Preoperative risk stratification models after radical cystectomy for bladder cancer: A multi-center study.

OBJECTIVE: We investigated preoperative patient factors associated with prognosis in 263 bladder cancer (BC) patients undergoing radical cystectomy (RC). We also developed new risk stratification models for prognosis. METHODS: This retrospective study included patients treated at Tottori University Hospital and affiliated hospitals between January 2010 and December 2019. The relationship between preoperative patient factors and overall recurrence-free and cancer-specific survival (CSS) was analyzed. The modified Glasgow prognosis score (mGPS) was calculated using serum albumin and C-reactive protein (CRP) levels. Statistical analyses included the log-rank test and Cox proportional hazards regression. RESULTS: Eastern Cooperative Oncology Group performance status (ECOG-PS), mGPS, and clinical tumor stage independently predicted CSS in multivariate analysis. A new risk stratification model included ECOG-PS ≥2, clinical tumor stage ≥3, serum albumin <3.5 g/dL, and serum CRP >0.5 mg/dL. Risk groups were defined as 0 factors (low risk), 1-2 factors (intermediate risk), and 3-4 factors (high risk). High-risk patients showed significantly poorer 3-year cancer-free survival: 86.9% (low risk), 76.7% (intermediate risk), and 50.0% (high risk). CONCLUSIONS: ECOG-PS, clinical tumor stage, and mGPS are predictive of poor cancer-free survival post-RC for BC. Our model offers the potential for prognostic prediction in these patients.

The Benefits of Adjuvant Chemotherapy for Upper Tract Urothelial Carcinoma Require at Least Three Cycles.

Background: Upper urinary tract urothelial carcinoma (UTUC) is uncommon. In advanced cases, radical nephroureterectomy (RNU) alone is not curative, and recurrence and metastasis are likely to occur. Adjuvant chemotherapy (AC) is an evidence-based treatment. However, the optimal number of AC cycles is not clear. This multicenter study investigated the number of cycles required for the beneficial effects of AC in Japanese patients with UTUC. Methods: Patients who were diagnosed with UTUC and underwent RNU at our hospital and affiliated hospitals from January 2010 to September 2020 were included in the study. Patients with pathological T3 or higher or lymph node metastasis were observed or given AC, and their responses were compared. The AC regimens included gemcitabine and cisplatin or carboplatin. Patients were also classified into two groups: the observation and two cycles of AC group and the three to four cycles of AC group. The survival curves for recurrence-free survival (RFS) and cancer-specific survival (CSS) were evaluated using Kaplan-Meier analyses. Results: Of the 133 patients enrolled in the study, 24 received 2 cycles of AC, 37 received 3-4 cycles, and 72 were observed only. The 5-year RFS was 67.1% for the 3-4 cycles of AC group and 41.7% for the observation and two cycles of AC group. The 5-year CSS was 72.2% for the 3-4 cycles of AC group and 35.9% for the observation and two cycles of AC group. RFS and CSS were significantly longer in the 3-4 cycles of AC group compared to the observation and 2 cycles group (P = 0.048 and P = 0.005 respectively). Conclusion: AC prolonged RFS and CSS in the real-world setting. However, at least three cycles of AC are required to achieve beneficial effects in patients with UTUC.

Excellent Response to 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy in a Patient with Treatment-Related Neuroendocrine Prostate Cancer with Urinary Retention and Rectal Obstruction: A Case Report.

Treatment-related neuroendocrine prostate cancer (tNEPC) occurs after androgen deprivation therapy and has a poor prognosis; however, there are few effective treatments for tNEPC. Therefore, tNEPC management is often challenging. This is a case of a 65-year-old Asian male patient with prostate adenocarcinoma who had metastases at initial presentation. After prostate biopsy revealed neuroendocrine prostate cancer (NEPC), he was treated with platinum-based systemic chemotherapy followed by pembrolizumab treatment. The primary tumor regions temporarily regressed, but progression of the primary tumor resulted in urinary retention and rectal obstruction; therefore, a transverse colostomy was performed, and a urethral catheter was inserted. Following somatostatin receptor scintigraphy (SRS), it was determined that the primary tumor expressed somatostatin receptors. Based on these results, treatment with 177Lu-DODATATE peptide receptor radionuclide therapy was prescribed. Subsequently, the primary tumor regressed remarkably, and the urethral catheter was removed. 177Lu-DOTATATE peptide receptor radionuclide therapy may be an effective option for tNEPC, which has few effective treatment options.

