Impact of the objective response to and number of cycles of platinum-based first-line chemotherapy for metastatic urothelial carcinoma on overall survival of patients treated with pembrolizumab.

OBJECTIVES: To investigate the impact of the number of cycles and objective response to chemotherapy on overall survival in patients with metastatic urothelial carcinoma treated with pembrolizumab. METHODS: This multicenter, retrospective study included 755 patients from 59 institutions with advanced, chemoresistant urothelial carcinoma who received pembrolizumab. The associations of the overall survival with the number of cycles and best objective response were investigated using Cox multiple regression analysis. RESULTS: Overall, 391 patients received standard first-line chemotherapy and pembrolizumab as a second-line treatment, and were included in the final analysis. Of the 391 patients, 185 received less than four cycles, 134 received four to six cycles and 72 received more than six cycles of first-line chemotherapy. An objective response (complete or partial response) to chemotherapy was observed in 145 patients (37.1%). Univariate analysis showed that the overall survival of patients who received more than six cycles or responded to chemotherapy (complete or partial response) was significantly longer than that of patients who received less than four cycles or did not respond to chemotherapy (stable or progressive disease). At multivariate levels, no correlations were observed between overall survival and the number of cycles of or the response to chemotherapy. CONCLUSIONS: Therapeutic benefit of pembrolizumab can be expected irrespective of the objective response to and number of cycles of platinum-based first-line chemotherapy.

[A Case of Penile Pyoderma Gangrenosum Treated by Urethrocutaneostomy without Penectomy].

We herein report a case of penile pyoderma gangrenosum that was successfully treated with prednisolone and by urethrocutaneostomy without penectomy. A man in his 50s visite dour department because of painful urination. Pyuria and redness of the external urethral meatus were present. Treatment for urethritis with antibiotics did not improve his symptoms, and a painful ulcer and fistula formation between the glans and urethra subsequently developed. Microbiological cultures revealed no growth, and punch biopsy showed only nonspecific inflammation, leading to a diagnosis of penile pyoderma gangrenosum. We initiated prednisolone (PSL) at 40 mg once daily following placement of an indwelling suprapubic cystostomy tube for dysuria. However, the treatment was ineffective. Therefore, the dosage of PSL was increased to 65 mg once daily. The ulcer disappeared， but urethral stricture remained. Six hundred days after PSL treatment, we performed urethrocutaneostomy. The patient became free of the cystostomy and was able to urinate spontaneously. In recent years, there has been an increasing number of reports of penile preservation in the treatment of penile pyoderma gangrenosum, but knowledge regarding which patients require urethral surgery is lacking. Urologists should keep in mind increased susceptibility to infection, pathergy and possible recurrence, when considering urethral surgery for penile pyoderma gangrenosum.

[Misdirection of an Indwelling Urethral Catheter into the Ureter in a Female Patient with Neurogenic Bladder : A Case Report].

We report a case of misdirection of an indwelling urethral catheter into the ureter. An 86-year-old women with neurogenic bladder had been undergoing chronic indwelling urethral catheter exchange for 1 year. She was referred to our hospital owing to lower abdominal pain and gross hematuria. A computed tomographic scan showed an indwelling urethral catheter in the right ureter. Retrograde ureterography showed that the ureter had no leakage and the catheter was removed under fluoroscopic guidance. Urethral catheterization is a common procedure. We reviewed 23 cases of an indwelling urethral catheter entering the ureter and we consider that this misdirection occurs particularly among female patients with neurogenic bladder.

[Two Cases of Inflammatory Myofibroblastic Tumor of the Urinary Bladder].

