Assessment of diagnostic accuracy for cryptorchidism and risk factors for delayed orchidopexy.

OBJECTIVES: Cryptorchidism (CO) diagnosis by palpation is challenging. Patients with suspected CO are primarily referred to pediatric urologists by general pediatricians and urologists. Currently, surgical treatment for CO is recommended earlier than in previous guidelines. In this study, we evaluated factors that lead to diagnosis discordance and delayed orchidopexy in patients referred with suspected CO in addition to timing of initial screening. METHODS: In total, 731 patients (1052 testes) with suspected CO were included. Risk factors for diagnostic discrepancy in CO diagnosis by pediatric urologists and risk of delayed orchiopexy were evaluated. RESULTS: Herein, 659 (90%) patients were diagnosed during routine public health checkups for infants and young children, and 419 (57%) patients were referred by pediatric practitioners. Of 1052 testes, 374 (36%) were diagnosed with CO by pediatric urologists. In multivariate analysis, risk factors of diagnostic discrepancy for CO diagnosis by pediatric urologists were bilateral testis (odds ratio [OR] = 9.17, p < 0.0001), >6 months old at initial diagnosis (OR = 1.036, p < 0.0001), and pediatric referral (OR = 4.60, p < 0.0001). In total, 296 patients underwent orchiopexy for CO. In multivariate analysis, risk factors for delayed orchiopexy were presence of comorbidities (OR = 3.43, p = 0.003) and >10 months old at referral (OR = 12.62, p < 0.0001). CONCLUSIONS: Pediatric referral is a risk factor for discordant CO diagnostics, and late age at referral brings a risk of delayed orchiopexy. It is necessary to enlighten pediatricians, who are mainly responsible for routine health checkups, in teaching CO diagnostic techniques to ensure early referral.

Long-term follow-up of congenital hydronephrosis in a single-center study.

OBJECTIVES: Many congenital hydronephroses spontaneously resolve. This study evaluated a long-term follow-up of more than 4 years of patients with congenital hydronephrosis at a single center. METHODS: In total, 215 patients (286 kidneys) with congenital hydronephrosis were included. Hydronephrosis outcomes (resolution, improvement, and persistence) and time-to-outcome were evaluated. RESULTS: Fourteen patients underwent early surgical intervention until the age of 2 years. A total of 189 congenital hydronephrosis cases (66%) showed resolution at a median of 16 months (interquartile range: 7-21 months) and 169 (80%) of 210 kidneys with grade I to II hydronephrosis showed resolution at a median of 14 months (interquartile range: 6-23 months). Of 76 kidneys with grade III to IV hydronephrosis, 24 (32%) showed resolution at a median of 29 months (interquartile range: 24-41 months), and 56 (74%) showed improvement to grade II or less at a median of 12 months (interquartile range: 5-23 months). Of the 76 kidneys with grade III to IV hydronephrosis, five required delayed pyeloplasty at a median of 66 months (interquartile range: 42-89 months). One patient was asymptomatic, with a marked worsening of hydronephrosis and decreased renal function 6 years after the resolution of hydronephrosis. CONCLUSIONS: None of the patients with grade I to II hydronephrosis required surgical treatment, and a shorter follow-up may be sufficient. Grade III to IV severe hydronephrosis should be considered for a longer and more careful follow-up, given the possibility of asymptomatic exacerbation of hydronephrosis.

Intravesical Bacillus Calmette-Guerin treatment-induced sleep quality deterioration in patients with non-muscle invasive bladder cancer: functional outcome assessment based on a questionnaire survey and actigraphy.

