Diagnosing Solid Lesions in the Pancreas With Multimodal Artificial Intelligence: A Randomized Crossover Trial.

Importance: Diagnosing solid lesions in the pancreas via endoscopic ultrasonographic (EUS) images is challenging. Artificial intelligence (AI) has the potential to help with such diagnosis, but existing AI models focus solely on a single modality. Objective: To advance the clinical diagnosis of solid lesions in the pancreas through developing a multimodal AI model integrating both clinical information and EUS images. Design, Setting, and Participants: In this randomized crossover trial conducted from January 1 to June 30, 2023, from 4 centers across China, 12 endoscopists of varying levels of expertise were randomly assigned to diagnose solid lesions in the pancreas with or without AI assistance. Endoscopic ultrasonographic images and clinical information of 439 patients from 1 institution who had solid lesions in the pancreas between January 1, 2014, and December 31, 2022, were collected to train and validate the joint-AI model, while 189 patients from 3 external institutions were used to evaluate the robustness and generalizability of the model. Intervention: Conventional or AI-assisted diagnosis of solid lesions in the pancreas. Main Outcomes and Measures: In the retrospective dataset, the performance of the joint-AI model was evaluated internally and externally. In the prospective dataset, diagnostic performance of the endoscopists with or without the AI assistance was compared. Results: The retrospective dataset included 628 patients (400 men [63.7%]; mean [SD] age, 57.7 [27.4] years) who underwent EUS procedures. A total of 130 patients (81 men [62.3%]; mean [SD] age, 58.4 [11.7] years) were prospectively recruited for the crossover trial. The area under the curve of the joint-AI model ranged from 0.996 (95% CI, 0.993-0.998) in the internal test dataset to 0.955 (95% CI, 0.940-0.968), 0.924 (95% CI, 0.888-0.955), and 0.976 (95% CI, 0.942-0.995) in the 3 external test datasets, respectively. The diagnostic accuracy of novice endoscopists was significantly enhanced with AI assistance (0.69 [95% CI, 0.61-0.76] vs 0.90 [95% CI, 0.83-0.94]; P < .001), and the supplementary interpretability information alleviated the skepticism of the experienced endoscopists. Conclusions and Relevance: In this randomized crossover trial of diagnosing solid lesions in the pancreas with or without AI assistance, the joint-AI model demonstrated positive human-AI interaction, which suggested its potential to facilitate a clinical diagnosis. Nevertheless, future randomized clinical trials are warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT05476978.

Preoperative H. pylori Eradication Therapy Facilitates Precise Delineation in Early Gastric Cancer with Current H. pylori Infection.

INTRODUCTION: Early gastric cancer with current Helicobacter pylori infection (HpC-EGC) is common, but it is still unclear whether H. pylori eradication therapy (Hp-ET) or endoscopic submucosal dissection (ESD) should be performed first. We evaluated Hp-ETs short-term effects on horizontal boundary delineations of HpC-EGC in ESD. METHODS: Prospectively enrolled HpC-EGC patients were randomly assigned to eradication or control groups. Operation scopes of HpC-EGC lesions were delineated with marking dots at 5 mm out of the endoscopic demarcation line by an independent endoscopist, unaware of eradication status, before formal circumferential incision. As representatives, precise delineation rate, the shortest distance of all marking dots to the pathological demarcation line in all slices of one intact resected specimen (Dmin), and negative marking dot specimen rate were examined. RESULTS: Twenty-three HpC-EGC patients (25 lesions) were allocated to eradication group and 26 patients (27 lesions) were allocated to the control group with similar eradication success rates and all were differentiated type. With improving background mucosa inflammation after Hp-ET and similar gastritis-like epithelium rates, 10 lesions (40.0%) in the eradication group were of precise delineation compared to control group with 2 lesions (7.4%) (relative risk = 5.40, 95% CI 1.31-22.28). Dmin of eradication and control groups were 4.17 ± 2.52 mm and 2.67 ± 2.30 mm (p = 0.029), accompanied by 4 (14.8%) and none (0.0%) specimens that exhibited positive marking dots (p = 0.11), respectively. CONCLUSION: For HpC-EGC patients, administrating eradication medication before ESD is beneficial for the precise delineation of lesions and reducing the risk of positive horizontal resection margins.

