Faculty Bibliography

BACKGROUND:Frailty and functional dependence are important factors in assessing preoperative risk. No studies to date have compared frailty with functional dependence as a predictor of surgical outcomes. We sought to compare the impact of frailty and functional dependence on early outcomes after gastrointestinal surgery. METHODS:Patients who underwent gastrointestinal surgery were identified using the American College of Surgeons National Surgical Quality Improvement Program database (2012-2015). Propensity score matching analysis was used to separately match dependent and independent patients, and patients with modified frailty index <3 and modified frailty index ≥3 on baseline characteristics. Multivariable logistic regression analysis was used. Postoperative outcomes were compared. RESULTS:Of 765,082 patients, 1.71% were dependent and 1.49% had a modified frailty index score ≥3. Similar outcomes were observed in matched cohorts for those who were dependent and patients with a modified frailty index score ≥3: readmission (15.61% dependent and 15.75% modified frailty index ≥3), overall morbidity (37.91% and 34.81%), serious morbidity (19.06% and 17.06%), mortality (6.73% and 5.43%), and reoperation (7.01% and 6.48%). Dependent and modified frailty index ≥3 patients had similar odds of outcomes on adjusted multivariable logistic analysis and shared 3 of the top 5 indicators for readmission: complication of surgical procedure (11.46% dependent and 11.23% mFI ≥3), intestinal obstruction (10.70% and 7.65%), and organ space surgical site infection (7.93% and 8.65%). Comparable outcomes and reasons for readmission were also obtained for dependent patients and colectomy patients with a modified frailty index score ≥3. CONCLUSION:Frailty and functional dependence are comparable in predicting postoperative outcomes after gastrointestinal surgery. Functional dependence should be considered an acceptable and practical alternative for preoperative risk stratification in a clinical setting.

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:Although previous studies have examined frailty as a potential predictor of adverse surgical outcomes, little is reported on its application. We sought to assess the impact of the 5-item modified frailty index (mFI) on morbidity in patients undergoing combined colorectal and liver resections. METHODS:Adult patients who underwent combined colorectal and liver resections were identified using the ACS-NSQIP database (2005-2015). The 5-item mFI consists of history of chronic obstructive pulmonary disease, congestive heart failure, hypertension, diabetes, and partial/total dependence. Patients were stratified into three groups: mFI 0, 1, or ≥ 2. The impact of the mFI on primary outcomes (30-day overall and serious morbidity) was assessed using multivariable logistic regression. Subgroup analyses by age and hepatectomy type was also performed. RESULTS:A total of 1928 patients were identified: 55.1% with mFI = 0, 33.2% with mFI = 1, and 11.7% with mFI ≥ 2. 75.9% of patients underwent wedge resection/segmentectomy (84.6% colon, 15.4% rectum), and 24.1% underwent hemihepatectomy (88.8% colon, 11.2% rectum). On unadjusted analysis, patients with mFI ≥ 2 had significantly greater rates of overall and serious morbidity, regardless of age and hepatectomy type. These findings were consistent with the multivariable analysis, where patients with mFI ≥ 2 had increased odds of overall morbidity (OR 1.41, 95% CI 1.02-1.96, p = 0.037) and were more than twice likely to experience serious morbidity (OR 2.12, 95% CI 1.47-3.04, p < 0.001). CONCLUSIONS:The 5-item mFI is significantly associated with 30-day morbidity in patients undergoing combined colorectal and liver resections. It is a tool that can guide surgeons preoperatively in assessing morbidity risk in patients undergoing concomitant resections.

BACKGROUND:Surgical management of colorectal cancer relies on accurate identification of tumor and possible metastatic disease. Hyperspectral (HS) sensing is a passive, non-ionizing diagnostic method that has been considered for multiple tumor types. The ability to use HS for identification of tumor specimens during surgical resection of colorectal cancers was explored. METHODS:Patients with colorectal cancer who underwent operative resection were enrolled. HS measurements were performed both intra- and extra-luminally. Spectral results were correlated with pathologic evaluation. RESULTS:Fifteen patient specimens were analyzed. For patients with confirmed colorectal cancer, extraluminal spectra analysis yielded 61.68% sensitivity with 90% specificity. For intraluminal specimens, sensitivity increased to 91.97% with 90% specificity. CONCLUSIONS:Hyperspectral sensing can reliably detect tumors in resected colon specimens. This research offers promising results for a diagnostic technology that is non-ionizing and does not require the use of contrast agents to achieve accurate colorectal cancer detection.

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.

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 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.

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.