Early gastric cancer with RhoGAP fusion is linked to frequent nodal metastasis and a part of microtubular-mucocellular histology.

INTRODUCTION: Gastric cancer with fusion genes involving the Rho GTPase-activating protein domain (RhoGAP-GC) is mainly included in the genomically stable type of The Cancer Genome Atlas classification. Clinical implications and histological characteristics of RhoGAP-GC in the early phase remain unclear. METHODS: We analyzed 878 consecutive pT1b GCs for RhoGAP and its partner genes using fluorescence in situ hybridization assay. RESULTS: RhoGAP fusion was detected in 57 (6.5%) GCs. Univariate analysis revealed that female sex, middle-lower third tumor location, advanced macroscopic type, tumor diameter > 2 cm, pT1b2, lymphatic invasion, venous invasion, negative EBER-ISH, and RhoGAP fusion were significantly associated with lymph node metastasis (LNM). Multivariate analysis presented RhoGAP fusion, lymphatic invasion, tumor diameter > 2 cm, advanced macroscopic type, venous invasion, and middle-lower third tumor location as independent risk factors for LNM. Notably, RhoGAP fusion had the highest odds ratio (3.92) for LNM among analyzed parameters (95% CI 2.12-7.27; p < 0.001). Compared to non-RhoGAP-GCs, RhoGAP-GCs were significantly frequent in younger females and showed the highest incidence of lymphatic invasion (56.2%) and LNM (49.1%) (p < 0.001). Histologically, microtubular architecture with pseudo-trabecular interconnection and small aggregations of tumor cells with a varied amount of cytoplasmic mucin, named "microtubular-mucocellular (MTMC) histology," was found in 93.0% (53 of 57) of RhoGAP-GCs in the intramucosal area. MTMC histology showed high sensitivity and negative predictive value (93.0% and 99.4%, respectively) for RhoGAP fusion, albeit positive predictive value is low (34.9%). CONCLUSION: RhoGAP-GC is linked to a characteristic MTMC histology and a high incidence of LNM.

Kinetics of the hepatitis B core-related antigen and treatment responses in chronic hepatitis B patients treated with tenofovir alafenamide.

AIM: An association between hepatitis B core-related antigen (HBcrAg) kinetics and hepatocarcinogenesis during nucleoside (t)id analog (NA) treatment has recently been reported. HBcrAg kinetics and factors associated with HBcrAg response during tenofovir alafenamide (TAF) administration remain unclear. In this multicenter retrospective study, we aimed to clarify the efficacy and safety of TAF in treatment-naïve patients with chronic hepatitis B, focusing on the reduction in HBcrAg levels. METHODS: Patients were treated with TAF monotherapy for 96 weeks, and the kinetics of HBcrAg during treatment and the factors associated with HBcrAg response (defined as a change in HBcrAg of -1 log IU/mL from baseline) were evaluated. RESULTS: The study population comprised 241 patients, 36.9% of whom were HBeAg-positive. The median baseline HBcrAg level was 4.7 log IU/mL. The median change in HBcrAg from baseline was -1.1 log IU/mL at 96 weeks after treatment. The HBcrAg response rate at 96 weeks was 56.6% (43/76). Multivariate analysis revealed high alanine transaminase level as an independent baseline factor associated with HBcrAg response at 96 weeks of treatment (p = 4.53 × 10-6). No correlation was found between the HBcrAg and hepatitis B surface antigen kinetics in patients treated with TAF monotherapy. CONCLUSIONS: In TAF monotherapy for patients with chronic hepatitis B, HBcrAg levels were significantly decreased and baseline alanine transaminase level is an important factor associated with HBcrAg reduction. As no correlation was found between HBcrAg and reduced hepatitis B surface antigen levels in this study, HBcrAg kinetics in addition to hepatitis B surface antigen may need to be monitored during TAF treatment.

Esophageal Motility Disorders: Diagnosis and Treatment Strategies.

