Transcriptomic changes and gene fusions during the progression from Barrett's esophagus to esophageal adenocarcinoma.

The incidence of esophageal adenocarcinoma (EAC) has surged by 600% in recent decades, with a dismal 5-year survival rate of just 15%. Barrett's esophagus (BE), affecting about 2% of the population, raises the risk of EAC by 40-fold. Despite this, the transcriptomic changes during the BE to EAC progression remain unclear. Our study addresses this gap through comprehensive transcriptomic profiling to identify key mRNA signatures and genomic alterations, such as gene fusions. We performed RNA-sequencing on BE and EAC tissues from 8 individuals, followed by differential gene expression, pathway and network analysis, and gene fusion prediction. We identified mRNA changes during the BE-to-EAC transition and validated our results with single-cell RNA-seq datasets. We observed upregulation of keratin family members in EAC and confirmed increased levels of keratin 14 (KRT14) using immunofluorescence. More differentiated BE marker genes are downregulated during progression to EAC, suggesting undifferentiated BE subpopulations contribute to EAC. We also identified several gene fusions absent in paired BE and normal esophagus but present in EAC. Our findings are critical for the BE-to-EAC transition and have the potential to promote early diagnosis, prevention, and improved treatment strategies for EAC.

Risk of De Novo Barrett's Esophagus Post Sleeve Gastrectomy: A Systematic Review and Meta-Analysis of Studies with Long-Term Follow-Up.

BACKGROUND & AIMS: Sleeve gastrectomy (SG) is one of the most commonly performed bariatric procedures worldwide. Gastroesophageal reflux disease (GERD) is a major concern in patients undergoing SG and is a risk factor for Barrett's esophagus (BE). We conducted a systematic review and meta-analysis to assess the incidence of and analyze predictive factors for post-SG BE. METHODS: A comprehensive literature search was conducted in April 2024, for studies reporting on incidence of BE, erosive esophagitis (EE), and hiatal hernia (HH) post-SG. Primary outcomes were post-SG pooled rates of de novo BE, EE, GERD symptoms, proton pump inhibitor use, and HH. Meta-regression analysis was performed to assess if patient and post-SG factors influenced the rates of post-SG BE. RESULTS: Nineteen studies with 2046 patients (79% females) were included. Mean age was 42.2 years (standard deviation, 11.1) and follow-up ranged from 2 to 11.4 years. The pooled rate of de novo BE post-SG was 5.6% (confidence interval, 3.5-8.8). Significantly higher pooled rates of EE (risk ratio [RR], 3.37], HH (RR, 2.09), GER/GERD symptoms (RR, 3.32), and proton pump inhibitor use (RR, 3.65) were found among patients post-SG. GER/GERD symptoms post-SG positively influenced the pooled BE rates, whereas age, sex, body mass index, post-SG EE, and HH did not. CONCLUSIONS: Our analysis shows that SG results in a significantly increased risk of de novo BE and higher rates of EE, proton pump inhibitor use, and HH. Our findings suggest that clinicians should routinely screen patients with SG for BE and future surveillance intervals should be followed as per societal guidelines.

Robotic-Assisted and Laparoscopic Bariatric Surgeries Still Have Clinically Comparable Outcomes.

