A new nomogram of urinary flow rate and volume based on multiple measurements per healthy adult Japanese men using a portable uroflowmeter (P-Flowdiary®).

BACKGROUND: To develop a nomogram of urinary volume and flow based on the data of Japanese men without lower urinary tract symptoms and multiple flows per participant whose characteristics were clear. METHODS: Overall, 101 Japanese male volunteers without lower urinary tract symptoms aged between 20 and 59 years were enrolled. A portable uroflowmeter (P-Flowdiary®) was used to record urinary information (flow rate and volume) for 2 successive days. The model (quadratic, linear, or logarithmic regression) most fit for the relationship between maximum flow rate and voided volume was determined. The maximum flow rate at > 150 mL was compared among the 20-29-, 30-39-, 40-49-, and 50-59-year age groups. Nomograms appropriate for the age groups were created. RESULTS: The mean age, International Prostate Symptom Score, and Overactive Bladder Symptom Score were 38.5 years, 0.42, and 0.24, respectively. The quadratic regression model was the most fit because its mean coefficient determination was 0.93 ± 0.06. The mean maximum flow rate was significantly lower in the 50-59-year age group (21.8 ± 5.05 mL/s, P < 0.01) than in the younger groups (24.14 ± 4.94, 24.05 ± 6.99, and 24.64 ± 5.72 mL/s). The 2 nomograms are Y = 28.99 {1 - exp(- 0.01 × X)} and Y = 25.67 {1 - exp(- 0.01 × X)} for the 20-49- and 50-59-year age groups, respectively. CONCLUSIONS: The nomogram can predict maximum flow rate based on voided volume in Japanese men aged 20-59 years without lower urinary tract symptoms.

Identification of diagnostic serum biomarkers for Hunner-type interstitial cystitis.

OBJECTIVES: Diagnosis of Hunner-type interstitial cystitis (HIC) relies on the ability to identify Hunner lesions endoscopically, which can lead to storage symptom misdiagnosis. Here, we examined serum biomarkers for HIC and verified their utility. METHODS: Based on the previous definition of the Japanese guidelines, which did not distinguish HIC and non-HIC diseases, we searched for serum biomarkers in 25 patients with interstitial cystitis (IC) and 25 control participants using metabolomics during 2013-2014. In 2019, we conducted a validation study in HIC and control groups. Serum samples were analyzed using liquid chromatography-tandem mass spectrometry, and candidate biomarker concentrations were compared between the groups using Mann-Whitney test. RESULTS: Metabolomics targeted 678 metabolites and revealed that the levels of 14 lysolipids, seven γ-glutamyl amino acids, and two monoacylglycerols were significantly different between the IC and control groups. The following metabolites were selected from each metabolite category as candidates: 1-linoleoylglycerophosphocholine (1-linoleloyl-GPC [18:2]), γ-glutamylisoleucine (γ-Glu-Ile), and 1-arachidonylglycerol (1-AG). The serum concentrations of 1-linoleoyl-GPC (18:2) in the HIC and control groups were 27 920 ± 6261 and 40 360 ± 1514 ng/mL (P = 0.0003), respectively. The serum concentrations of γ-Glu-Ile and 1-AG were not significantly different between the groups. When the cut-off value of 1-linoleoyl-GPC (18:2) was set at 28 400 ng/mL, the sensitivity and specificity were 68% and 84%, respectively. CONCLUSIONS: Serum 1-linoleoyl-GPC (18:2) is a candidate diagnostic biomarker for HIC. Additional studies on whether this biomarker can distinguish HIC from other diseases with high urination frequency are required for its clinical use.

Assessment of bladder function for stabilizing urinary volume overnight with recording of brain waves (ABSORB study).