BACKGROUND: Esophageal motility disorders (EMDs) are caused by the impaired relaxation of the upper/lower esophageal sphincter and/or defective esophageal peristaltic contractions, resulting in dysphagia and noncardiac chest pain. High-resolution manometry (HRM) is essential for the diagnosis of primary EMD; however, the recognition of EMD and HRM by general practitioners in Japan is limited. This review summarizes the diagnosis of and treatment strategies for EMD. SUMMARY: HRM is a specific test for the diagnosis of EMD, whereas endoscopy and barium swallow as screening tests provide characteristic findings (i.e., esophageal rosette and bird's beak sign) in some cases. It is important to note that manometric diagnoses apart from achalasia are often clinically irrelevant; therefore, the recently updated guidelines suggest additional manometric maneuvers, such as the rapid drink challenge, and further testing, including functional lumen imaging, for a more accurate diagnosis before invasive treatment. Endoscopic/surgical myotomy, pneumatic dilation, and botulinum toxin injections need to be considered for patients with achalasia and clinically relevant esophagogastric junction outflow obstruction. KEY MESSAGE: Since the detailed pathophysiology of EMD remains unclear, their diagnosis needs to be cautiously established prior to the initiation of invasive treatment.

Esophageal Dilation in Patients with Achalasia Is a Predictive Factor for the Inability to Traverse the Esophagogastric Junction with a Manometric Catheter.

INTRODUCTION: The insertion of a high-resolution manometry (HRM) catheter into the stomach is essential for accurate manometric diagnoses; however, it is impossible in some cases due to the inability to traverse the esophagogastric junction (EGJ). Predictive factors for these patients have not been investigated in detail, necessitating time-consuming and burdensome procedures for investigators and patients. Therefore, the present study investigated the percentage of and risk factors for failed intubation at the EGJ. METHODS: We initially reviewed the medical charts of consecutive HRM procedures performed at our hospital between September 2018 and January 2023. Patient characteristics and the findings of endoscopy and esophagography (where available) were compared between successful and failed procedures. A multivariate logistic regression analysis was conducted to identify predictive factors for the inability to traverse the EGJ. We then validated the predictive factors identified by reviewing consecutive procedures performed between February 2023 and August 2023. RESULTS: Among the 781 procedures performed, 55 (7.0%) failed due to the inability to traverse the EGJ. Achalasia was the most common disorder in these procedures. An older age and dilated esophagus of >34 mm were independent predictive factors for the inability to traverse the EGJ in patients with treatment-naïve achalasia. In the validation study, 7 out of 68 procedures (10.3%) failed due to the inability to traverse the EGJ. A flowchart using the findings of endoscopy and an esophageal diameter of >34 mm predicted the inability to traverse the EGJ with a sensitivity of 71.4% and specificity of 86.9%. CONCLUSION: Based on an esophageal diameter >34 mm and endoscopic findings, we predicted the inability to traverse the EGJ in more than 70% of patients. A multi-center prospective study is warranted in the future.

Potential of Direct Oral Anticoagulant in Bleeding After Gastric Endoscopic Submucosal Dissection: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: An increasing number of patients are undergoing gastric endoscopic submucosal dissection (ESD) with active prescriptions of direct oral anticoagulants (DOACs). Only a few reports have described the effects of DOAC intake on postoperative bleeding. We aimed to investigate the bleeding risk associated with DOACs after gastric ESD. METHODS: Clinical studies published up to April 2022 showing bleeding rates after gastric ESD in patients taking DOACs were identified using electronic searches. The primary outcome was the rate of bleeding after gastric ESD in patients receiving DOACs compared to those not receiving antithrombotic therapy. In this meta-analysis, odds ratios (ORs) were calculated and pooled using a random effects model. The secondary outcome was the difference in the bleeding rate between patients treated with DOACs and those treated with warfarin and antiplatelet drugs. RESULTS: Seven studies were included in this meta-analysis. The pooled analysis showed that DOACs had a higher bleeding rate than non-thrombotic therapy (17.0% vs. 3.4%; OR 5.72; 95% confidence interval [CI], 4.33-7.54; I2 = 0%). The bleeding risk associated with DOAC administration was similar to that associated with warfarin (17.0% vs. 20.0%; OR 0.83; 95% CI 0.59-1.18; I2 = 0%), whereas it was higher than that associated with antiplatelet administration (16.9% vs. 11.0%; OR 1.63; 95% CI 1.14-2.34; I2 = 8%). CONCLUSIONS: This meta-analysis reveals that the bleeding risk of DOACs is higher than that of non-antithrombotics and antiplatelets, whereas it is comparable to that of warfarin. Gastric ESD in patients on anticoagulants requires careful postoperative management.

