Endoscopic findings and outcomes of gastric mucosal changes relating to potassium-competitive acid blocker and proton pump inhibitor therapy.

Gastric mucosal changes associated with long-term potassium-competitive acid blocker and proton pump inhibitor (PPI) therapy may raise concern. In contrast to that for PPIs, the evidence concerning the safety of long-term potassium-competitive acid blocker use is scant. Vonoprazan (VPZ) is a representative potassium-competitive acid blocker released in Japan in 2015. In order to shed some comparative light regarding the outcomes of gastric mucosal lesions associated with a long-term acid blockade, we have reviewed six representative gastric mucosal lesions: fundic gland polyps, gastric hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like gastric mucosal changes, gastric black spots, and stardust gastric mucosal changes. For these mucosal lesions, we have evaluated the association with the type of acid blockade, patient gender, Helicobacter pylori infection status, the degree of gastric atrophy, and serum gastrin levels. There is no concrete evidence to support a significant relationship between VPZ/PPI use and the development of neuroendocrine tumors. Current data also shows that the risk of gastric mucosal changes is similar for long-term VPZ and PPI use. Serum hypergastrinemia is not correlated with the development of some gastric mucosal lesions. Therefore, serum gastrin level is unhelpful for risk estimation and for decision-making relating to the cessation of these drugs in routine clinical practice. Given the confounding potential neoplastic risk relating to H. pylori infection, this should be eradicated before VPZ/PPI therapy is commenced. The evidence to date does not support the cessation of clinically appropriate VPZ/PPI therapy solely because of the presence of these associated gastric mucosal lesions.

Problems with repairing gut sphincters malfunctions.

Correcting a gut sphincter malfunction is a difficult problem. Because each sphincter has two opposite functions, that of closure and opening, repairing one there is a risk of damaging the other. Indeed, widening a narrow sphincter, such as lower esophageal sphincter (LES) and anal sphincter, may cause gastroesophageal reflux and fecal incontinence, respectively, whereas narrowing a wide sphincter, may cause a difficult transit. All the corrective treatments for difficult or retrograde transit concerning LES and anal sphincter with their unwanted consequences have been analyzed and discussed. To overcome the drawbacks of sphincter surgical repairs, researchers have devised devices capable of closing and opening the gut lumen, named artificial sphincters (ASs). Their function is based on various mechanisms, e.g., hydraulic, magnetic, mechanical etc, operating through many complicated components, such as plastic cuffs, balloons, micropumps, micromotors, connecting tubes and wires, electromechanical clamps, rechargeable batteries, magnetic devices, elastic bands, etc. Unfortunately, these structures may facilitate the onset of infections and induce a local fibrotic reaction, which may cause device malfunctioning, whereas the compression of the gut wall to occlude the lumen may give rise to ischemia with erosions and other lesions. Some ASs are already being used in clinical practice, despite their considerable limits, while others are still at the research stage. In view of the adverse events of the ASs mentioned above, we considered applying bioengineering methods to analyze and resolve biomechanical and biological interaction problems with the aim to conceive and build efficient and safe biomimetic ASs.

Does Gastroesophageal Reflux Disease Increase the Risk of Sepsis and Its 28-day Mortality? A Causal Study Using a Mendelian Randomization Approach.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder. Recent studies indicate that GERD may exert systemic effects, potentially elevating the risk of severe infections, including sepsis. Nevertheless, the causal relationship between GERD and sepsis, as well as sepsis-related 28-day mortality, remains uncertain. AIM: The aim of this study is to investigate the causal relationship between GERD and the risk of sepsis, including 28-day mortality of sepsis. METHODS: This study utilized a two-sample Mendelian Randomization (MR) approach to analyze data from publicly available genome-wide association studies (GWAS) databases ( https://gwas.mrcieu.ac.uk/ ). The analysis comprised 129,080 cases and 473,524 controls for GERD; 11,643 patients and 474,841 controls for sepsis; and 1,896 patients and 484,588 controls for 28-day mortality from sepsis. The objective was to evaluate the causal impact of GERD on the risk of sepsis and 28-day sepsis mortality. Genetic variation data pertinent to GERD were obtained from the most recent genome-wide association studies (GWAS). The primary analysis employed the Inverse Variance Weighted (IVW) method. Sensitivity and pleiotropy analyses were performed to validate the robustness of the findings. RESULTS: MR analysis revealed a notable link between genetically predicted GERD and increased sepsis risk (odds ratio [OR] 1.37, 95% confidence interval [CI] 1.24-1.52; p = 2.79 × 10-9). Moreover, GERD correlated with elevated 28-day mortality of sepsis (OR 1.44, 95% CI 1.11-1.85; p = 5.34 × 10-3). These results remained consistent throughout various sensitivity analyses, indicating their resilience against potential pleiotropy and other biases. CONCLUSION: This study indicates that genetic predisposition to GERD may be linked to an elevated risk of sepsis and its associated 28-day mortality. However, the study does not establish a direct causal relationship for GERD itself, nor does it assess the impact of GERD treatment. Further research is needed to explore the underlying mechanisms and potential therapeutic interventions involved.