We describe two cases of inflammatory myofibroblastic tumor (IMT) of the urinary bladder. Case 1 : A 55-year-old man complained of urinary frequency. Transurethral biopsy of the bladder tumor was performed ; pathological examination revealed IMT. After steroid therapy for 1 year, the tumor was markedly reduced in size. Laparoscopic partial cystectomy was performed. The patient has now been free from recurrence for 3 years after the surgery. Case 2 : A 61-year-old man presented with gross hematuria. Transurethral biopsy of the bladder tumor revealed IMT. Despite steroid therapy for 6 months, the tumor size increased. Laparoscopic partial cystectomy and vesicoureteroneostomy were performed. The patient has now been free from recurrence for 1 year and 11 months after the surgery. IMT of the urinary bladder often responds well to steroid therapy. We experienced two cases of IMT. One showed a good response to steroid therapy and the other showed a poor response to steroid therapy. In both cases, we performed laparoscopic partial cyctectomy and the patients have remained free from recurrence IMT of the urinary bladder may have a good prognosis after complete surgical resection.

[Lymph Node Metastasis to the Prostatic Anterior Fat Pad in the Patients Treated with Prostatectomy].

We investigated the prostatic anterior fat pad (PAFP) for the presence of lymph nodes and lymph node metastases after excision during radical prostatectomy for the treatment of prostate cancer. From November 2013 to May 2017, 215 patients underwent radical prostatectomy for localized prostate cancer at our institution. PAFP was removed and sent for pathological analysis routinely to evaluate the presence of lymph nodes and lymph node metastases. Of the 215 patients, 20 (9.3%) had lymph nodes in the PAFP. Among the 20 patients with lymph nodes in the PAFP, 2 patients (10.0% ; 0.9% of all patients) were positive for metastatic prostate cancer. These patients did not have positive nodes elsewhere among the pelvic lymph nodes. There was no significant difference in the clinicopathological features between the patients with lymph nodes in the PAFP and those with no lymph nodes in the PAFP. The present findings are similar to those in the Western population. Considering the very low rate of lymph node metastasis in PAFP, it is necessary to discuss which patients should be selected for pathological analysis of PAFP.

[A Case of Primary Sigmoid Colon Lymphoma Presenting with Sigmoidovesical Fistula in a Patient with a Long History of Ulcerative Colitis].

A 73-year-old male patient with a 16-year history of ulcerative colitis presented to our hospital with a history of pneumaturia and fever. Cystoscopy and a computed tomography scan showed sigmoidovesical fistula. Colonoscopy showed a necrotic tumor along with sigmoidovesical fistula. A biopsy was not sufficient to make a definitive diagnosis of the tumor. Total colectomy with ileostomy and partial cystectomy were performed. A pathological examination showed diffuse large B-cell lymphoma of the sigmoid colon. On postoperative day 35, delayed dehiscence of the bladder wall was detected and a biopsy of the bladder wall showed lymphoma. Standard systemic chemotherapy (R-THP-COP) was administered and the defect of the bladder was closed. Three years and 2 months postoperatively, the patient has no local recurrence or distant metastasis.

[An Increase in Cases of Bladder Tamponade Due to Cystitis Among Elderly Women and Clinical Background Factors].

Bladder tamponade is thought to be caused mainly by bladder cancer or radiation cystitis. However, in women, it may often be caused by cystitis in clinical settings. This has not been noted in previous reports of bladder tamponade in Japan. Thus, we retrospectively analyzed the clinical features of 83 male and 41 female patients with bladder tamponade. Seventy-four patients were treated at Nishi-Kobe Medical Center between April 2005 and March 2015, and 50 were treated at Shizuoka City Shizuoka Hospital between November 2008 and March 2015. The patients'median age was 80 years. The cause of bladder tamponade was urological malignancies in 33 of the 83 male patients (40%), benign prostatic hyperplasia in 20 of the 83 male patients (24%), and cystitis in 33 of the 41 female patients (80%). Compared with the men, the women with bladder tamponade were significantly older and the proportion of patients with cerebrovascular disease, diabetes, and dementia was higher. In addition, more women were nursing home residents, with a higher rate of voiding with diapers and antithrombotic use than men. Causative strains of cystitis were diverse, and some were antibiotic resistant. Most of the cases of bladder tamponade in the women occurred in the elderly and were caused by cystitis. In an aging society, increases in the incidences of chronic, complicated cystitis due to impaired independent micturition, dysuria, and systemic diseases such as diabetes, and increased use of antithrombotic drugs may contribute to bladder tamponade in women.

