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The prognosis of high-risk metastatic hormone-naïve prostate cancer is poor, and real-world evidence of therapeutic options and sequences is lacking. The J-ROCK study aimed to evaluate the outcomes in a real-world setting in Japan.Patients with high-risk metastatic hormone-naïve prostate cancer diagnosed after May 2019 were eligible. Based on their treatment within 3 months after diagnosis, patients were allocated to either cohort 1 (androgen deprivation therapy alone or combined androgen blockade with bicalutamide) or cohort 2 (androgen deprivation therapy with abiraterone acetate+prednisolone, docetaxel, enzalutamide, or apalutamide).In this first interim analysis (cut-off January 2021), 410 patients were enrolled, including 163 patients in cohort 1 and 247 in cohort 2. The median follow-up period was 7.6 (range 0.1-20.5) months. A higher proportion of patients in cohort 2 (42.5%) achieved nadir prostate-specific antigen levels ≤0.2 ng/ml within a year, compared with cohort 1 (22.1%). Prostate-specific antigen-progression-free survival was also more favorable in cohort 2 (adjusted hazard ratio 0.629 [95% confidence interval 0.345-1.147]).The higher proportion of cohort 2 suggest a paradigm shift has occurred in the real-world treatment of high-risk metastatic hormone-naïve prostate cancer in Japan. Some factors including prostate-specific antigen may affect treatment selection but need further observation. Most patients in cohort 2 received abiraterone acetate+prednisolone. The proportion of patients in cohort 1 receiving combined androgen blockade was lower than previously reported in Japan. This analysis suggest that more intensive therapy tends to prolong prostate-specific antigen-progression-free survival in patients with high-risk metastatic hormone-naïve prostate cancer.

Background: Immune-related adverse events (irAEs) in patients treated with immune check inhibitors are associated with favourable response rate and survivals in multiple cancers, including renal cell carcinoma (RCC). The aim of this study was to investigate how irAEs were associated with improved survivals in advanced RCC patients treated with nivolumab plus ipilimumab. Materials and methods: This retrospective study included patients who received nivolumab plus ipilimumab between September 2018 and February 2022 at six centres. We assessed associations of the development and the number of irAEs with overall survival (OS) and progression-free survival (PFS). To eliminate immortal time bias, landmark analysis and a Cox model with time-dependent variables were used. Results: This study included 129 patients with a median follow-up of 12.3 months. The 2-year OS and PFS rates were 55% and 42%, respectively. Ninety six patients experienced irAEs. The development of irAEs was positively associated with OS and PFS rates (hazard ratio [HR] 0.328, 95% confidence interval [CI] 0.165–0.648, p = 0.001; HR 0.334, 95% CI 0.151–0.737, p = 0.007). Patients who experienced multiple irAEs had longer OS (HR 0.507, 95% CI 0.235–1.097, p = 0.085 or HR 0.245, 95% CI 0.110–0.544, p < 0.001) and PFS (HR 0.572, 95% CI 0.316–1.036, p = 0.085 or HR 0.267, 95% CI 0.113–0.628, p = 0.002) compared with those who experienced single or zero irAE. Conclusions: Developing irAEs, particularly multiple irAEs, is associated with favourable survivals in advanced RCC patients treated with nivolumab plus ipilimumab.

Tyrosine kinase inhibitors (TKIs) are used as targeted drugs for advanced renal cell carcinoma (RCC), although most cases eventually progress by acquiring resistance. Cancer stemness plays critical roles in tumor aggressiveness and therapeutic resistance, and dipeptidyl peptidase IV (DPP4) has been recently identified as a cancer stemness-related protein. A question arises whether DPP4 contributes to TKI efficacy in RCC. We established patient-derived RCC spheroids and showed that DPP4 expression is associated with stemness-related gene expression. TKI sunitinib resistance was rescued by DPP4 inhibition using sitagliptin or specific siRNAs in RCC cells and tumors. DPP4 expression can be inducible by retinoic acid and repressed by ALDH1A inhibition. Among type 2 diabetes patients with clinical RCC tumors, higher TKI efficacy is observed in those bearing DPP4high tumors treated with DPP4 inhibitors. This study provides new insights into TKI resistance and drug repositioning of DPP4 inhibitor as a promising strategy for advanced RCC.

