C-Reactive Protein Is a Potential Prognostic Marker in Patient with Advanced or Metastatic Urothelial Carcinoma Treated with Enfortumab Vedotin: A Multi-Center Retrospective Study.

BACKGROUND: In the EV-301 trial, enfortumab vedotin prolonged survival in patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum-based therapy and programmed cell death 1/programmed death-ligand 1 inhibitor. However, real-world Asian data are limited, and potential prognostic markers are non-existent. We aimed to investigate potential prognostic markers for enfortumab vedotin therapy in Asian patients. METHODS: We retrospectively enrolled 61 Japanese patients treated with enfortumab vedotin therapy at our hospital and affiliated hospitals between January 2019 and September 2023. RESULTS: Enrolled patients (38 men, 23 women; median age 74 [IQR: 68-79] years) had bladder cancer (26 patients) or upper-tract urothelial carcinoma (35 patients). Fifty-four patients reported adverse events (grade >3 in 12). Skin disorders, pruritus, and neuropathy were common adverse effects. The median overall survival was 17.1 months (95% confidence interval: 10.0-not applicable). In multivariate analysis, the C-reactive protein level was an independent marker predicting favorable overall survival with enfortumab vedotin. Patient characteristics did not differ between C-reactive protein-high and -low groups. CONCLUSIONS: Our study provides real-world data showing that enfortumab vedotin prolonged survival in Asian patients similar to the EV-301 trial. Additionally, the C-reactive protein level might be considered a prognostic marker of enfortumab vedotin therapy in such patients.

Urothelial carcinoma occurring in a defunctionalized bladder after urinary diversion due to the bladder exstrophy-epispadias complex.

Introduction: The bladder exstrophy-epispadias complex is a rare congenital disease. Urothelial carcinomas rarely occur in patients with this disease, and there have been few reports on its treatment. Case presentation: We report the case of a 44-year-old man with a hemorrhage from the external urethral meatus. He was diagnosed with bladder exstrophy-epispadias complex and underwent urinary diversion with substitution cystoplasty and Mitrofanoff appendicovesicostomy. Because computed tomography and magnetic resonance imaging suggested invasive bladder carcinoma in the defunctionalized bladder, we performed a cystectomy. The patient was diagnosed with urothelial carcinoma with glandular differentiation. One month after the surgery, nivolumab adjuvant chemotherapy was administered. The patient showed no signs of recurrence or metastasis after the treatment. Conclusion: This is the first case of adjuvant nivolumab therapy for urothelial carcinoma with the bladder exstrophy-epispadias complex.

Proton pump inhibitors and potassium competitive acid blockers decrease pembrolizumab efficacy in patients with metastatic urothelial carcinoma.

We elucidated the efficacy of gut microbiome-altering drugs on pembrolizumab efficacy in patients with metastatic urothelial carcinoma (mUC). Clinical data were analyzed retrospectively from 133 patients with mUC who received second-line pembrolizumab therapy between January 2018 and January 2021, following failed platinum-based chemotherapy. We evaluated the effects of gut microbiome-altering drugs (proton pump inhibitors [PPI]/potassium-competitive acid blockers [P-CAB], H2 blockers, antibiotics, non-steroidal anti-inflammatory drugs [NSAIDs], metformin, antipsychotics, steroids, and opioids), taken by patients within 30 days before/after pembrolizumab treatment, on progression-free survival (PFS) and overall survival (OS). Fifty-one patients received PPI/P-CAB (37/14, respectively); H2 blockers, 7; antibiotics, 35; NSAIDs, 22; antipsychotics, 8; metformin, 3; steroids, 11; and opioids, 29. Kaplan-Meier curves revealed PPI or P-CAB users showed shorter PFS than non-PPI-P-CAB users (p = 0.001, p = 0.005, respectively). Multivariate analysis highlighted PPI/P-CAB use as the only independent prognostic factor for disease progression (hazards ratio: 1.71, 95% confidence interval: 1.14-2.07, p = 0.010) but not death (p = 0.177). Proton pump inhibitors/potassium-competitive acid blockers may decrease the efficacy of pembrolizumab therapy for mUC, possibly via gut microbiome modulation.

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.

A narrative review of peripheral blood parameters for urothelial carcinoma treated with systemic antitumor drugs.

Background and Objective: The prognosis of advanced urothelial carcinoma (aUC) is poor. To date, the gold standard of treatment for patients with aUC has been cisplatin-based chemotherapy. More recently, immune checkpoint inhibitors (ICIs) have been widely used for such patients, which has led to an improvement in their prognosis. In clinical practice, predicting the effectiveness of antitumor drugs or the prognosis of patients is important for making decisions on treatment strategies. Various parameters obtained from blood tests in the pre-ICI era have been adopted for patients in the ICI era. In this review, we summarize the parameters reflecting the status of aUC patients treated with ICIs based on current evidence. Methods: We conducted a literature search using PubMed and Google Scholar. The publications chosen were all peer-reviewed journals published over an unlimited time period. Key Content and Findings: Numerous inflammatory or nutritional parameters can be obtained from routine blood tests. These reflect malnutrition or systemic inflammation in patients with cancer. As in the pre-ICI era, these parameters are useful for predicting the effectiveness of ICIs and the prognosis of patients treated with ICIs. Conclusions: Various parameters are related to systemic inflammation and malnutrition, and are easily obtained from a routine blood test. Using these parameters from various studies as reference points is useful in making decisions on treatment for aUC.

Clinical characteristics of Raoultella ornithinolytica bacteremia and antimicrobial susceptibility of Raoultellaornithinolytica.

