SLEEVE GASTRECTOMY INHIBITS TUMOR FORMATION IN A MOUSE MODEL OF FAMILIAL ADENOMATOUS POLYPOSIS

Background: Gastroesophageal reflux disease (GERD), with or without hiatal hernia (HH), affects millions of individuals worldwide, with a significant economic impact and loss of health-related quality of life. Laparoscopic fundoplication is the surgical technique of choice for treating GERD, but only few studies report a follow-up beyond 15 years. In order to determine the best treatment option, it is important to assess the long-term outcome of LARS. The aim of this study was to evaluate the results at least 20 years after LARS performed for GERD and/or large HH at a single referral center for esophageal diseases.
Methods: We prospectively collected data on a cohort of consecutive patients who underwent LARS between 1992 and 2001 at our department. Patients were divided into two groups: a GERD group, comprising patients with pathological esophageal acid exposure, and large hiatal hernia (HH), including patients with >3 cm type I HH and types II-IV hiatal hernias. The study population flowchart is shown on Figure 1. Patients were followed up for at least 20 years using a symptom score (SS), endoscopy, barium-swallow, esophageal manometry, and 24-hour pH-monitoring. LARS was judged to have failed in any of the following cases: a) GERD symptom recurrence (SS >10); b) recurrence of esophagitis; c) HH recurrence or slipped-fundoplication; d) pathological 24-hour pH-monitoring; e) BE progression or onset of adenocarcinoma.
Results: The study population consisted of 137 patients: 107 in the GERD group and 30 in the HH group. The characteristics of patients in the two groups are shown on Figure 2. Conversion to open surgery proved necessary in 8 patients (5.8%), and intraoperative and perioperative complications were recorded in 9 patients (6.5%). At a median follow-up of 22 years, the outcome was positive in 84.1% of the GERD patients, and 63.3% of the HH patients. Revisional surgery was necessary in 9 (6.5%) patients (4 GERD and 5 HH patients). Indications for revisional surgery were a slipped fundoplication or hernia recurrence in 6 cases, a pH-detected abnormal acid reflux and esophagitis resistant to medical therapy in 2 cases, and the herniation of the stomach inside the fundoplication (telescoping) in one case. Overall, GERD patients had a better failure-free survival rate than HH patients (p=0.02). Two decades after LARS, 88.8% of GERD patients and 86.7% of HH patients were satisfied with the procedure.
Conclusion: The present study concerns one of the largest populations of patients who had undergone LARS to have been followed up for more than 20 years at a single center. The findings showed that laparoscopic antireflux surgery is effective and durable (for >20 years) in patients with uncomplicated GERD and, to a lesser extent, in those with a large hiatal hernia. The satisfaction rate more than 20 years after surgery almost reached 90%.

Introduction: Up to 15-20% of patients undergoing stoma reversal surgery develop post-operative morbidity which is related to conventional practices such as prolonged pre-operative fasting, mechanical bowel preparation, delayed post-operative ambulation or resumption of orals. Enhanced Recovery After Surgery (ERAS) pathways have the potential to reduce the length of hospitalization and improve perioperative outcomes in these patients. This study was conducted to evaluate the feasibility, efficacy, and safety of ERAS protocol in patients undergoing elective stoma reversal surgery.
Methods: This was a single-centre, prospective, open-labelled, parallel arm, superiority randomized controlled trial carried out in a tertiary care hospital. Consecutive patients above 18 years of age who needed elective reversal of ileostomy or colostomy were pre-operatively randomized into standard care and ERAS care groups. Patients with American Society of Anaesthesiologists class ≥ 3, those needing laparotomy to reverse stoma, patients with cardiac, renal, neurological illnesses, bedridden patients and those on steroid medications were excluded. Eligible patients were randomly assigned in 1:1 ratio to either the standard care or ERAS care groups using a serially numbered opaque sealed envelope upon ward admission. Block randomization was done with block sizes of 4 and 6. Primary outcome was the length of hospitalization (LOH). Functional recovery parameters such as time for resolution of ileus, time to resumption of liquid, solid diet, time taken for mobilization and morbidity parameters were assessed.
Results: A total of 80 patients were recruited for the study between October 2020 and June 2022 with 40 patients each randomized into standard and ERAS care groups. The two groups were comparable in terms of demographic and clinicopathological characteristics (Table 1). Compared with standard care group, ERAS care group patients had significantly reduced LOH (5.3 ± 0.3 vs 7 ± 2.6; mean difference: 1.73 ± 0.98; p=0.0008) (Table 2). Functional recovery was earlier in ERAS care group compared to standard care group such as early resolution of ileus (median-2 days; p<0.001), time to first stool (median-3 days; p=0.0002), time to resumption of liquid diet (median-3 days; p<0.001) and solid diet (median-4 days; p<0.001) (Table 2). Surgical Site Infections (SSIs) were significantly lesser in ERAS care group (12.5% vs 32.5%; p=0.03) while post-operative nausea/vomiting (p=0.08), pulmonary complications (p=0.17) and urinary tract infections (p=0.56) were comparable in both groups.
Conclusion: ERAS pathways are feasible, safe and significantly reduces LOH in patients undergoing elective stoma reversal surgery.

