Pancreas-directed AAV8-hSPINK1 gene therapy safely and effectively protects against pancreatitis in mice.

OBJECTIVE: Currently, there is no cure for chronic pancreatitis (CP). Germline loss-of-function variants in SPINK1 (encoding trypsin inhibitor) are common in patients with CP and are associated with acute attacks and progression of the disease. This preclinical study was conducted to explore the potential of adeno-associated virus type 8 (AAV8)-mediated overexpression of human SPINK1 (hSPINK1) for pancreatitis therapy in mice. DESIGN: A capsid-optimised AAV8-mediated hSPINK1 expression vector (AAV8-hSPINK1) to target the pancreas was constructed. Mice were treated with AAV8-hSPINK1 by intraperitoneal injection. Pancreatic transduction efficiency and safety of AAV8-hSPINK1 were dynamically evaluated in infected mice. The effectiveness of AAV8-hSPINK1 on pancreatitis prevention and treatment was studied in three mouse models (caerulein-induced pancreatitis, pancreatic duct ligation and Spink1 c.194+2T>C mouse models). RESULTS: The constructed AAV8-hSPINK1 vector specifically and safely targeted the pancreas, had low organ tropism for the heart, lungs, spleen, liver and kidneys and had a high transduction efficiency (the optimal expression dose was 2×1011 vg/animal). The expression and efficacy of hSPINK1 peaked at 4 weeks after injection and remained at significant level for up to at least 8 weeks. In all three mouse models, a single dose of AAV8-hSPINK1 before disease onset significantly alleviated the severity of pancreatitis, reduced the progression of fibrosis, decreased the levels of apoptosis and autophagy in the pancreas and accelerated the pancreatitis recovery process. CONCLUSION: One-time injection of AAV8-hSPINK1 safely targets the pancreas with high transduction efficiency and effectively ameliorates pancreatitis phenotypes in mice. This approach is promising for the prevention and treatment of CP.

Prevalence and risk factors of fatigue and its association with quality of life among patients with chronic pancreatitis: A cross-sectional study.

BACKGROUND: Fatigue is a debilitating symptom found in various chronic diseases and is associated with more severe symptoms and worse quality of life (QoL). However, this symptom has not been adequately addressed in chronic pancreatitis (CP), and there have been no studies on fatigue in patients with CP. METHODS: This cross-sectional study was conducted at the Changhai Hospital in Shanghai, China. Data on the patients' sociodemographic, disease, and therapeutic characteristics were collected. Fatigue was assessed using the Multidimensional Fatigue Inventory-20. QoL was assessed utilizing the European Organization for the Research and Treatment of Cancer of QoL questionnaire (EORTC-QLQ-C30). Sleep quality, anxiety and depression, and pain was assessed using Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, and the Brief Pain Inventory, respectively. RESULTS: The prevalence of fatigue among Chinese patients with CP was 35.51 % (87/245). Multivariate analysis showed that steatorrhea (OR = 2.638, 95 % CI: 1.117-6.234), history of smoking (OR = 4.627, 95 % CI: 1.202-17.802), history of endoscopic treatment (OR = 0.419, 95 % CI: 0.185-0.950), depression (OR = 5.924, 95 % CI: 2.462-14.255), and sleep disorder (OR = 6.184, 95 % CI: 2.543-15.034) were influencing factors for the presence of fatigue. The scores for global health and all functional dimensions in the EORTC-QLQ-C30 significantly decreased, whereas the scores for all symptom dimensions significantly increased in patients with fatigue. CONCLUSIONS: This study indicated that Fatigue is a common symptom and has a negative impact on the QoL of patients with CP. Steatorrhea, smoking history, endoscopic treatment, depression, and sleep disorders were associated with fatigue.

Liquid biopsy of oesophageal squamous cell carcinoma: implications in diagnosis, prognosis, and treatment monitoring.

