Correlation of gastrointestinal symptom rating scale and frequency scale for the symptoms of gastroesophageal reflux disease with endoscopic findings.

BACKGROUND: Gastroesophageal Reflux Disease (GERD) is caused by the reflux of gastric contents into the esophagus and has a 13% global prevalence that is increasing. GERD symptoms negatively impact physical, social, and emotional quality of life. The Frequency Scale for the Symptoms of GERD (FSSG) and the Gastrointestinal Symptom Rating Scale (GSRS) determine the efficacy of treatment but may not correlate with endoscopically estimated esophageal mucosal injury severity. We aimed to probe the correlation between FSSG, GSRS, and esophageal injury severity to evaluate whether these scores can predict GERD severity. METHODS: A total of 2962 patients who underwent physical examinations, including upper gastrointestinal endoscopy, at the Kyoto Kuramaguchi Medical Center, Japan, were enrolled in this study. Upper gastrointestinal endoscopy was used to diagnose fundic mucosal atrophy, reflux esophagitis based on the Los Angeles (LA) classification, gastroesophageal flap value function (GEFV) based on Hill's classification, and Barrett's esophagus. Endoscopic diagnoses were examined for correlations with FSSG and GSRS scores. RESULTS: In reflux esophagitis, FSSG and GSRS scores correlated with LA-B and LA-C endoscopic diagnosis but not with LA-M and LA-A endoscopic findings. Multiple regression analysis results were similar. FSSG scores reflected advanced fundic gland mucosal atrophy, while GSRS scores associated with high grade of GEFV. CONCLUSIONS: This is the first report to examine the correlation between FSSG and GSRS scores and endoscopic findings in a relatively large patient population. Our findings suggest that these scores can diagnose the severity of reflux esophagitis.

Britannilactone 1-O-acetate induced ubiquitination of NLRP3 inflammasome through TRIM31 as a protective mechanism against reflux esophagitis-induced esophageal injury.

BACKGROUND: Reflux esophagitis (RE) is a disease in which inflammation of the esophageal mucosa owing to the reflux of gastric contents into the esophagus results in cytokine damage. Britannilactone 1-O-acetate (Brt) has anti-inflammatory effects, significantly inhibiting the activation of the NLRP3 inflammasome, leading to a decrease in inflammatory factors including IL-1 ß, IL-6, and TNF-α. However, the mechanism underlying its protective effect against RE-induced esophageal injury remains unclear. In the present study, we investigated the protective mechanism of TRIM31 against NLRP3 ubiquitination-induced RE both in vivo and in vitro. METHODS: A model of RE was established in vivo in rats by the method of "4.2 mm pyloric clamp + 2/3 fundoplication". In vitro, the mod was constructed by using HET-1A (esophageal epithelial cells) and exposing the cells to acid, bile salts, and acidic bile salts. The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay was used to screen the concentration of administered drugs, and the viability of HET-1A cells in each group. HE staining was used to assess the degree of pathological damage in esophageal tissues. Toluidine blue staining was used to detect whether the protective function of the esophageal epithelial barrier was damaged and restored. The enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of IL-1 ß, IL-6, and TNF-α factors in serum. Immunohistochemistry (IHC) was used to detect the expression level of NLRP3 in esophageal tissues. The molecular docking and Co-immunoprecipitation assay (Co-IP assay) were used to detect the TRIM31 interacts with NLRP3. Western blotting detected the Claudin-4, Claudin-5, The G-protein-coupled receptor calcium-sensitive receptor (CaSR), NLRP3, TRIM31, ASC, C-Caspase1, and Caspase1 protein expression levels. RESULTS: Brt could alleviate RE inflammatory responses by modulating serum levels of IL-1 ß, IL-6, and TNF-α. It also activated the expression of NLRP3, ASC, Caspase 1, and C-Caspase-1 in HET-1A cells. Brt also attenuated TRIM31/NLRP3-induced pathological injury in rats with RE through a molecular mechanism consistent with the in vitro results. CONCLUSIONS: Brt promotes the ubiquitination of NLRP3 through TRIM31 and attenuates esophageal epithelial damage induced by RE caused by acidic bile salt exposure. This study provides valuable insights into the mechanism of action of Brt in the treatment of RE and highlights its promising application in the prevention of NLRP3 inflammatory vesicle-associated inflammatory pathological injury.

Distal gastrectomy and Roux-en-Y reconstruction for refractory reflux esophagitis after proximal gastrectomy and esophagogastric anastomosis reconstruction.

Refractory gastroesophageal reflux disease can develop after proximal gastrectomy and esophagogastrostomy. We introduce a new method that combines distal gastrectomy and Roux-en-Y reconstruction to treat refractory reflux esophagitis in patients who have undergone proximal gastrectomy and esophagogastric anastomosis reconstruction. This novel method may be useful not only for alleviating the symptoms of gastroesophageal reflux disease but also for preventing future esophageal malignancies arising from long-term reflux esophagitis.

