Predictors of Response Following Neoadjuvant Cisplatin-Based Chemotherapy for Muscle Invasive Urothelial Bladder Cancer Using Molecular Profile: A Prospective Clinical Study.

OBJECTIVES: To predict response of patients with muscle invasive bladder cancer (MIBC) to neoadjuvant chemotherapy (NAC) through analysis of molecular profile assessed clinically (radiologically and by pathological examination of transurethral resection biopsy [TURBT] specimens) and definitively with histopathological examination after radical cystectomy (RC). METHODS: In a prospective study, tumor biopsies were obtained from patients with urothelial MIBC (T2-4a N0-2 M0) during TURBT. Patients were eligible for RC received 4 cycles of cisplatin-based NAC. DNA repair genes (BRACA1, ERCC1) & CTR gene m-RNA expression levels were assessed in resected tissue. The response to chemotherapy was assessed clinically (radiologically & TURBT) following NAC. Response was re-assessed for 64 patients who underwent RC and predictors of cancer-free survival (CFS) were calculated. Receiver operating characteristic (ROC) curve was used to delineate cutoff value copes with the best sensitivity and specificity for prediction of response to NAC. RESULTS: The study included 104 patients, 42 (40.4%) responded well to NAC clinically. Out of 64 patients who underwent RC, 26 (40.6%) showed good response to NAC. CFS at 18 months for patients who underwent RC was 60%. Statistical analysis showed that molecular profile was an independent predictor of good response to NAC both clinically and pathologically and also predicted better CFS. CONCLUSION: Molecular profile could play a decisive role in early detection of patients with MIBC who will get benefit from preoperative NAC.

The efficacy of the new Bosniak classification v.2019 in benign lesions prediction within the higher Bosniak cysts classes.

INTRODUCTION: Identification of benign lesions among higher classes of renal Bosniak cysts who are vulnerable to active surveillance instead of surgical approach is still questionable. We aimed in this study to delineate the efficacy of the new Bosniak v2019 classification in benign lesions identification among those cases with higher Bosniak classes in comparison with the final histopathology. MATERIALS: In a retrospective review between 2010 and 2021 for patients diagnosed as higher classes Bosniak renal masses was done. Patients' demographics and radiological data i.e.,: age, gender, and final Bosniak v2019 categorization for class III: (1) Enhancing thick wall/septa >4 mm (III-WS) and (2) Enhancing irregular wall/septa or convex protrusion with obtuse margins <3 mm (III-OP) and for class IV as: (1) Enhancing nodule or convex protrusion with obtuse margins >4 mm (IV-OP) and (2) Enhancing nodule or convex protrusion with acute margins of any size (IV-AP). RESULTS: A total of 137 patients were included. Bosniak III was identified in 56 patients. Malignancy was detected in 74.5% of resected masses. Among resected Bosniak III cyst, 46.4% were benign histopathologically. Male gender and Bosniak III-OP were independent risks for malignancy among the resected Bosniak III cysts. Conversely, in resected Bosniak IV renal cysts, only 9 of resected masses were benign. In univariate analysis, male gender, absence of multilocular cyst and endophytic masses were predictors for malignancy in resected Bosniak IV cyst. None of the previous predictors was significant in multivariate analysis. CONCLUSION: The Bosniak subclassification v.2019 can define benign lesions. Bosniak III-OP was an independent risk for malignancy detection among the resected Bosniak III cysts.

Bladder perforation as a complication of transurethral resection of bladder tumors: the predictors, management, and its impact in a series of 1570 at a tertiary urology institute.

OBJECTIVES: To report the incidence, predictors, the impact of bladder perforation (BP), and our protocol of management in patients who underwent trans-urethral resection of bladder tumor (TURBT). METHODS: This is a retrospective study, between 2006 and 2020, on patients who underwent TURBT for non-muscle-invasive bladder cancer (NMIBC). Bladder perforation was defined as any full thickness resection of the bladder wall. Bladder perforations were managed based on their severity and type. Small BP with no or mild symptoms were managed with prolongation of urethral catheters. Those with significant extraperitoneal extravasations were managed by insertion of a tube drain (TD). Abdominal exploration was done for extensive BP and all intraperitoneal extravasations. RESULTS: Our study included 1,570 patients, the mean age was 58 ± 11 years and 86% were males. Bladder perforation was recorded in 10% (n = 158) of the patients. The perforation was extraperitoneal in 95%, and in 86%, the perforation was associated with no symptoms, mild symptoms, or mild fluid extravasation that required only prolongation of the urethral catheter. On the other hand, active intervention was required for the 21 remaining patients (14%) with TD being the most frequent management. History of previous TURBT (p = 0.001) and obturator jerk (p = 0.0001) were the only predictors for BP. CONCLUSIONS: The overall incidence of bladder perforation is 10%; however, 86% required only prolongation of urethral catheter. Bladder perforation did not affect the probability for tumor recurrence, tumor progression nor radical cystectomy.