PURPOSE: We investigated sleep parameters and patient-reported outcomes before, during, and after induction Bacillus Calmette-Guerin therapy using questionnaires and actigraphy in patients with non-muscle invasive bladder cancer. METHODS: We investigated 10 patients who received Bacillus Calmette-Guerin therapy once weekly for 8 weeks. The International Prostate Symptom Score, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, Functional Assessment of Cancer Therapy-Bladder, and multi-item Short Form-8 tools were used to assess patient-reported outcomes. Participants completed all questionnaires before (baseline), at the 4th and 8th doses, and 1 month after the last Bacillus Calmette-Guerin dose. The MotionWatch8 was fastened to patients' waist throughout the study. Composite sleep quality was determined based on sleep duration, efficiency, and fragmentation. RESULTS: We observed a transient increase in frequency/nocturia subscores and the insomnia subscore. The number of patients with poor sleep quality increased from 0 (0%) at baseline to 7 (70%) at the 4th dose and to 6 (60%) patients at the 8th dose. Among 10 patients, 6 (60%) were assigned to the sleep deterioration group and 4 (40%) to the non-deterioration group. Sleep quality was restored to baseline levels in 5 of 6 patients (83%) within 1 month after the last dose in the sleep deterioration group, and the nocturia subscore of the International Prostate Symptom Score was significantly increased only in this group (P=0.03). CONCLUSIONS: This is the first study that confirms intravesical Bacillus Calmette-Guerin-induced sleep quality deterioration based on a questionnaire survey and actigraphy.

Association between urine 6-sulfatoxy-melatonin level and intravesical Bacillus Calmette-Guerin treatment-induced sleep quality deterioration in patients with non-muscle invasive bladder cancer.

PURPOSE: The level of 6-sulfatoxy-melatonin (SaMT), a metabolite of melatonin, in first-void morning urine reflects blood melatonin levels from the previous night. We investigated the association between urine SaMT and sleep quality deterioration in patients with non-muscle invasive bladder cancer (NMIBC) treated with intravesical Bacillus Calmette-Guerin induction therapy (iBCG). METHODS: We enrolled 51 patients who received iBCG once weekly for 6 or 8 weeks. Patient-reported outcomes were assessed with questionnaires including the International Prostate Symptom Score (IPSS) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQC30). Questionnaires were completed before (baseline), during, at completion, and 1 and 3 months after iBCG. Melatonin and SaMT levels at baseline were measured in serum and first-void morning urine samples, respectively. RESULTS: Based on changes in the QLQC30 insomnia subscale, 28 (55%) patients experienced sleep quality deterioration (deterioration group). Urine SaMT values in the deterioration group were lower than those in the non-deterioration group (P = 0.0015; 7.5 vs 15.4 ng/mg creatinine, respectively). Nocturia scores in the non-deterioration group decreased over time, while those of the deterioration group remained high after completion of iBCG. A binary logistic regression analysis revealed that low urine SaMT levels (≤ 9.6 ng/mg creatinine), high IPSS nocturia scores at baseline, and high IPSS storage subscores at baseline were associated with BCG-induced sleep quality deterioration. CONCLUSIONS: This study confirmed the association among urine SaMT levels, nocturia, and sleep disturbance in patients with NMIBC who receive iBCG. We should be aware of treatment-induced impairments to aid in appropriate decision-making.

Video-urodynamic effects of vibegron, a new selective ß3-adrenoceptor agonist, on antimuscarinic-resistant neurogenic bladder dysfunction in patients with spina bifida.

OBJECTIVES: To evaluate the efficacy, safety and tolerability of vibegron for the treatment of antimuscarinic-resistant neurogenic bladder dysfunction in patients with spina bifida. METHODS: In this retrospective study, 15 patients with antimuscarinic-resistant neurogenic bladder dysfunction due to spina bifida underwent a video-urodynamic study before and during the administration of vibegron 50 mg once daily instead of antimuscarinic agents from February 2019 through April 2021. The video-urodynamic study was carried out to evaluate bladder compliance, maximum cystometric bladder capacity, detrusor overactivity, detrusor leak point pressure and vesicoureteral reflux before and >3 months after the beginning of vibegron administration. RESULTS: Treatment with vibegron significantly improved bladder compliance and maximum cystometric bladder capacity compared with antimuscarinic agents, respectively (7.4 ± 4.2 vs 30.4 ± 48.2 mL/cmH2 O, P = 0.0001; 231.4 ± 81.2 vs 325.2 ± 106.5 mL, P = 0.0005). Detrusor overactivity did not change after the administration of vibegron. Bladder deformity, which was confirmed in 12 patients, improved in half of the patients after taking vibegron. Vesicoureteral reflux, which was confirmed in two patients, was extinguished after taking vibegron. Newly occurring adverse events were not observed, and all patients continued to take vibegron during the treatment period. CONCLUSIONS: Favorable efficacy of vibegron for antimuscarinic-resistant neurogenic bladder dysfunction due to spina bifida was shown video-urodynamically without apparent adverse events. Vibegron is a favorable option for the treatment of antimuscarinic-resistant neurogenic bladder dysfunction in patients with spina bifida.