OBJECTIVES: The bladder urothelium is not always impermeable. During sleep, the bladder might absorb urine in healthy individuals who sleep through the night. This study aimed to determine whether the bladder absorbs urine by using a method other than ultrasonic scanning and to simultaneously evaluate sleeping conditions. METHODS: Eleven participants (five males, six females) aged 20 to 49 years without lower urinary tract symptoms or urination while sleeping were enrolled. Bladder volume was estimated by studying the relationship between dilution and absorbance of indigo carmine dissolved in urine. A 12F Foley catheter was inserted into the bladder before sleep. Urine samples (5 mL) were extracted at 2, 3, 4, 5, and 6 am sleep stages were monitored with a single-channel portable electroencephalograph device. RESULTS: The estimated bladder volume at 6 am and voided volume immediately after rising were significantly correlated (Spearman's ρ = 0.62, P = .046). Eight participants (three males, five females) showed an absorption pattern of the estimated bladder volume change. In a male participant, the blue dye's strength gradually decreased until 4 am (estimated 859 mL) and increased from 5 am (estimated 455 mL). In another, the blue dye's strength increased at 4 am (estimated 449 mL) vs at 3 am (estimated 757 mL). In all participants, electroencephalograph data demonstrated that sleep was maintained despite having a full bladder. CONCLUSIONS: The bladder absorbs urine and maintains an approximate volume of functional bladder capacity during sleep to avoid incontinence and maintain sleep in adults due to an urge to void urine during the sleep cycle.

Clinical efficacy and safety of mirabegron and imidafenacin in women with overactive bladder: A randomized crossover study (the MICRO study).

AIMS: We aimed to compare the efficacy and safety of mirabegron, a ß3-adrenoceptor agonist, and imidafenacin, an anticholinergic agent, in overactive bladder patients. METHODS: We conducted a multicenter, prospective randomized cross-over study at 5 hospitals in Japan from December 2012 to June 2015. We enrolled female patients with overactive bladder aged ≥50 years, who had never received treatment for the condition. The patients were assigned to Group A or B. Group A patients were administered mirabegron (50 mg per day) for 8 weeks, followed by a 2-week washout period, and then imidafenacin (0.2 mg per day) for 8 weeks. This order of drug administration was reversed in Group B. RESULTS: A total of 33 and 18 patients in Group A and 37 and 26 patients in Group B continued to receive treatment at weeks 8 and 18, respectively. Mirabegron administration significantly improved overactive bladder symptom score (OABSS), the urinary frequency per 24 hr, voided volume per micturition, and number of nocturia episodes per night at week 8. Moreover, imidafenacin administration improved all these variables, except for the number of nocturia episodes per night at week 8. No significant difference was observed in the drug effects between mirabegron and imidafenacin. Although imidafenacin administration significantly increased the scores for dry mouth, blurred vision, and constipation, mirabegron administration did not. CONCLUSIONS: Mirabegron and imidafenacin have the same efficacy. Imidafenacin administration is associated with a higher rate of dry mouth, blurred vision, and constipation as compared to mirabegron administration. Neurourol. Urodynam. 36:1097-1103, 2017. © 2016 Wiley Periodicals, Inc.

Linkage of Lower Urinary Tract Symptoms to Sleep Quality in Elderly Men with Nocturia: A Community Based Study Using Home Measured Electroencephalogram Data.

PURPOSE: We objectively investigated the relationship between sleep quality/efficiency and factors associated with micturition using at-home electroencephalogram assessment. MATERIALS AND METHODS: Participants were recruited from among those enrolled in the Fujiwara-kyo Study, a community based longitudinal evaluation that began in Nara Prefecture, Japan, in 2007. Included participants were men at least 65 years old who woke up in the middle of the night/early morning at least 3 times per week with the urge to void. We evaluated lower urinary tract symptoms using the I-PSS and subjective sleep quality using the Pittsburgh Sleep Quality Index. Uroflowmetry and 3-day frequency volume charting measurements were also obtained. Electroencephalogram recordings were obtained during sleep to evaluate objective sleep quality. RESULTS: Final analysis included data from 47 participants. I-PSS-quality of life score and slow wave sleep time were independent predictors of good subjective sleep quality as determined by Pittsburgh Sleep Quality Index scores. Nocturnal urinary volume was an independent predictor of greater sleep efficiency. Maximum flow rate was an independent predictor of longer slow wave sleep time. CONCLUSIONS: In elderly men with nocturia, sleep quality is associated with lower urinary tract function. Higher subjective sleep quality is associated with longer slow wave sleep time and less severe lower urinary tract symptoms. Higher objective sleep quality is further associated with a higher urinary flow rate and lower nocturnal urinary volume.

[Urethral Fistula Caused by an Urethrovesical Foreign Body : A Case Report].

