GNRI Sustainability during One Cycle of First-Line Chemotherapy as a Prognostic Indicator in Patients with Metastatic Urothelial Carcinoma.

INTRODUCTION: This study evaluated the prognostic value of a sustained high Geriatric Nutritional Risk Index (GNRI) during first-line chemotherapy for patients with metastatic urothelial carcinoma (mUC). METHODS: Between January 2018 and February 2022, 123 patients received platinum-based chemotherapy at Nagoya City University Hospital and affiliated institutions. Of these, 118 eligible patients who showed an Eastern Cooperative Oncology Group performance status (ECOG-PS) between 0 and 2 were retrospectively examined. Based on body mass index and serum albumin levels, GNRI was calculated immediately before and after the first primary chemotherapy cycle. Patients were divided into two groups based on GNRI: GNRI sustained ≥92 in sustainable (n = 63) and GNRI <92 in unsustainable (n = 55) groups, respectively. Clinical outcomes were compared. RESULTS: No significant differences were noted between the two groups for age, gender, cycle of first-line treatment, and type of series of sequential treatments after failure of first-line therapy. Median overall survival from the start of first-line chemotherapy was 30.2 months (95% confidence interval [CI]: 20.9-NA) for sustainable and 12.6 months (95% CI: 9.0-21.2) for unsustainable groups, respectively (p < 0.05). Multivariate analysis identified ECOG-PS:2 and fatigue, an adverse event, as independent predictors of unsustainable GNRI transition (95% CI: 1.29-90.6, odds ratio [OR]: 10.8; 95% CI: 1.06-26.9, OR: 5.34, respectively). CONCLUSION: Sustaining a high level of GNRI was an important prognostic indicator in patients with mUC receiving first-line chemotherapy. Appropriate intervention for controlling adverse events, including fatigue, may enhance physical strength during cancer treatment.

Elevated eosinophils proportion as predictor of immune-related adverse events after ipilimumab and nivolumab treatment of advanced and metastatic renal cell carcinoma.

OBJECTIVES: Ipilimumab and nivolumab treatment against advanced and metastatic renal cell carcinoma (RCC) causes severe and lethal immune-related adverse events (irAEs). Predicting irAEs might improve clinical outcomes, however no practical biomarkers exist. This study examined whether eosinophils could be effective biomarkers for ≥grade 2 irAEs in RCC. METHODS: We retrospectively analyzed 75 patients with RCC treated with ipilimumab and nivolumab between August 2018 and March 2021 in a multicenter study. Eosinophils were examined before and 2 weeks after treatment, and immediately after irAEs development. The optimal cut-off value for ≥grade 2 irAEs was determined by a receiver operating characteristic (ROC) curve. Univariate and multivariate analyses were undertaken to identify predictors of ≥grade 2 irAEs. RESULTS: Two weeks after treatment, eosinophils were significantly upregulated in patients who had experienced ≥grade 2 irAEs than in those who had not experienced irAEs (mean, 5.7% vs. 3.2%; p < 0.05). The optimal cut-off value for eosinophils against ≥grade 2 irAEs was 3.0% (area under the curve = 0.69). In multivariate analyses, an eosinophil level ≥ 3.0% was a risk factor for ≥grade 2 irAEs (odds ratio 4.18, 95% confidence interval 1.16-15.1). The eosinophil level 2 weeks after treatment was upregulated by the onset of any type of irAEs including endocrine, gastrointestinal, pulmonary and skin disorders. CONCLUSIONS: An increased eosinophil level 2 weeks after treatment might be an effective biomarker for ≥grade 2 irAEs in patients with RCC treated with ipilimumab and nivolumab.

Hemoglobin and neutrophil levels stratified according to International Metastatic Renal Cell Carcinoma Database Consortium risk predict the effectiveness of ipilimumab plus nivolumab in patients with advanced metastatic renal cell carcinoma.

