Response to Pembrolizumab After Dose-Reduced Cisplatin Plus Gemcitabine Chemotherapy Is Inferior to That After Carboplatin Plus Gemcitabine Chemotherapy in Cisplatin-Unfit Patients With Advanced Urothelial Carcinoma.

INTRODUCTION: Response to pembrolizumab after first-line chemotherapy is vital to prolonged survival in advanced, unresectable, and/or metastatic urothelial carcinoma (aUC). However, there are sparse clinical data on host-tumor immune modification by first-line platinum-based chemotherapy. This study investigated the association between response to first-line gemcitabine plus cisplatin (GC) or carboplatin (GCarbo) chemotherapy and response to subsequent pembrolizumab treatment. PATIENTS AND METHODS: A multicenter-derived database registered 454 patients diagnosed with aUC between 2008 and 2020. Of these, 108 patients who received first-line GC or GCarbo followed by second-line or later pembrolizumab were eligible for investigation and were classified into 3 groups: 48 receiving full-dose GC, 21 receiving dose-reduced GC, and 39 receiving GCarbo. Overall survival (OS) was calculated using the Kaplan-Meier method and compared using the log-rank test. Possible factors associated with the response to pembrolizumab were evaluated using binary logistic regression methods. RESULTS: The rate of patients undergoing surgical removal of the primary organ was higher and creatinine clearance was lower in the dose-reduced GC and GCarbo groups than in the full-dose GC groups. Pembrolizumab responders had significantly better survival benefits than nonresponders. The rate of pembrolizumab responders was much higher in first-line chemotherapy responders than in first-line chemotherapy nonresponders. In contrast to the full-dose GC and GCarbo groups, the pembrolizumab responder rate was lower, and no association was observed between response to first-line chemotherapy and response to pembrolizumab in the dose-reduced GC group. CONCLUSION: Cisplatin and carboplatin may play an important role in the antitumor immune response, which could impact the outcome of subsequent pembrolizumab treatment. Given that the rate of response to pembrolizumab after dose-reduced GC chemotherapy was relatively low, this regimen is not recommended for cis-unfit patients with aUC. Further studies are required to understand the mechanisms responsible for the cross-reactivity of platinum and immune checkpoint inhibitors.

[A Case of Nephrocutaneous and Enterorenal Fistula Associated with Pyonephrosis].

A 57-year-old woman was referred to our hospital with a palpable mass in the left lumbar area. Computerized tomography revealed a diffusely enlarged destructed left kidney with impacted ureteropelvic junction stones and intense inflammatory stranding of the perirenal fat. This infiltration extended into the subcutaneous tissue. Since she refused to undergo nephrectomy, we performed transurethral ureterolithotripsy (TUL) two times. Retrograde ureterography before the third TUL showed communication between the renal pelvis and the jejunum. We performed a left-sided nephrectomy with a wedge resection of the jejunum. This is a rare case of nephrocutaneous and enterorenal fistula caused by pyonephrosis.

[Clinical Significance of Stone Cultures for Patients Undergoing Transurethral Lithotripsy].

This study aimed to evaluate the concordance of the microbiologic findings of preoperative urine cultures and intraoperative stone cultures in patients undergoing transurethral lithotripsy (TUL). A total of 164 patients treated with TUL for whom preoperative urine cultures and intraoperative stone cultures were performed were included in this study. The preoperative urine cultures were positive in 57 patients (34.8%) and the stone cultures were positive in 58 patients (35.4%). Enterococcus faecalis was the most common organism detected in the intraoperative stone cultures (22. 9%). The concordance rate between the preoperative urine cultures and intraoperative stone cultures was 45.6%. Eleven patients (6.7%) developed a fever of >38.5°C postoperatively. Among the 11 patients, 9 patients showed positive preoperative urine cultures and 10 patients showed positive stone cultures. The results of the urine culture performed when the patient had a fever of 38.5°C or higher showed 54.5% consistency with the results of the preoperative urine culture or stone culture. Although the results of the preoperative urine cultures and intraoperative stone cultures may not be highly consistent, these cultures should be actively performed because they provide useful information regarding postoperative infections.

[Spontaneous Tumor Lysis Syndrome in a Patient with Testicular Malignant Lymphoma : A Case Report].

A 75-year-old man, highly suspected as having malignant lymphoma originating from his left testis, underwent exploratory orchiectomy for a definitive diagnosis. Laboratory examinations before the surgery showed high lactate dehydrogenase (652 IU/l), elevated serum creatinine level (1.85 mg/dl) and sIL-2R level (8,930 U/ml). As the postoperative course passed uneventfully, the patient was discharged from the hospital on the eighth day after the surgery. Ten days after the surgery the patient was transferred to the emergency room of the hospital complaining of severe abdominal pain and malaise. Laboratory examinations revealed highly elevated lactate dehydrogenase (2,807 IL/l), uric acid (24.9 mg/dl) and serum creatinine (5.31 mg/dl). Computed tomography demonstrated rapid growth of the retroperitoneal mass and occurrence of bilateral hydronephroses. Under the diagnosis of spontaneous tumor lysis syndrome, the patient was urgently treated with hemodialysis, steroidal pulse and rituximab following percutaneous nephrostomy for the right kidney. After improvement of the laboratory data, the patient was transferred to another hospital for the treatment of malignant lymphoma.

[Predictive Factors of Biochemical Recurrence in Positive Surgical Margin Patients by Radical Prostatectomy].