Oesophageal squamous cell carcinoma (ESCC) is a common malignant tumour of the gastrointestinal tract. Early detection and access to appropriate treatment are crucial for the long-term survival of patients. However, limited diagnostic and monitoring methods are available for identifying early stage ESCC. Endoscopic screening and surgical resection are commonly used to diagnose and treat early ESCC. However, these methods have disadvantages, such as high recurrence, lethality, and mortality rates. Therefore, methods to improve early diagnosis of ESCC and reduce its mortality rate are urgently required. In 1961, Gary et al. proposed a novel liquid biopsy approach for clinical diagnosis. This involved examining exosomes, circulating tumour cells, circulating free DNA, and circulating free RNA in body fluids. The ability of liquid biopsy to obtain samples repeatedly, wide detection range, and fast detection speed make it a feasible option for non-invasive tumour detection. In clinical practice, liquid biopsy technology has gained popularity for early screening, diagnosis, treatment efficacy monitoring, and prognosis assessment. Thus, this is a highly promising examination method. However, there have been no comprehensive reviews on the four factors of liquid biopsy in the context of ESCC. This review aimed to analyse the progress of liquid biopsy research for ESCC, including its classification, components, and potential future applications.

Adverse events in endoscopic ultrasound-guided choledochoduodenostomy with lumen-apposing metal stents: A systematic review and meta-analysis.

BACKGROUND AND AIM: Several meta-analyses have analyzed the technical and clinical success of endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) by using lumen-apposing metal stents (LAMS) in malignant biliary obstruction, but those concerning adverse events (AEs) are scarce. The current systematic review and meta-analysis was conducted to evaluate the AEs after EUS-CDS with LAMS. METHODS: A comprehensive literature search of PubMed, Embase, Scopus, Web of Science, and the Cochrane Library was conducted for studies reporting the outcomes of EUS-CDS with LAMS. The main endpoints were the incidence of overall and specific AEs. Moreover, the stent dysfunction, and reintervention rates were evaluated independently. RESULTS: A total of 21 studies (n = 1438) were included in the final meta-analysis. The pooled rate of technical and clinical success was 93.5% (95% confidence interval [CI]: 91.3-95.1) and 88.0% (95% CI: 83.9-91.1), respectively. After EUS-CDS with LAMS, the pooled incidence of overall AEs was 20.1% (95% CI: 16.0-24.9). The estimated rate of early AEs was 10.6% (95% CI: 7.9-14.2), and late AEs was 11.2% (95% CI: 8.2-15.2). Infection/cholangitis was the commonest AE, with a pooled incidence of 6.1% (95% CI: 3.7-10.1). The estimated incidence of stent dysfunction and reintervention was 10.5% (95% CI: 7.5-14.4), and 12.1% (95% CI: 9.3-15.7), respectively. CONCLUSION: Despite with a high technical and clinical success rate, EUS-CDS with LAMS may be associated with overall AEs and stent dysfunction in one-fifth and one-tenth of cases, respectively. Further efforts are required to optimize its safety and long-term stent patency.

Endoscopic ultrasound-guided versus surgical pancreatic duct drainage after failed endoscopic retrograde pancreatography: a pilot comparative study.

BACKGROUND: Endoscopic ultrasound-guided pancreatic duct (PD) drainage (EUS-PDD) is being increasingly performed as an alternative method to surgical drainage to achieve PD decompression after failed endoscopic retrograde pancreatography (ERP). However, no directly study has compared EUS-PDD with surgical PD drainage after failed ERP in patients with chronic pancreatitis. METHODS: Consecutive patients who underwent EUS-PDD or longitudinal pancreaticojejunostomy after failed ERP were retrospectively identified from our endoscopy and medical information systems. The primary end point was the Izbicki pain score. The secondary end points were pain relief at the end of follow-up, procedure outcomes, adverse events, readmission, and reintervention. RESULTS: A total of 21 patients (11 EUS-PDD, 10 surgical drainages) were analyzed. There were no significant differences in mean Izbicki pain score (EUS-PDD, 13.6 ± 10.1 vs. surgical drainage 10.7 ± 7.9, p = 0.483) or complete/partial pain relief (60%/30% vs. 70%/30%, p = 0.752) at the end of follow-up of the two groups. The rates of overall adverse events (27.3% vs. 30.0%, p = 0.893) and readmission (63.6% vs. 40.0%, p = 0.290) were similar in the two treatment groups, while patients in EUS-PDD group required more reinterventions (45.5% vs. 0%, p = 0.039) compared with patients in the surgery group. CONCLUSION: EUS-PDD showed comparable pain relief and safety to surgical PD drainage after failed ERP, with a higher rate of reintervention. The selection of EUS-PDD or surgical drainage may be appropriate based on an individualized strategy.

