Are there differences in the characteristics of patients who respond to gemcitabine plus cisplatin chemotherapy and those who respond to pembrolizumab therapy for metastatic urothelial carcinoma? Multicenter retrospective study.

OBJECTIVES: To evaluate factors to predict overall survival of metastatic urothelial carcinoma patients treated with gemcitabine plus cisplatin chemotherapy or pembrolizumab therapy. METHODS: We retrospectively evaluated two metastatic urothelial carcinoma cohorts treated with (i) gemcitabine plus cisplatin or (ii) pembrolizumab. The gemcitabine plus cisplatin cohort was treated from December 2005 through December 2014 while the pembrolizumab cohort was treated from January 2018 through December 2020. Using multivariate analyses, we evaluated the risk factors for overall survival in each cohort and compared them. None of the gemcitabine plus cisplatin cohort patients were treated with pembrolizumab. All patients in the pembrolizumab cohort were treated with prior platinum-based chemotherapy. RESULTS: There were 184 patients in the gemcitabine plus cisplatin cohort and 91 in the pembrolizumab cohort. The mean follow-up periods were 714 and 284 days, respectively. In multivariate analysis, the risk factors for overall survival in the gemcitabine plus cisplatin cohort were liver metastasis, worse Eastern Cooperative Oncology Group performance status (1 or more), no primary site resection, and a high prognostic index (1 or more). In the pembrolizumab cohort, liver metastasis, bone metastasis, and worse Eastern Cooperative Oncology Group-performance status (1 or more), and high prognostic index (1 or more) were the risk factors for overall survival. In the pembrolizumab cohort, patients with a complete response or partial response during prior platinum-based chemotherapy had better overall survival with the following pembrolizumab treatment than those with stable or progressive disease (P = 0.004). CONCLUSIONS: Considering the similarity of these risk factors in two sequential treatments, it may be possible to predict the response to pembrolizumab according to the response to prior chemotherapy.

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) in urological malignancies: a multi-center retrospective study.

INTRODUCTION: We evaluated the incidence and risk factors for antiresorptive agent-related osteonecrosis of the jaw (ARONJ) in prostate and kidney cancer patients. MATERIALS AND METHODS: We retrospectively reviewed the clinical data of 547 patients from 13 hospitals. Prostate and kidney cancer patients with bone metastases who were treated with a bone-modifying agent (BMA) between January 2012 and February 2019 were enrolled. Exclusion criteria were BMA use for hypercalcemia, a lack of clinical data, a follow-up period of less than 28 days and a lack of evaluation by dentists before BMA administration. The diagnosis and staging of ARONJ were done by dentists. RESULTS: Two-hundred eighteen patients were finally enrolled in the study, including 168 prostate cancer patients and 50 kidney cancer patients. Of them, 49 (29%) prostate cancer patients and 18 (36%) kidney cancer patients needed tooth extraction prior to BMA initiation. The mean follow-up period after BMA initiation was 552.9 ± 424.7 days (mean ± SD). In the cohort, 23% of the patients were diagnosed with ARONJ in the follow-up period. The 1-year cumulative incidences of ARONJ were 9.4% and 15.4% in prostate and kidney cancer patients, respectively. Multivariate analysis indicated that kidney cancer, tooth extraction before BMA and a body mass index (BMI) ≥ 25 kg/m2 were significant predictors for ARONJ. CONCLUSION: ARONJ is not a rare adverse event in urological malignancies. Especially, kidney cancer, high BMI patients and who needed tooth extraction before BMA were high risk for developing ARONJ.

Does cognitive behavioral therapy using a self-check sheet improve night-time frequency in patients with nocturia? Results of a multicenter randomized controlled trial.