The association between salivary pepsin and gastroesophageal reflux disease: A meta-analysis.

BACKGROUND AND PURPOSE: The definitive diagnosis of gastroesophageal reflux disease (GERD) often requires invasive investigations like upper gastrointestinal endoscopy or reflux monitoring. We aimed to explore the relationship between salivary pepsin and GERD and its value as a non-invasive diagnostic tool. METHODS: Databases (PubMed, Web of Science, Cochran Library, and EMBASE) were searched from their inception to January 22, 2024 to explore the correlation of salivary pepsin with GERD. The meta-analysis data retrieved were summarized, including the salivary pepsin concentration, sensitivity of diagnosis (SEN), specificity of diagnosis (SPE), negative likelihood ratio, positive likelihood ratio, diagnostic odds ratio, and receiver operating characteristic (ROC) curve. RESULTS: The meta-analysis comparing salivary pepsin concentration in two groups (proven GERD and non-GERD) with 18 studies revealed that the proven GERD group had higher salivary pepsin concentration than the non-GERD group (SMD = 1.74 [95% CI 1.14-2.34]). The meta-analysis of salivary pepsin diagnostic value for proven GERD incorporated 23 studies. The results showed pooled SEN (0.73 [95% CI 0.66-0.80]), SPE (0.72 [95% CI 0.65-0.78]), positive likelihood ratio (2.61 [95% CI 2.02-3.39]), negative likelihood ratio (0.37 [95% CI 0.28-0.50]), diagnostic odds ratio (7.03 [95% CI 4.24-11.66]) and area under the SROC curve (0.79 [95% CI 0.75-0.82]). CONCLUSION: GERD patients presented a higher salivary pepsin concentration. Salivary pepsin is both sensitive and specific in identifying GERD, making it a promising non-invasive marker for diagnosis.

Exacerbation of symptoms, nocturnal acid reflux, and impaired autonomic function are associated with sleep disturbance in gastroesophageal reflux disease patients.

Background and aim: Gastroesophageal reflux disease (GERD) patients often report sleep disturbance (SD); however, the relationship between GERD and SD is unknown. This study investigated whether SD affects symptoms, acid reflux, and autonomic function in GERD patients. Methods: A total of 257 subjects (126 patients with SD and 99 patients without SD) participated in this survey from January 2020 to August 2022. Participants were required to complete questionnaires including the GERD impact scale (GIS), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD). Esophageal mucosal injury, acid exposure, peristaltic function, and autonomic function were assessed by upper endoscopy, high-resolution esophageal manometry (HRAM), 24-h multichannel intraluminal impedance with pH (24 h-MII-pH), and electrocardiography (ECG). Results: Gastroesophageal reflux disease patients with SD experienced a higher frequency of prolonged reflux (p < 0.001), longest reflux event (p < 0.001), acid exposure time (p < 0.001) during the recumbent period, and a higher incidence of erosive esophagitis (EE) (59.5 vs. 45.5%, p = 0.036) than those without SD. Pearson's correlation analysis showed that SD was positively correlated with GIS (r = 0.725, p < 0.001), HAMA (r = 0.680, p < 0.001), and HAMD (r = 0.323, p < 0.001) scores, and negatively correlated with parasympathetic or vagal nerve activity (r = -0.770, p < 0.001). Conclusion: Gastroesophageal reflux disease patients with SD experience more severe reflux symptoms and nocturnal acid reflux, which may be related to autonomic dysfunction.

