Gastric Research Articles

The application of hepatopancreatoduodenectomy in advanced gallbladder carcinoma: Patients’ selection, surgical outcome and influence on survival compared to radical cholecystectomy

Aimto investigate hepatopancreatoduodenectomy (HPD) application in gallbladder carcinoma (GBC) and compare it to radical cholecystectomy (RC) regarding patients’ characteristics, surgical outcome and survival. MethodsPatients treated in our center were included. Three groups (HPD, RC, no-surgery) were compared. Comparisons included basic characteristics, liver function, tumor biomarkers, surgical complications, outcome, and survival. Differences in severity, surgical risks and survival were investigated. ResultsIn total, 19 patients in HPD, 89 in RC and 20 in no-surgery groups were included. Median follow-up was 42.0 months. Compared to RC, HPD group revealed increased severity represented by significantly higher rates of elevated ALT, AST, TB, DB, preoperative biliary decompression, T3/4, N1/2, stage III/IV, and MVI. Similar severity was observed between HPD and no-surgery groups. Additionally, HPD presented higher risks of perioperative bleeding, transfusion and complications (grade III/IV). Pancreatic fistula and delayed gastric emptying were most encountered in HPD and only one mortality was recorded. Although HPD had shorter survival in general population (HPD: 17 ± 5.804, RC: 49 ± 11.433,P < 0.001); however, in matched (PSM) advanced stages, its benefits matched RC (HPD: 17 ± 4.793, RC: 11 ± 1.169, P = 0.966). Significant survival advantages were observed when comparing HPD to no-surgery group (HPD: 17 ± 5.804, no-surgery: 7 ± 0.836, P = 0.013). ConclusionCases benefiting from HPD are usually severe and comparable to unresectable cases. Although HPD complexity and complication risks are higher than RC, the survival benefits of HPD in advanced GBC stages are not inferior. Thus, HPD is a valuable option in such patients and can be the only approach to achieve R0 resection.

Physiology and pharmacology of effects of GLP-1 based therapies on gastric, biliary and intestinal motility.

Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) and the dual GLP-1 and glucose dependent insulinotropic polypeptide (GIP) receptor co-agonist tirzepatide (referred to here collectively as "GLP-1-based therapy") are incretin-based therapies being used increasingly in the management of both type 2 diabetes (T2D) and obesity. They are now recognized to have beneficial effects beyond improved glycemic control and weight loss, including cardiovascular and renal protection. GLP-1-based therapy also slows gastric emptying, which has benefits (lowering postprandial glucose), but also potential risks (e.g. hypoglycemia in individuals on insulin or sulphonylurea therapy). Their effects on the gallbladder may also be beneficial, contributing to reducing postprandial triglycerides, but they also potentially increase the risk of biliary disease. In this review, we summarize the effects of GLP-1 and incretin-based therapeutics on gastric, biliary and small intestinal function. An improved understanding of these effects will optimize the use of these drugs.

Glucagon-like peptide-1 receptor agonists and impaired gastric emptying: a pharmacovigilance analysis of the US Food and Drug Administration adverse event reporting system

BackgroundGlucagon-like peptide-1 receptor agonists (GLP-1RAs) potentially increase the risk of pulmonary aspiration resulting from impaired gastric emptying (IGE). We evaluated the association between GLP-1RAs and IGE using the US Food and Drug Administration Adverse Event Reporting System (FAERS). MethodsWe analysed FAERS data from 2004 Q1 to 2024 Q1, identifying the top 10 drugs linked to IGE and determining the proportion of GLP-1RA use. Disproportionality analysis using the reporting odds ratio was conducted to assess the relative IGE risk for each drug. Logistic regression analysed the impact of age, weight, and sex on IGE risk. Cumulative incidence and time to onset of IGE events were examined using Kaplan–Meier and Weibull shape parameter tests. ResultsAmong the top 10 drugs associated with IGE reports, five were GLP-1RAs, accounting for 49.5% (982/1982) of cases. Dulaglutide (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.94–1.00, P=0.033) and semaglutide (OR 0.96, 95% CI 0.94–0.97, P=0.001) showed lower IGE risk with older age. For exenatide, higher weight (OR 0.99, 95% CI 0.98–1.00, P=0.033) and male sex (OR 0.39, 95% CI 0.20–0.68, P=0.033) were associated with lower IGE risk. Median onset times ranged from 40.5 days (semaglutide) to 107.5 days (tirzepatide) from intitiation of therapy. The Weibull shape parameter β was <1 for all GLP-1RAs, indicating a higher IGE risk early in treatment. ConclusionsGLP-1RAs were notably associated with reports of impaired gastric emptying in the FAERS. Age, weight, and sex were significantly associated with impaired gastric emptying risk for certain GLP-1RAs. IGE events tended to occur early in treatment, with risk diminishing over time. These findings provide valuable references for future research on perioperative safety with GLP-1RAs.