Large-scale, national, family-based epidemiological study on Helicobacter pylori infection in China: the time to change practice for related disease prevention.

BACKGROUND AND AIMS: Current practice on Helicobacter pylori infection mostly focuses on individual-based care in the community, but family-based H. pylori management has recently been suggested as a better strategy for infection control. However, the family-based H. pylori infection status, risk factors and transmission pattern remain to be elucidated. METHODS: From September 2021 to December 2021, 10 735 families (31 098 individuals) were enrolled from 29 of 31 provinces in mainland China to examine family-based H. pylori infection, related factors and transmission pattern. All family members were required to answer questionnaires and test for H. pylori infection. RESULTS: Among all participants, the average individual-based H. pylori infection rate was 40.66%, with 43.45% for adults and 20.55% for children and adolescents. Family-based infection rates ranged from 50.27% to 85.06% among the 29 provinces, with an average rate of 71.21%. In 28.87% (3099/10 735) of enrolled families, there were no infections; the remaining 71.13% (7636/10 735) of families had 1-7 infected members, and in 19.70% (1504/7636), all members were infected. Among 7961 enrolled couples, 33.21% had no infection, but in 22.99%, both were infected. Childhood infection was significantly associated with parental infection. Independent risk factors for household infection were infected family members (eg, five infected members: OR 2.72, 95% CI 1.86 to 4.00), living in highly infected areas (eg, northwest China: OR 1.83, 95% CI 1.57 to 2.13), and large families in a household (eg, family of three: OR 1.97, 95% CI 1.76 to 2.21). However, family members with higher education and income levels (OR 0.85, 95% CI 0.79 to 0.91), using serving spoons or chopsticks, more generations in a household (eg, three generations: OR 0.79, 95% CI 0.68 to 0.92), and who were younger (OR 0.57, 95% CI 0.46 to 0.70) had lower infection rates (p<0.05). CONCLUSION: Familial H. pylori infection rate is high in general household in China. Exposure to infected family members is likely the major source of its spread. These results provide supporting evidence for the strategic changes from H. pylori individual-based treatment to family-based management, and the notion has important clinical and public health implications for infection control and related disease prevention.

Identification of novel factors that affect the onset of idiopathic chronic pancreatitis: The role for microRNA-323b-5p.

BACKGROUND: The c.194+2 T>C variant of serine protease inhibitor Kazal type 1 (SPINK1) is a known genetic risk factor found in Chinese patients with idiopathic chronic pancreatitis (ICP), but the early-onset mechanisms of ICP are still unclear. METHODS: Complementary experimental approaches were used to pursue other potential pathologies in the present study. The serum level of SPINK1 of ICP patients in the Han population in China was detected and verified by an enzyme-linked immunosorbent assay. Next, differentially expressed proteins and microRNAs from plasma samples of early-onset and late-onset ICP patients were screened by proteomic analysis and microarray, respectively. RESULTS: Combined with these advanced methods, the data strongly suggest that the regulatory effects of microRNAs were involved in the early-onset mechanism of the ICP by in vitro experiments. There was no significant difference in the plasma SPINK1 expression between the early-onset ICP and the late-onset patients. However, the expression of plasma glutathione peroxidase (GPx3) in early-onset ICP patients was markedly lower than that in late-onset ICP patients, although the level of hsa-miR-323b-5p was lower in late-onset patients compared to the early-onset ICP group. In vitro experiments confirmed that hsa-miR-323b-5p could increase apoptosis in caerulein-treated pancreatic acinar cells and inhibit the expression of GPx3. CONCLUSIONS: The up-regulated hsa-miR-323b-5p might play a crucial role in the early-onset mechanisms of ICP by diminishing the antioxidant activity through the down-regulation of GPx3.

Comparative Performance of Endoscopic Ultrasound-Based Techniques in Patients With Pancreatic Cystic Lesions: A Network Meta-Analysis.

