In grade C/D erosive esophagitis, vonoprazan ranks highest among PPIs and P-CABs for healing and maintaining remission.

SOURCE CITATION: Zhuang Q, Chen S, Zhou X, et al. Comparative efficacy of P-CAB vs proton pump inhibitors for grade C/D esophagitis: a systematic review and network meta-analysis. Am J Gastroenterol. 2024;119:803-813. 38345252.

Updates to the modern diagnosis of GERD: Lyon consensus 2.0.

The Lyon Consensus provides conclusive criteria for and against the diagnosis of gastro-oesophageal reflux disease (GERD), and adjunctive metrics that consolidate or refute GERD diagnosis when primary criteria are borderline or inconclusive. An international core and working group was assembled to evaluate research since publication of the original Lyon Consensus, and to vote on statements collaboratively developed to update criteria. The Lyon Consensus 2.0 provides a modern definition of actionable GERD, where evidence from oesophageal testing supports revising, escalating or personalising GERD management for the symptomatic patient. Symptoms that have a high versus low likelihood of relationship to reflux episodes are described. Unproven versus proven GERD define diagnostic strategies and testing options. Patients with no prior GERD evidence (unproven GERD) are studied using prolonged wireless pH monitoring or catheter-based pH or pH-monitoring off antisecretory medication, while patients with conclusive GERD evidence (proven GERD) and persisting symptoms are evaluated using pH-impedance monitoring while on optimised antisecretory therapy. The major changes from the original Lyon Consensus criteria include establishment of Los Angeles grade B oesophagitis as conclusive GERD evidence, description of metrics and thresholds to be used with prolonged wireless pH monitoring, and inclusion of parameters useful in diagnosis of refractory GERD when testing is performed on antisecretory therapy in proven GERD. Criteria that have not performed well in the diagnosis of actionable GERD have been retired. Personalisation of investigation and management to each patient's unique presentation will optimise GERD diagnosis and management.

Vonoprazan Versus Lansoprazole for Healing and Maintenance of Healing of Erosive Esophagitis: A Randomized Trial.

BACKGROUND & AIMS: For decades, proton pump inhibitors (PPIs) have been the mainstay of treatment for erosive esophagitis. The potassium-competitive acid blocker vonoprazan provides more potent acid inhibition than PPIs, but data on its efficacy for erosive esophagitis are limited. METHODS: Adults with erosive esophagitis were randomized to once-daily vonoprazan, 20 mg, or lansoprazole, 30 mg, for up to 8 weeks. Patients with healing were rerandomized to once-daily vonoprazan, 10 mg, vonoprazan, 20 mg, or lansoprazole, 15 mg, for 24 weeks. Primary end points, percentage with healing by week 8 endoscopy, and maintenance of healing at week 24 endoscopy, were assessed in noninferiority comparisons (noninferiority margins, 10%), with superiority analyses prespecified if noninferiority was demonstrated. Analyses of primary and secondary end points were performed using fixed-sequence testing procedures. RESULTS: Among 1024 patients in the healing phase, vonoprazan was noninferior to lansoprazole in the primary analysis and superior on the exploratory analysis of healing (92.9 vs 84.6%; difference, 8.3%; 95% confidence interval [CI], 4.5%-12.2%). Secondary analyses showed vonoprazan was noninferior in heartburn-free days (difference, 2.7%; 95% CI, -1.6% to 7.0%), and superior in healing Los Angeles Classification Grade C/D esophagitis at week 2 (difference, 17.6%; 95% CI, 7.4%-27.4%). Among 878 patients in the maintenance phase, vonoprazan was noninferior to lansoprazole in the primary analysis and superior on the secondary analysis of maintenance of healing (20 mg vs lansoprazole: difference, 8.7%; 95% CI, 1.8%-15.5%; 10 mg vs lansoprazole: difference, 7.2%; 95% CI, 0.2%-14.1%) and secondary analysis of maintenance of healing Grade C/D esophagitis (20 mg vs lansoprazole: difference, 15.7%; 95% CI, 2.5%-28.4%; 10 mg vs lansoprazole: difference, 13.3%; 95% CI, 0.02%-26.1%). CONCLUSIONS: Vonoprazan was noninferior and superior to the PPI lansoprazole in healing and maintenance of healing of erosive esophagitis. This benefit was seen predominantly in more severe erosive esophagitis. (ClinicalTrials.gov: NCT04124926).

S3260 An Interesting Case of Lymphocytic Esophagitis In Association With Pityriasis LichenoidesChronica and Rheumatoid Arthritis.

