Digestion最新文献

Background: Superficial non-ampullary duodenal epithelial tumors (SNADETs) were previously considered rare. However, the widespread use of health checkup endoscopy, improvements in endoscopic imaging and heightened awareness of SNADETs among endoscopists have recently led to an increase in their detection rate. Particularly for large SNADETs, the possibility of including cancer must be considered, and thus, complete and reliable resection is essential. Although surgical resection has traditionally been the standard treatment, its high invasiveness has led to increased interest in less invasive endoscopic treatments. Nevertheless, due to the unique anatomical and physiological features of the duodenum, endoscopic treatment in the duodenum remains highly challenging and presents many technical difficulties.

Summary: This review provides a comprehensive overview of current endoscopic treatment options for large SNADETs, including conventional endoscopic mucosal resection (C-EMR), underwater endoscopic mucosal resection (U-EMR), cold snare endoscopic mucosal resection (CS-EMR), endoscopic submucosal dissection (ESD), and laparoscopic-endoscopic cooperative surgery, incorporating the latest clinical findings. While C-EMR, U-EMR, and CS-EMR are associated with lower technical difficulty and favorable safety, they tend to show lower en bloc resection rates and higher recurrence rates for large SNADETs when compared to ESD. In contrast, ESD offers higher en bloc resection rates but carries a greater risk of complications due to its technical complexity. To overcome these limitations, several techniques have been developed, such as the pocket-creation method, water pressure method, improved closure strategies for mucosal defects, and drainage with endoscopic nasobiliary and pancreatic drainage to prevent exposure to pancreatic juice and bile.

Key messages: Multiple endoscopic strategies are available for the treatment of large SNADETs. However, due to the rarity of the disease and variation in institutional expertise, a standardized treatment strategy has not yet been established. Endoscopic treatment for large SNADETs is technically very challenging and carries a high risk. Therefore, careful consideration of the indication for each treatment method, along with a full understanding of their respective advantages and disadvantages, is essential. In recent years, the safety of endoscopic resection has been gradually improving due to various technical innovations and better management of adverse events, making ESD, which offers a high en bloc resection rate, an increasingly reasonable treatment option.

Background: Achalasia is a rare primary esophageal motility disorder of the esophageal smooth muscle, characterized by abnormal relaxation of the lower esophageal sphincter and associated with abnormal, spastic, or absent esophageal body peristalsis.

Summary: The primary pathophysiological defect is abnormal esophageal inhibitory nerve function from neuronal death in the esophageal neuronal plexuses and ganglia that control esophageal smooth muscle peristalsis. This is a consequence of an autoimmune cytotoxic insult from molecular mimicry following an intercurrent viral infection, typically herpes simplex virus, varicella zoster virus, human papillomavirus, measles virus, and even the COVID-19 virus. Neuronal inflammation rather than death can lead to an imbalance between excitatory and inhibitory forces, and varying degrees of retained spastic, premature or even normal peristalsis in the smooth muscle esophageal body. Chagas disease caused by Trypanosoma cruzi, eosinophilic inflammation, direct infiltration with neoplastic cells from adjacent cancers, or humoral autoimmune destruction from distant cancers can also result in an achalasia-like syndrome. Mechanical obstruction from tight strictures, anti-reflux or bariatric surgery, and extrinsic compression can mimic the manometric features of achalasia. Chronic opioid medication usage can result in a clinical and pathophysiological syndrome identical to spastic achalasia.

Key messages: Careful clinical evaluation and judicious interpretation of esophageal function tests following pathophysiological principles can lead to an accurate diagnosis of achalasia, opening the door to durable permanent disruption of the malfunctioning esophageal smooth muscle and resulting in symptom relief.

Introduction: Ulcerative colitis (UC) increases the risk of colorectal cancer (CRC). Although 5-aminosalicylic acid (5-ASA) has long been regarded as chemopreventive, it remains unclear whether 5-ASA therapy still confers this benefit when used concomitantly with tumour necrosis factor (TNF) inhibitors.

Methods: We performed a retrospective cohort study using the nationwide Japanese Medical Data Vision database. Patients with UC who initiated TNF inhibitors were followed from the first TNF inhibitor prescription until CRC diagnosis or disenrollment. Concomitant 5-ASA use was defined as prescription within 90 days before or after TNF initiation. Cumulative incidence was compared with Kaplan-Meier curves and the log-rank test; hazard ratios (HRs) were estimated with multivariable Cox regression and inverse probability of treatment weighting (IPTW), adjusting for age, sex, primary sclerosing cholangitis (PSC), diabetes, obesity, immunomodulator use, type of TNF agent, and prior advanced therapy exposure.