Could the bulbar urethral end location on the cystourethrogram predict the outcome after posterior urethroplasty for pelvic fracture urethral injury?

Objectives: To identify cystourethrogram (CUG) findings that independently predict the outcome of posterior urethroplasty (PU) following pelvic fracture urethral injury (PFUI). Methods: Findings of CUG included the location of the proximal end of the bulbar urethra in zones A (superficial) or B (deep) according to its relationship with the pubic arch. Others included the presence of pelvic arch fracture, bladder neck, and posterior urethral appearance. The primary outcome was the need for reintervention either endoscopically or by redo urethroplasty. Independent predictors were modeled using a logistic regression model and a nomogram was constructed and internally validated using 100-bootstrap resampling. Time-to-event analysis was performed to validate the results. Results: A total of 196 procedures in 158 patients were analyzed. The success rate was 83.7% with 32 (16.3%) procedures requiring direct vision internal urethrotomy, urethroplasty, or both in 13 (6.6%), 12 (6.1%), and 7 (3.6%) patients, respectively. On multivariate analysis, bulbar urethral end located at zone B (odds ratio [OR]: 3.1; 95% confidence interval [CI]: 1.1-8.5; p = 0.02), pubic arch fracture (OR: 3.9; 95%CI: 1.5-9.7; p = 0.003), and previous urethroplasty (OR: 4.2; 95% CI: 1.8-10.1; p = 0.001) were independent predictors. The same predictors were significant in the time-to-event analysis. The nomogram discrimination was 77.3% and 75% in the current data and after validation. Conclusions: The location of the proximal end of the bulbar urethra and redo urethroplasty could predict the need for reintervention after PU for PFUI. The nomogram could be used preoperatively for patient counseling and procedure planning.

Prediction of Wilms' Tumor Susceptibility to Preoperative Chemotherapy Using a Novel Computer-Aided Prediction System.

Wilms' tumor, the most prevalent renal tumor in children, is known for its aggressive prognosis and recurrence. Treatment of Wilms' tumor is multimodal, including surgery, chemotherapy, and occasionally, radiation therapy. Preoperative chemotherapy is used routinely in European studies and in select indications in North American trials. The objective of this study was to build a novel computer-aided prediction system for preoperative chemotherapy response in Wilms' tumors. A total of 63 patients (age range: 6 months-14 years) were included in this study, after receiving their guardians' informed consent. We incorporated contrast-enhanced computed tomography imaging to extract the texture, shape, and functionality-based features from Wilms' tumors before chemotherapy. The proposed system consists of six steps: (i) delineate the tumors' images across the three contrast phases; (ii) characterize the texture of the tumors using first- and second-order textural features; (iii) extract the shape features by applying a parametric spherical harmonics model, sphericity, and elongation; (iv) capture the intensity changes across the contrast phases to describe the tumors' functionality; (v) apply features fusion based on the extracted features; and (vi) determine the final prediction as responsive or non-responsive via a tuned support vector machine classifier. The system achieved an overall accuracy of 95.24%, with 95.65% sensitivity and 94.12% specificity. Using the support vector machine along with the integrated features led to superior results compared with other classification models. This study integrates novel imaging markers with a machine learning classification model to make early predictions about how a Wilms' tumor will respond to preoperative chemotherapy. This can lead to personalized management plans for Wilms' tumors.

A prospective trial investigating the role of Serum 25-Hydroxyvitamin D in diagnosis and prognosis of bladder cancer.

