Soroush T. Bazargani

Efficacy and Safety of Blue Light Flexible Cystoscopy with Hexaminolevulinate in the Surveillance of Bladder Cancer: A Phase III, Comparative, Multicenter Study

Purpose: We compared blue light flexible cystoscopy with white light flexible cystoscopy for the detection of bladder cancer during surveillance. Materials and Methods: Patients at high risk for recurrence received hexaminolevulinate intravesically before white light flexible cystoscopy and randomization to blue light flexible cystoscopy. All suspicious lesions were documented. Patients with suspicious lesions were referred to the operating room for repeat white and blue light cystoscopy. All suspected lesions were biopsied or resected and specimens were examined by an independent pathology consensus panel. The primary study end point was the proportion of patients with histologically confirmed malignancy detected only with blue light flexible cystoscopy. Additional end points were the false‐positive rate, carcinoma in situ detection and additional tumors detected only with blue light cystoscopy. Results: Following surveillance 103 of the 304 patients were referred, including 63 with confirmed malignancy, of whom 26 had carcinoma in situ. In 13 of the 63 patients (20.6%, 95% CI 11.5–32.7) recurrence was seen only with blue light flexible cystoscopy (p <0.0001). Five of these cases were confirmed as carcinoma in situ. Operating room examination confirmed carcinoma in situ in 26 of 63 patients (41%), which was detected only with blue light cystoscopy in 9 of the 26 (34.6%, 95% CI 17.2–55.7, p <0.0001). Blue light cystoscopy identified additional malignant lesions in 29 of the 63 patients (46%). The false‐positive rate was 9.1% for white and blue light cystoscopy. None of the 12 adverse events during surveillance were serious. Conclusions: Office based blue light flexible cystoscopy significantly improves the detection of patients with recurrent bladder cancer and it is safe when used for surveillance. Blue light cystoscopy in the operating room significantly improves the detection of carcinoma in situ and detects lesions that are missed with white light cystoscopy.

Interlukin-10, Interferon-γ and Tumor Necrosis Factor-α Genes Variation in Prostate Cancer and Benign Prostatic Hyperplasia

Background: The genetic background of prostate cancer (PCa) is not completely understood. Objective: To assess whether an association exists between interlukin-10 (IL-10), interferon-γ(IFN-γ), tumor necrosis factor-α(TNF-α) poly-morphisms and PCa and benign prostatic hyperplasia (BPH). Patients and Methods: Forty-one patients with PCa, 100 pa-tients with BPH and 100 healthy individuals were genotyped using the allele-specific oligonucleotide-polymerase chain reaction method. Results: The moderate expressing form of IFN-γ+874 (A/T) polymorphism is more frequent in PCa and BPH cases. The homozygous form of G/G or A/A genotype of IL-10 –1082 cytokine was significantly increased in the pa-tients groups. The TNF-α–308 polymorphism significant in-creased in low producing G/G genotyped in the PCa group. Conclusion: IL-10, IFN-γ, TNF-αexpression levels may play a role in the development of PCa and BPH.

Gastrointestinal Complications Following Radical Cystectomy Using Enhanced Recovery Protocol

