Faculty Bibliography

OBJECTIVES/OBJECTIVE:We sought to determine the yield of somatic mutational analysis from EUS-guided biopsies of pancreatic adenocarcinoma compared to that of surgical resection and to assess the impact of these results on oncologic treatment. METHODS:We determined the yield of EUS sampling and surgical resection. We evaluated the potential impact of mutational analysis by identifying actionable mutations and its direct impact by reviewing actual treatment decisions. RESULTS:Yield of EUS sampling was 89.5%, comparable to the 95.8% yield of surgical resection. Over a quarter in the EUS cohort carried actionable mutations, and of these, over one in six had treatment impacted by mutational analysis. CONCLUSIONS:EUS sampling is nearly always adequate for somatic testing and may have substantial potential and real impact on treatment decisions.

Background: Venous thromboembolism (VTE), including Portomesenteric vein thrombosis (PMVT), is a major complication of sleeve gastrectomy (SG). We changed our practice in July 2021 to routinely discharge all SG patients postoperatively with extended chemoprophylaxis for 30 days. Objectives: Evaluate the efficacy and safety of routine extended chemoprophylaxis compared to 2 prior timeframes using selective extended chemoprophylaxis. Setting: University Hospital. Methods: Between 2012"“2018, SG patients were discharged on extended chemoprophylaxis for patients deemed "high-risk" for VTE, including patients with body mass index (BMI) >50, and previous VTE. Between 2018"“2021, extended chemoprophylaxis was broadened to include patients with positive preoperative thrombophilia panels (including Factor VIII). After 2021, all SG were routinely discharged on extended chemoprophylaxis. The typical regimen was 30 days Lovenox BID (40-mg twice daily for BMI> 40, 60-mg twice daily for BMI >60). Outcomes evaluated were rate of VTE/PMVT and postoperative bleed, including delayed bleed. Results: A total of 8864 patients underwent SG. Average age and BMI were 37.5 years and 43.0 kg/m², respectively. The overall incidence of PMVT was 33/8864 (.37%). Converting from selective extended chemoprophylaxis (Group 1) to routine extended chemoprophylaxis (Group 3) decreased the rate of PMVT from .55% to .21% (P = .13). There was a significantly higher overall bleeding rate (.85%), including delayed bleeds (.34%) in the routine extended chemoprophylaxis patients (P < .05). These bleeds were mainly managed nonoperatively. Conclusions: Routine extended (30 day) chemoprophylaxis for all SG may reduce PMVT rate but lead to a higher bleeding rate post-operatively. The vast majority of the increased bleeds are delayed and can be managed non-operatively.

OBJECTIVE:To quantify the rate of low-yield surgery, defined as no high-grade dysplastic precursor lesions or T1N0M0 pancreatic cancer at pathology, during pancreatic cancer surveillance. BACKGROUND:Global efforts have been made in pancreatic cancer surveillance to anticipate the diagnosis of pancreatic cancer at an early stage and improve survival in high-risk individuals (HRIs) with a hereditary predisposition. The negative impact of pancreatic cancer surveillance when surgery is performed for low-grade dysplasia or a non-neoplastic condition is not well quantified. MATERIALS AND METHODS:A systematic search and prevalence meta-analysis was performed for studies reporting surgery with final diagnoses other than those defined by the Cancer of the Pancreas Screening (CAPS) goals from January 2000 to July 2023. The secondary outcome was the pooled proportion of final diagnoses matching the CAPS goals (PROSPERO: #CRD42022300408). RESULTS:Twenty-three articles with 5027 patients (median 109 patients/study, interquartile range 251) were included. The pooled prevalence of low-yield surgery was 2.1% (95% CI: 0.9-3.7, I2 : 83%). In the subgroup analysis, this prevalence was nonsignificantly higher in studies that only included familial pancreatic cancer subjects without known pathogenic variants, compared with those enrolling pathogenic variant carriers. No effect modifiers were found. Overall, the pooled prevalence of subjects under surveillance who had a pancreatic resection that contained target lesions was 0.8% (95% CI, 0.3-1.5, I2 : 24%]. The temporal analysis showed that the rate of low-yield surgeries decreased in the last decades and stabilized at around 1% (test for subgroup differences P <0.01). CONCLUSIONS:The risk of "low-yield" surgery during pancreatic cancer surveillance is relatively low but should be thoroughly discussed with individuals under surveillance.

Pancreatic ductal adenocarcinoma (PDAC) cells use glutamine (Gln) to support proliferation and redox balance. Early attempts to inhibit Gln metabolism using glutaminase inhibitors resulted in rapid metabolic reprogramming and therapeutic resistance. Here, we demonstrated that treating PDAC cells with a Gln antagonist, 6-diazo-5-oxo-L-norleucine (DON), led to a metabolic crisis in vitro. In addition, we observed a profound decrease in tumor growth in several in vivo models using sirpiglenastat (DRP-104), a pro-drug version of DON that was designed to circumvent DON-associated toxicity. We found that extracellular signal-regulated kinase (ERK) signaling is increased as a compensatory mechanism. Combinatorial treatment with DRP-104 and trametinib led to a significant increase in survival in a syngeneic model of PDAC. These proof-of-concept studies suggested that broadly targeting Gln metabolism could provide a therapeutic avenue for PDAC. The combination with an ERK signaling pathway inhibitor could further improve the therapeutic outcome.

