (12.9%). The median overall survival (OS) of the CR+PR (including CR+SD±PR), stable disease (SD), PD (including PD±SD) and MR groups was 16.0, 5.1, 5.4 and 4.3 months, respectively. There was no significant difference in the OS between the MR and CR+PR response groups (log-rank test, p=0.069). Conclusion A mixed response to pembrolizumab in advanced UC was not uncommon. Despite the non-significant difference in the OS between the mixed and CR+PR response groups, the OS of the MR group tended to be similar to that of the SD and PD response groups.

Background: Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare subtype of renal cell carcinoma (RCC) and generally considered a low-grade renal epithelial neoplasm composed of tubules, spindle cells, and extracellular mucin. MTSCC with distant metastases has been reported, with some cases showing a poor prognosis. While only a few case reports regarding the treatment of metastatic MTSCC have been reported, targeted agents and monotherapy of immune checkpoint inhibitors have shown some efficacy. To our knowledge, this is the first reported case of metastatic MTSCC of the kidney treated with combination therapy of nivolumab plus ipilimumab.Case presentation: A 26-year-old man consulted our hospital after a 72-mm tumor was detected at the upper pole of the left kidney with multiple osteolytic bone metastases by computed tomography (CT). A CT-guided biopsy of the renal tumor and bone metastases resulted in a diagnosis of MTSCC of the kidney with bone metastases (cT2aN0M1) and an ‘intermediate risk’ according to the International Metastatic Renal Cell Carcinoma Database Consortium criteria. He therefore received combination therapy of nivolumab plus ipilimumab therapy. After 4 cycles of combination nivolumab plus ipilimumab and 9 cycles of nivolumab monotherapy, he underwent cytoreductive nephrectomy because the tumor had shrunk, and sclerotic changes in the bone metastases were noted. In the excised specimen, the programmed cell death ligand 1 expression was higher in the spindle components than in the tubular components, but CD4- and CD8-positve T cells showed greater infiltration in the tubular components than in the spindle components. Furthermore, CD-4- and CD-8-positive T cells in both components of the resected specimen showed greater infiltration than they had at the pretreatment biopsy of the renal tumor and bone metastases.Conclusions: Combination immunotherapy of nivolumab and ipilimumab may be an effective treatment option for metastatic MTSCC of the kidney.

Nobuki Furubayashi,1 Takahito Negishi,1 Naotaka Sakamoto,2 Hozumi Shimokawa,3 Futoshi Morokuma,4 Yoohyun Song,5 Yoshifumi Hori,6 Toshihisa Tomoda,7 Noriaki Tokuda,4 Narihito Seki,5 Kentaro Kuroiwa,6 Motonobu Nakamura1 1Department of Urology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan; 2Department of Urology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; 3Department of Medical Oncology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; 4Department of Urology, Saga-ken Medical Centre Koseikan, Saga, Japan; 5Department of Urology, Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan; 6Department of Urology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan; 7Department of Urology, Oita Prefectural Hospital, Oita, JapanCorrespondence: Nobuki FurubayashiDepartment of Urology, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-Ku, Fukuoka, 811-1395, JapanTel +81-92-541-3231Fax +81-92-551-4585Email nobumduro@gmail.comBackground: To evaluate the organ-specific therapeutic effect of pembrolizumab after the failure of platinum-based chemotherapy for advanced urothelial carcinoma (UC).Materials and Methods: Patients with advanced UC who received pembrolizumab after the failure of platinum-based chemotherapy and who had measurable disease were retrospectively analyzed. The objective response rate (ORR) and organ-specific response rate (OSRR) were evaluated according to Response Evaluation Criteria in Solid Tumors, version 1.1.Results: We analyzed 69 patients (male, n=51; median age, 71 years) with 226 metastases. The ORR was 23.2%. In total, 32, 31, 16, 14, 13 and 7 patients had measurable lung (OSSR 31.3%), lymph node (OSSR 29.0%), local recurrence (OSSR 12.5%), primary tumor organ (OSSR 7.1%), liver (OSSR 23.1%) and bone (OSSR 28.6%) disease, respectively. The median overall survival (OS) for pembrolizumab was 10.9 months (95% confidence interval, 5.9‑13.7 months). Regarding organ-specific OS, a Log rank test significant differences in OS were confirmed between patients with and without primary tumor organ disease (p=0.046) and liver metastasis (p< 0.001).Conclusion: Metastases and primary tumor organ disease showed different tumor responses to pembrolizumab. The most prominent tumor response was found in lung metastasis and the least response was found in primary organ sites. The mechanisms of these different responses were unclear and there does not appear to be a constant trend between tumor shrinkage and OS in tumor sites. Further studies are needed.Keywords: urothelial carcinoma, platinum-based chemotherapy, pembrolizumab, organ-specific response rate, tumor microenvironment