Scrotal lymphangioma in a middle-aged man.

Scrotal lymphangioma is a rare, acquired, idiopathic conditions. Surgical resection can result in successful outcomes. A 43-year-old man presented with a painless scrotal mass. Ultrasonography and magnetic resonance imaging revealed a multifocal cystic mass in the scrotum that showed partial hypervascularity without connection to the skin. We performed complete surgical resection of the mass and histopathologically diagnosed the patient with lymphangioma. Acquired scrotal lymphangiomas are rare. Moreover, there was no apparent cause, such as injury; thus, this case was considered idiopathic. Complete surgical resection led to a successful resolution.

Ureteral fibroepithelial polyp: A case report.

Ureteral fibroepithelial polyps are rare, accounting for approximately 2-6% of all ureteral tumors. They can be diagnosed by ultrasonography, computed tomography, and retrograde pyelography; however, diagnosis can be difficult. Management is by resection of the polyp, and endoscopic resection is the standard treatment. Partial ureteral resection and ureteral reconstruction may be necessary depending on the size and location of the polyp. Imaging follow-ups for approximately a year post-surgery are recommended. This clinical case report aimed to highlight a case of a fibroepithelial ureteral polyp that was managed by endoscopic resection.

Mucosa-associated lymphoid tissue lymphoma of the bladder: Case report.

We report the cases of patient with primary mucosa-associated lymphoid tissue (MALT) lymphoma of the bladder who successfully treated with local radiation therapy after transurethral resection of the bladder tumor. She maintains good activity of daily living without relapse. We recommend this strategy for localized MALT lymphoma of the bladder, because it provide better quality of life for elderly patients.

Villous adenoma of the urachus obscuring urachal adenocarcinoma: A case report.

We report a case of a 78-year-old woman with a urachal tumor of the bladder wall. We performed a biopsy and revealed the tumor as a villous adenoma. We excised the tumor by partial cystectomy together with the umbilical ligament, because it was possible there was a co-existing malignancy. The tumor turned out to be villous adenoma and a urachal adenocarcinoma. Because the superficial section of the tumor consisted only of adenoma, a biopsy could not identify the malignant component. Villous adenoma of the urinary tract or the urachus is very rare, and it is considered as an intestinal premalignancy.

Spontaneous regression of metastatic renal cell carcinoma after cytoreductive nephrectomy: A case report.

We herein report a case involving a 59-year-old man with right lung and mediastinal lymph node metastases from renal cell carcinoma. After cytoreductive nephrectomy without neoadjuvant therapy, he achieved spontaneous regression. The regression was maintained 3 years after the operation. We immunohistochemically examined the surgical specimens and considered the possible mechanism underlying this phenomenon.

Site-dependent differences in the composite fibers of male pelvic plexus branches: an immunohistochemical analysis of donated elderly cadavers.

BACKGROUND: Although the pelvic autonomic plexus branches are considered to be a mixture of sympathetic and parasympathetic nerves, little is known regarding the composite fibers of the pelvic plexus branches. This study aimed to investigate the immunohistochemical features of sympathetic and parasympathetic nerves in the pelvic autonomic plexus branches. METHODS: Using 10 donated elderly male cadavers, the detailed topohistology of nerve fibers at and around the bladder, seminal vesicle, prostate, and rectum was examined. Neuronal nitric oxide synthase (nNOS) and vasoactive intestinal polypeptide (VIP) were used as parasympathetic nerve markers; tyrosine hydroxylase (TH) was used as a sympathetic nerve marker. The myenteric plexus of the colon was utilized as a positive control. RESULTS: Most nerve fibers in the bladder, seminal vesicle, prostate, and rectum were both nNOS- and TH-positive. Thus, pelvic plexus branches were classified into two types: 1) triple-positive mixed nerves (nNOS+, VIP+, TH+, thick myelinated fibers + or -) and 2) double-positive mixed nerves (nNOS+, VIP-, TH+, thick myelinated fibers + or -). Notably, triple-positive nerves were localized within the posterosuperior part of the plexus (near the rectum) and travelled anteroinferiorly toward the posterolateral corner of the prostate. The posteriorly and inferiorly located nerves were predominantly composed of parasympathetic, rather than sympathetic, fibers. In contrast, nerve fibers within and along the bladder and seminal vesicle contained either no or few VIP-positive nerves. These superiorly located nerves were characterized by clear sympathetic nerve dominance. CONCLUSIONS: The nerves of the pelvic plexus branches were clearly classified into nerves around the bladder and seminal vesicle (VIP-negative) and nerves around the prostate (VIP-positive). Although nNOS- and VIP-positive nerve fibers are candidate cavernous nerves, cavernous nerve identity cannot be definitively concluded for these nerves in the periprostatic region.