[A Case of Hyperammonemia Caused by Urinary Tract Infection Due to Urease-Producing Bacteria].

We present here a rare case of hyperammonemia without liver dysfunction or portal-systemic shunting. The patient was an 80-year-old woman with a history of neurogenic bladder. She was admitted to a nearby hospital for vomiting, diarrhea and consciousness disturbance. Two days after admission, she was transferred to our hospital because of persistant consciousness disturbance. Laboratory data revealed hyperammonemia, but there was no indication of liver dysfunction. Moreover abdominal computed tomography did not reveal any clear finding of liver disease or portal-systemic shunting, but we noted multiple large bladder diverticula. Antibiotic therapy, tracheal intubation, ventilator management and bladder catheterization were performed. The patient's level of consciousness improved rapidly. Urinary culture revealed Bacteroides ureolyticus (urease-producing bacteria). The patient was diagnosed with hyperammonemia and a urinary tract infection due to urease-producing bacteria. Thus, physicians should be aware that obstructive urinary tract infections due to urease-producing bacteria can also be the cause of hyperammonemia.

[A Case of ACD-Associated RCC with Lymph Node Metastasis and Contralateral Renal Carcinoma after Nephrectomy].

A 59-year-old man who had undergone hemodialysis for 13 years was diagnosed with left renal cell carcinoma (RCC),cT1aN0M0,in 2010. He had a laparoscopic left nephrectomy,and the pathological diagnosis at that time was clear cell carcinoma,pT1a (multifocal). At 1 year after surgery,he was diagnosed with a left renal hilar lymph node metastasis and a new right RCC,cT1aN0M0. Consequently,he underwent a right nephrectomy and retroperitoneal lymph node dissection in 2012. Pathologic diagnosis by the current classification of the right renal tumor was acquired cystic disease-associated renal cell carcinoma (ACD-associated RCC),and that of the left hilar lymph node was metastatic RCC with sarcomatoid change. According to the revised classification the pathological diagnosis of the left renal tumor was ACD-associated RCC. There has been no evidence of recurrence or metastasis for 3 years after the second operation. The specific classification of dialysis-related renal tumors and their characteristics should be standard knowledge for urologists.

[Assessing the effect of subcuticular buried sutures with subcutaneous closed suction drain to prevent surgical site infection in patients undergoing total cystectomy with urinary diversion using intestine].

We assessed the effect of subcuticular buried sutures with subcutaneous closed suction drain to prevent surgical site infection (SSI) in patients undergoing total cystectomy with urinary diversion using the intestine. We reviewed the clinical charts of 43 consecutive patients who underwent total cystectomy with urinary diversion using the intestine from February 2006 to March 2011 at Nishi-Kobe Medical Center. All patients received intravenous prophylactic antibiotics before and throughout surgery as well as for three days after surgery. Skin closure was performed with interrupted vertical mattress sutures with 2-0 nylon on the first 22 patients (mattress group), and with interrupted subcuticular buried sutures with 4-0 absorbable monofilament with subcutaneous closed suction drain on the remaining 21 patients (subcuticular buried suture with subcutaneous drain; SBD group). SSI occurred in 7 (31.8%) patients in the mattress group, but did not affect any patient in the SBD group. We compared risk factors for SSI between the groups, and found that the method of skin closure was significant risk factor for SSI (P = 0.005). We concluded that interrupted subcuticular buried sutures with 4-0 absorbable monofilament with subcutaneous suction drain is effective for prevention of SSI in total cystectomy with urinary diversion using the intestine.

[The safety and efficacy of sunitinib using a modified regimen (2 weeks on/1 week off) for treatment of metastatic renal cell carcinoma].