PURPOSE: Higher levels of serum 25-hydroxyvitamin D 25(OHD) are associated with better prognosis in breast and colorectal cancer. However, the evidence is still inconclusive for bladder cancer (BC). Herein, we investigated the diagnosis and prognosis roles of serum levels of 25(OHD) in suspected BC patients presented by hematuria. METHODS: This prospective cohort study involved suspected patients of BC presented with hematuria. Patients were evaluated by CT urogram, office cystoscopy and urine cytology with subsequent inpatient biopsy for positive findings. Baseline blood samples were collected for measurement of 25(OHD) by electrochemiluminescence binding assay at the time of diagnosis. Patients with non-muscle-invasive BC (NMIBC) underwent transurethral resection of bladder tumor (TURBT) and adjuvant intravesical chemotherapy or BCG instillation. Patients were followed up for their recurrence status during 10 to 24 months. Recurrence was defined as the first time of NMIBC pathological relapse during the follow up period. RESULTS: A total of 115 patients were included in the final analysis. Patients had proven pathological BC (64 with NMIBC, and 20 with muscle invasive) and 31 patients were considered as control group. Controls were those patients with BC-free workup (including cytology, cystoscopy, and upper tract imaging). BC group showed a lower level of 25(OHD) than control group 16.47±5.88 versus 28.99±3.19 ng/mL (p<0.001). In addition, muscle invasive group also showed a lower level than NMIBC group 13.17±4.5 versus 17.49±5.04 ng/mL (P = 0.003). During the follow-up period of, tumor recurrence occurred in 16 (25%) of NMIBC patients. The baseline 25(OHD) were decreased in patients who experienced early recurrence; without being statistically significant (15.99 ± 5.17 vs. 18.38 ± 5.14 ng/mL; p = 0.08). 25(OHD) deficiency/insufficiency occurred in 5 (16.1%) and 64 (76.2%) in control and BC patients, respectively, (odds-ratios (OR): 2.13; 95% confidence intervals (CI), 1.52-2.99; P < 0.0001). CONCLUSION: Serum 25(OHD) is significantly decreased in BC patients especially those with tumor muscle invasive group. However, the baseline serum 25(OHD) does not predict the recurrence in the NMIBC patients.

Oncologic Outcomes of Squamous Cell Carcinoma Versus Urothelial Carcinoma With Squamous Differentiation After Radical Cystectomy for Bladder Carcinoma.

INTRODUCTION: In this study we aim to compare clinicopathological characteristics and cancer specific survival between patients treated with radical cystectomy for pure squamous cell carcinoma (SCC) and urothelial carcinoma with squamous differentiation (SqD). PATIENTS AND METHODS: We reviewed data of 1737 consecutive patients treated with radical cystectomy and urinary diversion between January 2004 and February 2014. Only patients with pure SCC or SqD were included in the analysis. Squamous differentiation was defined as intercellular bridges or keratinization in the tumor. Clinicopathological data and recurrence free survival (RFS) were compared between patients diagnosed with SCC and SqD. RESULTS: SCC and SqD were found in 318 and 223 patients, respectively. Mean age was 57 ± 8.3 years in SCC and 58.8 ± 7.8 in SqD (P = .008). A higher proportion of female patients was observed in SCC group compared to SqD (31.8% vs. 22% P < .0001). Patients with SqD were more likely to have extravesical (58.3% vs. 46.2%: P = .006) and nodal positive disease (34.5% vs. 14.5%: P < .0001) than pure SCC patients. Bilharzial eggs were found in 61% of SCC vs. 46% of SqD (P = .001).; The median (IQR) follow up period for SCC and SqD was 63 (12-112) months and 23 months (9-74.7), respectively. The 5-year RFS for SCC and SqD were 77% and 59.8 %, respectively (P < .0001).; Multivariate cox regression analysis identified advanced pT stage (OR: 1.9, 95% CI: 1.3-2.86, P = .0001), nodal positive disease (OR: 1.6, 95% CI: 1.1-2.48, P = .01) and SqD histology (OR: 1.6, 95% CI: 1.14-2.31, P = .007 as independent predictors of 5-year RFS. CONCLUSION: Patient with SCC had significantly higher 5-year RFS in comparison to SqD. The higher rate of extravesical disease and lymph node metastasis in SqD patients is indicative of aggressive behavior of this histologic type.

Predictors and survival benefit of achieving pentafecta in a contemporary series of open radical cystectomy.