Endoscopic reflux esophagitis and decline in pulmonary function in nonsmokers: A retrospective cohort study.

BACKGROUND: The association between reflux esophagitis and pulmonary function remains controversial. Thus, evaluating the relationship between endoscopic reflux esophagitis and changes in pulmonary function over time in a nonsmoking population is an important clinical issue. METHODS: In this single-center retrospective cohort study, a medical examination database at Kameda Medical Center Makuhari was employed to identify nonsmokers who underwent upper gastrointestinal endoscopy and spirometry in 2010 and were followed up in 2015. Gastroenterologists carefully double-checked the diagnosis of reflux esophagitis. Multiple linear regression analyses were performed to compare the decline in the percentage of predicted vital capacity (%VC), forced vital capacity (%FVC), and forced expiratory volume in 1 s (%FEV1) between participants with reflux esophagitis and those without. Furthermore, using multivariable logistic regression analyses, we evaluated the factors associated with rapid decline in %VC, %FVC, and %FEV1, which is defined as a decrease of >10% in each parameter over the 5-year observation period. RESULTS: We identified 3098 eligible subjects, including 72 and 44 participants who had a Los Angeles classification grade A and B-C (severe) reflux esophagitis in 2010, respectively. The decline in %VC was significantly larger in the participants with severe reflux esophagitis than in the control subjects (standardized coefficient, -0.037; 95% confidence interval, -0.071 to -0.004). Moreover, reflux esophagitis was significantly associated with a rapid decline in %VC and %FVC but not in %FEV1 (P for trend: 0.009, 0.009, and 0.276, respectively). CONCLUSIONS: Severe reflux esophagitis among nonsmokers had clinical disadvantages in terms of a decline in %VC.

Antacids and reflux esophagitis as a risk factor for gastric neoplasm of fundic-gland type: A retrospective, matched case-control study.

BACKGROUND AND AIM: Since the first report of gastric adenocarcinoma of the fundic-gland type in 2010, the clinicopathological characteristics of gastric neoplasm of the fundic-gland type (GNFG) have become clearer; however, their risk factors remain unclear. This exploratory study aimed to identify the risk factors for GNFG. METHODS: We conducted a single-center, retrospective, matched case-control study using medical information recorded at our health management center from January 2014 to July 2023. During this period, 39 240 people underwent upper gastrointestinal endoscopy. GNFG were extracted as cases and matched to controls, according to age and sex, in a 1:8 ratio, excluding those with a history of gastrointestinal surgery and those with a history or comorbidity of cancer. Univariate analysis was used to compare patient background and endoscopic findings. Multivariable analysis was performed, adjusting for factors with P values < 0.1 and antacid use. RESULTS: A total of 20 GNFG cases and 160 matched healthy controls were included. In the univariate analysis, only reflux esophagitis was significantly more common in GNFG (40.0% vs 18.1%; P = 0.036). Factors antacids and duodenitis had P values < 0.1. Logistic regression analysis was performed, adjusting for antacids, reflux esophagitis, and duodenitis. Antacids and reflux esophagitis were the independent risk factors for GNFG (odds ratio = 3.68 [95% confidence interval: 1.04-11.91] and 3.25 [95% confidence interval: 1.11-9.35]). CONCLUSIONS: Although the sample of patients with GNFG was small, antacids and reflux esophagitis were identified as a risk factor. The pathogenesis of antacids and reflux esophagitis may be involved in the development of GNFG.

Incidence and risk factors of reflux esophagitis after peroral endoscopic myotomy.

BACKGROUND: Peroral endoscopic myotomy (POEM) is an effective and safe treatment for achalasia, but often leads to posttreatment gastroesophageal reflux disease. The aim of this study was to examine the incidence and severity of reflux esophagitis after POEM and to identify associated predictive factors. METHODS: Patients who underwent POEM between August 2011 and December 2022 were included. Multivariate logistic regression was used to assess predictive factors for reflux esophagitis after POEM. KEY RESULTS: In total, 252 patients were included; of which, 46% were female and age ranged between 18 and 87 years. Reflux esophagitis within 1 year after POEM was observed in 131 patients (52%), which was severe in 29 patients (LA grade C/D, 12%). Length of full-thickness myotomy (cm; OR 1.11, 95% CI 1.02-1.21), Eckardt scores before POEM (OR 0.84, 95% CI 0.74-0.96), previous pneumatic dilation (OR 0.51, 95% CI 0.29-0.91), and previous laparoscopic Heller myotomy (LHM; OR 0.44, 95% CI 0.23-0.86) were associated with reflux esophagitis after POEM. Alcohol use (none vs > 7 units per week; OR 3.51, 95% CI 1.35-9.11) and overweight (BMI ≥25 kg/m2; OR 2.67, 95% CI 1.17-6.09) were positive predictive factors and previous LHM (OR 0.13, 95% CI 0.02-0.95) was a negative predictive factor for severe reflux esophagitis after POEM (LA grade C/D). CONCLUSION: About half of the patients develop reflux esophagitis after POEM and 12% is graded as severe. Recognizing predictive factors of reflux esophagitis after POEM treatment leads to better patient selection before POEM and provides an opportunity to take preventive measures or start preemptive treatment.

