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.

[Needle Lost during Robot-Assisted Laparoscopic Radical Prostatectomy : A Case Report].

A 66-year-old man, who presented with prostate cancer, underwent robot-assisted laparoscopic radical prostatectomy. During surgery, a suture needle was lost after an assistant surgeon removed it from the AirSeal® access port. We were not able to find the needle using a portable radiograph with no contrast optimization. After disassembling the device, the needle was found in the groove of the port top. It should be acknowledged that the needle can become stuck in the AirSeal® port, even though it does not have a valve structure. An X-ray radiograph, with an appropriate gradation setting could be useful to retrieve suture needles.

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.

[Spontaneous Resolution of Renal Artery Pseudoaneurysm after Robotic-Assisted Partial Nephrectomy].

Partial nephrectomy (PN) for small renal tumors has become increasingly common. Complications of PN include renal artery pseudoaneurysm (PA), a potentially life-threatening condition. However, the true incidence and natural history of PA after PN remain unclear. Therefore, we conducted a retrospective study of the radiographic characteristics of robotic-assisted partial nephrectomy (RAPN) observed during the postoperative period. We selected 36 consecutive patients with renal carcinoma who underwent RAPN at our institution between December 2016 and May 2019. Patients with contraindications for the use of contrast medium were excluded. A total of 31 eligible patients underwent computed tomography angiography (CTA) during the early postoperative period after RAPN and the incidence of PA was evaluated. Among the patients with PASs, asymptomatic PAs were followed without intervention and their clinical course was assessed using CTA at 1 to 3 months postoperatively. PA was identified in 5 out of 31 (16.1%) patients after RAPN. Median duration between PN and the first CTA was 6 days (range, 1-8). Median PA size was 13 mm (range, 8-17). All (100%) PAs were asymptomatic and resolved spontaneously, as verified by CTA during the late postoperative period. Median duration between identification of PA on early postoperative CTA and subsequent resolution was 92 days (range, 35-106). Our findings indicated that asymptomatic PA after PN can be followed without intervention.

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.

[A Consideration for the Surgical Approach in Laparoscopic Total Pelvic Exenteration after Radiotherapy : A Case Report].

A 66-year-old woman underwent concurrent chemoradiotherapy (CCRT) for stage IIA cervical cancer. However, two recurrent masses were detected at the vaginal stump 6 years after CCRT, and we performed laparoscopic total pelvic exenteration to obtain a complete cure. Because the terminal ileum appeared white secondary to the effects of radiotherapy, we constructed an ileal conduit using the ileum, approximately 40 cm toward the mouth from the ileocecum. We performed transperineal resection of the vagina and urethra and intersphincteric resection as anal-preservation surgery along with transverse colostomy. We used a right short gracilis myocutaneous flap to reconstruct the pelvic floor and perineum. The operation time was 816 min, and the estimated blood loss was 1,168 ml. On histopathological examination of the resected specimen, the parauterine tissue showed a positive surgical margin. Patients with recurrent cervical cancer after CCRT show poor prognosis. Complete resection with a negative margin is associated with more favorable prognosis in patients with recurrent pelvic masses. Compared with an open procedure, laparoscopic pelvic exenteration is safe and feasible in these patients. Selection of an optimal surgical approach, urinary diversion, and pelvic floor reconstruction is important for complete resection and prevention of perioperative complications.

Complete atrioventricular dissociation and sinus arrest after pheochromocytoma resection.

INTRODUCTION: Although preoperative bradycardia has been reported in several pheochromocytoma cases, postoperative bradycardia has not. This is the first case report of complete atrioventricular dissociation and sinus arrest occurring after pheochromocytoma resection. CASE PRESENTATION: A 38-year-old woman was referred for a left adrenal incidentaloma. Twenty-four hour urinary collection showed elevated noradrenaline. Iodine-123-meta-iodobenzylguanidine scintigraphy showed high tracer uptake in the left adrenal region. Open left adrenalectomy was performed, and histopathological examination confirmed the diagnosis of pheochromocytoma. Thirty minutes following surgery, complete atrioventricular dissociation and sinus arrest developed. Vagal reflex attenuation due to decreased noradrenaline after tumor removal and perioperative pain and fear were believed to be the causes. A temporary pacemaker was implanted to prevent sudden death due to vagal overstimulation. CONCLUSION: Vagal reflex attenuation after pheochromocytoma resection can result in complete atrioventricular dissociation and sinus arrest. Adequate preoperative preparation and close monitoring during and after surgery are imperative.