INTRODUCTION: Evidence on the comparative diagnostic performance of endoscopic ultrasound (EUS)-based techniques for pancreatic cystic lesions (PCLs) is limited. This network meta-analysis comprehensively compared EUS-based techniques for PCL diagnosis. METHODS: A comprehensive literature search was performed for all comparative studies assessing the accuracy of 2 or more modalities for PCL diagnosis. The primary outcome was the diagnostic efficacy for mucinous PCLs. Secondary outcomes were the diagnostic efficacy for malignant PCLs, diagnostic success rate, and adverse event rate. A network meta-analysis was conducted using the ANOVA model to assess the diagnostic accuracy of each index. RESULTS: Forty studies comprising 3,641 patients were identified. The network ranking of the superiority index for EUS-guided needle-based confocal laser endomicroscopy (EUS-nCLE) and EUS-guided through-the-needle biopsy (EUS-TTNB) were significantly higher than other techniques for differentiating mucinous PCLs; besides, EUS-TTNB was also the optimal technique in identifying malignant PCLs. The evidence was inadequate for EUS-nCLE diagnosing malignant PCLs and contrast-enhanced harmonic EUS diagnosing both mucinous and malignant PCLs. Glucose showed a high sensitivity but low specificity, and molecular analysis (KRAS, GNAS, and KRAS + GNAS mutations) showed a high specificity but low sensitivity for diagnosing mucinous PCLs. Satisfactory results were not obtained during the evaluation of the efficiency of pancreatic cyst fluid (PCF) biomarkers in detecting malignant PCLs. DISCUSSION: For centers with relevant expertise and facilities, EUS-TTNB and EUS-nCLE were better choices for the diagnosis of PCLs. Further studies are urgently required for further improving PCF biomarkers and validating the diagnostic performance of the index techniques.

Classification of PRSS1 variants responsible for chronic pancreatitis: An expert perspective from the Franco-Chinese GREPAN study group.

BACKGROUND: PRSS1 was the first reported chronic pancreatitis (CP) gene. The existence of both gain-of-function (GoF) and gain-of-proteotoxicity (GoP) pathological PRSS1 variants, together with the fact that PRSS1 variants have been identified in CP subtypes spanning the range from monogenic to multifactorial, has made the classification of PRSS1 variants very challenging. METHODS: All currently reported PRSS1 variants (derived primarily from two databases) were manually reviewed with respect to their clinical genetics, functional analysis and population allele frequency. They were classified by variant type and pathological mechanism within the framework of our recently proposed ACMG/AMP guidelines-based seven-category system. RESULTS: The total number of distinct germline PRSS1 variants included for analysis was 100, comprising 3 copy number variants (CNVs), 12 5' and 3' variants, 19 intronic variants, 5 nonsense variants, 1 frameshift deletion variant, 6 synonymous variants, 1 in-frame duplication, 3 gene conversions and 50 missense variants. Based upon a combination of clinical genetic and functional analysis, population data and in silico analysis, we classified 26 variants (all 3 CNVs, the in-frame duplication, all 3 gene conversions and 19 missense) as "pathogenic", 3 variants (missense) as "likely pathogenic", 5 variants (four missense and one promoter) as "predisposing", 13 variants (all missense) as "unknown significance", 2 variants (missense) as "likely benign", and all remaining 51 variants as "benign". CONCLUSIONS: We describe an expert classification of the 100 PRSS1 variants reported to date. The results have immediate implications for reclassifying many ClinVar-registered PRSS1 variants as well as providing optimal guidelines/standards for reporting PRSS1 variants.

New US capsule endoscopy for superficial and submucosal imaging of the esophagus: the first-in-human study.

BACKGROUND AND AIMS: EUS is essential in diagnosing and staging of esophageal subepithelial lesions and tumors. However, EUS is invasive, relies on highly trained endoscopists, and typically requires sedation. The newly developed US capsule endoscopy (USCE), which incorporates both white-light and US imaging modalities into a tethered capsule, is a minimally invasive method for obtaining superficial and submucosal information of the esophagus. This study aimed to assess the feasibility and safety of this USCE system. METHODS: Twenty participants were enrolled: 10 healthy volunteers and 10 patients with esophageal lesions indicated for EUS. Participants first underwent USCE and subsequently EUS within 48 hours. The primary outcome was the technical success rate of USCE. Secondary outcomes were safety, visualization of the esophagus, and comfort assessment. RESULTS: The technical success rate of USCE was 95% because 1 patient failed to swallow the capsule. No adverse events were observed. The esophagus was well visualized, and all lesions were detected under USCE optical mode in 19 participants. For healthy volunteers, the US images of normal esophageal walls were all characterized by differentiated 7-layer architecture under both USCE and EUS. For 9 patients, the features of esophageal lesions were recognized clearly under USCE, and presumptive diagnoses derived from USCE were all consistent with those from EUS. Most participants preferred USCE to EUS. CONCLUSIONS: The novel USCE is feasible and safe to observe the esophageal mucosa and acquire submucosal information, which has the potential to be widely used in the clinic. (Clinical trial registration number: NCT05054933.).