PURPOSE/OBJECTIVE:The safety and feasibility of minimally invasive surgery (MIS) in the setting of colorectal cancer emergencies have been debated. We sought to compare postoperative outcomes of MIS with open techniques in the setting of colorectal cancer emergencies from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. METHODS:We included patients undergoing colectomy for colorectal cancer emergency between 2012 and 2019 "2012-2019" from the ACS-NSQIP dataset. We compared short-term morbidity, mortality, short-term oncological outcomes, and secondary outcomes for MIS vs open colectomies using propensity score matching. We then evaluated the trends of MIS versus open colectomies using linear regression analysis. RESULTS:We examined a total of 5544 patients (open n = 4070; MIS n = 1474) and included 1352 patients for our postoperative outcome analyses after propensity score matching 1:1 (open n = 676; MIS n = 676). Within the matched cohort, mortality was significantly higher in the open group (open 6.95% vs MIS 3.99%, OR 1.8, p = 0.023). Anastomotic leak rates were comparable between the  two groups (open 4.46% vs MIS 4.02%, OR 1.12, p = 0.787). Pulmonary complications were significantly higher after open surgery (open 10.06% vs MIS 4.73%, OR 2.25, p < 0.001). Rates of ileus were significantly higher amongst open patients (open 29.08% vs MIS 19.94%, p < 0.001). Patients stayed on average 1 day longer in the hospital after open surgery (p < 0.001). Rates of MIS for early tumors (N0 and T1/T2, n = 289) did not significantly change over 7 years (p = 0.597, rate = - 0.065%/year); however, utilization of MIS for late tumors (N1 or T3/T4, n = 4359) increased by 2.06% per year (p < 0.001). CONCLUSIONS:This study demonstrates that MIS was associated with superior postoperative outcomes compared to open surgery without compromising oncological outcomes in patients undergoing emergency colectomy for colon cancer. Within the matched cohort, MIS was associated with lower rates of mortality, pulmonary complications, ileus, and shorter postoperative length of stay.

INTRODUCTION:Reinforcement of crural closure with synthetic resorbable mesh has been proposed to decrease recurrence rates after hiatal hernia repair, but continues to be controversial. This systematic review aims to evaluate the safety, efficacy, and intermediate-term results of using biosynthetic mesh to augment the hiatus. METHODS:The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed throughout this systematic review. The Risk of Bias in Non-Randomized Studies of Interventions and Risk of Bias in Randomized Trials tools were used to perform qualitative assessment of all studies included in this review. Recommendations were then summarized for the following pre-defined key items: protocol, research question, search strategy, study eligibility, data extraction, study design, risk of bias, publication bias, and statistical analysis. RESULTS:The systematic literature search found 520 articles, 101 of which were duplicates and 355 articles were determined to be unrelated to our study and excluded. The full text of the remaining 64 articles was thoroughly assessed. A total of 18 articles (1846 patients) were ultimately included for this review, describing hiatal hernia repair using three different biosynthetic meshes-BIO-A, Phasix ST, and polyglactin mesh. Mean operative time varied from 127 to 223 min. Mean follow up varied from 12 to 54 months. There were no mesh erosions or explants. One mesh-related complication of stenosis requiring reoperation was reported with BIO-A. Studies showed significant improvement in symptom and quality-of-life scores, as well as satisfaction with surgery. Recurrence was reported as radiologic or clinical recurrence. Overall, recurrence rate varied from 0.9 to 25%. CONCLUSION:The use of biosynthetic mesh is safe and effective for hiatal hernia repair with low complications rates and high symptom resolution. The reported recurrence rates are highly variable due to significant heterogeneity in defining and evaluating recurrences. Further randomized controlled trials with larger samples and long-term follow-up should be performed to better analyze outcomes and recurrence rates.

BACKGROUND:With each succession along the surgical career pathway, from medical school to faculty, the percentage of those who identify as underrepresented in medicine (URiM) decreases. We sought to evaluate the demographic trend of surgical fellowship applicants, matriculants, and graduates over time. STUDY DESIGN:The Electronic Residency Application Service and the Graduate Medical Education Survey for general surgery fellowships in colorectal surgery, surgical oncology, pediatric surgery, thoracic surgery, and vascular surgery were retrospectively analyzed (2005 to 2020). The data were stratified by race and gender, descriptive statistics were performed, and time series were evaluated. Race/ethnicity groups included White, Asian, other, and URiM, which is defined as Black/African American, Hispanic/Latino(a), Alaskan or Hawaiian Native, and Native American. RESULTS:From 2005 to 2020, there were 5,357 Electronic Residency Application Service applicants, 4,559 matriculants, and 4,178 graduates to surgery fellowships. Whites, followed by Asians, represented the highest percentage of applicants (62.7% and 22.3%, respectively), matriculants (65.4% and 23.8% respectively), and graduates (65.4% and 24.0%, respectively). For URiMs, the applicants (13.4%), matriculants (9.1%), and graduates (9.1%) remained significantly low (p < 0.001). When stratified by both race and gender, only 4.6% of the applicants, 2.7% of matriculants, and 2.4% of graduates identified as both URiM and female compared to White female applicants (20.0%), matriculants (17.9%), and graduates (16.5%, p < 0.001). CONCLUSIONS:Significant disparities exist for URiMs in general surgery subspecialty fellowships. These results serve as a call to action to re-examine and improve the existing processes to increase the number of URiMs in the surgery subspecialty fellowship training pathway.