OBJECTIVE: To determine whether cognitive behavioral therapy using a self-check sheet is effective in improving night-time frequency of patients with nocturia. METHODS: We carried out a multicenter, open-labeled, randomized controlled trial in eight institutions. Patients having two or more episodes of nocturia were randomly assigned to either cognitive behavioral therapy with completion of frequency volume charts regularly (cognitive behavioral therapy group) or frequency volume charts regularly alone (frequency volume charts group). The cognitive behavioral therapy checklist was composed of eight items: wake up time/bedtime, mealtime, napping, alcohol/caffeine intake, water intake, salt intake, exercise and taking a bath. A physician explained cognitive behavioral therapy within 5 min using a brief manual. The patients in the cognitive behavioral therapy group filled out the self-check sheet every day. The primary end-point was the difference in night-time frequency based on the International Prostate Symptom Score Q7 at 4 weeks. RESULTS: Of the 100 first-visit patients randomly allocated, 37 in the cognitive behavioral therapy group and 41 in the frequency volume charts group completed the protocol. No difference was observed in the mean ± standard deviation of night-time frequency at 4 weeks between the cognitive behavioral therapy group (2.6 ± 1.0) and the frequency volume charts group (3.1 ± 1.2; P = 0.056). However, when six patients with achievement of cognitive behavioral therapy of <50% were excluded from the analysis, night-time frequency at 4 weeks was significantly lower in the cognitive behavioral therapy group (2.5 ± 1.0) than in the frequency volume charts group (3.1 ± 1.2; P = 0.027). CONCLUSIONS: The efficacy of cognitive behavioral therapy using a self-check sheet for nocturia remains to be shown. However, strictly practicing cognitive behavioral therapy might be beneficial to these patients.

Therapeutic options to reduce intravesical recurrence in newly diagnosed Ta high-grade bladder cancer according to risk stratification: A multicenter retrospective study.

OBJECTIVES: To evaluate the risk factors for intravesical recurrence in patients with newly diagnosed Ta high-grade non-muscle-invasive bladder cancer and the optimal management to reduce the risk of recurrence. METHODS: We retrospectively evaluated Ta high-grade bladder cancer in patients who were newly diagnosed by transurethral resection from January 2007 through October 2018. Using multivariate analyses, we evaluated the risk factors and therapeutic options affecting intravesical recurrence and stratified the patients according to the risk numbers. RESULTS: We included 390 patients and the median follow-up period was 31 months after the initial transurethral resection. According to multivariate analysis, having a previous history of upper urinary tract carcinoma, and multiple and sessile tumors were risk factors for intravesical recurrence (P = 0.001, P = 0.02 and P = 0.01, respectively). Risk groups were stratified according to these risk factors into favorable, intermediate and poor. In the entire cohort, induction and immediate intravesical instillation therapy were treatment options to reduce intravesical recurrence (P < 0.01 and P = 0.02, respectively). Analyses in each risk group showed that a second transurethral resection was the only therapeutic option to reduce intravesical recurrence in the favorable group (P = 0.048), whereas induction intravesical instillation therapy was effective in the intermediate and poor risk groups (P = 0.01 and P < 0.01, respectively), as was immediate intravesical instillation for the poor risk group (P < 0.001). CONCLUSIONS: Sessile, multiple tumors and a history of upper urinary tract carcinoma are risk factors for intravesical recurrence in Ta high-grade bladder cancer patients.

[Fever after Gemcitabine Administration is a Poor Prognostic Factor in Patients with Metastatic Urothelial Carcinoma : Multicenter Retrospective Study].

