Successful treatment with enfortumab-vedotin of metastatic signet ring cell cancer expressing nectin-4 and originating from the bladder.

Introduction: As an aggressive adenocarcinoma phenotype, primary signet ring cell carcinoma of the urinary bladder is an extremely rare variant. The prognosis of metastatic signet ring cell carcinoma of the urinary bladder is extremely poor and the clinical course for its specific pathogenesis remains unelucidated. Case presentation: A 64-year-old Japanese male patient was diagnosed with invasive urothelial carcinoma with glandular differentiation of a signet ring cell-type with pT4aN0M0, and he was eventually diagnosed with metastatic signet ring cell carcinoma of the urinary bladder. He was initially responsive to systemic combination induction chemotherapy of S-1 and cisplatin followed by avelumab switch maintenance therapy; however, signet ring cell carcinoma of the urinary bladder relapse occurred in the pathological findings of a biopsy from the right thigh. Immunohistochemical analysis of this specimen identified strong positive staining for nectin-4 and, following enfortumab-vedotin treatment, the patient showed a good response. Conclusion: We thus describe a rare case of metastatic signet ring cell carcinoma of the urinary bladder with nectin-4 expression diagnosed by a biopsy of a metastatic site.

Postoperative Bladder Neck to Pubic Symphysis Ratio Predictive for De Novo Overactive Bladder after Robot-Assisted Radical Prostatectomy.

BACKGROUND: The aim was to investigate the incidence and clinical predictive factors of de novo overactive bladder (OAB) after robot-assisted radical prostatectomy (RARP), including a Retzius-sparing (RS) approach, in the same period at a single institution. METHODS: Of a total of 113 patients with localized prostate cancer, 81 received conventional RARP (CON-RARP) and 32 received RS-RARP at our institution. The basic characteristics data of patients and self-assessment questionnaires, including IPSS and OABSS, were obtained preoperatively and 1, 3, and 6 months after RARP. In addition, a retrospective biomarker analysis was also performed of predictive clinical parameters obtained from cystography that included a postoperative bladder neck to pubic symphysis (BNPS) ratio. RESULTS: Patients' basic characteristics were similar between CON-RARP and RS-RARP groups. With respect to the surgical procedure, anastomosing time was found to be significantly longer for patients in the RS-RARP compared to the CON-RARP group (p < 0.01). Compared to the CON-RARP group, the RS-RARP group showed a significantly lower postoperative BNPS and aspect ratio (p < 0.001). The incidence of de novo OAB in patients of the CON-RARP group was greater than for those in the RS-RARP group (40.7% CON-RARP vs. 25.0% RS-RARP), though this was not significant. Regarding the emergence of de novo OAB, the following were revealed in univariate analysis to be independent prognostic factors: age > 64 years (hazards ratio [HR]: 4.32, 95% confidence interval [CI]: 1.51-12.3), postoperative BNPS ratio > 0.44 (HR: 8.7, 95% CI: 6.43-54.5), postoperative aspect ratio > 1.18 (HR: 3.36, 95% CI: 1.49-7.61). Additionally, multivariate analysis identified a sole significant prognostic factor: postoperative BNPS ratio > 0.44 (HR: 13.3, 95% CI: 4.33-41.1). CONCLUSION: Our findings indicate that the postoperative BNPS ratio may be a practical predictive indicator of the emergence of de novo OAB after RARP.

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.

A Multicenter, Prospective, Non-randomized Study Evaluating Surgical hand Preparation between Double-Gloving and Single-Gloving for Preventing Postoperative Infection in Robotic and Laparoscopic Minimally Invasive Surgeries.

PURPOSE: This study aimed to analyze a feasible and suitable surgical precautionary preparatory technique. The techniques of double-gloving with hygienic hand wash (DH) and single-gloving with surgical hand wash (SS) were compared for their ability to prevent postoperative infection in robotic and laparoscopic minimally invasive surgeries. MATERIALS AND METHODS: A prospective, non-randomized, multicenter study was conducted between January 2016 and June 2020. We divided the robotic and laparoscopic cases into two groups: DH and SS. Data on infectious outcomes were collected. Propensity score matching was performed to control for operative characteristics between the two groups. The primary endpoint was the presence of fever and surgical site infections (SSIs) indicating postoperative infection. RESULTS: Among four medical centers, seven surgeons were allocated to either the DH or the SS group. A total of 221 and 251 patients underwent DH and SS, respectively. Propensity score matching, which included 171 cases from each group, showed that the incidence of fever during hospitalization was significantly lower in the DH group than that in the SS group (11.7% vs. 23.4%, p=0.007). Multivariable analysis revealed that DH was associated with a reduced odds ratio for developing postoperative fever during hospitalization (risk ratio: 0.49, p=0.043). No differences were found in SSI before and after hospitalization between the two groups. CONCLUSION: DH resulted in less postoperative fever and had a comparable effect in preventing SSIs. This procedure could be an alternative to the SS protocol in some minimally invasive surgeries.