INTRODUCTION: Lymphocytic esophagitis (LyE) is a rare esophageal disorder of unknown etiology, characterized by dense peripapillary lymphocytes without neutrophils or eosinophils, and spongiosis. Patients typically present with symptoms such as dysphagia or chest pain. Here, we describe a notable case of lymphocytic esophagitis in a patient who presented with food impaction. CASE DESCRIPTION/METHODS: A 53-year-old woman with a history of pityriasis lichenoideschronica and rheumatoid arthritis reported chronic dysphagia and sought emergency care for food impaction. A subsequent upper endoscopy revealed a long submucosal tear in the upper esophagus during intubation (see Figure 1A), leading to the procedure's cessation. A follow-up upper endoscopy 9 weeks later, employing an ultra-slim scope, identified severe stenosis in the upper esophagus (see Figure 1B). Dilation was performed using a Savary dilator. Examination of the esophageal lining revealed edema, rings, and furrows. Proximal and distal esophageal biopsies were obtained, indicating a marked increase in intraepithelial lymphocytes, with an absence of eosinophils or neutrophils. The squamous epithelium exhibited evidence of spongiosis and necrotic keratinocytes, consistent with a diagnosis of lymphocytic esophagitis. The patient continued omeprazole 40 mg twice daily and started budesonide at 1 mg twice daily. A repeat upper endoscopy with esophageal biopsies demonstrated a significant improvement in lymphocytic infiltration (see Figure 2A-B). DISCUSSION: LyE typically manifests in females during their 5th-6th decades, presenting a notable contrast to eosinophilic esophagitis (EOE), which predominantly affects males in their 2nd-3rd decades. However, the endoscopic appearance of LyE often mirrors that of EOE. Studies suggest potential associations between LyE and Crohn's disease in children, as well as primary esophageal dysmotility in adults. Notably, our patient has a history of rheumatoid arthritis, a correlation observed in 2 other cases in the literature. While limited literature exists on pityriasis lichenoideschronica with esophageal involvement, specifically presenting as LyE, this singular case underscores the interconnection of these 2 disease processes. These observations raise the possibility of an autoimmune etiology. There is no consensus on the lymphocyte count threshold for diagnosis, a challenge compounded by the rarity of the disease, leading to a lack of definitive guidelines for optimal management.JOURNAL/ajgast/04.03/00000434-202410001-03261/figure1/v/2024-10-11T031912Z/r/image-tiff.

Comparative Efficacy of P-CAB vs Proton Pump Inhibitors for Grade C/D Esophagitis: A Systematic Review and Network Meta-analysis.

INTRODUCTION: Los Angeles grade C/D esophagitis is a severe manifestation of gastroesophageal reflux disease that require active treatment and close follow-up. Potassium competitive acid blockers (P-CAB) are promising alternatives to proton pump inhibitors (PPI). We aimed to compare the efficacy and safety of P-CAB and PPI in healing grade C/D esophagitis to aid clinical decision-making. METHODS: A systematic literature search was performed using PubMed, MEDLINE, and Cochrane Central Register of Controlled Trials. Randomized controlled trials were eligible for inclusion if efficacy of P-CAB and PPI in healing grade C/D esophagitis was reported. Pooled risk ratios and risk difference with 95% credible intervals were used to summarize estimated effect of each comparison. The benefit of treatments was ranked using the surface under the cumulative probability ranking score. RESULTS: Of 5,876 articles identified in the database, 24 studies were eligible. Studies included incorporated 3 P-CAB (vonoprazan, tegoprazan, and keverprazan) and 6 PPI (lansoprazole, esomeprazole, omeprazole, rabeprazole extended-release (ER), pantoprazole, and dexlansoprazole). Based on the failure to achieve mucosal healing, 20 mg of vonoprazan q.d. ranked the first among PPI in initial and maintained healing of grade C/D esophagitis (surface under the cumulative probability ranking score = 0.89 and 0.87, respectively). Vonoprazan had similar risk of incurring adverse events, severe adverse events, and withdrawal to drug when compared with PPI. For those who attempted lower maintenance treatment dose, 10 mg of vonoprazan q.d. was a reasonable choice, considering its moderate efficacy and safety. DISCUSSION: Vonoprazan has considerable efficacy in initial and maintained healing of grade C/D esophagitis compared with PPI, with moderate short-term and long-term safety.

Comparing Gastrointestinal Endoscopy Findings in Children with Autism, Developmental Delay, or Typical Development.