Although nivolumab plus ipilimumab has become a standard treatment regimen for metastatic clear cell renal cell carcinoma (ccRCC), its efficacy in non-clear cell carcinoma (nccRCC) has not been fully examined. In the current study, we evaluated the clinical outcomes of nivolumab plus ipilimumab in nccRCC compared with ccRCC.We retrospectively analyzed 22 patients with metastatic and/or locally advanced unresectable nccRCC who received nivolumab plus ipilimumab as a first-line therapy and compared them with 107 patients with ccRCC. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and toxicity were compared between the nccRCC and ccRCC groups.The histology of nccRCC included eight papillary, six unclassified, three chromophobe, two collecting duct carcinoma, and three other subtypes. Best objective response in nccRCC patients included three complete responses and five partial responses, resulting in an ORR of 36%, while that in ccRCC patients was 50% (p = 0.22). With a median follow-up of 11.9 months, OS was significantly shorter in patients with nccRCC than in those with ccRCC (median 20.8 months vs. not reached, p = 0.04), while there was no significant difference in PFS (median 6.3 vs. 10.8 months, p = 0.21). Treatment-related adverse events occurred in 14 (64%) nccRCC patients and 81 (76%) ccRCC patients.Combination treatment with nivolumab and ipilimumab demonstrated modest clinical efficacy in patients with nccRCC compared with patients with ccRCC, suggesting it could be a therapeutic option for metastatic nccRCC patients.

Real-world incidence of immune-related adverse events (irAEs) associated with nivolumab plus ipilimumab in patients with renal cell carcinoma (RCC) has been rarely demonstrated. The present study aims to report the safety outcomes of this combination therapy in the real-life population. We conducted a multi-institutional retrospective observational study that assessed the incidence and severity of irAEs associated with nivolumab plus ipilimumab in 41 Japanese patients with metastatic and/or locally advanced RCC. The irAEs were classified into endocrine and non-endocrine irAEs. The median age and follow-up period were 68 years and 13.0 months, respectively. Endocrine irAEs were observed in 66% of patients, including hypopituitarism in 44%, hyperthyroidism in 41%, and primary hypothyroidism in 22%, while non-endocrine irAEs were observed in 54%. All patients experiencing hypopituitarism presented with adrenocorticotropic hormone deficiency, causing secondary adrenal insufficiency, which required permanent corticosteroid replacement therapy. There was an association between the incidence of endocrine irAEs and high-grade non-endocrine irAEs other than skin-related irAEs (p = 0.027). When patients experienced two or more endocrine irAEs, they had a 35% chance of experiencing high-grade non-endocrine irAEs other than skin-related irAEs. Nivolumab plus ipilimumab may lead to a high prevalence of endocrine irAEs in “real-world” patients. Endocrine irAEs may be associated with non-endocrine irAEs other than skin-related irAEs.

OBJECTIVES To develop a prediction tool based on physical findings and environmental conditions without utilizing color Doppler ultrasonography to guide non-urologists and patients' families in determining the testicular torsion possibility among patients with acute scrotal pain. METHODS Overall, 110 consecutive patients aged ≤30 years with acute scrotal pain at Saitama Medical Center between 2012 and 2014 were retrospectively evaluated. Physical examination results, including scrotal inspection, palpation and gait observation, and environmental conditions at pain onset (time range and ambient temperature) were collected. Multivariate analysis identified significant and independent risk factors for testicular torsion, and a nomogram predicting testicular torsion was constructed. The model underwent prospective validation in an independent set of 123 consecutive patients admitted with acute scrotal pain to our institution between 2015 and 2017. RESULTS Testicular torsion diagnosis rates were 27% (30/110) and 26% (32/123) in the training and validation cohorts, respectively. Logistic regression analysis showed four risk factors for developing testicular torsion: abnormal testicular position, walking difficulty, midnight to early morning onset and ambient temperature

Diffusion-weighted whole-body magnetic resonance imaging with background suppression (DWIBS) is increasingly used in cancer imaging. However, little is known about its usefulness in the management of metastatic seminoma, in which evaluation of the viability of postchemotherapy residual nodules is pivotal. To date, 2–18fluoro-deoxy-d-glucose positron emission tomography (FDG-PET) has been recommended for post-chemotherapeutic assessment. We describe a case of metastatic seminoma in a 27-year-old man in which the viability of post-chemotherapy residual nodules tested false-positive on FDG-PET, but true-negative on DWIBS. DWIBS may be a good alternative technique to evaluate post-chemotherapy seminoma, although further studies are required to determine its usefulness. Keywords: Whole-body imaging, Diffusion magnetic resonance imaging, Seminoma, Chemotherapy, Positron-emission tomography