Pembrolizumab has been available for the treatment of radical resectable urothelial carcinoma (UC) when it is exacerbated after chemotherapy since December 2017 in Japan. However, the efficacy of chemotherapy for cases progressing after pembrolizumab is unclear. The present study compared the outcomes and toxicities in patients with metastatic UC after failure of platinum-based chemotherapy and pembrolizumab, who were selected to receive paclitaxel and carboplatin (TC) chemotherapy, with those in patients who received the best supportive care (BSC). A total of 36 patients received pembrolizumab for metastatic UC at four institutions between January 2018 and August 2019. Of the 21 patients who progressed after pembrolizumab, 7 received TC chemotherapy (TC group) and 14 selected BSC (BSC group). The median observation period was 4.1 months. The 7 aforementioned patients who received TC chemotherapy (4 male and 3 female; median age, 62 years; range, 57-79 years) were analyzed in the present study. The ECOG performance status was 0 in three patients, 1 in one patient, 2 in two patients and 3 in one patient. Two patients had upper urinary tract UC, two had bladder UC and three had both types of UC. Six patients had visceral metastasis. The number of chemotherapy regimens before pembrolizumab was one in four patients, two in two patients and three in one patient. The objective response rate was 28.6% (partial response, 2 patients; stable disease, 4 patients; progressive disease, 1 patient), the median progression-free survival time was 3.4 months and the median overall survival time was 10.9 months (vs. 2.7 months in BSC group; P=0.0156). Although grade ≥3 adverse events developed in five patients, there were no treatment-associated deaths. The present results suggested that TC chemotherapy may be a preferred option for patients who require aggressive treatment after the failure of platinum-based chemotherapy and pembrolizumab.

BackgroundTo evaluate the optimal timing of sequencing from platinum-based chemotherapy to pembrolizumab with advanced urothelial carcinoma (UC) in real-world clinical practice.MethodsA total of 34 patients who received pembrolizumab as second-line treatment after first-line platinum-based chemotherapy for advanced UC at 4 institutions between January 2018 and August 2020 were retrospectively evaluated.ResultsThe gemcitabine and cisplatin regimen was administered to 27 patients (79.4%), and the gemcitabine and carboplatin regimen was administered to 6 patients (20.6%). Regarding the number of chemotherapy cycles administered before pembrolizumab, ≤4 cycles were administered to 22 patients (64.7%), 5-6 cycles to 4 patients (11.8%) and ≥7 cycles to 8 patients (23.5%). When the number of cycles was divided into 4 courses, the median overall survival (OS) for ≤4 and >4 prior chemotherapy cycles was 7.0 months and 25.5 months, respectively (P=0.034). When the number of cycles was divided into 6 courses, the median OS for ≤6 and >6 prior chemotherapy cycles was 11.3 months and 6.6 months, respectively (P=0.658). Multivariate analyses for the OS of pembrolizumab revealed that the Eastern Cooperative Oncology Group Performance Status (≥2: hazard ratio [HR] 9.994, 95% CI=1.854-53.879, P=0.007), liver metastases (positive: HR 3.751, 95% CI=0.958-13.603, P=0.047) and time from previous chemotherapy (≥3 months: HR 0.094, 95% CI=0.023-0.357, P4 prior chemotherapy cycles was 17.3 months and 37.1 months, respectively (P6 prior chemotherapy cycles was 18.6 months and 27.3 months, respectively (P=0.276).ConclusionsThese real-world findings suggest that the optimal timing of sequencing from platinum-base chemotherapy to pembrolizumab in advanced UC is around six cycles, even if no exacerbations are observed with first-line chemotherapy.