Patients with gastroesophageal reflux disease (both reflux oesophagitis and non-erosive reflux disease): Prevalence and severity of erosive tooth wear and saliva properties.

BACKGROUND: The prevalence between erosive tooth wear (ETW) in association with reflux oesophagitis (RO) has been reported. However, the severity of both diseases and the relationship between ETW and non-erosive reflux disease (NERD) is unclear. OBJECTIVES: The prevalence and severity of ETW were investigated in RO, NERD and healthy controls. METHODS: 135 patients with RO, 65 with NERD and 40 healthy controls were recruited for this case-control study. A modified tooth wear index was used to evaluate the prevalence and severity of ETW. Salivary secretion and buffer capacity were assessed prior to endoscopy. The prevalence and severity of ETW, saliva properties among each group were analysed using Pearson's chi-squared test. RESULTS: A total of 135 cases (56.3%) were categorised as the patient with ETW (55 with mild RO, 49 with severe RO and 31 with NERD). There was a significant relationship between the prevalence of RO and ETW, while there was no significant correlation between the prevalence of NERD and ETW. There was a significant difference related to the severity between RO and ETW. For salivary secretion, there was a significant difference between with and without ETW in patients with mild RO, severe RO and NERD. There was a significant difference between with and without ETW for salivary buffer capacity in patients with mild and severe RO. CONCLUSION: There was a significant association of the prevalence and severity between RO and ETW. Clinical signs such as ETW and salivary buffer capacity depended on the severity of RO.

Factors associated with prevalence and severity of erosive tooth wear in patients with reflux oesophagitis.

BACKGROUND: Extrinsic factors for erosive tooth wear (ETW) have been widely reported, but the intrinsic factors for wear remain unclear. OBJECTIVES: The aim of this study was to evaluate the factors associated with the prevalence of ETW in patients with reflux oesophagitis (RO). To prevent severe ETW with RO, factors associated with severity of ETW were also evaluated. METHODS: A total of 270 patients with RO were recruited. A modified tooth wear index was used to evaluate the prevalence and severity of ETW. Salivary secretion and buffering capacity were assessed prior to endoscopy. Subjects were asked to complete a medical condition and oral self-care questionnaire. Univariate and multivariate analyses were employed to identify factors collectively associated with the prevalence and severity of ETW. RESULTS: A total of 212 cases were categorized as patients with ETW (148 with mild ETW and 64 with severe ETW). Multivariate analyses indicated that saliva secretion, severity of RO and proton pump inhibitor (PPI) resistance were associated with the prevalence of ETW, whereas age, BMI and severity of RO were associated with the severity of ETW. The odds ratio of saliva secretion and BMI were less than 1, meaning that higher saliva secretion resulted in a lower prevalence of ETW and lower BMI was associated with severe ETW. CONCLUSION: Saliva secretion, severity of RO and PPI resistance were associated with the prevalence of ETW, whereas age, BMI and severity of RO were associated with the severity of ETW. Lower saliva secretion and BMI were significant factors for ETW.

Among females older than 50 years, saliva secretion is significantly lower in non-erosive reflux disease patients than in healthy controls.