Testicular seminoma arising from infertile testes 6 years after microdissection testicular sperm extraction.

INTRODUCTION: In Western countries, the risk of a testicular germ cell tumor in men with male factor infertility is greater than in the general population. However, Japanese data on this risk are lacking. Additionally, the clinical course for the pathogenesis involved has not been clearly characterized. CASE PRESENTATION: A 35-year-old Japanese male underwent a right orchiectomy because of a mass in his right scrotum. He had a previous history of microdissection testicular sperm extraction undertaken 6 years ago. The final diagnosis of the right scrotal mass was a stage I seminoma. However, a relapse occurred in the left inguinal lymph node 2 years after surgery and the patient was consequently treated with systemic chemotherapy. Pathological analysis of a microdissection testicular sperm extraction sample yielded a germ cell neoplasia in situ in the right testis. CONCLUSION: In Japan, men who seek an evaluation for infertility might be more likely to develop testicular germ cell tumor.

Change in the central control of the bladder function of rats with focal cerebral infarction induced by photochemically-induced thrombosis.

The photochemically-induced thrombosis (photothrombosis) method can create focal cerebral infarcts anywhere in the relatively superficial layers of the cerebrum; it is easy to implement and minimally invasive. Taking advantage of this versatility, we aimed to establish a new rat model of urinary frequency with focal cerebral infarction, which was characterized by its simplicity, nonlethal nature, and high reproducibility. The prefrontal cortex and the anterior cingulate cortex, which are involved in lower urinary tract control, were targeted for focal cerebral infarction, and urinary parameters were measured by cystometrogram. Cystometric analysis indicated that micturition intervals significantly shortened in photothrombosis-treated rats compared with those in the sham operative group on Days 1 and 7 (P < 0.01), but prolonged after 14 days, with no difference between the two groups. Immunopathological evaluation showed an accumulation of activated microglia, followed by an increase in reactive astrocytes at the peri-infarct zone after photothrombotic stroke. Throughout this study, all postphotothrombosis rats showed cerebral infarction in the prefrontal cortex and anterior cingulate cortex; there were no cases of rats with fatal cerebral infarction. This model corresponded to the clinical presentation, in that the micturition status changed after stroke. In conclusion, this novel model combining nonlethality and high reproducibility may be a suitable model of urinary frequency after focal cerebral infarction.

Rare case of immunoglobulin G4-related disease arising in gonadal glands with long-term remission without steroid treatment: Discussion and literature review.

INTRODUCTION: Immunoglobulin G4-related disease embraces a wide range of extra-pancreatic manifestations. However, localized pathogenesis in gonadal glands, including testes or seminal vesicles, is rare. The clinical course and therapeutic strategy for this disease have not been clearly characterized. CASE PRESENTATION: A 61-year-old Asian male had a left orchiectomy and right seminal vesicle biopsy because of a mass in the left testis and right seminal vesicle. Histological findings showed an infiltration of immunoglobulin G4-positive plasma cells in the respective tissues and met immunoglobulin G4-related disease diagnostic criteria. No recurrence and exacerbation have been observed after 12 years' follow-up without any clinical intervention. To date, immunoglobulin G4-related disease in gonadal tissue is rare. This is the first case with mass-forming lesions in both the testis and seminal vesicle. CONCLUSION: Based on the clinical course of our case and the literature, for patients with accurately diagnosed inactive gonadal immunoglobulin G4-related disease, watchful waiting is a feasible clinical treatment option.

Novel case of androgen receptor-positive cancer of unknown primary without serum prostate-specific antigen elevation that became progression free in the long term after primary combined androgen blockade.

INTRODUCTION: The prognosis of cancer of unknown primary is very poor. Such a prognosis can be improved by characterizing primary characteristics and developing tailored site-specific therapy, especially for androgen receptor-positive adenocarcinoma. However, in such cases without elevated prostate-specific antigen, the efficacy of androgen deprivation therapy is unclear. CASE PRESENTATION: Herein, we report a case that presented with a retroperitoneal cancer of unknown primary that was confirmed as an androgen receptor-positive adenocarcinoma without prostate-specific antigen elevation. Pelvic magnetic resonance imaging did not reveal any suspicious cancer lesions in the prostate. Furthermore, malignant cells were not present in a prostate biopsy specimen. In spite of the prostate-specific antigen level, on the basis of immunohistochemical analyses, including NKX3.1, the patient was first treated with androgen deprivation therapy, leading to long-term progression-free survival. CONCLUSION: Early androgen deprivation therapy based on immunohistochemical analyses might lead to a good outcome in androgen receptor-positive adenocarcinoma cancer of unknown primary patients regardless of prostate-specific antigen level.