BACKGROUND The development of enhanced recovery after surgery (ERAS) protocols for patients undergoing radical cystectomy (RC) represents a significant advance in perioperative care. OBJECTIVE To evaluate gastrointestinal (GI) complications following RC and urinary diversion (UD) using our institutional ERAS protocol. DESIGN, SETTING, AND PARTICIPANTS We identified 377 consecutive cases of open RC and UD for which our ERAS protocol was used from May 2012 to December 2015. Exclusion criteria were consent refusal; non-bladder primary disease; palliative, salvage, or additional surgery; and prolonged postoperative intubation. A matched cohort of 144 patients for whom a traditional postoperative protocol (pre-ERAS) was used between 2003 and 2012 was selected for comparison. RESULTS AND LIMITATIONS A total of 292 ERAS patients with median age of 70 yr were included in the study, 65% of whom received an orthotopic neobladder. The median time to first flatus and bowel movement was 2 d. The median length of stay was 4 d. GI complications occurred in 45 patients (15.4%) during the first 30 d following RC, 93% of which were of minor grade. The most common GI complication was postoperative ileus (POI) in 34 cases (11.6%). Some 22 patients (7.5%) required a nasogastric tube, and parenteral nutrition was required in three patients. The rate of 30-d GI complications was significantly lower in the ERAS cohort than in the control group (13% vs 27%; p=0.003), as was the rate of POI (7% vs 23%; p<0.001). This effect was independent of other variables (hazard ratio 0.38, 95% confidence interval 0.18-0.82; p=0.01). CONCLUSIONS Our institutional ERAS protocol for RC is associated with significantly improved perioperative GI recovery and lower rates of GI complications. This protocol can be tested in multi-institutional studies to reduce GI morbidity associated with RC. PATIENT SUMMARY In this study, we showed that an enhanced recovery protocol for patients undergoing radical cystectomy for bladder cancer was associated with a significantly shorter length of hospital stay and lower rates of gastrointestinal complications, especially postoperative ileus.

Midline Extraperitoneal Approach to Retroperitoneal Lymph Node Dissection in Testicular Cancer: Minimizing Surgical Morbidity

BACKGROUND Retroperitoneal lymph node dissection (RPLND) is an important component of the management of testicular germ cell tumor (GCT) but carries significant surgical morbidity. OBJECTIVE To describe our experience with a midline extraperitoneal (EP) approach to RPLND for seminomatous and nonseminomatous GCT. DESIGN, SETTING, AND PARTICIPANTS From 2010 to 2015, 122 consecutive patients underwent RPLND from a prospective database. Patients requiring aortic resection or retrocrural dissection or with intraperitoneal disease were excluded. The remaining 69 patients underwent midline EP-RPLND. SURGICAL PROCEDURE Open midline EP-RPLND was performed using a standardized technique. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Perioperative and long-term outcomes were analyzed. Complications were graded using the Clavien-Dindo classification. A descriptive analysis using SAS software was performed. RESULTS AND LIMITATIONS A total of 68 patients underwent midline EP-RPLND successfully (98.6%). The median age was 28 yr (range 17-55). On preoperative imaging the size of the retroperitoneal mass or lymphadenopathy was <2cm in 29 patients, 2-4.9cm in 15 patients, and >5cm in 24 patients, of which 19 were >10cm. The median estimated blood loss was 325ml (interquartile range [IQR] 200-612.5). The median number of lymph nodes resected was 36 (IQR 24.5-49); the median number of positive nodes was one (IQR 0-4). The median time for return of bowel function was 2 d (IQR 1-2) and hospital stay 3 d (IQR 3-4). There were no cases of ileus. Eleven patients had 12 (17.6%) 90-d complications. Of these, six (55%) were Clavien grade 1, five (45%) were grade 2, and one was grade 3b (1.5%). Antegrade ejaculation rates were 91.6% in the primary group and 96.8% in the post-chemotherapy group. CONCLUSIONS Midline EP-RPLND can be performed safely without compromising the completeness of the resection. This approach is associated with rapid return of bowel function, minimal rates of ileus, and short hospital stay. PATIENT SUMMARY A midline extraperitoneal approach for retroperitoneal lymph node dissection in testicular cancer is safe and effective and leads to faster return of bowel function and earlier discharge.