Enlarged bone metastasis from renal cell carcinoma (RCC) can cause skeletal-related events, and thus treatment to inhibit the growth of bone metastases is often required. Although radiotherapy for RCC bone metastases can achieve a certain degree of local control, evidence is lacking regarding the effects of systemic therapy to improve bone metastasis. The present study aimed to assess the treatment efficacy of targeted therapy and immune checkpoint inhibitors, and to determine whether systemic therapy without radiotherapy can shrink bone metastases of RCC. The present study retrospectively reviewed 44 patients with RCC with bone metastases treated via systemic therapy, including targeted therapy or immune checkpoint inhibitors. Patients were divided into two groups: Those who underwent systemic therapy with radiotherapy for bone lesions (n=29); and those who underwent systemic therapy without radiotherapy for bone lesions (n=15). The radiographical efficacy of systemic therapy and the time to progression of bone metastases were compared between groups. The overall response rate of systemic therapy with radiotherapy was 44%, and in total, 13 patients demonstrated a partial response. Only one patient (6%) had a partial response among those who were treated via systemic therapy without radiotherapy. The time to progression of bone metastasis was 9.5 and 2.1 months in patients treated with and without radiotherapy, respectively (P

The aim of the present study was to investigate the association between clinical parameters and the overall survival (OS) of Japanese patients with metastatic renal cell carcinoma (mRCC). The medical records of 59 consecutive mRCC patients receiving molecular-targeted therapy were retrospectively assessed. Kaplan-Meier and log-rank analyses were used to evaluate the progression-free survival (PFS) and OS, and a multivariate Cox proportional hazard model was used to analyze the clinical parameters for their prognostic relevance. The median OS for all patients was 23.7 months [95% confidence interval (CI): 17.9–30 months], and the median OS stratified by the Memorial Sloan Kettering Cancer Center risk classification was 28.5, 20.9 and 8.1 months for the favorable-, intermediate- and poor-risk groups, respectively (P=0.137; degree of freedom: 2). Univariate analyses identified prior nephrectomy, number of metastatic sites, anemia, best response to first-line treatment and PFS with first-line treatment as prognostic variables. Multivariate analyses identified number of metastatic sites [2: hazard ratio (HR)=3.351, 95% CI: 1.460–8.201, P=0.004; ≥3: HR=6.397, 95% CI: 1.939–20.209, P=0.003], time from diagnosis to therapy (≥1 year: HR=0.334, 95% CI: 0.137–0.755, P=0.008), PFS with first-line treatment (≥5.1 months: HR=0.353, 95% CI: 0.156–0.766, P=0.008) and number of lines of molecular-targeted agents (≥3: HR=0.248, 95% CI: 0.091–0.664, P=0.006) as independent prognostic factors. The results indicated that the PFS of first-line treatment may be a meaningful intermediate endpoint for OS in patients with mRCC who received treatment with molecular-targeted therapy.