Raoultella ornithinolytica (R. ornithinolytica) is a gram-negative rod that was considered related to Klebsiella oxytoca and was classified as R. ornithinolytica in 2001. R. ornithinolytica is known as a histamine-producing bacterium that causes mackerel poisoning. Although only few clinical cases of R. ornithinolytica infection in humans have been reported, the number of diagnosed cases is expected to increase owing to the advancements in identification methods. In the present study, we performed a retrospective analysis of cases of R. ornithinolytica infection detected at our hospital. From September 2019 to July 2021, 62 specimens positive for R. ornithinolytica were obtained after removing duplicates. The clinical courses of these cases were investigated retrospectively based on electronic medical records. Of the 62 specimens, 24 were sputum, 19 were urine, three were stool, six were blood, four were bile, and six were other specimens. All the six blood culture specimens in which R. ornithinolytica was detected were from male patients, and the causative diseases were cholangitis in four cases and complicated pyelonephritis in two cases. Of these, two patients with cholangitis succumbed to death due to the worsening of underlying cancer. Identification of R. ornithinolytica is reportedly difficult, and some instruments may misidentify it as Klebsiella oxytoca. The prognosis of R. ornithinolytica infection has been reported to be good when susceptible drugs are used. However, high mortality rates were also reported despite the use of these drugs, suggesting the need for further investigation of clinical features of R. ornithinolytica infection.

Role of HIKESHI on Hyperthermia for Castration-Resistant Prostate Cancer and Application of a Novel Magnetic Nanoparticle with Carbon Nanohorn for Magnetic Hyperthermia.

The prognosis of castration-resistant prostate cancer (CRPC) is technically scarce; therefore, a novel treatment for CRPC remains warranted. To this end, hyperthermia (HT) was investigated as an alternative therapy. In this study, the analysis focused on the association between CRPC and heat shock protein nuclear import factor "hikeshi (HIKESHI)", a factor of heat tolerance. Silencing the HIKESHI expression of 22Rv1 cells (human CRPC cell line) treated with siRNAs inhibited the translocation of heat shock protein 70 from the cytoplasm to the nucleus under heat shock and enhanced the effect of hyperthermia. Moreover, a novel magnetic nanoparticle was developed via binding carbon nanohorn (CNH) and iron oxide nanoparticle (IONP) with 3-aminopropylsilyl (APS). Tumor-bearing model mice implanted with 22 Rv1 cells were examined to determine the effect of magnetic HT (mHT). We locally injected CNH-APS-IONP into the tumor, which was set under an alternative magnetic field and showed that tumor growth in the treatment group was significantly suppressed compared with other groups. This study suggests that HIKESHI silencing enhances the sensitivity of 22Rv1 cells to HT, and CNH-APTES-IONP deserves consideration for mHT.

A rare case of a clear cell carcinoma in a female urethral diverticulum.

Introduction: Urethral clear cell carcinoma is rare and often arises from a urethral diverticulum and rarely from the Müllerian duct. However, an explanation for this correlation remains unknown. Case presentation: We report the case of a 46-year-old woman who presented with hypermenorrhea. Magnetic resonance imaging revealed a papillary tumor in a cystic lesion in the dorsal urethra. We performed a robot-assisted radical cystourethrectomy and created an ileal conduit. Since pathological findings revealed microvascular and lymphovascular invasions around the urethra, adjuvant radiation therapy was administered. The patient showed no signs of recurrence or metastasis after treatment. Conclusion: We report a case of clear cell carcinoma in a female urethral diverticulum originating from a Müllerian duct cyst. While postoperative radiation therapy has been shown to produce a good outcome in carcinoma cases similar to this one, we recommend that a radical cystourethrectomy be performed.

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.

A rare case of long-term survival from metachronous bilateral adrenal metastasis of lung adenocarcinoma after combined surgical removal and immunochemotherapy.

Introduction: The prognosis of adrenal metastasis from non-small cell lung cancer is very poor. A recent report described the efficacy of the surgical removal of adrenal metastasis when solitary. However, metachronous bilateral adrenal metastasis is extremely rare, and a treatment strategy has not been established. Case presentation: Herein, we describe a 52-year-old Asian male who presented with a right adrenal metastasis of non-small cell lung cancer 8 months after immunochemotherapy and surgical resection of the lung. He underwent combined systemic treatment and a laparoscopic right adrenalectomy; however, after 9 months, a metachronous left adrenal metastasis emerged. A subsequent laparoscopic left adrenalectomy and systemic treatment led to long-term progression-free survival. Conclusion: The appropriate surgical indication and combined systemic treatment of a metachronous bilateral adrenal metastasis in non-small cell lung cancer may extend the prognosis.

A case of metastatic treatment-emergent small cell/neuroendocrine prostate cancer with BRCA2 mutation diagnosed by liver biopsy.

Introduction: Treatment-emergent small cell/neuroendocrine prostate cancer occurs predominantly in advanced or metastatic castration-resistant prostate cancer that arises when prostate adenocarcinoma is transformed after androgen deprivation therapy. The clinical course for the pathogenesis involved or associated genetic information have not been clearly elucidated. Case presentation: A Japanese male, 63-year-old, underwent a para-aortic lymph biopsy due to sudden severe bilateral leg edema, with a final diagnosis of stage IV prostate adenocarcinoma. He was initially responsive to upfront abiraterone with androgen deprivation therapy; however, relapse occurred in the liver and bone 10 months after initial treatment, with serum neuron-specific enolase elevation and without prostate-specific antigen elevation. Pathological findings of liver tumor revealed treatment-emergent small cell/neuroendocrine prostate cancer. FoundationOne® CDx was used for cancer-related gene profiling of liver tumor specimen; a BRCA2 mutation was identified. Conclusion: Early detection of this transformation and pathological diagnosis can improve patient survival when genetic mutations, including BRCA 1/2.