Background: Functional dyspepsia is common among older adults, with postprandial distress syndrome (PDS) as the main subtype. Clinical guidelines recommend prokinetic agents as first-line treatment for symptom relief of PDS. However, concerns over side effects limit their application with older patients. We investigated the efficacy and safety of pancreatin in treating older PDS patients. Methods: In this multicenter, real-world study, 175 older patients (age >= 60 years) diagnosed with PDS were divided into three groups: itopride monotherapy (56 patients), pancreatin enteric-coated capsule (PECC) monotherapy (62 patients), and combination therapy with PECC and itopride (57 patients). We compared the efficacy and safety of the treatments over a 2-week period, with follow-up 2 weeks post-treatment. The primary outcome was symptom improvement, change in Leuven postprandial distress scale (LPDS) score. Secondary outcomes were percentage changes in patient anxiety (generalized anxiety disorder-7 [GAD-7]) and depression (patient health questionnaire-9 [PHQ-9]) scores and adverse event incidence. Results: Baseline characteristics were similar among groups (P > 0.05). All groups experienced symptom relief from day 1 of treatment, with significant improvement through weeks 1 and 2 (P < 0.05). Changes in LPDS scores were not significantly different between the treatment groups at any time point. Average PHQ-9 scores for all groups decreased during treatment and stabilized after discontinuation. GAD-7 scores also significantly decreased then remained stable, with no significant difference among groups. No treatment-related adverse events were observed. Conclusion: PECC monotherapy effectively and safely treats PDS, with efficacy comparable to itopride monotherapy and combination therapy with pancreatin and itopride.

BACKGROUND AND AIMS:Gastric variceal bleeding (GVB) carries high mortality, and conventional endoscopy offers limited efficacy. This study aimed to evaluate the efficacy and safety of EUS-guided coils embolization combined with cyanoacrylate injection (EUS-Coils+CYA) versus transjugular intrahepatic portosystemic shunt combined with variceal embolization (TIPS+VE) in patients with GVB. METHODS:This multicenter retrospective study used a propensity score-matching (PSM) analysis. The primary outcomes were technical success rate, recurrent bleeding rate, and mortality rate. RESULTS:Of the 187 initially enrolled patients with cirrhosis and GVB, 124 were matched (62 per group). After 1:1 PSM, 124 patients were analyzed (62 in the EUS-Coils+CYA group and 62 in the TIPS+VE group). The technical success rate was 100% in both groups. No significant differences were found in the overall recurrent bleeding rate (11.29% vs 9.68%; P = .769) or mortality rate (4.84% vs 1.61%; P = .611). Regarding other adverse events, the TIPS+VE group had a higher incidence of postprocedural abdominal pain and overall hepatic encephalopathy (HE) than the EUS-Coils+CYA group (14.52% vs 1.61%; P = .008; 14.52% vs 1.61%; P = .008). Multivariate analysis identified the treatment method as a factor associated with HE development (hazard ratio = 8.84; 95% CI, 1.12-69.79; P = .039). Conversely, the incidence of ectopic embolism (all pulmonary embolisms) was higher in the EUS-Coils+CYA group than in the TIPS+VE group (9.68% vs 0%; P = .036). CONCLUSIONS:EUS-Coils+CYA and TIPS+VE showed comparable outcomes in controlling gastric varix recurrent bleeding and survival. Patients treated with EUS-Coils+CYA had a lower incidence of HE but carried a risk of ectopic embolism.