PURPOSE: Bariatric surgery is considered the main treatment option for patients with severe obesity. The objective of our study is to compare intra- and postoperative outcomes between the robotic and laparoscopic approaches within the sleeve gastrectomy (SG), duodenal switch (DS), and Roux-en-Y gastric bypass (RYGB). MATERIALS AND METHODS: The data from the MBSAQIP were collected for patients who underwent SG, DS, and RYGB between 2015 and 2021. The postoperative and procedural outcomes including 30-day morbidity and mortality as well as operation length were analyzed using regression models. RESULTS: Our analysis included 1,178,886 surgeries with SG comprising the majority (70%) followed by RYGB (28%) and DS (1%). Other than a higher adjusted risk of unplanned reoperation for robotic RYGB (relative risk (RR) 1.07) and a statistically significant higher rate of postoperative wound disruption in robotic SG for robotic surgery (RR 1.56), there were no statistically significant between-approach differences including infection, wound disruption, death, or reoperation for DS, RYGB, or SG. Our data showed no significant difference in anastomotic leak rate between laparoscopic and robotic approaches in either the DS (p = 0.521) or RYGB (p = 0.800) procedures. Across our study period, the median operation lengths decreased significantly per year for both the robotic SG and DS. CONCLUSIONS: Robotic and laparoscopic bariatric surgical procedures have statistically similar 30-day patient outcomes. Robotic bariatric procedures do have significantly longer median operative times than laparoscopic procedures. The decision to use a robotic approach or laparoscopic approach should be made based upon surgeon experience and possibly cost.

Video consent significantly improves patient knowledge of general surgery procedures.

INTRODUCTION: Informed consent is essential in ensuring patients' understanding of their medical condition, treatment, and potential risks. The objective of this study was to investigate the impact of utilizing a video consent compared to standard consent for patient knowledge and satisfaction in selected general surgical procedures. METHODS AND PROCEDURES: We included 118 patients undergoing appendectomy, cholecystectomy, inguinal hernia repair, and fundoplication at two hospitals in Omaha, NE. Patients were randomized to either a standard consent or a video consent. Outcomes included a pretest and posttest objective knowledge assessment of their procedure, as well as a satisfaction survey which was completed immediately after consent and following discharge. Given the pre-post design, a linear mixed-effect model was estimated for both outcomes. A two-way interaction effect was of primary interest to assess whether pre-to-post change in the outcome differed between patients randomized to standard or video consent. RESULTS: Baseline characteristics were mostly similar between groups except for patient sex, p = 0.041. Both groups showed a statistically significant increase in knowledge from pretest to posttest (standard group: 0.25, 95% CI 0.01 to 0.51, p = 0.048; video group: 0.68, 95% CI 0.36 to 1.00, p < 0.001), with the video group showing significantly greater change (interaction p = 0.043) indicating that incorporating a video into the consent process resulted in a better improvement in patient's knowledge of the proposed procedure. Further, both groups showed a decrease in satisfaction post-discharge, but no statistically significant difference in the magnitude of decrease between the groups (interaction p = 0.309). CONCLUSION: Video consent lead to a significant improvement in a patient's knowledge of the proposed treatment. Although the patient satisfaction survey didn't show a significant difference, it did show a trend. We propose incorporating videos into the consent process for routine general surgical procedures.

Bariatric Surgery Outcomes in Patients with Inflammatory Bowel Disease in the United States: An Analysis of the Nationwide Readmissions Database.

PURPOSE: Bariatric surgery has been reported to produce durable weight loss in the management of obesity; sleeve gastrectomy (SG) is the most common bariatric procedure. Obesity is a common comorbidity of inflammatory bowel disease (IBD), and the impact of IBD on short-term SG outcomes has not been widely reported. This study assessed whether IBD was associated with adverse post-SG outcomes. MATERIALS AND METHODS: Hospitalizations of patients undergoing SG in the United States were identified using the 2010-2020 Nationwide Readmissions Database (NRD) and stratified by IBD diagnosis. The SG cohort was propensity-matched based on age, biological sex, body mass index (BMI), comorbid diabetes, hypertension, depression, chronic obstructive pulmonary disease, and discharge in quarter four. Primary aims were to compare in-hospital mortality, post-operative complications, and all-cause 90-day readmission between patients with and without IBD. Secondary outcomes were length of stay (LOS) and total hospital cost. RESULTS: A total of 2030 hospitalizations were matched. The odds of complication were 48% higher for hospitalizations of patients with IBD (11.1% vs. 7.8%; aOR 1.48, aOR 95% CI 1.10-2.00, p = .009). The most common complication was nausea (4.9% vs. 3.7%, p = .187). No statistically significant difference was observed for all-cause 90-day readmissions, LOS, or hospital cost. CONCLUSION: Hospitalizations of patients with IBD who underwent SG experienced significantly higher post-operative complication rates. However, the similar lengths of stay and readmission rates compared to propensity-matched SG hospitalizations without IBD suggest many complications were minor. SG remains a safe weight loss procedure for patients suffering from IBD and obesity.

miRNA profiling of esophageal adenocarcinoma using transcriptome analysis.