Cost-effectiveness analysis of tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced gastric or gastroesophageal junction adenocarcinoma: perspectives from the United States and China.

The efficacy of tislelizumab plus chemotherapy in improving progression-free survival (PFS) and overall survival (OS) in unresectable gastric or gastroesophageal junction cancer (GC/GEJC) has recently been emphasized. This study compared the cost-effectiveness of tislelizumab plus chemotherapy versus placebo plus chemotherapy for the United States (US) and Chinese populations. Using data from the RATIONALE-305 phase 3 trial, a Markov model was developed to analyze quality-adjusted life years (QALYs), incremental cost-effectiveness ratios (ICERs), incremental net health benefits (INHBs), and incremental net monetary benefits (INMBs). The health state utilities and direct medical costs were obtained from the relevant literature and local cost databases. The model uncertainty was evaluated using sensitivity analyses. In the base-case analysis, the addition of tislelizumab to chemotherapy yielded an ICER of $37,768.48 per QALY in China, slightly below the willingness-to-pay (WTP) threshold of $38,042.49 per QALY, showing marginal cost-effectiveness with an INHB of 0.05 QALYs and an INMB of $1,852.49. Subgroup analyses revealed ICERs of $23,853.52 for patients with a PD-L1 TAP score ≥ 5% (TAP ≥ 5%). In the US, the ICER was $502,786.22 per QALY in the intent-to-treat (ITT) and $321,395.28 per QALY in the TAP ≥ 5% subgroup, exceeding the US WTP threshold of $150,000.00. In China, tislelizumab plus chemotherapy is a cost-effective first-line therapy for unresectable GC/GEJC in both ITT and TAP ≥ 5% subgroups. In the US, tislelizumab plus chemotherapy is not cost-effective.

Robotic versus laparoscopic pancreaticoduodenectomy for pancreatic and periampullary tumors: a meta-analysis.

The value of robotic pancreaticoduodenectomy (RPD) compared with laparoscopic pancreaticoduodenectomy (LPD) for pancreatic and periampullary tumors is controversial. This study aims to assess the available literature and compare the short outcomes of RPD and LPD. The PubMed, Cochrane Library, Embase, and Web of Science databases were searched to identify available research published up to 24 July, 2024. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Seventeen studies with a total of 9417 patients (RPD group: 3334 patients; LPD group: 6083 patients) were included in this meta-analysis. The RPD group had lower overall morbidity (RR, 0.79), conversion (RR, 0.29) and blood transfusion rates (RR, 0.61), shorter length of stay (MD, -0.72 days), and higher number of harvested lymph nodes (MD, 0.62) than the LPD group. There were no significant differences in 90-day mortality (RR, 0.89), major complications (RR, 0.87), operative time (MD, -3.74 mins), blood loss (MD, -24.14 mL), reoperation (RR, 0.94), bile leak (RR, 0.62), postoperative pancreatic hemorrhage (RR, 0.96), postoperative pancreatic fistula (RR, 0.74), delayed gastric emptying (RR, 1.24), and R0 resection (RR, 1.00) between the groups. Compared with LPD, RPD for pancreatic and periampullary tumors could be safe and effective, and it has superior surgical outcomes. Further randomized controlled trials to verify the potential advantages of RPD over LPD are necessary. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=581133, identifier CRD42024581133.