SI-ViT: Shuffle instance-based Vision Transformer for pancreatic cancer ROSE image classification.

BACKGROUND AND OBJECTIVE: The rapid on-site evaluation (ROSE) technique improves pancreatic cancer diagnosis by enabling immediate analysis of fast-stained cytopathological images. Automating ROSE classification could not only reduce the burden on pathologists but also broaden the application of this increasingly popular technique. However, this approach faces substantial challenges due to complex perturbations in color distribution, brightness, and contrast, which are influenced by various staining environments and devices. Additionally, the pronounced variability in cancerous patterns across samples further complicates classification, underscoring the difficulty in precisely identifying local cells and establishing their global relationships. METHODS: To address these challenges, we propose an instance-aware approach that enhances the Vision Transformer with a novel shuffle instance strategy (SI-ViT). Our approach presents a shuffle step to generate bags of shuffled instances and corresponding bag-level soft-labels, allowing the model to understand relationships and distributions beyond the limited original distributions. Simultaneously, combined with an un-shuffle step, the traditional ViT can model the relationships corresponding to the sample labels. This dual-step approach helps the model to focus on inner-sample and cross-sample instance relationships, making it potent in extracting diverse image patterns and reducing complicated perturbations. RESULTS: Compared to state-of-the-art methods, significant improvements in ROSE classification have been achieved. Aiming for interpretability, equipped with instance shuffling, SI-ViT yields precise attention regions that identifying cancer and normal cells in various scenarios. Additionally, the approach shows excellent potential in pathological image analysis through generalization validation on other datasets. CONCLUSIONS: By proposing instance relationship modeling through shuffling, we introduce a new insight in pathological image analysis. The significant improvements in ROSE classification leads to protential AI-on-site applications in pancreatic cancer diagnosis. The code and results are publicly available at https://github.com/sagizty/MIL-SI.

Comparison of Fine-Needle Biopsy (FNB) versus Fine-Needle Aspiration (FNA) Combined with Flow Cytometry in the Diagnosis of Deep-Seated Lymphoma.

Evidence comparing ultrasound endoscopy-guided fine-needle biopsy (EUS-FNB) with EUS-guided fine-needle aspiration (EUS-FNA) in deep-seated lymphoma tissue sampling is insufficient. This study aims to evaluate the diagnostic efficacy of immunohistochemistry (IHC) or flow cytometry (FCM) on specimens obtained from EUS-FNB and EUS-FNA in the diagnosis and staging of deep-seated lymphomas. This real-world, dual-center study prospectively evaluated all eligible specimens from patients who underwent EUS-FNB/FNA over an 8-year period. 53 patients were enrolled, with 23 patients in the EUS-FNB group and 30 patients in the EUS-FNA group. FNB yielded specimens with longer core tissues (0.80 mm [0.55, 1.00] vs. 0.45 mm [0.30, 0.50], p = 0.009) and higher scores of specimen adequacy [4 (3.75, 4.00) vs. 3 (1.00, 4.00), p = 0.025]. Overall analysis revealed that the diagnostic accuracy of IHC based on specimens acquired from EUS-FNB was significantly higher than that of EUS-FNA (91.30% vs. 60.00%, p = 0.013). After controlling confounding factors including lesion size and endoscopists, EUS-FNB with IHC maintained a higher-level diagnostic accuracy compared to EUS-FNA (OR = 1.292 [1.037-1.609], p = 0.023). When FCM was additionally used to analyze the specimen acquired from EUS-FNA, the diagnostic yield was significantly improved (ROC AUC: 0.733 vs. 0.550, p = 0.015), and the AUC of FNB alone or combined with FCM was 0.739 and 0.761. Conclusions: FNB needles generate higher histopathological diagnostic accuracy and specimen quality than FNA for the deep-seated lymphoma. Though the application of FCM significantly improves the diagnostic efficacy of EUS-FNA, FNB was still the preferred diagnostic modality with a shorter procedure time, comparable diagnostic accuracy, and better cost-effectiveness.

Insights into the Oncogenic, Prognostic, and Immunological Role of BRIP1 in Pan-Cancer: A Comprehensive Data-Mining-Based Study.