BACKGROUND:The gut microbiome plays a pivotal role in the development and progression of liver disease. Liver sinusoidal endothelial cells (LSECs), as the first hepatic barrier exposed to blood from the portal circulation, may be influenced by gut-derived microbiota and their byproducts. This study aimed to investigate the interaction between gut microbiota and LSECs and to clarify how this interaction impacts the progression of liver cirrhosis. METHODS:Liver cirrhosis was induced by carbon tetrachloride (CCl4) injection and bile duct ligation (BDL). CCl4 and BDL mice were administered rifaximin. The primary LSECs were isolated from mice and treated with LPS. 16S rRNA sequencing was conducted to examine changes in the gut microbiota of cirrhotic mice following rifaximin treatment. RESULTS:Rifaximin attenuated liver fibrosis and LSEC dysfunction in CCl4 and BDL mice. Liver cirrhosis induced remarkable changes in the gut microbiome while rifaximin treatment could partially reverse these alterations. Serum lipopolysaccharides (LPS) level was elevated in cirrhotic mice, while reduced following rifaximin treatment. Furthermore, LPS treatment could induce LSEC dysfunction by inhibiting eNOS mRNA expression, which was attenuated by TLR4 inhibitor, indicating that TLR4 signaling was involved in LPS-induced LSEC dysfunction. CONCLUSIONS:Intestinal microbiota dysbiosis allows more LPS to enter the portal circulation, which may in turn exacerbate LSEC dysfunction and liver fibrosis. Intestinal decontamination with rifaximin improves LSEC function and alleviates liver fibrosis, a process linked to the reconstruction of the gut microbiome and a reduction in gut-derived LPS.

BACKGROUND:Esophageal bronchogenic cysts (EBCs) are usually discovered incidentally during radiologic or endoscopic examinations. They are rare and prone to misdiagnosis or mistreatment. As a submucosal lesion, the endoscopic ultrasonography (EUS) characteristics of EBCs are unclear. AIM:To analyze the clinicopathological and EUS characteristics of EBCs. METHODS:A total of 22 patients with a histological diagnosis of EBCs who underwent EUS examination were retrospectively included. The clinicopathological and EUS features were collected and analyzed. RESULTS:Most of the EBCs were asymptomatic, and no malignant transformation or precancerous changes was found histologically. Most of the EBCs were located in the lower esophagus (72.7%, 16/22). A total of 90.9% (20/22) of the EBCs originated from the muscularis propria, and 9.1% (2/22) originated from the submucosa. All of the lesions had clear boundaries. In terms of echo, 77.3% (17/22) had a hypoechoic pattern, and 22.7% (5/22) had an anechoic pattern. We found floating echoes inside the lesion, which presented as a punctiform hyperecho in 45.5% (10/22) and a flocculent hypoecho in 36.4% (8/22) of the patients. A total of 45.5% (10/22) displayed posterior wall enhancement. Fourteen patients underwent color doppler, and no blood flow signal was identified. On EUS elastography, the EBCs presented a yellow-green or green pattern (100%, 6/6). When contrast-enhanced EUS was used, the EBCs showed no enhancement (100%, 5/5). CONCLUSION:When a submucosal lesion located at the lower esophagus originates from the intrinsic muscle layer, the possibility of EBCs should be noted, the EUS characteristics of which include a hypoecho with a clear boundary and a posterior wall enhancement, a floating echo inside and no blood flow signal, a yellow-green or green pattern on elastography, and no enhancement on contrast EUS.