Novel Endoscopic Findings of Lesions with a Short White Hair-like Appearance in the Lower Esophagus.

Objective The presence of a short white hair-like appearance in the lower esophagus has recently been noted during esophagogastroduodenoscopy (EGD) at our institution. Histological findings showed that this formation was a spiked protrusion of the esophageal papilla. The results regarding the prevalence of such lesions in individuals who underwent EGD examinations as part of medical checkup procedures are herein presented. Methods The EGD results of 14,338 individuals (9,225 males, 5,113 females; mean age 54.0±9.8 years) were examined. The findings related to the presence of multiple lesions with a short white hair-like appearance in the lower esophagus of patients with reflux esophagitis, esophageal squamous papilloma, or gastric mucosal atrophy (GMA), as well as the hiatal hernia width, were investigated. Results Endoscopic findings indicating short white hair-like appendages in the lower esophagus were noted in 167 patients, with a prevalence rate of 1.2%. A female sex, younger age, lower body mass index, lower percentages of habitual smoking and drinking, and the presence of esophageal squamous papilloma were characteristic features of cases with such findings. In addition, a significantly lower prevalence of reflux esophagitis and a smaller diaphragmatic hiatus size were observed. A multiple logistic regression analysis indicated that a female sex, absence of reflux esophagitis, presence of esophageal squamous papilloma, and a smaller diaphragmatic hiatus were factors significantly related to the presence of these short white hair-like appendages. An analysis of circumferential localization revealed the main location to be the left-posterior wall. Conclusion This study is the first to report the prevalence of multiple short white hair-like appendages in the lower esophagus. The occurrence of such lesions is inversely associated with the presence of reflux esophagitis.

In females, salivary secretion was significantly lower in patients with severe reflux esophagitis than in healthy controls.

BACKGROUND: The salivary secretion in patients with mild reflux esophagitis (RE) and non-erosive reflux disease is significantly lower in females, but not in males. However, sex differences in salivary secretion in patients with severe RE remain unknown. Therefore, the present study investigated sex differences in saliva secretion in patients with severe RE. METHODS: Subjects consisted of 23 male patients with severe RE, 24 male healthy controls (HCs), 26 female patients with severe RE, and 25 female HCs. Saliva secretion was assessed as follows: each patient chewed sugarless gum for 3 min prior to endoscopy, and the amount and pH of saliva secreted before and after acid loading as an index of the acid-buffering capacity were measured. RESULTS: In males, no significant differences were observed in the amount of saliva secretion, salivary pH, or the acid-buffering capacity between severe RE patients and HCs. In females, the amount of saliva secretion (severe RE: 2.4 [1.8-4.1], HCs: 5.3 [3.4-7.5], p = 0.0017), salivary pH (severe RE: 7.0 [6.7-7.3], HCs: 7.2 [7.1-7.3], p = 0.0455), and the acid-buffering capacity (severe RE: 5.9 [5.3-6.2], HCs: 6.2 [6.1-6.5], p = 0.0024) were significantly lower in severe RE patients than in HCs. CONCLUSION: Among females, the salivary secretion was significantly lower in severe RE patients than in HCs. This reduction in salivary secretion may contribute to the pathophysiology of severe RE in females.

A Three-Arm Randomized Controlled Trial of Primary One-Anastomosis Gastric Bypass: With FundoRing or Nissen Fundoplications vs. without Fundoplication for the Treatment of Obesity and Gastroesophageal Reflux Disease.

