Sarcopenia and the rate of change of the neutrophil/lymphocyte ratio as predictors of pembrolizumab efficacy in advanced urothelial carcinoma.

The objective was to evaluate the usefulness of sarcopenia and the neutrophil/lymphocyte ratio (NLR) as therapeutic efficacy predictors in patients who received pembrolizumab after platinum-based chemotherapy for advanced urothelial carcinoma (aUC). Forty-four patients with aUC were enrolled. Patients' background characteristics and clinical factors, the skeletal muscle index, and the psoas muscle index were evaluated. The NLR before and during treatment was calculated, and the rate of change of NLR was calculated. The median age was 70 years; the follow-up period was 13.2 months. The response rate was 54%. The nonresponding group had significantly more sarcopenia cases (P = 0.007) and a high rate of change of NLR (P = 0.0076). Progression-free survival (PFS) was significantly shorter in the group with sarcopenia (P = 0.002). Both PFS and overall survival were significantly shorter with an NLR rate of change greater than or equal to 1 (P = 0.001 and P = 0.002). On multivariate analysis, the presence of immune-related adverse events [hazard ratio (HR), 0.3723; 95% confidence interval (CI), 0.14-0.97; P = 0.04] and the NLR rate of change (HR, 3.986; 95% CI, 1.01-15.70; P = 0.048) were independent predictors of PFS. Sarcopenia and the rate of change of NLR appear to be useful as predictors of pembrolizumab efficacy in aUC.

Tadalafil 5 mg Once Daily Improved Each IPSS Subscore, QOL, and Nocturia in Elderly BPH Patients over 70 Years Old in a Real-World Clinical Setting.

OBJECTIVE: No reports have evaluated the treatment effects of tadalafil by age group in a positive, noninterventional observational study of Japanese men. The present study aimed to evaluate the treatment effects of tadalafil by age group in a positive, noninterventional observational study of Japanese men. We therefore divided patients into 2 groups about the age of 70 years and investigated the treatment effects of tadalafil regarding voiding and storage functions by age group. METHODS: Changes from baseline in each parameter (International Prostate Symptom Score [IPSS], quality of life [QOL] score, Overactive Bladder Symptom Score [OABSS], and residual urine volume) at 4, 12, and 24 weeks after initiating tadalafil for benign prostatic hyperplasia (BPH) patients were compared between groups (50-69 years vs. ≥70 years). In addition, side effects of tadalafil were investigated by age group. RESULTS: In the 50-69 years group, significant improvements from baseline were seen in IPSS total and QOL score for all time points. In addition, significant improvements in IPSS storage subscore from baseline were observed at the 4- and 24-week time points. In the ≥70 years group, significant improvements from baseline were seen in IPSS total, IPSS voiding and storage subscores, and QOL score at each time point. CONCLUSIONS: Tadalafil 5 mg once daily appeared effective in clinical settings for elderly BPH patients even over 70 years old.

5-Aminolevulinic acid has the potential to prevent bladder dysfunction in cyclophosphamide-induced hemorrhagic cystitis.

OBJECTIVES: To investigate the effects of pretreatment with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate on bladder dysfunction in cyclophosphamide-induced hemorrhagic cystitis in rats. METHODS: Male Wistar rats (340-460 g) were pretreated with vehicle or with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate (100/157 or 300/471 mg/kg/day, po) once daily for 7 days before cystometry. Saline or cyclophosphamide (150 mg/kg, ip) was administered 2 days before cystometry. Cystometry was performed under urethane anesthesia (0.8 g/kg, ip) via a catheter inserted into the bladder. After cystometry, bladder tissues were collected to perform hematoxylin and eosin staining for pathological evaluation (neutrophil infiltration, edema, and bleeding scores), and for enzyme-linked immunosorbent assay and real-time polymerase chain reaction for investigating tissue levels of myeloperoxidase, and mRNA levels of haem oxygenase-1 as a cytoprotective molecule. RESULTS: Compared to controls, cyclophosphamide induced a shorter intercontraction interval, lower bladder compliance, increased number of non-voiding contractions, and increased pathological scores and myeloperoxidase expression in the bladder. Pretreatment with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate (300/471 mg/kg/day) significantly improved cyclophosphamide-induced intercontraction interval shortening and increases in number of non-voiding contractions and neutrophil infiltration/bleeding scores and enhanced haem oxygenase-1 expression in the bladder. In addition, cyclophosphamide-induced decreases in bladder compliance and increases in myeloperoxidase were not detected with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate pretreatment. CONCLUSIONS: Pretreatment with 5-aminolevulinic acid expects protective effects on bladder dysfunction in cyclophosphamide-induced hemorrhagic cystitis by improving inflammatory changes in bladder tissues perhaps via up-regulation of haem oxygenase-1.