OBJECTIVE: To identify biomarkers associated with the effectiveness of ipilimumab plus nivolumab against advanced metastatic renal cell carcinoma. METHODS: We retrospectively analyzed the data of 75 patients treated with ipilimumab plus nivolumab at seven hospitals between August 2018 and April 2021. Prognostic biomarkers were assessed prior to initiating treatment with ipilimumab plus nivolumab. Median overall survival and progression-free survival were examined using the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify predictors of disease progression. The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factors most important for predicting disease progression were determined using classification and regression tree analysis. RESULTS: Median overall survival and progression-free survival were longer in the intermediate IMDC risk group than in the poor IMDC risk group (overall: not reached vs. 18.3 months; progression-free: not reached vs. 13.5 months). The multivariate analysis identified poor IMDC risk as a risk factor for disease progression (hazard ratio 2.61, 95% confidence interval: 1.05-6.51). Based on the results of the classification and regression tree analysis, the cohort was divided into non-anemia, anemia + neutro-Low, and anemia + neutro-High groups. Median overall survival and progression-free survival were longer in the non-anemia and anemia + neutro-Low groups than in the anemia + neutro-High group (overall: not reached vs. 29.3 months vs. 4.3 months: progression-free: not reached vs. 29.0 months vs. 3.9 months). CONCLUSION: Hemoglobin and neutrophil levels may represent crucial biomarkers for predicting the effectiveness of ipilimumab plus nivolumab therapy in patients with renal cell carcinoma.

Survival Outcome after Reduced-Port Laparoscopic Radical Cystectomy for Bladder Cancer: Long-Term Follow-Up Analysis.

INTRODUCTION: This study had two objectives: (i) to evaluate oncological outcomes in a long-term follow-up of patients with bladder cancer after reduced-port laparoscopic radical cystectomy (RP-LRC) and (ii) to assess the effect of modified Glasgow prognostic scores (mGPS) on patient outcomes. METHODS: Consecutive patients (n = 100) who received RP-LRC between March 2012 and December 2018 at our institution and affiliated hospital were retrospectively reviewed. Preoperative serum albumin and C-reactive protein levels were determined. Patients were grouped based on clinical T stage (≤cT2: n = 75, ≥cT3: n = 25) using pooled cumulative data. Oncological outcomes and mGPS as a prognostic biomarker were analyzed retrospectively. Kaplan-Meier curves displayed recurrence and survival rates. Univariate and multivariate Cox regression analyses evaluated potential prognostic factors for recurrence-free survival (RFS) and cancer-specific survival (CSS). RESULTS: Patient characteristics between the two groups were statistically similar for preoperative hematological and mGPS status, blood loss level, rate of allogeneic transfusion, and pneumoperitoneum time. After a median follow-up period of 55 months, 40/100 patients experienced disease relapse. RFS and CSS for ≤cT2 were significantly less than for ≥cT3 (p < 0.001, p < 0.05, respectively). Distant metastasis occurred in 30 patients with similar distributions of relapse sites between T-stage cohorts. Median RFS for mGPS 1/2 were 18.9 (95% confidence interval [CI]: 8.8-not assessed [NA]) and 35.0 (95% CI: 8.7-NA) months, respectively, significantly worse than for mGPS 0 (median NA, 95% CI: NA-NA); CSS was similar. Univariate and multivariate analyses revealed ≥cT3 stage, worse clinical N stage, and poor mGPS status were significant prognostic factors for short RFS and CSS. CONCLUSIONS: A large proportion of bladder cancer patients who undergo RP-LRC experience relapse, with ≥cT3 stage, worse clinical N stage or poor mGPS status identified as significant prognostic factors. Our findings may contribute to improved surgical procedures for such patients.