Background and Objectives: Obesity and gastroesophageal reflux disease (GERD) are steadily increasing world weight and antireflux surgery must be performed simultaneously with bariatric surgery in obese patients. The purpose of this study is to compare bariatric and antireflux results after OAGB with different methods of fundoplication using the excluded stomach and without fundoplication. Materials and methods: This open-label, randomized, parallel three-arm trial was conducted from March 2019 and December 2021. All patients underwent laparoscopic one-anastomosis gastric bypass and suture cruroplasty, and then had a follow-up at 24 months. Group 1 of patients had fundoplication FundoRing using the excluded stomach (FundoRingOAGB); Group 2, with Nissen fundoplication using the excluded stomach (NissenOAGB); and Group 3, without fundoplication (OAGB). We studied changes in BMI, GERD symptoms (GERD-HRQL), and the VISICK score. Results: Of 219 participants screened, 150 were randomly allocated to 3 groups: FundoRingOAGB group (n = 50), NissenOAGB group (n = 50), and OAGB group (n = 50). At post-treatment month 24, BMI changes were as follows: from 40.7 ± 5.9 (31-53) to 24.3 ± 2.8 (19-29) kg/m2 in FundoRingOAGB group; from 39.9 ± 5.3 (32-54) to 26.3 ± 2.9 (23-32) kg/m2 in Nissen group; and from 40.9 ± 6.2 (32-56) to 28.5 ± 3.9 (25-34) kg/m2 in OAGB group. The mean pre-operative GERD-HRQL heartburn score improved post-op in FundoRingOAGB group from 20.6 ± 2.24 (19.96, 21.23) to 0.44 ± 0.73 (0.23, 0,64); in NissenOAGB group from 21.34 ± 2.43 (20.64, 22.03) to 1.14 ± 1.4 (0.74, 1.53); and in OAGB group 20.5 ± 2.17 (19.9, 21.25) to 2.12 ± 1.36 (1.73, 2.5). GERD-HRQL total scores were from pre-op 25.2 ± 2.7 (24.4, 25.9) to 4.34 ± 1.3 (3.96, 4.7) post-op in FundoRingOAGB group; 24.8 ± 2.93 (24, 25.67) pre-op to 5.42 ± 1.7 (4.9, 5.9) in the NissenOAGB group; and from 21.46 ± 2.7 (20.7, 22.2) to 7.44 ± 2.7 (6.6, 8.2) in the OAGB group. The mean VISICK score improved from 3.64 ± 0.94 (3.7, 3.9) to 1.48 ± 1.26 (1.12, 1.84) in FundoRingOAGB, from 3.42 ± 0.97 (3.1, 3,7) to 2.5 ± 1.46 (2.06, 2.9) in NissenOAGB group and from 3.38 ± 0.88 (3.1, 3,69) to 2.96 ± 1.19 (2.62, 3.2) in OAGB group. Conclusions: Antireflux and bariatric results of FundoRingOAGB are better than using the NissenOAGB method and significantly better than OAGB without the use of fundoplication.

Clinicopathological and genomic features of superficial esophageal squamous cell carcinomas in nondrinker, nonsmoker females.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is sometimes detected in non-drinker and non-smoker females who are considered to have very low risk of ESCC development in daily practice. This study examined the clinicopathological and genomic characteristics of ESCCs in females with no history of drinking and smoking. METHODS: The sample comprised 118 ESCC lesions occurring in 95 female patients who underwent endoscopic submucosal dissection at our department between January 2008 and December 2019. The patients were categorized into two groups: 51 lesions in 49 patients with no history of drinking and smoking (nondrinker/nonsmoker [NDNS] group) and 69 lesions in 45 patients with a history of drinking or smoking (drinker/smoker [DS] group). We analyzed the differences in clinicopathological and cancerous genomic characteristics between the groups. Significant genomic alterations were validated using immunohistochemistry. RESULTS: Multiple logistic regression revealed that older age, fewer multiple Lugol-voiding lesions (LVLs), and reflux esophagitis (RE) were independently associated with the occurrence of ESCCs in the NDNS group. ESCC lesions in the NDNS group were predominantly located in the mid-thoracic esophagus, posterior wall side, with 0-IIa, the aspect ratio of the lesion >2 (vertical/horizontal), and endoscopic keratinization. Genetic analysis showed that CDKN2A driver alterations were significantly more frequent and KMT2D alterations were significantly less frequent in the NDNS group than in the DS group. KMT2D alterations were strongly correlated with immunostaining. CONCLUSION: Older nondrinker, nonsmoker females with RE and fewer multiple LVLs may develop longitudinal 0-IIa ESCC with keratinization of the posterior wall of the mid-thoracic esophagus. ESCCs in nondrinker, nonsmoker females had fewer KMT2D alterations and more CDKN2A alterations, which may be a biomarker for treatment.

[Pathomorphological criteria and features of immune response in eosinophilic esophagitis and reflux esophagitis]. / Patomorfologicheskie kriterii i osobennosti immunnogo otveta pri eozinofil'nom ezofagite i reflyuks-ezofagite.