BACKGROUND: Saliva secretion is significantly lower in patients with non-erosive reflux disease (NERD) than in healthy controls (HC). A previous study on HC showed that saliva secretion was lower in females than in males. Saliva secretion may be lower in female patients with NERD than in male patients. Therefore, the present study investigated sex differences in saliva secretion in patients with NERD. METHODS: Subjects older than 50 years were included in the present study and consisted of 20 male patients with NERD, 19 male HC, 25 female patients with NERD, and 23 female HC. Saliva secretion was assessed as follows: each patient chewed sugar-free gum for 3 min prior to endoscopy, and the amount and pH of saliva 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 stimulated saliva secretion or salivary pH between NERD patients and HC. However, the acid-buffering capacity (NERD: 6.1 [5.9-6.5], HC: 6.4 [6.2-6.6]) was significantly lower in NERD patients than in HC. In females, the amount of stimulated saliva secretion (NERD: 2.6 [2.0-4.1], HC: 5.8 [3.7-7.5]), salivary pH (NERD: 7.0 [6.8-7.2], HC: 7.2 [7.0-7.2]), and the acid-buffering capacity (NERD: 5.8 [5.4-6.2], HC: 6.2 [6.0-6.5]) were significantly lower in NERD patients than in HC. CONCLUSION: Among females older than 50 years, saliva secretion was significantly lower in NERD patients than in HC. This reduction in saliva secretion may contribute to the pathophysiology of NERD in females.

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.

Remarkable response as a new indicator for endoscopic evaluation of local efficacy of non-surgical treatments for esophageal cancer.

In Japan, standard of care of the patients with resectable esophageal cancer is neoadjuvant chemotherapy (NAC) followed by esophagectomy. Patients unfitted for surgery or with unresectable locally advanced esophageal cancer are generally indicated with definitive chemoradiotherapy (CRT). Local disease control is undoubtful important for the management of patients with esophageal cancer, therefore endoscopic evaluation of local efficacy after non-surgical treatments must be essential. The significant shrink of primary site after NAC has been reported as a good indicator of pathological good response as well as favorable survival outcome after esophagectomy. And patients who could achieve remarkable shrink to T1 level after CRT had favorable outcomes with salvage surgery and could be good candidates for salvage endoscopic treatments. Based on these data, "Japanese Classification of Esophageal Cancer, 12th edition" defined the new endoscopic criteria "remarkable response (RR)", that means significant volume reduction after treatment, with the subjective endoscopic evaluation are proposed. In addition, the finding of local recurrence (LR) at primary site after achieving a CR was also proposed in the latest edition of Japanese Classification of Esophageal Cancer. The findings of LR are also important for detecting candidates for salvage endoscopic treatments at an early timing during surveillance after CRT. The endoscopic evaluation would encourage us to make concrete decisions for further treatment indications, therefore physicians treating patients with esophageal cancer should be well-acquainted with each finding.

Clinical outcomes of antithrombin III-based therapy for patients with portal vein thrombosis: A retrospective, multicenter study.

AIM: The association between thrombolytic therapy and the outcome in patients with portal vein thrombosis (PVT) remains controversial. This study aimed to evaluate the outcome in patients with PVT who received antithrombin III-based therapy. METHODS: This study was a retrospective, multicenter study to investigate the liver-related events and the survival rates in 240 patients with PVT who received the therapy. RESULTS: The patients comprised 151 men and 89 women, with a median age of 69 years. The rate of favorable response, defined as maximum area of PVT changed to ≤75%, was 67.5% (162/240). The cumulative rates of liver-related events at 1, 2, and 3 years were 38.2%, 53.9%, and 68.5%, respectively. The multivariate analysis showed that viable hepatocellular carcinoma, absence of maintenance therapy, non-responder, and PVT progression were significantly associated with liver-related events. The PVT progression was observed in 23.3% (56/240). The multivariate analysis identified older age, absence of maintenance therapy, and non-responder as independent factors associated with PVT progression. The multivariate analysis revealed that younger age, no hepatocellular carcinoma, presence of maintenance therapy, and lower Model for End-stage Liver Disease-Sodium score significantly contributed to 3-year survival. Of the 240 patients, 13 (8.9%) prematurely discontinued treatment due to any adverse events. CONCLUSIONS: This study suggests that maintenance therapy, favorable response, and absence of PVT progression may suppress or control liver-related events in antithrombin III-based therapy for patients with PVT. Specifically, maintenance therapy could suppress not only liver-related events, but also PVT progression and improve the prognosis.