Involvement of the bone morphogenic protein/SMAD signaling pathway in the etiology of congenital anomalies of the kidney and urinary tract accompanied by cryptorchidism.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT), such as renal dysplasia, hydronephrosis, or vesicoureteral reflux, are the most common causes of end-stage renal disease. However, the genetic etiology of CAKUT remains unclear. In this study, we performed whole exome sequencing (WES) to elucidate the genetic etiology of symptomatic CAKUT and CAKUT accompanied by cryptorchidism. METHODS: Three patients with unilateral renal dysplasia accompanied by ipsilateral cryptorchidism were included in this analysis. Genomic DNA was extracted from peripheral blood, and WES was performed. Disease-specific single nucleotide polymorphisms (SNPs) were determined by comparison with the human genome reference sequence (hg19). Additionally, we searched for SNPs that were common to all three patients, with a particular focus on the coding regions of the target genes. RESULTS: In total, 8710 SNPs were detected. Of the genes harboring these SNPs, 32 associated with renal or testicular development were selected for further analyses. Of these, eight genes (i.e., SMAD4, ITGA8, GRIP1, FREM1, FREM2, TNXB, BMP8B, and SALL1) carried a single amino acid substitution that was common to all three patients. In particular, SNPs in SMAD4 (His290Pro and His291Pro) have not been reported previously in patients with symptomatic CAKUT. Of the candidate genes, four genes (i.e., ITGA8, GRIP1, FREM1, and FREM2) were Fraser syndrome-related genes, encoding proteins that functionally converged on the glial cell-derived neurotrophic factor/RET/bone morphogenic protein (BMP) signaling pathways. As another candidate gene, the protein encoded by BMP8B activates the nuclear translocation of SMAD4, which regulates the expression of genes associated with the differentiation of primordial germ cells or testicular development. Additionally, BMP4, a member of the BMP family, regulates the interaction between metanephric mesenchyme and ureteric buds by suppressing GDNF. CONCLUSIONS: Taken together, our findings suggested that the development of the kidney and urinary tract is intimately linked with that of male reproductive organs via BMP/SMAD signaling pathways.

Two-year-old girl with impacted ureteral stone successfully treated with a single session of combined percutaneous nephrostomy and ureteroscopy.

Impacted stones frequently cause changes in the ureter, including edema of the ureteral wall, stone embedding in the ureteral mucosa or ureteral bending, which often preclude spontaneous passing of the stone and increase the risk of complications during surgery. When stone impaction is suspected preoperatively, management should be adapted accordingly. However, surgical treatment strategies remain controversial in pediatric patients because of the scarcity of cases reported. We describe the case of a 2-year-old girl with a right impacted ureteral stone who presented with gross hematuria and pyuria, but no metabolic risk factors or hematological abnormalities. Ureteroscopy was carried out in the presence of a percutaneous nephrostomy catheter. At the 7-month follow up, hydronephrosis had improved from grade 3 to grade 1, and the ureter was free from residual or recurrent stones. No complications were noted. We believe that percutaneous nephrostomy before the lithotripsy facilitates treatment for impacted stones in pediatric patients.

Hemiscrotal agenesis: Pathogenesis and management strategies.

Hemiscrotal agenesis is among the rarest anomalies in scrotal development disorders. As it has only been reported in three cases, the clinical manifestations remain unclear. We report a case of hemiscrotal agenesis with ipsilateral cryptorchidism. Based on the thermal assessment of the scrotum, concurrent scrotoplasty and orchiopexy were carried out, and the scrotoplasty improved the thermal environment of the fixed left testis. Furthermore, the low expression of androgen receptor and steroid-5-alpha-reductase, alpha polypeptide 2 in the affected side of the scrotum likely resulted in the characteristics of absent scrotal rugae, and pigmentation on histological and biological analyses. For future fertility, we believe that scrotoplasty should be considered as a management option for hemiscrotal agenesis.

Distinctive changes in histone H3K4 modification mediated via Kdm5a expression in spermatogonial stem cells of cryptorchid testes.