Blue light cystoscopy for the diagnosis of bladder cancer: Results from the US prospective multicenter registry

INTRODUCTION Blue light cystoscopy (BLC) using hexaminolevulinate (HAL/Cysview/Hexvix) has been previously shown to improve detection of non-muscle-invasive bladder cancer (NMIBC). Herein, we evaluated the detection of malignant lesions in a heterogenous group of patients in the real world setting and documented the change in risk category due to upstaging or upgrading. METHODS Prospective enrollment during April 2014 to December 2016 of consecutive adult patients with suspected or known non-muscle-invasive bladder cancer based on prior cystoscopy or imaging, undergoing transurethral resection of bladder tumor at 9 different referral medical centers. HAL was instilled in the bladder for 1 to 3 hours before evacuation and inspection. Sensitivity and specificity of BLC, white light cystoscopy (WLC), and the combination of both BLC and WLC for detection of any malignancy was reported on final pathology. Number of patients with a change in American Urological Association (AUA) risk category based on BLC findings leading to a possible change in management and adverse events were recorded. RESULTS Overall, 1,632 separate samples from bladder resection or biopsy were identified from 641 BLC procedures on 533 patients: 85 (16%) underwent repeat BLC (range: 2-5). Sensitivity of WLC, BLC, and the combination for diagnosis of any malignant lesion was 76%, 91%, and 98.5%, respectively. Addition of BLC to standard WLC increased detection rate by 12% for any papillary lesion and 43% for carcinoma in-situ. Within the WLC negative group, an additional 206 lesions in 133 (25%) patients were detected exclusively with BLC. In multifocal disease, BLC resulted in AUA risk-group migration occurred in 33 (6%) patients and a change in recommended management in 74 (14%). False-positive rate was 25% for WLC and 30% for BLC. One mild dermatologic hypersensitivity reaction (0.2%). CONCLUSIONS BLC increases detection rates of carcinoma in-situ and papillary lesions over WLC alone and can change management in 14% of cases. Repeat use of HAL for BLC is safe.

MP80-10 MIDLINE EXTRAPERITONEAL APPROACH TO RETROPERITONEAL LYMPH NODE DISSECTION IN TESTICULAR CANCER: MINIMIZING SURGICAL MORBIDITY

post-chemotherapy setting for metastatic seminoma. However, false positive results can be a problem. We sought to identify a new methodology to interpret FDG-PET scans using a more objective approach to reduce false positive results. METHODS: We identified patients who had FDG-PET imaging available for re-review with a diagnosis of germ cell tumor at our institution from 2006 to 2016. Twenty-six scans were identified. All images were re-reviewed by an experienced radiologist who was blinded to patient treatments and outcomes. Radiographic variables recorded were mass size, standard uptake values (SUV), liver and blood pool values, and date of scan. Liver and blood ratios were calculated for each scan by dividing the SUV of the index lesion by the liver and blood pool values, respectively. A ratio of 1 would be considered a negative scan. A 5-point scale was assigned to each scan based on the dominant FDG-avid lesion using a similar system to the Deauville scale for lymphoma with 5 representing significant uptake and 1 for no uptake. RESULTS: A total of 26 patients were identified. The median follow-up from the PET scan was 21 months (range 1-96). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the original PET scan interpretation was 100%, 81%, 77%, and 100% respectively. If the liver ratio was included as an objective measurement, the sensitivity, specificity, PPV, and NPV would have improved to 100%, 88%, 83%, 100%, respectively. Thus, the increase in specificity would have resulted in a decrease of false positive results. Of the 26 PET studies, 3 (12%) were false positives and 0 (0%) were false negatives. Four patients underwent a RPLND due to positive findings on the PET study. Of these, 3 were found to have seminoma and 1 had necrosis on final pathology. The median SUV value of the 3 PCRPLND patients with seminoma was 6.7, with a liver ratio of 2.68. The patient with necrosis had an SUV of 2.5, with liver ratio of 0.9. The blood ratio and 5-point scoring system did not add additional significant information. CONCLUSIONS: By including the liver ratio in interpreting PET scans, we believe we can reduce the number of false positive scans.