A 68-year-old man presented with the chief complaint of swelling of the penis. A pencil had been inserted into his urethra by a commercial sex worker for sexual stimulation. On a computed tomography (CT) scan, a foreign object was visible throughout the urethra and in the urinary bladder. Cystoscopy performed under spinal anesthesia showed a pencil in the urethra. We attempted removing the object endoscopically by using a Holmium laser. However, the endoscopic procedure failed and finally, we removed the object by transvesical open surgery. At the same time, suprapubic cystostomy was performed for the disorder of the urethra. An anterior urethrocutaneous fistula was formed 5 days after the operation. After removal of the urethral catheter, he was managed with only suprapubic cystostomy. Conservative management of the urethrocutaneous fistula was effective. The fistula was completely closed 26 days after the operation. He was discharged 33 days after the operation.

Guidance on water intake effectively improves urinary frequency in patients with nocturia.

OBJECTIVES: To evaluate how guidance on water-intake impacts the degree of nocturia. METHODS: A total of 67 male patients were enrolled in the present study. Patients were asked to adjust their water and food intakes so that their 24-h urine production/bodyweight would be equal or lower than 30 mL/kg. One month after the treatment, the therapeutic gain from and adverse effects of fluid restriction were examined by comparing the pretreatment and post-treatment value of various parameters. RESULTS: Overall, 65 eligible patients were evaluated. In 44 patients (67%), the frequency of nocturia was improved to one or more times. The change in frequency of nocturia showed a positive correlation with the change in nocturnal urine volume. The change in nocturnal urine volume showed a positive correlation with the changes in 24-h urine production/bodyweight, 24-h drinking volume and daytime drinking volume. The changes in 24-h urine production/bodyweight and daytime drinking volume were independent factors influencing therapeutic effect. None of the participants reported any adverse event. CONCLUSIONS: In patients with a 24-h urine production/bodyweight equal or higher than 30 mL/kg, guidance on water intake might be considered effective and safe as a lifestyle therapy. Water restriction should be carried out not only in the evening, but also during daytime.

Preliminary Experience with Low-dose Desmopressin Treatment and Urinary Arginine Vasopressin Concentration as a Response Predictor for Patients with Nocturia with Nocturnal Polyuria.

OBJECTIVES: To assess whether urinary arginine vasopressin (AVP) concentrations adjusted for urinary creatinine (Cr) can predict responsiveness to low-dose desmopressin for nocturia with nocturnal polyuria (NP). METHODS: Nine NP patients aged 64-84 years with ≥ 2 nocturnal voids received 2.5 µg of intranasal desmopressin for 4 weeks and were evaluated for its effectiveness. Prior to treatment, urinary AVP/Cr concentrations at first morning void and serum sodium and plasma natriuretic peptide (BNP) concentrations were measured, and all patients underwent 5% hypertonic saline infusion. RESULTS: Six responders to 2.5 µg desmopressin had average decreases in nocturnal frequency from 3.2 to 1.8 voids nightly and in nocturnal diuresis by 40%, without clinically significant adverse events. Non-responders remained unaffected even with dose escalation to 5.0 µg desmopressin. For responders, urinary AVP/Cr concentrations were less than 14 pg/mg · Cr, which is lower than in non-responders. Within a physiological range of plasma osmolality, plasma AVP release in response to 5% hypertonic saline infusion was less in responders than in non-responders. Blood pressure measurements and BNP concentrations were unchanged. CONCLUSIONS: Urinary AVP/Cr at first morning void may have potential clinical value as a predictor for responsiveness to low-dose desmopressin in nocturia with NP.

[A case of domestic violence-related Page kidney].

Page kidney is caused by the accumulation of blood in the perinephric or subcapsular space, resulting in compression of the involved kidney, renal ischemia and high renin hypertension. We describe a case of domestic violence-related Page kidney. This report also reviews previously described cases of Page kidney.

[Tumor thrombus arising from the superior vena cava and extending into the right atrium in a patient with advanced testicular germ cell tumor].

