Faculty Bibliography

BACKGROUND:The incidence of squamous cell carcinoma (SCC) of the anal canal has been rising over the past decades, especially in patients infected with human immunodeficiency virus (HIV). Despite the advent of potent multidrug regimens to treat HIV-termed highly active antiretroviral therapy (HAART), anal SCC rates have not declined, and the impact of HAART on anal SCC remains controversial. AIM:The purpose of this study was to define outcomes of anal SCC treatment in HIV-positive and HIV-negative patients. METHODS AND MATERIALS:A retrospective single-institution analysis was performed on all patients with anal SCC treated at the Johns Hopkins Hospital between 1991 and 2010. The primary outcomes measured were 5-year overall survival (5-year OS), median survival, and relapse rates. RESULTS:Our search identified 93 patients with anal SCC. Patients had a mean age of 54 years; 37.6% were male, and 21.5% were HIV-positive. Median follow-up was 28 months. Relapse occurred in 16.1% of patients. Median time to relapse was 20 months. Relapse rates were slightly higher with HIV-positive versus negative patients (30.0 vs. 12.3%) but did not reach statistical significance (p = 0.06). Among HIV-positive patients, those who relapsed were more likely to be on HAART than those who did not relapse (83.3 vs. 14.3%, p = 0.007). 5-year OS was 58.9% for the total group of patients with no significant difference between those who relapsed versus those who did not (76.2 vs. 54.5%, p = 0.20). No survival difference was seen between HIV-positive and negative patients. Survival was associated with AJCC stage in all patients. CONCLUSION:In our small series, HIV infection was not associated with a significantly higher relapse rate or worse 5-year OS among patients with anal SCC. HAART was associated with a higher rate of relapse in HIV-positive patients. AJCC staging predicted survival in both relapsed and non-relapsed patients regardless of HIV status.

BACKGROUND:Creation of a J pouch is the gold standard surgical intervention in the treatment of chronic ulcerative colitis (UC). Pouchoscopy prior to ileostomy takedown is commonly performed. We describe the frequency, indication, and findings on pouchoscopy, and determine if pouchoscopy affects rates of complications after takedown. METHODS:All UC or indeterminate inflammatory bowel disease patients with a J pouch were retrospectively evaluated from January 1994 to December 2014. Cases were defined as having routine (asymptomatic) pouchoscopy after pouch creation but before ileostomy takedown. Controls were defined as having no pouchoscopy or pouchoscopy on the same day as that of takedown. RESULTS:The study included 178 patients (81.5% cases, 18.5% controls). Fifty two percent of pouchoscopies were reported as normal. Common abnormal endoscopy findings included stricture (35%), pouchitis (7%), and cuffitis (0.7%). Length of stay during takedown hospitalization was shorter for cases than controls (3 vs. 5 days; p = 0.001), but neither short- nor long-term complications were statistically different between cases and controls. Abnormalities on pouchoscopy were not predictive for short-term complications (p = 0.73) or long-term complications (p = 0.55). Routine pouchoscopy did not delay takedown surgery in any of the included patients. CONCLUSIONS:Routine pouchoscopy may not be necessary prior to ileostomy takedown; its greatest utility is in patients with suspected pouch complications.

BACKGROUND:Timing of surgical intervention for acute ulcerative colitis has not been fully examined during the modern immunotherapy era. Although early surgical intervention is recommended, historical consensus for "early" ranges widely. The purpose of this study was to evaluate outcomes according to timing of urgent surgery for acute ulcerative colitis. METHODS:All non-elective total colectomies in ulcerative colitis patients were identified in the National Inpatient Sample from 2002 to 2014. Procedures, comorbidities, diagnoses, and in-hospital outcomes were collected using International Classification of Disease, 9th Revision codes. An operation was defined as early if within 24 hours of admission. Results were compared between the early versus delayed surgery groups. RESULTS:We found 69,936 patients that were admitted with ulcerative colitis, and 2650 patients that underwent non-elective total colectomy (3.8%). Early intervention was performed in 20.4% of patients who went to surgery. More early operations were performed laparoscopically (28.1% versus 23.3%, p = 0.021) and on more comorbid patients (Charlson Index, p = 0.008). Median total hospitalization costs were $20,948 with an early operation versus $33,666 with a delayed operation (p < 0.001). Delayed operation was an independent risk for a complication (OR = 1.46, p = 0.001). Increased hospitalization costs in the delayed surgery group were statistically significantly higher with a reported complication (OR = 3.00, p < 0.001) and lengths of stay (OR = 1.26, p < 0.001). CONCLUSION/CONCLUSIONS:Delayed operations for acute ulcerative colitis are associated with increased postoperative complications, increased lengths of stay, and increased hospital costs. Further prospective studies could demonstrate that this association leads to improved outcomes with immediate surgical intervention for medically refractory ulcerative colitis.