BACKGROUND: Pentafecta provides a comprehensive approach for standardized reporting of surgical and oncologic outcomes after radical cystectomy and urinary diversion. We aimed to report the rate, predictors of achieving pentafecta and its impact on long-term survival in a contemporary series of open radical cystectomy (ORC). METHODS: A retrospective analysis of a computerized database of patients treated with ORC between 2004 till 2014 was performed. Pentafecta criteria included negative soft tissue surgical margin (STSM), retrieval of ≥16 lymph nodes, absence of clinical recurrence within 12 months after surgery, absence of high-grade complication (GIII-V) within 90 days after surgery, and absence of urinary diversion related complications at 12 months follow-up. Multivariate analysis was used to identify predictors of achieving pentafecta. RESULTS: Pentafecta was achieved in 545 (33.6%) patients out of 1624 included in the study. Absence of ≥16 LN yield was the first cause of missing pentafecta (49.5%). Multivariate analysis identified: ASA Score grades ≥III (OR=0.7, 95%CI 0.6-0.9, P=0.04), BMI≥35 (OR=0.5, 95%CI 0.3-0.8, P=0.007), perioperative blood transfusion (≥4 units) (OR=0.5, 95%CI 0.3-0.7, P=0.001), and ileal conduit (OR=0.7, 95%CI 0.5-0.9, P= 0.01) as independent predictors of missing pentafecta. Patients who achieved pentafecta had higher estimated 5-year RFS than their counterparts (81.7% vs. 62.5%; P<0.0001). CONCLUSIONS: Pentafecta was achieved in nearly one third of patients after ORC. Achievement of pentafecta was associated with better long-term recurrence-free survival. Obesity (class II, III), perioperative blood transfusion (>4 units), associated comorbidities, and ileal conduit were independent predictors of missing pentafecta.

Clinical efficacy of mebeverine for persistent nocturnal enuresis after orthotopic W-neobladder.

OBJECTIVES: To investigate the efficacy of mebeverine for nocturnal incontinence in male patients with an ileal orthotopic bladder substitute (OBS). PATIENTS AND METHODS: A randomised controlled trial was carried out for adult male patients who were nocturnal incontinent. Patients were allocated to receive mebeverine 200 mg or placebo once a day in the evening for 3 months. The primary outcome was to compare the continence status between groups, assessed by the urinary domain of the Bladder Cancer Index (BCI) and pad usage. The secondary outcomes were to assess the safety of mebeverine. RESULTS: There were 55 patients in the placebo group and 58 in mebeverine group who completed the follow-up. The median (interquartile range) interval between OBS surgery and starting treatment was 9 (4-13) years in the placebo group and 9 (6-13) years in the mebeverine group. The mean (SD) 3-month urinary domain score of the BCI was 70.8 (5.6) and 86.4 (14.2) in the placebo and mebeverine groups, respectively (P < 0.001). At 3 months, 54 (98.2%) and 26 (44.8%) patients required the use of a night-time pad in the placebo and mebeverine groups, respectively. Mebeverine reduced the risk of pad use by 53.4% (95% confidence interval 40.1-66.6; P < 0.001). Constipation occurred in one (2.1%) and three (5.8%) patients in the placebo and mebeverine groups, respectively; abdominal distention occurred in two (3.8%) of the patients in the mebeverine group (P = 0.25). CONCLUSION: Mebeverine decreases night-time pad use and improves the quality of life in male patients with an ileal OBS and is associated with minimal adverse events.

Holmium Laser En-bloc Resection Versus Conventional Transurethral Resection of Bladder Tumors for Treatment of Non-muscle-invasive Bladder Cancer: A Randomized Clinical Trial.