Long-term outcomes of treatment for achalasia: Laparoscopic Heller myotomy versus POEM.

Achalasia is a rare esophageal motility disorder characterized by nonrelaxation of the lower esophageal sphincter. Laparoscopic Heller myotomy (LHM) is the gold standard treatment for achalasia. Peroral endoscopic myotomy (POEM), a less invasive treatment, is performed extensively, and the selection of the intervention method remains debatable to date. In addition to the availability of extensive studies on short-term outcomes, recent studies on the long-term outcomes of LHM and POEM have shown similar clinical success after 5 y of follow-up. However, gastroesophageal reflux disease (GERD) was more common in patients who had undergone POEM than in those who had undergone LHM. Moreover, existing studies have compared treatment outcomes in various disease states. Some studies have suggested that POEM is superior to LHM for patients with type III achalasia because POEM allows for a longer myotomy. Research on treatment for sigmoid types is currently in progress. However, the long-term results comparing LHD and POEM are insufficient, and the best treatment remains controversial. Further research is needed, and treatment options should be discussed with patients and tailored to their individual needs and pathologies.

Gastroesophageal reflux disease and risk for arrhythmias: a Mendelian randomization analysis.

Background: Clinical observations and epidemiological studies suggest a potential linkage between gastroesophageal reflux disease (GERD) and arrhythmias, yet the underlying mechanism remains elusive. This study investigates the causal relationship between GERD and four types of arrhythmia through a genetic lens, employing Mendelian randomization analysis to elucidate the directionality of these associations. Methods: Selected single nucleotide polymorphisms (SNPs) from genome-wide association study (GWAS) data were utilized as instrumental variables. The inverse variance weighting (IVW) method, MR-Egger regression analysis, and the weighted median method were employed in two-sample Mendelian randomization analysis. Horizontal pleiotropy was detected and corrected using the MR-PRESSO test and MR-Egger regression. The stability and reliability of the Mendelian randomization results were assessed using the leave-one-out method, Cochran's Q test, and funnel plots. The causal relationship between GERD and four types of arrhythmias was evaluated using the odds ratio (OR). Results: IVW results indicated that GERD could increase the risk of arrhythmias. A one standard deviation increases in the logarithmically transformed GERD score resulted in a 34% increase in the risk of arrhythmia (OR = 1.34; 95% CI 1.19-1.51; p = 1.66E-06). No significant correlation was found between GERD and other arrhythmias. Conclusion: A causal relationship exists between GERD and arrhythmias, suggesting that GERD increases the risk of developing these arrhythmias.

Treating acid reflux without compressing the food passageway: 4-year safety and clinical outcomes with the RefluxStop device in a prospective multicenter study.

INTRODUCTION: RefluxStop is an implantable device for laparoscopic surgical treatment of gastroesophageal reflux disease (GERD) to restore and maintain lower esophageal sphincter and angle of His anatomy without encircling and putting pressure on the food passageway, thereby avoiding side effects such as dysphagia and bloating seen with traditional fundoplication. This study reports the clinical outcomes with RefluxStop at 4 years following implantation of the device. METHODS: A prospective, single arm, multicenter clinical investigation analyzing safety and effectiveness of the RefluxStop device in 50 patients with chronic GERD. RESULTS: Available data are presented for 44 patients at 4 years with the addition of three patients at 3 years carried forward. At 4 years, median GERD-HRQL score was 90% reduced compared to baseline. Two patients (2/44) used regular daily proton pump inhibitors (PPIs) despite subsequent 24-h pH monitoring off PPI therapy yielding normal results. There were no device-related adverse events (AEs), esophageal dilations, migrations, or explants during the entire study period. AEs reported between 1 and 4 years were as follows: one subject with heartburn and a pathologic pH result with device positioned too low at surgery; one subject with dysphagia, thus, 46/47 patients reported no dysphagia-related AEs between years 1 and 4. Two patients (2/47) were dissatisfied with treatment despite normal 24-h pH monitoring, of whom one had manometry-verified dysmotility at 6 months, indicating dissatisfaction for reasons other than acid reflux. CONCLUSION: These results confirm the excellent and already published 1-year results as stable in the long-term, supporting the safety and effectiveness of the RefluxStop device in treating GERD for over 4 years. GERD-HRQL score, pH testing, and PPI usage indicate treatment success without dysphagia or gas-bloating and only minimal incidence of other AEs. This favorably low rate of AEs is likely attributable to RefluxStop's dynamic physiologic interaction and non-encircling nature.