OBJECTIVE: To compare endoscopic and histologic upper endoscopy (esophagogastroduodenoscopy [EGD]) findings in children with autism spectrum disorders (ASD) to age- and gender-matched controls with developmental delay (DD) or with typical development (TD). METHODS: Retrospective, cross-sectional study of children undergoing EGD, identifying those diagnosed with ASD, and matching on age and gender to children with DD or TD in ratio of 1:1:2. Rates of EGD findings were compared between the 3 groups using χ² or Fisher exact test. Multivariable linear regression was performed to identify predictors of abnormal histology. RESULTS: A total of 2104 patients were included (526 ASD; 526 DD; 1052 TD). Children with ASD had higher rates of abnormal esophageal histology (ASD 38.4%; DD 33.4%; TD 30.4%, P = .008), particularly esophagitis. In multivariable modeling, ASD diagnosis was an independent predictor of abnormal esophageal histology (OR [95% CI] 1.38 [1.09, 1.76]) compared with TD. Stomach findings did not differ among the groups. In the duodenum, histologic abnormalities were observed with lower frequency in ASD (ASD 17.0%; DD 20.1%; TD 24.2%, P = .005). In multivariable analysis, ASD diagnosis was not a significant predictor (OR 0.78 [0.56, 1.09]) of abnormal duodenal histology. CONCLUSIONS: Children with ASD have higher rates of histologic esophagitis compared with age- and gender-matched DD and TD controls. ASD was a significant independent predictor of abnormal esophageal, but not, duodenal, histology. These results underscore the importance of EGD in children with ASD.

Impact of metabolic unhealthiness and its changes on the risk of erosive esophagitis: a cohort study.

BACKGROUND AND AIM: We aimed to compare the risk of erosive esophagitis (EE) among individuals with different phenotypes based on metabolic health status and obesity and investigate the role of changes in metabolic health in EE risk. METHODS: A cohort of 258 892 asymptomatic adults without EE at baseline who underwent ollow-up esophagogastroduodenoscopy (EGD) were categorized into the following four groups according to metabolic health and obesity status: (i) metabolically healthy (MH) non-obese; (ii) metabolically unhealthy (MU) non-obese; (iii) MH obese; and (iv) MU obese. EE was defined as the presence of grade A or higher mucosal breaks on EGD. RESULTS: During a median follow-up of 4.5 years, the incidence rates of EE were 0.6/103 person-years (PY), 1.7/103 PY, 1.7/103 PY, and 3.1/103 PY in the MH non-obese, MU non-obese, MH obese, and MU obese groups, respectively. The multivariable-adjusted hazard ratio (HR) (95% confidence intervals [CI]) for developing EE comparing the MH obese, MU non-obese, and MU obese groups with the MH non-obese group were 1.49 (1.29-1.71), 1.56 (1.25-1.94), and 2.18 (1.90-2.49), respectively. The multivariable-adjusted HR (95% CI) comparing the progression of MH to MU, regression of MU to MH, and persistent MU with the persistent MH group were 1.39 (1.10-1.76), 1.39 (1.09-1.77), and 1.86 (1.56-2.21), respectively. The increased risk of EE among the persistent MU group was consistently observed in individuals without obesity or abdominal obesity. CONCLUSION: Metabolic unhealthiness and obesity were independent risk factors for the development of EE, suggesting that maintaining both normal weight and metabolic health may help reduce the risk of EE.

Association of metabolic dysfunction-associated steatotic liver disease with erosive esophagitis development: a longitudinal observational study.

BACKGROUND AND AIM: Although erosive esophagitis (EE) is associated with fatty liver and metabolic dysregulation, the association between EE and metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. Thus, this study aimed to investigate the longitudinal association between MASLD and EE. METHODS: We included 1578 patients without EE at baseline who underwent more than two health checkups over 2 years. Generalized estimation equations were used to analyze associations between MASLD and EE according to repeated measures at baseline and most recent stages. RESULTS: EE development rates in men and women were 14.5% and 7.2%, respectively. After adjusting for lifestyle habits, the odds ratios of MASLD for EE development in men and women were 1.907 (95% confidence interval [CI]: 1.289-2.832, P < 0.005) and 1.483 (95% CI: 0.783-2.811, P = 0.227), respectively. In the subgroup analysis, after adjusting for lifestyle habits, among men and women aged ≥50 years with more than three MASLD components, the odds ratios for EE development were 2.408 (95% CI: 1.505-3.855, P < 0.001) and 2.148 (95% CI: 1.093-4.221, P < 0.05), respectively. After adjusting for various factors, the significant risk factors for EE development were different between men and women. CONCLUSION: The influence of MASLD and other factors on EE development differed by sex and age. Particularly, patients aged ≥50 years with MASLD and with an increased number of MASLD components should be considered at increased risk for EE.