A 24-year-old man was referred to our hospital with a painless mass on the left side of his neck. Ultrasonography detected right testicular tumor and computerized tomography scanning revealed a left supraclavicular lymph node mass and bulky retroperitoneal lymph node mass. He initially underwent right high orchiectomy, combination chemotherapy and retroperitoneal lymph node dissection for advanced testicular non-seminomatous germ cell tumor. Six years later, late relapse was detected in the lung. After complete remission of the lung metastasis with chemotherapy, the serum alpha-fetoprotein began to increase because of superior vena caval thrombus extending into the right atrium. Emergency surgical excision was performed successfully using extracorporeal circulation to prevent pulmonary embolism and the resected specimen pathologically revealed adenocarcinoma interpreted as teratoma malignant transformation. Adjuvant chemotherapy consisting of paclitaxel, ifosfamide and nedaplatin were administered for subsequent slight elevation of serum F-human chorionic gonadotropin beta, resulting in successful normalization again. Later, he suddenly died of cerebral infarction without any evidence of recurrence 138 months after his initial presentation. We report herein an extremely uncommon case of advanced testicular germ cell tumor with development of superior vena caval thrombus extending into the right atrium.

Clinicopathological review of 46 primary retroperitoneal tumors.

OBJECTIVES: To clarify the clinical factors including diagnostic imaging findings that may correlate with the histopathological malignancy in primary retroperitoneal tumors. METHODS: The clinical backgrounds and imaging findings of 22 benign and 24 malignant primary retroperitoneal tumors were retrospectively investigated, and the prognosis of patients with malignant retroperitoneal tumors was assessed. RESULTS: There were significant correlations between the presence of symptoms and malignancy (P < 0.01), as well as between the irregularity of tumor margins and malignancy (P < 0.01). On dynamic magnetic resonance imaging (MRI), 90% of malignant tumors showed early enhancement either with quick or slow washout, while 75% of benign tumors showed delayed and no enhancement (P < 0.002). All malignant and benign paraganglioma showed the same early enhancement with quick washout. Malignant lymphoma showed various enhancement patterns. The 2-year and 5-year cause-specific survival rates of the patients with malignant retroperitoneal tumors were 68.0% and 43.2%, respectively. All malignant lymphoma patients were mainly treated with chemotherapy after being diagnosed histologically. Malignant paraganglioma patients who could not meet complete resection needed chemotherapy for promising survival. CONCLUSION: The symptoms, the irregularity of the margins, and the specific enhancement pattern on the dynamic MRI may be important predictive factors of the primary malignant retroperitoneal tumors. Histological diagnosis was needed for malignant definition of paraganglioma because both benign and malignant paraganglioma showed similar clinical and imaging findings. Preoperative biopsy should be considered for selection of the appropriate treatment particularly in patients that are likely to have malignant lymphoma that could not be diagnosed definitively by the clinical and imaging findings.

A case of small cell carcinoma of the kidney.

A 47-year-old man had a retroperitoneal tumor measuring 18 cm in maximum diameter of the left kidney that was diagnosed with computed tomography (CT)-guided needle biopsy as small cell carcinoma. Microscopically, the tumor cells showed immunohistochemical reaction for neural cell adhesion molecule antibodies. This patient with advanced renal small cell carcinoma and multiple metastatic lesions was treated with the first-line combination chemotherapy of cisplatin, etoposide and ifosphamide, which showed a partial response of primary renal tumor and a complete response of liver metastasis, and with the second-line chemotherapy of cisplatin and irinotecan, which showed a complete response of Virchow's nodal metastasis. Thereafter, in spite of salvage chemotherapy of amurubicin hydrochloride for persistent and refractory renal small cell carcinoma, he died 32 months after the first presentation due to local progression. However, combination chemotherapy of these anticancer agents made his prognosis more favorable than we expected before treatment. The extrapulmonary small cell carcinomas are generally known to be more aggressive and malignant than the lung small cell carcinomas, and small cell carcinoma arising from the kidney is an extremely rare malignant neoplasm, with only 34 cases reported in the English or Japanese literature. The prognosis of renal small cell carcinomas is currently limited as compared with the lung small cell carcinomas, and therefore a cumulative investigation of a larger number of cases treated with multidisciplinary modalities including combination chemotherapy is necessary.

[Operative position suitable for transvaginal excision of urethral diverticulum or closure of urethrovaginal fistula].