Robotic Repair of a Paraesophageal Hernia After an Open Nissen Fundoplication: Case Presentation and Clinical Discussion.

We present a female in her sixties with a recurrent paraesophageal hernia status post open Nissen fundoplication and multiple esophageal dilations who underwent a robotic paraesophageal hernia repair, with extensive lysis of adhesions. The stomach and esophagus were dissected off the crura and the previous wrap was undone. Once the entirety of the stomach and esophagus were freed from their surrounding structures, the hernia sac was able to be excised. The crural defect was closed and gastropexy was performed. The patient had an uneventful postoperative course and was discharged home. This case is presented to provide evidence that robotic repair presents a viable option in the reoperation of patients following an open Nissen fundoplication as well as provide an overview of the types of hiatal hernias and the indications and options for surgical intervention.

A Comprehensive Review on the Efficacy and Safety of Vonoprazan in the Management of Gastric Acid-Related Diseases.

Gastric acid-related diseases, including gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), and Helicobacter pylori (H. pylori) infection, present significant clinical challenges due to their prevalence and potential for severe complications. Effective management of these conditions is essential for symptom relief, mucosal healing, and prevention of complications. This review aims to evaluate the efficacy and safety of vonoprazan, a novel potassium-competitive acid blocker (P-CAB), in the treatment of gastric acid-related diseases and to compare it with traditional proton pump inhibitors (PPIs). A comprehensive analysis of clinical trials and studies was conducted to assess the effectiveness of vonoprazan in managing GERD, PUD, and H. pylori infection. The safety profile of vonoprazan was also reviewed, and comparisons were made to PPIs and other gastric acid suppressants. Vonoprazan demonstrates superior and more consistent acid suppression than PPIs, resulting in rapid and sustained symptom relief and mucosal healing. Clinical trials have shown its efficacy in treating GERD, PUD, and H. pylori infection, with higher eradication rates for H. pylori when used in combination therapies. The safety profile of vonoprazan is favorable, with fewer adverse effects and drug interactions compared to PPIs. Vonoprazan offers a promising alternative to traditional PPIs for the management of gastric acid-related diseases. Its unique mechanism of action and superior efficacy make it a valuable option for patients requiring effective and reliable acid suppression. Further research is warranted to explore its potential in broader clinical applications and to establish long-term safety data.

Gastroesophageal reflux following peroral endoscopic myotomy for achalasia: Bumps in the road to success.

Achalasia can significantly impair the quality of life. The clinical presentation typically includes dysphagia to both solids and liquids, chest pain, and regurgitation. Diagnosis can be delayed in patients with atypical presentations, and they might receive a wrong diagnosis, such as gastroesophageal reflux disease (GERD), owing to overlapping symptoms of both disorders. Although the cause of achalasia is poorly understood, its impact on the motility of the esophagus and gastroesophageal junction is well established. Several treatment modalities have been utilized, with the most common being surgical Heller myotomy with concomitant fundoplication and pneumatic balloon dilatation. Recently, peroral endoscopic myotomy (POEM) has gained popularity as an effective treatment for achalasia, despite a relatively high incidence of GERD occurring after treatment compared to other modalities. The magnitude of post-POEM GERD depends on its definition and is influenced by patient and procedure-related factors. The long-term sequelae of post-POEM GERD are yet to be determined, but it appears to have a benign course and is usually manageable with clinically available modalities. Identifying risk factors for post-POEM GERD and modifying the POEM procedure in selected patients may improve the overall success of this technique.

Gastroesophageal Reflux Disease and Preterm Birth: Univariate and Multivariate Mendelian Randomization.