Background: BRCA1 interacting helicase 1 (BRIP1), an ATP-dependent DNA helicase which belongs to an Iron-Sulfur (Fe-S) helicase cluster family with a DEAH domain, plays a key role in DNA damage and repair, Fanconi anemia, and development of several cancers including breast and ovarian cancer. However, its role in pan-cancer remains largely unknown. Methods: BRIP1 expression data of tumor and normal tissues were downloaded from the Cancer Genome Atlas, Genotype-Tissue Expression, and Human Protein Atlas databases. Correlation between BRIP1 and prognosis, genomic alterations, and copy number variation (CNV) as well as methylation in pan-cancer were further analyzed. Protein-protein interaction (PPI) and gene set enrichment and variation analysis (GSEA and GSVA) were performed to identify the potential pathways and functions of BRIP1. Besides, BRIP1 correlations with tumor microenvironment (TME), immune infiltration, immune-related genes, tumor mutation burden (TMB), microsatellite instability (MSI), and immunotherapy as well as antitumor drugs were explored in pan-cancer. Results: Differential analyses showed an increased expression of BRIP1 in 28 cancer types and its aberrant expression could be an indicator for prognosis in most cancers. Among the various mutation types of BRIP1 in pan-cancer, amplification was the most common type. BRIP1 expression had a significant correlation with CNV and DNA methylation in 23 tumor types and 16 tumor types, respectively. PPI, GSEA, and GSVA results validated the association between BRIP1 and DNA damage and repair, cell cycle, and metabolism. In addition, the expression of BRIP1 and its correlation with TME, immune-infiltrating cells, immune-related genes, TMB, and MSI as well as a variety of antitumor drugs and immunotherapy were confirmed. Conclusions: Our study indicates that BRIP1 plays an imperative role in the tumorigenesis and immunity of various tumors. It may not only serve as a diagnostic and prognostic biomarker but also can be a predictor for drug sensitivity and immunoreaction during antitumor treatment in pan-cancer.

Endoscopic mucosal resection using cold snare versus hot snare in treatment for 10-19 mm non-pedunculated colorectal polyps: protocol of a non-inferiority randomised controlled study.

INTRODUCTION: Cold polypectomy has the advantages of simple operation, less time-consuming and fewer complications. Guidelines have recommended cold snare polypectomy (CSP) to resect small polyps sized ≤5 mm and sessile polyps sized 6-9 mm. However, evidence is scarce regarding cold resection for non-pedunculated polyps sized ≥10 mm. Cold snare endoscopic mucosal resection (CS-EMR) combining CSP and submucosal injection was designed to improve the complete resection rate and reduce adverse events. We hypothesise that CS-EMR is non-inferior to conventional hot snare endoscopic mucosal resection (HS-EMR) in the resection of 10-19 mm non-pedunculated colorectal polyps. METHODS AND ANALYSIS: This study is a prospective, randomised, open-label, non-inferiority, single-centre trial. Outpatients scheduled to undergo a colonoscopy and present eligible polyps will be randomised to receive either CS-EMR or HS-EMR. The primary endpoint is the complete resection. Considering that HS-EMR of 10-19 mm colorectal polyps will yield a complete resection rate of at least 92% and a non-inferiority margin of -10%, a total of 232 polyps will be included (one-sided α, 2.5%; ß, 20%). The analyses are intended to evaluate first non-inferiority (lower limit 95% CI greater than -10% for group difference) and then superiority (lower limit 95% CI>0%) if non-inferiority is achieved. Secondary endpoints include en-bloc resection, the occurrence of adverse events, the use of endoscopic clips, resection time and cost. ETHICS AND DISSEMINATION: The study has been approved by the institutional review board of the Peking Union Medical College Hospital (No. K2203). All participants in the trial will provide written informed consent. The results of this trial will be published in an open-access way. TRIAL REGISTRATION NUMBER: NCT05545787.

A Chinese prospective multicenter cohort study evaluating EUS-guided drainage of pancreatic fluid collections using the Hot AXIOS system.