[Use of Vacuum-Assisted Closure Therapy in the Treatment of Postoperative Inguinal Lymphocele after Lymphadenectomy for a Vulvar Apocrine Adenocarcinoma : A Case Report].

A 79-year-old man with vulvar apocrine adenocarcinoma and right inguinal lymph node metastasis underwent wide excision and free skin graft reconstruction of the primary lesion and right inguinal lymphadenectomy. However, left inguinal lymph node metastasis was noted after 11 months, and left inguinal lymphadenectomy was performed. Twelve days postoperatively, the patient developed left inguinal lymphocele. The lymphocele was drained percutaneously and compressed, but lymph secretion persisted and lymphocele skin necrosis was observed. Therefore, debridement and vacuum-assisted closure (VAC) therapy were performed in cooperation with the department of plastic surgery. Subsequently, lymph secretion declined and eventually stopped. The lymphocele scar was reconstructed with a free skin graft, and after further observation for 8 months, right lymph node swelling was noted. Nevertheless, on the left inguinal site, neither lymphocele recurrence nor inguinal lymph node metastasis was observed. In conclusion, VAC therapy might be beneficial in the treatment of postoperative inguinal lymphocele after lymphadenectomy.

[A Case of Renal Cell Carcinoma withIpsilateral Renal Pelvic Metastasis Mimicking Double Cancer].

A 71-year-old man with left flank pain was referred to our hospital. Computed tomography (CT) revealed a left renal tumor, left renal pelvic wall thickening, bilateral adrenal gland swelling, multiple pulmonary nodules, and a bone metastatic tumor. Further, positron emission tomography/CT revealed increased 18F fluorodeoxyglucose uptake in the left renal tumor, multiple pulmonary nodules, and bone metastatic tumor. Accordingly, we performed biopsies of the thickening of the left renal pelvic wall and bone metastatic tumor, and histological examinations revealed an unknown type carcinoma and bone metastasis from clear cell carcinoma. Without a precise preoperative diagnosis of the thickening of the left renal pelvic wall, laparoscopic left nephrectomy was performed, and the renal and renal pelvic wall tumors were diagnosed as clear cell carcinoma on pathological examination. Therefore, we made a final diagnosis of renal cell carcinoma with lung, bone, and renal pelvic metastases. Although axitinib was administered, cervical spine metastasis developed. Unfortunately, the patient died from disease progression five months following the surgery.

[Advanced Adenocarcinoma of the Bladder after Augmentation Gastrocystoplasty].

A 29-year-old woman had undergone gastrocystoplasty with Mitrofanoff appendicovesicostomy for urethral trauma at 9 years of age. Since then, she was being followed up for performing clean intermittent self-catheterization at regular intervals. Twenty years after the surgery, she presented with gross hematuria. Ultrasonographic findings revealed bilateral hydronephrosis. Cystoscopy and computed tomography (CT) revealed invasive bladder cancer with pelvic lymph node metastases. A biopsy confirmed the diagnosis of adenocarcinoma with signet ring cell carcinoma. Subsequently, neo-adjuvant combination chemotherapy with TS-1 and cisplatin (CDDP) was initiated, which was followed by open radical cystectomy with extended pelvic lymphadenectomy. The tumor was found to infiltrate from the anastomotic site into the entire native bladder and histopathological diagnosis was muscle invasive adenocarcinoma with neuroendocrine differentiation and lymph node metastasis (ypT3bN2). TS-1 was continued as adjuvant chemotherapy and the patient did not have any evidence of recurrence for 12 months postoperatively.