Vignesh T. Packiam

Extended Duration Enoxaparin Decreases the Rate of Venous Thromboembolic Events after Radical Cystectomy Compared to Inpatient Only Subcutaneous Heparin

Purpose: Venous thromboembolic events are a significant source of morbidity after radical cystectomy. At our institution subcutaneous heparin was historically given to patients undergoing radical cystectomy immediately before incision and throughout the inpatient stay. In an effort to decrease the overall rate of venous thromboembolism and post‐discharge venous thromboembolism, a regimen including extended duration enoxaparin was initiated for patients undergoing radical cystectomy. Materials and Methods: In January 2013 thromboprophylaxis was modified for patients undergoing radical cystectomy by replacing a regimen of subcutaneous heparin before induction and then every 8 hours until discharge home with enoxaparin daily for postoperative prophylaxis continued until 28 days after discharge. Data from our institutional radical cystectomy database for patients undergoing surgery from January 2011 to May 2014 were reviewed. The primary outcome was clinically symptomatic postoperative venous thromboembolism. Secondary outcomes included timing of venous thromboembolism and blood transfusions. Multivariate logistic regression was used to control for differences between cohorts. Results: Of the 402 patients 234 underwent radical cystectomy before the change and 168 after. The enoxaparin regimen decreased the rate of venous thromboembolism (12% vs 5%, p=0.024) with the main benefit on post‐discharge venous thromboembolism (6% vs 2%, p=0.039). Overall 17 of 37 (46%) venous thromboembolisms occurred after discharge home. Multivariate analysis confirmed that the enoxaparin regimen was independently associated with reduced odds of venous thromboembolism (OR 0.33, 95% CI 0.14–0.76, p=0.009). Intraoperative and postoperative transfusion rates were similar between cohorts. Conclusions: Thromboprophylaxis with extended duration enoxaparin decreased the rate of venous thromboembolism after radical cystectomy compared to inpatient only subcutaneous heparin with no increased risk of bleeding.

Rhabdomyolysis After Major Urologic Surgery: Epidemiology, Risk Factors, and Outcomes

OBJECTIVE To study the epidemiology, risk factors, and outcomes of rhabdomyolysis (RM) after major urologic surgery. MATERIALS AND METHODS The National Inpatient Sample (2003-2011) was used to identify patients who underwent radical prostatectomy, radical or partial nephrectomy, or radical cystectomy. Demographics included age, sex, race, and comorbidities. Factors examined included bleeding, hospital teaching status, minimally invasive technique, and development of RM. Multivariate logistic regression was used to identify independent risk factors of RM. Outcomes of mortality, acute kidney injury (AKI), length of stay, and charges in patients with RM were compared with those of controls. RESULTS A weighted population of 1,016,074 patients was identified with 870 (0.1%) developing RM, which was significantly more likely for radical or partial nephrectomy and radical cystectomy patients compared with radical prostatectomy patients. On multivariate analysis, independent risk factors for RM included younger age, male sex, diabetes, chronic kidney disease, obesity, and bleeding. Race, minimally invasive technique, and teaching status were not associated with RM when controlling for other factors. Patients with RM experienced increases in mortality, AKI, length of stay, and hospital charges. CONCLUSION Rhabdomyolysis is a rare complication after urologic surgery. Risk factors include male sex, younger age, diabetes, chronic kidney disease, obesity, and perioperative bleeding. Patients who develop RM have a higher risk of AKI, mortality, prolonged hospital stay, and increased charges.

Non-muscle-invasive bladder cancer: Intravesical treatments beyond Bacille Calmette-Guérin.

An unmet need exists for patients with high‐risk non–muscle‐invasive bladder cancer for whom bacille Calmette‐Guérin (BCG) has failed and who seek further bladder‐sparing approaches. This shortcoming poses difficult management dilemmas. This review explores previously investigated first‐line intravesical therapies and discusses emerging second‐line treatments for the heterogeneous group of patients for whom BCG has failed. The myriad of recently published and ongoing trials assessing novel salvage intravesical treatments offer promise to patients who both seek an effective cure and want to avoid radical surgery. However, these trials must carefully be contextualized by specific patient, tumor, and recurrence characteristics. As data continue to accumulate, there will potentially be a role for these agents as second‐line or even first‐line intravesical therapies. Cancer 2017;123:390–400.