Esophageal adenocarcinoma (EAC) occurs following a series of histological changes through epithelial-mesenchymal transition (EMT). A variable expression of normal and aberrant genes in the tissue can contribute to the development of EAC through the activation or inhibition of critical molecular signaling pathways. Gene expression is regulated by various regulatory factors, including transcription factors and microRNAs (miRs). The exact profile of miRs associated with the pathogenesis of EAC is largely unknown, though some candidate miRNAs have been reported in the literature. To identify the unique miR profile associated with EAC, we compared normal esophageal tissue to EAC tissue using bulk RNA sequencing. RNA sequence data was verified using qPCR of 18 selected genes. Fourteen were confirmed as being upregulated, which include CDH11, PCOLCE, SULF1, GJA4, LUM, CDH6, GNA12, F2RL2, CTSZ, TYROBP, and KDELR3 as well as the downregulation of UGT1A1. We then conducted Ingenuity Pathway Analysis (IPA) to analyze for novel miR-gene relationships through Causal Network Analysis and Upstream Regulator Analysis. We identified 46 miRs that were aberrantly expressed in EAC compared to control tissues. In EAC tissues, seven miRs were associated with activated networks, while 39 miRs were associated with inhibited networks. The miR-gene relationships identified provide novel insights into potentially oncogenic molecular pathways and genes associated with carcinogenesis in esophageal tissue. Our results revealed a distinct miR profile associated with dysregulated genes. The miRs and genes identified in this study may be used in the future as biomarkers and serve as potential therapeutic targets in EAC.

Bariatric Surgery Emergencies in Acute Care Surgery.

Patients who have undergone bariatric surgery present unique challenges in the acute care surgery setting. This review includes the presentation, workup, and management of most common bariatric surgery emergencies encountered by acute care surgery.

Robotic-Assisted Bariatric Surgery Is Associated with Increased Postoperative Complications Compared to Laparoscopic: a Nationwide Readmissions Database Study.

PURPOSE: Robotic-assisted (RA) bariatric surgery has been increasingly used without consistent benefit over a laparoscopic approach (LA). We compared intra- and post-operative complications and 30- and 90-day all-cause readmissions between RA and LA using the Nationwide Readmissions Database (NRD). MATERIALS AND METHODS: We identified hospitalizations with adult patients who underwent RA or LA bariatric surgery from 2010 to 2019. Primary outcomes included intra- and post-operative complications and 30- and 90-day all-cause readmissions. Secondary outcomes included in-hospital death, length of stay (LOS), cost, and cause-specific readmissions. Multivariable regression models were estimated; analyses accounted for the NRD sampling design. RESULTS: A total of 1,371,778 hospitalizations met inclusion criteria with 7.1% using RA. Patient demographic and clinical characteristics were mostly similar between groups. Adjusted odds of complication were 13% higher for RA (adjusted odds ratio [aOR]: 1.13, 95% CI: 1.03-1.23 p = .008); aORs differed across bariatric procedures. The most common complications included nausea/vomiting, acute blood loss anemia, incisional hernia, and transfusion. Adjusted odds of 30- and 90-day readmission were 10% higher for RA (aOR: 1.10, 95% CI: 1.04-1.17, p = .001 and aOR: 1.10, 95% CI: 1.04-1.16, p <.001, respectively). LOS was similar (1.6 vs. 1.6 days, p = .253); although, hospital costs were 31.1% higher for RA ($15,806 vs. $12,056, p < .001). CONCLUSION: RA bariatric surgery is associated with 13% higher odds of complication, 10% higher odds of readmission, and 31% hospital costs. Subsequent studies are required using databases that can include additional patient-, facility-, surgery-, and surgeon-specific characteristics.