Bilateral Xp11.2 translocation renal cell carcinoma: a case report.

BACKGROUND: Xp11.2 translocation renal cell carcinoma (RCC) is a rare variety of a kidney neoplasm. We report a case of bilateral Xp11.2 translocation RCC occurring metachronously and discuss this very rare entity with reference to the literature. CASE PRESENTATION: The patient was a 56-year-old woman who presented with a right renal tumor. The patient had undergone left radical nephrectomy 7 years previously, which resulted in a histopathological diagnosis of clear cell RCC. Open right partial nephrectomy was performed under the presumptive diagnosis of recurrence of clear cell RCC. The present right renal tumor was pathologically diagnosed Xp11.2 translocation RCC. More than 70% of the tumor cells in the present right tumor were strongly positive for transcription factor E3 (TFE3) expression by immunohistochemical analysis with an anti-TFE3 antibody. A break-apart of the TFE3 genes in the bilateral tumors was identified by fluorescence in situ hybridization analysis. Real time-polymerase chain reaction analysis for the alveolar soft part sarcoma locus-TFE3 fusion gene was performed, which gave a positive result in the bilateral tumors. Pathological comparison of each of the tumors might lead to a final diagnosis of Xp11.2 translocation RCC occurring metachronously. CONCLUSIONS: We present the bilateral Xp11.2 translocation RCC. A combination of immunohistochemical, cytogenetic and molecular biological approaches allowed the final diagnosis of such a rare RCC.

BCG-induced pneumonitis with lymphocytic pleurisy in the absence of elevated KL-6.

BACKGROUND: Pneumonitis is a rare complication of bacillus Calmette-Guerin (BCG) immunotherapy seen in patients with urothelial cancer following the repeated administration of BCG. However, no case of BCG-induced pleurisy has been reported. CASE PRESENTATION: We here report the first case of pneumonitis with lymphocytic pleurisy following bacillus Calmette-Guerin (BCG) immunotherapy. Although marked T helper cell alveolitis was found by bronchoalveolar lavage and transbronchial biopsies, no acid-fast bacillus could be identified in recovered BALF or pleural effusion. The lymphocyte stimulation test of BCG was strongly positive. However, levels of serum and bronchoalveolar lavage fluid KL-6, a useful marker for hypersensitivity pneumonitis (HP), were within normal ranges. CONCLUSION: We speculate that the pathogenesis of our case may be a hypersensitive reaction to the proteic component of BCG entering the lung and pleural space, which is different from the etiology of the common type of HP.

Vibegron 50 mg Once Daily Improves OABSS, OAB-q SF Score in OAB Patients ≥80 Years Old in Real-World Clinical Settings and Switching from Other OAB Drugs May Reduce Residual Urine Volume.

Objective: The treatment effects of vibegron have not previously been evaluated in a prospective, non-interventional observational study of elderly Japanese patients, particularly those ≥80 years old. In addition, no reports have referred to residual urine volume in switching cases. We therefore grouped patients by condition and investigated the treatment effects of vibegron on Overactive Bladder Symptom Score (OABSS), Overactive Bladder Questionnaire Short Form (OAB-q SF), and residual urine volume in each group. Methods: This multicenter, prospective, non-interventional, observational study consecutively enrolled OAB patients with total OABSS score ≥3 and OABSS question 3 score ≥2. Sixty-three patients from six centers were recruited. Vibegron 50 mg once daily was administered for 12 weeks as first-line monotherapy (first-line group), monotherapy switching from antimuscarinics or mirabegron due to failure of prior therapy (no washout period), or combination therapy with antimuscarinics (second-line group). OABSS, OAB-q SF, and residual urine volume were collected after 4 and 12 weeks. Adverse events were also recorded at each visit. Results: Of the 63 patients registered, 61 were eligible for analysis (first line, n=36; second line, n=25). The OABSS, excluding daytime frequency scores, and OAB-q SF scale showed significant improvement in all conditions. Switching from mirabegron to vibegron significantly reduced residual urine volume. No serious treatment-related adverse events were encountered. Conclusion: Vibegron 50 mg once daily significantly improved OABSS and OAB-q SF even in patients ≥80 years old. Notably, switching from mirabegron to vibegron resulted in significant improvements to residual urine volume.

Extragonadal seminoma presenting as a large mass in the pelvic cavity without c-kit-activating mutations.