Among the various surgeries in female urology, transvaginal excision of urethral diverticulum needs careful and meticulous procedures in order to avoid some operative complications, such as urethral stricture or urethrovaginal fistula. In the present report, we present a woman with urethral diverticulum who initially underwent transvaginal excision of diverticulum in the dorsal lithotomy position, but she was complicated with urethrovaginal fistula postoperatively. Unfortunately, we failed to repair her fistula when she underwent excision of the fistula in the dorsal lithotomy position. With reconsideration of an operative position useful for transvaginal surgery, we succeeded in fistula closure in the Jackknife prone reverse-lithotomy position, and thereafter, two subsequent patients with urethral diverticulum were successfully treated with transvaginal excision of diverticulum in this operative position. In the transvaginal approach to the peri-urethral disorders, the Jackknife prone reverse-lithotomy position was notably superior to the dorsal lithotomy position with the following advantages: (1) the surgeons can easily operate in a bright and large surgical site without any blind view. (2) the surgeons can dissect and suture safely and accurately. (3) the assistants also can help in the operation bimanually in the same view as the surgeon when the posterior vaginal wall is fixed with a retractor.

[Case of proximal-type epithelioid sarcoma of the perineum].

A 31-year-old man was referred to our department for investigation and treatment of a rapidly-growing mass in the perineal region. MRI showed a periurethral tumor in the perineal region measuring 3.5cm in maximum diameter and bilateral inguinal lymph nodes enlargement. Therefore, the tumor was extirpated immediately with bilateral inguinal lymphadenectomy. The pathological examination with immunohistochemistry revealed that the tumor was proximal-type epithelioid sarcoma. Multidisciplinary therapy with irradiation, chemotherapy, and tumor ablation with a microwave tissue coagulator, was not effective for local recurrence and metastasis, and finally he died of progressive disease 14 months after the operation. Epithelioid sarcoma originating from the thigh or trunk is classified into the proximal-type, which shows significantly poorer prognosis than the distal-type that develops in the distal extremities. The proximal-type epithelioid sarcoma of the perineum is rare and, to our knowledge, the present report is the fourth case in the Japanese literatures.

[A case of primary and solitary bone metastasis of testicular seminoma after orchiectomy].

A 40-year-old man with stage I left testicular seminoma who had been followed for 18 months after orchiectomy, complained of pain in his left upper extremity and dysbasia. Magnetic resonance imaging (MRI) and bone scintigraphy suggested multiple bone lesions in the thoracic vertebrae and right ischium, and bone biopsy revealed metastasis of seminoma. There was no evidence of other metastatic lesions. After he was treated with 2 courses of first-line chemotherapy consisting of peplomycin, etoposide, and cisplatin, which were followed by 2 courses of high-dose chemotherapy with carboplatin, etoposide, and ifosfamide, the metastatic lesions were nearly in complete response on MRI and bone scintigraphy and the result of fluorodeoxyglucose-positron emission tomography was negative, but the hCG-beta level remained slightly elevated. In most advanced testicular tumors, bone metastasis usually coexists with other metastatic lesions and appears as a secondary lesion. Herein, we report this rare case of primary and solitary bone metastasis from testicular seminoma after orchiectomy.

[A case of vesical paraganglioma with intrapelvic multiplicity].

A 35-year-old woman, who had a past history of hypertension due to paraganglioma of the urinary bladder and in the pelvis, was referred to us 12 years after the initial diagnosis of paraganglioma. Before coming to us and during the follow-up after enucleation of myoma uteri, she was again diagnosed as having a bladder tumor by a gynecologist. Cystoscopy revealed a non-papillary broad-based tumor, measuring 2 cm in diameter, on the trigone of the urinary bladder. Magnetic resonance imaging also showed two solid tumors, each measuring 2 cm in diameter, on the bilateral peri-vesical sides in the pelvis. Endocrinologic examination disclosed increased levels of serum and urinary catecholamines. Histopathologic examination revealed that the bladder tumor specimen obtained by transurethral resection was paraganglioma. She underwent partial cystectomy and resection of these intrapelvic tumors via a retroperitoneal approach. These tumors were histopathologically diagnosed as multiple paragangliomas. She has been followed up for 10 months after operation without any evidence of recurrence. Herein, we report this rare case of vesical paraganglioma and present a brief review of the relevant literature.