Usefulness of clinical factors for diagnosing and differentiating types of testicular malposition in boys: A retrospective study.

OBJECTIVE: To investigate useful objective variables and factors supporting the diagnosis of retractile testis and cryptorchidism by primary care providers, including urologists. METHODS: This retrospective study included 512 boys diagnosed with retractile testis or cryptorchidism at our institute. Boys with retractile testis were followed up and underwent orchiopexy once the testis became undescended, while boys with cryptorchidism underwent orchiopexy immediately. We investigated trends in the prevalence of testicular malposition and explored useful diagnostic factors for retractile testis and cryptorchidism. RESULTS: Of 512 boys, 199 were diagnosed with retractile testis and 313 were diagnosed with cryptorchidism. Comparison of clinical information between retractile testis and cryptorchidism showed that age at diagnosis, laterality, and location of the testis were significantly different between the groups (P < 0.0001, P < 0.0001, and P < 0.0001, respectively). The comparison of surgical information also showed that epididymal abnormality and state of processus vaginalis is patency or closure were significantly different between the groups (P = 0.0088 and P = 0.0003, respectively). Multivariate analysis showed that diagnosis at age 0-1 years, unilaterality, and canalicular testis were predictive factors for cryptorchidism (P = 0.001, P < 0.0001, and P < 0.0001, respectively). CONCLUSIONS: Age at diagnosis, laterality, and location of the testis could be factors to aid the diagnosis of retractile testis and cryptorchidism.

Trends in treatment outcomes for retractile testis in Japanese boys: A single-center study.

OBJECTIVES: To investigate the natural course of retractile testis by analyzing its prevalence and outcomes. METHODS: This retrospective study included 215 boys in whom retractile testis was diagnosed after reviewing the medical history and physical examinations of the patients. Orchiopexy was performed once the testis became undescended. We investigated the trends in the prevalence and outcomes of retractile testis and compared clinical factors between cases that resolved spontaneously and those that required orchiopexy. RESULTS: Of 215 boys, 145 were finally evaluated. The mean age at diagnosis was 2 years, and 100 boys were aged ≤2 years when they were hospitalized. Seventy-three boys were referred to our institution through health examinations as babies. The condition improved spontaneously in 89 boys, while 43 boys underwent orchiopexy, and 13 boys remained under follow-up. The follow-up period between diagnosis and resolution was significantly longer in the spontaneous resolution group than in the surgical intervention group (P = 0.011). Bilateral retractile testis improved spontaneously in significantly more boys compared to unilateral retractile testis (P = 0.0010). Spontaneous resolution was observed in boys of all ages, but those diagnosed at ≤3 years of age had a significantly higher rate of spontaneous resolution compared to those who were diagnosed at >3 years of age (P = 0.0019). CONCLUSIONS: Our findings suggest that retractile testis cannot be affirmed as a variant of normal testis. Performing examinations at a young age is critical for preventing misdiagnosis, screening failures, and unnecessary surgery.

[Retrospective Analysis of Severe Renal Infections Requiring Nephrectomy to Control Infection].