Extragonadal germ cell tumors are relatively rare tumors, which usually occur in the mediastinum or retroperitoneum. In this report, we present a case of primary seminoma arising in the pelvic cavity. A 58-year-old man with urinary retention and abdominal distension was admitted to our hospital. Computed tomography and magnetic resonance imaging demonstrated a large mass in the pelvic cavity. Histological examination of the specimens obtained by open biopsy revealed seminomatous malignant cells. Immunohistochemical studies detected vimentin, placental alkaline phosphatase and c-kit. Taking these results together with the patient's other clinical manifestations, this case was diagnosed as extragonadal seminoma without c-kit-activating mutations, and chemotherapy followed by radiation therapy was successful. Primary seminoma in the pelvic cavity is extremely rare, but should be considered a cause of pelvic mass formation.

[The clinical value of 3 tesla diffusion-weighted magnetic resonance imaging in the diagnosis of prostate cancer].

Diffusion-weighted imaging (DWI) is a magnetic resonance imaging (MRI) method and is considered potentially useful for detecting prostate cancer. We evaluated the clinical value of DWI with apparent diffusion coefficient (ADC) maps in addition to T2-weighted imaging (T2WI) using 3 tesla (3 T) MRI. Thirty-three patients with elevated prostate specific antigen were evaluated by MRI with T2WI and DWI prior to transperineal template-guided mapping biopsy. The MRI findings were compared with the pathology of biopsy specimens in six parts of prostate : both sides of outer peripheral zones, inner peripheral zones, and transition zones. The sensitivities, specificities and accuracies were 42.1, 84.4 and 76.3％ in T2WI, 57.1, 84.7 and 80.8% in T2WI/DWI, and 87.5, 85.2 and 85.4% in DWI/ADC using 0.951×10 -3 mm2/s as cutoff ADC value. The hazard ratio of patients whose ADC values were under the cutoff was 25.86 by multivariate analysis. Mean ADC values were significantly different between cancer positive and negative cores (p＜0.001). The ADC value showed a negative correlation with increasing tumor length (p＝0.0047). Although further study with a large number of patients is necessary, DWI/ADC using 3 T MRI is a useful tool for detecting prostate cancer.

Oncocytic variant, a novel subtype of chromophobe renal cell carcinoma: a report of two cases and a literature review.

A novel variant of chromophobe renal cell carcinoma showing an oncocytic phenotype is proposed. Two new cases of this rare entity are presented and discussed along with six previous cases from our colleagues. A 76-year-old man and a 78-year-old man had a 3.4-cm and a 3.2-cm-diameter renal mass, respectively. On histopathological examination of surgical specimens, uniform eosinophilic cuboidal cells without a perinuclear halo growing in a tubular pattern were seen, and differential diagnosis from oncocytoma was necessary. Immunohistochemical staining for cytokeratin 7 and E-cadherin showed diffusely positive patterns in both, as in the previous reports. Although monosomy of chromosomes 7, 10, 13, and 17 was commonly observed in the previous reports, gains of chromosome 19 were observed in the two present cases. Immunohistochemical and cytogenetic approaches lead to exclusion of oncocytoma and the diagnosis of an oncocytic variant of chromophobe renal cell carcinoma.

[Successful response of reccurent adult wilms' tumor to multiagent chemotherapy].

We report a case of successful response of lung metastases of reccurent adult Wilms' tumor by multiagent chemotherapy. The patient was a 19-year-old woman who had undergone left radical nephrectomy and adjuvant chemotherapy (actinomycin D, vincristine) for stageadult Wilms' tumor when she was 16 years old. Coputed tomography (CT) revealed multiple lung metastases (right parietal pleura, left S10, right S10). We treated the patient with thoracoscopic partial resection of inferior lobe of lung. Then she received multiagent chemotherapy (vincristine, adriamycin, etoposide, cyclophosphamide). CT scan showed complete response of the lung metastases at 8 months.

[Clinical experience with transurethral resection of bladder tumor (TUR-Bt) guided by photodynamic diagnosis (PDD)].