Evaluation of Incontinence after Robot-Assisted Laparoscopic Radical Prostatectomy: Using the International Consultation on Incontinence Modular Questionnaire Short Form and Noting the Number of Safety Pads Needed by Japanese Patients.

BACKGROUND: The definition of continence after robot-assisted laparoscopic radical prostatectomy (RARP) has not been consistently defined, with many studies only noting the amount of safety pads used. We therefore examined what definition of continence would be appropriate, employing both the International Consultation on Incontinence Modular Questionnaire Short Form (ICIQ-SF) and the number of pads used by patients. We also evaluated the relationship between the number of pads used and degree of incontinence. METHODS: Patients who underwent RARP between October 2010 and July 2014 in our department were included in the present study. All patients were evaluated by ICIQ-SF and the number of pads used 1, 3, 6 and 12 months after surgery. Frequency of incontinence and amount of incontinence were evaluated by ICIQ-SF Questions 1 and 2 respectively at 12 months. Quality of life (QOL) was evaluated by ICIQ-SF Question 3 at 1, 3, 6, and 12 months after RARP. RESULTS: The overall study population was 156 patients. In Question 1, 19 patients answered that they leaked urine several times a day, but 5 patients did not use pads, and 8 patients were using only 1 pad a day. In Question 2, 8 patients answered that they leaked a moderate amount of urine, but 2 patients did not use any pads, and 3 patients used only 1 pad a day. QOL showed significant differences between using no pad, 1 pad, or ≥ 2 pads at 1, 3, 6, and 12 months after RARP. CONCLUSION: Simply noting the number of pads used by a patient is an insufficient way to evaluate incontinence after RARP. Assessment by an appropriate questionnaire is also needed.

A prognostic model for predicting urinary incontinence after robot-assisted radical prostatectomy.

BACKGROUND: The aim of this study is to develop a novel prognostic model for estimating the risk of postoperative urinary incontinence (UI) after robot-assisted radical prostatectomy (RARP). METHODS: Participants comprised 131 men who underwent RARP at our hospital from 2011 to 2013. Cox regression analyses were performed to evaluate associations between UI and preoperative factors including filling cystometry and pressure-flow study results and magnetic resonance imaging. RESULTS: Logistic regression analyses revealed significant associations between membranous urethral length or levator thickness and UI at 3 and 6 months. Stratification produced high (membranous urethral length < 9.5 mm or levator thickness < 9.0 mm) and low (membranous urethral length ≥ 9.5 mm and levator thickness ≥ 9.0 mm) UI risk groups. These inter-group differences in UI rate were significant. CONCLUSIONS: We developed a novel prognostic model based on preoperative patient data that can be used for patient counselling.

Impact of antioxidants on seminal vesicles function and fertilizing potential in diabetic rats.

Diabetes mellitus significantly affects the male reproduction and sexual function. In the present study, we investigated the diabetes-induced dysfunction of seminal vesicles (SVs) in the diabetes-rat model and the role of antioxidants. Streptozotocin-induced diabetes after 4 weeks caused smaller size of the organs, hypercontractility, histological abnormalities, increased concentrations of malondialdehyde in the serum and tissue, overexpression of oxidative stress markers, and cleaved caspase-3 as identified by immunohistochemistry in the SVs. In addition, diabetes resulted in deceased levels of serum testosterone and no newborns after the mating studies. Antioxidants significantly normalized all the above parameters, except for the severely decreased serum testosterone levels and the negative outcome of the mating studies. The present study gives evidence for the important role of diabetes-induced oxidative stress in the function and structure of these androgen-dependent organs. Antioxidants may be a promising supplementary therapy for diabetic male patients to alleviate ejaculatory disorders but alone is not efficient treatment for the mitigation of infertility.

