Society: SSAT

BACKGROUND: Despite the advances in the multidisciplinary treatment of gastric adenocarcinoma, the overall 5-year survival remains only 33.3% in North America. R0 resection with adequate lymphadenectomy remains the mainstay therapy. The National Comprehensive Cancer Network (NCCN) guidelines recommend harvesting 16 or more lymph nodes for adequate staging. This study examines the rate of adequate lymphadenectomy over recent years and its potential association with overall survival.

METHOD: The National Cancer Database (NCDB) was utilized to identify patients who underwent surgical treatment for gastric adenocarcinoma between 2006-2019. Trend analysis was performed for lymphadenectomy rates during the study period. Logistic regression and the Kaplan-Meier survival methods were utilized.

RESULTS: A total of 57,039 patients who underwent surgical treatment for gastric adenocarcinoma were identified. Most patients were male (65.9%), Caucasian (73.8%), with a mean age of 67 years old (SD±11.3). Subtotal gastrectomy was the most common surgery type (48%), followed by total gastrectomy (42.4%). A total of 64.2% of patients underwent surgery in low-volume facilities (1-10 gastrectomies/year). Most patients were American Joint Commission on Cancer (AJCC) stage III (37.6%) and were treated in Academic Research Programs (44.6%). Only 50.6% of the patients had retrieval of ≥16 nodes. Trend analysis showed that this rate significantly improved over the years, from 35.1% in 2006 to 63.3% in 2019 (Cochran-Armitage test: p<.0001). The independent predictors of adequate lymphadenectomy included surgery between 2015-2019 (OR: 1.68; 95%CI: 1.57-1.70), surgery in a high-volume facility with ≥ 31 gastrectomies/year (OR:1.68; 95%CI:1.54-1.84), AJCC stage III (OR: 1.55; 95%CI:1.48-1.62), and preoperative chemotherapy (OR:1.53; 95%CI:1.46-1.61). Compared to patients who received adequate lymphadenectomy, patients who underwent gastrectomy with the removal of < 16 lymph nodes had a worse overall survival: 43 months versus 59 months (Log-Rank: p<.0001). Adequate lymphadenectomy was independently associated with improved overall survival (HR:0.80; 95%CI:0.78-0.82). Other factors associated with improved survival included Asian race (HR:0.72; 95%CI:0.68-0.76), surgery in an Academic facility (HR: 0.91; 95%CI:0.88-0.95), high-volume facility (HR:0.87; 95%CI:0.81-0.90), surgery between 2015-2019 (HR:0.87; 95%CI:0.84-0.90), and receipt of perioperative chemotherapy (HR: 0.62;95%CI:0.59-0.66).

CONCLUSIONS: Although there was a significant improvement in the rate of adequate lymphadenectomy over the study period, as of 2019, 36.7% of patients lacked removal of 16 lymph nodes or more, which was independently associated with poorer overall survival. These findings identify areas for improving the quality of surgical treatment of gastric cancer in North America is warranted.

Figure 1. Mosaic plots showing the increased rate of adequate lymphadenectomy over the years. <br /> Footnote:<b> A:</b> Lymphadenectomy < 16 nodes; <b>B:</b> Lymphadenectomy ≥ 16 nodes. Cochran-Armitage trend test: P <.0001.

Figure 1. Mosaic plots showing the increased rate of adequate lymphadenectomy over the years.
Footnote: A: Lymphadenectomy < 16 nodes; B: Lymphadenectomy ≥ 16 nodes. Cochran-Armitage trend test: P <.0001.

Kaplan-Meier plot comparing the overall survival between patients who underwent gastrectomy for adenocarcinoma with and without adequate lymphadenectomy.<br /> Footnote:<b> Group 1:</b> Lymphadenectomy < 16 nodes; <b>Group 2: </b>Lymphadenectomy ≥ 16 nodes.

Kaplan-Meier plot comparing the overall survival between patients who underwent gastrectomy for adenocarcinoma with and without adequate lymphadenectomy.
Footnote: Group 1: Lymphadenectomy < 16 nodes; Group 2: Lymphadenectomy ≥ 16 nodes.

Background: Due to the aging population, the number of elderly patients (>80 years old) diagnosed with locally advanced gastric cancer (LAGC) in the US will continue to rise. According to NCCN guidelines, neoadjuvant treatment (NAT) is a recommended approach for locally advanced disease. However, most patients over the age of 80 have upfront surgery.