Background and Objectives: The Hot AXIOS system, which features a cautery-enhanced lumen-apposing metal stent, facilitates EUS-guided transmural drainage of pancreatic fluid collection (PFC). We aimed to evaluate the safety and efficacy of stents in a multicenter Chinese cohort. Patients and Methods: Thirty patients from nine centers with a single pancreatic pseudocyst (PP) or walled-off necrosis (WON) who underwent EUS-guided transgastric or transduodenal drainage with the novel stent were prospectively enrolled. Results: We included 15 (50%) patients with PPs and 15 (50%) with WONs. The mean diameter of the PFCs was 11.06 ± 3.56 cm. Stent placement was technically successful in all patients (100%), whereas clinical success was achieved in 93.3% of patients (28/30). Clinical success was defined as the alleviation of clinical symptoms combined with at least a 50% reduction in PFC diameter within 60 days after surgery. 73.3% (22/30) of AXIOS stents were removed after reaching clinical success in the 1st month of follow-up. A total of 14 (46.7%) PFC-associated infections occurred (4 pre- and 10 postoperation), which recovered within 1 week after treatment. Other complications included three (10%) partially or fully blocked stents and two (6.7%) stent migrations. Regarding the fully opened stent without blocking, complete remission of PFCs within 1 month was independently predicted by a previous pancreatitis attack > 6 months prior (adjusted odds ratio: 11.143; 95% confidence interval: 1.108-112.012; P = 0.041). Conclusion: EUS-guided drainage of PFCs using the Hot AXIOS system is safe and efficient. Regarding completely patent stents, a previous pancreatitis attack > 6 months prior predicts a greater chance of achieving 100% remission of PFCs within 1 month of AXIOS treatment.

Distinct lipid profile in haemolytic anaemia-related gallstones compared with the general gallstone.

BACKGROUND: Pigment gallstones are not uncommon among patients with chronic haemolytic anaemia. But their clinical characteristics have not been described in detail and not been directly compared with the general gallstone population. METHODS: Patients at Peking Union Medical College Hospital with haemolytic anaemia and subsequent gallstones from January 2012 to December 2022 were included. Cases were matched (1:2) based on age, sex and location of stones to randomly select non-anaemia patients with gallstones (controls). RESULTS: Screening 899 cases of gallstones, we finally included 76 cases and 152 controls. Total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) for cases were 3.02 ± 0.98 mmol/L, 0.89 ± 0.30 mmol/L and 1.58 ± 0.70 mmol/L, respectively, significantly lower than those in the control group (all p < 0.001). TC and HDL were both lower than the normal range, but triglyceride and LDL were within the normal range. Multiple stones were significantly more common for cases (n = 59, 78%) than for controls (n = 44, 29%, p < 0.001). The mean diameter of the maximal gallstone was 1.2 ± 0.6 cm and 1.5 ± 1.0 cm for cases and controls (p = 0.120), respectively. Stones in the elderly (p = 0.002 for univariate analysis, and 0.001 for multivariate analysis) and stones in the bile duct (p = 0.005 for univariate analysis, and 0.009 for multivariate analysis) were found to occur in a shorter period after anaemia. CONCLUSION: The lipid profile of haemolytic anaemia with gallstones was distinct, low TC, low HDL, and increased-to-normal LDL, compared with the general gallstone population. Patients with haemolytic anaemia were recommended an abdominal ultrasound if aged older than 50 years, with more frequent follow-up visits.KEY MESSAGESClinical characteristics of gallstones following chronic haemolytic anaemia were described and compared with the general gallstone population.The lipid profiles were distinctly different between the patients with gallstones following chronic haemolytic anaemia and the general gallstone population.Elder patients were complicated with gallstones in a shorter period after anaemia and thus were recommended an abdominal ultrasound if aged older than 50 years, with more frequent follow-up visits.

MSHT: Multi-stage Hybrid Transformer for the ROSE Image Analysis of Pancreatic Cancer.

