Obstructive jaundice is a common digestive disorder with multiple etiologies. Non-tuberculous mycobacterial (NTM) infection is an opportunistic disease that may present with localized pulmonary involvement or disseminated multi-organ manifestations. However, biliary involvement in disseminated NTM infection is rare, and its characteristics and progression remain poorly understood. We report a patient with progressive jaundice who was eventually considered to have probable biliary NTM infection after comprehensive evaluation, exclusion of alternative etiologies, and a favorable therapeutic response despite negative microbiological testing. Endoscopic retrograde cholangiopancreatography (ERCP) was performed to relieve biliary obstruction, but the patient developed recurrent and refractory ampullary bleeding requiring repeated endoscopic interventions. Clinical improvement was achieved following combined antimycobacterial therapy and immunomodulatory treatment. Biliary NTM infection is a rare cause of obstructive jaundice, and ERCP remains necessary for biliary decompression, while post-ERCP bleeding risk should be carefully monitored.

BACKGROUND AND AIM:Peroral endoscopic myotomy is a standard treatment for achalasia (AC). The conventional approach involves circular muscle myotomy (CMM), but full-thickness myotomy (FTM) may offer more profound lower esophageal sphincter (LES) reduction. This randomized controlled noninferiority trial primarily determined whether FTM achieved clinical success noninferior to CMM. METHODS:This single-center, randomized noninferiority trial enrolled 69 patients with type I or II AC assigned to the FTM group (n = 34) or the CMM group (n = 35). The primary outcome was clinical success (Eckardt score ≤3) at 6 months after the procedure. A noninferiority margin of -10% was prespecified. Secondary outcomes included procedure-related metrics, safety outcomes or adverse events, physiological and anatomical outcomes, and GERD-related outcomes. RESULTS:In the intention-to-treat analysis, clinical success rates were 91.2% in the FTM group and 85.7% in the CMM group, with a group difference of 5.5% (90% CI, -7.1% to 18.1%). Because the lower CI bound (-7.1%) was above -10%, FTM was noninferior to CMM. FTM was associated with significantly higher insufflation-related events (32.35% vs 11.43%; P = .035). There was a trend toward more frequent moderate-to-severe intraoperative bleeding in the FTM group (41.18% vs 22.86%; P = .103). FTM resulted in significantly lower basal LES pressure than CMM (6.85 vs 11.70 mm Hg; P = .024). Postoperative esophagitis showed a numerical trend toward an increase in the FTM group (36.36% vs 18.18%; P = .097). CONCLUSIONS:FTM was noninferior to CMM in short-term efficacy. However, FTM was associated with a significantly higher incidence of insufflation-related events and demonstrated a potential increase in postprocedural reflux. Despite the comparable efficacy, the disadvantages in the safety of FTM limit its recommendation as a routine alternative to CMM in the management of AC.

Background/objective Prophylactic endoloop or hemoclip application and endoscopic mucosal resection (EMR) have been usually performed for large pedunculated colorectal polyps. However, their comparison remains unclear. This study aimed to compare the efficacy and safety of the prophylactic pretreatment and EMR in the large pedunculated polyps. Methods We reviewed 1994 pedunculated polyps detected in Peking Union Medical College Hospital from 2012 to 2024. Large pedunculated polyps (head size ≥2.0 cm) receiving EMR or prophylactic closure before polypectomy were included. Polyp morphology, endoscopic procedural variables, and adverse events were compared using propensity score matching and inverse probability of treatment weights. Logistic regression was performed to analyze the risk factors of adverse events. Results 204 pedunculated polyps undergoing prophylactic pretreatment and 262 polyps resected via EMR were included. Less clips (P = 0.002) and lower operational material-related costs (P < 0.001) presented in the prophylactic closure group than the EMR group, while the procedural time was comparable (prophylactic closure vs. EMR: median 13.0 vs. 10.0 min, P = 0.059). There were no differences in postpolypectomy bleeding (15.2% vs. 12.5%, P = 0.466) and postpolypectomy coagulation syndrome (1.5% vs. 0.7%, P = 0.509) between the two groups. Stalk width ≥0.6 cm (OR = 2.34, P = 0.02), number of hemoclips (OR = 1.44, P < 0.01), procedure time ≥10 min (OR = 2.03, P = 0.08), and malignant lesion (OR = 1.74, P = 0.08) were associated with high risks of immediate bleeding. The endoscopic procedure did not affect the risks of immediate or delayed bleeding. Conclusion The prophylactic closure with hemoclip or endoloop and conventional EMR are both effective and safe methods for large pedunculated colorectal polyps. Prophylactic closure has advantages in the hemoclips demand and average procedure costs compared to EMR.