Comparison between pancreatojejunostomy and pancreaticogastrostomy in pancreaticoduodenectomy in a gastroenterology and hepatology teaching hospital

Background: Pancreatoduodenectomy (PD) is a surgical procedure used to treat diseases of the pancreatic Head, the distal common bile duct (CBD), and the duodenum, as well as trauma to the head of the pancreas. Once the pancreatic head and the duodenum are resected, the surgeon needs to reconnect the stomach, the biliary tract, and the pancreatic stump. The technique for reconstructing the biliary tract is fairly standard, represented by the anastomosis of the CBD to the jejunum, but the reconstruction of the pancreatic stump is a matter of debate. In general, two procedures can be used: pancreaticojejunostomy (PJ), which is an anastomosis between the pancreatic stump and the jejunum, and pancreaticogastrostomy (PG), which is an anastomosis between the pancreatic stump and the stomach. Aim: The objective of this study was to compare the impact of PJ and PG on the occurrence of postoperative pancreatic fistula (POPF), morbidity, and mortality following PD. Patients and Methods: This study took place between April 1, 2021 and April 1, 2023 at Gastroenterology and Hepatology Teaching Hospital in Baghdad Medical City. The cases in the study were designed prospectively. It is a comparison between PG and PJ after undergoing Whipple surgery. A total of 30 patients were selected and divided into two groups. The first group consisted of 16 patients who underwent PJ, while the second group consisted of 14 patients who underwent PG. The cases were prepared in the surgical consultation clinic. On the one hand, through PG, it was determined whether the texture of the pancreas was soft and the size of the main pancreatic duct (MPD) was less than 3 mm. On the other hand, through PJ, it was determined whether the texture of the pancreas was firm or hard and the size of the MPD was more than 3 mm. Results: The age group of males and females ranged from 11 to 68 (median 57) years. There were a total of 16 males and 14 females. The ampullary tumor was present in 11 patients of the PJ group and 7 patients of the PG group. Histopathology of tumors showed adenocarcinoma in 13 patients of the PJ group and in 6 patients of the PG group. POPF occurred in 3 patients of the PJ group, type A in 1 patient and type B in 2 patients, and no POPF was observed in the PG group. Hemorrhage occurred in 1 patient of the PG group and 2 patients of the PJ group. Delayed gastric emptying occurred in 5 patients: 3 patients of the PJ group (type A) and 2 patients of the PG group. SSI (surgical site infection) occurred in 7 patients: 5 patients of the PJ and 2 patients of the PG group. Finally, mortality occurred in 3 patients of the PJ group. Conclusion: Pancreatic intestinal anastomosis must be tailored to the surgeon's preferences and experience level, and any innovative technique that reduces the prevalence of POPF is welcome in pancreatic surgery. PG seems to be associated with less POPF, morbidity, and mortality than PJ after undergoing Whipple surgery, especially given the soft texture of the pancreas and the size of the MPD &lt; 3 mm. Recommendations: 1. Because our study included a limited number of samples, further prospective randomized studies with larger samples are required to confirm that PG had fewer complications. 2 Surgeons should be encouraged to use PG more frequently in the future.

Central ligation or partial preservation of the right gastric artery does not seem to affect conduit or anastomotic perfusion during robot-assisted resection of gastroesophageal junction cancer: a randomized clinical trial.

The gastric conduit can be created with partial preservation or a central ligation of the right gastric artery. Central ligation may facilitate complete removal of lymph node (LN) station 3; however, whether this influences conduit and anastomotic perfusion is unknown. Hence this study investigated whether a central ligation of the right gastric artery would affect conduit or anastomotic perfusion compared with partial preservation (local standard) during robot-assisted resection of gastroesophageal junction cancer. Patients scheduled for robot-assisted resection of gastroesophageal junction cancer were randomized to either central ligation or partial preservation of the right gastric artery. Perfusion was assessed using quantified indocyanine green angiography: before gastric mobilization, after conduit formation, and after anastomosis. Hemodynamic variables during surgery and surgical outcomes were recorded. We included 70 patients between June 2020 and October 2021, of whom 5 were excluded from the final analysis. The two patient groups did not differ in conduit (0.07 [interquartile range (IQR), 0.05-0.08] vs. 0.07 u [IQR, 0.05-0.08], P = 0.86) or anastomotic perfusion (0.08 [standard deviation (SD), ±0.02] vs. 0.08 u [SD, ±0.02], P = 0.21), nor did they differ in intraoperative blood loss, anastomotic leaks, postoperative complications, or 1-year survival. However, more LNs were resected in the central ligation group (36 [IQR, 30-44] vs. 28 [IQR, 23-43], P = 0.02). Introducing a central ligation of the right gastric artery did not seem to affect conduit or anastomotic perfusion, compared with partial preservation. However, significantly more LNs were resected.