Methods: Patients 80 years and older who had a surgical resection for LAGC (stage IB-IIIC) were identified in the 2003-2017 National Cancer Database. Patients were grouped based on therapy sequence: those that received NAT prior to surgery, those that underwent surgery alone, and those that underwent up front surgery followed adjuvant therapy (UFS+AT). Multivariable logistic regressions were used to determine independent factors for R0 resection and receipt of AT and NAT. Overall survival (OS) from time of surgery was assessed using Kaplan-Meier analyses and Cox-proportional-hazards regression analyses examined for the impact of treatment pathway on the risk of death.

Results: Of 2731 patients, 68% received surgery alone, 18% had UFS+AT, and the remaining 15% NAT. During the latter half of the study period there was an increase in usage of NAT to 23% from 6%. Factors independently associated with receipt of NAT were diagnosis year 2011-2017, age <86, male gender, treatment at an academic facility, comorbidity score of 0, cT3 tumors, and cN1-2 disease (all p<0.001). Factors independently associated with receipt of adjuvant therapy were diagnosis year 2011-2017, age <86, Asian/Pacific Islander race, comorbidity score of 0, travel distance of 50-100mi, and node positive disease (all p<0.001). Factors independently associated with R0 resection include extent of surgery more than local excision, later date of diagnosis, treatment at an academic center, cT1 and cN0 disease, and grade I-II tumors (all p<0.001). Kaplan-Meier analyses showed a 29.5 month median OS for the NAT group (95% CI, 22.8-35.9) vs 29.5 months for surgery with AT (95% CI, 25.9-39.6) and 17.8 months for surgery alone (95% CI, 16.1-19.6) (P <0.0001). In a landmark analysis used to account for immortal time bias, NAT significantly improved overall survival compared to the UFS+AT group (p=0.018).

Conclusion: Of older patients with LAGC, less than 1/3 received some form of adjuvant or neoadjuvant therapy, which is the standard of care. NAT was associated with improved survival when compared to surgery followed by adjuvant therapy. Clinicians should advocate for receipt of NAT in older patients with LAGC.

Introduction: An estimated 30% of patients may develop de-novo or worsen pre-existing gastroesophageal reflux disease (GERD) after Sleeve Gastrectomy (LSG). For those with medically refractory GERD after LSG, laparoscopic conversion of LSG to Gastric Bypass (RYGB) has been offered and a few single center cases series (with 10 to 25 patients) and a multi-center study with 80 patients have been published. However, all studies present mostly symptoms resolution as the outcome measure and surgical technique varied. We evaluated perioperative, physiologic, endoscopic, and symptomatic outcomes of laparoscopic conversion of LSG to RYGB due to GERD following a standardized technique.
Methods: All consecutive patients converted from LSG to RYGB due to GERD at a quaternary medical center were studied. Laparoscopic technique for conversion included routine esophageal hiatus dissection and repair, creation of a small 3 to 4-cm-long gastric pouch while removing any excess fundus with the division of the lateral aspect of the pouch at 2 cm lateral from the Angle of His, circular stapled gastrojejunostomy, and closure of both mesenteric defects. Primary outcomes were changes in distal esophageal acid exposure measured by 48h wireless pH-monitoring, esophagitis, and GERD symptoms. Secondary outcomes were perioperative outcomes.
Results: 35 patients were studied, 100% female, median age 41 years (range 30-69), median BMI 38.3 kg/m2 at conversion (range 27.3-52.5). Hiatal hernia was present in 29 patients (83%, 2-10cm), esophagitis was found in 21 patients (60%, LA Grades C or D in 7 patients), and Barrett’s Esophagus (BE) in 3 (9%). Median follow-up was 22 months (range 3 to 58). All parameters of distal esophageal acid exposure decreased significantly and normalized in all patients after conversion (Table). Esophagitis healed in all patients. Complete symptom resolution occurred in 30/35 (86%), and five had residual GI symptoms. Median BMI at latest follow-up decreased by 6.5 kg/m2 (range 0.4-23.3). Perioperative complications occurred in 6 patients (17%); three were GJ strictures treated with endoscopic dilation, two post-operative bleeding that required transfusion, one readmission for dehydration. Length of stay was 2.4 days (range 2-5). There were no reoperations or deaths.
Conclusion: These results provide objective evidence to support that conversion from LSG to RYGB due to GERD, when following certain technical aspects, is an effective treatment. Laparoscopic LSG conversion to RYGB should be considered the preferred method to treat medically refractory GERD after LSG.