BACKGROUND: En-bloc resection of bladder tumors achieves complete tumor removal, improves the quality of resection, decreases perioperative complication, and potentially improves recurrence rates. OBJECTIVE: To assess the efficacy and safety of holmium laser en-bloc resection (HolERBT) versus conventional transurethral resection of bladder tumor (cTURBT). DESIGN, SETTING, AND PARTICIPANTS: Between September 2015 and September 2018, 100 patients with non-muscle-invasive bladder cancer were randomly allocated to cTURBT or HolERBT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was detection of residual tumor in reTURBT specimens at 4 wk after the primary resection. Operative parameters, specimen quality, perioperative complications, and recurrence-free survival (RFS) were compared. Independent sample t tests, χ2 tests, and Kaplan-Meier curves were used, as appropriate. RESULTS AND LIMITATIONS: The patient and tumor baseline characteristics were comparable between the groups. Residual tumors were detected in 7% and 27.7% of cases after HolERBT and cTURBT, respectively (p=0.01). Detrusor muscle was sampled in 98% of HolERBT and 62% of cTURBT cases (p<0.001). Lamina propria invasion substaging was feasible in only 68.2% of HolERBT and 18.4% of cTURBT cases (p<0.001). Following HolERBT, catheterization time (p<0.001) and hospital stay (p=0.001) were shorter when compared to cTURBT. Immediate postoperative instillation of chemotherapy in indicated cases was feasible for 100% of the HolERBT group and 91.5% of the cTURBT group (p=0.04). After follow-up of 20 ± 9.9 mo (13-36), RFS was 31.76 mo (95% confidence interval [CI] 28.67-34.86) in the HolERBT group and 28.25 mo (95% CI 24.87-31.64) in the cTURBT group (hazard ratio 0.43, 95% CI 0.17-1.1; p=0.07). However, this study was not powered to detect a difference in RFS. CONCLUSIONS: Compared to cTURBT, HolERBT is a safer procedure for bladder tumor resection. It fulfills the oncological criteria of optimized resection with less residual tumor and better specimen quality. PATIENT SUMMARY: En-bloc resection of bladder cancer tumors using a holmium laser is safer than the conventional technique. It has the advantages of less residual tumor and better specimen quality, with a similar tumor recurrence rate. This study is registered at ClinicalTrials.gov as NCT02555163.

A Randomized Trial to Examine the Utility of Mebeverine on the Early Return of Continence Following Orthotopic Bladder Substitution.

PURPOSE: We assessed the effect of mebeverine in the enhancement of the orthotopic bladder substitute continence. MATERIALS AND METHODS: A randomized trial was carried out for incontinent adult male patients during the first year post-orthotopic bladder substitute surgery. Patients were allocated to receive mebeverine 135 mg or placebo 3 times a day for only 3 months. The primary outcome was to compare the continence improvement between groups, assessed by the urinary domain of the Bladder Cancer Index and sanitary pad use. The secondary outcomes were to assess the safety of the drugs used. RESULTS: In placebo group 47 and in mebeverine group 52 patients completed followup. The median (range) interval time between orthotopic bladder substitute surgery and starting treatment was 7 (3-10) months and 6.5 (3-10) months in the placebo and mebeverine group, respectively (p=0.3). Compared to the baseline evaluation, the 3-month urinary domain of Bladder Cancer Index scores improved in both groups with significant improvement in the mebeverine group. The mean±SD 3-month urinary domain of Bladder Cancer Index was 67.79±13.05 and 83.27±12.21 in the placebo and mebeverine group, respectively (p <0.001). Also, the 3-month patient pad use decreased to 30 (63.8%) and 19 (36.5%) patients in the placebo and mebeverine group, respectively (p=0.007). Constipation occurred in 1 (2.1%) and 3 (5.8%) patients in the placebo and mebeverine group, respectively; abdominal distention occurred in 2 (3.8%) in the mebeverine group (p=0.25). CONCLUSIONS: Mebeverine accelerated continence development in male patients with ileal orthotopic bladder substitute during the first year post-orthotopic bladder substitute construction.

Parastomal hernia after ileal conduit urinary diversion: re-visiting the predictors radiologically and according to patient-reported outcome measures.

PURPOSE: To evaluate the predictors of post-ileal conduit (IC) parastomal hernia (PSH) based on a standard grading methodology and according to the patients reported outcome measures (PROM). METHODS: A prospective evaluation for patients with IC attending their scheduled follow-up was conducted between December 2013 and October 2015. The hernia stage was determined according to the European Hernia Society (EHS) classification as types I and II included defect size < 5 cm without and with a concomitant incisional hernia, respectively. Types III and IV included defect size > 5 cm without and with a concomitant incisional hernia (high-grade hernia). The evaluation was performed by a non-contrast CT scan. PROM were defined as symptomatic if there were hernia-related abdominal discomfort, appliance problems, and/or bowel complications. Perioperative parameters were modeled for prediction of high-grade and PROM outcomes. RESULTS: PSH was diagnosed in 138 (39.9%) patients, symptomatic in 119 (34.4%) and high-grade in 59 (17%). Independent predictors of radiologically diagnosed PSH were hypoalbuminemia (odds ratio [OR]: 1.7; 95% Confidence interval [CI]: 1.1-2.7; p = 0.02), localised disease (OR: 0.6; 95% CI: 0.3-0.9; p = 0.04) and negative lymphadenopathy (OR: 0.4; 95%CI: 0.2-0.8; p = 0.004). Predictors of symptomatic PSH were hypoalbuminemia (OR: 2; 95%CI: 1.2-2.3: p = 0.003) and previous hernia surgery (OR: 2.1; 95%CI: 1.1-4.2; p = 0.024). CONCLUSIONS: Only a small proportion of patients with PSH were asymptomatic. Preoperative hypoalbuminemia was the most significant factor contributing to the development and symptomatizing of PSH. Previous hernia surgery further contributed to the patient complaint.