Gemcitabine (GEM) is currently a standard chemotherapeutic agent for metastatic urothelial carcinoma (mUC). Fever isknown to be an adverse effect of GEM ; however, itsincidence, etiology and clinical significance have not been evaluated. The objective of this study was to elucidate the characteristics and clinical significance of fever associated with GEM in patients with mUC receiving GEM plus cisplatin (GC) chemotherapy. Between 2005 and 2014, 184 patientswith mUC who received first-line GC therapy at 10 institutions were enrolled. GEM-associated fever (GEMAF) was defined as a body temperature ≥37.5ºC within 96 hours after administration of GEM with no evidence of specific conditions causing fever including infection. Clinical parametersbefore GC therapy were evaluated to determine predictorsof GEMAF. Furthermore, the impact of GEMAF on clinical outcomeswasals o evaluated. The median age was70 years and median follow-up was14.2 months. GEMAF wasobs erved in 44 patients (23.9%). In multivariate analysis, elevated C-reactive protein (CRP) before chemotherapy was an independent predictive factor for GEMAF (oddsratio 2.450, p＝0.041). There was a significant difference in progression-free survival (median 6.7 vs 8.0 months, p＝0.031) and cancer-specific survival (median 12.0 vs 15.8 months, p＝0.045) between patients with and without GEMAF. Results of this study suggest that GEMAF is a common adverse event of GC therapy for mUC and can be a poor prognostic factor. GEMAF may be associated with systemic inflammatory response induced by the tumor in patients with mUC.

Selective culture of Escherichia coli to prevent infective complications of transrectal ultrasound-guided prostate biopsy: Clinical efficacy and analysis of characteristics of quinolone-resistant Escherichia coli.

OBJECTIVES: To evaluate a regimen of targeted prophylaxis using rectal swab culture in patients undergoing transrectal ultrasound-guided prostate biopsy, and to investigate the characteristics of isolated fluoroquinolone-resistant Escherichia coli. METHODS: A prospective study was carried out from June 2013 through December 2014. Rectal swabs were cultured on agar plates containing either 2 µg/mL levofloxacin or 1 µg/mL sitafloxacin before transrectal ultrasound-guided prostate biopsy. Patients with susceptible organisms received levofloxacin or sitafloxacin, whereas those with resistant organisms received directed antimicrobial prophylaxis according to the results of the antimicrobial susceptibility test. Patients with infectious complications after prostate biopsy were identified, and characteristics of patients carrying fluoroquinolone-resistant Escherichia coli were analyzed. RESULTS: A total of 397 men underwent transrectal ultrasound-guided prostate biopsy. Of these patients, 74 (18.6%) had fluoroquinolone-resistant Escherichia coli. All fluoroquinolone-resistant Escherichia coli were susceptible to amikacin and meropenem. The risk factor for possible fluoroquinolone-resistant Escherichia coli was age of ≥73 years. Three (0.7%) patients who received appropriate antimicrobial prophylaxis had high-grade fever after the prostate biopsy. However, the pathogens were not fluoroquinolone-resistant Escherichia coli. CONCLUSIONS: Targeted antimicrobial prophylaxis in patients undergoing transrectal ultrasound-guided prostate biopsy can be associated with reducing severe infectious complications caused by fluoroquinolone-resistant Escherichia coli.

Neoadjuvant chemotherapy with gemcitabine and cisplatin for muscle-invasive bladder cancer: multicenter retrospective study.

OBJECTIVES: The aim of this study was to evaluate the efficacy of neoadjuvant gemcitabine and cisplatin (GC) therapy for muscle-invasive bladder cancer (MIBC). METHODS: We retrospectively evaluated patients who underwent neoadjuvant GC therapy followed by radical cystectomy from April 2009 through December 2015 in the Sapporo Medical University Urologic Consortium. The efficacy of neoadjuvant chemotherapy (NAC) was assessed based on the pathological T0 (pT0) rate in radical cystectomy specimens, and the recurrence-free survival, cause-specific survival and overall survival (OS) rates. To compare the oncological benefit of NC with GC to that of the methotrexate, vinblastine, adriamycin and cisplatin (MVAC) regimen, we also utilized historical clinical data of patients who were treated with MVAC as NAC followed by radical cystectomy in our institute from 1986 through 2010. RESULTS: Fifty-eight patients receiving neoadjuvant GC therapy and 74 receiving neoadjuvant MVAC were included. The pT0 achieving rates were comparable between the two groups (20.7% vs. 18.9%, P = 0.83). Neoadjuvant GC was associated with a better 2-year OS rate than neoadjuvant MVAC for clinical T2 disease (95.2% vs. 70.8%, P = 0.036). In contrast, in patients with clinical T3 or more advanced disease, neoadjuvant MVAC provided more pT0 (20.0% vs. 5.6%, P = 0.07) and better 2-year OS than neoadjuvant GC (71.1% vs. 55.0%, P = 0.142), although the difference did not reach statistical significance. CONCLUSIONS: Neoadjuvant GC had no inferiority in oncological outcomes to MVAC for MIBC.