The Impact of Minimally Invasive Surgery on Major Iatrogenic Ureteral Injury and Subsequent Ureteral Repair During Hysterectomy: A National Analysis of Risk Factors and Outcomes

OBJECTIVE To identify risk factors for ureteral injury during hysterectomy and to assess outcomes of concurrent minimally invasive vs converted to open repairs. METHODS We queried the American College of Surgeons-National Surgical Quality Improvement Program database between 2005 and 2013 to identify abdominal hysterectomy (AH), minimally invasive hysterectomy (MIH), or vaginal hysterectomy. Ureteral injury was identified based on intraoperative or delayed management. Multivariate logistic regression was performed to assess the effect of hysterectomy approach on risk of ureteral injury while controlling for covariates. For patients with ureteral injury during MIH, we compared 30-day outcomes following minimally invasive vs converted open repairs. RESULTS There were 302 iatrogenic ureteral injuries from 96,538 hysterectomies, with 0.18%, 0.48%, and 0.04% from AH, MIH, and vaginal hysterectomy, respectively. Patients who underwent MIH were younger and had decreased comorbidities compared to patients who underwent AH (all P < .001). MIH resulted in lower overall complications (6.6% vs 14.8%, P < .001) but higher ureteral injury rate (0.48% vs 0.18%, P < .001) compared to AH. On multivariate analysis, the minimally invasive approach was associated with increased risk of ureteral injury (odds ratio 4.2, P < .001). Patients undergoing minimally invasive ureteral repairs (89%) during MIH had shorter operating room time and length of stay but similar overall perioperative complications compared to those with converted open repairs (11%). CONCLUSION Using a large national series, we show that the minimally invasive approach for hysterectomy is an independent risk factor for iatrogenic ureteral injuries. During MIH, concurrent minimally invasive ureteral repairs resulted in comparable 30-day outcomes compared to converted to open repairs.

The Effect of Obesity on Perioperative Outcomes for Open and Minimally Invasive Prostatectomy

OBJECTIVE To compare the impact of obesity on perioperative outcomes between open radical prostatectomy (ORP) and minimally invasive prostatectomy (MIP). METHODS Using the National Surgical Quality Improvement Program public use files for 2008-2013, we identified patients undergoing prostatectomy using Current Procedural Terminology codes. Those without body mass index (BMI) or comorbidity information were excluded. BMI was treated as a categorical variable according to the World Health Organization classification. Demographic and comorbid conditions were compared between BMI groups, and multivariable logistical regression was used to identify independent predictors of adverse perioperative events. RESULTS We identified 17,693 MIP and 4674 ORP for analysis. Of the entire cohort, only 18.7% had a BMI within the normal range (18.5-24.9), whereas the remaining 81.3% were at least overweight (BMI > 25). Class I, II, and III obesity accounted for 25.0%, 7.0%, and 2.3% of the cohort, respectively. Overall, complications were higher with ORP (19.0%) than with MIP (5.3%), which held true across all BMI categories. The rate of wound, renal, thromboembolic, infectious, neurologic, Clavien grade III-V, and overall complications among MIP were directly related to BMI. Only wound and renal complications were related to BMI in ORP. In multivariable analysis, obesity was found to be an independent predictor of wound, renal, and thromboembolic complications. CONCLUSION Obesity has a larger impact on morbidity for MIP compared to ORP. Overall morbidity, however, remains lower for MIP across all BMI groups.

30-Day Morbidity and Reoperation Following Midurethral Sling: Analysis of 8772 Cases Using a National Prospective Database

OBJECTIVE To determine 30-day complications, risk of readmission, and reoperation for midurethral slings (MUS). METHODS The National Surgical Quality Improvement Program database from 2006 to 2013 was queried for MUS alone by excluding concurrent reconstructive, urologic, or gynecologic procedures. We assessed baseline characteristics, 30-day perioperative outcomes and 30-day readmission. Logistic regression analysis identified risk factors for the frequent complications. RESULTS There were 8772 women who underwent MUS, of which 3830 (43.7%) and 4942 (56.3%) were performed by urologists and gynecologists, respectively. Patients of urologists were older, had higher frailty, and were more likely diabetic (all P < .05). Patients of gynecologists were more likely to have resident involvement compared to urologists (16.4% vs 11.2%, P < .001). Mean operative time was shorter for urologists compared to gynecologists (35.6 ± 29.2 minutes vs 38.1 ± 34.3 minutes, P < .001). The overall 30-day rate of any complication was 3.52%. Urinary tract infection (UTI) occurred in 2.2% vs 3.5% of the urologic and gynecologic patients, respectively (P=.001). After adjusting for frailty, body mass index, steroid use, age, operative time, and residency involvement, gynecologic performed surgery incurred an increased risk of UTI (OR 1.67, 95% CI 1.27-2.19; P=.001). Sixty-five (0.90%) patients were readmitted within 30 days, most commonly due to urinary symptoms. Sling revision for urinary obstruction occurred in 15 patients; 10 underwent repair of the bladder, urethra, or vagina. CONCLUSION To our knowledge, we present the largest American cohort of MUS 30-day outcomes to date, stratified by specialty of performing surgeon. Overall, morbidity is low. UTI is the most common complication, and occurs at increased frequency for patients of gynecologists.