A Primer on General Surgery Applicants Who Have Graduated From Indian Medical Schools.

Background: Graduates of Indian medical schools account for the greatest proportion of non-US born international medical graduates applying to general surgery residency programs.Purpose: Provide information to facilitate fair and holistic review of applicants from Indian medical schools.Research Design: Comprehensive review of the Indian medical education system, including history, regulatory agencies, medical school admission, curriculum, cultural differences, immigration issues, and outcomes after residency.Results: The Indian medical education system is one of the world's oldest. The number of medical schools and graduates continues to increase. Medical school admission criteria are variable. Recent regulatory changes have improved the quality of applicants entering the US. Emphasis on academic performance over volunteerism as well as communication styles differ from US graduates. The success of graduates during and after residency is well documented.Conclusions: Understanding the differences in the US and Indian medical education systems will provide a basis for the fair evaluation of applicants.

Long-term survival outcomes associated with robotic-assisted minimally invasive esophagectomy (RAMIE) for esophageal cancer.

BACKGROUND: Minimally Invasive esophagectomy for esophageal cancer is associated with less morbidity compared to open approach. Whether robotic-assisted minimally invasive esophagectomy (RAMIE) results in better long-term survival compared with open esophagectomy (OE) and minimally invasive esophagectomy (MIE) is unclear. METHODS: We analyzed data from the National Cancer Database (NCDB) for patients with primary esophageal cancers who underwent esophagectomy in 2010-2017. Those with unknown staging, distant metastasis, or diagnosed with another cancer were excluded. Patients were stratified by RAMIE, MIE, and OE operative techniques. The Kaplan-Meier method and associated log-rank test were employed to compare unadjusted survival outcomes by surgical technique, our primary outcome. Multivariable Cox proportional hazards regression model was employed to discern factors independently contributing to survival. RESULTS: A total of 5170 patients who underwent esophagectomy were included in the analysis; 428 underwent RAMIE, 1417 underwent MIE, and 3325 underwent OE. Overall median survival was 42 months. In comparison to RAMIE, there was an increased risk of death for those that underwent either MIE [Hazard Ratio (HR) = 1.19; 95% Confidence Interval (CI): > 1.00 to 1.41; P < 0.047)] or OE (HR = 1.22; 95% CI: 1.04 to 1.43; P < 0.017). Academic vs community program facility type was associated with decreased risk of death (HR = 0.84; 95% CI: 0.76 to 0.93; P < 0.001). In general, males from areas of lower income with advanced stages of cancer who received neoadjuvant chemotherapy or radiation were at increased risk of death. Factors that were not associated with survival included race and ethnicity, Charlson-Devo Score, type of health insurance, zipcode level education, and population density. CONCLUSIONS: Overall survival was significantly longer in patients with esophageal cancers that underwent RAMIE in comparison to either MIE or OE in a 7-year NCDB cohort study.

Robotic Hiatal Hernia Repair Associated with Higher Morbidity and Readmission Rates Compared to Laparoscopic Repair: 10-Year Analysis from the National Readmissions Database (NRD).