Vonoprazan is superior to lansoprazole for healing of severe but not mild erosive esophagitis: A systematic review with meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Healing rates of severe erosive esophagitis (EE; Los Angeles [LA] Grade C/D) in patients treated with a proton pump inhibitor (PPI) is suboptimal (~60-70%). Vonoprazan, a potassium-competitive acid blocker, is suggested to have better healing rates in patients with severe EE. This meta-analysis compares the efficacy and safety of vonoprazan 20 mg versus lansoprazole 30 mg daily in healing EE, specifically in those with LA Grade C/D. METHODS: We searched MEDLINE, Embase, and CENTRAL on May 24, 2023. Studies that randomized EE patients to vonoprazan 20 mg daily or lansoprazole 30 mg daily and compared healing rates were included. The risk of bias was assessed using Cochrane's Risk of Bias 2 tool. The fixed-effect model was used to obtain the pooled efficacy and safety outcomes. Subgroup analysis was done to compare healing rates in mild (LA Grade A/B) versus severe EE and based on study location. RESULTS: Four randomized controlled trials (RCTs) with low risks of bias comprising 2208 participants were included. Vonoprazan 20 mg was superior to lansoprazole 30 mg daily in healing severe EE at all weeks (Week 2 RR 1.294 [95% CI 1.169-1.433], Week 4 1.160 [1.059-1.270], and Week 8 1.175 [95% CI 1.107-1.247]), but was similar for mild EE at all weeks (P-interaction < 0.01). Vonoprazan 20 mg was more efficacious than lansoprazole 30 mg at Week 8 in Western versus Asian studies (P-interaction < 0.01). Any, serious, and drug-related treatment-emergent adverse events were comparable between groups. CONCLUSION: Vonoprazan 20 mg is superior to lansoprazole 30 mg for healing severe EE but not mild EE. Vonoprazan 20 mg daily has a similar safety profile to lansoprazole 30 mg daily.

Cystine and theanine for chemoradiotherapy-induced esophagitis in non-small cell lung cancer: a prospective observational study.

PURPOSE: Although several potential radioprotectants have been explored, radiation esophagitis is still difficult to control. Further development of supportive therapies is required. Our purpose was to investigate the efficacy and safety of cystine and theanine for esophagitis in non-small cell lung cancer (NSCLC) patients undergoing chemoradiotherapy (CRT). METHODS: This study is a prospective observational study. The participants were recruited from unresectable locally advanced NSCLC who had scheduled to receive weekly paclitaxel or nab-paclitaxel/carboplatin plus radiation therapy (60 Gy in 30 fractions) for 6 weeks. They took an oral amino acid supplement containing 700 mg cystine and 280 mg theanine once daily regardless of CRT timing from the start of CRT until completion. The primary endpoint was the incidence of any grade esophagitis. The secondary endpoints were quality of life (QoL) and adverse events (AEs). RESULTS: A total of 26 patients were evaluated. All participants completed 60 Gy of RT in 30 fractions. The overall incidence of esophagitis was 73%; however, no ≥ grade 3 was reported. There were no AEs likely to be related to cystine and theanine. The mean EuroQoL 5-Dimension 5-Level health index score before and after chemoradiotherapy was 0.952 ± 0.0591 and 0.952 ± 0.0515 (P = 0.89), and the mean Visual Analogue Scale scores before and after treatment were 67.9 ± 15.4 and 79.4 ± 13.2 (P = 0.0047), respectively. CONCLUSION: Our study showed no severe esophagitis, any AEs, nor QoL decrease in NSCLC patients receiving CRT. Cystine and theanine are potentially effective to reduce severe CRT-induced esophagitis. TRIAL REGISTRATION: UMIN000052622, 26 October 2023, retrospectively registered.

Long-term outcomes of laparoscopic Heller's myotomy with angle of His accentuation in patients of achalasia cardia.

BACKGROUND: Laparoscopic Heller's myotomy (LHM) is an established treatment for achalasia cardia. Anti-reflux procedures (ARP) are recommended with LHM to reduce the post-operative reflux though the optimal anti-reflux procedure is still debatable. This study reports on the long-term outcomes of LHM with Angle-of-His accentuation (AOH) in patients of achalasia cardia. METHODS: One hundred thirty-six patients of achalasia cardia undergoing LHM with AOH between January 2010 to October 2021 with a minimum follow-up of one year were evaluated for symptomatic outcomes using Eckardt score (ES), DeMeester heartburn (DMH) score and achalasia disease specific quality of life (A-DsQoL) questionnaire. Upper gastrointestinal endoscopy, high resolution manometry (HRM) and timed barium esophagogram (TBE) were performed when feasible and rates of esophagitis and improvement in HRM and TBE parameters evaluated. Time dependent rates of success were calculated with respect to improvement in ES and dysphagia-, regurgitation- and heartburn-free survival using Kaplan-Meier analysis. RESULTS: At a median follow-up of 65.5 months, the overall success (ES ≤ 3) was 94.1%. There was statistically significant improvement in ES, heartburn score and A-DsQoL score (p < 0.00001, p = 0.002 and p < 0.00001). Significant heartburn (score ≥ 2) was seen in 12.5% subjects with 9.5% patients reporting frequent PPI use (> 3 days per week). LA-B and above esophagitis was seen in 12.7%. HRM and TBE parameters also showed a significant improvement as compared to pre-operative values (IRP: p < 0.0001, column height: p < 0.0001, column width: p = 0.0002). Kaplan-Meier analysis showed dysphagia, regurgitation, and heartburn free survival of 75%, 96.2% and 72.3% respectively at 10 years. CONCLUSIONS: LHM with AOH gives a lasting relief of symptoms in patients of achalasia cardia with heartburn rates similar to that reported in studies using Dor's or Toupet's fundoplication with LHM. Hence, LHM with AOH may be a preferred choice in patients of achalasia cardia given the simplicity of the procedure.