We prospectively investigated the safety and efficacy of sunitinib using a modified regimen (2 weeks on/1 week off) in 24 patients (22 males, 2 females ; age range 39-86 years, median 64 years) with metastatic renal cell carcinoma (RCC). During the observation period (3-62 weeks, median 21 weeks), thrombocytopenia was seen in 13 (54.2%), leukopenia in 11 (45.8%), hand-foot syndrome in 5 (20.8%), hypertension in 4 (16.7%), and hypothyroidism in 3 (12.5%) patients, while grade 3 or higher adverse events were found in 4 (16.7%), 1 (4.2%), 1 (4.2%), 2 (8.3%), and 0 patients, respectively. Of the 21 patients evaluable for response, 5 (23. 8%) showed partial response, 8 (38.1%) stable disease, and 8 (38.1%) progressive disease. This new modified regimen may lead to a reduction in adverse events for treatment of patients with metastatic RCC as a substitute for the standard dosing regimen of sunitinib.

A case of renal cell carcinoma with antiphospholipid syndrome treated by robot-assisted partial nephrectomy.

Introduction: Antiphospholipid syndrome is an autoimmune disease that presents with thrombus hyperplasia. Although very rare, this disease is reported to become severe after the surgical invasion and other interventions. To our knowledge, there are no reports of partial nephrectomy in patients with antiphospholipid. Case presentation: A 45-year-old man visited our hospital for treatment of left renal cell carcinoma. He had a history of antiphospholipid syndrome and took two antithrombotic agents. We performed a robot-assisted partial nephrectomy. We selectively ligated only the feeding branch during the procedure. Postoperatively, there were no complications, and the patient was discharged on postoperative day 10. One year after surgery, there was no worsening of antiphospholipid syndrome. Conclusion: We reported the first case of robot-assisted partial nephrectomy for an antiphospholipid syndrome patient. Selective ligation of the renal artery might not have contributed to the severe antiphospholipid syndrome.

Antimicrobial prophylaxis to prevent perioperative infection in urological surgery: a multicenter study.

We prospectively investigated the rates of incidence of surgical site infection (SSI), urinary tract infection (UTI), and remote infection (RI) in 4,677 patients who underwent urological surgery from January to December 2010, including 2,507 endourological cases, 1,276 clean cases, 807 clean-contaminated cases, and 87 contaminated cases involving bowel segments. A single dose of antimicrobial prophylaxis (AMP) was administered in the endourological, clean, and clean-contaminated surgery cases, except for patients who underwent transurethral resection of the prostate (TURP) or percutaneous nephrolithotripsy (PNL). AMP was administered within 72 h in TURP and PNL, and AMP was administered within 48 h in contaminated surgery cases. In cases of endourological surgery, UTI was observed in 4% and RI in 0%, and SSI, UTI, and RI were seen in 1%, 1%, and 1%, respectively, of clean surgery cases, in 3%, 3%, and 2%, respectively, of clean-contaminated surgery cases, and in 17%, 30%, and 10%, respectively, of contaminated surgery cases. In multivariate analysis of the risk factors for infection, operative time was a significant risk factor for UTI in endourological surgery, and American Society of Anesthesiologists score and operative time were significant risk factors for RI in clean surgery. No significant risk factor was found in analyses of clean-contaminated and contaminated surgery cases. A single-dose AMP regimen was shown to be effective and feasible for prevention of perioperative infection in urological surgery.

Tolerability and treatment outcome of pembrolizumab in patients with advanced urothelial carcinoma and severe renal dysfunction.