Clinical significance of definite muscle layer in TUR specimen for evaluating progression rate in T1G3 bladder cancer: multicenter retrospective study by the Sapporo Medical University Urologic Oncology Consortium (SUOC).

PURPOSE: To evaluate the clinical impact on progression and recurrence according to presence and absence of a muscle layer, we conducted a retrospective, multicenter study. METHODS: We retrospectively reviewed 247 patients who received transurethral resection (TUR) of bladder tumors and were pathologically diagnosed as having T1G3 bladder cancer from 1990 to 2009. We ruled out 8 patients who received immediate cystectomy and analyzed the remaining 239 T1G3 patients. Patients who had invasion to the prostatic urethra and patients who underwent a second TUR were not included. RESULTS: TUR specimens from 194 patients were confirmed to have a definite muscle layer and those from 45 did not. The median follow-up period was 53 months, ranging from 3 to 181 months. The progression-free survival rates at 5 years after TUR were 91.1 % for patients who had a muscle layer in their specimen and 77.3 % for those who did not (p = 0.005, log-rank test). Multivariate analysis indicated that the absence of a muscle layer was a risk factor for progression (p = 0.006, Cox proportional hazards analysis). CONCLUSIONS: Patients without a muscle layer in the specimen had high risk for progression. The initial TUR must have a muscle layer in the specimen. Variations of progression rates in previous studies might be due to different proportions of patients who had a muscle layer in TUR specimens.

Construction of predictive models for cancer-specific survival of patients with non-muscle-invasive bladder cancer treated with bacillus Calmette-Guérin: results from a multicenter retrospective study.

OBJECTIVE: The aims of this study were to clarify the prognostic factors and to validate the bacillus Calmette-Guérin failure classification advocated by Nieder et al. in patients with non-muscle-invasive bladder cancer who had intravesical recurrence after bacillus Calmette-Guérin therapy. METHODS: Data from 402 patients who received intravesical bacillus Calmette-Guérin therapy between January 1990 and November 2011 were collected from 10 institutes. Among these patients, 187 with bacillus Calmette-Guérin failure were analyzed for this study. RESULTS: Twenty-nine patients (15.5%) were diagnosed with progression at the first recurrence after bacillus Calmette-Guérin therapy. Eighteen (62.1%) of them died of bladder cancer. A total of 158 patients were diagnosed with non-muscle-invasive bladder cancer at the first recurrence after bacillus Calmette-Guérin therapy. Of them, 23 (14.6%) underwent radical cystectomy. No patients who underwent radical cystectomy died of bladder cancer during the follow-up. On multivariate analysis of the 135 patients with bladder preservation, the independent prognostic factors for cancer-specific survival were age (≥70 [P = 0.002]), tumor size (≥3 cm [P = 0.015]) and the Nieder classification (bacillus Calmette-Guérin refractory [P < 0.001]). In a subgroup analysis, the estimated 5-year cancer-specific survival rates in the groups with no positive, one positive and two to three positive factors were 100, 93.4 and 56.8%, respectively (P < 0.001). CONCLUSIONS: Patients with stage progression at the first recurrence after bacillus Calmette-Guérin therapy had poor prognoses. Three prognostic factors for predicting survival were identified and used to categorize patients with non-muscle-invasive bladder cancer treated with bacillus Calmette-Guérin into three risk groups based on the number of prognostic factors in each one.