Combination of high-density cholesterol level, elastic score, and severity of exocrine pancreatic dysfunction may be useful for a predictive factor for patients with early chronic pancreatitis.

BACKGROUND: This study aimed to clarify whether any risk factors including clinical characteristics, endosonographic features, and exocrine pancreatic dysfunction may be useful for a predictive factor for patients with early chronic pancreatitis. METHODS: A total of 163 consecutive patients that presented with functional dyspepsia with pancreatic enzyme abnormalities (FD-P) (n = 46), early chronic pancreatitis (ECP) (n = 47), and asymptomatic patients with pancreatic enzyme abnormalities (AP-P) (n = 70) based on the Rome III classification and the Japan Pancreatic Association were included in this study. The enrolled patients were evaluated using endosonography (EUS) and EUS elastography. The levels of the five pancreatic enzymes were measured. Pancreatic exocrine function was analyzed using N-benzoyl-l-tyrosyl-p-aminobenzoic acid (BT-PABA). RESULTS: There were no significant differences in clinical characteristics such as age, gender, body mass index, alcohol consumption, and smoking among patients with AP-P, FD-P, and ECP. The ratio of BT-PABA test less than 35% in patients with ECP was significantly (P = 0.043) higher than in AP-P patients. Elastic score was a useful tool to differentiate the FD-P group from the ECP group. The high-density cholesterol levels in patients with ECP were significantly lower than those in AP-P. In addition, the combination of total and high-density cholesterol levels, BT-PABA test, and elastic score has a higher area under the curve value (0.708) of patients with ECP than in the other groups. CONCLUSIONS: The combination of high-density cholesterol levels, elastic score, and severity of exocrine pancreatic dysfunction may be useful for a predictive factor for patients with ECP.

Apolipoprotein A2 isoforms associated with exocrine pancreatic insufficiency in early chronic pancreatitis.

BACKGROUND AND AIM: Apolipoprotein A2 (apoA2) isoforms have been reported to undergo the aberrant processing in pancreatic cancer and pancreatic risk populations compared with that in healthy subjects. This study aimed to clarify whether apoA2 isoforms were as useful as N-benzoyl-p-aminobenzoic acid (BT-PABA) test for exocrine pancreatic dysfunction markers in patients with early chronic pancreatitis (ECP). METHODS: Fifty consecutive patients with functional dyspepsia with pancreatic enzyme abnormalities (FD-P) (n = 18), with ECP (n = 20), and asymptomatic patients with pancreatic enzyme abnormalities (AP-P) (n = 12) based on the Rome IV classification and the Japan Pancreatic Association were enrolled in this study. The enrolled patients were evaluated using endoscopic ultrasonography and endoscopic ultrasonography elastography. Five pancreatic enzymes were estimated. Pancreatic exocrine function was analyzed using the BT-PABA test. Lighter and heavier apoA2 isoforms, AT and ATQ levels were measured by enzyme-linked immunosorbent assay methods. RESULTS: There were no significant differences in clinical characteristics such as age, gender, body mass index, alcohol consumption and smoking among patients with AP-P, FD-P, and ECP. The BT-PABA test and lighter apoA2 isoform, AT level in the enrolled patients had a significant correlation (P < 0.01). The BT-PABA test in patients with ECP was significantly lower (P = 0.04) than that in AP-P. ApoA2-AT level in patients with ECP was lower than that in AP-P, albeit, insignificantly. Interestingly, apo A2-AT level was significantly (P = 0.041) associated with exocrine pancreatic insufficiency by multiple logistic regression analysis. CONCLUSIONS: ApoA2-AT level is a useful tool to evaluate exocrine pancreatic insufficiency in the early stage of chronic pancreatitis.