The endoscopic findings of gastric mucosa-associated lymphoid tissue (MALT) lymphoma are highly nonspecific and the sampling error or false-negative probabilities during conventional biopsy make its diagnosis more challenging. Confocal laser endomicroscopy is a novel technology which allows in vivo microscopic analysis of gastrointestinal mucosa. Here we present a case of gastric MALT lymphoma by targeted biopsy guided by magnifying endoscopy and probe-based confocal laser endomicroscopy.

BACKGROUND AND AIMS:Differentiating autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC) remains a diagnostic challenge. Although there is limited evidence that endoscopic ultrasound (EUS) is useful for diagnosing AIP, its full potential has yet to be leveraged in practice. This study aimed to develop an interpretable and accurate multi-modal AIP diagnostic model with clinical applicability by combining EUS features with clinical parameters. METHODS:This was a retrospective study of 577 patients attending six centers in China undergoing EUS and diagnosed with AIP or PDAC between January 2013 and April 2024. AIP and PDAC cases were randomly divided 1:1 into primary (n=289) and validation (n=288) cohorts. LASSO regression with five-fold cross-validation was used to determine the optimal clinical (n=5) and EUS (n=17) features discriminating AIP from PDAC. Multivariable logistic regression analysis was performed to develop a predictive model assessed in primary and validation cohorts with ROC-AUC and calibration curves. Comparator models based on clinical and EUS features alone were also evaluated using the same framework. Logistic regression coefficients were scaled to develop a clinical nomogram. RESULTS:Most clinical and endoscopic ultrasound features differed significantly between patients with AIP and PDAC. Patients with AIP were slightly younger, were much more likely to have elevated IgG4, and their ultrasound features were more consistent with a diffuse pancreatic parenchymal pathology. LASSO regression identified 16 non-zero coefficients, from which the top four features with the largest, non-collinear coefficients (elevated IgG4, elevated CA19-9, vascular involvement, and diffuse reduced echogenicity) produced a highly discriminative and well-calibrated model for AIP, with an AUC of 0.994 (95% CI 0.986-0.999; 97.2% accuracy, 96.7% sensitivity, 97.8% specificity) for the primary cohort and an AUC of 0.984 (95% CI 0.972-0.994; 95.5% accuracy, 93.5% sensitivity, 97.8% specificity) for the validation cohort. The integrated model showed more balanced diagnostic performance than clinical- or EUS-only models, particularly with respect to validation sensitivity. CONCLUSIONS:Combining EUS features with clinical and serological variables yields more balanced diagnostic performance for differentiating AIP from PDAC than either modality alone. Given the retrospective design, risk of overfitting, and lack of independent external validation, prospective validation is required prior to routine clinical implementation.

Abstract Background: Stanniocalcin 1 (STC1) is an immune checkpoint in macrophages that promotes tumor immune evasion and resistance to immunotherapy. This study aims to elucidate the functional role and underlying regulatory mechanisms of STC1 in gastric cancer (GC) and its associated tumor microenvironment. Methods: GC cells were transfected with STC1 -knockout (KO- STC1 ) and overexpression (OE- STC1 ) plasmids. To evaluate the effect of STC1 expression on the polarization of tumor-associated macrophages (TAMs) into the M2 phenotype, KO- STC1 GC cells were cocultured with M0 macrophages. To understand whether STC1 modulates the malignant behaviors of GC cells through the promotion of TAM polarization into the M2 state and elucidate the regulatory mechanisms, Cell Counting Kit-8 (CCK8), Transwell, Western blotting (WB), and enzyme-linked immunosorbent assays (ELISA) were performed. Results: In patients with GC, the expression level of STC1 markedly increased ( P <0.0001), which resulted in an unfavorable clinical prognosis. Dysregulated STC1 bound integrin subunit beta 6 (ITGB6) to modulate the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway in vitro and in vivo , which influenced the malignant behavior of GC cells, including proliferation, migration, invasion, apoptosis, and epithelial-mesenchymal transition (EMT). STC1 modulated the polarization of TAMs into the M2 state, which affected the proliferation, invasion, and EMT of GC cells. KO- STC1 GC cells cocultured with M0 macrophages inhibited the progression of GC through the inactivation of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway in TAMs, which suppressed M2 polarization and the secretion of interleukin-10 (IL-10). Conclusions: STC1 binds ITGB6 and modulates the progression of GC through the activation of the PI3K/AKT pathway, polarization of TAMs into the M2 state, and secretion of IL-10 via the JAK2/STAT3 pathway. This study may imply that STC1 has the potential to be a new target to suppress the development of GC.