The combined immunotherapy of nivolumab and ipilimumab causes a variety of autoimmune-related adverse events (irAEs). The current report details a 70-year-old woman with clear cell renal cell carcinoma metastasis in the lung. Two weeks after two courses of treatment, the patient complained of headache, dizziness and nausea. Cerebrospinal fluid (CSF) analysis revealed an elevated protein level of 195 mg/dl and a significantly elevated white blood cell (WBC) count of 830/mm3 (lymphocytes, 825/mm3; neutrophils, 5/mm3). The results excluded malignancy and infection. The patient was diagnosed with aseptic meningitis and was administered intravenous prednisolone (1 mg/kg/day). On the 49th day of the 2nd course of treatment, no recurrence of clinical symptoms was exhibited during maintenance oral steroid treatment (prednisolone 10 mg/day) and CSF analysis revealed that the WBC count had dropped to 44/mm3 (lymphocytes only). Therefore, the 3rd course of treatment was readministered the next day. After two weeks, the patients again complained of nausea, anorexia and fatigue. CSF analysis demonstrated that the WBC count was not increased from the result obtained previously. However, brain MRI scans revealed the mild diffuse enlargement of the pituitary and endocrine system tests revealed reduced adrenocorticotropic hormone (ACTH; 2.0 pg/ml) and cortisol (1.12 µg/dl) levels. The patient was diagnosed with isolated ACTH deficiency and oral hydrocortisone was administered after prednisolone cessation. On the 25th day of the 3rd course of treatment, the patient complained of headache and anorexia. CSF examination revealed that the WBC count had increased a second time (53/mm3; lymphocytes only) and laboratory data revealed hepatic dysfunction. The patient was then diagnosed with relapse of aseptic meningitis and liver dysfunction. While continuing oral hydrocortisone treatment, the administration of intravenous prednisolone was started. The observed liver dysfunction and aseptic meningitis gradually improved. The current report may be useful for avoiding delays in the diagnosis and treatment of this life-threatening and uncommon irAE, in which CSF examinations are useful for diagnosis and management.

Cisplatin-based systemic chemotherapy is the gold-standard approach for the first-line treatment of patients with advanced or metastatic urothelial carcinoma (UC). However, the optimal number of cycles is still unclear. The current study retrospectively assessed the clinical outcome in patients who received gemcitabine and cisplatin (GC) chemotherapy as first-line treatment for metastatic urothelial cancer to clarify the timing of switching from GC therapy. A total of 61 patients with locally advanced or metastatic UC who received first-line chemotherapy with GC were retrospectively reviewed at National Hospital Organization Kyushu Cancer Center between June 2009 and August 2017. The progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method. The significance of associations between the clinical parameters and OS was assessed using the Cox proportional hazards regression model. The median cycle number for GC chemotherapy was 4. The median PFS and OS of all cases was 5.2 and 14.1 months, respectively. The multivariate analyses revealed that a neutrophil-to-lymphocyte ratio ≥3.0 (hazard ratio [HR], 2.521, 95% confidence interval [CI]=1.179–5.624; P=0.017) and best response to GC therapy of CR+PR (HR 0.110; 95% CI=0.028–0.411; P4) was not an independent prognostic factor (P=0.387). The current retrospective study indicated that changes to therapy should be considered at an early stage for cases with a therapeutic effect of SD or less, regardless of the number of GC therapy cycles.

Nivolumab is a monoclonal immunoglobulin G antibody blocking programmed death receptor-1 (PD-1) that promotes the restoration of the natural T-cell-mediated immune response against cancer cells; however, it also causes a number of autoimmune-related adverse events (irAEs) that often involve the endocrine system. The present report describes a 71-year-old man with clear cell renal cell carcinoma metastasis in the lung. Following the 14th course of nivolumab therapy, the patient complained of general malaise, loss of appetite and mild consciousness disturbance. Laboratory tests revealed a severely elevated eosinophil ratio (26.2%) and low sodium value (122 mmol/l). Endocrine system tests revealed that the patient's adrenocorticotropic hormone (ACTH; 4.5 pg/ml) and cortisol (0.1 µg/dl) levels were lower than normal, while those of other pituitary hormones were higher than normal. This case was therefore diagnosed as isolated ACTH deficiency induced by nivolumab. Magnetic resonance imaging (MRI) showed normal pituitary glands. Hydrocortisone replacement therapy improved the clinical symptoms early and enabled the patient to restart nivolumab therapy. Isolated ACTH deficiency due to nivolumab, a PD-1 immune checkpoint inhibitor antibody, is a rare occurrence. This report may be useful for avoiding delays in the diagnosis and treatment of this life-threatening irAE even if no pituitary abnormalities are identified via MRI.