Background Guillain–Barre syndrome (GBS) is an acute inflammatory neuropathy characterized by areflexic quadriparesis. Urinary dysfunction has been known to occur in approximately 25% of GBS patients during the clinical course and usually emerges during peak motor weakness. According to the diagnostic criteria for GBS, bladder dysfunction at onset makes the diagnosis of GBS rather doubtful. We report here a rare case of GBS that initially manifested as motor weakness with urinary dysfunction and hyperreflexia. Case presentation A 66-year-old Japanese man experienced mild weakness in his hands that extended to the entire upper extremities the following day. At the same time, he started experiencing difficulty voiding. On the fourth day after the onset of weakness, he was admitted to Saitama Medical Center, Kawagoe, Japan, because of an inability to stand up without support. Neurological examination revealed moderate generalized weakness, hyperreflexia, and poor urinary volume and flow. Early in hospitalization, his deep tendon reflexes gradually decreased and ultimately he became areflexic. A nerve conduction study indicated the axonal form of GBS. He was treated with immunoadsorption plasmapheresis, followed by two sessions of intravenous immunoglobulin G treatment. The motor weakness and urinary dysfunction gradually ameliorated, and he was discharged and transferred for rehabilitation on hospital day 47. Conclusions The present case suggests that urinary dysfunction in GBS might not necessarily occur during peak motor weakness, but could start at onset. Physicians should consider GBS in differential diagnosis of patients presenting with initial symptoms of motor weakness and urinary dysfunction.

A 47-year-old woman was transferred to our hospital in June 2014 in hemorrhagic shock due to rupture of a huge right renal angiomyolipoma (AML). Selective right renal arterial embolization performed that same day reversed the shock immediately. Despite the huge abdominal tumor, the patient was discharged 2 weeks later after refusing any further treatment.Two weeks later she noticed the abdominal tumor growing. One month after discharge, she was readmitted due to dyspnea caused by restriction of her breathing by the growing tumor mass. A CT revealed a massive increase in tumor size with internal liquefaction, a thrombus in the left common iliac vein, and a 12 mm aneurysm in the right renal artery. The patient requested removal of the abdominal tumor since her ADL had deteriorated. We decided to perform a right nephrectomy with consideration of the left common iliac vein thrombus and right renal arterial aneurysm.As a precaution against pulmonary embolism in case the left common iliac vein thrombus dislodged, a retrievable inferior vena cava (IVC) filter was inserted before surgery. We were also concerned about possible rupture of the right renal aneurysm, so the right renal artery was embolized before surgery. After these procedures, a right nephrectomy was performed via a transperitoneal approach.The surgery was uneventful. The tumor weighed about 11 kg including 7,000 mL of bloody fluid. The IVC filter was removed the day after surgery, but the thrombus in the left common iliac vein remained, and an anticoagulant was started. Three months later, the thrombus had disappeared, and the anticoagulant was discontinued six months after surgery.According to the treatment guidelines for deep vein thrombosis, anticoagulants are the drugs of choice. IVC filters are seldom used to prevent pulmonary embolism. We initially administered an anticoagulant for the thrombus in the left iliac vein. However, an increase in abdominal tumor size suggested the drug had caused internal rebleeding and it had to be discontinued. Ultimately, we used a temporary retrievable IVC filter during the right nephrectomy with success.There is currently no consensus on when to use an IVC filter. Moreover, very little data exists on the use of an IVC filter during the perioperative period. Therefore, given the risk of potential thromboembolism, although we were able to use it successfully in our surgery, it should not be employed without a thorough benefit-risk assessment.