Patients who contract severe renal infections often suffer from urosepsis. Therefore, early diagnosis and treatment are required. Sometimes, the treatment with antibiotics is not enough for control of the infections. Most of the patients also require surgical interventions including transurethral drainage and nephrectomy. Twenty-two patients with severe renal infections treated between April 2010 and October 2019 at our institute were evaluated retrospectively. Eleven patients had undergone nephrectomy. Open nephrectomy was performed on 10 patients. Laparoscopic nephrectomy was attempted in the other patient but was converted to open nephrectomy because severe adhesion was found around the tissues. Nephrectomy was performed by the retroperitoneal approach on 9 patients and by the transperitoneal approach on 2 patients. The reteroperitoneal approach was used on two patients who suffered postoperative colon perforation. Inflammatory involvement of renal pelvis, hilum and adjacent structures leads to dense fibrotic reaction and obliteration of tissue planes, which makes the nephrectomy procedure challenging. Therefore, it is important to choose the most appropriate nephrectomy procedure for each patient when they have contracted severe renal infections.

Rationale, design, and methods of electroencephalography-based investigation of the effects of oral desmopressin on improving slow-wave sleep time in nocturnal polyuria patients (the DISTINCT study): protocol for a single-arm, open-label, single-assignment trial.

BACKGROUND: Nocturia is one of the most bothersome lower urinary tract symptoms and often impairs sleep quality in the elderly. Although previous studies on nocturia have indicated that the successful treatment of nocturia improves sleep quality, most used questionnaires and activity devices to analyze sleep/wake patterns. Therefore, there is little information about the treatment effects of desmopressin on objective sleep quality. The aim of the DISTINCT study is to investigate the change in subjective and objective sleep quality using electroencephalography (EEG) and the Pittsburgh Sleep Quality Index (PSQI) after the administration of desmopressin in patients with nocturia due to nocturnal polyuria. METHODS: A total of 20 male patients, ≥65 years old, with nocturnal polyuria, defined as a nocturnal polyuria index (NPi) (nocturnal urine volume / 24 h urine volume) value ≥0.33, will participate in this study. The participants must have a nocturnal frequency of ≥2 and the first uninterrupted sleep period (FUSP) must occur within < 2.5 h. Desmopressin 50 µg per day will be orally administered before going to bed for 4 weeks. Urinary frequency volume charts (FVC) and EEG will be recorded prior to treatment and at 1 week and 4 weeks after the initiation of treatment. The PSQI will be completed before and 4 weeks after treatment. The primary endpoint is the change from baseline in the mean time of slow-wave sleep (sleep stages N3 and N4) at 4 weeks. The secondary endpoints include the change in the mean value of each sleep variable, the mean delta power during the FUSP, the correlation between nocturnal urinary frequency and slow-wave sleep time, and the change in PSQI score before and after treatment. DISCUSSION: The DISTINCT study will provide valuable evidence to indicate that oral desmopressin treatment for nocturnal polyuria prolongs the FUSP, resulting in the extension of slow-wave sleep time associated with sleep quality. TRIAL REGISTRATION: The Japan Registry of Clinical Trials ( jRCTs051190080 ). Registered 9 December, 2019.

Initial experience of complete laparoscopic radical nephroureterectomy combined with transvesical laparoscopic excision of distal ureter in patients with upper urinary tract cancer.

BACKGROUND: Selecting the treatment procedure for cancer patients is a challenging task. We report our initial experience of complete laparoscopic radical nephroureterectomy (RNU) for patients with upper urinary tract urothelial cancer (UTUC). METHODS: A total of four patients with UTUC underwent complete laparoscopic RNU combined with transvesical laparoscopic excision of the distal ureter using three 5-mm ports. Transvaginal specimen extraction was applied in female patients to reduce incisional pain and improve cosmesis. Peri-operative complications were evaluated using the Clavien-Dindo classification system. Postoperative pain was evaluated during hospitalization using a numeric pain rating scale (scales of 1 to 10). Patients who underwent retroperitoneal laparoscopic surgery combined with open excision of the distal ureter during the same period were included as a control group (conventional RNU, consisting of laparoscopic nephrectomy combined with open bladder cuff excision) for pain scale evaluation. RESULTS: The novel surgery was successfully completed for all four patients (two males and two females). The mean pneumoperitoneum time for retroperitoneoscopic nephroureterectomy and specimen extraction was 174 min, while the mean pneumovesicum time for the ureteral orifice excision was 88 min. One male patient had bladder leakage at the suture site of the bladder wall, which lasted for 2 weeks. No patient experienced recurrent disease during the follow-up period (median, 10 months). Mild to moderate pain lasted for 5 or 6 days after RNU. A couple of days after surgery, the numeric pain rating scale of complete laparoscopic RNU and conventional RNU group reached its peak level at 3.0 ± 1.8 and 5.3 ± 2.8, respectively. There was no statistical difference in the degree of postoperative pain (P = 0.31). CONCLUSIONS: We described our initial experience and outcome of complete laparoscopic RNU for UTUC. Further experience and research are required to determine whether this advanced laparoscopic technique yields better outcomes and has true clinical value.