Introduction:
Leaks of the gastrointestinal tract are a devastating complication that can occur after foregut operations. It has been suggested that the pathogenesis of foregut leaks is directly influenced by the gut microbiome. The purpose of this study was to evaluate the composition of the microbiome within and between patients with gastrointestinal leaks to better understand the pathogenesis of these leaks.

Methods:
Patients undergoing interventions for gastrointestinal leaks from October 2021 to October 2022 were included in this study. During endoscopic and surgical interventions for gastrointestinal leaks, both microbial and host samples were collected. Genomic DNA of microbial samples were extracted and amplified. PCR products were sequenced using Illumina Nextera protocol. Effective sequence of bacterial 16S-rRNA gene was clustered into OTUs for analysis.

Results:
A total of 196 samples were collected from 16 patients (13 females; 3 males) with 49 samples used for the 16S analysis. The majority (56.2%) of patients required multiple interventions for their leaks, while a smaller portion (43.8%) underwent a single intervention. 42/49 samples (85.7%) included in the 16S analysis were from patients requiring multiple interventions with a mean of 4.6 interventions performed per patient in this group. In the entire cohort, Firmicutes was consistently the most abundant bacteria present. For patients that required multiple interventions, the microorganism composition changed over the course of treatment. At the index procedure, Firmicutes and Actinobacteria were on average the most abundant phyla present. By the end of treatment, Firmicutes remained dominant. However, abundances of Bacteroidetes and Proteobacteria increased, and the abundance of Actinobacteria decreased. Notably, there was a significant reduction in the Firmicutes to Bacteroidetes ratio by the end of treatment. In one patient who was not progressing well clinically, they were noted to have an increase in their Firmicutes to Bacteroidetes ratio and a much higher abundance of Proteobacteria when compared to other patients.

Conclusions:
In conclusion, data from our study indicates that the Firmicutes to Bacteroidetes ratio of the gut microbiome significantly changed throughout the treatment of gastrointestinal leaks. A better understanding of this ratio and its role in gastrointestinal leaks could allow for more effective prevention and treatment strategies.

Introduction: Existing human studies have shown conflicting effects of bariatric surgery on colorectal cancer (CRC) risk[1] [2]. These equivocal findings are likely due in part to the heterogeneity of CRC. We have previously found that sleeve gastrectomy (SG) leads to increased colonic tumor growth in a mouse model of colitis-associated cancer, but the effect of SG on genetic CRC syndromes such as Familial Adenomatous Polyposis (FAP) remains unknown. In the murine analogue of FAP, mice with a mutated Adenomatous Polyposis Coli (APC) allele, known as APC^Min, develop gastrointestinal (GI) tumors predominantly in the small bowel. Here we examine the effects of SG on tumor formation in APC^Min mice.

Methods: Thirty 12-week-old C57BL/6J-APC^Min mice were randomized to SG (n=18) or sham (n=12) operation. Five days postoperatively, the mice were begun on a high-fat diet to promote tumor formation. Mice were weighed daily for the first postoperative week and then at three-to-four day intervals until sacrifice 25 days after surgery. At sacrifice, tumors were counted in the colon and proximal, mid, and distal small bowel, and tumor numbers in SG and sham mice were compared using t-tests. Small bowel samples were analyzed for mRNA expression of five cytokines: IL-1b, IL-6, IL-23, IL-33, and TNFa. Additionally, RNA sequencing (RNA-Seq) was performed on colonic tissue to identify transcriptional differences between SG and sham mice.

Results: SG mice developed significantly fewer GI tumors than sham mice (10.9 vs 21.3; p < 0.0001; Figure 1A) with fewer tumors in the mid small bowel (1.7 vs 5.5; p < 0.0001; Figure 1B) and distal small bowel (6.8 vs 12.8; p < 0.01; Figure 1B). TNFa expression was significantly lower in SG mice while IL-1b, IL-6, and IL-23 trended lower. RNA-Seq showed upregulation of 209 genes and downregulation of 107 genes in SG mice compared to sham mice, and transcriptional pathway analysis demonstrated decreased expression of major histocompatibility complex (MHC) class I associated genes in SG mice compared to sham mice.

Conclusions: SG protects against APC-related tumors. SG is associated with a reduction in intestinal inflammatory cytokines and MHC class I pathways, highlighting a potential role of cell-mediated immunity in tumor control after SG.




[1] Bailly L, Fabre R, Pradier C, Iannelli A. Colorectal Cancer Risk Following Bariatric Surgery in a Nationwide Study of French Individuals With Obesity. JAMA Surg. 2020;155(5):395–402. doi:10.1001/jamasurg.2020.0089

[2] Tao, W., Artama, M., von Euler-Chelpin, M., Hull, M., Ljung, R., Lynge, E., Ólafsdóttir, G.H., Pukkala, E., Romundstad, P., Talbäck, M., Tryggvadottir, L. and Lagergren, J. (2020), Colon and rectal cancer risk after bariatric surgery in a multicountry Nordic cohort study. Int. J. Cancer, 147: 728-735. https://doi.org/10.1002/ijc.32770