Background: Observational studies have established a connection between Gastroesophageal reflux disease (GERD) and preterm birth (PTB). Nevertheless, these correlations can be affected by residual confounding or reverse causality, resulting in ambiguity regarding the connection. The objective of this study was to assess the relationship between genetically predicted GERD and PTB. Methods: Initially, we performed bidirectional univariate Mendelian randomization (UVMR) analysis utilizing publicly accessible genome-wide association studies (GWAS) data. The primary analytical approach employed to determine the causal impact between GERD and PTB is the inverse variance weighted technique (IVW). Subsequently, we utilized multivariate Mendelian randomization (MVMR) to adjust for potential factors that could influence the results, such as body mass index (BMI), maternal smoking around birth, educational attainment, household income, and Townsend deprivation index (TDI). Furthermore, we performed a sequence of comprehensive sensitivity analyses to assess the reliability of our MR findings. Results: The UVMR analysis results showed a significant correlation between GERD and PTB (odds ratio [OR]: 1.810; 95% confidence interval [CI]: 1.344-2.439; P=9.60E-05) in the IVW model, and the Weighted median method (OR=1.591, 95% CI=1.094-2.315, P=0.015) revealed consistent results. The inverse MR findings suggest no causal link between PTB and the incidence of GERD. In addition, the sensitivity analysis did not detect heterogeneity or horizontal pleiotropy, and the "leave-one-out" examination confirmed that the causal estimation is unlikely to be influenced by the single nucleotide polymorphisms (SNPs) effect. The MVMR analysis demonstrated that the causal association between GERD and PTB still existed after considering BMI, maternal smoking around birth, educational attainment, household income, and TDI (OR=1.921, 95% CI=1.401-2.634, P=5.08E-05). Conclusion: This study presents evidence indicating that genetically predicted GERD can heighten the risk of PTB. Therefore, it is advisable to perform focused screening for pregnant women with GERD in order to find the initial signs of PTB and promptly apply intervention strategies to extend the duration of pregnancy.

Leisure television watching exerts a causal effect on gastroesophageal reflux disease: evidence from a two-step mendelian randomization study.

BACKGROUND: Previous studies have shown that physical activity (PA) and leisure sedentary behaviors (LSB, including leisure television watching) are linked to gastroesophageal reflux disease (GERD). However, the associations between PA/LSB and GERD remain controversial. In this study, we aimed to reveal whether these associations reflect causal relationships and reveal the potential mechanisms of these relationships using bidirectional and two-step Mendelian randomization (MR) analyses. METHODS: We obtained genome-wide association study (GWAS) summary statistics for PA/LSB, four common risk factors (including cigarettes smoked per day, alcoholic drinks per week, triglycerides, total cholesterol) and GERD from published GWASs. A bidirectional MR analysis was performed to identify causal relationships between PA/LSB and GERD. Then, a series of sensitivity analyses were performed to verify the robustness of the results. Finally, a mediation analysis via two-step MR was conducted to investigate any effects explained by common risk factors in these relationships. RESULTS: Genetically predicted per 1-SD increase in leisure time television watching significantly increased the risk of GERD in the bidirectional MR analysis (OR = 1.33; 95% CI: 1.14-1.56; P = 2.71 × 10- 4). Sensitivity analyses successfully verified the robustness of the causal relationship. Further mediation analysis showed that this effect was partly mediated by increasing cigarettes smoked per day, with mediated proportions of 18.37% (95% CI: 11.94-39.79%). CONCLUSION: Our findings revealed a causal relationship between leisure television watching and an increased risk of GERD, notably, the causal effect was partially mediated by cigarettes smoked per day. These findings may inform prevention and management strategies directed toward GERD.

Association between Oral Microbiome and Gastroesophageal Reflux Severity.