BACKGROUND:The diagnosis of gastric inflammatory fibroid polyps (IFPs) mainly depends on pathological confirmation after endoscopic or surgical treatment. Gastric IFP have typical manifestations under endoscopic ultrasonography (EUS), but atypical EUS features have also been reported. Previous studies have found that atypical features of gastric IFPs observed under EUS have corresponding histological manifestations. At present, there is no study elaborating the EUS manifestations of gastric IFPs at different pathological stages. We hypothesize that gastric IFPs at different pathological stages may have different EUS features. AIM:To describe EUS features of gastric IFPs and compare with their pathological characteristics. METHODS:Clinical data of 53 inpatients with pathologically diagnosed gastric IFPs after endoscopic treatment were collected. All patients underwent preoperative EUS. We analyzed the EUS characteristics of the lesions and compared with the pathological characteristics and staging of the resected specimens. RESULTS:Most gastric IFPs showed medium-low echo (67.9%), homogeneous echo (90.6%), and unclear boundaries (83%), and involved the second and third layers of the gastric wall (69.8%) under EUS. The echogenicity level and echo homogeneity were significantly correlated with the pathological stage of gastric IFP. Gastric IFPs in the nodular stage presented hypoechoic and homogeneous echo. Gastric IFPs in the fibrovascular stage mostly showed medium-low echo and homogeneous echo. Gastric IFPs in the sclerotic stage showed different echogenicity levels and echo homogeneity. The accuracy of EUS in diagnosing gastric IFPs was 66.0% (35/53), and the accuracy in determining the origin layer of gastric IFPs was 73.4% (39/53). CONCLUSION:Gastric IFPs at different pathological stages have different EUS features. In order to improve the diagnostic rate, it is necessary to combine EUS with EUS-guided fine-needle aspiration or artificial intelligence.

Differences in the distribution of hydrophilic and hydrophobic bile acids (BA) are observed in mouse models of non-alcoholic fatty liver disease (NAFLD) induced by a high-fat-cholesterol "Western-style" diet (WD), and cholesterol gallstone disease (CGD) induced by a lithogenic diet. Despite sharing common pathological processes, these models exhibit distinct characteristics in their BA pools. The study investigates the impact of hydrophobic BA (HphoBA) and hydrophilic BA (HphilBA) on CGD development using cytochrome-P450-2c70 knockout (C70-KO) mice (miceC70-KO), genetically modified to resemble humans with a hydrophobic BA pool. All miceC70-KO fed the WD develop CGD, resembling human cholelithiasis patients, while WD-fed wild-type (WT) mice (miceWT) show cholesterol-saturated bile but rarely form gallstones. Compared to miceWT, WD-fed miceC70-KO display caveolae microdomain redistribution in the gallbladder mediated by the HphoBA, FXR, and miR30c/e axis, which enhances the Sp1 transcriptional activity of mucin-1 (MUC1) genes through nuclear translocation of protein kinase Cζ (PKCζ). These changes contribute to increased production of pronucleating agents (MUC1 and MUC5ac) and accelerate crystallization of gallbladder cholesterol. The data also suggest that WD-fed miceC70-KO appropriately model human CGD since lithogenic diet-fed miceWT have a larger BA pool that masks the negative effects of gallbladder FXR on CGD development.

Introduction: Achalasia is a primary motility disorder affecting the esophageal body and lower esophageal sphincter. Although the linkage between achalasia and elevated esophageal cancer risk is already known, the precise mechanisms remain poorly elucidated due to the disease’s relative scarcity. We aim to summarize the clinical characteristics of esophageal cancer (EC) secondary to achalasia and improve the understanding of achalasia combined with EC and further reduce the risk of ECs. Case Presentations: Retrospective statistics were conducted on patients with ECs secondary to achalasia in our hospital from 2009 to 2023. We categorized all achalasia cases with their initial treatment and recorded subsequent interventions when the symptoms recurred. Additionally, we performed detailed analyses of both EC characteristics and therapeutic regimens. We present a case series comprised of 5 patients with achalasia who presented with EC. Three of the patients diagnosed with achalasia were treated by endoscopy or operation to improve symptoms. One patient was treated by pneumatic dilation. All were histologically diagnosed as squamous cell carcinoma. The validity period of endoscopic treatment has been lost in all patients. The erosions were all distributed over the thoracic esophagus. Conclusion: The high relative risk of ECs was demonstrated in achalasia patients, even in the treated achalasia patients. Therefore, surveillance endoscopy may be recommended regularly in the treated patients.