Impact of postoperative phosphodiesterase type 5 inhibitor treatment on lower urinary tract symptoms after robot-assisted radical prostatectomy: a longitudinal study.

OBJECTIVE: This study aimed to assess the role of tadalafil, a phosphodiesterase type 5 inhibitor (PDE5-I), in recovery of lower urinary tract symptoms (LUTS) after robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: All patients treated with RARP between October 2010 and August 2013 were enrolled in this retrospective study on prospectively collected data. Patients were retrospectively divided into groups according to postoperative treatment: patients taking tadalafil twice weekly from 1 month to 6 months after RARP, and patients not taking tadalafil. The International Prostate Symptom Score (IPSS), the Overactive Bladder Symptom Score (OABSS) and urinary continence (UC) were assessed preoperatively (2 days before RARP) and at 1, 3, 6, 9 and 12 months after RARP. RESULTS: There was no difference in the overall IPSS score between the groups. At 6 and 9 months, the IPSS storage symptom scores were significantly lower in patients taking tadalafil than in patients not taking tadalafil. In patients with overactive bladder (OAB) before RARP (n = 22), no differences in the total scores of OABSS were seen between patients taking tadalafil and patients not taking tadalafil. On the other hand, in non-OAB patients before RARP (n = 68), at 3, 6 and 9 months, the total scores of OABSS were significantly lower in patients taking tadalafil than in patients not taking tadalafil. No differences in UC rates after surgery were seen between the groups. CONCLUSION: Postoperative tadalafil treatment may be temporarily effective for the recovery of the IPSS storage symptom scores and OABSS.

Anandamide transporter-mediated regulation of the micturition reflex in urethane-anesthetized rats.

PURPOSE: The aim of this study was to investigate the effects of an anandamide transporter inhibitor that can increase endogenous anandamide concentration on the micturition reflex in urethane-anesthetized rats. METHODS: Continuous cystometrograms were performed in female Sprague-Dawley rats under urethane anesthesia. After stable micturition cycles were established, VDM11 (1, 3 and 10 mg/kg), an anandamide membrane transporter inhibitor, was administered intravenously to evaluate changes in bladder activity. In experiments examining the effects of cannabinoid (CB) receptor antagonists, VDM11 (10 mg/kg) was injected intravenously when the first bladder contraction was observed after intravenous administration of AM251, a CB1 receptor antagonist (3 mg/kg), or AM630, a CB2 receptor antagonist (3 mg/kg). RESULTS: Intravenous administration of VDM11 increased intercontraction intervals and threshold pressure at doses of 3 mg/kg or higher in dose-dependent fashion. When AM251 was administered one voiding cycle before VDM11 administration, the increases in intercontraction intervals and threshold pressure induced by VDM11 administration alone were not seen. In contrast, when AM630 was administered before VDM11 administration, increases in intercontraction intervals and threshold pressure were observed, as they were after VDM11 alone. CONCLUSION: These results suggest that anandamide, an endogenous CB ligand, can modulate the micturition reflex and that anandamide transporters play an important role in this modulation. In urethane-anesthetized rats, inhibition of the uptake of anandamide can inhibit the micturition reflex and these inhibitory effects of VDM11 are at least in part mediated by the CB1 receptor.

Spinal glycine transporter-1 inhibition influences the micturition reflex in urethane-anesthetized rats.