BACKGROUND: Eosinophilic esophagitis (EoE) is an immune-mediated disease, manifested by dysphagia and characterized by intraepithelial infiltration: more than 15 eosinophils per field of view at x400 magnification, and requiring differential diagnosis with reflux esophagitis (RE). OBJECTIVE: To access the implication of EoE histologic scoring system (EoEHSS) for differential diagnosis of EoE and RE and to characterize features of immune response in these diseases. MATERIAL AND METHODS: 38 patients with EoE and 38 patients with RE were enrolled in the study. All the patients had esophagogastroduodenoscopy with biopsy. Biopsy specimens were stained with H&E and combined PAS/Alcian blue staining. Immunohistochemical evaluation was conducted with antibodies to CD3, CD4, CD8, CD20, CD56 and CD68. RESULTS: Grade score of EoEHSS in EoE was 2.4 times more than in RE (p<0.05). Stage score in EoE was 2.75 more than in RE (p<0.05). Intraepithelial count of CD3+ T-lymphocytes comprised 87 (76-95.5) in high-power view in EoE and 45 (38.5-48.5) in high-power view in RE. Intraepithelial count of CD4+ T-lymphocytes was 35 (28-41.5) in high-power view in EoE and 19 (16.5- 22.5) in high-power view in RE. Intraepithelial count of CD8+ T-lymphocytes comprised 59 (50.5-67.5) in high-power field in EoE and 27 (24-28.5) in high-power field in RE. CONCLUSION: The use of the EoEHSS histological rating scale for eosinophilic esophagitis is effective in the differential diagnosis of EoE and EC. Predominant cells in intraepithelial infiltrate are CD3+ T-lymphocytes both in EoE and RE, CD8+ cells prevail over CD4+ cells. In EoE intraepithelial count of CD3+ T-lymphocytes is 1.93 times more, count of intraepithelial CD4+ lymphocytes is 1.84 times more and count of CD8+ lymphocytes is 2.19 times more than in RE.

Xuanfu Daizhe Tang alleviates reflux esophagitis in rats by inhibiting the STAT1/TREM-1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Reflux esophagitis (RE) is a common chronic inflammatory disease of the esophageal mucosa with a high prevalence and recurrence rate, for which a satisfactory therapeutic strategy is still lacking. Chinese medicine has its characteristics and advantages in treating RE, and the clinical application of Xuanfu Daizhe Tang (XDT) in treating RE has achieved sound therapeutic effects. However, there needs to be more research on its mechanism of action. AIM OF THE STUDY: The present work aimed to investigate the mechanism of XDT action in RE through the Signal Transducer and Activator of Transcription 1 (STAT1)/Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) pathway. MATERIALS AND METHODS: The main active components of XDT were analyzed by ultra-performance liquid chromatography-mass spectrometer (UPLC-MS). The effect of XDT on RE was evaluated in a rat model of RE induced by "Cardioplasty + pyloric ligation + Roux-en-Y esophagojejunostomy". Each administration group was treated by gavage. The degree of damage to the esophageal mucosa was evaluated by visual observation, and the Potential of Hydrogen (PH) method and Hematoxylin-eosin staining (HE) staining were performed. Serum levels of Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6), Tumor Necrosis Factor alpha (TNF-α), and Inducible Nitric Oxide Synthase (iNOS) were measured by ELISA. Quantitative Real-time PCR (qPCR), Western Blot (WB), and Immunofluorescence (IF) methods were used to detect Claudin-4, Claudin-5, TREM-1, and p-STAT1 in esophageal tissues for studying the mechanism of action and signaling pathway of XDT. Immunohistochemistry (IHC) analysis was used to detect the expression of TREM-1 and CD68 in esophageal tissues. Flow Cytometry (FC) was used to detect the polarization of macrophages in the blood. After conducting preliminary experiments to verify our hypothesis, we performed molecular docking between the active component of XDT and STAT1 derived from rats and parallel experiments with STAT1 inhibitor. The selective increaser of STAT1 transcription (2-NP) group was used to validate the mechanism by which XDT acts. RESULTS: XDT alleviated esophageal injury and attenuated histopathological changes in RE rats. XDT also inhibited the inflammatory response and decreased serum IL-1ß, IL-6, TNF-α, and iNOS levels in RE rats. qPCR and WB results revealed that XDT inhibited the expression of Claudin-4, Claudin-5, TREM-1, and STAT1 in the esophageal mucosa of RE rats. IHC and FC results showed that XDT reduced TREM-1 levels in esophageal tissues and polarized macrophages toward M2. The molecular docking results showed that rat-derived STAT1 can strongly bind to Isochronogenic acid A in XDT. The parallel experimental results of STAT1 inhibitor showed that XDT has anti-inflammatory effects similar to STAT1 inhibitors. The 2-NP group confirmed that XDT exerts its therapeutic effect on reflux esophagitis through the STAT1/TREM-1 pathway, with STAT1 as the upstream protein. CONCLUSIONS: This study suggests that XDT may treat reflux esophagitis by modulating the STAT1/TREM-1 pathway.

Comprehensive Assessment of Esophageal Disorders Associated with Hiatus Hernia: Insights from Big Data Analysis.