Small-sized versus standard magnetic capsule endoscopy in adults: a two-center, double-blinded randomized controlled trial.

BACKGROUND : Certain patients experience difficulty swallowing a video capsule endoscopy (VCE) device owing to its relatively large size. The newly developed small-sized magnetically controlled capsule endoscopy (MCE) device is the smallest VCE device ever reported. We aimed to evaluate the performance of the small-sized MCE device in terms of ingestion and examination efficacy. METHODS : Patients in two centers were prospectively enrolled and randomized to the small-sized or standard MCE groups. Differences in capsule ingestion difficulties, visualization of the gastrointestinal tract, and capsule transit times were compared. RESULTS : 96 patients were enrolled (48 in each group). In the small-sized MCE group, the mean (SD) difficulty score and time to swallow the capsule, and success rate for swallowing the capsule at the first attempt were 0.6 (1.0), 3.4 (1.3) seconds, and 89.6 %, which was significant better compared with the standard MCE group with 3.1 (1.7), 12.0 (14.3) seconds and 60.4 %, respectively (all P < 0.001). Visualization of the esophagus, stomach, and small bowel were comparable between the two groups. The small-sized MCE group had a significantly shorter gastric transit time (49.4 minutes vs. 66.2 minutes; P = 0.04) and longer small-bowel transit time (5.8 hours vs. 5.0 hours; P = 0.045). CONCLUSIONS : The small-sized MCE device is feasible and safe for gastrointestinal examination, alleviating difficulties in capsule ingestion, improving gastric emptying under magnetic control, and prolonging the small-bowel transit time.

Adverse events of pancreatic extracorporeal shock wave lithotripsy: a literature review.

Pancreatic stones are the result of pathophysiologic changes in chronic pancreatitis with an incidence of more than 90%. At present, pancreatic extracorporeal shock wave lithotripsy (P-ESWL) can be used as the first-line treatment for large or complex stones. Although a large number of studies have proven the safety and effectiveness of P-ESWL, we should also pay attention to postoperative adverse events, mainly due to the scattering of shock waves in the conduction pathway. Adverse events can be classified as either complications or transient adverse events according to the severity. Because the anatomic location of organs along the shock wave conducting pathway differs greatly, adverse events after P-ESWL are varied and difficult to predict. This paper outlines the mechanism, definition, classification, management and risk factors for adverse events related to P-ESWL. It also discusses the technique of P-ESWL, indications and contraindications of P-ESWL, and adverse events in special populations.

A novel capsule endoscopy for upper and mid-GI tract: the UMGI capsule.

BACKGROUNDS AND AIMS: Complete and consecutive observation of the gastrointestinal (GI) tract continues to present challenges for current endoscopy systems. We developed a novel upper and mid gastrointestinal (UMGI) capsule endoscopy using the modified detachable string magnetically controlled capsule endoscopy (DS-MCE) and inspection method and aimed to assess the clinical application. METHODS: Patients were recruited to undergo UMGI capsule endoscopy followed by esophagogastroduodenoscopy. All capsule procedures in the upper gastrointestinal (UGI) tract were conducted under the control of magnet and string. The main outcome was technical success, and the secondary outcomes included visualization of the UMGI tract, examination time, diagnostic yield, compliance, and safety evaluation. RESULTS: Thirty patients were enrolled and all UMGI capsule procedures realized repeated observation of the esophagus and duodenum with detection rates of 100.0%, 80.0%, and 86.7% of Z-line, duodenal papilla, and reverse side of pylorus, respectively. String detachment was succeeded in 29 patients (96.7%) and the complete examination rate of UMGI tract was 95.45% (21/22). All UMGI capsule procedures were well tolerated with low discomfort score, and had a good diagnostic yield with per-lesion sensitivity of 96.2% in UGI diseases. No adverse events occurred. CONCLUSIONS: This new capsule endoscopy system provides an alternative screening modality for the UMGI tract, and might be indicated in cases of suspected upper and small bowel GI bleeding. Trial registration DS-MCE-UGI and SB, NCT04329468. Registered 27 March 2020, https://clinicaltrials.gov/ct2/results?cond=&term=NCT04329468 .