Trends in treatment outcomes of hydrocele in Japanese children: A single-institute experience.

OBJECTIVES: To investigate trends in treatment outcomes of surgical intervention versus observation for pediatric hydrocele. METHODS: This retrospective study included 175 patients diagnosed with hydrocele at our institution. Hydrocele was diagnosed based on medical history, physical examination and ultrasonography findings. The treatment for these patients was divided into two options: surgical intervention or careful follow up; the outcomes were investigated. RESULTS: The median age at diagnosis was 3 months, and a total of 11 patients (6%) were premature at birth. Hydrocele was diagnosed on the right side, the left side and bilaterally in 106 (61%), 46 (26%) and 23 (13%) patients, respectively. A total of 136 patients showed spontaneous improvement at the median 7 months after diagnosis, and 54 patients underwent surgical intervention. The rate of spontaneous resolution deceased with age, but spontaneous resolution was observed in patients aged >2 years. CONCLUSIONS: Our findings suggest that spontaneous resolution can be observed in patients aged >2 years, and surgical intervention can be carried out effectively and safely. Infant hydrocele should be followed up carefully for at least 1 year without surgical intervention since diagnosis. Investigation of the optimal timing of and appropriate reason for surgical intervention can lead to better management and outcomes in patients with hydrocele. Further research is warranted to support the current clinical practice.

Dual benefit of supplementary oral 5-aminolevulinic acid to pelvic radiotherapy in a syngenic prostate cancer model.

BACKGROUND: Normal tissue damage caused by radiotherapy remains the largest dose-limiting factor in radiotherapy for cancer. Therefore, the aim of this study was to investigate the supplementary oral 5-aminolevulinic acid (ALA) to standard radiation therapy as a novel radioprotective approach that would not compromise the antitumor effect of radiation in normal rectal and bladder mucosa in a syngenic prostate cancer (PCa) model. METHODS: To evaluate the radiosensitizing effect of ALA in vitro, clonogenic survival assays were performed in DU145, PC3, and MyC-CaP cell lines. To evaluate the effect of ALA in vivo a single dose (25 Gy) of radiation with or without ALA was given to healthy mice. Next, a syngenic PCa model of MyC-CaP cells in FVB mice was created, and multiple doses (12 Gy total) of radiation were administered to the mouse pelvic area with or without ALA administration. Resected tumors, recta, and urinary bladders were immunostained with antibodies against Ki-67, γ-H2AX, CD204, and uroplakin-III. Total RNA levels in recta and urinary bladders were analyzed via RT2 Profiler polymerase chain reaction (PCR) arrays related to "Stress & Toxicity PathwayFinder," "Mitochondria," and "Inflammasomes." RESULTS: The addition of in vitro single or in vivo repeated administration of exogenous ALA acted as a radiosensitizer for PCa cells. Rectal toxicity was characterized by histological changes including loss of surface epithelium, fibrosis, severe DNA damage, and the aggregation of M2 macrophages. Urinary bladder toxicity was characterized by bladder wall thickening and urothelium denuding. The higher dose (300 mg/kg/day) of ALA exerted a better radioprotective profile than the lower dose (30 mg/kg/day) in normal recta and urinary bladders. Out of the 252 genes tested, 35 (13.4%) were detected as relevant genes which may be involved in the radioprotective role of ALA administration. These included interleukin-1a (IL-1a), IL-1b, IL-12, chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL3, and NLRP3. CONCLUSIONS: Our study provides novel and comprehensive insights into the dual benefits including radiosensitizing PCa tumor tissues and radioprotection of normal pelvic organs from radiation therapy. Knowledge of the underlying mechanism will facilitate the search for optimal treatment parameters for supplemental oral ALA during radiotherapy for PCa.