Objective To compare the efficacy and safety of single half-dose silodosin and single full-dose tamsulosin in Japanese men with lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH). Methods Japanese men aged ≥50 years with LUTS/BPH and an International Prostate Symptom Score (IPSS) of ≥8 were enrolled in the randomized crossover study and divided into silodosin-preceding (S-T) and tamsulosin-preceding (T-S) groups. The S-T group received 4 mg silodosin once daily for 4 weeks followed by 0.2 mg tamsulosin once daily for 4 weeks. The T-S group received the reverse treatment sequence. A washout period prior to drug crossover was not included. Subjective and objective efficacy parameters including IPSS, quality of life (QOL) index, uroflowmetry, and safety were compared between the two groups. Results Thirty of 34 men (S-T group n = 16; T-S group n = 14) completed the study. Both drugs significantly improved all IPSS items and QOL index in the first treatment period. Subjective improvement in nocturia by silodosin was observed in both the first and crossover treatment periods. Objective improvement in maximum flow rate by silodosin was only observed in the first treatment period. Adverse events occurred more frequently with silodosin than with tamsulosin; however, none of the adverse events required treatment discontinuation. Ejaculation disorders occurred in three participants (10%) and were associated with silodosin use. Conclusion Single half-dose silodosin has a similar efficacy to full-dose tamsulosin in Japanese men with LUTS/BPH and thus, may represent an effective, safe, and affordable treatment option.

OBJECTIVES Patients' use of a head-mounted display during their sonographic examinations could provide them with information about their diseases in real time and might help improve "patient-centered care." We conducted this prospective study to evaluate the feasibility of a modern head-mounted display for patient self-monitoring of sonographic examinations. METHODS In November and December 2013, 58 patients were enrolled. Patients wore a head-mounted display (HMZ-T2; Sony Corporation, Tokyo, Japan) during their sonographic examinations and watched their own images in real time. After the sonographic examinations, the patients completed a questionnaire, in which they evaluated the utility of the head-mounted display, their understanding of their diseases, their satisfaction with using the head-mounted display, and any adverse events. Until November 26, 2013, patients' names were requested on the questionnaire; after that date, the questionnaire was changed to be anonymous. RESULTS Of the 58 patients, 56 (97%) elected to participate in this study. The head-mounted display was reported to have good image quality by 42 patients (75%) and good wearability by 39 (70%). Thirty-six patients (64%) reported they had deepened their understanding of their diseases. There were no major complications, and only 2 patients (4%) had mild eye fatigue. There was no significant association between questionnaire results and patient characteristics. None of the questionnaire results changed significantly after the questionnaire was made anonymous. CONCLUSIONS The use of a modern head-mounted display by patients during sonographic examinations provided good image quality with acceptable wearability. It could deepen their understanding of their diseases and help develop patient-centered care.

(Objectives) Testicular torsion (TT) is a socially and clinically important urological emergency condition because delayed diagnosis and treatment can lead to testicular loss. Although a possible association between TT and low ambient temperature has been argued, the clinical significance of the association has not been fully elucidated. We retrospectively collected acute scrotum cases and investigated the association between the risk of TT among acute scrotums and ambient temperatures on the day of onset. (Patients and methods) We studied 105 consecutive acute scrotum patients with suspected TT who underwent urgent surgical exploration between October 2004 and October 2014. The patients' age, residential area, time and date of onset, laboratory findings, and operative findings were collected from their medical records. Climate data, including daily mean ambient temperature (DMAT), diurnal temperature change (DTC), humidity, and atmospheric pressure at the time of onset, were obtained from the Japan Meteorological Agency website. The chi-square and Wilcoxon rank sum tests were used to evaluate statistical differences. Logistic regression analysis used to identify significant predictors of TT. (Results) The median age of the patients was 13 years (range, 1-43 years). The affected side was the right/left/bilateral side in 46/58/1 of the patients. Surgical exploration revealed TT in 67 patients. The remaining 38 non-TT patients included 12 with testicular appendage torsions, 12 with epididymal appendage torsions, 9 with epididymitis, 2 with orchitis, 2 with idiopathic hematomas, and 1 with allergic purpura. The median DMATs at the day of onset were 10.8°C (1.8-29.4°C) in the TT patients and 19.4°C (1.9-29.1°C) in the non-TT patients. The incidence of TT among the patients with acute scrotum explored surgically (TT incidence) in days with DMATs