The oncological benefit of pelvic lymph node dissection (PLND) for prostate cancer (PCa) remains unclear. The therapeutic effect of PLND on the elimination of microscopic metastases during radical prostatectomy (RP) for PCa was examined in the current study. A total of 348 Japanese patients with high- or intermediate-risk PCa without lymph node metastasis, who underwent antegrade RP at the Kyushu Cancer Center (Fukuoka, Japan) between August 1998 and May 2013 were retrospectively analyzed. The patients were divided into the standard (obturator + internal iliac nodes) group and the expanded (standard + additional nodes) group according to the extent of PLND. Preoperative and postoperative characteristics were also analyzed to determine the factors associated with prostate-specific antigen (PSA) failure. Standard and expanded PLND were performed in 70.9% (247/348) and 29.1% (101/348) of cases, respectively. The results revealed that preoperative PSA levels were the only marked difference between the two groups. No differences were observed in the other preoperative and postoperative characteristics. Furthermore, the rate of PSA recurrence in each group did not differ to a statistically significant extent (P=0.3622). Reducing the area of dissection from expanded PLND to standard PLND significantly reduced the number of dissected lymph nodes (P

There is no established standard second-line chemotherapy after the failure of the first-line cisplatin-based chemotherapy for patients with advanced or metastatic urothelial carcinoma. With regards to second-line chemotherapy, methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) was used from July 2009 onwards, and paclitaxel and carboplatin (TC) was introduced in April 2014 at the National Kyushu Cancer Center. The present study aimed to assess the prognostic factors for overall survival (OS) in second-line treatment that included best supportive care (BSC), and the tolerability and efficacy of TC chemotherapy. In total, 52 patients who were confirmed to have disease progression with first-line gemcitabine and cisplatin (GC) between June 2009 and November 2016 were enrolled in the current study. In addition, 28 patients selected BSC as second-line treatment, while 24 patients received second-line chemotherapy (MVAC, n=8; TC, n=16). The median OS for BSC, MVAC and TC was 2.8, 5.4, and 12.7 months, respectively. The difference between BSC and MVAC was not statistically significant (P=0.596). However, the difference between BSC and TC was statistically significant after Bonferroni correction (P=0.002). Multivariate analyses revealed that anemia [hazard ratio (HR), 7.047; 95% confidence interval (CI), 1.553-35.636; P=0.011], the presence of visceral metastasis (HR, 4.174; 95% CI, 1.506-13.429; P=0.005) and second-line treatment (TC HR, 0.296; 95% CI, 0.124-0.636; P=0.003) were independent prognostic factors. TC achieved an 18.7% overall response rate and a 56.2% disease control rate. Myelosuppression was the most common grade ≥3 toxicity, but no treatment-associated mortalities occurred during the study period. TC was associated with favorable benefits and safety, and may be considered a preferred regimen after the failure of GC.