Background/Objectives: Gastroesophageal reflux disease (GORD) is caused by gastric contents refluxing back into the oesophagus and oral cavity. It can lead to injuries to the mucosa in the form of erosion and ulcers. Our past research have shown acid reflux severity and disease progression is associated with alternations in the microbiota of the distal oesophagus. The aim of this study was to explore whether changes in the oral microbiota occurred in GORD patients and establish any associations with reflux severity. Methods: Fresh mouthwash samples were collected from 58 patients experiencing reflux symptoms referred for 24 h pH monitoring. The participants were categorised into three groups based on their DeMeester scores: Normal (<14.72), Mild (14.2-50), and Moderate/severe (>51). Microorganism identity and diversity were generated using hypervariable tag sequencing and analysing the V1-V3 region of the 16S rRNA gene. Results: No differences in microbiota diversity were found in oral microbiota between groups using the Chiao1 diversity index and Shannon diversity index. Microbiota in the Mild group showed reductions in Rothia dentocariosa and Lautropia, while Moryella and Clostridiales_1 were increased compared with the Normal group. In the Moderate/severe group, the abundance of Rothia aeria was reduced compared with the Normal group, while Schwartzia, Rs_045, Paludibacter, S. satelles, Treponema, and T. socranskii all had increased abundance. The abundance of Prevotella pallens was higher in the Mild group compared with Moderate/severe, while S. satelles and Paludibacter abundances were lower. Conclusions: Our study shows the oral microbiome show significant differences between acid reflux severity groups, as categorised by DeMeester score.

The foregut in cystic fibrosis.

The aerodigestive organs share a kindred embryologic origin that allows for a more complete explanation as to how the foregut can remain a barrier to normalcy in people with cystic fibrosis (pwCF). The structures of the aerodigestive tract include the nasopharynx, the oropharynx, the hypopharynx, the esophagus, the stomach, as well as the supraglottic, glottic, and subglottic tubular airways (including the trachea). Additional gastrointestinal (GI) luminal/alimentary organs of the foregut include the duodenum. Extraluminal foregut structures include the liver, the gall bladder, the biliary tree, and the pancreas. There are a variety of neurologic controls within these complicated anatomic compartments to separate the transit of food and liquid from air. These structures share the same origin from the primitive foregut/mesenchyme. The vagus nerve is a critical structure that unites respiratory and digestive functions. This article comments on the interconnected nature of cystic fibrosis and the GI tract. As it relates to the foregut, this has been typically treated as simple "reflux" as the cause of worsened lung function in pwCF. That terms like gastroesophageal reflux (GER), gastroesophageal reflux disease (GERD), heartburn, and regurgitation are used interchangeably to reflect pathology further complicates matters; we offer a more physiologically accurate term called "GI-related aspiration" or "GRASP." Broadly, this term reflects that aspiration of foregut contents from the duodenum through the stomach to the esophagus, into the pharynx and the respiratory tree in pwCF. As a barrier to normalcy in pwCF, GRASP is fundamentally two disease processes-GERD and gastroparesis-that likely contribute most to the deterioration of lung disease in pwCF. In the modulator era, successful GRASP management will be critical, particularly in those post-lung transplantation (LTx), only through successful management of both GERD and gastroparesis. Standardization of clinical management algorithms for GRASP in CF-related GRASP is a key clinical and research gap preventing normalcy in pwCF; what exists nearly exclusively addresses surgical evaluations or offers guidance for the management of GI symptoms alone (with unclear parameters for respiratory disease considerations). We begin first by describing the result of GRASP damage to the lung in various stages of lung disease. This is followed by a discussion of the mechanisms by which the digestive tract can injure the lungs. We summarize what we anticipate future research directions will be to reduce the impact of GRASP as a barrier to normalcy in pwCF.

