Transvaginal vesicovaginal fistula closure: A retrospective study of 28 cases at a single facility in Japan.

OBJECTIVES: We aimed to report the background of patients with vesicovaginal fistulas (VVFs) at our center, which has treated a relatively large number of such patients in Japan, as well as the ingenuity and outcomes of vesicovaginal fistula closure (VVFC). We also investigated the causes of VVFs. METHODS: A retrospective review was performed for 28 patients with VVFs treated at our center. Age, body mass index, etiology, site of fistula, and postoperative outcomes were investigated. RESULTS: Twenty-one (75%) fistulas occurred following hysterectomy. The overall success rate of VVFC was 85.7%, and the success rate limited to the first attempt was 89.5%. In 68% of cases, no bladder injury suspected as the cause of VVF was noticed during the surgery. Energy devices were used in all 12 patients for whom information on the type of device used for hysterectomy was confirmed. CONCLUSIONS: To our knowledge, this is the first report to evaluate a relatively large number of VVFCs in Japan. Although VVF is thought to be caused by bladder injury during hysterectomy, delayed thermal damage might also result in this pathology, even if there is no apparent intraoperative bladder injury.

Prognostic model for overall survival that includes the combination of platelet count and neutrophil-lymphocyte ratio within the first six weeks of sunitinib treatment for metastatic renal cell carcinoma.

BACKGROUND: The association between the combination of platelet count and neutrophil-lymphocyte ratio (COP-NLR) at the time of adverse events during sunitinib treatment and prognosis is unclear, and prognostic models combining the prognostic factors of sunitinib have not been well studied. Thus, we developed a prognostic model that includes the COP-NLR to predict the prognosis of patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib. METHODS: We performed a retrospective cohort study of 102 patients treated with sunitinib for mRCC between 2008 and 2020 in three hospitals associated with Showa University, Japan. The primary outcome was overall survival (OS). The collected data included baseline patient characteristics, adverse events, laboratory values, and COP-NLR scores within the first 6 weeks of sunitinib treatment. Prognostic factors of OS were analyzed using the Cox proportional hazards model. The integer score was derived from the beta-coefficient (ß) of these factors and was divided into three groups. The survival curves were visualized using the Kaplan-Meier method and estimated using a log-rank test. RESULTS: The median OS was 32.3 months. Multivariable analysis showed that the number of metastatic sites, Memorial Sloan Kettering Cancer Center risk group, number of metastases, non-hypertension, modified Glasgow Prognostic Score, and 6-week COP-NLR were significantly associated with OS. A higher 6-week COP-NLR was significantly associated with a shorter OS (p < 0.001). The ß values of the five factors for OS were scored (non-hypertension, mGPS, and 6-week COP-NLR = 1 point; number of metastatic sites = 2 points; MSKCC risk group = 3 points) and patients divided into three groups (≤ 1, 2-3, and ≥ 4). The low-risk (≤ 1) group had significantly longer OS than the high-risk (≥ 4) group (median OS: 99.0 vs. 6.2 months, p < 0.001). CONCLUSIONS: This study showed that the COP-NLR within the first 6 weeks of sunitinib treatment had a greater impact on OS than the COP-NLR at the start of sunitinib treatment. The developed prognostic model for OS, including the 6-week COP-NLR, will be useful in decision-making to continue sunitinib in the early treatment stage of patients with mRCC.

[INITIAL TREATMENT OF NOCTURIA CAUSED BY NOCTURNAL POLYURIA WITH LOW-DOSE DESMOPRESSIN].