Niemann-Pick C1-like 1 (NPC1L1) is distributed in the human liver and intestine but only slightly expressed in the mouse liver. While it is well established that intestinal NPC1L1 is crucial for the absorption of exogenous cholesterol, the physiological and pathological roles of canalicular membrane-localized NPC1L1 in human hepatic cholesterol transport remain unclear. In this review, we discussed the potential function of human hepatic NPC1L1 and proposed that the disparity in NPC1L1 abundance between humans and mice in the liver may be attributable to their distinct bile hydrophobicity. Human hepatic NPC1L1 might interact with other proteins in the canalicular membrane, regulate membrane cholesterol homeostasis, and contribute to the stability of the canalicular lipid bilayer membrane in response to the greater detergent properties of human bile salts. We hoped to provide novel perspectives on hepatic NPC1L1 for future investigations.

Background and Objectives:Bleeding from isolated gastric varix type I (IGV1) is less common but more dangerous and fatal than other varices. This study compared the safety and efficacy of endoscopic clipping and cyanoacrylate injection (EC-CYA) with EUS-guided coil and cyanoacrylate injection (EUS-coil/CYA) in the secondary prophylaxis of IGV1. Methods:A retrospective study was conducted on 131 patients with cirrhosis and a history of IGV1 bleeding who underwent either EC-CYA (n = 55) or EUS-coil/CYA (n = 76) at three medical centers. Primary outcomes were gastric variceal rebleeding and ectopic embolism. Secondary outcomes were technical success, variceal obliteration rate, cyanoacrylate volume, cyanoacrylate embolization efficiency, other causes of rebleeding, other adverse events, and mortality. Results:In the EC-CYA group, the gastric variceal rebleeding rate (14.5% vs. 8.7%, P = 0.307), technical success rate (96.4% vs. 94.7%, P > 0.999), other causes of rebleeding rate (12.7% vs. 5.8%, P = 0.303), other adverse events rate (5.5% vs. 5.8%, P > 0.999), and mortality (12.7% vs. 8.7%, P = 0.467) showed no significant differences compared with the EUS-coil/CYA group. No ectopic embolism was found in either group. The EC-CYA group had a higher cyanoacrylate volume (3.14 ± 1.45 mL vs. 1.99 ± 0.72 mL, P < 0.001) and a higher variceal obliteration rate at first follow-up (82.23% ± 27.09% vs. 66.59% ± 30.28%, P = 0.032). However, the EUS-coil/CYA group was superior to the EC-CYA group in terms of cyanoacrylate embolization efficiency (2.85 ± 2.05 cm2/mL vs. 1.98 ± 1.46 cm2/mL, P = 0.044). Conclusions:Both EC-CYA and EUS-coil/CYA are safe and effective in preventing rebleeding of IGV1. The EUS-coil/CYA has better embolization efficiency, whereas EC-CYA has better operational convenience.

BACKGROUND Gastrointestinal schwannomas (GIS) are rare neurogenic tumors arising from Schwann cells in the gastrointestinal tract. Studies on GIS are limited to small case reports or focus on specific tumor sites, underscoring the diagnostic and therapeutic challenges they pose. AIM To comprehensively examine the clinical features, pathological characteristics, treatment outcomes, associated comorbidities, and prognosis of GIS. METHODS The study population included patients diagnosed with GIS at the First Affiliated Hospital, Zhejiang University School of Medicine, between June 2007 and April 2024. Data were retrospectively collected and analyzed from medical records, including demographic characteristics, endoscopic and imaging findings, treatment modalities, pathological evaluations, and follow-up information. RESULTS In total, 229 patients with GIS were included, with a mean age of 56.00 years and a male-to-female ratio of 1:1.83. The mean tumor size was 2.75 cm, and most (76.9%) were located in the stomach. Additionally, 6.6% of the patients had other malignant tumors. Preoperative imaging and endoscopy frequently misdiagnosed GIS as gastrointestinal stromal tumors. However, accurate preoperative diagnosis was achieved using endoscopic ultrasound-guided fine-needle aspiration combined with immunohistochemical analysis, in which S100 and SOX-10 markers were mostly positive. Smaller tumors were typically managed with endoscopic resection, while larger lesions were treated with surgical resection. Follow-up results showed that most patients experienced favorable outcomes. CONCLUSION Preoperative diagnosis of GIS via clinical characteristics, endoscopy, and imaging examinations remains challenging but crucial. Endoscopic therapy provides a minimally invasive and effective option for patients.