Urinary nerve growth factor can predict therapeutic efficacy in children with monosymptomatic nocturnal enuresis.

AIM: To determine the urinary levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in children with monosymptomatic nocturnal enuresis (MNE) and evaluate whether these factors can be used as biomarkers for the treatment outcome. METHODS: NGF and BDNF levels were measured and compared in 38 children (28 boys and 10 girls) with MNE and 25 children (18 boys and 7 girls) with no urinary symptoms were assessed. The mean ages in the patient and control groups were 9 and 10 years, respectively (P = .49). The patients were treated with either alarm or desmopressin therapy. RESULTS: The urinary NGF/creatinine and BDNF/creatinine ratios were significantly higher in the patient group than in the control group (P = .0003 and P = .0095, respectively). NGF and BDNF levels showed a significant positive correlation (P = .0020, r = 0.40). With respect to the degree of response, 19 patients (50%) showed complete response (CR) or partial response (PR), and 19 patients (50%) showed nonresponse (NR). The urinary NGF/creatinine and BDNF/creatinine ratios were significantly higher in the NR group than in the CR and PR groups (P = .0003 and P = .0003, respectively). CONCLUSIONS: Urinary NGF/creatinine and BDNF/creatinine ratios were significantly higher in children with MNE than in healthy controls. Urinary NGF/creatinine can be predictive factors of a poor treatment outcome in children with MNE.

The diagnostic utility of retroperitoneoscopic tissue biopsy for unresectable retroperitoneal lesions excluding urogenital cancers.

BACKGROUND: Retroperitoneal tumors are an uncommon disease known to consist of a diverse group of benign and malignant neoplasms. Treatment of unresectable retroperitoneal lesions requires pathological diagnosis. Here, we report the utility and safety of retroperitoneoscopic biopsy for unresectable retroperitoneal lesions excluding urogenital cancers. METHODS: We analyzed 47 patients consisting of 23 (49%) and 24 (51%) cases that underwent retroperitoneoscopic tissue biopsy and open biopsy, respectively. The clinicopathological features, including postoperative complications, were compared between the two groups. RESULTS: Tumor pathology was diagnosed successfully with a single operation in all patients. Malignant pathology (68%) was more common than benign pathology (32%). The most common pathology was malignant lymphoma, which accounted for about 50% of all cases. There was no significant difference with respect to the age, sex, tumor size, presence of tumor-related symptom, histopathology, operative time, and complications. Three (13%) of 23 patients in the retroperitoneoscopic biopsy group received percutaneous needle biopsy before laparoscopic excisional biopsy because the evaluation of needle cores failed to confirm subclasses of diagnosed pathologies. One patient was converted to open surgery just after the initiation of operation due to severe adhesion of adjacent structures. We had two cases with iatrogenic urinoma due to ureteral injury after retroperitoneoscopic biopsy. CONCLUSIONS: We conclude that retroperitoneoscopic biopsy is a safe and useful tool for benign and malignant retroperitoneal lesions, in comparison to open biopsy. It is critical to carefully examine the preoperative imaging for the location of tumors, especially those close to the renal pelvis and ureter.

Tadalafil, a phosphodiesterase type 5 inhibitor, improves bladder blood supply and restores the initial phase of lower urinary tract dysfunction in diabetic rats.