PURPOSE: Gonocytes differentiate into spermatogonial stem cells, which make it possible to maintain spermatogenesis continuously throughout life. We previously reported attenuated spermatogonial stem cell activity in cryptorchid testes, which resulted in altered spermatogenesis and affected fertility. However, few groups have examined the differentiation process from gonocytes to spermatogonial stem cells. To clarify the underlying mechanisms comprehensively we performed microarray analysis to assess differential expression of transcripts between normal and undescended testes in juvenile rats. MATERIALS AND METHODS: Using microarray analysis we compared whole mRNA expression of normal and cryptorchid testes in a rat model. We subsequently validated differential expression of candidate genes by real-time reverse transcriptase-polymerase chain reaction and performed immunohistochemistry. We also investigated the methylation status of histone H3K4 in cryptorchid testes and the GC-1 spermatogonial cell line. RESULTS: We detected 24 up-regulated and 39 down-regulated genes. Of these genes Kdm5a expression was significantly higher in undescended testes. Immunohistochemistry showed that Kdm5a was localized in the nuclei of gonocytes, spermatogonia and spermatocytes. H3K4me2/me3 expression levels were decreased in undescended testes at 9 days postpartum. Furthermore, Kdm5a over expression in GC-1 cells led to increased expression of Esr2, Neurog3, Pou5f1, Ret and Thy1. CONCLUSIONS: Recent investigations revealed that not only genetic but also epigenetic regulation has a role in spermatogenesis. Kdm5a is likely involved in the transformation of gonocytes into spermatogonial stem cells by transcriptional regulation of specific genes via H3K4 histone modification. To our knowledge this is the first report of epigenetic analysis of germ cell differentiation during early spermatogenesis.

Elucidation of distinctive genomic DNA structures in patients with 46,XX testicular disorders of sex development using genome wide analyses.

PURPOSE: Although several genes, including the SRY gene, are involved in testicular differentiation, the entire mechanism of this differentiation remains unclear. We performed genome wide analysis in patients with 46,XX testicular disorders of sex development to comprehensively elucidate the mechanisms of testicular differentiation. MATERIALS AND METHODS: Whole genomic DNA was extracted from the peripheral blood of 4 patients with 46,XX testicular disorders of sex development who were SRY negative. Genomic DNA was hybridized to a GeneChip® human mapping 250K array set. Compared to normal female data, we detected common loss of heterozygosity and copy number variation regions in 4 patients using Genotyping Console™ software. RESULTS: Loss of heterozygosity was detected in 19 regions of 11 chromosomes. A total of 27 genes or nearby genomic areas were included in the applicable regions. Copy number loss was recognized in 13 regions of 10 chromosomes, and these regions included 55 genes. Copy number gain was detected in 6 regions of 4 chromosomes, which included the upstream region of the SOX3 gene. CONCLUSIONS: The regions with loss of heterozygosity did not contain genes associated with testicular differentiation. However, the upstream area of the SOX3 gene, which is located in Xq27.1, was included in the region of copy number gain. These results suggest that high expression of the SOX3 gene led to testicular differentiation despite SRY gene loss. As this applicable area is not within a coding region, genome wide analyses were valuable for detecting the novel regions associated with testicular differentiation.

Expression profiling of microRNA in cryptorchid testes: miR-135a contributes to the maintenance of spermatogonial stem cells by regulating FoxO1.

PURPOSE: We elucidated the mechanism of spermatogonial stem cell disturbance of cryptorchidism and investigated the expression of miRNAs and their target genes in undescended testes. MATERIALS AND METHODS: Using microarray analysis we compared total miRNA expression in unilateral undescended testes with that in contralateral descended and normal testes in a rat model of cryptorchidism. The model was derived by administering flutamide to pregnant Sprague Dawley® rats. We identified mRNA targets of miRNAs by bioinformatic analysis, followed by in situ hybridization and immunohistochemistry to localize candidate miRNAs and mRNAs, respectively. We also investigated whether miRNAs could inhibit target protein expression in vitro. RESULTS: Microarray analysis and subsequent quantitative reverse transcriptase-polymerase chain reaction showed that only miR-135a was expressed at a lower level in undescended testes. We identified its target as FoxO1, which is essential for stem cell maintenance. miR-135a and FoxO1 localized to spermatogonial stem cells. FoxO1 localized to the spermatogonial stem cell nucleus less frequently in undescended testes, indicating that the activity of FoxO1, which acts as a transcription factor, is altered in undescended testes. Finally, miR-135a transfection into spermatogonia in vitro resulted in down-regulation of FoxO1 expression. CONCLUSIONS: In cryptorchid testes there is a decreased number of spermatogonial stem cells in which FoxO1 is activated, indicating that failure of spermatogonial stem cell maintenance results in spermatogenesis alteration. We also noted interaction between miR-135a and FoxO1, and propose that miR-135a contributes to spermatogonial stem cell maintenance through modulation of FoxO1 activity.