The predictive factors for biochemical recurrence (BCR) were investigated in patients with positive surgical margin of the extirpated prostate by radical retropubic prostatectomy (RRP). The records of 365 patients who underwent RRP in our hospital between January 2002 and December 2014 were retrospectively analyzed. Patients who had received additional therapy before or after RRP, who had not been followed up for more than a year after surgery, and who had pN1 lesions were excluded from the study. Positive surgical margin was observed in 112 cases. Prostate specific antigen (PSA) before surgery ≥20 ng/ml, biopsy positive core ratio ≥40%, Gleason score of the surgical specimen ≥8, and postoperative PSA nadir ≥0.01 ng/ml were identified as significant predictors of BCR.

[Predictive Factors of Positive Surgical Margin in Radical Prostatectomy].

To identify the predictive factors for positive surgical margin after radical prostatectomy, we retrospectively analyzed the records of 381 patients who underwent radical prostatectomy in our hospital between January 2002 and December 2014. Patients who had received hormonal therapy before surgery were excluded from the study. Positive surgical marginwas observed in121 cases (31.8%), and prostate specific antigen (PSA) before surgery ≧10 ng/ml (HR1.89 : 95%CI 1.17-3. 07) and BMI≧25 kg/m2 (HR2.73 : 95%CI 1.60-4. 68) were identified as significant predictors of positive surgical margin. The existence of PSM significantly correlated to the operation time of 240 minutes or longer (HR2.27 : 95%CI 1. 35-3.79), pT2c or higher local stage (HR2.08 : 95%CI 1.17-3.72) and 7 or higher Gleason score of the resected specimen(HR1.63 : 95%CI 1.03-2.59).

[Causative Bacterial Strains and Sensitivityto Antimicrobial Agents in Female Acute Uncomplicated Cystitis].

Recently, wide spreading of fluoloquinolone resistant Escherichia coli is a serious problem inthe treatment of urinary tract infection. To investigate the causative bacterial strains of female acute uncomplicated cystitis (AUC) in the community and their sensitivity to antimicrobial agents, we retrospectively reviewed the medical records of 215 female AUC patients treated at our clinics from April 2014 to June 2015. Two hundred and nineteen strains were isolated as the causative bacteria from the patients'urine samples, including E. coli of 179 strains (82%) followed by Klebsiella pneumoniae (5.5%). One hundred and forty five strains (81%) of the isolated E. coli were sensitive to levofloxacin, whereas 32 strains (17.9%) were levofloxacin-resistant. To fosfomycin, the isolated E. coli showed the highest sensitivity (93.9%) among all antimicrobial agents tested. In univariate analysis, factors associated with levofloxacinresistant E. coli included two or more episodes of cystitis within the past year and levofloxacin use at the latest episode of cystitis. Inmultivariate analysis, two or more episodes of cystitis withinthe past year were found to be associated with levofloxacinresistan ce (p＝0.004). To prevent the increasing prevalence of infections caused by antibiotic-resistant bacteria, it is important to confirm the sensitivity of the causative agents for optimal antimicrobial therapy. The community-based surveillance data should be collected and considered when selecting empirical antimicrobial agents.

[Bladder Metastasis of Renal Cell Carcinoma 7 Years after Ex Vivo Partial Nephrectomy and Auto-Transplantation : A Case Report].

Metastasis of renal cell carcinoma (RCC) to urinary bladder is extremely rare. We report a case of metastasis arising from RCC to the urinary bladder 7 years after treatment of bilateral RCC. A 74-year-old man was diagnosed with bilateral multiple renal tumors (T1aN0M1, PUL, OSS) with two lesions in the right kidney and a solitary lesion of the left kidney in 2008. He underwent laparoscopic radical nephrectomy for the right side in September 2008. The next month, ex vivo partial nephrectomy and auto-transplantation was performed for the left kidney because the tumor was located very close to the collecting system. Metastatectomies for the lung and bone followed and the histopathological findings of all lesions were clear cell carcinoma. The following years went well without any recurrence. Seven years after the surgery, the patient complained of asymptomatic gross hematuria and cystoscopy revealed a solitary non-papillary tumor of the bladder. Transurethral resection of the tumor was performed in June 2015 and the histopathological diagnosis of the resected specimens was clear cell carcinoma. Because the additional immunohistochemical examinations were positive for CD10 and negative for CK7, we diagnosed the bladder tumor as metastasis arising from RCC. Direct dissemination of the tumor cells into the urinary tract during partial nephrectomy followed by implantation to the bladder mucosa is a probable mechanism of metastasis in this case.

[Multiple Recurrences in Perirenal Fatty Tissue 10 Years after Enucleation for Treatment of T1a Renal Cell Carcinoma : A Case Report].

A 71-year-old man underwent simple enucleation for T1a renal cell carcinoma of the left kidney 10 years ago, and, the capsule of the tumor was injured during that surgery. The histopathological diagnosis of the tumor was papillary renal cell carcinoma type1 pT1a, G2 and the surgical margin was negative. Eight years after the surgery, computed tomography (CT) scan imaging showed a mass 13 mm in diameter which was adjacent to the left kidney. In the following year, the mass had grown to 22 mm in diameter. Thus it was suspected as local recurrence of renal cell carcinoma. Magnetic resonance imaging revealed multiple tumors in the left perirenal fatty space and positron emission tomography CT showed abnormal uptake in the same lesions with a maximal standardized uptake value of 3.2. We diagnosed multiple local recurrences of renal cell carcinoma and planned open radical nephrectomy and extirpation of perirenal fat including tumors entirely. The histopathological diagnosis of the tumor was papillary renal cell carcinomas type 1, Fuhrman grade 2＞3. The patient had no recurrence or metastases 10 months after the surgery. It is possible that the tumor cells were disseminated during the first surgery due to an injury to the capsule of the tumor and resulted in multiple local recurrences.