AIMS: To investigate the effect of tadalafil on bladder blood flow and lower urinary tract function in a rat model of diabetes. MATERIALS AND METHODS: We studied female Sprague-Dawley rats and induced diabetes in some using a single intraperitoneal injection of streptozotocin. We divided the rats into nondiabetes (ND), diabetes (D), and diabetes with tadalafil (DT) groups. The rats were raised for an additional 7 weeks after diabetes induction. The DT group received oral tadalafil (2 mg/kg/day) for 7 days before the experiments. At 7 weeks after diabetes induction, we performed cystometry, resected the bladders for immunohistochemistry (hypoxia-inducible factor-1α [HIF-1α] and 8-oxo-2'-deoxyguanosine [8-OHdG] staining), and measured bladder blood supply using a laser blood flow meter. RESULTS: The opening pressure, when the urethra opens and urine flow starts, was significantly lower in the DT group than in the D group (24.9 ± 5.9 vs 43.6 ± 12.3 cmH2 O). The inter-contraction interval was significantly longer in the D group than in the ND and DT groups (1566.2 ± 168.7 vs 702.9 ± 165.2 and 787.4 ± 148.8 s). Immunohistochemistry showed positive staining of the urothelial layer for both HIF-1α and 8-OHdG in the D group, but not in the ND or DT groups. Bladder blood flow was significantly lower in the D group than in the ND or DT groups. CONCLUSIONS: Tadalafil improves bladder blood supply and lower urinary tract function in diabetic rats. Tadalafil may be a promising drug that restores lower urinary tract dysfunction in the early phase of diabetes.

Clinical utility of bioelectrical impedance analysis in patients with locoregional muscle invasive or metastatic urothelial carcinoma: a subanalysis of changes in body composition during neoadjuvant systemic chemotherapy.

PURPOSE: The aim of this study was to determine the clinical utility of bioelectrical impedance analysis (BIA) in a cohort of patients with advanced urothelial carcinoma (UC). METHODS: We prospectively evaluated body composition in 35 patients with locoregional muscle invasive (≥ T2 and N0-2M0) or metastatic UC. Body composition was evaluated using multifrequency BIA at baseline (n = 35) and during chemotherapy in patients receiving neoadjuvant chemotherapy (n = 14). The BIA-predicted body composition index was compared with the computed tomography-measured muscle index and the prognostic nutrition index. Changes in body composition during neoadjuvant chemotherapy were recorded and compared with the incidence of hematological adverse events. RESULTS: There was a significant correlation between the BIA-predicted skeletal muscle index and the computed tomography-measured skeletal muscle index (P = 0.004), while there was no significant correlation between the prognostic nutrition index and the BIA-predicted nutrition index. After the completion of 3 cycles of neoadjuvant chemotherapy, the skeletal muscle index showed a significant decrease (P = 0.016), while the total body fat mass (P = 0.025), body fat percentage (P = 0.013), and body mass index (P = 0.004) showed a significant increase (a tendency toward "sarcopenic obesity"). Patients who experienced grade 2-3 anemia during neoadjuvant chemotherapy showed a significantly lower increase in body mass index compared with patients who did not experience high-grade toxicities (P = 0.032). CONCLUSIONS: BIA could contribute to other methods of nutrition and muscle assessment for pretreatment risk stratification in patients with UC. Further study of a larger cohort is required to elucidate the clinical impact of changes in body composition during chemotherapy.

Diagnostic and prognostic role of urinary collagens in primary human bladder cancer.

Collagen type 4 alpha 1 (COL4A1) and collagen type 13 alpha 1 (COL13A1) produced by urothelial cancer cells support the vital oncogenic property of tumor invasion. We investigated the diagnostic and prognostic capability of COL4A1 and COL13A1 in voided urine and compared the observed values with those of fragments of cytokeratin-19 (CYFRA21-1), nuclear matrix protein 22 (NMP-22), and voided urine cytology in bladder cancer (BCa). We collected voided urine samples from 154 patients newly diagnosed with BCa, before surgery and from 61 control subjects. Protein levels of COL4A1, COL13A1, CYFRA21-1, and NMP-22 in urine supernatants were measured using enzyme-linked immunosorbent assays. Diagnostic performance and optimal cut-off values were determined by receiver operating characteristic analysis. Urine levels of COL4A1, COL13A1, the combined values of COL4A1 and COL13A1 (COL4A1 + COL13A1), and CYFRA21-1 were significantly elevated in urine from patients with BCa compared to the controls. Among these biomarkers, the optimal cut-off value of COL4A1 + COL13A1 at 1.33 ng/mL resulted in 57.4%, 83.7%, 56.1%, 80.7%, and 91.7% sensitivity for low-grade tumors, high-grade tumors, Ta, T1, and muscle invasive disease, respectively. We evaluated the prognostic value of preoperative urine levels in 130 non-muscle invasive BCa samples after the initial transurethral surgery. A high urinary COL4A1 + COL13A1 was found to be an independent risk factor for intravesical recurrence. Although these data need to be externally validated, urinary COL4A1 and COL13A1 could be a potential diagnostic and prognostic biomarker for BCa. This easy-to-use urinary signature identifies a subgroup of patients with a high probability of recurrence and progression in non-muscle invasive and muscle invasive BCa.