BACKGROUND: Laparoscopic techniques have been used for hiatal hernia repair. Robotic-assisted repairs have been increasingly used with unproven benefits. The aim of this study was to compare outcomes between laparoscopic and robotic-assisted hiatal hernia repair. METHODS: The Nationwide Readmissions Database (NRD) was used to identify hospitalizations for laparoscopic or robotic hiatal hernia repair from 2010 to 2019. Primary outcomes included post-operative complications and 30- and 90-day readmission rates. Secondary outcomes included in-hospital death, length of stay, and inflation-adjusted hospital cost. Multivariable models were estimated for overall complication and readmission rates. RESULTS: Approximately 517,864 hospitalizations met inclusion criteria with 11.3% including robotic repairs. Robotic repair was associated with a higher overall complication rate (9.2% vs. 6.8%, odds ratio [OR]: 1.4, 95% CI: 1.3-1.5, p < .001); however, the trend showed more similar complication rates across years. The higher overall complication rate remained after adjusting for patient and facility characteristics (adjusted OR [aOR]: 1.3, 95% CI: 1.2-1.4, p < .001). Robotic repairs were associated with higher 30-day (6.1% vs. 7.4%, aOR: 1.2, 95% CI: 1.2-1.3, p < .001) and 90-day readmission rates (9.4% vs. 11.2%, aOR: 1.2, 95% CI: 1.2-1.3, p < .001). In-hospital mortality and length of stay were similar, although, higher hospital costs were associated with robotic repairs. Both complications and readmission rates were lower as annual procedural volume increased. CONCLUSION: Robotic repairs had higher unadjusted and adjusted complication and readmission rates. The overall complication rate has shown a trend towards improvement which may be a result of increasing experience with robotic surgery.

The Role of Microbiota in the Pathogenesis of Esophageal Adenocarcinoma.

Esophageal adenocarcinoma (EAC) is associated with poor overall five-year survival. The incidence of esophageal cancer is on the rise, especially in Western societies, and the pathophysiologic mechanisms by which EAC develops are of extreme interest. Several studies have proposed that the esophageal microbiome may play an important role in the pathophysiology of EAC, as well as its precursors-gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE). Gastrointestinal microbiomes altered by inflammatory states have been shown to mediate tumorigenesis directly and are now being considered as novel targets for both cancer treatment and prevention. Elucidating molecular mechanisms through which the esophageal microbiome potentiates the development of GERD, BE, and EAC will provide a foundation on which new therapeutic targets can be developed. This review summarizes current findings that elucidate the molecular mechanisms by which microbiota promote the pathogenesis of GERD, BE, and EAC, revealing potential directions for additional research on the microbiome-mediated pathophysiology of EAC.

Impact of Paraesophageal Hernia Repair on Respiratory Function: A Systematic Review.

Background and Objectives: Surgical repair of hiatal and paraesophageal hernia is widely accepted for the treatment of gastroesophageal reflux symptoms. The respiratory benefit of this surgery is less clear. The objective of this review is to quantify the benefit to pulmonary function and subjective dyspnea of paraesophageal hernia repair with the aim of refining the indications and contraindications for elective paraesophageal hernia repair. Methods: Articles were gathered from systematic searches of the Medline Complete Database via the Creighton University Health Sciences Library literature search services. Publications with both pre and postoperative pulmonary function data or both pre and postoperative subjective dyspnea data with regards to surgical paraesophageal hernia repair were included. Results: Six studies were included in this review. The majority of studies in this review show improvement in pulmonary function postoperatively with regards to FEV1, FVC, and VC when stratified by % intrathoracic stomach (ITS), particularly in groups >50% ITS. No significant change was seen in postoperative DLCO or FEV1/FVC. Conclusion: Paraesophageal hernia repair has shown to improve pulmonary function both objectively and subjectively. This review was limited by the paucity of literature on the subject as well as the lack of a standardized method for measurement of %ITS.

Esophagogastric Junction Morphology on Hill's Classification Predicts Gastroesophageal Reflux with Good Accuracy and Consistency.