Lemborexant Attenuates Regurgitation without Worsening Objective Parameters on Reflux Monitoring in Patients with Gastroesophageal Reflux Disease and Insomnia: A Single-Arm Proof-of-Concept Study.

INTRODUCTION: Esophageal hypersensitivity is associated with gastroesophageal reflux disease (GERD). Since sleep disturbance causes esophageal hypersensitivity, hypnotics may ameliorate GERD. However, zolpidem prolongs esophageal acid clearance. Lemborexant is a new hypnotic with higher efficacy and fewer adverse events than zolpidem. Therefore, the present study investigated the effects of lemborexant on GERD. METHODS: Patients with heartburn and/or regurgitation and insomnia who did not take acid suppressants or hypnotics in the last month were recruited. Symptom assessments using GerdQ and reflux monitoring were performed before and after a 28-day treatment with 5 mg lemborexant at bedtime. The primary outcome was a change in the total GerdQ score, excluding the score for insomnia. Secondary outcomes were changes in each GerdQ score and the following parameters on reflux monitoring: the acid exposure time (AET), number of reflux events (RE), acid clearance time (ACT), and post-reflux swallow-induced peristaltic wave (PSPW) index. RESULTS: Sixteen patients (age 45.0 [33.3-56.0], 11 females [68.8%]) completed the intervention (1 patient did not tolerate the second reflux monitoring). The total GerdQ score, excluding the score for insomnia, did not significantly change (8.0 [6.0-9.0] before vs. 7.0 [6.3-9.0] after p = 0.16). GerdQ showed the significant attenuation of regurgitation (2.0 [2.0-3.0] vs. 1.0 [0-2.8] p = 0.0054) but not heartburn (2.5 [1.0-3.0] vs. 1.0 [0.3-2.0] p = 0.175). No significant differences were observed in AET, RE, ACT, or PSPW index before and after the intervention. CONCLUSION: Lemborexant attenuated regurgitation without the worsening of objective reflux parameters. A randomized placebo-controlled study is warranted in the future.

Saliva Secretion Is Significantly Lower in Female Patients with Mild Reflux Esophagitis than in Female Healthy Controls.

INTRODUCTION: Saliva secretion is significantly lower in patients with mild reflux esophagitis than in healthy controls. A previous study on healthy controls showed that stimulated saliva secretion was lower in females than in males. Saliva secretion may be lower in female patients with mild reflux esophagitis than in male patients. Therefore, the present study investigated sex differences in saliva secretion in patients with mild reflux esophagitis. METHODS: Twenty-five male patients with mild reflux esophagitis, 25 male healthy controls, 24 female patients with mild reflux esophagitis, and 24 female healthy controls were recruited for this case-control study. Saliva secretion was assessed as follows: each patient chewed sugar-free gum for 3 minutes prior to endoscopy, and the volume and pH of saliva before and after acid loading as an index of the acid-buffering capacity were measured. RESULTS: No significant differences were observed in the amount of stimulated saliva secretion, salivary pH, or the acid-buffering capacity between male patients with mild reflux esophagitis and healthy controls. No significant differences were noted in salivary pH between female patients with mild reflux esophagitis and healthy controls; however, the amount of stimulated saliva secretion was significantly lower (p = 0.0023) in the former (2.5 [1.9-4.1]) than in the latter (4.6 [3.2-6.6]), while the acid-buffering capacity was slightly lower (p = 0.0578) in the former (5.9 [5.7-6.2]) than in the latter (6.2 [6.0-6.5]). CONCLUSION: The amount of stimulated saliva secretion was significantly lower in female patients with mild reflux esophagitis than in female healthy controls. This reduction in saliva secretion may affect the pathophysiology of mild reflux esophagitis in females.

Proton Pump Inhibitor Treatment Has Little Effects on Secretion of Saliva in Patients with Proton Pump Inhibitor-Responsive Mild Reflux Esophagitis and Non-Erosive Reflux Disease.