PURPOSE: To report our clinical experience regarding transurethral resection of bladder tumor (TUR-Bt) guided by photodynamic diagnosis (PDD) with intravesical instillations of 5-aminolevulinic acid (ALA) and to assess the usefulness of the therapeutic method. MATERIALS AND METHODS: TUR-Bt guided by PDD was performed in 57 patients of which 47 were men and 10 women with a median age of 74.3 years (range 45-90), 36 were primary cases and 21 were recurrent cases with non-muscle invasive bladder cancer. Two to two and half hours prior to endoscopy 1.5 g ALA dissolved in 50 ml of 8.4% sodium hydrogen carbonate (NaHCO3) solution was instilled intravesically. For fluorescence excitation a blue light source (D-LIGHT System, Karl Storz Endoscopy Japan K.K.) was used. The tumorous lesions under white light guidance and the lesion with fluorescent excitation under blue (fluorescence) light guidance were taken by cold cup as a biopsy and also resected sequentially. To evaluate the accuracy of PDD, the levels in images of the ALA-induced fluorescence were compared with the pathological results. To evaluate the availability of TUR-Bt guided by PDD, survival Analysis regarding vesical recurrence was retrospectively examined compared to the cases underwent conventional TUR-Bt under white light guidance. Moreover, in these cases, multivariate analysis using Cox proportional-hazards model was performed to detect the clinico-pathological factor independently contribute to improving prognosis. (Results) In the 301 specimens obtained from 57 patients, the sensitivity and specificity of PDD were 92.5% and 60.1%, whereas the sensitivity and specificity of conventional endoscopic examination under white light guidance were 81.6% and 79.5%, respectively. Median follow-up period was 19.1 (range 8.6-49.9) months in 57 patients underwent TUR-Bt guided by PDD. Eight of 57 patients recurred and recurrence-free survival rate was 88.2 +/- 0.1% (at 12 months) and 76.2 +/- 0.1% (24-48 months). Median follow-up period was 49.9 (5.0-145.0) months in 149 patients underwent conventional TUR-Bt. Ninety-nine of 149 patients recurred and recurrence-free survival rate was 60.3 +/- 0.0% (12 months) and 31.6 +/- 0.0% (24-48 months). There was statistical significance in recurrence-free survival rate between these 2 therapeutic groups (p < 0.001). Moreover, multivariate analysis revealed the independent factor contribute to improving prognosis was only TUR-Bt guided by PDD (hazard ratio 0.279, p = 0.001). CONCLUSION: It was suggested that TUR-Bt guided by PDD might reduce the risk of vesical recurrence in the early stage after operation of non-muscle invasive bladder cancer.

Pathological risk factors in upper urinary tract cancer.

AIMS: To evaluate pathological factors for prognosis, intravesical recurrence and distant metastasis of upper urinary tract cancer. METHODS: This clinical study included 105 patients with renal pelvic and ureteral cancer who were treated at the Kochi Medical School Hospital between 1982 and 2008. Of these patients, 90 who underwent nephroureterectomy were analyzed for pathological risk factors using uni- and multivariate analysis. RESULTS: The mean follow-up period of the 105 patients was 53 months. The disease-specific survival rates were 70% and 62% at 3 and 5 years. Twenty-three patients (23%) developed intravesical recurrence, and the mean and median times to recurrence were 18.8 and 9.2 months, respectively. Seventeen patients (19%) had distant metastasis, and the mean and median times to distant metastasis were 25.2 and 25.3 months, respectively. Multivariate analysis identified the pathological grade as an independent risk factor for prognosis (P = 0.031), age (≥67 years) and tumor diameter (≥3 cm) as independent risk factors for intravesical recurrence (P = 0.007 and 0.003, respectively), and the pathological grade (G1,2 vs G3) and lymphatic invasion as independent risk factors for distant metastasis (P = 0.006 and 0.003, respectively). CONCLUSION: Patients with higher-grade upper urinary tract cancer show a poor prognosis, and often develop distant metastasis, suggesting the need for careful postoperative follow-up. Those with lymphatic invasion or tumors of 3 cm or more in diameter frequently develop intravesical recurrence and distant metastasis, respectively, indicating the need for strict follow-up.

Extensive rhabdomyosarcomatous differentiation in recurrent low-grade urothelial carcinoma of the bladder after transurethral resection: a case report.

INTRODUCTION: Sarcomatoid carcinoma of the urinary bladder is a rare bidirectional malignant neoplasm with epithelial and mesenchymal differentiation. The epithelial component is mainly high-grade urothelial carcinoma, and the mesenchymal component includes rhabdomyosarcoma. However, proper differential diagnosis of adult rhabdomyosarcomatous tumors of the bladder can be a challenge. Moreover, low-grade urothelial carcinoma as the epithelial component of sarcomatoid carcinoma has not been reported. CASE PRESENTATION: A 64-year-old Asian man with a history of transurethral resection of low-grade urothelial carcinoma of the bladder visited our department with complaints of frequent urination and macroscopic hematuria. Computed tomography and magnetic resonance imaging demonstrated a large mass located in the anterior wall of the bladder. Pathological diagnosis of transurethral biopsy was low-grade, non-invasive papillary urothelial carcinoma, and tumor tissue was removed by total cystectomy. Immunohistochemical studies and fluorescence in situ hybridization assay of the resected neoplastic tissue revealed extensive rhabdomyosarcomatous differentiation causing the formation of a large pedunculated polyp with a papillary appearance of recurrent low-grade urothelial carcinoma. No evidence of recurrence was detected during 2 years of follow-up without further treatment. CONCLUSIONS: Urothelial carcinoma of the urinary bladder with extensive rhabdomyosarcomatous differentiation is rare, but it should be considered in the differential diagnosis even when urothelial carcinoma coexisting with a rhabdomyosarcomatous component is low-grade and non-invasive.