PD62-11 PREDICTIVE ROLE OF EPITHELIAL TUMOR MARKER LEVEL ELEVATION AT FOLLOW-UP FOR TUMOR RECURRENCE AND ONCOLOGICAL OUTCOMES IN UROTHELIAL BLADDER CANCER

RESULTS: Significant upregulation of miRNA 485-3p, miRNA 520d, miRNA 410, miRNA 872, and miRNA 1304 was observed in nonresponders versus complete responders. KEGG pathway analysis revealed significant upregulation of the hsa03430 pathway, implicated in DNA mismatch repair, the hsa03420 pathway, implicated in nucleotide excision repair, and the hsa03410 pathway, involved in base excision repair, among pT0 patients. CONCLUSIONS: Differential miRNA and mRNA expression within the initial tumor specimen of patients with complete pathologic regression versus progression indicates a possible role in determiningneoadjuvant chemo-sensitivity. Upregulation of DNA repair mechanisms in the primary tumor may signify chemo-sensitivity and help stratify MIBC patients being considered for neoadjuvant chemotherapy.

V6-01 MIDLINE EXTRAPERITONEAL RPLND IN TESTIS CANCER: MINIMIZING SURGICAL MORBIDITY

INTRODUCTION AND OBJECTIVES: Retroperitoneal lymph node dissection (RPLND) is an important component of the management of testicular germ cell tumor (GCT) but its surgical morbidity is not insignificant. Herein we describe our updated experience with a midline extraperitoneal (EP) approach to RPLND for seminomatous and nonseminomatous GCT. METHODS: Between 2010 and 2015, from a prospectively collected IRB approved database, 122 consecutive patients underwent RPLND. Patients requiring aortic resection, retrocrural dissection or access to intraperitoneal disease were excluded. The remaining 69 patients underwent midline EP-RPLND. All post-chemotherapy (PC) cases underwent bilateral template dissection; all primary cases underwent extended ipsilateral templates. Perioperative and long-term outcomes were analyzed and a descriptive analysis using SAS was performed. RESULTS: 68 patients underwent midline EP-RPLND successfully (98.6%). Median age was 28 years (range1⁄417-55). Median follow up was 15.3 months (IQR: 5.7-24.3). On pre-operative imaging the size of retroperitoneal mass or lymphadenopathy was <2 cm in 29 patients, 2-5 cm in 15 patients, and >5 cm in 24 patients, of which 19 were >10cm. 3 patients underwent cavectomy. Median EBL was 325 mL (IQR: 200-612.5). Median number of lymph nodes (LN) resected was 36 (IQR: 24.5-49); median number of positive nodes was 1 (IQR: 04). Median return of bowel function was 2 days (1-3) and LOS was 3 days (2-4). There were no cases of ileus. 13 patients (19.1%) had complications within 90-days: 12 were Clavien grade 2 (17.6%), there was 1 grade 3b complication (1.5%). Antegrade ejaculation rates were 91.6% in the primary group and 96.8% in the PC group. CONCLUSIONS: Midline EP-RPLND can be performed safely without compromising completeness of resection. This approach is associated with a faster return of bowel function, lower rates of ileus and shorter LOS.

PD38-09 PROSPECTIVE EVALUATION OF CONTINENCE FOLLOWING OPEN RADICAL CYSTECTOMY AND ORTHOTOPIC URINARY DIVERSION AND THE EFFECT OF PELVIC FLOOR PHYSICAL THERAPY