INTRODUCTION: The secretion of saliva, which is triggered by acid reflux into the esophagus via the esophagosalivary reflex, plays a crucial role in the defensive mechanisms of the esophagus. The volume of saliva secreted in patients with gastroesophageal reflux disease (GERD) is reduced. However, the effects of proton pump inhibitors (PPI) on the secretion of saliva have rarely been reported. Therefore, the present study investigated changes in the volume and pH of saliva after the cessation of PPI. MATERIALS AND METHODS: We retrospectively reviewed the records of consecutive patients previously diagnosed with mild reflux esophagitis (RE) or non-erosive reflux disease (NERD) controlled with PPI (including vonoprazan) who performed the salivary secretion test before and after a 2-week cessation of PPI. The volume, pH, and pH after acid loading (buffering capacity) of saliva were compared before and after the cessation of PPI. RESULTS: Thirty-two patients (25 NERD, 7 mild RE) were included. The second saliva test was performed a median interval of 14 months [12.0-15.3] after the first test. No significant differences were observed in the volume of saliva secreted before and after the cessation of PPI (before 4.0 mL [2.7-6.0] vs. after 4.0 mL [2.3-5.9], p = 0.894). No significant differences were noted in pH or changes in pH after acid loading before and after the cessation of PPI (pH: before 7.1 ± 0.24 vs. after 7.0 ± 0.24, p = 0.1. Delta pH after acid loading: before 1.0 [0.8-1.2] vs. after 1.0 [0.8-1.2], p = 0.844). CONCLUSION: The cessation of PPI did not appear to affect the volume, pH, or buffering capacity of saliva in patients with PPI-responsive mild RE and NERD.

Chronological Changes in Mucosal Deformity by Endoscopic Suturing after Gastric Endoscopic Submucosal Dissection: A Multicenter Retrospective Analysis.

INTRODUCTION: Endoscopic suturing of a mucosal defect is expected to prevent postoperative bleeding after endoscopic submucosal dissection (ESD). Endoscopic suturing causes mucosal deformity, which may interfere with endoscopic surveillance thereafter. We retrospectively investigated long-term chronological changes in mucosal suturing by endoscopic suturing. METHODS: Forty-three patients who underwent endoscopic hand suturing (EHS) after gastric ESD at three institutions were enrolled. First, our hypothesis that the suturing sites healed via inflammation, disappearance of mucosal inversion, and flattening was validated. Subsequently, the duration required to reach each healing step was evaluated. RESULTS: A total of 137 follow-up endoscopies were assessed, in which all cases showed the hypothesized chronological course on the suturing sites. The 95th percentiles of the duration when showing the disappearance of the inflammatory change and the inverted change were 63 days and 15.5 months after the procedure, respectively. DISCUSSION/CONCLUSION: The data show that the mucosal deformity induced by EHS disappeared within 16 months. Endoscopic suturing is thus considered to have a negligible effect on endoscopic surveillance following the procedure.

Prophylactic use of steroids for a mucosal defect with a circumference of less than three-fourths prevents both symptomatic and asymptomatic stricture after esophageal endoscopic submucosal dissection.

BACKGROUND: Subclinical stricture after esophageal endoscopic submucosal dissection (ESD) makes the detection and re-ESD of metachronous lesions difficult. This study aimed to investigate the effectiveness of prophylactic steroid use after esophageal ESD for mucosal defects with a circumference less than 75% for the prevention of symptomatic and asymptomatic stricture. METHODS: In 80 retrospectively enrolled patients, we collected paired endoscopic images of a mucosal defects immediately after resection and a scar thereafter. After calculating circumference by image analysis software, all patients were classified into three groups in reference to mucosal defect circumference (MDC; ≤ 50%, 50-75%, ≥ 75%). Frequency of steroid use and symptomatic stricture were compared, and in < 75% MDC patients, a degree of asymptomatic stricture with or without steroid was compared by calculating a scar contraction rate (SCR). RESULTS: In the ≤ 50% (43 patients), 50-75% (27 patients) and ≥ 75% (10 patients) MDC groups, steroids were used in 12%, 59% and 100%, respectively, and symptomatic stricture occurred in 0%, 7% and 40%, respectively. In < 75% MDC patients, SCR in the steroid cohort was significantly lower than that in the nonsteroid cohort (42% vs. 65%, p = 0.002). No steroid-related adverse events occurred. CONCLUSION: Steroid use even for mucosal defects with < 75% circumference appears effective for the reduction of the risk on both symptomatic and asymptomatic stricture after esophageal ESD.