Clinical findings of acute necrotizing esophagitis complicated by diabetic ketoacidosis.

Acute necrotizing esophagitis (ANE) is a rare and potentially life-threatening complication of diabetic ketoacidosis (DKA). While its association with DKA is established, specific clinical characteristics that predict ANE in DKA patients remain less understood. This study aimed to identify these characteristics by analyzing data from 30 DKA patients admitted from January 2018 to September 2022. Seven patients in this study presented with ANE, forming the ANE group. The remaining 23 constituted the non-ANE group. We compared the clinical parameters and computed tomography (CT) between the groups. The mean age of participants was 57.7 ± 20.4 years, and their mean HbA1c was 11.1 ± 3.3%. Notably, ethanol intake was significantly higher in the ANE group (44.4 ± 25.4 g/day) compared to the non-ANE group (6.8 ± 14.0 g/day; p = 0.013). Additionally, sodium-glucose transport protein 2 inhibitor use was significantly more prevalent in the ANE group (p = 0.013). Gastrointestinal symptoms were also significantly more pronounced in the ANE group, with vomiting occurring in 85.7% of patients compared to only 13.0% in the non-ANE group. Admission CT scans revealed further distinguishing features, with the ANE group showing significantly higher rates of esophageal wall thickening, intra-esophageal effusion, and calcification of the celiac artery origin (p < 0.0001, 0.0038, 0.0038, respectively). In conclusion, our study suggests that heavy alcohol consumption and strong gastrointestinal symptoms in DKA patients warrant a heightened suspicion of ANE. Early consideration of CT or upper gastrointestinal endoscopy is recommended in such cases.

Evaluation of the effectiveness of mother milk exosomes in the experimental corrosive esophagitis model.

PURPOSE: We aimed to examine the effectiveness of mother milk exosomes in treating corrosive esophageal burns. MATERIALS AND METHODS: 32 rats were separated into four equal groups and weighed individually before the procedure. A corrosive esophageal burn model was created with 12.5% sodium hydroxide by a 3F Fogarty catheter. Group 1 did not apply any process or treatment, Group 2 was burned, and no treatment was performed. Group 3 was burned, and then 0.5 cc/day of mother milk exosome extract was given. Group 4 was not applied any process, and 0.5 cc/day mother milk exosome extract was given. All rats were weighed again and sacrificed. Biopsy samples were sent to the pathology laboratory for histopathological examination (in terms of inflammation, fibrosis, and necrosis).Kindly check and confrm all email ids.The e-mail addresses and affiliation of all authors were checked. Affiliation departments are as stated on the title page. There is no change. RESULTS: A significant difference was found in the results of inflammation and fibrosis. There was a meaningful difference in fibrosis between the 2nd and 3rd groups. There was weight gain in groups 1, 3 and 4. Statistical evaluations for each group were significant. CONCLUSION: It was observed that breast milk exosomes may be effective in inflammation and fibrosis formation in treating corrosive esophageal burns. This suggested that breast milk exosomes reduce stricture formation due to esophageal corrosion.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [specify authors given name] Last name [specify authors last name]. Also, kindly confirm the details in the metadata are correct.The names and affiliation of all authors were checked. Affiliation departments are as stated on the title page. There is no change. Also we confirm the details in the metadata.

[Porphyromonas gingivalis promotes the occurrence of esophageal squamous cell carcinoma via an inflammatory microenvironment].