Extravesical robot-assisted laparoscopic ureteral reimplantation for vesicoureteral reflux: initial experience in Japan with the ureteral advancement technique.

OBJECTIVES: To report our initial experience with robot-assisted laparoscopic extravesical ureteral reimplantation using the ureteral advancement technique. METHODS: A total of 15 ureters from nine patients (age range 2-25 years) underwent robot-assisted laparoscopic extravesical ureteral reimplantation for the management of vesicoureteral reflux. The reflux was classified as grade I in one ureter, grade II in two ureters, grade III in seven ureters, grade IV in three ureters and grade V in two ureters. One of the five female patients had a bilateral duplex system, and reflux was observed in all four ureters. The da Vinci surgical system was utilized. Ureteral advancement was carried out in all cases. We also compared the operative outcomes between conventional laparoscopic procedure and robotic surgery. RESULTS: The console time was 211.5 ± 87.4 min (median ± standard deviation) in the bilateral cases and 144.0 ± 40.8 min in the unilateral cases. Urethral catheters were removed at one or two postoperative days. None of the patients suffered postoperative complications, such as urine leakage or urinary retention. Postoperative voiding cystourethrography showed that the reflux had been resolved in 14 of the 15 ureters (success rate 93.3%). In the remaining case, the reflux grade decreased from III to I. The operative outcomes of robotic surgery were favorable and safe compared with conventional laparoscopic procedure. CONCLUSIONS: Our preliminary results showed that robot-assisted laparoscopic surgery is a feasible and useful approach to extravesical ureteral reimplantation, even for patients with bilateral reflux.

Intratesticular pressure after testicular torsion as a predictor of subsequent spermatogenesis: a rat model.

OBJECTIVE: To assess the correlation between intratesticular pressure (ITP) after testicular torsion and subsequent testicular function using a rat model and to show that ITP at surgery is a useful predictor of future spermatogenesis. MATERIALS AND METHODS: Fourteen rats were divided into a torsion group (n= 7) and a control group with sham operation (n= 7). Torsion was created by 720° rotation of the left testis in a counter-clockwise direction. Using a handheld compartment monitor, the ITP of the torsed testes was measured three times: before torsion (pre-torsion), just before torsion repair (pre-detorsion) and 5 min after torsion repair (post-detorsion). We evaluated the correlation between ITP and testicular weight, epididymal sperm count or pathological findings, such as the seminiferous tubule diameter (STD) and the modified Johnsen's score, 4 weeks after surgery. RESULTS: Mean (se) pre-torsion, pre-detorsion and post-detorsion ITP values in the torsion group were 5.9 (2.5), 19.7 (10.7) and 8.2 (4.8) cm H(2) O, respectively. The ITP in torsed testes significantly increased after torsion (P < 0.01) and decreased after detorsion (P < 0.01). Strong correlations were observed between the reduction of ITP after detorsion and testicular weight (r= 0.87, P < 0.05), epididymal sperm count (r= 0.94, P < 0.05), STD (r= 0.87, P < 0.05) or the Johnsen's score (r= 0.99, P < 0.001). CONCLUSION: A smaller reduction in ITP after detorsion can be a risk factor for subsequent disturbance of spermatogenesis, suggesting that ITP can be an index for determining whether the affected testis should be removed after testicular torsion.

Feasible etiology of vanishing testis regarding disturbance of testicular development: histopathological and immunohistochemical evaluation of testicular nubbins.

OBJECTIVES: To identify the causes of vanishing testis besides vascular events secondary to testicular torsion. METHODS: A total of 102 boys with vanishing testis were treated in our hospital from 1984 to 2011. Of these cases, 91 testicular nubbins were excised. Immunohistochemical analysis of testicular nubbins was carried out using anti-Wilms tumor 1 antibody, which is a stable marker of Sertoli cells. Reverse transcription polymerase chain reaction was also carried out using Wilms tumor 1-specific primers. RESULTS: Most testicular nubbins were associated with inguinal lesion (51 patients, 56.0%). Light microscopy showed that 11 patients (12.5%) had seminiferous tubules (with germ cells in three patients [3.4%]), and 77 patients lacked seminiferous tubules, some of which had calcification (26 patients, 29.5%), and/or deposition of hemosiderin (21 patients, 23.9%). Immunohistochemical analysis showed Wilms tumor 1 expression not only in the Sertoli cells of the seminiferous tubules in the seminiferous tubule-positive patients, but also in the interstitium of testicular nubbins in the seminiferous tubule-negative patients. Reverse transcription polymerase chain reaction showed Wilms tumor 1 messenger ribonucleic acid expression in the testicular nubbins of both seminiferous tubule-positive and tubule-negative patients. CONCLUSIONS: The presence of Wilms tumor 1-positive cells in the interstitium of vanishing testis lacking seminiferous tubules suggests that the disturbance of testicular development after Sertoli cell differentiation and during testicular tubule formation might be involved in the etiology of vanishing testis.