Fine-needle biopsy with 19G needle is effective in combination with endoscopic ultrasound-guided tissue acquisition for genomic profiling of unresectable pancreatic cancer.

OBJECTIVES: Comprehensive genomic profiling (CGP) has been approved in Japan since June 2019, enabling mutation-specific therapy. Although tissue sampling via endoscopic ultrasound-guided tissue acquisition (EUS-TA) is standard in pancreatic cancer, reports on obtaining appropriate samples for CGP, especially for the OncoGuide NCC Oncopanel System (NOP) and FoundationOne CDx (FOne), are lacking. Therefore, we investigated the success rate and factors related to appropriate EUS-TA sampling for CGP analysis suitability in unresectable pancreatic ductal adenocarcinoma (UR-PDAC). METHODS: Participants comprised 150 UR-PDAC patients who underwent EUS-TA and tumor sample evaluation for CGP analysis suitability between June 2019 and December 2021. The proportion of patients meeting the criteria was evaluated considering tumor size, puncture lesion, presence of metastasis, type and size of puncture needle, suction method, number of punctures, and puncture route. RESULTS: In total, 39.2% (60/153) of samples met NOP analysis suitability criteria and 0% met FOne analysis suitability criteria. The suitability rate was significantly higher with 19G fine-needle biopsy (FNB) (56.0%; 42/75) than with 22G FNB (32.6%; 14/43) and 22G fine-needle aspiration (11.4%; 4/35). Nineteen-gauge needle (odds ratio [OR] 2.53; 95% confidence interval [CI] 1.15-5.57; P = 0.021) and FNB (OR 3.57; 95% CI 1.05-12.20; P = 0.041) were independent factors contributing to NOP analysis suitability. Among 30 patients who underwent actual NOP analysis, the analysis success rate was 100% (30/30). CONCLUSION: In sample collection via EUS-TA, 19G and FNB needles contribute to NOP analysis suitability.

High-resolution manometry with additional maneuvers using the Starlet system: normative thresholds and diagnostic yields for relevant esophagogastric junction outflow disorders.

BACKGROUND: Chicago classification version 4.0 suggests additional maneuvers, such as upright testing, multiple rapid swallows (MRS), and the rapid drink challenge (RDC), for high-resolution manometry (HRM) to minimize ambiguity in the diagnosis of esophageal motility disorders. The present study investigated normative thresholds for these new metrics using the Starlet system as well as their diagnostic yields for relevant esophagogastric outflow disorders (EGJOD). METHODS: In study 1, 30 asymptomatic volunteers prospectively performed HRM including MRS and RDC in the supine/upright positions. We calculated normative thresholds for the new metrics, such as upright integrated relaxation pressure (IRP), upright intrabolus pressure (IBP), and IRP during RDC (RDC-IRP). In study 2, we retrospectively analyzed the HRM tracings of 82 patients who underwent HRM in both positions at our hospital to assess the diagnostic yields of HRM metrics. RESULTS: Based on the results of study 1, we adopted the following normative thresholds: upright IRP < 20 mmHg, upright IBP < 21 mmHg, and RDC-IRP < 16 mmHg. In study 2, 45 patients with dysphagia or chest pain were included in the analysis to identify predictive factors for clinically relevant esophagogastric outflow disorders (true EGJOD). Supine/upright IRP, RDC-IRP, and pan-esophageal pressurization > 20 mmHg during RDC (RDC-PEP) predicted true EGJOD with RDC-PEP with the highest sensitivity of 91.7%. CONCLUSIONS: HRM with additional maneuvers may facilitate the diagnosis of clinically relevant EGJOD.