PURPOSE: Glycine is an inhibitory neurotransmitter in the central nervous system. So far, two types of glycine transporters (GlyTs), GlyT-1 and GlyT-2, have been cloned. The aim of this study is to investigate the effects of a selective GlyT-1 inhibitor that can increase endogenous glycine concentration on the micturition reflex in urethane-anesthetized rats. METHODS: Continuous cystometrograms (0.04 ml/min) were performed in female Sprague-Dawley rats (232-265 g) under urethane anesthesia. After stable micturition cycles were established, ALX5407, a selective GlyT-1 inhibitor, was administered intrathecally or intracerebroventricularly to evaluate changes in bladder activity. Cystometric parameters were recorded and compared before and after drug administration. RESULTS: Intrathecal administration of ALX5407 (1, 3, 10 and 30 µg) increased intercontraction intervals at doses of 3 µg or higher in a dose-dependent fashion. Intrathecal administration of ALX5407 (1, 3, 10 and 30 µg) also increased pressure threshold at doses of 3 µg or higher in a dose-dependent fashion. However, when ALX5407 (1, 3, 10 and 30 µg) was administered intracerebroventricularly, there were no significant changes in intercontraction intervals, pressure threshold, maximum voiding pressure or baseline pressure or post-void residual urine volume at any doses tested. CONCLUSION: The results of our study indicate that GlyT-1 plays an important role in the modulation of micturition. Furthermore, these findings indicate that in urethane-anesthetized rats suppression of GlyT-1 can inhibit the micturition reflex at the spinal cord level. Thus, GlyT-1 could be a potential target for the treatment of bladder dysfunction such as overactive bladder.

[New findings of clinical anatomy in pelvis].

Surgical anatomy involves clarifying the mutual relationships of each structure in the operative field. Knowledge of new surgical anatomy has arisen via new methods or approaches. Associated with the development and spread of laparoscopic surgery in recent years, adaptation to changes in surgical techniques using knowledge of classical pelvic anatomy has been difficult. Better knowledge of the delicate structures surrounding the prostate is essential in order to provide both cancer control and functional preservation with regard to radical prostatectomy. In this report, we review the progress in knowledge of pelvic anatomy, particularly regarding the endopelvic fascia, prostatic fascia and Denonvilliers' fascia.

Comparison of the overactive bladder symptom score and the overactive bladder symptom score derived from the bladder diaries.

AIMS: The overactive bladder symptom score (OABSS) is a useful tool for assessing the four key symptoms of overactive bladder (OAB), but it sometimes misrepresents a patient's actual voiding status. To examine whether the patient-determined OABSS underestimates or overestimates the true status, its results were compared to those of the OABSS derived from a 7-day bladder diary (OABSS-BD). METHODS: Records of patients who visited our outpatient clinic with lower urinary tract symptoms were evaluated retrospectively. The patients were asked to complete the OABSS and the 7-day bladder diary (BD). The OABSS-BD was created from the 7-day BD. Questions were compared between the OABSS and the OABSS-BD. RESULTS: A total of 44 men and 31 women were evaluated. For daytime frequency, the mean OABSS score was 1.03 ± 0.57 and the OABSS-BD score was 0.69 ± 0.52 (P < 0.01). For nighttime frequency, the mean OABSS score was 2.27 ± 0.84, and the OABSS-BD score was 1.96 ± 1.00 (P = 0.04). For urinary urgency, the mean OABSS score was 2.49 ± 1.83, and the OABSS-BD score was 2.70 ± 1.90 (P = 0.27). For urgency incontinence, the mean OABSS score was 1.67 ± 1.92, and the OABSS-BD score was 1.52 ± 1.87 (P = 0.28). For the total score, the mean OABSS total score was 7.26 ± 3.92, and the OABSS-BD score was 6.98 ± 3.26 (P = 0.23). CONCLUSIONS: The OABSS is a very simple and useful tool. However, compared to the results from the 7-day FVC, the present patients overestimated daytime and nighttime frequency.

Vesicovascular reflexes in the spontaneously hypertensive rat.

AIMS: We investigated the effects of hypertension and acute blood pressure changes on rats' vesicovascular reflexes (VVRs). MAIN METHODS: Twelve-week-old male Wistar rats and spontaneously hypertensive rats (SHRs) were anesthetized with urethane, and underwent real-time cystometry and blood pressure monitoring. The SHRs were administered nifedipine or valsartan intravenously. The Wistar rats were administered intravenous noradrenaline continuously. The intercontraction intervals, maximum detrusor pressures, blood pressure during the voiding and the urine storage phases, blood pressure elevations associated with the VVRs, and arterial pulses were assessed. Plasma adrenaline and noradrenaline concentrations were measured using HPLC. The degree of atherosclerosis was assessed histologically based on the aortic wall thickness. KEY FINDINGS: Blood pressure elevations associated with the voiding reflexes were significantly lower and intercontraction intervals were significantly shorter in the SHRs compared with the Wistar rats. Although nifedipine and valsartan reduced the systolic blood pressure and noradrenaline increased the systolic blood pressure, they failed to alter the blood pressure elevations associated with the VVRs and the intercontraction intervals. No significant differences occurred with respect to the maximum detrusor pressures among the experimental groups. The reflected waves' shapes were normal in the Wistar rats, but they almost disappeared in the SHRs. The aortic walls were significantly thicker in SHRs compared with those in Wistar rats. SIGNIFICANCE: The blood pressure elevations associated with the VVRs were lower in the SHRs than in the Wistar rats. Acute blood pressure reductions failed to ameliorate the blood pressure elevations associated with VVRs in the SHRs.