(Objective) Nocturia, an important male lower urinary tract symptom (LUTS), is often difficult to treat. Herein, we report our experience of the initial treatment of nocturia with the novel drug desmopressin. (Subjects and methods) Subjects included 25 patients with LUTS treated with desmopressin who had the chief complaint of nocturia. Before treatment, the frequency of nocturnal urination (≥2) and nocturnal polyuria index (≥0.33) were confirmed based on the urination diary for ≥ 72 h. Before sleep, 25 or 50 mg desmopressin (Minirin® Melt OD tablets) was administered once daily. The frequency of nocturnal urination, volume of nocturnal urine, time from falling asleep to first urination, first urinary volume after falling asleep, nocturnal polyuria index, International Prostate Symptom Score (IPSS), quality of life index, Overactive Bladder Symptom Score, and residual urine volume were comparatively evaluated before and 4 weeks after treatment. Treatment effect was self-evaluated by patients 4 weeks after the treatment. Safety was evaluated by interview and blood testing 1 and 4 weeks after the treatment. (Results) Decrease in the frequency of nocturnal urination and improvement in IPSS were observed. According to self-evaluation of the treatment, 72.6% of the patients considered the treatment efficacious. Regarding safety, adverse events were observed in 28% of the patients, particularly hyponatremia (12% of the patients). (Conclusion) Desmopressin is a potential key drug for the treatment of nocturia caused by nocturnal polyuria.

[EFFICACY AND SAFETY OF 25 AND 50 µg DESMOPRESSIN ORALLY DISINTEGRATING TABLETS IN NOCTURIA DUE TO NOCTURNAL POLYURIA IN JAPANESE MALE PATIENTS].

(Purpose) To conduct a prospective study on the efficacy and safety of desmopressin for nocturnal polyuria. (Materials and methods) We selected 51 Japanese men, aged ≥50 years, with complaints of nocturia and a nocturnal polyuria index of ≥0.33. We administered 25 or 50 µg desmopressin (Minirinmelt Orally Disintegrating Tablet®), once daily at bedtime. We evaluated the nighttime urinary frequency and urine volume, nocturnal polyuria index, time to the first urination after falling asleep, and International Prostate Symptom Score (IPSS) at baseline and at 4, 8, and 12 weeks after administration. In addition, they underwent clinical examinations and blood tests at 1, 4, and 12 weeks to evaluate the safety of the drug. (Results) We observed a decrease in the nighttime urinary frequency and urine volume, and nocturnal polyuria index, increased prolonged time to the first urination after falling asleep, and improved IPSS at and after 4 weeks, compared to baseline data. Furthermore, the drug remained effective even at 12 weeks for all parameters. We observed adverse events in 31.3% of the patients. The incidence of hyponatraemia was particularly high in 15.7% of the patients. Those with a lower serum sodium level and lesser body weight at baseline were more likely to develop hyponatraemia. (Conclusion) Desmopressin was identified as a potential drug for the treatment of nocturnal polyuria. However, hyponatraemia, an important adverse event, resulted in treatment discontinuation in several patients. A sodium level lower than the normal level and low body weight at baseline were the risk factors for hyponatraemia.

Development of a Highly Sensitive Technique for Capturing Renal Cell Cancer Circulating Tumor Cells.

PURPOSE: Liquid biopsy is becoming increasingly important as a guide for selecting new drugs and determining their efficacy. In urological cancer, serum markers for renal cell and urothelial cancers has made the development of liquid biopsy for these cancers strongly desirable. Liquid biopsy is less invasive than conventional tissue biopsy is, enabling frequent biopsies and, therefore, is considered effective for monitoring the treatment course. Circulating tumor cells (CTCs) are a representative liquid biopsy specimen. In the present study, we focused on developing our novel technology for capturing renal cell cancer (RCC)-CTCs using an anti-G250 antibody combined with new devices. Basic experiments of our technology showed that it was possible to detect RCC-CTC with a fairly high accuracy of about 95%. Also, RCC-CTC was identified in the peripheral blood of actual RCC patients. Additionally, during the treatment course of the RCC patient, change in the number of RCC-CTC was confirmed in one case. We believe that the technology we developed will be useful for determining the treatment efficacy and drug selection for the treatment of renal cell cancer (RCC). In order to solve issues such as thresholds setting of this technology, large-scale clinical trials are expected.

Systematic review and two new cases of primary upper urinary tract neuroendocrine carcinomas.