The aim of the present study was to evaluate the palliative effects and adverse events of strontium-89 (Sr-89) in patients with bone metastasis from prostate cancer. A total of 18 patients with prostate cancer and painful bone metastases, as diagnosed on bone scintigraphy, who were treated with Sr-89 at the National Kyushu Cancer Center between February, 2008 and April, 2014 were reviewed. Of the 18 subjects, 13 (72.2%) achieved a pain response, whereas 5 were classified as pain non-responders (27.8%). According to a logistic regression analysis, the pre-administration characteristics, including age, prostate-specific antigen (PSA), alkaline phosphatase (ALP), history of bone-modifying agent administration, opioid use or palliative radiation therapy, time after the combined androgen blockade nadir and time since the pain onset, were not found to be significant predictors of the pain response. Similarly, the post-administration characteristics, including pain flares and the PSA and ALP response, were not found to be significant predictors of the pain response. Although no patients exhibited leukocyte toxicities, 2 patients experienced myelosuppression, involving anemia and thrombocytopenia, requiring transfusion of red cell or platelet concentrate following Sr-89 treatment. Of the 18 patients, 5 (27.8%) reported pain flares, all of whom were successfully treated with rescue drugs alone. According to the logistic regression analysis, of the pre-administration characteristics, only ALP was identified as a significant predictor of bone marrow suppression in the univariate and multivariate analyses (P=0.006). Therefore, Sr-89 treatment was found to be effective in ameliorating bone pain associated with metastasis from prostate cancer. Although it is difficult to identify the patients who will receive pain relief prior to Sr-89 administration, this drug should be administered during the early stages due to the potential for bone marrow suppression in patients with high ALP levels.

The aim of the present study was to evaluate the hypothesis that a positive resection margin (RM1) of an excised specimen may not reflect the true margin in patients that have undergone radical prostatectomy (RP). Between September 2003 and March 2011, 370 Japanese patients underwent an antegrade RP at the National Kyushu Cancer Center (Fukuoka, Japan), however, 95 of these patients were excluded from the study due to a history of receiving hormonal therapy or insufficient preoperative clinical data. The incidence of biochemical failure (BCF) was evaluated using multivariate analysis, which revealed that the preoperative prostate-specific antigen (PSA) level, pathological tumor stage, RP Gleason score and a PSA nadir

The aim of the present study was to demonstrate that the treatment outcome of transperitoneal ureterocutaneostomy using the transverse mesocolon is not inferior to that of conventional retroperitoneal ureterocutaneostomy. The enrolled subjects were 26 patients who underwent ureterocutaneostomy among a total of 160 cases of urinary diversion performed at our institution between March, 2004 and November, 2011. A total of 11 cases and 18 ureters were treated by transperitoneal ureterocutaneostomy via the transverse mesocolon, with 7 bilateral ureterocutaneostomy cases. All the cases of retroperitoneal ureterocutaneostomy were unilateral, totaling 15 patients and 15 ureters. Postoperative adverse events (ileus, acute pyelonephritis), catheter-free status and renal function [blood urea nitrogen (BUN) and serum creatinine (Cr) values] were retrospectively evaluated between the groups treated by the different surgical procedures. Ileus was only observed in 1 case and improvement was achieved through conservative therapy alone (P=0.827). Acute pyelonephritis developed in 3 (27.3%) transperitoneal and 8 (53.3%) retroperitoneal cases, with all the cases recovering following treatment with antibiotics alone (P=0.199). A catheter-free status was achieved in 3 cases (27.3%) and 4 ureters (22.2%) in the transperitoneal group and in 2 cases and 2 ureters (13.3%) in the retroperitoneal group (P=0.393). There was no significant change in renal function (BUN and serum Cr values) in the transperitoneal ureterocutaneostomy cases at the postoperative, early postoperative (1 month following surgery) or the final follow-up examination (P=0.739 and 0.078). In conclusion, transperitoneal ureterocutaneostomy allows for the construction of a cutaneous stoma using a shorter ureter, with a treatment outcome that is comparable to that of retroperitoneal ureterocutaneostomy.

Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare clinicoradiological syndrome that is characterized by neurological symptoms, including seizures, headaches, visual abnormalities, confusion and encephalopathy, accompanied by vasogenic edema of the posterior white matter observed on neuroimaging. Sorafenib is an inhibitor of pro-angiogenic receptor tyrosine kinases, such as vascular endothelial growth factor receptor 2, platelet-derived growth factor receptor β, and vascular endothelial growth factor receptor 3. In the previous research literature, only one case of sorafenib-induced RPLS, in a patient with hepatocellular carcinoma, has been reported. The current report presents two cases of sorafenib-induced RPLS in patients with metastases from a renal cell carcinoma. In the first case, a 75-year-old female patient developed a fever, fell down and was unable to move her limbs as instructed after 11 days of sorefenib treatment. Brain magnetic resonance imaging (MRI) demonstrated no typical RPLS findings. As all of the symptoms were resolved after sorafenib discontinuation, sorafenib was restarted. However, the patient remained unable to walk steadily and to articulate properly after 10 days. MRI again demonstrated no notable findings, and her condition improved only after discontinuation of the sorafenib. In the second case, a 75-year-old male patient experienced a fall due to loss of consciousness. T2-weighted and fluid-attenuated inversion recovery MRI revealed high-intensity signals on both sides of the cerebellar hemisphere and pons, and also partially on both sides of the frontal lobe. At 33 days after sorafenib discontinuation, he had recovered sufficiently to walk by himself with a walker, and a repeat MRI revealed a significant improvement. Although one case took a longer time, both cases were fortunately reversible by discontinuation of sorafenib treatment and administration of combined-modality therapy (including oxygen, steroids, verapamil, digoxin and nicardipine hydrochloride). The oncology community should be alerted to this uncommon and life-threatening adverse event.

Objective To assess the characteristics of biochemical recurrence in the late period (>5 years after radical prostatectomy) and the differences in the predictors of biochemical recurrence in different periods, we conducted a multicenter retrospective study. Methods We reviewed 478 men who underwent radical prostatectomy for clinically localized prostate cancer. All of the patients were followed up for at least 5 years. The cohort was then divided into three groups; no recurrence group, recurrence

Surgical anatomy around the kidney remains controversial. We therefore examined the constitutions of renal fascia and retroperitoneal space around the kidney through the close observations of intraoperative views. The surface of the removed kidney was covered with a smooth membrane, which is the so-called renal fascia. However, such a smooth membrane could not be observed at the dissection site around the kidney during surgery. Only an intricate connective tissue could be observed. On the other hand, using an operative procedure such as dissection or pulling tissue in some direction, an intricate connective tissue changed to a membranous structure. These results suggest that the retroperitoneal area around the kidney would be filled with connective tissue including some fat, which is arranged in a chaotic manner without any specific alignment tridimentionally. As a result of operative procedures, such connective tissue would be grouped, which would be recognized as renal fascia.

In this study, the region between the prostate and the rectum was examined. We reviewed, macroscopically, the clinical anatomy of the perioperative regions and excised specimens. Moreover, using fixed specimens from three cases of total pelvic exenteration, we histologically reviewed the regions between the prostate and rectum. Following bladder neck transection, the deferent duct was observed in connective tissues that continued to Denonvilliers’ fascia. When the prostate was pulled ventrally, this connective tissue was identified as a sheet of membrane that traversed from the anterior prostate to the dorsal rectum. The dorsal surface of the specimen appeared to be covered with a thin membrane, and the regions that continued from this thin membrane were judged macroscopically as a stump. Between the prostate and the rectum, intricate connective tissue was present in the fixed specimen that was removed via a total pelvic exenteration. This connective tissue continued to the connective tissue surrounding the seminal vesicles and prostate. The complex connective tissue was present anatomically between the prostate and rectum. As a result of the surgical procedures, this connective tissue was identified surgically as Denonvilliers’ fascia.

The present study aimed to determine the adequate pelvic lymph node dissection (PLND) range for Japanese males undergoing radical prostatectomy. A total of 467 Japanese patients who underwent antegrade radical prostatectomy at the National Kyushu Cancer Center (Fukuoka, Japan) were retrospectively reviewed. The patients were divided into two groups according to the PLND extent: The standard (obturator + internal iliac nodes) group and the expanded (standard + additional nodes) group, which accounted for 64.5% (301/467) and 35.5% (166/467) of the patients, respectively. No differences were observed in the preoperative and postoperative characteristics of the two groups. In addition, there was no difference in PSA recurrence between the two groups. There were no differences between the standard and expanded groups in the low-, intermediate- and high-risk groups (P=0.1456, P=0.1581, P=0.2125, respectively). The median number of lymph node dissection was 13 and 19, in the standard and expanded groups respectively (P