Effects of Tegoprazan, Potassium-Competitive Acid Blocker, on the Gastric Emptying and Postprandial Symptoms in Healthy Humans.

Proton pump inhibitors are potent gastric acid inhibitors. However, they may worsen symptoms such as postprandial fullness and early satiation by reducing gastric emptying (GE). This study aims to evaluate the effects of tegoprazan, a new potassium-competitive acid blocker, on GE and dyspeptic symptoms. A randomized, double-blind, placebo-controlled design was adopted for this study. Participants underwent GE tests and responded to a questionnaire regarding gastrointestinal symptoms before and after administration of tegoprazan 50mg. GE was assessed using scintigraphy over 4h with a standardized solid meal. Thirty participants were recruited (19 men, mean age 28.2 ± 7.3years). After medication, no significant differences were observed in gastric half emptying time (T1/2) and gastric retention at 4h (GE 4h) between the tegoprazan and the control group (114.2 ± 48.9min vs. 93.7 ± 34.7min, P = 0.20; 10.1 ± 12.0% vs. 4.3 ± 5.4%, P = 0.11, respectively). Furthermore, there were no statistically significant differences detected in the changes within each group between two groups (T1/2, 9.9 ± 52.7min vs. -4.7 ± 30.5min, P = 0.36; GE 4h, 5.2 ± 13.9% vs. -1.3 ± 6.5%, P = 0.12). The changes in dyspeptic symptom scores after tegoprazan administration did not significantly differ from those in the control group with no correlation between symptoms and GE parameters. In healthy adults, the administration of tegoprazan did not show a significant impact on GE and dyspeptic symptoms, especially postprandial fullness or early satiation.

Secretin infusion decreases food intake in healthy men – a randomized, placebo-controlled, double-blind, crossover study

Abstract Design The hormone secretin, best known for regulating pH in the duodenum, has anorectic properties in mice proposedly mediated via secretin-induced brown adipose tissue (BAT) activation. We investigated the effects of exogenous secretin on ad libitum food intake, BAT activity, and postprandial physiology in healthy male volunteers. Methods In a randomized, placebo-controlled, double-blind, crossover study, 25 healthy men underwent two 5-hour i.v. infusions of secretin (1 pmol/kg/min) and placebo (saline), respectively, with an interposed two-month wash-out period. After 30 min of infusion, a standardized liquid mixed meal was ingested and after 5 hours, food intake and meal duration were assessed during an ad libitum meal test. BAT activity was assessed regularly by thermal imaging-measured supraclavicular skin temperature. Results Compared to placebo, secretin significantly decreased ad libitum food intake by 173 ± 88 kcal [95% CI 0.76 to 0.99, P = 0.039], but did not alter ad libitum meal duration. Secretin acutely decreased BAT activity but increased it postprandially compared to placebo. Acetaminophen-assessed gastric emptying was not affected by exogenous secretin, but secretin increased gallbladder volume, bile acid synthesis, and circulating levels of lipase, amylase and triglycerides, while decreasing plasma Na+. Compared to placebo, secretin infusion was associated with 24.0 ± 10.8% (95% CI 0.3 to 1, P = 0.025) more adverse events (headache, nausea, diarrhoea, and vomiting). Conclusions In healthy men, secretin infusion decreased ad libitum food intake concomitantly with a postprandial increase in BAT activity as assessed by thermal imaging-measured supraclavicular skin temperature. Trial registration Clinicaltrials.gov, NCT04613700

Temporal single-cell RNA sequencing dataset of gastroesophagus development from embryonic to post-natal stages

Gastroesophageal disorders and cancers impose a significant global burden. Particularly, the prevalence of esophageal adenocarcinoma (EAC) has increased dramatically in recent years. Barrett’s esophagus, a precursor of EAC, features a unique tissue adaptation at the gastroesophageal squamo-columnar junction (GE-SCJ), where the esophagus meets the stomach. Investigating the evolution of GE-SCJ and understanding dysregulation in its homeostasis are crucial for elucidating cancer pathogenesis. Here, we present the technical quality of the comprehensive single-cell RNA sequencing (scRNA-seq) dataset from mice that captures the transcriptional dynamics during the development of the esophagus, stomach and the GE-SCJ at embryonic, neonatal and adult stages. Through integration with external scRNA-seq datasets and validations using organoid and animal models, we demonstrate the dataset’s consistency in identified cell types and transcriptional profiles. This dataset will be a valuable resource for studying developmental patterns and associated signaling networks in the tissue microenvironment. By offering insights into cellular programs during homeostasis, it facilitates the identification of changes leading to conditions like metaplasia and cancer, crucial for developing effective intervention strategies.