Pelvic Anatomical Features After Retzius-Sparing Robot-Assisted Radical Prostatectomy Intended for Early Recovery of Urinary Symptoms.

Purpose: To elucidate factors contributing to early urinary continence recovery after retzius-sparing robot-assisted radical prostatectomy (RS-RARP) by evaluating postoperative pelvic anatomical features between RS-RARP and conventional RARP (CON-RARP). Materials and Methods: We retrospectively examined 50 men who underwent RS-RARP (n = 25; the RS-RARP group) and CON-RARP (n = 25; the CON-RARP group) between October 2017 and June 2018. Perioperative outcomes and postoperative urinary continence were assessed in both groups. Anatomical features including the bladder neck-to-pubic symphysis ratio (determined from cystograms) and membranous urethral length (MUL) (determined from magnetic resonance imaging) were evaluated. Result: The daily urinary incontinence rate at discharge was significantly lower in the RS-RARP group than in the CON-RARP group (0.046 [range: 0.014-0.160] vs 0.357 [range: 0.139-0.616], p < 0.001). Postoperative urinary continence at 1, 3, 6, and 12 months was 80%, 92%, 96%, and 96% in the RS-RARP group and 24%, 40%, 68%, and 84% in the CON-RARP group, respectively (p < 0.001). The urgency scores in the international prostate symptom score (IPSS) questionnaire at 1 and 3 months were significantly lower in the RS-RARP than in the CON-RARP group (p = 0.028 and 0.033, respectively). The quality of life (QOL) indices were more significantly improved in the RS-RARP group than in the CON-RARP group 1 month (p = 0.027) and 3 months (p = 0.045) postoperatively. Receiver operating characteristic analysis revealed that a postoperative MUL of 12.1 mm (area under the curve: 0.852) was the optimal cutoff value predictive of continence recovery after 1 month. Multivariate analysis demonstrated that RS-RARP (odds ratio [OR]: 23.6; p < 0.001) and prostate volume (OR: 0.926; p = 0.049) were the independent factors of a longer MUL. Conclusions: RS-RARP results in an early continence recovery and a better urgency score in the IPSS by suppressing the descent of the bladder and maintaining a long MUL. RS-RARP may contribute to a better QOL recovery after RARP.

Microscopic pulmonary tumor embolism from adenocarcinoma of the prostate.

INTRODUCTION: Microscopic pulmonary tumor embolisms from prostate cancer are extremely rare. In this case of prostate cancer, microscopic pulmonary tumor embolism developed during androgen deprivation therapy. CASE PRESENTATION: A 56-year-old man was diagnosed with prostate cancer and underwent androgen deprivation therapy. Three months after starting treatment, he noticed shortness of breath and developed acute progressive dyspnea. He was diagnosed with pulmonary hypertension; however, the cause was not found. His dyspnea was progressive and he died 40 days after the onset of symptoms. Autopsy proved that the cause of pulmonary hypertension was microscopic pulmonary tumor emboli from prostate cancer. Furthermore, histology revealed differences in the androgen receptors in the prostate and emboli, with significantly greater Ki-67 expression in the emboli than in the prostate. CONCLUSION: Prostate cancer proliferated in the pulmonary artery after hematogenous metastasis, caused vascular occlusion, and formed microscopic pulmonary tumor embolisms.

Rare case of Richter syndrome with testicular involvement successfully obtained good prognosis with rapid operation and immunochemotherapy.

INTRODUCTION: Richter syndrome refers to the transformation from chronic lymphocytic leukemia to assaultive lymphoma, often a diffuse large B-cell lymphoma, and has a greatly poor prognosis. Richter syndrome is characterized by rapidly growing lymphadenopathy but rarely presents with extra-nodal involvement, common sites being the digestive tract, lungs, kidneys, and central nervous system. However, Richter syndrome with testicular involvement is extremely rare. CASE PRESENTATION: Herein we report a very scare case of a male at the age of 72 with Richter syndrome and testicular involvement, diagnosed by the investigation of bilateral scrotal swellings. The patient had attained disease-free survival for over a year with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and the intrathecal administration of chemotherapeutic agents after diagnosis by immediate orchiectomy. CONCLUSION: An early pathological diagnosis by immediate orchiectomy and the early initiation of induction immunochemotherapy may be good prognostic factors in Richter syndrome involving the testes.