A rare case of pyoderma gangrenosum occurring at the site of laparoscopic port following laparoscopic radical nephrectomy.

Introduction: Pyoderma gangrenosum is a rare dermatological disease associated with underlying inflammatory conditions. Case presentation: A 59-year-old man was diagnosed with right renal cancer cT1aN0M0 and laparoscopic right radical nephrectomy was performed. Five days after surgery, he had a high-grade fever, surgical site flare, and severe pain. At first, we diagnosed surgical site infection and wound dehiscence. Despite treatment for infection, his general condition and dermatological symptoms did not improve. Thereafter, a dermatologist advised us to perform a skin biopsy and blood culture examinations. Finally, the man was diagnosed with pyoderma gangrenosum according to the pathology of the skin biopsy and negative blood culture. After both intravenous administration of predonisolone and a topical corticosteroid, the high-grade fever and dermatological symptoms improved greatly. Conclusion: Although pyoderma gangrenosum is a rare disease, we should bear in mind the disease since the treatment strategy is completely different from that for surgical site infection.

Efficacy of treatment with carbapenems and third-generation cephalosporins for patients with febrile complicated pyelonephritis.

The purpose of this study was to clarify the clinical relevance of carbapenem and third-generation cephalosporin treatment for febrile complicated pyelonephritis, which often leads to urosepsis. Parenteral antimicrobial treatment with a carbapenem or third-generation cephalosporin was administered to febrile patients and the treatment was switched to oral antimicrobial agents after they became afebrile. In principle, the duration of the course of antimicrobial chemotherapy was limited to a total of 14 days. Clinically, the success rates were 97.3% in the carbapenem group and 96.0% in the third-generation cephalosporin group. For microbiological efficacy, the success rates were 89.2% in the carbapenem group and 92.0% in the third-generation cephalosporin group. There were no serious adverse events in the course of the study. The treatment regimen with a carbapenem or a third-generation cephalosporin was highly effective for patients with febrile complicated pyelonephritis and was well tolerated. Either of these regimens could become one of the standard treatments for patients with febrile complicated pyelonephritis.

Upper tract urothelial carcinoma following intravesical bacillus Calmette-Guérin therapy for nonmuscle-invasive bladder cancer: Results from a multi-institutional retrospective study.

OBJECTIVES: The aim of this study was to clarify the prognostic indicators for upper tract urothelial carcinoma (UTUC) following intravesical bacillus Calmette-Guérin (BCG) therapy for nonmuscle-invasive bladder cancer (NMIBC). METHODS: Data from 402 patients who received intravesical BCG therapy between January 1990 and November 2011 were collected from 10 institutes. The median follow-up interval from transurethral resection of the bladder tumor (TURBT) followed by BCG treatment was 50.0 months (IQR: 31.8-77.0). Of these patients, 186 (46.3%) had intravesical recurrence during the follow-up period after BCG therapy. RESULTS: Thirty patients (7.5%) were diagnosed with UTUC after BCG therapy. The 10-year recurrence-free survival rates for UTUC (RFS-UTUC) was 87.5%. In univariate and multivariate analyses, the independent predicting factors for UTUC were intravesical recurrence (P = 0.016) and tumor morphology at TURBT before BCG (P = 0.045). The 10-year RFS-UTUC of patients with intravesical recurrence and others, were 80.6% and 95.0%, respectively. The 10-year RFS-UTUC of patients with papillary pedunculated tumors and nonpapillary or nonpedunculated were 96.1% and 84.6%, respectively. CONCLUSIONS: The frequency of UTUC in patients with NMIBC after BCG therapy is not negligible. Two independent predicting factors (intravesical recurrence and nonpapillary nonpedunculated at TURBT before BCG) were identified for UTUC. These results might be useful to predict UTUC after BCG therapy for NMIBC.

Molecular-targeted Therapy and Surgery May Prolong Survival of Renal Cell Carcinoma Patients with Bone Metastasis: A Multi-institutional Retrospective Study in Japan.