BACKGROUND: Upper urinary tract neuroendocrine carcinoma (UUT-NEC) is extremely rare and has a poor prognosis. Although a few cases of successful treatment have been reported, no treatment has shown established efficacy. PATIENTS AND METHODS: We analyzed 70 UUT-NEC patients, including 68 with small cell neuroendocrine carcinoma (SCNEC) and large cell neuroendocrine carcinoma (LCNEC) reported between 1985 and 2017 and 2 treated at our hospital. RESULTS: Median patient age was 66 years, 58.6% were men, and 60% were of Asian descent. Most UUT-NECs were SCNEC (68; 95.7%), whereas LCNEC was very rare (2; 2.9%). More than half of the patients had accompanying other histological components, the most common being urothelial carcinoma (51.5%), whereas 41.4% had NEC alone. Of the 70 patients, 27 underwent additional therapy (e.g., chemotherapy and radiotherapy) along with surgery. Median survival was 15 months. In univariate analysis, stages T1-2 disease showed better prognosis than stages T3-4 (P < 0.001). Additional treatment (e.g., chemotherapy and radiotherapy) significantly improved prognosis (P = 0.014). Moreover, platinum-based chemotherapy also was associated with improved prognosis (P = 0.017). For platinum-based chemotherapy, multicollinearity with additional treatments was strong, and, thus, these data were not included in the analysis. Multivariate analysis revealed pathological stage (T1-2 vs. T3-4; P = 0.003) and additional treatment (P = 0.028) to be independent predictors of improved prognosis. CONCLUSION: Although UUT-NEC has a poor prognosis, additional treatment along with surgery and therapeutic intervention and stage T1-2 disease are independent factors to improve prognosis.

INITIAL EXPERIENCE OF THE ENZALUTAMIDE TREATMENT FOR CASTRATION-RESISTANT PROSTATE CANCER.

(Objective) Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with castration-resistant prostate cancer (CRPC). We retrospectively evaluated clinical efficacy and safety of enzalutamide in CRPC. (Patients and methods) We reviewed clinical records of 73 patients who had received enzalutamide for the CRPC at Showa University and affiliated 7 hospitals. Enzalutamide was given at a dose of 160 mg/day, but some patients were treated at lower dose because of there age or poor performance status. Prostrate-specific antigen (PSA) response, prior docetaxel use and the previously administered agents were evaluated retrospectively. (Results) The median patients age was 77 years, the median Gleason score was 9 and the median PSA level at baseline was 26.9 ng/ml. The patients who had prior docetaxel use were 29 (39.7%) and the median of total docetaxel dose was 460 mg/body. The median number of total prior treatments (anti-androgens, Estramustine and steroid) was 3. Twenty seven (61.4%) patients with docetaxel-naïve achieved over 50% reduction of PSA level from baseline, but only 7 (24.1%) in patients previously treated with docetaxel. The most common adverse events included fatigue (24.7%), anorexia (24.7%) and the nausea (16.4%). We found a small proportion of responders to enzalutamide experienced a PSA flare. (Conclusion) Our results of the use of Enzaltamide for CRPC were similar with previous reports. PSA flare was found in some patients with CRPC who responded to enzaltamide. It should be noted that this possible PSA flare phenomenon.

[A CASE OF PROSTATE CANCER WITH UNUSUAL PATTERN OF RECURRENCE AFTER RADIOTHERAPY].

An 82-year-old man underwent radiotherapy (brachytherapy, external beam radiotherapy) for prostate cancer, followed approximately five years later by endocrine therapy for biochemical recurrence, which controlled the prostate-specific antigen (PSA) level. His later admission due to severe gross hematuria and dysuria is described. Computed tomography and magnetic resonance imaging findings revealed a cystic tumor continuous with the prostate between the prostate and rectum, and this tumor was thought to be the cause of the hematuria and dysuria. Transrectal biopsy and transurethral resection of the prostate were performed for pathological diagnosis and improvement of dysuria. The pathological diagnosis was remnant prostate cancer, and the cystic tumor was thought to have developed as a result of prostate cancer recurrence. Although chemotherapy using docetaxel was considered postoperatively, the patient refused this treatment. Even though the PSA level was under control, the patient's condition progressed rapidly, with onset of pulmonary and cervical lymph node metastases within a short period of time, and the patient subsequently died.