The diagnosis of autoimmune pancreatitis (AIP) is multidisciplinary. Pathological diagnosis is pivotal when distinguishing AIP from malignancies. In this study, we aim to compare the diagnostic performance and sample adequacy of 19-gauge endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) needles with 20-gauge endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) needles in patients with suspected AIP. We conducted a single-centre, parallel-group, prospective, randomized controlled trial at Peking Union Medical College Hospital (Beijing, China). Patients with suspected AIP were enrolled between October 2018 and August 2023 and were randomly assigned to undergo tissue specimen collection using either a 19-gauge EUS-FNA needle or a 20-gauge EUS-FNB needle. The primary endpoint was the diagnostic accuracy against International Consensus Diagnostic Criteria, with secondary endpoints including histologic sensitivity, technical success rate, tissue adequacy, and adverse event rate. 46 patients were enrolled and 45 underwent EUS (FNB n = 23, FNA n = 22), amongst 42 had a final diagnosis of AIP. Diagnostic accuracy, as the primary endpoint, was 52.2

Pancreatic head-type autoimmune pancreatitis (PH-AIP) with elevated CA19-9 is sometimes difficult to distinguish from pancreatic head cancer (PHC) with elevated CA19-9. At times, IgG4 proves inadequate in offering assistance. The study aimed to elucidate the performance of CA19-9/DBil in distinguishing between the two conditions. This was a retrospective study. We collected serologic indicators from participants in PH-AIP and PHC Group. Three logistic regression equations were established ranging from non-adjustment (Model 1, only CA19-9/DBil included) to adjusting for sex, age, and CEA (Model 2 and Model 3) to explore the relationship between CA19-9/DBil and PH-AIP probability. ROC, Decision Curve Analysis (DCA), calibration curve were conducted. P for AUCs and net reclassification improvements (NRI) were computed to evaluate differences in discrimination and the improvement in risk reclassification between models. The study included 90 PHC and 35 PH-AIP patients, all with elevated CA19-9. The ORs for CA19-9/DBil in three models were similar (0.915 to 0.921). ROC revealed that Model 1 had an AUC of 0.772. The sensitivity, specificity, and accuracy at the best threshold were all > 0.7. Model 1, although simple, was not inferior in its discriminative ability compared to complex models: the difference in discrimination between Model 1 and each of two adjusted models was not statistically significant (P > 0.05, both AUC and NRI). Additionally, calibration curve and DCA suggested that Model 1 had good calibration and clinical utility. CA19-9/DBil exhibited promising diagnostic performance in differentiating between CA19-9-elevated PH-AIP and PHC.

BACKGROUND:Gastric GISTs (GG) are significant mesenchymal tumors. No biomarker has been identified for GG detection. We first observed mucosal atrophy surrounding GG tumors, leading to the hypothesis that localized atrophy may alter serum pepsinogen (PG) levels. Therefore, we developed a machine learning (ML) model incorporating serum PG levels and clinical features to predict GG and differentiate it from gastric cancer (GC). METHODS:We retrospectively analyzed GG and GC patients with tested PG levels before medical intervention. Seven ML algorithms were assessed, and feature importance was determined using SHapley Additive exPlanations (SHAP). Gastric atrophy was assessed histologically using the updated Sydney System. RESULTS:After screening 562 GG and 1090 GC patients, 100 GG and 174 GC samples were included. The multilayer perceptron (MLP) model achieved the highest AUC. The final MLP model, which included 4 features-gender, PGI levels, PGI/PGII ratio, and CEA-predicted GG with an AUC of 0.854. Considering clinical practice and the feature importance identified by the final MLP model, we established a Positive-Gastric-GIST-PG-CEA criterion (PGI < 70 ng/mL, PGI/PGII ratio ≥ 3.0, and CEA ≤ 5 μg/L) referring to the cutoff values revealed by the ROC curve. The Positive-Gastric-GIST-PG-CEA displayed exceptional performance in predicting GG (AUC = 0.772, accuracy = 0.748, specificity = 0.787, sensitivity = 0.680), with performance comparable to the final MLP model (ΔAUC = 0.082, p > 0.05). The contributions of PGI levels, PGI/PGII ratio, and CEA in the Positive-Gastric-GIST-PG-CEA model performance were 0.33, 0.15, and 0.13 based on SHAP analysis. Histopathological evaluation of gastric mucosal atrophy in 50 GG patients revealed peri-tumoral glandular atrophy in 29 cases (58%). CONCLUSIONS:The Positive-Gastric-GIST-PG-CEA criterion is valuable for detecting GG and distinguishing it from GC. Integrating our criteria into existing PG tests could help in GG detection without additional economic expense.