Contemporary Population-Based Comparison of Localized Ductal Adenocarcinoma and High-Risk Acinar Adenocarcinoma of the Prostate

OBJECTIVE To compare pathological characteristics, treatment patterns, and survival in patients with ductal adenocarcinoma (DC) compared to those with acinar adenocarcinoma (AC). MATERIALS AND METHODS Using the National Cancer Database, we identified patients diagnosed with clinically localized (cN0, cM0) pure DC (n = 1328) and AC (n = 751,635) between 1998 and 2011. High-risk AC was defined as Gleason 8-10. Demographic, treatment, pathological, and survival characteristics of patients were compared. RESULTS Compared to patients with Gleason 8-10 AC, those with DC presented with lower mean prostate-specific antigen (10.3 vs 16.2 ng/mL, P <.001), had similar rates (11.7% vs 11.5%, P = .8) of clinical extra-capsular extension (stage ≥ cT3), and were more likely to undergo prostatectomy (54% vs 36%, P <.001). Compared to patients with Gleason 8-10 AC undergoing prostatectomy, those with DC had more favorable pathology: stage ≥ T3 (39% vs 52%, P <.001), fewer positive lymph nodes (4% vs 11%, P <.001), and fewer positive margins (25% vs 33%, P <.001). On Kaplan-Meier analysis, patients with DC had similar 5-year survival (75.0%, 95% confidence interval [CI] [71.7-78.9]) compared to those with Gleason 8-10 AC (77.1%, 95% CI [76.6%-77.6%], P = .2). On Cox multivariable analysis, patients with Gleason 8-10 AC had a similar risk of death compared to those with DC (hazards ratio = 0.92, 95% CI [0.69-1.23], P = 6). CONCLUSION In this large contemporary population-based series, patients with DC of the prostate presented with lower prostate-specific antigen, had more favorable pathological features, and similar overall survival compared to men with Gleason 8-10 AC.

Lessons from 151 ureteral reimplantations for postcystectomy ureteroenteric strictures: A single-center experience over a decade☆

OBJECTIVES Ureteroenteric anastomotic strictures are common after cystectomy with urinary diversion. Endoscopic treatments have poor long-term success, although ureteral reimplantation is associated with morbidity. Predictors of successful open repair are poorly defined. Our objective was to characterize outcomes of ureteral reimplantation after cystectomy and identify risk factors for stricture recurrence. PATIENTS AND METHODS We performed a retrospective review of 124 consecutive patients with a total of 151 open ureteral reimplantations for postcystectomy ureteroenteric strictures between January 2006 and December 2015. Baseline clinicopathologic characteristics and perioperative outcomes were examined. Predictors for stricture recurrence were assessed by univariable testing and univariate Cox proportional hazards regression. RESULTS Most patients underwent preoperative drainage by percutaneous nephrostomy (PCN; 43%) or percutaneous nephroureterostomy (PCNU; 44%). Major iatrogenic injuries included enterotomies requiring bowel anastomosis (3.2%) and major vascular injuries (2.4%). Overall, 60 (48%) patients suffered 90-day complications, of which 15 (12%) patients had high-grade complications. Median length of stay was 6 days [interquartile range: 5, 8] and median follow-up was 21 months [interquartile range: 5, 43]. The overall success rate per ureter was 93.4%. On univariate analysis, the only significant predictor of stricture recurrence was preoperative PCNU placement compared with PCN placement or no drainage (success rates: 85.5% vs. 98.9%, respectively, P = 0.002). Cox proportional hazards regression demonstrated that preoperative PCNU placement yielded a hazard ratio of 10.2 (95% CI: 1.27-82.6) for stricture recurrence (P<0.005). Stricture recurrence was independent of previous endoscopic interventions (P = 0.42). Stricture length was unable to be assessed. CONCLUSIONS Postcystectomy ureteral reimplantation was associated with relatively low rates of major iatrogenic injuries and high-grade complications. Preoperative PCN placement rather than PCNU may yield better results.