Impact of glucagon-Like peptide-1 agonists in optimizing abdominal wall Reconstruction patients.

Pre-optimization of obese patients prior to abdominal wall reconstruction (AWR) is essential in mitigating their increased preoperative risks. Traditionally diet, exercising, bariatric surgery are the tools typically prescribed for weight loss. The advent of glucagon-like peptide-1 agonists (GLP-1A) which stimulate insulin secretion and inhibit gastric emptying have improved the weight loss armamentarium. However, there is a limited amount of literature on GLP-1A effectiveness and postoperative outcomes in AWR patients. This study compares the efficacy of GLP-1A to Bariatric Surgery (BAS) in perioperative AWR patient. A prospectively maintained database was retrospectively reviewed to identify all patients undergoing AWR at our institution between January 2021 and March 2024. We included patients who required GLP-1A or BAS for weight optimization prior to AWR. We excluded patients on GLP1-A or history BAS not performed for AWR preoptimization. Basic demographics such as age, sex, race, weight and BMI at initial clinic visit and at surgery were compared. Primary endpoints included time to surgery, time to bowel recovery and length of stay (LOS). Time to surgery was defined as the number of months between the initial clinic visit and AWR. Time to bowel recovery was defined as the number of days it took for the first postoperative bowel function. Secondary endpoints included standard 30-days postoperative variables. Nominal variables were analyzed using a Fisher exact test and continuous variables were analyzed with Student's T test. 35 patients were included in this study (GLP-1A: 17, BAS: 18). The GLP-1A cohort had a lesser BMI at the initial clinic visit (40.8 vs 43.4, p = 0.188). GLP-1A cohort made it to the operating room faster (9.1 months vs 13.5 months, p = 0.06) from the first clinic visit; and (7.9 months vs 9.7 months, p = 0.4) from initiation of weight loss intervention. Albeit losing less weight (14.9 kg vs 27.1 kg, p = 0.008) with a lesser reduction in the BMI (4.69 vs 9.23, p = 0.004). The GLP-1A cohort showed a non-significant elevated LOS (5.2 days vs 3.6 days, p = 0.25) and an increased ileus rate (17.6% vs 0%, p = 0.1). However, there were no differences noted in time to bowel recovery (2.9 days vs 3.1 days, p = 0.76). GLP-1A is effective in optimizing patients needing weight loss before AWR. They shorten the timeline to AWR intervention and have comparable peri-operative outcomes to BAS patients.

Impact of L-carnitine supplementation on gastric emptying and bowel function in pediatric ketogenic diet therapy: a clinical trial

Ketogenic diet (KD) is an excess fat, enough protein, and minimal carbohydrate diet. The high fat content in KD lowers the oesophageal sphincter tone, slows gastric emptying, and decreases intestinal transit time. The primary aim of the current clinical trial was to study the effect of L-carnitine supplementation on gastric emptying in children with drug resistant epilepsy (DRE) on KD. Assessment of the protective effect of L-carnitine on bowel function and habits in those patients was a secondary aim. The current study recruited 30 patients aged 12 months to 18 years newly diagnosed with DRE assigned to start KD who were following up at the Pediatric Clinical Nutrition and Neurology Outpatient Clinics or were admitted due to DRE at the Pediatric Neurology Inpatient Department, Children’s Hospital, Ain Shams University (Egypt). Participants were assigned randomly into 2 arms; arm I: received KD with L-carnitine supplementation, arm II: received KD only. Patients were assessed at baseline and after 3 months of starting KD, the assessments of children included: 24-hour dietary recall, Chalfont Seizures Severity Scale, gastrointestinal symptoms score and Bristol stool chart, frequency of defecation per week, anthropometric measurements assessment, fasting serum lipid profile and measurement of the antral length by ultrasound. There was significant increase in antral length in the patients who received KD with L-carnitine supplementation compared to the non-supplemented group. The antral length showed a significant negative correlation with GI symptoms score in all cases and the L-carnitine supplemented group. It also showed a significant positive correlation with Bristol stool score in all patients and a significant positive correlation with stool frequency in the L-carnitine supplemented group only. L-carnitine supplementation to children with DRE on KD has a significant role in improving gastric motility and it increases the frequency of defecation. Further studies are recommended to explore additional benefits, meanwhile it is prudent to advise L-carnitine supplementation for such patients.