Prophylaxis against renal ischemia-reperfusion injury in canine model: Stem cell approach.

INTRODUCTION: Stem cell therapy at the time of ischemia/reperfusion (I/R) injury has been hypothesized to attenuate the severity of acute kidney injury and to accelerate the regeneration process in lower animal models. Data in higher animal models is limited and discordant. We aimed to explore the reno-protective effects of stem cells on I/R related renal injury in a canine model. MATERIALS AND METHODS: Twenty-seven dogs that were treated with bone marrow-derived mesenchymal stem cells (BM-MSCs) were compared with another 27 dogs treated with adipose tissue-derived MSCs (AT-MSCs) following 90 min of warm ischemia to assess IR injury. Each group was divided into three subgroups (nine dogs each), according to the stem cell dose (5, 10, 15 × 106 in 500 µl volume) injected directly into the renal cortex after reperfusion. All dogs were re-evaluated by renogram, histopathology, and pro-inflammatory markers at 2 weeks, 2, and 3 months. RESULTS: In Group I, there was a mean reduction of creatinine clearance by 78%, 64%, and 74% at the three used doses, respectively, at 2 weeks. At 3 months, these kidneys regained a mean of 84%, 92%, and 72%, respectively, of its basal function. In Group II, the reduction of clearance was much more modest with mean of 14%, 6%, and 24% respectively at 2 weeks with more intense recovery of renal function by mean of 90%, 100%, and 76%, respectively, at 3 months. Group I had significantly more tubular necrosis and delayed regeneration compared with the Group II. Expressions of pro-inflammatory markers were upregulated in both the groups with a higher and more sustained expression in Group I. CONCLUSION: Stem cells protected against ischemic reperfusion injury in a canine model. AT-MSCs provided better protection than BM-MSCs.

Venous thromboembolism after radical cystectomy and urinary diversion: a single-center experience with 1737 consecutive patients.

Background: To investigate the incidence, timing, and risk factors of venous thromboembolic events (VTE) following radical cystectomy and urinary diversion in a large cohort of patients.Patients and Methods: The electronic data base of patients underwent radical cystectomy and urinary diversion in a tertiary referral center between January 2004 and February 2014 was retrospectively reviewed. Patients developed VTE namely deep vein thrombosis (DVT) and pulmonary embolism (PE) within 90 days after surgery were identified and compared to those without VTE. Univariate and multivariate analyses were used to evaluate the predictors of the VTE.Results: Out of 1737 patients, 77 VTE have occurred in 70 (4%) patients. DVT and PE occurred in 34 (2%) and 43 (2.5%) patients, respectively. PE was the leading cause of mortality in 17 patients. The median (range) time for VTE was 11 days (1-92) with 39 (50.6%) events developed after the stoppage of thrombo-prophylaxis. On multivariate analysis, older age ≥60 years (OR = 1.9; p = 0.009), female gender (OR = 1.9; p = 0.02), morbid obesity (BMI ≥35 kg/m2) (OR = 2.4; p = 0.008) and preoperative platelet count (≥300.000/cc) (OR = 1.6; p = 0.045) were significant predictors for developing VTE.Conclusion: The overall incidence of VTE is 4% with more than half of events occurred after the stoppage of thromboprophylaxis highlighting the necessity of adopting an extended protocol. Independent predictors included older age, female gender, morbid obesity and preoperative thrombocytosis. These group of patients require particular attention for the prevention of this complication.

Renoprotective effect of local sildenafil administration in renal ischaemia-reperfusion injury: A randomised controlled canine study.