Pancreatic cancer is one of the most malignant cancers with high mortality. The rapid on-site evaluation (ROSE) technique can significantly accelerate the diagnostic workflow of pancreatic cancer by immediately analyzing the fast-stained cytopathological images with on-site pathologists. However, the broader expansion of ROSE diagnosis has been hindered by the shortage of experienced pathologists. Deep learning has great potential for the automatic classification of ROSE images in diagnosis. But it is challenging to model the complicated local and global image features. The traditional convolutional neural network (CNN) structure can effectively extract spatial features, while it tends to ignore global features when the prominent local features are misleading. In contrast, the Transformer structure has excellent advantages in capturing global features and long-range relations, while it has limited ability in utilizing local features. We propose a multi-stage hybrid Transformer (MSHT) to combine the strengths of both, where a CNN backbone robustly extracts multi-stage local features at different scales as the attention guidance, and a Transformer encodes them for sophisticated global modeling. Going beyond the strength of each single method, the MSHT can simultaneously enhance the Transformer global modeling ability with the local guidance from CNN features. To evaluate the method in this unexplored field, a dataset of 4240 ROSE images is collected where MSHT achieves 95.68% in classification accuracy with more accurate attention regions. The distinctively superior results compared to the state-of-the-art models make MSHT extremely promising for cytopathological image analysis. The codes and records are available at: https://github.com/sagizty/ Multi-Stage-Hybrid-Transformer.

Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy.

BACKGROUND: A high prevalence of diabetes mellitus (DM) coexisting with autoimmune pancreatitis (AIP) is observed. However, evidence on the circumstances under which corticosteroid therapy (CST) for AIP improves or worsens DM is scarce. This study aimed to demonstrate and identify predictors of DM control under the influence of CST. METHODS: Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed: pre-existing DM (pDM), concurrent DM (cDM), and non-DM (nDM). The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as 'improvement' and 'non-improvement' (including 'no change' and 'exacerbation'). RESULTS: Among 101 patients with type 1 AIP, 52 (51.5%) patients were complicated with DM at the time of AIP diagnosis, with 36 patients in the cDM group and 16 patients in the pDM group. The incidences of diffuse pancreatic swelling (72.2%) and pancreatic body/tail involvement (91.7%) were significantly higher in the cDM group than in both the pDM and nDM groups. Of the 52 patients with DM, CST was administered in 48 cases. Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase (GGT) level at AIP diagnosis [odds ratio (OR) = 0.032, 95% confidence interval (CI): 0.003-0.412, P = 0.008] and pancreatic atrophy after CST (OR = 0.027, 95% CI: 0.003-0.295, P = 0.003) were negatively associated with DM control improvement. CONCLUSIONS: Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis. CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis, particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.

Endoscopic ultrasound-guided tissue acquisition with or without rapid on-site evaluation for solid pancreatic lesions: five years of experience from a single center.

BACKGROUND: Endoscopic ultrasound (EUS)-guided tissue acquisition (TA) by EUS-guided fine needle aspiration (FNA) or fine needle biopsy (FNB) is a standard diagnostic procedure for solid pancreatic lesions. Whether rapid on-site evaluation (ROSE) should be used to support EUS-TA remains controversial. Here we assessed the diagnostic performance of EUS-TA with or without self-ROSE for solid pancreatic masses. METHODS: Three hundred and seventy EUS-TA cases with self-ROSE and 244 cases without ROSE were retrospectively enrolled between August 2018 and June 2022. All procedures including ROSE were performed by the attending endoscopist. Clinical data, EUS characteristics, and diagnostic performance for distinguishing benign from malignant solid pancreatic masses including accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were compared between groups. RESULTS: Self-ROSE improved the diagnostic accuracy of solid pancreatic lesions by 16.7% in the EUS-TA group (p < 0.001) and by 18.9% in the EUS-FNA alone group (p < 0.001). Self-ROSE also improved the diagnostic sensitivity by 18.6% in the EUS-TA group (p < 0.001) and by 21.2% in the EUS-FNA alone group (p < 0.001). Improvements in the diagnostic accuracy by self-ROSE in the EUS-FNB group were not significant. 2.2 ± 0.7, 2.4 ± 0.9, 2.3 ± 0.7, 2.5 ± 0.9, 2.1 ± 0.6, and 2.1 ± 0.7 needle passes were required in the EUS-TA, EUS-FNA, and EUS-FNB with or without self-ROSE groups, respectively. CONCLUSIONS: Self-ROSE significantly improved the accuracy and sensitivity of EUS-FNA alone and EUS-TA diagnosis of solid pancreatic lesions and helped to reduce needle passes during the procedure. Whether self-ROSE benefits EUS-FNB and whether EUS-FNB alone is comparable to EUS-FNA with self-ROSE require further clarification.