Hiatus hernia (HH) is a prevalent endoscopic finding in clinical practice, frequently co-occurring with esophageal disorders, yet the prevalence and degree of association remain uncertain. We aim to investigate HH's frequency and its suspected association with esophageal disorders. We reviewed endoscopic reports of over 75,000 consecutive patients who underwent gastroscopy over 12 years in two referral centers. HH was endoscopically diagnosed. We derived data on clinical presentation and a comprehensive assessment of benign and malignant esophageal pathologies. We performed multiple regression models to identify esophageal sequela associated with HH. The overall frequency of HH was (16.8%); the majority (89.5%) had small HHs (<3 cm). Female predominance was documented in HH patients, who were significantly older than controls (61.1±16.5 vs. 52.7±20.0; P < 0.001). The outcome analysis of esophageal pathology revealed an independent association between HH, regardless of its size, and erosive reflux esophagitis (25.7% vs. 6.2%; OR = 3.8; P < 0.001) and Barrett's esophagus (3.8% vs. 0.7%; OR = 4.7, P < 0.001). Furthermore, following rigorous age and sex matching, in conjunction with additional multivariable analyses, large HHs were associated with higher rates of benign esophageal strictures (3.6% vs. 0.3%; P < 0.001), Mallory Weiss syndrome (3.6% vs. 2.1%; P = 0.01), and incidents of food impactions (0.9% vs. 0.2%; P = 0.014). In contrast, a lower rate of achalasia was noted among this cohort (0.55% vs. 0%; P = 0.046). Besides reflux-related esophageal disorders, we outlined an association with multiple benign esophageal disorders, particularly in patients with large HHs.

Prevalence and risk factors for medication-refractory reflux esophagitis in patients with systemic sclerosis in Japan.

BACKGROUNDS: Patients with systemic sclerosis (SSc) often have esophageal motility abnormalities and weak esophago-gastric junction (EGJ) barrier function, which causes proton pump inhibitor (PPI)-refractory reflux esophagitis (RE). The aims of this study were to clarify the current management of RE and prevalence and risk factors of medication-refractory RE in patients with SSc in Japan. METHODS: A total of 188 consecutive patients with SSc who underwent both esophageal high-resolution manometry (HRM) and esophagogastroduodenoscopy (EGD) were reviewed. The presence of RE and grades of the gastroesophageal flap valve (GEFV) were assessed. Esophageal motility was assessed retrospectively according to the Chicago classification v3.0. When RE was seen on a standard dose of PPI or any dose of vonoprazan (VPZ), it was defined as medication-refractory RE. RESULTS: Approximately 80% of patients received maintenance therapy with acid secretion inhibitors regardless of esophageal motility abnormalities. Approximately 50% of patients received maintenance therapy with PPI, and approximately 30% of patients received VPZ. Medication-refractory RE was observed in 30 patients (16.0%). In multivariable analyses, the number of EGD and absent contractility were significant risk factors for medication-refractory RE. Furthermore, combined absent contractility and GEFV grade III or IV had higher odds ratios than did absent contractility alone. CONCLUSIONS: Patients with persistent reflux symptoms and those with absent contractility and GEFV grade III or IV should receive maintenance therapy with strong acid inhibition to prevent medication-refractory RE.

Safety and short-term outcomes of a modified valvuloplastic esophagogastrostomy versus gastric tube anastomosis after laparoscopy-assisted proximal gastrectomy: a retrospective cohort study.

BACKGROUND: There is no optimal reconstruction method after proximal gastrectomy. The valvuloplastic esophagogastrostomy can reduce postoperative reflux esophagitis, but it is technically complex with a long operation time. The gastric tube anastomosis is technically simple, but the incidences of reflux esophagitis and anastomotic stricture are higher. METHODS: We have devised a modified valvuloplastic esophagogastrostomy after laparoscopy-assisted proximal gastrectomy (LAPG), the arch-bridge anastomosis. After reviewing our prospectively maintained gastric cancer database, 43 patients who underwent LAPG from November 2021 to April 2023 were included in this cohort study, with 25 patients received the arch-bridge anastomosis and 18 patients received gastric tube anastomosis. The short-term outcomes were compared between the two groups to evaluate the efficacy of the arch-bridge anastomosis. Reporting was consistent with the STROCSS 2021 guideline. RESULTS: The median operation time was 180 min in the arch-bridge group, significantly shorter than the gastric tube group (p = 0.003). In the arch-bridge group, none of the 25 patients experienced anastomotic leakage, while one patient (4%) experienced anastomotic stricture requiring endoscopic balloon dilation. The postoperative length of stay was shorter in the arch-bridge group (9 vs. 11, p = 0.034). None of the patients in the arch-bridge group experienced gastroesophageal reflux and used proton pump inhibitor (PPI), while four (22.2%) patients in the gastric tube group used PPI (p = 0.025). The incidence of reflux esophagitis (Los Angeles grade B or more severe) by endoscopy was lower in the arch-bridge group (0% vs. 25.0%). CONCLUSION: The arch-bridge anastomosis is a safe, time-saving, and feasible reconstruction method. It can reduce postoperative reflux and anastomotic stricture incidences in a selected cohort of patients undergoing laparoscopy-assisted proximal gastrectomy.