Plasmacytoid Urothelial Carcinoma of the Bladder That Manifests Disseminated Carcinomatosis of the Bone Marrow: A Case Report of Extremely Rapid Progression.

Plasmacytoid urothelial carcinoma (PUC) of the bladder is a rare variant of invasive urothelial carcinoma (UC) with aggressive behavior. Despite its prognosis being poorer than that of conventional UC, a median overall survival of approximately 2 years is ensured when it is treated with radical cystectomy (RC), and few patients die within a few months of RC. In this paper, we report the case of a patient with PUC who developed widespread bone metastasis only 6 weeks after RC, which resulted in death within 2 months postoperatively.

Characterization of the urethral plate and the underlying tissue defined by expression of collagen subtypes and microarchitecture in hypospadias.

OBJECTIVES: In hypospadia patients, the urethral plate and the underlying tissue were previously thought to be the main cause of penile curvature and, because of this, they used to be excised to correct the curvature. Currently, they are preserved as they are not thought to cause penile curvature anymore. The aim of the present histology study was to elucidate the characteristic structure of the tissue beneath the urethral plate. METHODS: The experimental group consisted of 27 hypospadiac patients with moderately severe penile curvature, who underwent one-stage urethroplasty after dividing the urethral plate. Excised tissues were observed under light microscopy and transmission electron microscopy (TEM). Furthermore, the presence of collagen subtypes I, III and IV was examined with immunohistochemical staining and western blotting. RESULTS: Light microscopy showed the existence of many massed and intertwined collagen fibers and vessels that resembled those of the cavernous sinus. TEM showed the existence of many collagen fibers, capillary vessels and other structures. Immunohistochemical staining showed collagen subtype I in the interfascicular space and collagen fibers were densely stained. Collagen subtype IV was found in the basement membrane of vessels, but collagen subtype III was not detected. The same results were obtained by western blotting. CONCLUSIONS: The tissue beneath the urethral plate was considered to originate from the corpus spongiosum penis. The distribution of collagen subtypes suggests that the presence of the tissue might affect ventral penile curvature. Long-term follow up is required after one-stage hypospadias repair with preservation of the urethral plate and the underlying tissue.

Myocarditis and myasthenia gravis by combined nivolumab and ipilimumab immunotherapy for renal cell carcinoma: A case report of successful management.

Ipilimumab plus nivolumab (Ipi/Nivo) has revolutionized advanced renal cell carcinoma (RCC) treatment. However, it encompassed fatal immune-related adverse events (irAEs). Myocarditis with concomitant myasthenia gravis (MG) has a mortality rate of 50%, and a high dose of methylprednisolone (mPSL) should be administered with careful attention to MG exacerbation. We present the case of a 59-year-old man with progressing lung metastasis of RCC. After one cycle of Ipi/Nivo, he experienced myocarditis and MG, managed by mPSL pulse therapy, plasma exchange, and high-dose intravenous immunoglobulin. We share the therapeutic course, aiming to contribute to the limited literature on rare but aggressive irAEs.

Initial treatment outcome and feasibility of low-dose cabazitaxel against docetaxel- and castration-resistant prostate cancer in a Japanese hospital.