BACKGROUND:An inflammatory fibrotic polyp (IFP) of the gastrointestinal tract is generally considered benign and noninvasive. An IFP in the duodenum is very rare. Here we report the case of an aggressive and infiltrative duodenal IFP resembling a malignancy and the patient subsequently underwent surgery. To the best of our knowledge, this is the first case of duodenal IFP invading the subserosa. CASE SUMMARY:A 50-year-old female patient presented with recurrent epigastric pain for more than 1 month. Gastroscopy revealed a mass in the duodenal bulb involving the pylorus. Endoscopic ultrasound suggested that the lesion was a hypoechoic mass involving the muscularis propria, and duodenal bulb stromal tumor was considered based on abdominal computed tomography and gastric magnetic resonance imaging findings. A distal gastrectomy was subsequently performed. Based on the histopathology and immunohistochemical results, the lesion was finally diagnosed as duodenal IFP. The patient recovered well after surgery and had no recurrence at the 27-month follow-up. CONCLUSION:This duodenal IFP invading subserosa indicates that IFP has specific invasion characteristics, and accurate diagnosis is critical to avoid inadequate treatment.

Background:Esophageal neuroendocrine carcinoma (ENEC) is a rare, aggressive malignancy with limited comparative data between Eastern and Western populations. Optimal management strategies remain unclear, and prognostic tools for risk stratification are lacking. Objectives:To analyze differences in clinicopathological features, treatment patterns, and survival outcomes between Chinese and American ENEC patients, and to develop a prognostic nomogram for unresectable disease. Design:A retrospective comparative cohort study. Methods:We analyzed 88 ENEC patients from a Chinese institution and 545 from the Surveillance, Epidemiology, and End Results (SEER) database. Demographic, tumor, treatment, and survival data were compared using Chi-square tests and Kaplan-Meier analysis. Cox regression identified prognostic factors for cancer-specific survival. A nomogram for unresectable ENEC was developed using SEER data and evaluated using C-index, calibration curves, and receiver operating characteristic analysis. Results:Significant population differences included age distribution (46-65 years: 51.1% Chinese vs 35.4% SEER, p < 0.001), tumor location (lower esophagus: 22.7% vs 62.2%), histology (small cell: 38.6% vs 76.9%), and metastatic presentation (M1: 28.4% vs 54.1%, all p < 0.01). Among non-metastatic patients, 77.8% Chinese underwent surgery versus 19.2% SEER (p < 0.001). Despite this treatment disparity, median survival was similar for surgical patients (48 vs 32 months, p = 0.93). Metastatic disease and age >65 were independent adverse prognostic factors in both cohorts. The Chinese cohort showed additional prognostic factors including tumor location and histology. The nomogram incorporating age, tumor location, N stage, M stage, and chemotherapy achieved a C-index of 0.725 with excellent calibration at 12 and 24 months. Conclusion:ENEC demonstrates distinct population-specific characteristics between Chinese and Western patients, with fundamental differences in treatment approaches but comparable surgical outcomes. The validated nomogram provides superior risk stratification for unresectable disease compared to traditional staging. These findings support population-tailored management strategies rather than universal treatment paradigms for ENEC.