Characteristics of proton pump inhibitor-resistant severe reflux esophagitis and efficacy of vonoprazan in elderly (older than 75 years) and non-elderly groups.

Background and Aim: Previous studies on age differences in proton pump inhibitor (PPI)-resistant reflux esophagitis (RE) have found that stenosis and bleeding complications were significantly more common in the elderly than in the non-elderly. We sought to examine differences between two groups of elderly (75 years or older) and non-elderly (<75 years) patients with (PPI)-resistant severe RE and also the efficacy of vonoprazan (VPZ) in these patients. Methods: There were 14 patients in the elderly group and 15 in the non-elderly group. Information was obtained on patient background (sex, body mass index [BMI], gastric mucosal atrophy, and the presence of hernia and collagen disease), and all patients underwent the saliva secretion test and esophagogastroduodenoscopy (EGD). The saliva secretion test (amount of saliva secreted, salivary pH, and the acid-buffering capacity) was performed by chewing sugar-free gum for 3 min before EGD. The efficacy of VPZ in both groups was also assessed. Results: Saliva secretion, sex, BMI, and the presence of gastric mucosal atrophy did not significantly differ between the two groups. The number of hernias larger than 4 cm was significantly higher in the elderly PPI-resistant group, and significantly more patients had collagen disease in the non-elderly group. The efficacy of VPZ was not significantly different between the two groups; however, 10 patients in the non-elderly group had collagen disease, and 4 did not achieve esophageal mucosal healing even with VPZ 20 mg. Conclusion: The number of large hernias (>4 cm) was significantly higher in the elderly group, while significantly more non-elderly patients had collagen disease. In the non-elderly group with scleroderma, the efficacy of VPZ 20 mg may not be sufficient.

Combined thoracoscopic and laparoscopic surgery for epiphrenic diverticulum with associated gastroesophageal reflux disease: a case report.

BACKGROUND: Surgery is indicated for symptomatic epiphrenic esophageal diverticula. Based on the features of a case, thoracoscopic or laparoscopic approaches may be used. Epiphrenic diverticula are often associated with esophageal motility disorders, but cases of reflux esophagitis have rarely been reported. In this report, we describe a case of an epiphrenic esophageal diverticulum with reflux esophagitis, which was successfully treated by thoracoscopic diverticulectomy and laparoscopic fundoplication. CASE PRESENTATION: A 69-year-old man visited the hospital with a chief complaint of eructation and hiccup. Upper gastrointestinal endoscopy revealed a diverticulum in the left wall of the esophagus, which was 37-45 cm distal to the incisors. High-resolution manometry (HRM) showed no esophageal motility disorders. Due to the large size of the diverticulum, a thoracoscopic resection of the esophageal diverticulum was performed. Additionally, the patient had reflux esophagitis due to a hiatal hernia. The anti-reflux mechanism would be more impaired during the diverticulectomy; therefore, we decided that anti-reflux surgery should be performed simultaneously. Thoracoscopic esophageal diverticulectomy and laparoscopic Dor fundoplication were performed. The patient had an uncomplicated postoperative course and was discharged on the tenth operative day. He has been symptom-free without acid secretion inhibitors for 21 months after the surgery. CONCLUSIONS: We described a rare case of a large epiphrenic diverticulum with reflux esophagitis. A good surgical outcome was achieved by thoracoscopic resection of the diverticulum and laparoscopic Dor fundoplication.

The Effect of STW5 (Iberogast) on Reflux Symptoms in Patients With Concurrent Dyspeptic Symptoms: A Double-blind Randomized Placebo-controlled Crossover Trial.