Unraveling the causality between gastroesophageal reflux disease and increased cancer risk: evidence from the UK Biobank and GWAS consortia.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common condition characterized by the reflux of stomach contents into the esophagus. Despite its widespread prevalence worldwide, the causal link between GERD and various cancer risks has not been fully established, and past medical research has often underestimated or overlooked this relationship. METHODS: This study performed Mendelian randomization (MR) to investigate the causal relationship between GERD and 19 different cancers. We leveraged data from 129,080 GERD patients and 473,524 controls, along with cancer-related data, obtained from the UK Biobank and various Genome-Wide Association Studies (GWAS) consortia. Single nucleotide polymorphisms (SNPs) associated with GERD were used as instrumental variables, utilizing methods such as inverse variance weighting, weighted median, and MR-Egger to address potential pleiotropy and confounding factors. RESULTS: GERD was significantly associated with higher risks of nine types of cancer. Even after adjusting for all known risk factors-including smoking, alcohol consumption, major depression, and body mass index (BMI)-these associations remained significant, with higher risks for most cancers. For example, the adjusted risk for overall lung cancer was (OR, 1.23; 95% CI: 1.14-1.33), for lung adenocarcinoma was (OR, 1.18; 95% CI: 1.03-1.36), for lung squamous cell carcinoma was (OR, 1.35; 95% CI: 1.19-1.53), and for oral cavity and pharyngeal cancer was (OR, 1.73; 95% CI: 1.22-2.44). Especially noteworthy, the risk for esophageal cancer increased to (OR, 2.57; 95% CI: 1.23-5.37). Mediation analyses further highlighted GERD as a significant mediator in the relationships between BMI, smoking, major depression, and cancer risks. CONCLUSIONS: This study identifies a significant causal relationship between GERD and increased cancer risk, highlighting its role in cancer development and underscoring the necessity of incorporating GERD management into cancer prevention strategies.

Does practice make perfect? Studying the relationship between surgeon experience and patient outcomes for paraesophageal hernia repairs.

BACKGROUND: It has been reported that higher surgeon experience leads to better patient outcomes. In this study, we look at surgeon experience and its association with postoperative outcomes and variation among the practice of surgeons performing paraesophageal hernia repairs (PEH). METHOD: This was a retrospective study of 1155 patients who underwent PEH repair at a single institution (2010-2023). Surgeon experience was defined as the number of surgeries performed per surgeon and was split using the median surgeries (n = 100), with surgeons performing at or above the median categorized as high-experience and below the median as low-experience surgeons. A multivariable logistic regression model was used to test correlation between surgeon experience and variables, including demographics and intra- and post-operative outcomes. RESULTS: High-experience surgeons performed more elective cases (93.4% vs 85.5%), but low-experience surgeons operated more on emergent (2.7% vs 0.9%), semi-elective (2.3% vs 1.4%), and urgent cases (9.5% vs 4.3%). Low-experience surgeons operated more on patients who were older (67.5 vs 63.2 years, p < 0.001) and had an increased risk of CVD (72.9% vs 61.5%, p < 0.001). Intraoperative OR time was considerably less for high-experience surgeons (115.8 vs 172.9 min, p < 0.001). Low-experience surgeons had increased risk of intra-operative complications (4.5% vs 1.8%, p = 0.021) and post-op pneumonia within 30 days (1.8% vs 0.3%). However, long-term outcomes such as hernia recurrence (OR: 1.10, CI: 0.78-1.54) and redo-operations for hiatal hernia (OR: 1.10, CI: 0.65-1.75) were similar for both groups. CONCLUSION: High-experience surgeons perform more complex revisional surgeries in less time with fewer complications. Low-experience surgeons operated more on patients with higher comorbidities but had significantly higher OR times. Long-term results of recurrence and redo-operations were comparable. These variations suggest that high-experience surgeons are more efficient while operating on more complex cases. These findings have pivotal implications to facilitate mentorship and education among less-experienced surgeons.

Cholelithiasis and cholecystectomy increase the risk of gastroesophageal reflux disease and Barrett's esophagus.

Background: Cholelithiasis or cholecystectomy may contribute to the development of gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC) through bile reflux; however, current observational studies yield inconsistent findings. We utilized a novel approach combining meta-analysis and Mendelian randomization (MR) analysis, to assess the association between them. Methods: The literature search was done using PubMed, Web of Science, and Embase databases, up to 3 November 2023. A meta-analysis of observational studies assessing the correlations between cholelithiasis or cholecystectomy, and the risk factors for GERD, BE, and EACwas conducted. In addition, the MR analysis was employed to assess the causative impact of genetic pre-disposition for cholelithiasis or cholecystectomy on these esophageal diseases. Results: The results of the meta-analysis indicated that cholelithiasis was significantly linked to an elevated risk in the incidence of BE (RR, 1.77; 95% CI, 1.37-2.29; p < 0.001) and cholecystectomy was a risk factor for GERD (RR, 1.37; 95%CI, 1.09-1.72; p = 0.008). We observed significant genetic associations between cholelithiasis and both GERD (OR, 1.06; 95% CI, 1.02-1.10; p < 0.001) and BE (OR, 1.21; 95% CI, 1.11-1.32; p < 0.001), and a correlation between cholecystectomy and both GERD (OR, 1.04; 95% CI, 1.02-1.06; p < 0.001) and BE (OR, 1.13; 95% CI, 1.06-1.19; p < 0.001). After adjusting for common risk factors, such as smoking, alcohol consumption, and BMI in multivariate analysis, the risk of GERD and BE still persisted. Conclusion: Our study revealed that both cholelithiasis and cholecystectomy elevate the risk of GERD and BE. However, there is no observed increase in the risk of EAC, despite GERD and BE being the primary pathophysiological pathways leading to EAC. Therefore, patients with cholelithiasis and cholecystectomy should be vigilant regarding esophageal symptoms; however, invasive EAC cytology may not be necessary.