Anxiety, depression, and coping styles among patients with chronic pancreatitis in East China.

BACKGROUND: Anxiety and depression are common psychological comorbidities in patients with chronic pancreatitis (CP). There is still a lack of epidemiological studies on anxiety and depression in Chinese CP patients. This study aimed to identify the incidence and related factor of anxiety and depression among East Chinese CP patients and explore the relationship between anxiety, depression, and coping styles. METHODS: This prospective observational study was conducted from June 1, 2019 to March 31, 2021 in Shanghai, China. Patient diagnosed with CP were interviewed using the sociodemographic and clinical characteristics questionnaire, Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), and Coping Style Questionnaire (CSQ). Multivariate logistic regression analysis was conducted to identify the related factors of anxiety and depression. Correlation test was preformed to analyze the correlation between anxiety, depression, and coping styles. RESULTS: The incidence of anxiety and depression in East Chinese CP patients was 22.64% and 38.61%, respectively. Patients' previous health status, level of disease coping, frequency of abdominal pain episodes, and pain severity were significantly associated with anxiety and depression. Mature coping styles (Problem solving, Seeking for help) had a positive impact on anxiety and depression, while immature coping styles (Self-blame, Fantasy, Repression, Rationalization) had negative effects on anxiety and depression. CONCLUSION: Anxiety and depression were common in patients with CP in China. The factors identified in this study may provide references for the management of anxiety and depression in CP patients.

The Impacts of Genetic and Environmental Factors on the Progression of Chronic Pancreatitis.

BACKGROUND & AIMS: Both environmental factors, such as alcohol consumption and smoking, and genetic factors are strongly associated with the risk of developing chronic pancreatitis (CP). However, comprehensive understanding of their impacts on the progression of CP remains elusive. METHODS: A prospective cohort study was performed on a large cohort of CP patients with known genetic backgrounds. The cumulative incidence of pancreatic insufficiency after the onset of CP was analyzed using Kaplan-Meier survival curves. Multivariate Cox proportional hazards regression analysis also was performed. RESULTS: A total of 798 patients were enrolled in the study and followed up for 10.5 years. Rare pathogenic genotypes in the SPINK1, PRSS1, CTRC, or CFTR genes were identified in 410 (51.4%) patients. The development of pancreatic insufficiency was significantly earlier in patients with a history of smoking and/or alcohol consumption in both the positive (P < .001) and negative (P = .001) gene mutation groups. However, the development of pancreatic insufficiency did not differ significantly between patients with and without gene mutations despite alcohol and/or smoking status, with P values of .064 and .115, respectively. Multivariate Cox regression analysis showed that age at onset of CP (hazard ratio, [HR], 1.02; P < .001) and alcohol consumption (HR, 1.86; P < .001) were independent risk factors for the development of diabetes, while male sex (HR, 1.84; P = .022) and smoking (HR, 1.56; P = .028) were predictors of steatorrhea. CONCLUSIONS: Although rare pathogenic mutations in the 4 major susceptibility genes for CP were not correlated significantly with the development of pancreatic insufficiency, environmental factors (either alcohol consumption or smoking) significantly accelerated disease progression (ClinicalTrials.gov: NCT04574297).

Association between sedation and small neoplasm detection during diagnostic esophagogastroduodenoscopy: a propensity score-matched retrospective study.