Introduction: Cabazitaxel (CBZ) is used worldwide for castration-resistant prostate cancer after docetaxel treatment. In July 2014 the drug was approved in Japan with the same induction dose used for Caucasian patients. In this study, we examined and compared the results of an initial low-dose CBZ treatment in patients admitted to our hospital. Patients and Methods: Between July 2014 and August 2018, sixteen mCRPC patients were enrolled and underwent a low-dose CBZ treatment at our hospital. We compared the results with those of a Japanese metastatic docetaxel- and castration-resistant prostate cancer Phase I study. Results: The median patient age was 77 years (range, 53-84 years). Of the 16 patients, eight (50%) had a lymph node metastasis and 11 (68.8%) had a distant metastasis, 10 of whom had only a bone metastasis. The median dose of CBZ was 30 mg (range, 20-32 mg) and the median number of CBZ cycles was 2.5 (range, 1-18). The PSA level of 9 (56.3%) patients decreased after CBZ treatment, including 4 (25%) who showed a decrease to <50%. The median time interval in which the PSA level decreased was 2 months (range, 1-18 months). The observed adverse events (AE) were neutropenia (31.3%), febrile neutropenia (6.3%), fatigue (43.8%), nausea (18.8%), diarrhea (12.5%), decreased appetite (25%), dysgeusia (6.3%), white blood cell count decrease (43.8%), platelet count decrease (12.3%), and anemia (75%). However, no patient listed an AE as the reason for discontinuing the treatment. Conclusions: Even at a low dose, CBZ could improve the PSA value in patients with CRPC previously treated with docetaxel. Dose reduction and prophylactic administration of sustained G-CSF were also safe treatment options. Further studies involving an introduction period including a modulation of duration and dose are necessary, especially in Japanese patients.

Disorganization of claudin-11 and dysfunction of the blood-testis barrier during puberty in a cryptorchid rat model.

BACKGROUND: Cryptorchidism is known to impair spermatogenesis. The blood-testis barrier (BTB) becomes defined in seminiferous tubules around puberty and provides a suitable environment for germ cells. Little is known about the BTB in undescended testes (UDT). OBJECTIVES: To determine the role of BTB during puberty in UDT using a non-surgical cryptorchid rat model. MATERIAL AND METHODS: Unilateral cryptorchid male rats were intraperitoneally injected with non-steroidal antiandrogen during intrauterine development; the testes were harvested at 4, 5, and 6 weeks after birth. Testicular histology, expression levels of the BTB proteins (claudin-11, occludin, zonula occludens-1), and apoptotic cells were evaluated by immunohistochemistry, Western blotting, and TUNEL assay. The functionality of the BTB was investigated by electron microscopy using the lanthanum tracer method. RESULTS: The testicular histology of undescended testes 6 weeks after birth showed maturation arrest at the spermatocyte level. The BTB protein distributions were altered in the UDT, with a noticeable difference in claudin-11(CLDN11) localization from 4 to 5 weeks after birth between control and UDT samples. BTB protein levels were similar. More apoptotic germ cells were detected in the adluminal compartment of tubules in the UDT than in the control testes. Electron microscopy showed that the lanthanum tracer was limited to the BTB of control testes, whereas it penetrated the BTB of UDT. DISCUSSION: Here, loss of normal BTB function and impaired spermatogenesis were observed in UDT during puberty. CLDN11 is a pivotal tight junction protein belonging to the BTB. Tight junctions are considered as essential for normal spermatogenesis, and abnormal CLDN11 organization may cause UDT-associated male infertility. CONCLUSION: CLDN11 disorganization within the BTB may cause spermatogenic impairment, possibly by limiting the BTB function.

A case of laparoscopic fenestration surgery for pelvic lymphocele occurring after laparoscopic radical prostatectomy.

A 76-year-old Japanese man visited a nearby medical clinic complaining of abdominal distention. He had undergone extraperitoneal laparoscopic prostatectomy at our institution 5 months before the onset of abdominal distention. An imaging study revealed a large cystic lesion, and biochemical examination of a sample obtained via cyst puncture led to a diagnosis of lymphocele. As the lymphocele was resistant to puncture, drainage, and sclerotherapy with minomycin, laparoscopic fenestration was performed. Although the patient developed an adhesive ileus postoperatively, the cyst has not recurred. Fenestration surgery is a feasible option for lymphocele refractory to various conservative therapies.