Gastroesophageal reflux disease increases the risk of rheumatoid arthritis: a bidirectional two-sample Mendelian randomization study.

Rheumatoid arthritis (RA) is a common autoimmune disease, and some observational studies have indicated an association between Gastroesophageal Reflux Disease (GERD) and RA. However, the causal relationship between the two remains uncertain. We used Mendelian randomization (MR) to assess the causal relationship between GERD and RA. Two-sample Mendelian randomization analysis was performed using pooled data from large-scale genome-wide association studies. In addition, we performed multivariate MR analyses to exclude confounding factors between GERD and RA, including smoking quantity, drinking frequency, BMI, depression, and education attainment. The MR results for GERD on RA suggested a causal effect of the genetic susceptibility of GERD on RA (discovery dataset, IVW, odds ratio [OR] = 1.41, 95% confidence interval [CI] 1.22-1.63, p = 2.81 × 10-6; validation dataset, IVW, OR = 1.38, 95% CI 1.23-1.55, P = 1.76 × 10-8). Multivariate MR analysis also supports this result. But the results of the reverse MR analysis did not reveal compelling evidence that RA can increase the risk of developing GERD. Our bidirectional Two-Sample Mendelian randomization analysis and multivariate MR analysis provide support for the causal effect of GERD on RA. This discovery could offer new insights for the prevention and treatment of RA.

Magnetic sphincter augmentation vs subtotal gastrectomy with Roux-en-Y reconstruction for the treatment of postsleeve gastrectomy gastroesophageal reflux disease.

BACKGROUND: Obesity affects more than one-third of Americans and can be treated with bariatric surgery, most commonly sleeve gastrectomy (SG). SG has been shown to increase the incidence of gastroesophageal reflux disease (GERD) in some patients, which can be refractory to medical management. Surgical options for post-SG GERD include magnetic sphincter augmentation (MSA) and subtotal gastrectomy with Roux-en-Y reconstruction (SGRY). A comparative analysis of MSA and SGRY for post-SG GERD was performed to evaluate postoperative outcomes. METHODS: A retrospectively maintained prospectively gathered database from 2018 to 2023 was used to identify patients who underwent MSA or SGRY for the indication of GERD after SG. Differences among patient characteristics; GERD assessments, including the health-related quality of life (HRQL) questionnaire and the reflux symptom index (RSI); and procedure outcomes were collected and analyzed according to surgery type. RESULTS: A total of 92 patients (85 females and 7 males) met the inclusion criteria. The study included 17 patients in the MSA group, 71 patients in the SGRY group, and 4 patients who underwent both procedures. The average preoperative body mass index (BMI) of all patients was 33.3. Compared with patients who underwent MSA, those who underwent SGRY presented with higher BMI (29.4 vs 34.2, respectively; P = .013), preoperative GERD-HRQL (35 vs 52, respectively; P = .046), and RSI (14 vs 28, respectively; P = .017). Postoperatively, patients who underwent SGRY demonstrated a higher decrease in mean postoperative DeMeester score than those who underwent MSA (44.2 vs 13.9, respectively; P = .040), with 22 patients (50%) in the SGRY group vs 10 patients (20%) in the MSA group achieving normalization. CONCLUSION: Although MSA remains a viable surgical alternative, our study indicated that SGRY can produce better symptom control and decrease acid exposure compared with MSA in patients with post-SG GERD.