BACKGROUND: Esophagogastroduodenoscopy (EGD) is fundamental for detecting upper gastrointestinal (GI) neoplasms. However, the impact of sedation on small neoplasm detection during EGD has not been evaluated. The aim of this study was to investigate whether EGD with sedation could improve small upper GI neoplasm detection. METHODS: This propensity score-matched retrospective study analyzed the medical records of outpatients undergoing diagnostic EGD at a large tertiary center between January 2013 and December 2018. The primary outcome was the detection rate of small upper GI neoplasms (≤10 mm). The secondary outcomes were biopsy rate and small neoplasms in different anatomic subsites. RESULTS: After propensity score matching, 20,052 patients undergoing diagnostic EGD with or without propofol sedation were identified. A higher detection rate of small upper GI neoplasms was observed in the sedation group (2.80% vs. 2.02%; p < .001). In particular, the detection rate of small cancers in the sedation group was 3-fold higher than that in the no-sedation group (0.16% vs. 0.05%; p = .023). Small neoplasms were more likely identified at the gastric antrum (1.60% vs. 1.09%; p = .002) and angulus (0.66% vs. 0.45%; p = .044) in the sedation group. In addition, endoscopists were more likely to take biopsies when performing sedated EGD (41.4% vs. 36.4%, p < .001), and a higher biopsy rate was associated with an increased detection rate of small neoplasms. CONCLUSIONS: Sedation was significantly associated with a higher detection rate of small upper GI neoplasms and might be recommended for improving the quality of EGD.

Feasibility and Accuracy of Artificial Intelligence-Assisted Sponge Cytology for Community-Based Esophageal Squamous Cell Carcinoma Screening in China.

INTRODUCTION: Screening is the pivotal strategy to relieve the burden of esophageal squamous cell carcinoma (ESCC) in high-risk areas. The cost, invasiveness, and accessibility of esophagogastroduodenoscopy (EGD) necessitate the development of preliminary screening methods. METHODS: Residents aged 40-85 years were recruited in a high-risk area of ESCC. Esophageal cells were collected using an approved novel capsule sponge, and cytology slides were scanned by a trained artificial intelligence (AI) system before cytologists provided confirmation. Atypical squamous cell or more severe diagnosis was defined as positive cytology. AI-based abnormal cell counts were also reported. EGD was performed subsequently with biopsy as needed. Diagnostic accuracy, adverse events, and acceptability of cytology testing were assessed. Esophageal high-grade lesions (ESCC and high-grade intraepithelial neoplasia) were the primary target lesions. RESULTS: In total, 1,844 participants were enrolled, and 20 (1.1%) high-grade lesions were confirmed by endoscopic biopsy. The AI-assisted cytologist-confirmed cytology showed good diagnostic accuracy, with a sensitivity of 90.0% (95% confidence interval [CI], 76.9%-100.0%), specificity of 93.7% (95% CI, 92.6%-94.8%), and positive predictive value of 13.5% (95% CI, 7.70%-19.3%) for detecting high-grade lesions. The area under the receiver operation characteristics curve was 0.926 (95% CI, 0.850-1.000) and 0.949 (95% CI, 0.890-1.000) for AI-assisted cytologist-confirmed cytology and AI-based abnormal cell count, respectively. The numbers of EGD could be reduced by 92.5% (from 99.2 to 7.4 to detect 1 high-grade lesion) if only cytology-positive participants were referred to endoscopy. No serious adverse events were documented during the cell collection process, and 96.1% participants reported this process as acceptable. DISCUSSION: The AI-assisted sponge cytology is feasible, safe, and acceptable for ESCC screening in community, with high accuracy for detecting esophageal squamous high-grade lesions.

Homozygosity of short VNTR lengths in the CEL gene may confer susceptibility to idiopathic chronic pancreatitis.