Adjuvant chemoradiotherapy plus PD-1 inhibitor for pN3 gastric cancer: a randomized, multicenter, Phase III trial.

D2 surgery followed by adjuvant chemotherapy has been established as the standard of care for patients with locally advanced gastric cancer in Asian countries. However, its efficacy is still unsatisfactory, especially for pathological N3 disease. The RACING trial is a randomized, multicenter, Phase III trial designed to compare the efficacy and safety of chemotherapy alone versus chemotherapy in combination with PD-1 inhibitor and radiotherapy in patients with pN3 gastric or gastroesophageal junction adenocarcinoma. A total of 433 patients will be assigned at a 1:1 ratio to the two arms. The primary end point is the 3-year disease-free survival rate. The secondary end points include the 3-year overall survival rate, 3-year local recurrence-free survival rate, treatment-related adverse events and quality of life.Clinical Trial Registration: NCT04997837 (ClinicalTrials.gov).

SARCINA VENTRICULI-RELATED GASTRITIS: A RARE CASE OF GASTRIC INFECTION IN A PATIENT WITH DELAYED GASTRIC EMPTYING

Sarcina ventriculi (SV), which is also called Clostridium ventriculi, is a rare, non-motile, aerobic, Gram-positive coccus that breaks down carbohydrates through fermentation. It thrives in acidic environments, making the human stomach a suitable habitat, particularly in conditions associated with gastric stasis. SV belongs to the Clostridiaceae family. Recent studies have implicated Sarcina ventriculi in severe gastrointestinal conditions, including emphysematous gastritis, pyloric stenosis, gastroparesis, gastric outlet obstruction, gastric perforation, and gastric adenocarcinoma. Increased awareness of this organism and further studies are essential to understanding its role in human disease.

Increased gallbladder emptying and reduced GLP-1 response in pregnancy with and without gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) has been associated with reduced postprandial glucagon-like peptide 1 (GLP-1) responses. As pregnancy induces changes in gallbladder motility and bile acids stimulate GLP-1 secretion, we investigated postprandial gallbladder emptying and GLP-1 responses in women with GDM. Women with and without GDM underwent two 240-min mixed meal tests; one during third trimester of pregnancy and one 3-6 months postpartum. We evaluated ultrasonography-assessed gallbladder emptying, plasma concentrations of glucometabolic hormones including GLP-1, paracetamol absorption (proxy for gastric emptying) and circulating factors known to affect gallbladder dynamics. Fifteen women with GDM and 15 pregnant women with normal glucose tolerance (NGT) (baseline median age 31 (interquartile range 29;33) versus 32 (28;33) years, body mass index (BMI) 27.2 (24.7;30.7) versus 28.4 (26.2;31.0) kg/m2, HbA1c 30 (29;32) versus 30 (28;31) mmol/mol) were included. No differences in postprandial gallbladder emptying or GLP-1 responses were observed between women with and without GDM, neither during pregnancy nor postpartum. Pregnancy increased fasting gallbladder volumes by 69 (30;122)% and 103 (59;156)% and postprandial gallbladder emptying by 77 (28;236)% and 99 (37;190)% compared with postpartum in women with and without GDM, respectively. Postprandial GLP-1 responses were reduced by 60 (3;82)% and 81 (11;90)% during pregnancy compared with postpartum in women with and without GDM, respectively. Pregnancy-induced changes in gallbladder motility seem to play no or a limited role in previously reported GDM-associated reduced postprandial GLP-1 responses as gallbladder emptying was greater and postprandial GLP-1 response was lower in pregnancy than postpartum regardless of GDM status.