Objectives: To design a new canine model to assess the renoprotective effect of local sildenafil administration, as the renoprotective effect of systemic sildenafil administration in renal ischaemia-reperfusion (IR) injury in animal models has been shown but its local effects have not been established to date. Materials and methods: In all, 120 dogs were assigned to five groups: sham, oral control (OC) group (right nephrectomy + left renal ischaemia for 60 min), oral sildenafil (OS) group (oral sildenafil 1 mg/kg, 60 min before ischaemia), local control (LC) group (local renal perfusion with saline and heparin for 5 min) and local sildenafil (LS) group (perfusion with sildenafil 0.5 mg/kg). Renal functions, histopathological changes, expression of caspase-3, nuclear factor erythroid 2-related factor 2 (Nrf2), inflammatory cytokines (intracellular adhesion molecule 1, tumour necrosis factor α and interleukin 1ß) and endothelial nitric oxide synthase (eNOS) in renal tissues were assessed in all groups at 1, 3, 7 and 14 days. Results: There were significant improvements in renal functions and cortical and medullary damage scores in the sildenafil-treated groups compared to their control groups (P < 0.05). Also, the LS group showed significantly better improvement of renal functions and cortical and medullary damage scores than the OS group (P < 0.05). Moreover, sildenafil significantly decreased the expression of caspase-3 and inflammatory cytokines and increased the expression of Nrf2 and eNOS in renal tissue, which were statistically significant in the LS group. Conclusion: LS has a greater renoprotective effect against renal IR injury than systemic administration via anti-inflammatory, antioxidant and anti-apoptotic pathways. Abbreviations: BUN: blood urea nitrogen; Ct: cycle threshold; eNOS: endothelial nitric oxide synthase; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; H&E: haematoxylin and eosin; IL-1ß: interleukin 1ß; NO: nitric oxide; Nrf2: nuclear factor erythroid 2-related factor 2; OC: oral control; OS: oral sildenafil; LC: local control; LS: local sildenafil.

Expression and prognostic utility of PD-L1 in patients with squamous cell carcinoma of the bladder.

OBJECTIVES: Checkpoint inhibitors are approved for the treatment of urothelial bladder cancer. However, there have been no reports on the prognostic value of programmed-death receptor ligand 1 (PD-L1) expression in squamous cell carcinoma (SCC) of the bladder. We assessed the relationship between PD-L1 expression, clinicopathological features, and oncologic outcomes in bladder SCC. METHODS AND MATERIALS: Immunohistochemistry of PD-L1 was performed on 151 radical cystectomy specimens with pure SCC treated in Mansoura, Egypt from 1997 to 2004. RESULTS: Median patient age was 52 years (range: 36-74 years) and median length of follow up was 63 months (range: 1-100 months). Schistosomiasis was present in 81% of the specimens and 93% had muscle-invasive disease on pathologic staging. PD-L1 expression was negative in 50 (33%) of the specimens. Negative PD-L1 expression was associated with higher pathologic tumor stage (P = 0.04), higher grade lesions (P = 0.01), and the presence of lymphovascular invasion (P < 0.01). Kaplan-Meier analyses showed that negative PD-L1 expression is associated with worse recurrence-free (P = 0.01) and worse cancer-specific survival (P = 0.01). Multivariable Cox regression analyses showed negative PD-L1 expression was an independent predictor of disease recurrence (hazards ratio 2.05, 95% confidence interval 1.06-3.96, P = 0.03) and cancer-specific mortality (hazards ratio 2.89, 95% confidence interval 1.22-6.82, P = 0.02). CONCLUSIONS: Negative PD-L1 expression is associated with higher pathologic tumor stage, higher grade lesions, presence of lymphovascular invasion, and worse oncologic outcomes after radical cystectomy for SCC. These findings support the need for the inclusion of patients with bladder SCC into immunotherapy clinical trials.