Relationship of liver fat content with systemic metabolism and chronic complications in patients with type 2 diabetes mellitus.

OBJECTIVE: This study investigated the correlation of liver fat content (LFC) with metabolic characteristics and its association with chronic complications in type 2 diabetes mellitus (T2DM) patients. METHODS: Eighty-one prospectively enrolled T2DM patients were divided into non-alcoholic fatty liver disease (NAFLD) group and the non-NAFLD group according to the presence of NAFL complications. LFC was determined by MRI IDEAL-IQ Sequence, and patients were divided into 4 groups according to LFC by quartile method. Basic information, metabolic indexes, and occurrence of chronic complications in different groups were analyzed and compared. RESULTS: BMI, SBP, DBP, TG, ALT, AST, GGT, UA, HbA1c, FCP, 2 h CP, HOMA-IR, and HOMA-IS in the NAFLD group were significantly higher than the non-NAFLD group (P < 0.05). The incidences of chronic complications in the NAFLD group were higher than in the non-NAFLD group but not statistically significant (P > 0.05). BMI, SBP, DBP, TC, TG, ALT, AST, FCP, 2 h CP, HOMA-IR, and HOMA-IS showed significant differences between the patients with different LFC, and these indexes were significantly higher in patients with higher LFC than those with lower LFC (P < 0.05). Moreover, diabetes duration, TC, HOMA-IR, and LFC were the risk factors for ASCVD complications, while diabetes duration, TG, and LDL-C were risk factors for DN complications. Also, diabetes duration and SBP were risk factors for both DR and DPN complications in T2DM patients (P < 0.05). CONCLUSION: LFC is positively correlated with the severity of the systemic metabolic disorder and chronic complications in T2DM patients.

A single-center experience on endoscopic ultrasonography-guided ethanol ablation of insulinomas.

BACKGROUND/OBJECTIVES: As the most frequent functional pancreatic neuroendocrine tumor, insulinomas may cause a plethora of symptoms and severe impairment in the living of patients by endogenous hyperinsulinemia and subsequent hypoglycemia. Surgery has been regarded as the first choice although a high risk of complications. Ethanol ablation is a promising non-surgical option that could achieve tumor shrinking in a short-term period. But the impact of symptom control and the long-term efficacy lack sufficient and good-quality evidence. METHODS: A total number of 14 endoscopic ultrasonography-guided ethanol ablations were performed in 9 patients between September 2016 and September 2018 in Peking Union Medical College Hospital. The data were collected and prospectively analyzed. RESULTS: The follow-up duration ranged from 21 to 1567 days in 9 patients, with a median of 994 days. 4 patients were free from relapse during a median follow-up of 1108 days (range: 994-1567 days). In 5 patients who suffered relapses, the median duration with symptom relief after the first ablation was 128 days (range: 13-393 days). If only repeated ablation was taken into consideration, the median duration with symptom relief was 26 days (range: 1-516 days). No complications happened during the procedures. The severe complication rate after the first ablation was 0.0% (0/9), compared to 7.14% (1/14) if each procedure was counted separately. The only severe complication documented was acute pancreatitis which was completely relieved after symptomatic treatment. CONCLUSIONS: For patients who are not suitable for surgical resections, endoscopic ultrasonography-guided ethanol ablation of insulinomas could be an effective and safe alternative to relieve symptoms of hypoglycemia.

Fine needle biopsy versus fine needle aspiration in the diagnosis of immunohistochemistry-required lesions: A multicenter study with prospective evaluation.

