Sanjaya Swain

The role of epigenetics in kidney malignancies

Introduction Renal cell carcinomas (RCC) are collectively the third most common type of genitourinary neoplasms, surpassed only by prostate and bladder cancer. Cure rates for renal cell carcinoma are related to tumor grade and stage; therefore, diagnostic methods for early detection and new therapeutic modalities are of paramount importance. Epigenetics can be defined as inherited modifications in gene expression that are not encoded in the DNA sequence itself. Epigenetics may play an important role in the pursuit of early diagnosis, accurate prognostication and identification of new therapeutic targets. Material and methods We used PubMed to conduct a comprehensive search of the English medical literature using search terms including epigenetics, DNA methylation, histone modification, microRNA regulation (miRNA) and RCC. In this review, we discuss the potential application of epigenetics in the diagnosis, prognosis and treatment of kidney cancer. Results During the last decade, many different types of epigenetic alterations of DNA have been found to be associated with malignant renal tumors. This has led to the research of the diagnostic and prognostic implications of these changes in renal malignancies as well as to the development of novel drugs to target these changes, with the aim of achieving a survival benefit. Conclusions Epigenetics has become a promising field in cancer research. The potential to achieve early detection and accurate prognostication in kidney cancer might be feasible through the application of epigenetics. The possibility to reverse these epigenetic changes with new therapeutic agents motivates researchers to continue pursuing better treatment options for kidney cancer and other malignancies.

Robotic Partial Nephrectomy with the Da Vinci Xi.

Purpose. The surgical expertise to perform robotic partial nephrectomy is heavily dependent on technology. The Da Vinci Xi (XI) is the latest robotic surgical platform with significant advancements compared to its predecessor. We describe our operative technique and experience with the XI system for robotic partial nephrectomy (RPN). Materials and Methods. Patients with clinical T1 renal masses were offered RPN with the XI. We used laser targeting, autopositioning, and a novel “in-line” port placement to perform RPN. Results. 15 patients underwent RPN with the XI. There were no intraoperative complications and no operative conversions. Mean console time was 101.3 minutes (range 44–176 minutes). Mean ischemia time was 17.5 minutes and estimated blood loss was 120 mLs. 12 of 15 patients had renal cell carcinoma. Two patients had oncocytoma and one had benign cystic disease. All patients had negative surgical margins and pathologic T1 disease. Two postoperative complications were encountered, including one patient who developed a pseudoaneurysm and one readmitted for presumed urinary tract infection. Conclusions. RPN with the XI system can be safely performed. Combining our surgical technique with the technological advancements on the XI offers patients acceptable pathologic and perioperative outcomes.

Pelvic lipomatosis: Bladder sparing extirpation of pelvic mass to relieve bladder storage dysfunction symptoms and pelvic pain

Pelvic lipomatosis is a rare benign disease, associated with overgrowth of fat in the perivesical and perirectal area. It is of unknown etiology. We describe a 45–year–old male with pelvic lipomatosis causing bladder storage dysfunction symptoms and pelvic pain that affected his quality of life. Surgical excision of the pelvic mass with bladder preservation was performed. After surgery, the patient had a marked improvement in his quality of life, with resolution of bladder storage dysfunction symptoms and pelvic pain.

A comparison of overall survival and perioperative outcomes between partial and radical nephrectomy for cT1b and cT2 renal cell carcinoma-Analysis of a national cancer registry