Objective: To investigate the role of an inflammatory microenvironment induced by Porphyromonasgingivalis (P. gingivalis) in the occurrence of esophageal squamous cell carcinoma (ESCC) in mice. Methods: A total of 180 C57BL/6 mice were randomly divided into 6 groups, i.e. control group, P. gingivalis group, 4NQO group, 4NQO + P. gingivalis group, 4NQO + P. gingivalis + celecoxib group, and 4NQO + P. gingivalis + antibiotic cocktail (ABC, including metronidazole, neomycin, ampicillin, and vancomycin) group, with 30 mice in each group, using the random number table. All mice were normalized by treatment with ABC in drinking water for 2 weeks. In the following 2 weeks, the mice in the control group and the P. gingivalis group were given drinking water, while the other 4 groups were treated with 30 µg/ml 4NQO in the drinking water. In weeks 11-12, the mice in the P. gingivalis group, the 4NQO + P. gingivalis group, the 4NQO + P. gingivalis + celecoxib group, and the 4NQO + P. gingivalis + ABC group were subjected to ligation of the second molar in oral cavity followed by oral P. gingivalis infection thrice weekly for 24 weeks in weeks 11-34. In weeks 13-34, the mice in 4NQO + P. gingivalis+celecoxib group and 4NQO + P. gingivalis + ABC group were administered with celecoxib and ABC for 22 weeks, respectively. At the end of 34 weeks, gross and microscopic alterations were examined followed by RT-qPCR and immunohistochemistry to examine the expression profiles of inflammatory- and tumor-molecules in esophagi of mice. Results: At 34 weeks, 4NQO treatment alone did not affect the foci of papillary hyperproliferation, diseased area, and the thickness of the esophageal wall, but significantly enhanced the foci of hyperproliferation (median 1.00, P＜0.05) and mild/moderate dysplasia (median 2.00, P＜0.01). In addition, the expression levels of IL-6 [8.35(3.45,8.99)], IL-1ß [6.90(2.01,9.72)], TNF-α [12.04(3.31,14.08)], c-myc [2.21(1.80,3.04)], pSTAT3, Ki-67, and pH2AX were higher than those in the control group. The pathological changes of the esophageal mucosa were significantly more overt in the 4NQO + P. gingivalis group in terms of the foci of papillary hyperproliferation (median 2.00), diseased area (median 2.51 mm2), the thickness of the esophageal wall (median 172.52 µm), the foci of hyperproliferation (median 1.00, P＜0.05), and mild/moderate dysplasia (median 1.00, P＜0.01). In mice of the 4NQO + P. gingivalis group, the expression levels of IL-6 [12.27(5.35,22.08)], IL-1ß [13.89(10.04,15.96)], TNF-α [19.56(6.07,20.36)], IFN-γ [11.37(8.23,20.07)], c-myc [2.62(1.51,4.25)], cyclin D1 [4.52(2.68,7.83)], nuclear pSTAT3, COX-2, Ki-67, and pH2AX were significantly increased compared with the mice in the control group. In mice of the 4NQO + P. gingivalis group, the diseased area, invasive malignant foci as well as pSTAT3 and pH2AX expression were significantly blunted by celecoxib. Treatment with ABC markedly reduced the papillary hyperproliferative foci, invasive malignant foci, and pSTAT3 expression but not pH2AX. Conclusions: P. gingivalis promotes the occurrence of esophageal squamous cell carcinoma in mice by inducing an inflammatory microenvironment primed with 4NQO induced DNA damage. Clearance of P. gingivalis with ABC or anti-inflammatory intervention holds promise for prevention of esophageal squamous cell malignant pathogenesis via blockage of IL-6/STAT3 signaling and amelioration of inflammation.

[A case of immune-related gastroesophagitis with laryngopharyngitis caused by immune checkpoint inhibitors in nonsmall cell lung cancer].

With the advent of immune checkpoint inhibitors (ICI), cancer treatment options have widened in recent years. However, ICI-specific adverse events (irAEs) have been reported. Lower gastrointestinal lesions, such as colitis and enteritis, account for most gastrointestinal irAEs, and reports of upper gastrointestinal lesions are rare. We report a rare case of gastroesophagitis associated with ICI. The patient was a 64-year-old male. He was diagnosed with lung adenocarcinoma stage IIIB (cT2aN3M0), and pembrolizumab (PEM) was started as a first-line treatment. Severe gastroesophagitis with laryngopharyngitis was confirmed 5 months after PEM administration. These improved after withdrawal of PEM and steroid administration. Reports of ICI-associated gastritis remain limited, especially with laryngopharyngitis;therefore, we consider this case as valuable, in which we confirmed the clinical features of ICI-associated gastroesophagitis and its therapeutic effects.

Outcomes of definitive carbon-ion radiotherapy for cT1bN0M0 esophageal squamous cell carcinoma.

BACKGROUND: A recent phase I/II study determined the optimal dose of definitive carbon-ion radiotherapy (CIRT) for cT1bN0M0 esophageal cancer. This study aimed to further confirm the efficacy and feasibility of the recommended dose fractionation of CIRT with long-term follow-up results in a larger sample size. METHODS: This single center retrospective study evaluated patients with cT1bN0M0 esophageal squamous cell carcinoma treated with the recommended dose fractionation of 50.4 Gy relative biological effectiveness in 12 fractions, between 2012 and 2022. RESULTS: Thirty-eight patients underwent CIRT at our hospital. Although eight (21.1%) patients were older than 80 years, 15 (39.5%) had high surgical risk, and seven (18.4%) were at high risk for chemotherapy, all patients underwent CIRT as scheduled. Grade 3 esophagitis occurred in eight (21.1%) patients and grade 3 pneumonia in one (2.6%) patient in this study, but no grade 4 adverse events occurred. The only grade 3 late adverse event was pneumonia in one patient (2.6%). The 5-year overall survival rate, local control rate, and disease-free survival rates were 76.6% (95% CI, 90.9-62.4), 74.9% (95% CI, 90.7-59.0), and 66.4% (95% CI, 83.3-49.5), respectively. Additionally, post CIRT recurrence was as follows: seven (18.4%) patients had recurrence in another part of the esophagus, three (7.9%) in the primary site, three (7.9%) in lymph nodes outside the irradiated area, and one (2.6%) patient had liver metastasis. CONCLUSIONS: Our study demonstrates that CIRT using the recommended dose fractionation is feasible and effective for cT1bN0M0 esophageal squamous cell carcinoma.