BACKGROUND:High dose-rate Intra-Operative Radiation Therapy (HD-IORT) is used to provide effective local control for patients with high-risk locally advanced or recurrent tumors. However, the utility of HD-IORT for patients with bladder cancer has not been studied. OBJECTIVE:To characterize our institutional experience with HD-IORT in patients with cancer requiring genitourinary surgery, in an effort to identify patients with bladder cancer that may benefit from HD-IORT. METHODS:We performed a retrospective review of all patients who have undergone HD-IORT during genitourinary surgery at our institution. Patients were stratified by surgical margin status, and primary outcomes assessed were overall survival, recurrence free survival and 90-day complications. Patients undergoing cystectomy and HD-IORT with sarcomatoid urothelial cancer were compared to a similar cohort undergoing cystectomy alone. A sample case of one such patient is discussed in detail. RESULTS:84 patients at our institution have undergone HD-IORT with genitourinary surgery. Positive surgical margin status was the greatest predictor of both OS (HR = 3.42) and RFS (HR = 2.61). The overall 90-day complication rate was 61%, with wound infections (43%) and GI complications (21%) being most common. 4 of these patients had sarcomatoid urothelial histology, and all are still alive with >2 yrs follow up. This compares to a 52% 1 yr survival in our sarcomatoid urothelial cohort (25 pts) that did not undergo HD-IORT. CONCLUSIONS:Our institutional experience with HD-IORT has been promising, particularly among patients with locally advanced disease and sarcomatoid histology. We are currently enrolling patients in a multi-institutional registry to assess the utility of HD-IORT in high risk bladder cancer.

BACKGROUND AND AIMS/OBJECTIVE:NLRP3 inflammasome is known to be involved in inflammatory bowel diseases. However, it is controversial whether it is pathogenic or beneficial. This study evaluated the roles of NLRP3 inflammasome in the pathogenesis of inflammatory bowel disease in IL-10-/- mice and humans. METHODS:NLRP3 inflammasome in colonic mucosa, macrophages, and colonic epithelial cells were analysed by western blotting. The NLRP3 inflammasome components were studied by sucrose density gradient fractionation, chemical cross-linking, and co-immunoprecipitation. The role of NLPR3 inflammasome in the pathogenesis of colitis was extensively evaluated in IL-10-/- mice, using a specific NLPR3 inflammasome inhibitor glyburide. RESULTS:NLRP3 inflammasome was upregulated in colonic mucosa of both IL-10-/- mice and Crohn's patients. NLRP3 inflammasome activity in IL-10-/- mice was elevated prior to colitis onset; it progressively increased as disease worsened and peaked as macroscopic disease emerged. NLRP3 inflammasome was found in both intestinal epithelial cells and colonic macrophages, as a large complex with a molecular weight of ≥ 360 kDa in size. In the absence of IL-10, NLRP3 inflammasome was spontaneously active and more robustly responsive when activated by LPS and nigericin. Glyburide markedly suppressed NLRP3 inflammasome expression/activation in IL-10-/- mice, leading to not only alleviation of ongoing colitis but also prevention/delay of disease onset. Glyburide also effectively inhibited the release of proinflammatory cytokines/chemokines by mucosal explants from Crohn's patients. CONCLUSIONS:Abnormal activation of NLRP3 inflammasome plays a major pathogenic role in the development of chronic colitis in IL-10-/- mice and humans. Glyburide, an FDA-approved drug, may have great potential in the management of inflammatory bowel diseases.

OBJECTIVE:A relatively large proportion of patients with Crohn disease (CD) develop complications including abscess formation, stricture, and penetrating disease. A subset of patients will have genital and reproductive organ involvement of CD, resulting in significant morbidity. These special circumstances create unique management challenges that must be tailored to the activity, location, and extent of disease. Familiarity with the epidemiology, pathogenesis, imaging features, and treatment strategies for patients with genital CD can aid imaging diagnoses and guide appropriate patient management. The purpose of this study is to illustrate the spectrum of CD in the genital tract and reproductive organs and discuss the complex management strategies in these patients as it relates to imaging. CONCLUSION:Given the impact on patient outcome and treatment planning, familiarity with the epidemiology, pathogenesis, imaging features, and treatment of patients with genital Crohn disease can aid radiologic diagnoses and guide appropriate patient management.

BACKGROUND:Intraoperative radiotherapy (IORT) has advantages over external beam radiation therapy (EBRT). Few studies have described side effects associated with its addition. We evaluated our institution's experience with abdominopelvic IORT to assess safety by postoperative complication rates. METHODS:Prospectively collected IRB-approved database of all patients receiving abdominopelvic IORT (via high dose rate brachytherapy) at Johns Hopkins Hospital between November 2006 and May 2014 was reviewed. Patients were discussed in multidisciplinary conferences. Those selected for IORT were patients for whom curative intent resection was planned for which IORT could improve margin-negative resection and optimize locoregional control. Perioperative complications were classified via Clavien-Dindo scale for postoperative surgical complications. RESULTS:A total of 113 patients were evaluated. Most common diagnosis was sarcoma (50/113, 44%) followed by colorectal cancer (45/113, 40%), most of which were recurrent (84%). There were no perioperative deaths. A total of 57% of patients experienced a complication Grade II or higher: 24% (27/113) Grade II; 27% (30/113) Grade III; 7% (8/113) Grade IV. Wound complications were most common (38%), then gastrointestinal (25%). No radiotherapy variables were significantly associated with complications on uni/multi-variate analysis. CONCLUSIONS:Our institution's experience with IORT demonstrated historically expected postoperative complication rates. IORT is safe, with acceptable perioperative morbidity.