OBJECTIVES Partial nephrectomy (PN) is the standard management of cT1a renal cell carcinoma (RCC), and there is a basis for expanding its indications to larger tumors (cT1b and cT2). We analyzed a large population-based cancer registry to compare the overall survival (OS) and perioperative outcomes in patients with cT1b and cT2 RCC undergoing PN with those undergoing radical nephrectomy (RN). MATERIALS AND METHODS Patients with cT1bN0M0 and cT2N0M0 RCC were identified from the National Cancer Database (2004-2013). Patients were classified by the surgery performed and 1:1 propensity matched based on the likelihood of receiving PN. They were then compared for OS, 30-day readmission rates and 30- and 90-day mortality. RESULTS A total of 6,072 patients underwent PN. PN was associated with better OS in cT1b tumors on multivariate analyses (OR = 0.8; 95% CI: 0.72-0.89; P<0.001). For cT2 tumors, PN was associated with better OS, however this was not statistically significant (OR = 0.8; 95% CI: 0.62-1.04; P = 0.092). Unplanned readmission at 30 days was significantly more common in patients undergoing PN (4.2%) vs. RN (2.9%) but there was no difference in 30- and 90-day mortality between the 2 groups. CONCLUSIONS PN was associated with a significantly better OS than RN for cT1b but not cT2 RCC. PN had a higher 30-day readmission rate than RN in these tumors and appropriate patient selection is crucial. These results require further validation, ideally via randomized trials.

Comprehensive pelvic floor physical therapy program for men with idiopathic chronic pelvic pain syndrome: a prospective study

Background Male chronic pelvic pain syndrome (CPPS) is a heterogeneous constellation of symptoms that causes significant impairment and is often challenging to treat. In this prospective study, we evaluated men with CPPS who underwent comprehensive pelvic floor physical therapy (PFPT) program. We used the previously validated Genitourinary Pain Index (GUPI) to measure outcomes. Methods We included 14 men who underwent physical therapy for idiopathic CPPS from October 2015 to October 2016. Men with clearly identifiable causes of pelvic pain, such as previous surgery, chronic infection, trauma, prostatitis and epididymitis were excluded. Treatment included: (I) manual therapy (internal and external) of pelvic floor and abdominal musculature to facilitate relaxation of muscles; (II) therapeutic exercises to promote range of motion, improve mobility/flexibility and strengthen weak muscles; (III) biofeedback to facilitate strengthening and relaxation of pelvic floor musculature; (IV) neuromodulation for pelvic floor muscle relaxation and pain relief. GUPI questionnaires were collected at initial evaluation and after the 10th visit. Higher scores reflect worse symptoms. Previous validation of the GUPI calculated a reduction of 7 points to robustly predict being a treatment responder (sensitivity 100%, specificity 76%) and a change in 4 points to predict modest response. Data are presented as medians (ranges). Results A total of 10 patients completed 10 visits, and the remaining four patients completed between 5 and 9 visits. The median National Institute of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) score at initial evaluation was 30.8 [16–39] and decreased to 22.2 [7–37] at the tenth visit. Five of the 10 patients (50%) in the study had a reduction of greater than 7 points indicating a robust treatment response, and two (20%) had a change of greater than 4 indicating moderate response. Three patients (30%) did not have any meaningful change in NIH-CPSI and the remaining four are in the process of completing 10 sessions. Duration of therapy appears to predict treatment response. Longer duration has better response. Conclusions Male CPPS is difficult to treat and often requires a multimodal approach. Based on the results of our pilot study, pelvic floor rehabilitation may be an effective treatment option for select patients. A larger study with a control group is needed to validate the routine use of pelvic floor rehabilitation in men with CPPS and predict characteristics of men who would respond to therapy.

MP38-04 IS AN UPGRADED PIRADS 4 EQUIVALENT TO A TRUE PIRADS 4? A VALIDATION OF PIRADS VERSION 2 IN A PROSPECTIVE COHORT OF MEN UNDERGOING MRI-US FUSION BIOPSY OF THE PROSTATE