Background: Sleeve gastrectomy is currently the most performed bariatric technique in several countries. The main drawback of this operation is probably postoperative gastroesophageal reflux disease (GERD). The GERD incidence may be related to technical points leading to disruption of natural antireflux mechanism or creating points of pressurization of the gastric tube. There is no standardization of technique what may explain differences of GERD incidence among distinct groups. However, it is not uncommon to find a variable range of GERD within the experience of the same surgeon. This may lead to the assumption that two gastric tubes may not be born the same even though performed by the same surgeon. The main goal of this study is to evaluate the agreement of technical key-points based on auto and heteroevaluation.
Methods: Ten experienced (> 30 sleeve gastrectomy/year) surgeons (9 males, mean age 55years) were invited to participate in the study. Individuals were asked to send an unedited video with a typical laparoscopic sleeve gastrectomy performed by them. The videos were cropped into small clips comprising 11 key-points of the technique. All anonymized clips (including their own) were returned to all surgeons. Individuals were asked to agree or not with the technique demonstrated. We followed the Delphi process for consensus evaluation. After the round in which all surgeons declared their agreement or not with the technique (first round), the percentage of investigators that agreed was presented to the entire group and they were asked for a second vote (second round). Cronbach Alpha test was used for internal consistency. Inter-rater Reliability (IRR) was calculated to assess inter-observer agreement.
Results: Table 1 shows the agreement rate among surgeons. During first round, agreement was poor/fair for all points except hiatal repair that had a very good agreement. For second round, there was slight increase in agreement for distance esophagogastric junction / proximal stapling and gastric mobilization for stapling; and slight decrease in agreement for gastric tube final shape. Only 1 (10%) surgeon recognized that he evaluated his own video. Five (50%) of the surgeons disagreed with themselves in regards to 1 or more points: diaphragmatic crus dissection (n=2), distance pylorus / distal stapling (n=2), angle of His (n=1), distance esophagogastric junction / proximal stapling (n=1), and omental fixation (n=1).
Conclusions: Laparoscopic sleeve gastrectomy lacks intra and intersurgeon agreement in technical key-points that may affect gastroesophageal reflux disease after the procedure.

Table 1. Round of voting for agreement on technical key-points for sleeve gastrectomy (10 clips / 10 surgeons). Value of K strength of agreement: < 0.20 Poor; 0.21 - 0.40 Fair; 0.41 - 0.60 Moderate; 0.61 - 0.80 Good; 0.81 - 1.00 Very good

Table 1. Round of voting for agreement on technical key-points for sleeve gastrectomy (10 clips / 10 surgeons). Value of K strength of agreement: < 0.20 Poor; 0.21 - 0.40 Fair; 0.41 - 0.60 Moderate; 0.61 - 0.80 Good; 0.81 - 1.00 Very good