INTRODUCTION AND OBJECTIVES: The development of prostate cancer (PC) has been associated with numerous lifestyle factors (obesity, physical activity, nutrition) and metabolic perturbations. We aimed to prospectively characterize an integrative metabolic profile of men undergoing diagnostic prostate biopsies. METHODS: We prospectively evaluated 51 consecutive men for body composition, metabolic syndrome, glucoseand lipid-related measures and lifestyle factors including physical function and nutritional intake prior to prostate biopsy. These factors were related to the Gleason score obtained from the extended (16-26 cores) transrectal ultrasound guided biopsy performed for prostate cancer diagnosis. one-way Analysis of Variance (ANOVA) and linear regression were used. RESULTS: Mean age and BMI of the participants were 66 years with and 28.2 kg/m2. Metabolic syndrome was identified in 32 of 51 (63%) participants based on criteria from the International Diabetes Federation. Serum C-peptide concentrations were significantly greater (p

To compare the efficacy and safety of single half-dose silodosin and single full-dose tamsulosin in Japanese men with lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH).Japanese men aged ≥50 years with LUTS/BPH and an International Prostate Symptom Score (IPSS) of ≥8 were enrolled in the randomized crossover study and divided into silodosin-preceding (S-T) and tamsulosin-preceding (T-S) groups. The S-T group received 4 mg silodosin once daily for 4 weeks followed by 0.2 mg tamsulosin once daily for 4 weeks. The T-S group received the reverse treatment sequence. A washout period prior to drug crossover was not included. Subjective and objective efficacy parameters including IPSS, quality of life (QOL) index, uroflowmetry, and safety were compared between the two groups.Thirty of 34 men (S-T group n = 16; T-S group n = 14) completed the study. Both drugs significantly improved all IPSS items and QOL index in the first treatment period. Subjective improvement in nocturia by silodosin was observed in both the first and crossover treatment periods. Objective improvement in maximum flow rate by silodosin was only observed in the first treatment period. Adverse events occurred more frequently with silodosin than with tamsulosin; however, none of the adverse events required treatment discontinuation. Ejaculation disorders occurred in three participants (10%) and were associated with silodosin use.Single half-dose silodosin has a similar efficacy to full-dose tamsulosin in Japanese men with LUTS/BPH and thus, may represent an effective, safe, and affordable treatment option.

Purpose We tested a new head-mounted display (HMD) system for surgery on the upper urinary tract. Surgical Technique Four women and one man with abnormal findings in the renal pelvis on computed tomography and magnetic resonance imaging underwent surgery using this new system. A high definition HMD (Sony, Tokyo, Japan) is connected to a flexible ureteroscope (Olympus, Tokyo, Japan) and the images from the ureteroscope are delivered simultaneously to various participants wearing HMDs. Furthermore, various information in addition to that available through the endoscope, such as the narrow band image, the fluoroscope, input from a video camera mounted on the lead surgeon’s HMD and the vital monitors can be viewed on each HMD. Results Median operative duration and anesthesia time were 53 and 111 minutes, respectively. The ureteroscopic procedures were successfully performed in all cases. There were no notable negative outcomes or incidents (Clavien-Dindo grade ≥1). Conclusion The HMD system offers simultaneous, high-quality magnified imagery in front of the eyes, regardless of head position, to those participating in the endoscopic procedures. This affordable display system also provides various forms of information related to examinations and operations while allowing direct vision and navigated vision.

Evaluation of the malignant potential of a pheochromocytoma (PCC) remains controversial. PCC is regarded as a neuroendocrine tumor (NET), and the classification of NETs has gradually been defined over the last decade, particularly for gastroenteropancreatic NET. The present study describes a case of locally advanced, carcinoma-like, nonfunctional PCC, which may be regarded as neuroendocrine carcinoma (NEC) rather than a malignant PCC. A 72-year-old man was referred to Saitama Red Cross Hospital (Saitama, Japan), presenting with a 2-month history of right flank pain. Computed tomography revealed a right adrenal gland tumor, which measured 6.0 cm in diameter, invading the hilum of the right kidney, liver and inferior vena cava (IVC). Radical surgery was performed with en bloc resection of the right kidney, and adjacent parts of the liver and IVC. Immunohistochemical examination demonstrated that all of the resected tissues were positive for cytokeratin AE1/AE3, chromogranin A, synaptophysin, cluster of differentiation 56 and Ki-67, and the specimen had a Ki-67 index of 80%. A diagnosis of carcinoma-like PCC or NEC of the adrenal gland was confirmed. Reports of NEC of the adrenal gland are extremely rare in the literature, and classification of PCC as a NET has not yet been fully discussed. The present case may therefore contribute to the classification of NETs in the adrenal gland.