the outcome of 12-core transrectal ultrasound (TRUS) guided prostate biopsy. Herein, we aim to decipher the predictive value of mp-MRI in detection and exclusion of prostate cancer using TRUS prostate biopsy. METHODS: UK multicentre study. Data from 592 patients scheduled to undergo mp-MRI and/or 12-core TRUS-guided prostate biopsy from January till September 2016 was reviewed retrospectively from a prospective database. Mp-MRIs were reported using the Prostate Imaging Reporting and Data System (PI-RADS). Only patients who had pre biopsy mp-MRIs followed by prostate biopsy were included in the study. 108 patient were excluded as they did not have mp-MRI or biopsy due to contraindications. RESULTS: Prebiopsy mp-MRIs followed by a 12-core TRUSguided prostate biopsy were completed in 484 patients. The sensitivity and specificity of mp-MRI for prostate cancer detected on prostate biopsy were 92.6% and 74.4%, respectively. The negative predictive and positive predictive values of mp-MRI for prostate cancer detected on biopsy were 89.7% and 80.8%, respectively. 129 patients had a PIRADS score of 5 on mp-MRI, with prostate cancer detected in 92%(n1⁄4119) of patients on biopsy. The incidence of Gleason scores 6,7,8 and 9 in patients with PI-RADS 5 were 15.9%(n1⁄419), 51.2%(n1⁄461), 6.7%(n1⁄48) and 26%(n1⁄431), respectively. 117 patients had a PI-RADS score of 4 on mp-MRI, with prostate cancer detected in 53.8%(n1⁄463) of patients on biopsy. The incidence of Gleason scores 6,7,8 and 9 in patients with PI-RADS 4 were 60%(n1⁄436), 33.3% (n1⁄421), 4.7% (n1⁄43) and 1.5% (n1⁄41), respectively. 153 patients had a PI-RADS score of 3 on mp-MRI, with prostate cancer detected in 29% (n1⁄445) of patients on biopsy. The incidence of Gleason scores 6,7 and 9 cancers in patients with PI-RADS score of 3 were 68% (n1⁄431), 26.6% (n1⁄412) and 4.4% (n1⁄42), respectively. Overall there was a statistically significant association between patients with PIRADS scores 3 and cancer positive biopsies (p1⁄40.001). CONCLUSIONS: Mp-MRI has a high predictive value for both diagnosing and excluding prostate cancer. Patients with PI-RADS scores 3 had a significant association with detection of prostate cancer on biopsy. These findings could aid in guiding follow-up protocols in men suspected of prostate cancer.

MP54-11 COMPARISON OF READMISSION AND SHORT-TERM MORTALITY RATES BETWEEN DIFFERENT TYPES OF URINARY DIVERSION IN PATIENTS UNDERGOING RADICAL CYSTECTOMY

between 2008 and 2013 using the National Cancer Database. Quality indicators were defined as 1) surgical margin status, 2) lymph node yield, and 3) receipt of neoadjuvant chemotherapy. Univariate analysis and multivariate analysis was used to assess the relationship between academic facility type and annual cystectomy volume and quality indicators while controlling for demographic and pathologic characteristics. RESULTS: A total of 12,083 patients met our inclusion criteria. On multivariate analysis, while controlling for demographic and pathologic characteristics, treatment at academic facilities was associated with higher rates of negative margins (OR: 0.80; 95%CI: [0.67-0.95], p1⁄40.01), greater lymph node yields (OR: 0.49; [0.44-0.55], p<0.001), and higher rates of neoadjuvant chemotherapy(OR: 0.73; [0.64-0.55], p<0.001). High volume facilities (>24 cystectomies/year) were associated with greater lymph node yields (OR: 2.69; [2.08-3.47], p<0.001), but not significantly associated with increased neoadjuvant chemotherapy use. Intermediate volume centers (12-24 cystectomies/year) were associated with increased neoadjuvant chemotherapy use (OR: 1.60; [1.36-1.88], p<0.001). CONCLUSIONS: At a national level, high quality indicators of cystectomy (negative surgical margin, adequate lymph node yields, and receipt of neoadjuvant chemotherapy) were more likely to occur at academic facilities. High volume centers were associated with higher lymph node yields. Such data support the regionalization of cystectomy care to these centers.