INTRODUCTION AND OBJECTIVES: Continent cutaneous diversion (CCD) is a less commonly utilized diversion choice following open or robotic cystectomy. We have previously described a novel technique for robotic intracorporeal CCD. Meanwhile, continent cutaneous augmentation cystoplasty (CCAC) is a viable option for patients with neurogenic bladder. There is limited worldwide experience performing intracorporeal CCD and no studies describing intracorporeal CCAC. Principles developed in robotic CCD can be readily applied to robotic CCAC. We share our experience with these novel robotic procedures. METHODS: Robotic cystectomy was performed in patients undergoing CCD using a standard 6-port technique. The patient and robot were then repositioned for intracorporeal bowel mobilization and segmentation, ileocolonic anastomosis, uretero-colonic anastomoses, pouch construction, tapering of catheterization channel, reinforcement of ileocecal valve, and stoma creation. All patients were placed on an evidencebased Enhanced Recovery after Surgery protocol postoperatively. Operative times, intraoperative blood loss (EBL), length of stay (LOS), and complications occurring within 90 days of surgery were reviewed. RESULTS: Ten robotic intracorporeal right colon urinary diversions, including four robotic intracorporeal CCAC and six robotic intracorporeal CCD, were performed. Mean total operative times for cystectomy and intracorporeal urinary diversion were 7.8 and 10 hours for CCAC or CCD respectively (5.4-9.5; 7.9-12.9). Mean EBL was 181ml (75-300) for CCAC and 250ml (100-500) for CCD. Mean LOS for CCAC and CCD groups was 10 and 8.8 days respectively (5-18, 4-18). A single CCAC patient required transfusion postoperatively. Two high grade complications (Clavien III or greater) were reported in the CCAC group (50%). One high grade complication was reported in the CCD group (17%). Within 30 days of surgery, no CCAC and two CCD patients required readmission (0%, 33%). With a median follow up of 17 months, no incontinence was reported and all patients were able to catheterize without difficulty. CONCLUSIONS: We demonstrate that robotic intracorporeal CCD and CCAC are technically feasible and safe with good functional outcomes. Further evaluation of these novel surgical techniques along with comparative studies are needed.

Bladder Cancer: Non-invasive IMP15-02 BLUE LIGHT CYSTOSCOPY FOR DIAGNOSIS OF UROTHELIAL BLADDER CANCER: RESULTS FROM A PROSPECTIVE MULTICENTER REGISTRY

INTRODUCTION AND OBJECTIVES: Blue Light Cystoscopy (BLC) using hexaminolevulinate (Cysview) improves the detection of non-muscle invasive bladder cancer (NMIBC). We report on our experience from the multi-center prospective BLC with Cysview Registry and its utility in different scenarios. METHODS: Under IRB approval, we prospectively enrolled consecutive patients undergoing transurethral resection of bladder lesions into the registry at 9 different centers. Patients who refused catheter insertion (8), had pure upper tract or prostatic urethral lesions (7) or were lost to follow-up (10) were excluded from the study. RESULTS: Between April 2014 and Oct 2016, 1325 separate lesions were identified from 517 BLC procedures on 426 patients (mean age 72 years, 84% male). 68 patients (16%) underwent repeat use (2-5). Using final pathology as the reference standard, the sensitivity of WL, BL and the combination for any malignant lesion was 75%, 90% and 98.5% respectively. The addition of BL to standard WLC increased the detection rate by 12% for any papillary lesions and 44% for CIS (Table 1). Within the WL negative group, an additional 170 lesions in 105 (25%) patients were detected exclusively with the addition of BL. In multifocal disease, in addition to WL-detected lesions, BLC resulted in upstaging in 54 (13 %) patients, resulting in a change in management. Overall false-positive (FP) rate was 26% for WL and 32% for BL. 164 (39%) patients received BCG at least 6 weeks prior to BLC, with a positive predictive value (PPV) of BLC-detected malignancy being 55% (FP1⁄435%). 82 biopsies were taken from margins of a previous resection site (with more than 6 weeks interval), wherein the PPV of BLC was 51% for malignancy (FP1⁄433%) (figure 2). Among the positive/suspicious cytology patients who had no lesions on WL (144 total), BL was able to detect an extra 57 malignant lesions in 36 patients (sensitivity 92%). There was one mild dermatologic hypersensitivity reaction noted (0.2%). 40 (12%) patients eventually underwent cystectomy, 4 (10%) of whom exclusively because of lesions detected by BLC. CONCLUSIONS: BLC significantly increases detection rates of CIS and papillary lesions over WLC alone and can result in upstaging or upgrading in about 13% of patients. Recent BCG therapy does not appear to impact BLC accuracy. Repeat use of Cysview for BLC is safe. Source of Funding: None