AIM: To determine prognostic factors for overall survival (OS) in renal cell carcinoma (RCC) patients with bone metastasis in the targeted-therapy era. PATIENTS AND METHODS: We conducted a retrospective multi-institutional review of the medical records of 149 RCC patients with bone metastasis. Survival was estimated using the Kaplan-Meier method and compared with the log-rank test. Univariate and multivariate Cox proportional hazard regression analyses were performed to identify independent factors associated with OS. RESULTS: The median OS was 13.4 months. In multivariate analysis, molecular-targeted therapy, nephrectomy and surgery for bone metastasis were independent prognostic factors. Bone-modifying agents (BMAs) were not associated with OS. The median OS of patients receiving molecular-targeted therapy after diagnosis of bone metastasis was significantly better than that of those who did not receive targeted therapy. CONCLUSION: Molecular-targeted therapy, nephrectomy and surgery for bone metastasis should be considered for RCC patients with metastasis in the bones.

[Acute normovolemic hemodilution in urologic surgery].

PURPOSE: We report the clinical results and efficacy of acute normovolemic hemodilution (ANH) in urologic surgery. PATIENTS AND METHODS: Between October 1996 and February 2001 we performed ANH on 47 patients who were expected to have moderate blood loss during surgical procedures in our hospital. We then evaluated the postoperative hematological features and avoidance of homologous transfusion. RESULTS: Estimated median surgical blood loss was 400 ml (range 10-2,340 ml), and the median amount of whole blood collection was 800 ml (300-1,023 ml). In 14 patients whose blood loss was more than 1,000 ml, the hematocrit (Hct) level in the day after surgery was significantly higher than the Hct level calculated by blood loss. Ninety-eight percent of the series (46/47 cases) and ninety-four percent of patients (15/16 cases) who were underwent radical cystectomy and radical prostatectomy could avoid homologous transfusion. CONCLUSIONS: Our results indicate that ANH is useful during urological surgery, especially in patients with a blood loss of more than 1,000 ml during surgery. ANH is an efficient method for autologous transfusion by means of not only avoidance of homologous transfusion but also by saving red blood cells during surgeries.

[Laparoscopic pelvic lymph node dissection for staging procedure in patients with T1-T3 prostate cancer].

PURPOSE: We evaluated the usefulness and morbidity of laparoscopic pelvic lymph node dissection (LPLND) as a staging procedure for prostate cancer. MATERIALS AND METHODS: Twenty-seven patients with T1-T3 prostate cancer scheduled for conformal radiation therapy underwent LPLND. RESULTS: The median operation time was 103 minutes (range; 58-137 minutes), and the median intraoperative estimated blood loss was 5 ml. (range; very little-273 ml.). This procedure covered obturator nodes and the median number of dissected lymph nodes was 8.0. Median days to oral intake and return to normal activity were 1.0 days and 1.0 days, respectively. CONCLUSIONS: LPLND appears to be a safe, minimally invasive and useful procedure as a means of accurate staging for patients with prostate cancer undergoing radiation therapy.

Prediction of muscle invasion of bladder cancer by cystoscopy.

OBJECTIVES: Urologists make a decision on whether to indicate staging procedures for primary lesions of bladder cancer by findings of cystoscopy. However, cystoscopic findings for prediction of muscle-invasive bladder cancer have not been fully evaluated. METHODS: Two hundred seventy consecutive events of 165 patients with bladder cancer were included in this study. Multivariate analysis by a logistic regression model was applied to analyze cystoscopic findings for prediction of muscle invasion of bladder cancer. RESULTS: Logistic regression analysis revealed that the size, stalk and configuration of the cancer were independent and significant factors that predict muscle invasion of bladder cancer. CONCLUSIONS: Cystoscopic findings of bladder cancer may predict muscle invasion. When invasion is suggested by cystoscopy, imaging studies may be necessary before TUR of the cancer as well as deep resection of it.