Site-dependent and interindividual variations in Denonvilliers' fascia: a histological study using donated elderly male cadavers.

BACKGROUND: Site-dependent and interindividual histological differences in Denonvilliers' fascia (DF) are not well understood. This study aimed to examine site-dependent and interindividual differences in DF and to determine whether changes in the current approach to radical prostatectomy are warranted in light of these histological findings. METHODS: Twenty-five donated male cadavers (age range, 72-95 years) were examined. These cadavers had been donated to Sapporo Medical University for research and education on human anatomy. Their use for research was approved by the university ethics committee. Horizontal sections (15 cadavers) or sagittal sections (10 cadavers) were prepared at intervals of 2-5 mm for hematoxylin and eosin staining. Elastic-Masson staining and immunohistochemical staining were also performed, using mouse monoclonal anti-human alpha-smooth muscle actin to stain connective tissues and mouse monoclonal anti-human S100 protein to stain nerves. RESULTS: We observed that DF consisted of disorderly, loose connective tissue and structures resembling "leaves", which were interlacing and adjacent to each other, actually representing elastic or smooth muscle fibers. Variations in DF were observed in the following: 1) configuration of multiple leaves, including clear, unclear, or fragmented behind the body and tips of the seminal vesicles, depending on the site; 2) connection with the lateral pelvic fascia at the posterolateral angle of the prostate posterior to the neurovascular bundles, being clear, unclear, or absent; 3) all or most leaves of DF fused with the prostatic capsule near the base of the seminal vesicles, and periprostatic nerves were embedded in the leaves at the fusion site; and 4) some DF leaves fused with the prostatic capsule anteriorly and/or the fascia propria of the rectum posteriorly. CONCLUSIONS: Site-dependent and interindividual variations in DF were observed in donated elderly male cadavers. All or most DF leaves are fused with the prostatic capsule near the base of the seminal vesicles and some DF leaves are fused with the fascia propria of the rectum posterior. Based on our results, surgeons should be aware of variations and search for them to create a suitable dissection plane to avoid iatrogenic positive margins and rectal injury.

Robot-assisted radical prostatectomy in an initial Japanese series: the impact of prior abdominal surgery on surgical outcomes.

OBJECTIVES: To evaluate the influence of prior abdominal surgery on surgical outcomes of robot-assisted radical prostatectomy in an early single center experience in Japan. METHODS: We reviewed medical records of patients with localized prostate cancer who underwent robot-assisted radical prostatectomy from October 2010 to September 2013 at Tottori University Faculty of Medicine, Yonago, Tottori, Japan. Patients with prior abdominal surgery were compared with those with no prior surgery with respect to total operative time, port-insertion time, console time, positive surgical margin and perioperative complication rate. Furthermore, the number of patients requiring minimal adhesion lysis was compared between the two groups. RESULTS: Of 150 patients who underwent robot-assisted radical prostatectomy, 94 (63%) had no prior abdominal surgery, whereas 56 patients (37%) did. The mean total operative time was 329 and 333 min (P = 0.340), mean port insertion time was 40 and 34.5 min (P = 0.003), mean console time was 255 and 238 min (P = 0.145), a positive surgical margin was observed in 17.9% and 17.0% patients (P = 0.896), and the incidence of perioperative complications was 25% and 23.4% (P = 0.825), respectively, in those with and without prior abdominal surgery. In the prior abdominal surgery group, 48 patients (80.4%) required adhesion lysis at the time of trocar placement or while operating the robotic console. CONCLUSION: Robot-assisted radical prostatectomy appears to be a safe approach for patients with prior abdominal surgery without increasing total operative time, robotic console time, positive surgical margin or the incidence of perioperative complications.