Complete response to low-dose sorafenib in a patient with metastatic renal cell carcinoma: A case report.

We present a case of a patient with metastatic renal cell carcinoma (mRCC) who was treated solely with low-dose sorafenib and achieved a complete response (CR). A 79-year-old man with cytokine-refractory mRCC involving the lung, abdominal wall and lymph nodes was treated with low-dose sorafenib (400 mg/day) as a second-line therapy. Five months into treatment, CR was confirmed by follow-up computed tomography. No severe adverse events were observed and sorafenib treatment was continued without appearance of new lesions. Although sorafenib has been approved for mRCC treatment, complete clinical recovery is uncommon and has rarely been described. In this case, low-dose sorafenib appears to be sufficient for achieving CR while suppressing toxicity. Furthermore, long-term continuous administration induces the patient to obtain disease stabilization. However, considering toxicity and treatment costs, it is debatable whether treatment should be discontinued or sustained after CR.

The effects of chlormadinone acetate on lower urinary tract symptoms and erectile functions of patients with benign prostatic hyperplasia: a prospective multicenter clinical study.

Purpose. To evaluate the effects of chlormadinone acetate (CMA), progesterone-derived antiandrogen, on lower urinary tract symptoms (LUTS) and erectile functions of benign prostatic hyperplasia (BPH). Methods. A multicenter, single-cohort prospective study was conducted. A total of 114 patients received CMA for 16 weeks. The endpoints were changes in International Prostate Symptom Scores (IPSS), IPSS-QOL, International Index of Erectile Function-5, Q max prostate volume, and residual urine volume. Results. Significant improvements were observed in IPSS from week 8 to week 48 (32 weeks after treatment). IPSS-QOL improvements were also significant from week 8 to week 48. Q max increased to a maximum at Week 16 and remained elevated throughout the study. Moreover, a decrease of 25% in prostate volume was observed at Week 16. IPSS, QOL, and Qmax changes during the study were not different between the previously treated and untreated patients. IPSS storage subscore changes differed between the age groups. Few severe adverse reactions were observed, except for erectile dysfunction. Conclusions. CMA rapidly and significantly reduced prostate volume and improved voiding and storage symptoms and QOL. Our results suggest that CMA is safe and beneficial, especially for elderly patients with LUTS associated with BPH.

[Changes in serum prostate specific antigen and testosterone levels after chlormadinone acetate treatment in patients with benign prostatic hyperplasia : a prospective multicenter clinical study].

In this prospective multicenter study, we investigated the changes in serum prostate-specific antigen (PSA) and testosterone levels after treatment with antiandrogen chlormadinone acetate (CMA) in patients with benign prostatic hyperplasia (BPH). The inclusion criteria for the patients were as follows : PSA value of C10 ng/ml, maximum urine flow rate of ＜15 ml/s, estimated prostate volume of B20 ml, International Prostate System Score (IPSS) of B8, and IPSS-quality of life (QOL) index of B2. Of the 115 patients who registered, 114 qualified for this study. The patients were treated with CMA (50 mg/day) for 16 weeks ; this was followed by a no-CMA phase of 32 weeks. When compared with the baseline PSA level, the levels at 8 and 16 weeks of treatment had decreased by 56.4% (95% confidence interval [CI], 51.1-1.2) and 57.6% (95% CI, 52.3-62.4), respectively. Similarly, when compared with the baseline testosterone level, the levels at 8 and 16 weeks of treatment had decreased by 90.1% (95% CI, 87.8-91.9) and 84.4% (95% CI, 80.7-87.4), respectively. After treatment discontinuation, the PSA levels gradually increased and returned to baseline in 32 weeks. However, the testosterone levels returned to baseline in only 8 weeks. Although patients over 80 years of age showed a gradual decrease in these levels when compared with younger patients, the changes in the levels of PSA and testosterone were not affected by age. Thus, in order to use antiandrogen agents including CMA for treating BPH, we need to determine the PSA value that converted it into double.