Background: Marginal ulceration (MU) is a significant cause of morbidity after Roux-en-Y gastric bypass (RYGB) surgery. Proton pump inhibitor (PPI) therapy is the mainstay of treatment, though the method of administration may vary. There is limited retrospective evidence that the use of “open-capsule” PPI (OC-PPI) improves the healing of MU after RYGB compared to “intact-capsule” PPI (IC-PPI). Yet, the data remains disputable with several confounding factors and effect modifiers that can cloud the result, necessitating further validation. This retrospective cohort study aims to compare the healing times of MU after RYGB when treated with OC-PPI versus IC-PPI.
Materials and Methods: We retrospectively analyzed patients with a history of RYGB who were diagnosed with gastrojejunal MU on endoscopy at a large, tertiary care center from January 1^st, 2012 to August 29^th, 2022. We identified all patients with documented healing times as treated with either OC-PPI or IC-PPI, followed by 1:4 matching for age and gender. Patients without documented healing, those requiring revision surgery or mechanical closure for treatment-resistant ulcers, and those with unclear PPI administration methods were excluded. The primary outcome was time to ulcer healing. The log-rank test was used to test the null hypothesis (no difference between the MU healing times in the two groups) followed by Kaplan Meier survival curve analysis.
Results: A total of 519 RYGB patients with confirmed MU were included for review. After stringent review, 33 patients were included in the OC-PPI group and 42 in the IC-PPI group for final analysis. There were more females in the IC-PPI group, but no difference in race, age, BMI, concurrent sucralfate usage, or other known risk factors for marginal ulcer formation, aside from the use of non-steroidal anti-inflammatories (NSAIDs), which was more common in the OC-PPI group. There was a significant decrease in mean [standard error] MU healing time by 147 days in the OC-PPI group compared to the IC-PPI group (164.82 [22.70] vs. 311.67 [50.61], respectively [p=0.02]). Kaplan Meier survival curve visualized a distinct divergence of healing time of MU at approximately 100 days (p=0.0135).
Conclusion: Our study showed a significantly shorter MU healing time using OC-PPI compared to IC-PPI in RYGB patients by 147 days. Further, the benefit of OC-PPI over IC-PPI persisted despite higher NSAID use in the OC-PPI group. These results are consistent with prior limited data and further support a growing paradigm shift to the use of OC-PPI as the standard of care in treating MU in gastric bypass patients. By reducing healing time and the need for repeated endoscopic monitoring of MUs, we not only improve bariatric outcomes for patients but also decrease the social and healthcare burden of post-surgical complications.

Introduction: Bariatric surgery is the most effective treatment for morbid obesity. Laparoscopic Sleeve Gastrectomy (LSG) is the most performed bariatric surgery. However, new weight-loss medications such as glucagon-like peptide-1 receptor agonists (e.g., Semaglutide), have attracted increased attention due to non-invasiveness and effectiveness in the short term. Our study aimed to assess the cost-effectiveness of Semaglutide compared to LSG.

Methods: A state-transition Markov cohort model was constructed to compare LSG with Semaglutide from the U.S. healthcare system’s perspective. The base case was a 45-year-old patient with Class II obesity having a BMI of 37. In the LSG strategy, patients were subjected to the risks of perioperative mortality and complications with resultant costs and initial decrement in quality of life (QOL). Both strategies experienced quality-of-life improvements associated with weight loss. Probabilities, costs and QOL estimates of the model were derived from published literature. Costs were reported in U.S. dollars ($) adjusted to the year 2022 using the consumer price index with health outcomes recorded in quality-adjusted life years (QALYs). A five-year time horizon with a cycle length of one month with the application of a 3% discount rate was utilized. The main outcome measure was the incremental cost-effectiveness ratio (ICER) with a willingness-to-pay threshold of $100,000/QALY. One-way and probabilistic sensitivity analyses were performed. Price-threshold analysis was also performed for the dominated strategy.

Results: At 5 years, LSG strongly dominated Semaglutide (ICER: -$238,686/QALY) due to the lower cost and higher effectiveness of the procedure. The results remained robust on one-way sensitivity analysis. Due to intolerance and other causes, ~20% of modeled patients dropped out of the Semaglutide strategy. LSG achieved and sustained greater weight loss over 5 years for the modeled patients compared to Semaglutide. (BMI of 29.9 vs. 33.1). Using a willingness-to-pay threshold of $100, 000 per QALY, LSG was cost-effective compared to Semaglutide with a probability of 0.01%, 46.41%, 96.08%, 99.93%, and 100% over 1, 2, 3, 4, and 5 years, respectively on probabilistic sensitivity analysis. The annualized price of Semaglutide to achieve non-dominance of LSG with an ICER threshold of $100,000/QALY was $5135, currently priced at $13,618.

Conclusion: LSG is cost-effective compared to Semaglutide for the treatment of Class II obesity, strongly dominating the medical therapy at 5 years. This is driven by higher cost, increased dropouts, and lower clinical effectiveness with Semaglutide. Future studies comparing these strategies on different classes of obesity would provide a better understanding regarding the optimal use of these treatment options.

Background: Obesity is a known risk factor for cancer, including pancreatic adenocarcinoma (PDAC). Bariatric surgery is the most effective treatment for obesity and metabolic comorbidities but has also been shown to reduce the risk of PDAC before the age of 50 and among patients with diabetes. We aim to characterize the effects of bariatric surgery on pancreatic cancer risk in the U.S. population using a large, population-based database.