MP53-15 LOCAL THERAPY IN METASTATIC PROSTATE CANCER: DOES THE BURDEN OF DISEASE MATTER? RESULTS FROM A NATIONAL POPULATION-BASED CANCER REGISTRY

any urinary leak) after RP and post IMRT was achieved in 29 (69%) and 27 (64.3%), respectively. After a median follow up of 3.4 years, a PSA recurrence and clinical recurrence were observed in 7 (16.7%) and 4 (9.5%) patients. A 5-year biochemical and clinical recurrencefree survival rate were 70.7% and 84.0%, respectively. 5-year overall free survival was 93.6%. None of patients died for prostate cancer during follow up. CONCLUSIONS: This phase II trial test a novel multimodal treatment paradigm for high-risk prostate cancer. Toxicity was acceptably low and long term oncological outcomes were good. Further studies are needed to compare this novel treatment paradigm to the standard of care.

MP04-18 SMOKING INTENSITY AS A PREDICTOR OF SURVIVAL IN BLADDER CANCER PATIENTS: RESULTS FROM A POPULATION-BASED FLORIDA CANCER REGISTRY (1981-2009)

INTRODUCTION AND OBJECTIVES: Our group has previously demonstrated that blood-based tumor markers can be useful clinical outcome predictors for non-muscle invasive urothelial carcinoma of the bladder (UCB) Our aim in this study is to further evaluate the predictive value of CEA, CA 19-9 and CA 125 on disease recurrence and progression. METHODS: We prospectively included 328 consecutive patients between February 2008 and August 2014 to measure preoperative serum levels of CEA, CA 19-9 and CA 125 before first transurethral resection of the bladder (TUR). Institutional Ethical Committee approval was obtained prior to this study. Patients diagnosed with pT2 UBC were excluded (42), leaving 286 patients for analysis of recurrence or progression. After first TUR, patients were followed with routine cystoscopy, cytology and ultrasound every 6 months. All patients with non-muscle invasive (NMI) bladder cancer with high-grade disease, previous recurrence, carcinoma in situ (CIS) or T1 received induction and maintenance intravesical BCG. RESULTS: We found that CEA and CA 19-9 levels were significantly higher in patients who had either tumor recurrence and/or progression compared to those who had no UBC recurrence during follow-up (p1⁄40.02; p1⁄40.03). As we had found previously, however, CA 125 levels did not differ between the two groups (p1⁄40.42). Overall, mean CEA level was 2.1 (0.2-12.8), CA 19-9 was 17.1 (0.4-189.9) and CA 125 was 12.5 (1.2-103.9). In patients who presented tumor recurrence and/or progression, mean CEA was 5.5, mean CA 19-9 was 21.0 and CA 125 was 13.8, while in the non-recurring group, mean CEA was 3.1, mean CA 19-9 was 11.1 and CA 125 was 11.3. Mean follow-up was 4.9 years. Patients were 70.3% males (201); 63.3% (181) of patients had pTa at first TUR. Concomitant carcinoma in situ was present in 25 cases (8.7%). CONCLUSIONS: Biomarkers utilized in routine follow-up of other malignancies, such as CEA and CA 19-9, can also be included in UCB management, since it proved able to distinguish a higher risk group of patients that could be managed accordingly. Future studies may add these blood-based tumor markers to a predictive model and validated in a larger cohort. Although CA 125 was not significantly associated with oncologic outcome, further studies are required before excluding this potential biomarker in UBC.

Current Status of Nephron-Sparing Surgery (NSS) in the Management of Renal Tumours

Nephron-sparing surgery has emerged as the surgical treatment of choice for small renal masses over the past two decades, replacing the traditional teaching of radical nephrectomy for renal cell carcinoma. With time, there has been an evolution in the techniques and indications for partial nephrectomy. This review summarizes the current status of nephron-sparing surgery for renal carcinoma and also deals with the future of this procedure.