A pilot study of quality of life of patients with hormone-refractory prostate cancer after gene therapy.

BACKGROUND: The effects on quality of life (QOL) after a Phase I/II clinical trial of a combination of osteocalcin promoter-driven herpes simplex virus thymidine kinase (Ad-OC-TK) gene therapy and valacyclovir (VAL) were investigated for patients with hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: The QOL of six patients was prospectively assessed after gene therapy on days 0, 14, and 28. A modified questionnaire was created based on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire's prostate cancer-specific module (EORTC QLQ-PR25). RESULTS: The scores of all items significantly improved along with the total score. Further, bodily pain was significantly reduced on day 28. Moreover, the rate of change in the serum prostate-specific antigen levels from day 0 to day 28 was significantly correlated with the rate of change in bodily pain. CONCLUSION: In this clinical trial, Ad-OC-TK plus VAL treatment significantly improved the short-term QOL and bodily pain of patients with localized recurrence or bone metastases of HRPC.

Influence of hospital and surgeon volumes on operative time, blood loss and perioperative complications in radical nephrectomy.

OBJECTIVES: We conducted a nationwide multi-center survey using medical record-based data to investigate the relationship between hospital/surgeon volumes and various outcomes, including operative time, volume of blood loss, and incidence of perioperative complications, in radical nephrectomy for renal cell carcinoma. METHODS: We investigated a total of 1704 patients who underwent radical nephrectomy at 461 hospitals in Japan between November 2006 and February 2007. The association between hospital/surgeon volumes and operative time, volume of blood loss, and incidence of perioperative complications were independently analyzed using multivariate regression analysis against age, gender, operation site, cancer stage, serum creatinine levels, comorbid conditions, and surgical technique (open surgery or minimally invasive surgery). RESULTS: Neither hospital volume nor surgeon volume was a significant predictor of operative time or volume of blood loss. We did not identify any association between hospital volume and perioperative complications. High-volume (> 100) surgeons were unlikely to have perioperative complications compared to low-volume (< 20) surgeons, but the relation was not significant (odds ratio, 0.50; 95% confidence intervals, 0.14-1.87; P = 0.30). CONCLUSIONS: Volume-outcome relationships were not confirmed for radical nephrectomy. According to our study, the justification of regionalizing radical nephrectomy to centers of excellence is not yet clear.

Long-term outcome of phase I/II clinical trial of Ad-OC-TK/VAL gene therapy for hormone-refractory metastatic prostate cancer.

We evaluated the long-term safety and efficacy of Ad-OC-TK (recombinant adenoviral vector carrying an osteocalcin promoter-driven herpes simplex virus thymidine kinase gene) plus VAL (valacyclovir) gene therapy for hormone-refractory prostate cancer. Ad-OC-TK/VAL therapy is the first in vivo adenovirus-mediated gene therapy to be used to treat metastatic prostate cancer, including bone metastasis. Six patients were enrolled in this trial, and two doses of Ad-OC-TK (2.5 x 10(9) or 2.5 x 10(10) plaque-forming units) were injected into locally recurrent tumor or bone metastasis on day 1 and day 8. Patients were also given VAL (3 g/day) for 21 days. Safety and efficacy were evaluated for at least 8 months in each patient. All patients tolerated this therapy with no serious adverse events. One prostate-specific antigen (PSA) response (from 318.3 to 4.9 ng/ml) was observed with a time to PSA progression (TTP) of 12 months. Docetaxel (30 mg/m2 per week) and estramustine (560 mg/day) combination chemotherapy (DE) was given to three docetaxel-naive patients on PSA failure after gene therapy. All three patients had a PSA response to DE therapy with 21, 7, and 4 months of TTP. These results suggest that additional trials are warranted.