Methods: We performed a retrospective cohort analysis utilizing the National Inpatient Sample (NIS) database from October 2015 to December 2020. All adult subjects with a BMI > 40 or BMI >35 with presence of other comorbidities – hypertension (HTN), Diabetes (DM), hyperlipidemia (HLD) and/or obstructive sleep apnea (OSA) – were identified and stratified into those with and without history of bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy). Baseline characteristics and comorbidities among the two groups were compared using chi-squared and Wilcoxon rank-sum tests. We then performed logistic regression analysis to assess the risk of PDAC after adjusting for risk factors, including tobacco use, acute and chronic pancreatitis, diabetes mellitus and various stages of obesity.

Results: Over 19 million subjects were included, 1,656,329 of whom had a history of bariatric surgery. Patients with a history of bariatric surgery had significantly lower rates of hypertension, hyperlipidemia, chronic kidney disease, tobacco use, and acute and chronic pancreatitis (p<0.001), while having higher rates of obstructive sleep apnea (p<0.001). History of bariatric surgery further significantly reduced the risk of PDAC (OR; 95% CI) on both univariable (0.50; 0.44-0.56) and multivariable analysis (0.68; 0.61-0.77) (p<0.001), when adjusted for multiple comorbidities and confounders.

Conclusion: Bariatric surgery independently exhibits a protective effect against PDAC oncogenesis. This is the largest study to date showing the benefits of surgically-assisted weight loss on PDAC risk. With advancements in minimally invasive bariatric procedures, expanded patient eligibility and acceptance of such procedures may serve to further reduce the burden of pancreatic cancer.

Table 1. Baseline characteristics

Table 2. Univariable and multivariable analysis of pancreatic cancer risk

Table 2. Univariable and multivariable analysis of pancreatic cancer risk

Esophagogastric junction adenocarcinomas (EGJA) have been surgically treated based on the epicentre of the tumor on pre-operative work up according to Siewert classification. Molecular classification may help to distinguish the tumor biologically and may add auxiliary information into treatment decision making. Immunohistochemistry is a cost-effective and easy-to-apply method that can be used instead of difficult and expensive molecular techniques. Aim: To classify the EGJA according to the immunoexpression of molecular markers and to compare these findings to Siewert classification. Methods: 71 patients with EJGA were enrolled from 2011 to 2018 for immunoexpression of markers by tissue microarray from specimens of biopsies and/or surgical tumor resection. Tumors were classified into four groups according to the immunoexpression: chromosomal instability (CIN): p53 and amplification of HER-2; Epstein-Barr virus (EBV): EBV in situhybridization and PD-L1; microsatellite instability (MSI): MLH-1 silencing; and genomically stable (GS): E-cadherin silencing. Siewert classification was defined according to endoscopy, computed tomography or surgical findings. Demographic data, clinical and histological features were evaluated. Results: Nineteen patients were classified as Siewert I, 27 as Siewert II and 25 as Siewert III. Male gender was associated to Siewert III (96%) compared to I (84%) and II (70%) (p=0.048). Clinical characteristics including age, body mass index, alcohol and cigarette consumption were similar in all three Siewert groups (p=NS). According to Lauren classification, the intestinal type was more frequently observed (74% in I, 85% in II and 56% in Siewert III). Positive p53 immunostaining was more significantly noticed in Siewert I (74%) and Siewert II (78%) than type III (16%) (p< 0.0001). HER-2 amplification was only detected in Siewert I (6/19; 31%) and II (5/27; 19%), while positive EBV was only seen in Siewert III patients (7/25; 28%). E-cadherin silencing was rarely and equally detected in all three Siewert groups (I= 16%; II= 15%; III= 13%). PD-L1 was positive in a high percentage of all three groups of patients (Siewert I= 42%; II= 54%; III= 42%) (p=0.59). MLH1 silencing was only observed in 3 patients, 2 in Siewert II and 1 in Siewert III group. Conclusions: 1. Immunohistochemical panel of markers helps to differentiate the EJGA and might influence on treatment strategy; 2. Siewert III tumors represent a distinct biological entity and should be treated differently; 3. High PD-L1 positivity in all sites of EJGA indicates that PD-L1 blockade may be utilized as a complementary therapy.

Flavio Roberto Takeda

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