Achalasia: laparoscopic Heller myotomy with fundoplication versus peroral endoscopic myotomy-a systematic review and meta-analysis.

There are various therapeutic options for achalasia. Nevertheless, peroral endoscopic myotomy (POEM) and laparoscopic Heller myotomy with fundoplication (LHM) are distinguished by their efficacy and low incidence of complications. Compare POEM and LHM regarding several outcomes in patients with achalasia. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. An exhaustive literature search was performed using PubMed, Web of Science, and Cochrane Library databases. Studies comparing several outcomes between POEM and LHM in patients with achalasia were included. Data on clinical success, operative time, intraoperative complications, length of stay, reintervention rates, postoperative pain, overall complications, occurrence of GERD symptoms, use of proton bomb inhibitors and esophagitis were extracted. Quality assessment of the included studies was performed using the MINORS scale. We included 20 retrospective observational studies with a combined total of 5139 participants. The results demonstrated that there was no statistically significant difference in terms of intraoperative complications, postoperative complications, reintervention rate, occurrence of GERD symptoms, GERD HRQL, use of proton pump inhibitors, and esophagitis between POEM and LHM groups. Conversely, POEM was associated with higher clinical success and shorter operative time, length of stay, and postoperative pain. This meta-analysis concludes that both POEM and LHM, are effective and safe treatments for achalasia. However, POEM demonstrates better results regarding clinical success, operative time, length of stay, postoperative pain, and a tendency towards lower recurrence.

Outcomes of Heller Myotomy for Esophageal Achalasia: Lessons From a 48-Year Prospective Experience With 4 Different Techniques.

OBJECTIVE: To provide information on long-term outcomes of Heller myotomy for esophageal achalasia with or without an antireflux fundoplication. BACKGROUND: Since the adoption of the Heller myotomy, surgeons have modified the original technique in order to balance the cure of dysphagia and the consequent cardial incontinence. METHODS: Totally, 470 patients underwent primary Heller myotomy between 1955 and 2020. A long abdominal myotomy (AM) was performed in 83 patients, the Ellis limited transthoracic myotomy (TM) in 30, the laparotomic Heller-Dor (L-HD) in 202, the videolaparoscopic Heller-Dor (VL-HD) in 155. The HD was performed under intraoperative manometric assessment. Starting on 1973 these patients underwent a prospective follow-up program of timed lifelong clinical, radiological, endoscopic evaluations. RESULTS: Median follow-up time was 23.06 years [interquantile range (IQR): 15.04-32.06] for AM, 29.22 years (IQR: 13.46-40.17) for TM, 14.85 years (IQR: 11.05-21.56) for L-HD and 7.51 years (IQR: 3.25-9.60) for VL-HD. In AM, relapse of dysphagia occurred in 25/71 (35.21%), in TM in 11/30 (36.66%), in LH-D in 10/201 (4.97%), in VL-HD in 3/155 (1.93%). Erosive-ulcerative esophagitis was diagnosed for AM in 28.16%, for TM in 30%, for L-HD in 8.45%, for VL-HD in 2.58%. Overall, the outcome was satisfactory in 52.11% for AM, 41.9% for TM, 89.05% for L-HD, 96.12% for VL-HD. CONCLUSIONS: The Dor fundoplication drastically reduces postmyotomy gastroesophageal reflux. The Heller-Dor operation is a competitive option for the cure of esophageal achalasia if this operation is performed according to the rules of surgical physiology learned by means of intraoperative manometry.

AGA Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors: Expert Review.