Objectives: The superiority of EUS-guided fine-needle biopsy (EUS-FNB) over fine-needle aspiration (FNA) remains controversial. This study aimed to compare the efficacy of FNB and FNA in immunohistochemistry (IHC)-required lesions, including, type 1 autoimmune pancreatitis (AIP), neuroendocrine tumor (NET), mesenchymal tumor, and lymphoma. Methods: In this multicenter study, specimens from all eligible patients who underwent EUS-FNB/FNA with these specific lesions were prospectively evaluated. Demographics, adequacy of specimens for IHC, diagnostic accuracy, and integrity of tissue were analyzed. Subgroup analysis and multivariate logistic regression were also performed to control confounders. Results: A total of 439 patients were included for analysis. Most lesion types were type 1 AIP (41.69%), followed by NET, mesenchymal tumor, and lymphoma. FNB yielded specimens with better adequacy for IHC (82.41% vs. 66.67%, P < 0.001) and higher diagnostic accuracy (74.37% vs. 55.42%, P < 0.001). The superiority of FNB over FNA in adequacy for IHC (odds ratio, 2.786 [1.515-5.291]) and diagnostic accuracy (odds ratio, 2.793 [1.645-4.808]) remained significant after control of confounders including needle size, lesion site, lesion size, and endoscopists. In subgroup analysis, FNB showed higher diagnostic accuracy in AIP and mesenchymal tumor, whereas no statistically significant difference was observed in NET and lymphoma. Conclusions: FNB was superior to FNA needles in obtaining tissues with better adequacy and integrity. These results suggest that FNB should be considered a first-line modality in the diagnosis of IHC-required lesions, especially AIP and mesenchymal tumor. However, a randomized controlled trial with larger sample size is needed to further confirm our findings.

Gastroblastoma Treated by Endoscopic Submucosal Excavation with a Novel PTCH1::GLI2 Fusion: A Rare Case Report and Literature Review.

Gastroblastoma is an extremely rare stomach tumor that primarily presents in adolescent and early adulthood, with a biphasic cell morphology of epithelioid and spindle cells. In light of its similarity to other childhood blastomas, it has been named gastroblastoma. Few patients showed a potential of metastasis and recurrence, however, most of the reported cases were alive, with no evidence of the disease after surgical treatment. Commonly, MALAT1-GLI1 fusion has been considered to be the most relevant mutation. Herein, we present a case of an asymptomatic 58-year-old man who happened to find a submucosal gastric mass during a gastroscope and received endoscopic submucosal excavation (ESE). He turned out to have a gastroblastoma with a novel PTCH1::GLI2 fusion confirmed by Sanger sequencing. The patient was discharged two days after ESE without any complication and was recurrence-free during his one-year follow-up. According to the previous literature and our own experience, in cases with characteristic histopathology and immunohistochemistry patterns, a diagnosis of gastroblastoma should be considered even without a MALAT1-GLI1 fusion. Gastroblastoma pursues a favorable clinical outcome and endoscopic therapy could be an effective alternative treatment choice.

Mendelian randomization in blood metabolites identifies triglycerides and fatty acids saturation level as associated traits linked to pancreatitis risk.

Background: There is very limited evidence on the causal effects of blood metabolites on pancreatitis risks. To reveal the causal associations between plasma metabolites and pancreatitis risks, we performed two-sample Mendelian randomization (MR) and Bayesian model averaging (MR-BMA) analyses in European ancestry. Methods: The summary-level statistics from two genome-wide association studies with 249 and 123 metabolic traits derived from two separate cohorts involving ~115,000 (UK Biobank) and ~25,000 individuals from European ancestry were used for the analyses. The summary statistics of four pancreatitis datasets from FinnGen R5 and two pancreatitis datasets from UK Biobank were exploited as the outcome. We first performed univariable MR analysis with different metabolic GWAS data on multiple pancreatitis datasets to demonstrate the association pattern among different metabolites categories. Next, we exploited the MR-BMA method to pinpoint the dominating factors on the increased risk of pancreatitis. Results: In the primary analysis with 249 traits, we found that plasma triglycerides were positively associated with pancreatitis risk. Intriguingly, a large number of traits associated with saturation or unsaturation of fatty acids also demonstrated causal associations. The replication study analyzing 123 metabolic traits suggested that bisallylic groups levels and omega-3 fatty acids were inversely correlated with pancreatitis risk. MR-BMA analyses indicated that the ratio of triglycerides to total lipid in various HDL particles played leading roles in pancreatitis susceptibility. In addition, the degree of unsaturation, the ratio of polyunsaturated fatty acids to monounsaturated fatty acids and the level of monounsaturated fatty acids showed causal associations with either decreased or increased pancreatitis susceptibility. Conclusions: Our MR study provided an atlas of causal associations of genetically predicted blood metabolites on pancreatitis, and offered genetic insights showing intervention in triglycerides and the supplementation of unsaturated fatty acids are potential strategies in the primary prevention of pancreatitis.