High-grade lung neuroendocrine carcinomas (Lu-NECs) are clinically refractory malignancies with poor prognosis and limited therapeutic advances. The biological and molecular features underlying the histological heterogeneity of Lu-NECs are not fully understood. In this study, we present a multi-omics integration of whole-exome sequencing and deep proteomic profiling in 93 Chinese Lu-NECs to establish the first comprehensive proteogenomic atlas of this disease spectrum. Our analyses revealed a high degree of mutational concordance among the subtypes at the genomic level; however, distinct proteomic profiles enabled a clear differentiation of histological subtypes, unveiling subtype-specific molecular and biological features related to tumor metabolism, immunity, and proliferation. Furthermore, RB1 mutations confer divergent prognostic effects through subtype-specific cis- and trans-proteomic regulation. In addition, we identified potential protein biomarkers for histological subtype classification and risk stratification, which were validated by immunohistochemistry in an independent cohort. This study provides a valuable proteogenomic resource and insight into Lu-NEC heterogeneity.

Carcinosarcoma of the gallbladder (CSGB) is an extremely rare subtype of primary gallbladder malignancy, which with a high rate of preoperative misdiagnosis due to its nonspecific clinical symptoms and imaging findings, as well as a high rate of recurrence within a short period of time after surgery, resulting in a very poor prognosis. Through a search of the medical literature, we found that there are few reports of CSGB receiving comprehensive treatments and achieving relatively good outcomes. Here, we report a rare case of CSGB with KRAS G12V mutation that achieved survival time of 32 months after receiving a combination of treatments including surgery, chemotherapy, radiotherapy, and immunotherapy, and we conducted a literature review for the disease with the aim of raising awareness of the disease.

BACKGROUND:Interleukin-1 receptor-associated kinase 1 (IRAK1), an active serine/threonine kinase, is an indispensable mediator of inflammatory responses and innate immunity. Emerging evidence has highlighted the oncogenic role of IRAK1 in tumors. However, the role of IRAK1 in gastric cancer (GC) progression remains unclear. METHODS:IRAK1 expression levels in patients with GC at Peking Union Medical College Hospital were assessed by Western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry. To elucidate the role of IRAK1 in GC pathogenesis, we established GC cells with clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) mediated IRAK1 knockout and lentiviral vector-mediated IRAK1 overexpression and subsequently conducted in vitro and in vivo experiments. Additionally, we assessed the effect of IRAK1 expression levels in GC cells on the M2 polarization of tumor-associated macrophages (TAMs) via a Transwell coculture system. Functional assays were subsequently carried out to determine whether IRAK1 regulates the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of GC cells through the induction of TAM M2 polarization and to clarify the associated regulatory mechanisms. RESULTS:IRAK1 expression was progressively increased during GC progression. Clinicopathological feature analysis revealed that high IRAK1 expression predicted poor survival outcomes. In vitro and in vivo experiments revealed that IRAK1 was highly expressed in GC cells and facilitated the proliferation, migration, invasion, and EMT of GC cells via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. More interestingly, IRAK1 affected the malignant biological behavior of GC cells by inducing M2-like polarization of macrophages. Mechanistically, coculturing M0 macrophages with IRAK1 -knockout GC cells suppressed interleukin (IL)-8 secretion, thereby inhibiting Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway activation in TAMs. Inactivation of the JAK2/STAT3 pathway suppressed the M2 polarization of TAMs, ultimately inhibiting GC progression. CONCLUSIONS:IRAK1 influences the malignant biological behavior of GC cells by activating the PI3K/AKT/mTOR pathway and inducing the M2-like polarization of macrophages via the IL-8/JAK2/STAT3 pathway in TAMs. Our findings provide a novel diagnostic biomarker and a promising therapeutic strategy for GC.

Esophageal stricture is a common complication after esophageal endoscopic submucosal dissection (ESD). Pathological scars may predict stricture development, but clinical studies exploring their relationship are limited. This study aimed to investigate the link between concurrent pathological scarring and post-ESD esophageal stricture and develop a predictive risk model. This retrospective single-center study included patients who underwent ESD for superficial esophageal lesions (SELs) over the past decade. Data on demographics, endoscopy, pathology, and concurrent scarring were collected. Multivariate logistic regression identified risk factors, followed by validation using subgroup analysis and propensity score matching. A nomogram was developed and internally validated. Of 255 patients, 28 (11.0