Background/Aims: It has been suggested that STW5 (Iberogast) reduces heartburn symptoms in patients with functional dyspepsia, but underlying mechanisms of action are unclear. The aim of this study is to investigate whether STW5 affects esophageal sensitivity or esophageal motility, thereby reducing occurrence and perception of reflux events. Methods: We performed a double-blind, randomized, placebo-controlled, crossover trial in patients with functional dyspepsia (Rome IV) and reflux symptoms. After 4 weeks of treatment with either placebo or STW5, patients were studied with an esophageal acid perfusion test and ambulatory 24-hour pH-impedance monitoring. Results: A total of 18 patients (7 men, median age 54, range [19-76]), were included in the study. Although we found no statistical difference in our primary outcome the total Reflux Disease Questionnaire score 2.33 (0.25-4.33) vs 2.67 (1.17-4.00), P = 0.347, "gastroesophageal reflux disease" and "regurgitation" subscale scores were lower after STW5 treatment compared to placebo (P = 0.049 and P = 0.007). There was no statistical difference in number of reflux events, acid exposure time and acid sensitivity scores between STW5 and placebo. In a subgroup analysis of patients with pH-metry confirmed gastroesophageal reflux disease, treatment with STW5 significantly reduced the total number of acidic reflux events (P = 0.028). Moreover, in patients with reflux esophagitis, the median lag time to acid perception increased after STW5 treatment (P = 0.042). Conclusions: We found some indications pointing towards a beneficial effect of STW5 on reflux symptoms in dyspeptic patients, with reduction of esophageal hypersensitivity as a potential underlying mechanism. Our findings will have to be confirmed in larger studies.

Esophagogastroscopic Abnormalities Potentially Guided Patients Younger than 50 Years Old to Undergo Colonoscopy Earlier: A Retrospective Cross-Sectional Study.

BACKGROUND: The incidence of early-onset colorectal cancer (CRC) is continuously increasing worldwide. Current guidelines in China recommend average-risk individuals starting CRC screening at age 50. AIMS: To investigate the relationship between the gastric histopathology and colorectal neoplasms to identify CRC risk factors which potentially guide earlier colonoscopy in individuals aged < 50 years. METHODS: A retrospective cross-sectional study was conducted on 8819 patients younger than age 50 who underwent gastroscopy and colonoscopy simultaneously between November 7, 2020 and November 14, 2022. Multivariate logistic regression was used to evaluate whether various gastric histopathology are risk factors for different types of colorectal polyps, reporting odds ratios (ORs) with corresponding 95% confidence intervals (CIs). RESULTS: A total of 3390 cases (38.44%) under 50 years old were diagnosed as colorectal polyps. Advanced age (OR 1.66, 95%CI 1.57-1.76), male sex (OR 2.67, 95%CI 2.33-3.08), Helicobacter pylori (H. pylori) infection (OR 1.43, 95%CI 1.24-1.65), gastric polyps (OR 1.29, 95%CI 1.10-1.52), and low-grade intraepithelial neoplasia (LGIN) (OR 2.52, 95%CI 1.39-4.57) were independent risk factors for colorectal adenomas. For non-adenomatous polyps, reflux esophagitis (OR 1.38, 95%CI 1.11-1.71) was also an independent risk factor. Besides, older age (OR 1.90, 95%CI 1.66-2.18), male sex (OR 2.15, 95%CI 1.60-2.87), and H. pylori infection (OR 1.67, 95%CI 1.24-2.24) were associated with a higher risk of advanced neoplasms (advanced adenoma and CRC). CONCLUSIONS: Earlier colonoscopy for identification and screening may need to be considered for individuals younger than 50 years old with H. pylori infection, LGIN, gastric polyps, and reflux esophagitis. Risk-adapted CRC screening initiation age allows a personalized and precise screening.

Frontiers in Endoscopic Treatment for Gastroesophageal Reflux Disease.

BACKGROUND: The 3rd edition of the evidence-based clinical practice guidelines for gastroesophageal reflux disease (GERD) 2021 from the Japanese Society of Gastroenterology states that the treatment strategy for potassium-competitive acid blocker (PCAB)-refractory GERD remains unclear. Furthermore, even if GERD improves with the administration of an acid secretion inhibitor, it is feared that GERD may flare up after discontinuation of the drug, resulting in some cases in which patients are forced to take vonoprazan semipermanently (the so-called PCAB-dependent cases). From a global perspective, PCAB is not yet used in all countries and regions, and measures that can be taken now for cases in which a conventional proton pump inhibitor (PPI) is inadequately effective need to be devised. SUMMARY: Endoscopic treatment for GERD may be effective in cases where conventional proton pump inhibitors are ineffective; however, there are insufficient long-term studies to corroborate this, and its cost effectiveness is unknown. Other treatment options for PCAB or PPI-refractory GERD include surgical procedures (Nissen and Toupet operations), which have a longer history than endoscopic treatment for GERD. However, their long-term results are not as good as those of acid secretion inhibitors, and they are not cost effective. Endoscopic treatment for GERD may fill gaps in inadequate surgical treatment. In April 2022, endoscopic anti-reflux mucosal resections (ARMS [anti-reflux mucosectomy] and ESD-G [endoscopic submucosal dissection for GERD]) were approved for reimbursement, making endoscopic treatment of GERD possible throughout Japan. KEY MESSAGES: It is important to identify the background factors in cases in which endoscopic treatments are effective.