An additional gastrojejunostomy may reduce the incidence of moderate and severe delayed gastric emptying after distal segmental duodenectomy for gastrointestinal stromal tumors

BackgroundTo investigate whether an additional gastrojejunostomy reduces the incidence of delayed gastric emptying (DGE) following a distal segmental duodenectomy for duodenal and proximal jejunal gastrointestinal stromal tumors (GIST).Materials and methodsThis retrospective review of the GIST database at Peking University Cancer Hospital included 50 patients who underwent distal segmental duodenectomies for primary GIST in the duodenum or proximal jejunum within 20 cm of Treitz’s ligament between January 2008 and December 2023. The patients were divided into two groups: non-bypass (without gastrojejunostomy) and bypass (with gastrojejunostomy and Braun’s jejunojejunostomy). Perioperative characteristics and postoperative complications were analyzed.ResultsAmong the 50 patients, 27 underwent duodenojejunostomies without gastrojejunostomies and 23 with gastrojejunostomies and Braun’s jejunojejunostomies. The incidence of grade B-C DGE was significantly lower in the bypass group (43.5% vs. 74.1%, p = 0.028). In addition, non-bypass surgery was an independent risk factor for increased grade B-C DGE (OR 3.67, 95% CI 1.07–12.64, p = 0.039). The bypass group showed a trend towards a shorter postoperative hospital stay (median: 14 days, range: 10–56) compared to the non-bypass group (median: 28 days, range: 6–75), but this difference did not reach statistical significance (p = 0.070). Operative time (min) was significantly longer in the multi-visceral resection group (381.0 ± 108.8 vs. 227.3 ± 87.6, p < 0.001), for tumors ≥ 6.3 cm compared to < 6.3 cm (337.0 ± 116.4 vs. 228.3 ± 99.8, p = 0.002), and in patients with positive preoperative symptoms versus asymptomatic patients (319.9 ± 118.0 vs. 210.2 ± 90.3, p = 0.031).ConclusionThe addition of gastrojejunostomy and Braun’s jejunojejunostomy in distal segmental duodenectomy can reduce the incidence of grade B-C DGE, potentially facilitating timely adjuvant imatinib therapy. Future multicenter studies are needed to confirm these findings.

Predictors of outcomes after gastric peroral endoscopic myotomy for refractory gastroparesis: a systematic review

Background: Gastroparesis is a debilitating gastroduodenal disorder for which gastric peroral endoscopic myotomy (GPOEM) has emerged as an efficacious treatment option. However, response to GPOEM varies between 50-80%, such that preoperative predictors of treatment success are needed to guide patient selection. Methods: We performed a systematic review to identify predictors of clinical and functional response to GPOEM among adult patients with gastroparesis (PROSPERO: CRD42023457359). MEDLINE, Embase, and CENTRAL databases were searched systematically for studies reporting outcomes after GPOEM in September 2023. A narrative synthesis of predictive factors on univariable and multivariable analysis was performed with consideration of response rates via meta-analysis, and evaluation of discrimination if prognostic models were developed. ROBINS-E was used for risk of bias assessment. Results: Of 1899 articles reviewed, 30 were included. The GPOEM response rate was 63.1% (95% confidence interval 56.3%-69.5%) with most studies defining clinical success on the basis of improvement in gastroparesis cardinal symptom index (87%, 26/30). Older age, shorter duration of gastroparesis, non-diabetic etiology, lower body mass index, and response to intrapyloric botulinum toxin were associated with positive response to GPOEM on multivariable analyses. Predictors on physiological tests such as EndoFLIP or gastric emptying scintigraphy were inconsistent. No prognostic models underwent external validation. Conclusion: Currently, there are limited reproducible predictors of response to GPOEM among patients with refractory gastroparesis. Robust prospective studies investigating scalable, reproducible, and actionable biomarkers of treatment response are required.