OBJECTIVE: The carboxyl-ester lipase (CEL) gene contains a variable number of tandem repeats (VNTR) region. It remains unclear whether the number of repeats in the CEL VNTR is related to the risk of pancreatic diseases. The aim of this study was to investigate whether CEL VNTR length is associated with idiopathic chronic pancreatitis (ICP), alcoholic chronic pancreatitis (ACP), or pancreatic cancer in a cohort of Chinese patients. METHODS: CEL VNTRs were genotyped in patients diagnosed with ICP (n = 771), ACP (n = 222), or pancreatic cancer (n = 263), and in healthy controls (n = 927). CEL VNTR lengths were determined using a screening method combining PCR and DNA fragment analysis. RESULTS: Overall, the CEL VNTR lengths ranged from 5 to 22 repeats, with the 16-repeat allele ('normal' size, N) accounting for 73.82% of all observed alleles. The VNTR allele frequencies and genotype distributions were not significantly different between healthy controls and patients with ACP or pancreatic cancer. For the ICP group, allele frequencies did not differ significantly from the controls, while the frequency of the SS genotype (homozygosity for 5-15 repeats) was significantly higher in the patients (4.67%) than in the controls (1.94%) (p = 0.0014; OR = 2.47; 95% CI = 1.39-4.39). CONCLUSIONS: There were no associations between the CEL VNTR length and ACP or pancreatic cancer. However, homozygosity for short VNTR lengths may confer susceptibility to ICP.

SPINK1 mutations and risk of pancreatic cancer in a Chinese cohort.

OBJECTIVE: The relationship between SPINK1 and pancreatic cancer (PC) remains controversial. The current study aimed to determine the effect of SPINK1 mutations on PC development among patients with chronic pancreatitis (CP). METHODS: This is a prospective observational study including a large cohort of 965 CP patients with 11-year follow-up. Patients' demographic characteristics and clinical CP outcomes were documented in detail. Genetic testing was performed. The effect of SPINK1 mutations on the clinical development of PC was explored using Cox proportional hazards regression. Subgroup analyses conducted included the consideration of gender, onset age of CP (early- and late-onset), etiologies of CP, smoking, and alcoholic drinking status. RESULTS: PC was diagnosed in 2.5% (24/965) of patients, and the cumulative incidence rates were 0.2%, 0.8%, and 1.5% at 3, 5, and 10 years since the onset of CP, respectively. In this cohort, SPINK1 c.194+2T > C was the most common variant with a proportion of 39.1%. And the risk of PC development varied marginally between patients with and without SPINK1 mutations (Cox HR 0.39(0.14-1.04), P = 0.059). In the subgroup analyses, patients carrying SPINK1 mutations had a significantly lower risk of PC (Cox HR 0.18(0.04-0.80), P = 0.025) in the non-smoking group. SPINK1 mutations showed no significant effect in the other subgroups considered. CONCLUSIONS: CP patients harboring SPINK1 mutations do not have an elevated risk of PC development compared to mutation-negative CP patients. On the contrary, SPINK1 mutations may be a protective factor in non-smoking patients with CP.

Use of artificial intelligence for detection of gastric lesions by magnetically controlled capsule endoscopy.

BACKGROUND AND AIMS: Magnetically controlled capsule endoscopy (MCE) has become an efficient diagnostic modality for gastric diseases. We developed a novel automatic gastric lesion detection system to assist in diagnosis and reduce inter-physician variations. This study aimed to evaluate the diagnostic capability of the computer-aided detection system for MCE images. METHODS: We developed a novel automatic gastric lesion detection system based on a convolutional neural network (CNN) and faster region-based convolutional neural network (RCNN). A total of 1,023,955 MCE images from 797 patients were used to train and test the system. These images were divided into 7 categories (erosion, polyp, ulcer, submucosal tumor, xanthoma, normal mucosa, and invalid images). The primary endpoint was the sensitivity of the system. RESULTS: The system detected gastric focal lesions with 96.2% sensitivity (95% confidence interval [CI], 95.7%-96.5%), 76.2% specificity (95% CI, 75.97%-76.3%), 16.0% positive predictive value (95% CI, 15.7%-16.3%), 99.7% negative predictive value (95% CI, 99.74%-99.79%), and 77.1% accuracy (95% CI, 76.9%-77.3%) (sensitivity was 99.3% for erosions; 96.5% for polyps; 89.3% for ulcers; 87.2% for submucosal tumors; 90.6% for xanthomas; 67.8% for normal; and 96.1% for invalid images). Analysis of the receiver operating characteristic curve showed that the area under the curve for all positive images was 0.84. Image processing time was 44 milliseconds per image for the system and 0.38 ± 0.29 seconds per image for clinicians (P < .001). The kappa value of 2 times repeated reads was 1. CONCLUSIONS: The CNN faster-RCNN-based diagnostic program system showed good performance in diagnosing gastric focal lesions in MCE images.