An open label, single-arm, phase II multicenter study of the safety and efficacy of CG0070 oncolytic vector regimen in patients with BCG-unresponsive non–muscle-invasive bladder cancer: Interim results

OBJECTIVES CG0070 is a replication-competent oncolytic adenovirus that targets bladder tumor cells through their defective retinoblastoma pathway. Prior reports of intravesical CG0070 have shown promising activity in patients with high-grade non-muscle invasive bladder cancer (NMIBC) who previously did not respond to bacillus Calmette-Guérin (BCG). However, limited accrual has hindered analysis of efficacy, particularly for pathologic subsets. We evaluated interim results of a phase II trial for intravesical CG0070 in patients with BCG-unresponsive NMIBC who refused cystectomy. PATIENTS AND METHODS At interim analysis (April 2017), 45 patients with residual high-grade Ta, T1, or carcinoma-in-situ (CIS) ± Ta/T1 had evaluable 6-month follow-up in this phase II single-arm multicenter trial (NCT02365818). All patients received at least 2 prior courses of intravesical therapy for CIS, with at least 1 being a course of BCG. Patients had either failed BCG induction therapy within 6 months or had been successfully treated with BCG with subsequent recurrence. Complete response (CR) at 6 months was defined as absence of disease on cytology, cystoscopy, and random biopsies. RESULTS Of 45 patients, there were 24 pure CIS, 8 CIS + Ta, 4 CIS + T1, 6 Ta, 3 T1. Overall 6-month CR (95% CI) was 47% (32%-62%). Considering 6-month CR for pathologic subsets, pure CIS was 58% (37%-78%), CIS ± Ta/T1 50% (33%-67%), and pure Ta/T1 33% (8%-70%). At 6 months, the single patient that progressed to muscle-invasive disease had Ta and T1 tumors at baseline. No patients with pure T1 had 6-month CR. Treatment-related adverse events (AEs) at 6 months were most commonly urinary bladder spasms (36%), hematuria (28%), dysuria (25%), and urgency (22%). Immunologic treatment-related AEs included flu-like symptoms (12%) and fatigue (6%). Grade III treatment-related AEs included dysuria (3%) and hypotension (1.5%). There were no Grade IV/V treatment-related AEs. CONCLUSIONS This phase II study demonstrates that intravesical CG0070 yielded an overall 47% CR rate at 6 months for all patients and 50% for patients with CIS, with an acceptable level of toxicity for patients with high-risk BCG-unresponsive NMIBC. There is a particularly strong response and limited progression in patients with pure CIS.

Open Vs Minimally Invasive Adult Ureteral Reimplantation: Analysis of 30-day Outcomes in the National Surgical Quality Improvement Program (NSQIP) Database

OBJECTIVE To examine 30-day outcomes of robotic-assisted and pure laparoscopic ureteral reimplantation (LUR) vs open ureteral reimplantation (OUR) in adult patients for benign disease. METHODS We identified adult patients undergoing LUR or OUR by urologists between 2006 and 2013 using the American College of Surgeons National Surgical Quality Improvement Program database, excluding those with concomitant partial cystectomy or ureterectomy. Multivariable regression modeling was used to assess for the independent association of minimally invasive surgery (MIS) with 30-day complications, reoperations, or readmissions. RESULTS Of 512 patients identified, 300 underwent LUR and 212 underwent OUR. Baseline characteristics including age, race, body mass index, and cardiovascular comorbidities were similar between LUR and OUR (all P > .05). Patients who underwent LUR had higher median preoperative serum creatinine (1.1 mg/dL vs 1.0 mg/dL, P = .03), increased presence of a resident (51% vs 34%, P < .01), and shorter hospitalization (1 [interquartile range 0-3] days vs 4 [interquartile range 3-6] days, P < .01) compared to patients who underwent OUR. LUR had lower overall complications (9% vs 28%, P < .01), especially with regard to transfusions (1% vs 11%, P < .01), superficial wound infections (0% vs 5%, P < .01), and urinary tract infections (5% vs 11%, P = .03). On multiple regression analyses, MIS was an independent predictor of lower overall complication rate (odds ratio [OR] 0.24 [0.14-0.40], P < .01), but was not predictive of readmission (OR 0.93 [0.44-1.98], P = .16) or reoperation (OR 2.09 [0.90-4.82], P = .10). CONCLUSION In the largest current series assessing the impact of MIS on adult ureteral reimplantation, data from the National Surgical Quality Improvement Program demonstrate that LUR results in decreased 30-day complications.