Optimizing therapeutics: A novel mutual prodrug of ketoprofen and Chlorzoxazone for enhanced efficacy and safety

The development of mutual prodrugs signifies a pivotal advancement in the optimization of therapeutic profiles for established pharmaceuticals. This study explores the synthesis and evaluation of an innovative mutual prodrug combining the nonsteroidal anti-inflammatory drug (NSAID) Ketoprofen and the skeletal muscle relaxant Chlorzoxazone. Designed to alleviate gastric irritation inherent to NSAIDs while capitalizing on the synergistic benefits of both agents, the synthesized mutual prodrug was characterized and confirmed through extensive physicochemical and spectroscopic studies. Solubility and partition coefficient analyses indicated heightened lipophilicity, enhancing the prodrug's suitability for oral administration compared to its parent drugs. Additionally, protein binding studies revealed a low binding affinity, suggesting improved bioavailability. Subsequent in vitro hydrolysis studies assessed the prodrug's stability across various pH levels (1.2, 3, 5 and 7.4) simulated gastric and intestinal fluids, plasma and rat liver homogenate, with quantitative evaluation performed by high-performance liquid chromatography. The prodrug remained stable and unhydrolyzed in the stomach after absorption, but underwent rapid cleavage by esterase's in blood and rat liver homogenate, releasing the active parent drugs. Our investigation underscores the transformative potential of mutual prodrug design in optimizing the efficacy and safety profile of combining NSAIDs with muscle relaxants. This approach offers a novel therapeutic strategy that enhances patient outcomes while minimizing adverse effects, paving the way for innovative treatments in managing musculoskeletal conditions and improving overall quality of life.

Erectile Dysfunction Therapy of Bariatric Patients: Tadalafil Biopharmaceutics and Pharmacokinetics Before vs. After Gastric Sleeve/Bypass

Bariatric surgery introduces significant changes in the gastrointestinal tract, which may affect oral drug absorption/bioavailability. Here we investigate the phosphodiesterase-5 inhibitor (PDE5i) tadalafil for potentially impaired post-bariatric solubility/dissolution and absorption. Solubility was studied in vitro in different pHs, and ex vivo in gastric content aspirated from patients pre/post-surgery. Dissolution was studied in conditions mimicking pre/post-surgery stomach. Finally, the experimental data were used in physiologically-based pharmacokinetic (PBPK) model (GastroPlus®) to simulate pre- vs. post-surgery tadalafil PK. Tadalafil demonstrated low and pH-independent solubility, both in vitro and ex vivo. Tadalafil release from all drug products and under all gastric conditions was incomplete, with particularly poor dissolution (2%) of the highest dose under post-bariatric conditions. PBPK simulations revealed altered tadalafil PK after gastric bypass—but not after sleeve gastrectomy—compared to unoperated individuals, with 44–48% decreased Cmax, 35–56% decreased AUC and 44% shorter Tmax. This mechanistic analysis suggests that tadalafil may be as effective after sleeve gastrectomy as before the procedure; meanwhile, results after gastric bypass raise concerns regarding the bioperformance of the drug. In addition, the drug's duration of action may be much shorter after gastric bypass. Thus, the effectiveness of tadalafil, widely regarded as the ‘weekend pill’, may be shorter than expected among gastric bypass patients.Graphical

The Inhibitory Effect of Hedera helix and Coptidis Rhizome Mixture in the Pathogenesis of Laryngopharyngeal Reflux: Cleavage of E-Cadherin in Acid-Exposed Primary Human Pharyngeal Epithelial Cells.

Laryngopharyngeal reflux disease (LPRD) is a prevalent upper airway disorder characterized by inflammation and epithelial damage due to the backflow of gastric contents. Current treatments, primarily proton pump inhibitors (PPIs), often show variable efficacy, necessitating the exploration of alternative or adjunctive therapies. This study investigates the therapeutic potential of a mixture of Hedera helix and Coptidis rhizome (HHCR) in mitigating the pathophysiological mechanisms of LPRD. Using an in vitro model of human pharyngeal epithelial cells exposed to acidic conditions, we observed that acid exposure significantly increased the expression of adenosine A3 receptor (adenosine A3) and matrix metalloproteinase-7 (MMP-7), leading to E-cadherin cleavage and compromised epithelial integrity. Treatment with the HHCR mixture effectively suppressed adenosine A3 expression and MMP-7 activity, thereby reducing E-cadherin cleavage and preserving cellular cohesion. These results highlight the HHCR mixture's ability to modulate the adenosine A3-MMP-7-E-cadherin pathway, suggesting its potential as a valuable adjunctive therapy for LPRD, particularly for patients unresponsive to conventional PPI treatment. This study provides new insights into the molecular interactions involved in LPRD and supports further clinical evaluation of HHCR as a complementary treatment option.