Pancreatic cystic neoplasms (PCNs) are a complex group of lesions with a spectrum of malignancy. Accurate differentiation of PCN types is crucial for patient management, as misdiagnosis can result in unnecessary surgeries or treatment delays, affecting the quality of life. The significance of developing a non-invasive, accurate diagnostic model is underscored by the need to improve patient outcomes and reduce the impact of these conditions. We developed a machine learning model capable of accurately identifying different types of PCNs in a non-invasive manner, by using a dataset comprising 449 MRI and 568 CT scans from adult patients, spanning from 2009 to 2022. The study’s results indicate that our multimodal machine learning algorithm, which integrates both clinical and imaging data, significantly outperforms single-source data algorithms. Specifically, it demonstrated state-of-the-art performance in classifying PCN types, achieving an average accuracy of 91.2%, precision of 91.7%, sensitivity of 88.9%, and specificity of 96.5%. Remarkably, for patients with mucinous cystic neoplasms (MCNs), regardless of undergoing MRI or CT imaging, the model achieved a 100% prediction accuracy rate. It indicates that our non-invasive multimodal machine learning model offers strong support for the early screening of MCNs, and represents a significant advancement in PCN diagnosis for improving clinical practice and patient outcomes. We also achieved the best results on an additional pancreatic cancer dataset, which further proves the generality of our model.

BACKGROUND:The association between serological indexes and occurrence of complications in patients with autoimmune gastritis (AIG) remains unclear. METHODS:91 patients with AIG were recruited and their clinical information were collected. The differences between serological indexes and complications of AIG were analyzed. And potential biomarker for early prediction and diagnosis of AIG with complications was explored. RESULTS:AIG patients in our study was 58.12 ± 11.68 years old, containing 31 males and 60 females. G17 was elevated in 49 of 52; PGI/II decreased in 43/49; GPA positive in 48/61; Anemia presented 28 in 80; Vitamin B12 deficiency occurred 23 in 58. Neuroendocrine tumor (NET) was the most common complication in AIG patients, accounting for 27/91. The second was polyps, making up for 14/91. There is also 9/91 of gastric mucosa neoplasia happened in AIG. No significant difference of G7, PGI, PGII, PGI/II and VB12 in AIG was found in different gastric mucosal lesions (P > 0.05). However, AIG patients with TPOAb positive had a higher risk in the occurrence of NET simultaneously (P = 0.0212). Those AIG with NET patients exhibited a significantly higher TPOAb level (P = 0.0078). ROC curve suggested that TPOAb can predict the existence of NET in AIG (AUC = 0.7410, P < 0.05). CONCLUSION:We found that TPOAb can serve as a predictive biomarker of NET in AIG. This accessible test is helpful for endoscopy specialists to pay attention to gastric mucosal lesions in TPOAb-positive AIG patients, improving early diagnosis and intervention of comorbidities ability.

Objectives: This study aimed to confirm whether premedication with pronase before endoscopy improves mucosal visualization and increases precancerous lesion and cancer lesion detection rates. Materials and Methods: From June 2018 to April 2019, out-patients scheduled for endoscopy from 13 hospitals were screened to be randomly allocated in a 2:1 ratio to premedication with pronase (group A) and water (group B). The primary endpoint was mucosal visibility scores, and the secondary endpoint was precancerous and cancer lesion detection rates. This trial was registered at Chinese Clinical Trial Registry, and the registration number was ChiCTR1800016853. Results: Group A showed significantly lower mucosal visibility scores (better mucosal visibility) of esophagus, stomach, and duodenum than group B, with all P -values <0.001. The overall cancer detection rates between group A and group B were 0.83 and 1.08%, and overall detection rates of precancerous and cancer lesion were 4.4 and 4.9%, both without significant difference ( P =1.000 and 0.824). In addition, the flushing volume (milliliter) of group A (10.52±23.41) was less than group B (36.30±52.11) ( P <0.001), and the flushing frequency of group A (0.46±1.01) was fewer than group B (1.62±2.12) ( P <0.001). Conclusions: Premedication with pronase could achieve better mucosal visibility and decrease flushing frequency and volume, but may not increase lesion detection rates.