Epidermal growth factor expression as a predictor of chemotherapeutic resistance in muscle-invasive bladder cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) overexpression is believed to be associated with bladder cancer (BC) progression and poor clinical outcomes. In vivo studies have linked EGFR subcellular trafficking and chemo-resistance to cisplatin-based chemotherapies. This has not been studied in the clinical adjuvant setting. We aimed to investigate the prognostic significance of EGFR expression in patients receiving cisplatin-based adjuvant chemotherapy following radical cystectomy for advanced BC. METHODS: The database from the Urology and Nephrology Center at Mansoura University was reviewed. BC patients who were treated with radical cystectomy and adjuvant chemotherapy for adverse pathological features or node positive disease were identified. Patients who underwent palliative cystectomy, had histological diagnoses other than pure urothelial carcinoma, or received adjuvant radiotherapy were excluded from the study. Immunohistochemical staining for EGFR expression was performed on archived bladder specimens. The following in vitro functional analyses were performed to study the relationship of EGFR expression and chemoresponse. RESULTS: The study included 58 patients, among which the mean age was 57 years old. Majority of patients had node positive disease (n = 53, 91%). Mean follow up was 26.61 months. EGFR was overexpressed in 25 cystectomy specimens (43%). Kaplan-Meier analysis revealed that EGFR over-expression significantly correlated with disease recurrence (p = 0.021). Cox proportional hazard modeling identified EGFR overexpression as an independent predictor for disease recurrence (p = 0.04). Furthermore, in vitro experiments demonstrated that inhibition of EGFR may sensitize cellular responses to cisplatin. CONCLUSIONS: Our findings suggest that EGFR overexpression is associated with disease recurrence following adjuvant chemotherapy for advanced BC. This may aid in patient prognostication and selection prior to chemotherapeutic treatment for BC.

Efficacy and safety of low-intensity shock wave therapy in penile rehabilitation post nerve-sparing radical cystoprostatectomy: a randomized controlled trial.

AIM: To evaluate the role of low-intensity extra corporeal shock wave therapy (LI-ESWT) in penile rehabilitation (PR) post nerve-sparing radical cystoprostatectomy (NS-RCP). MATERIALS AND METHODS: This study included 152 sexually active men with muscle invasive bladder cancer. After bilateral NS-RCP with orthotopic diversion by a single expert surgeon between June 2014 and July 2016, 128 patients were available categorized into three groups: LI-ESWT group (42 patients), phosphodiesterase type-5 inhibitors (PDE5i) group (43 patients), and control group (43 patients). RESULTS: Mean age was 53.2 ± 6.5 years. Mean ± SD follow-up period was 21 ± 8 months. During first follow-up FU1, all patients of the three groups had insufficient erection for vaginal penetration; with decrease of preoperative IIEF-EF mean score from 27.9 to 6.9. Potency recovery rates at 9 months were 76.2%, 79.1%, and 60.5% in LI-ESWT, PDE5i, and control groups, respectively. There was statistically significant increase in IIEF-EF and EHS scores during all follow-up periods in all the study groups (p < 0.001). However, there was no significant difference between the three groups during all follow-up periods. Statistical evaluation showed no significant difference in continence and oncological outcomes during all follow-up points among the three groups (p = 0.55 and 0.07, respectively). CONCLUSIONS: During last follow-up, 16% more patients in LI-ESWT group had recovery of potency as compared to the control group. Although the difference is not statistically significant, but of clinical importance. LI-ESWT is safe as oral PDE5i in penile rehabilitation post nerve-sparing radical cystoprostatectomy.

Acute kidney injury following radical cystectomy and urinary diversion: predictors and associated morbidity

ABSTRACT Introduction: Acute kidney injury (AKI) after major surgeries is associated with significant morbidity and mortality. We aim to report incidence, predictors and associated comorbidities of AKI after radical cystectomy in a large cohort of patients. Materials and Methods: We conducted a retrospective analysis of 1000 patients who underwent open radical cystectomy in a tertiary referral center. Perioperative serum creatinine measurements were used to define AKI according to the RIFLE criteria (as Risk, Injury and Failure). The predictors of AKI after surgery were determined using univariate and multivariate analyses. Results: Out of 988 evaluable patients, AKI developed in 46 (4.7%). According to RIFLE criteria; AKI-Risk, AKI-Injury and AKI-Failure occurred in 26 (2.6%), 9 (0.9%) and 11 (1.1%) patients, respectively. Multivariate analysis showed that performing nephroureterectomy with cystectomy (Odds ratio [OR]: 4.3; 95% Confidence interval [CI]: 1.3-13.6; p=0.01) and the development of high grade complications (OR: 3.8; 95% CI 1.9-7.2; p<0.0001) were independently associated with AKI. Conclusions: AKI is a significant morbidity after radical cystectomy and the term should be included during routine cystectomy morbidity assessment.