INTRODUCTION: Hill's classification provides a reproducible endoscopic grading system for esophagogastric junction morphology and competence, specifically whether the gastroesophageal flap valve (GEFV) is normal (grade I/II) or abnormal (grades III/IV). However, it is not routinely used in clinical practice. We report a systematic review and meta-analysis to determine association between abnormal GEFV and gastroesophageal reflux disorder (GERD). METHODS: A comprehensive literature search of MEDLINE and Scopus databases was conducted to identify studies that reported the association between abnormal GEFV and GERD. The search and quality assessment were performed independently by two authors. Fixed- and random-effects meta-analyses were conducted using symptomatic GERD and erosive esophagitis as outcomes. RESULTS: A total of 11 studies met inclusion criteria that included a total of 5054 patients. In the general population, patients with abnormal GEFV had greater risk of symptomatic GERD compared to patients with a normal GEFV (risk ratio [RR] 1.88, 95% CI 1.57-2.24). Further, in patients with symptomatic GERD, patients with abnormal GEFV had greater risk of erosive esophagitis compared to patients with normal GEFV (RR 2.17, 95% CI 1.40-3.36). Finally, the specificity of abnormal GEFV for symptomatic GERD was 73.3% (95% CI 69.3-77.0%) and 75.7% (95% CI 65.9-83.4%) for erosive esophagitis in symptomatic GERD. CONCLUSION: Our systematic review and meta-analysis showed consistent association between abnormal GEFV indicated by Hill's classification III/IV and symptomatic GERD and erosive esophagitis. Our recommendation is to include Hill's classification in routine endoscopy reports and workup for GERD.

Pressure-Sensing Gastric Calibration Tube for Minimizing Sleeve Volume Variation in Sleeve Gastrectomy Compared with Current Standard Technique.

The sleeve gastrectomy technique is dependent on the size of the bougie and the surgeon's technical skills. Standardization of the sleeve gastrectomy technique may potentially minimize the volume inconsistency and improve outcomes. A volume and pressure-sensitive gastric calibration tube may create a standard sleeve size and minimize interoperator variation. The objective of preliminary testing was to establish the variability of sleeve gastrectomy size in gastric explants, and to compare that with the variability of sleeve gastrectomy size when performed with a volume and pressure-sensitive gastric calibration tube. Three operators performed six sleeve gastrectomies each on commercially processed porcine gastric explants, half with a 40 Fr bougie, and a half with a pressure-sensing and volume-controllable gastric calibration tube prototype. The resulting sleeves were evaluated using standard statistical methods. The pressure-sensitive gastric calibration tube demonstrated superior consistency to a standard 40 Fr bougie by common measures of variation. However, further investigation is warranted to characterize the significance of this difference.

Obesity is Associated with Significantly More Anastomotic Leaks After Minimally Invasive Esophagectomy: A NSQIP Database Study.

BACKGROUND: This study assessed the association between obesity status and postoperative outcomes for patients who underwent transthoracic esophagectomy (TTE) or transhiatal esophagectomy (THE) via an open or minimally invasive (MIE) surgical approach. METHODS: The 2016-2018 national surgical quality improvement program esophagectomy-targeted database was used to identify adult patients who underwent TTE or THE, with stratification of patients by obesity status and surgical approach. Using a multivariable regression model for each outcome, the study evaluated whether the adjusted difference between obese and non-obese patients varied between the open and MIE approaches. RESULTS: In this study, 1260 patients underwent TTE (28.1% obese; 51.7% MIE), and 386 patients underwent THE (29.3% obese; 43.0% MIE). The obese patients in the TTE cohort who underwent MIE had 3.4 times higher odds of failing to wean from mechanical ventilation within 48 h (95% confidence interval [CI] 1.8-6.4), 1.7 times greater odds of returning to the operating room (95% CI 1.1- 3.0), 2.4 times greater odds of having an index hospital stay longer than 30 days, (95% CI 1.0-6.0), and 2.5 times greater odds of experiencing a grade 3 anastomotic leak (95% CI 1.3-4.9). No differences between obese and non-obese patients were observed among those who underwent TTE via an open approach or THE. CONCLUSIONS: The findings showed that obese patients undergoing TTE via an MIE approach had greater odds of failing to wean from mechanical ventilation within 48 h, returning to the operating room, having an index hospital stay longer than 30 days, and having a grade 3 anastomotic leak. These results are in contrast to the previously published literature and require replication as additional data become available.

Retraction Note to: TREM-1 associated macrophage polarization plays a significant role in inducing insulin resistance in obese population.

An amendment to this paper has been published and can be accessed via the original article.