The present study aimed to evaluate the possibility of performing radical prostatectomy (RP) alone to achieve a radical cure for prostate cancer in the intermediate-risk group. Samples were collected from 638 Japanese patients who underwent antegrade RP between August 1998 and May 2013; subsequently, 157 patients were excluded. According to the D'Amico criteria, the low-, intermediate- and high-risk groups comprised 107, 222 and 152 patients, respectively. The 5-year prostate-specific antigen (PSA) failure-free survival rates in the low-, intermediate-, and high-risk groups were 96.5, 88.9 and 72.6%, respectively (P

Cutaneous ureterostomy cannot be carried out by the retroperitoneal method in cases showing an insufficient length of the available ureter. We therefore proposed and carried out cutaneous ureterostomy transperitoneally on a ureter of minimum length using the transverse mesocolon. The right and left ureters are drawn from the retroperitoneum into the peritoneal cavity in the renal hilus area. The right ureter is then led from the root of the transverse mesocolon to the area attached to the transverse colon under the subserous part of the transverse mesocolon, and penetrates the gastrocolic ligament. The left ureter is led to the area attached to the transverse mesocolon under the subserous part of the transverse mesocolon, and penetrates the transverse mesocolon, bursa omentalis and gastrocolic ligament. Next, both the right and left ureters are drawn up to the abdominal wall and a ureterstoma is constructed. The transverse mesocolon can be used as supporting tissue for the ureter. Furthermore, this also ensures blood flow in the ureter.

Although sunitinib is associated with a variety of adverse events, cases of sunitinib-related acute cholecystitis have rarely been reported. We herein report two cases of sunitinib-related acute acalculous cholecystitis in patients with clear cell renal cell carcinoma. In both cases, the gallbladder was surgically removed because it was difficult to improve the patient’s condition with the cessation of sunitinib and non-surgical treatment only. Attention must be paid to the possibility of sunitinib-related acute cholecystitis, which, although uncommon, can be life-threatening.

This study aimed to evaluate the usefulness of ultra-sensitive prostate-specific antigen (PSA) following radical prostatectomy (RP). Between September, 2003 and March, 2009, a total of 311 prostate cancer patients underwent antegrade RP; following the exclusion of 111 patients due to prior hormonal therapy, 200 patients were finally included in this study. The results of the multivariate analysis identified RP Gleason score, extraprostatic extension, lymph node metastasis and PSA nadir as significant predictors of biochemical failure (P=0.0116, 0.0216, 0.0178 and

Cutaneous ureterostomy cannot be carried out by the retroperitoneal method in cases showing an insufficient length of the available ureter. We therefore proposed and carried out cutaneous ureterostomy transperitoneally on a ureter of minimum length using the transverse mesocolon. The right and left ureters are drawn from the retroperitoneum into the peritoneal cavity in the renal hilus area. The right ureter is then led from the root of the transverse mesocolon to the area attached to the transverse colon under the subserous part of the transverse mesocolon, and penetrates the gastrocolic ligament. The left ureter is led to the area attached to the transverse mesocolon under the subserous part of the transverse mesocolon, and penetrates the transverse mesocolon, bursa omentalis and gastrocolic ligament. Next, both the right and left ureters are drawn up to the abdominal wall and a ureterstoma is constructed. The transverse mesocolon can be used as supporting tissue for the ureter. Furthermore, this also ensures blood flow in the ureter.

In order to demonstrate the original and infiltrating patterns of prostatic carcinoma, the change of histological characteristics associated with increasing total cancer volume was investigated. Tissue specimens from 196 histopathological cases, obtained at the Kyushu Cancer Center, were reviewed in embedded whole-mount antegrade radical prostatectomy specimens with adenocarcinoma. Three groups (