OBJECTIVES: Pembrolizumab, an anti-PD-1 monoclonal antibody, revolutionized the treatment of advanced urothelial carcinoma. However, the tolerability and outcomes of pembrolizumab in patients with severe renal dysfunction [creatinine clearance (CrCl) <30 ml/min] are unclear because no clinical trials included such patients. We analyzed the safety profile and outcomes of these patients in the real world. METHODS: We extracted data for 739 pembrolizumab-treated patients from a Japanese nationwide cohort of platinum-refractory metastatic urothelial carcinoma. Using propensity score matching, the overall survival (OS) and adverse events (AEs) of patients with CrCl <30 and ≥30 were compared. RESULTS: Ninety-two patients (12.4%) had CrCl <30 ml/min. The median number of doses was similar between the CrCl ≥ 30 and CrCl <30 groups (5 and 4, respectively), and there was no difference in the frequency of grade ≥2 treatment-related AEs between the groups (35.5% vs. 35.7%). The overall response rate was similar between the groups (27.2% vs. 29.7%, P = 0.184). Using propensity score matching, the median OS times in the CrCl ≥30 and CrCl <30 groups were 10.3 (95% confidence interval [CI] = CI 7.3-13.0) and 8.1 months (95% CI = 5.4-14.6, P = 0.626), respectively. The 1-year OS rates in these groups were 41.5% and 38.2%, respectively, and the 2-year OS rates were 21.3% and 20.2%, respectively. In multivariate Cox regression analysis, performance status ≥2 (hazard ratio [HR] = 5.56, 95% CI = 2.64-11.71, P < 0.0001) and neutrophil-to-lymphocyte ratio ≥3 (HR = 2.20, 95% CI =1.15-4.19, P = 0.013) were independently associated with patient prognosis in the CrCl <30 group. CONCLUSIONS: This report illustrated that pembrolizumab can be safely administered to patients with severe renal dysfunction, who had similar outcomes as patients without severe renal dysfunction.

Pembrolizumab for treating advanced urothelial carcinoma in patients with impaired performance status: Analysis of a Japanese nationwide cohort.

BACKGROUND: The benefits of pembrolizumab in patients with advanced urothelial carcinoma (UC) and impaired performance status (PS) remain unknown. This study assessed the safety and efficacy of pembrolizumab in patients with platinum-refractory UC and Eastern Cooperative Oncology Group PS ≥2 to identify which subgroups may benefit from this drug. METHODS: This retrospective nationwide cohort study collected clinicopathological information for 755 patients from 59 institutions. The overall response rate (ORR) and overall survival (OS) were compared among the patients with PS 0-1, 2, and 3-4. Multivariate analysis was conducted to identify factors predicting OS in patients with PS ≥2. RESULTS: The numbers of patients with PS 0-1, 2, and 3-4 were 602, 98, and 55, respectively; the ORRs in these groups were 29.5, 15.3, and 9.1%, respectively, and the median OS times were 14.3, 3.1, and 2.4 months, respectively. In multivariate Cox regression analysis, a neutrophil-lymphocyte ratio (NLR) ≥3.5 (hazard ratio [HR] = 1.897) and liver metastasis (HR = 2.072) were associated with OS in the PS ≥2 subgroup. The median OS of patients with PS ≥2 without either risk factor was 6.8 months, compared with 3.1 months for patients with one risk factor and 2.3 months for patients with both risk factors. CONCLUSIONS: PS ≥2 portended worse ORR and OS than PS ≤1 despite a comparable safety profile. Among the patients with impaired PS, patients with NLR <3.5 and no liver metastasis may most greatly benefit from pembrolizumab therapy.

Obstructive azoospermia as an unusual complication associated with herniorrhaphy of an omphalocele: a case report.

INTRODUCTION: Iatrogenic damage to the seminal tract is one of the causes of obstructive azoospermia, which can be an indication for reconstruction surgery. We present a case of obstructive azoospermia as an unusual complication after neonatal herniorrhaphy of an omphalocele. CASE PRESENTATION: A 30-year-old Japanese man was diagnosed with obstructive azoospermia. He had undergone herniorrhaphy of an omphalocele immediately after birth. Reconstruction surgery of both seminal tracts was performed to pursue the possibility of naturally achieved pregnancy. Intra-operative findings demonstrated that both vasa deferentia were interrupted at the internal inguinal rings, although the abdominal end of the right vas leading to the seminal vesicle was found in the abdominal cavity. The discharge from the stump of the testicular end had no sperm, although the right epididymal tubules were dilated with motile sperm. Therefore, we performed right-sided vasovasostomy in the internal inguinal ring and ipsilateral epididymovasostomy simultaneously. CONCLUSION: To the best of our knowledge, this is the first report describing obstructive azoospermia as an unusual complication of herniorrhaphy of an omphalocele. It is important to pay attention to the existence of seminal tracts in such surgery as well as in inguinal herniorrhaphy.