Integrative Assessment of Pretreatment Inflammation-, Nutrition-, and Muscle-Based Prognostic Markers in Patients with Muscle-Invasive Bladder Cancer Undergoing Radical Cystectomy.

OBJECTIVE: The present study evaluated the clinical relevance of an integrative preoperative assessment of inflammation-, nutrition-, and muscle-based markers for patients with muscle-invasive bladder cancer (MIBC) undergoing curative radical cystectomy (RC). METHODS: The analysis enrolled 117 patients and the variables included age, body mass index (BMI), neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, modified Glasgow Prognostic Score (mGPS), prognostic nutritional index (PNI), Controlling Nutritional Status score, psoas muscle index (PMI), and peak expiratory flow (PEF). The correlations among the variables were evaluated and their prognostic values after RC were tested. RESULTS: Three inflammation markers (ratios of blood cell counts) were positively correlated (p < 0.0001). The PNI and the BMI were positively correlated (p = 0.04), although they were inversely correlated with the three inflammation markers (p < 0.0001). Age was not significantly correlated with the inflammation markers and PMI, although older age was associated with lower PNI and lower PEF. The disease-specific survival was independently predicted by T4 tumor, positive N status, and decreased PNI. Overall survival was independently predicted by T4 tumor, mGPS, and pretreatment sarcopenia status. CONCLUSIONS: The inflammation-, nutrition-, and muscle-based markers would be useful risk assessment tools for MIBC.

Clinical impact of postoperative loss in psoas major muscle and nutrition index after radical cystectomy for patients with urothelial carcinoma of the bladder.

BACKGROUND: Although the significance of preoperative nutritional status has been investigated, there is no report regarding the relationship of their postoperative changes on outcomes in patients who underwent radical cystectomy for bladder cancer. Here, we report the clinical impact of the change, from baseline, in nutritional status and volume of abdominal skeletal muscle mass and adipose tissue after radical cystetomy. METHODS: A retrospective analysis of 89 patients with bladder cancer, who underwent curative radical cystectomy, was conducted to assess the time course of change, from baseline, in body composition and nutritional status at 1, 3, 6, 12, and 24 months, after surgery. Skeletal muscle mass and abdominal adipose tissue mass were quantified by unenhanced computed tomography images. Two different nutritional indices, the Prognostic Nutritional Index and the Controlling Nutritional Status score were calculated from laboratory blood tests. We evaluated the prognostic value of the rate of change in the body composition and nutritional status after radical cystectomy. RESULTS: The cross-sectional area at the level of the third lumbar vertebra of the psoas major muscle and nutritional indices showed a transient deterioration at 1 and 3 months after radical cystectomy, with a return to baseline values from 6 to 24 months. A ≤ -10% loss in the area of the psoas muscle was associated with a shorter overall survival, compared to those with a > -10 change [hazard ratio (HR) 2.2, P = 0.02]. Multivariate analyzes identified sarcopenia status at baseline (HR 2.2, P = 0.03) and a ≤ -10% loss in the psoas muscle (HR 2.4, P = 0.02) were identified as independent prognostic factors for overall survival. A subanalysis of patients without sarcopenia identified a worse survival outcome for patients with a ≤ -10% loss in the psoas muscle (HR 2.6, P = 0.03) and ≤ - 5 change in the Prognostic Nutritional Index (HR 3.6, P = 0.01). CONCLUSION: Further research is required to establish appropriate rehabilitation protocols and nutritional interventions after radical cystectomy for maintaining skeletal muscle mass and nutrition status which could counteract physical deterioration and improve outcomes.

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.