DESCRIPTION: Proton pump inhibitors (PPIs) are among the most commonly used medications in the world. Developed for the treatment and prevention of acid-mediated upper gastrointestinal conditions, these agents are being used increasingly for indications where their benefits are less certain. PPI overprescription imposes an economic cost and contributes to polypharmacy. In addition, PPI use has been increasingly linked to a number of adverse events (PPI-associated adverse events [PAAEs]). Therefore, de-prescribing of PPIs is an important strategy to lower pill burden while reducing real costs and theoretical risks. The purpose of this clinical update was to provide Best Practice Advice (BPA) statements about how to approach PPI de-prescribing in ambulatory patients. METHODS: Our guiding principle was that, although PPIs are generally safe, patients should not use any medication when there is not a reasonable expectation of benefit based on scientific evidence or prior treatment response. Prescribers are responsible for determining whether PPI use is absolutely or conditionally indicated and, when uncertainty exists, to incorporate patient perspectives into PPI decision making. We collaboratively outlined a high-level "process map" of the conceptual approach to de-prescribing PPIs in a clinical setting. We identified the following 3 key domains that required BPA guidance: documentation of PPI indication; identifying suitable candidates for consideration of de-prescribing; and optimizing successful de-prescribing. Co-authors drafted 1 or more potential BPAs, supported by literature review, for each domain. All co-authors reviewed, edited, and selected or rejected draft BPAs for inclusion in the final list submitted to the American Gastroenterological Association Governing Board. Because this was not a systematic review, we did not carry out a formal rating of the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: All patients taking a PPI should have a regular review of the ongoing indications for use and documentation of that indication. This review should be the responsibility of the patient's primary care provider. BEST PRACTICE ADVICE 2: All patients without a definitive indication for chronic PPI should be considered for trial of de-prescribing. BEST PRACTICE ADVICE 3: Most patients with an indication for chronic PPI use who take twice-daily dosing should be considered for step down to once-daily PPI. BEST PRACTICE ADVICE 4: Patients with complicated gastroesophageal reflux disease, such as those with a history of severe erosive esophagitis, esophageal ulcer, or peptic stricture, should generally not be considered for PPI discontinuation. BEST PRACTICE ADVICE 5: Patients with known Barrett's esophagus, eosinophilic esophagitis, or idiopathic pulmonary fibrosis should generally not be considered for a trial of de-prescribing. BEST PRACTICE ADVICE 6: PPI users should be assessed for upper gastrointestinal bleeding risk using an evidence-based strategy before de-prescribing. BEST PRACTICE ADVICE 7: Patients at high risk for upper gastrointestinal bleeding should not be considered for PPI de-prescribing. BEST PRACTICE ADVICE 8: Patients who discontinue long-term PPI therapy should be advised that they may develop transient upper gastrointestinal symptoms due to rebound acid hypersecretion. BEST PRACTICE ADVICE 9: When de-prescribing PPIs, either dose tapering or abrupt discontinuation can be considered. BEST PRACTICE ADVICE 10: The decision to discontinue PPIs should be based solely on the lack of an indication for PPI use, and not because of concern for PAAEs. The presence of a PAAE or a history of a PAAE in a current PPI user is not an independent indication for PPI withdrawal. Similarly, the presence of underlying risk factors for the development of an adverse event associated with PPI use should also not be an independent indication for PPI withdrawal.

What is the Prevalence of Clinically Significant Endoscopic Findings in Subjects With Dyspepsia? Updated Systematic Review and Meta-analysis.

BACKGROUND & AIMS: The prevalence of clinically significant endoscopic findings in people with dyspepsia and understanding how symptoms can predict endoscopic pathology can help inform dyspepsia guidelines. We evaluated this in an updated systematic review and meta-analysis. METHODS: We searched MEDLINE, EMBASE, Cochrane CENTRAL, and the Cochrane Database of Systematic Reviews from 2010 through to January 2022 to identify relevant articles. Eligible studies enrolled adults from the community, workplace, blood donation or screening clinics, family physician offices, or internal medicine clinics. Studies were required to report prevalence of dyspepsia and perform esophagogastroduodenoscopy (EGD). Prevalence of clinically significant endoscopic findings in subjects with and without dyspepsia was pooled for all studies and compared using odds ratios and 95% confidence intervals (CIs). The data were pooled with those of the 9 studies included in the prior review. RESULTS: Of 511 papers evaluated, 184 reported prevalence of dyspepsia. Fifteen reported prevalence of endoscopic findings among 41,763 participants (40.4% with dyspepsia). Erosive esophagitis was the most common abnormality (pooled prevalence, 11.0%; 95% CI, 8.9%-13.2%) followed by peptic ulcer (pooled prevalence, 4.4%; 95% CI, 2.5%-6.7%). The only finding encountered more frequently in individuals with dyspepsia, compared with those without, was peptic ulcer (odds ratio, 1.61; 95% CI, 1.08-2.39). More than 85% of EGDs were completely normal. Gastroesophageal cancer was rare (<0.4%) and equally prevalent among those with and without dyspepsia. CONCLUSIONS: Erosive esophagitis was the most common clinically significant finding at EGD, whereas gastroesophageal cancers were rare. Most pathology, including esophagitis and cancer, were found in similar proportions in both groups. These findings support noninvasive approaches to managing dyspepsia in the community, with EGD reserved for those at high risk of malignancy.