Results: Among 9,919 eligible patients, 8,387 (84.6%) received concomitant 5-ASA. During follow-up (median 3.14 years), 161 CRC events occurred: crude incidence 3.67/1,000 person-years (with 5-ASA use) versus 4.58/1,000 person-years (without 5-ASA use) (p = 0.421). Concomitant 5-ASA was not associated with CRC risk (adjusted HR 1.25, 95% CI 0.76-2.04; IPTW-adjusted HR: 1.28, 95% CI: 0.78-2.11). Independent risk factors were older age, male sex, and PSC.

Conclusions: We found no measurable chemopreventive benefit of concomitant 5-ASA in UC patients receiving TNF inhibitors during this treatment phase. Accordingly, 5-ASA need not be prioritised for CRC prevention at this stage. Longer observation is required to clarify any benefit beyond the early years of TNF inhibitors.

Background: Endoscopic resection (ER) is a minimally invasive alternative to surgical resection for superficial non-ampullary duodenal epithelial tumors (SNADETs); however, it carries a high risk of adverse events (AEs) due to the thin duodenal wall and the technical challenges of endoscopic maneuverability. This review discusses the management of intraoperative and delayed postoperative AEs associated with duodenal ER.

Summary: Various ER techniques for SNADETs, including cold snare polypectomy (CSP), endoscopic mucosal resection (EMR), underwater EMR (UEMR), and endoscopic submucosal dissection (ESD), present different risk profiles. CSP has a very low risk of AEs, while EMR and UEMR exhibit moderate AE risks (up to 18.7%) and high recurrence rates, particularly in cases of piecemeal resections. ESD enables high en bloc resection rates but is associated with a considerable risk of AEs (up to 45.5%). Intraoperative AEs can be managed endoscopically using various closure techniques. To prevent intraoperative AEs during ESD, the use of scissor-type knives and specialized methods such as the pocket-creation method and water pressure method may be employed. Delayed AEs require effective closure of mucosal defects to prevent delayed perforation, which poses a high risk of conversion to surgical intervention.

Key messages: Careful patient selection and implementation of preventive strategies are essential to minimize AEs and optimize the safety of duodenal ER. A comprehensive understanding of the risk profiles of different ER techniques, along with appropriate preventive measures, is critical for safe and effective treatment. A multidisciplinary approach involving experienced endoscopists, surgeons, and radiologists is crucial to optimizing patient outcomes.

Background: The recognition of superficial non-ampullary duodenal epithelial tumors (SNADETs) has increased with advancements in endoscopic technology and increased awareness among clinicians. White light imaging (WLI) remains the primary diagnostic modality for SNADETs. However, data for standardized endoscopic diagnostic approaches are lacking.

Summary: SNADETs are typically identified by their whitish, flat-elevated appearance and are predominantly located in the descending duodenum. The whitish mucosa is referred to as milk white mucosa (MWM). Although biopsies are traditionally performed for the diagnosis, biopsies have limited sensitivity for histological grading and may cause submucosal fibrosis, which complicates subsequent endoscopic resection. SNADETs are classified as gastric, gastrointestinal, or intestinal mucin phenotypes. Gastric SNADETs are usually found in the pre-ampullary region and are typically lacking MWM, whereas intestinal-type SNADETs often exhibit MWM. Several endoscopic features under WLI, such as lesion color, size, surface depression, and morphology, are useful for predicting the grade of dysplasia. Features such as a submucosal tumor-like appearance, deep depression, and oral side location are important for assessing submucosal invasion.

Key messages: WLI plays an important role in the detection and initial assessment of SNADETs. Although differentiating SNADETs from other duodenal lesions using WLI alone remains challenging, understanding the endoscopic features associated with each mucin phenotype aids in accurate distinction of high-grade dysplasia from low-grade dysplasia. Future studies are warranted to establish a comprehensive endoscopic diagnostic system for SNADETs.

Introduction: Multichannel intraluminal impedance and pH monitoring (MII-pH) is the gold standard for diagnosing gastroesophageal reflux disease (GERD). However, the clinical value of the symptom-reflux association (SRA) obtained using MII-pH remains unknown. The current study aimed to investigate the effect of SRA on the efficacy of secondary treatment in refractory true GERD.

Methods: This study included patients who underwent MII-pH monitoring for evaluating proton pump inhibitor (PPI)- or potassium-competitive acid blocker (P-CAB)-refractory GERD symptoms and who were diagnosed with abnormal acid reflux (acid exposure time >6%). Patients with a positive symptom index (SI) and symptom association probability on the MII-pH monitoring were included in the SRA-positive group and the remaining ones in the SRA-negative group. The differences in the subsequent treatment efficacy between the two groups were retrospectively analyzed. Treatment efficacy was evaluated using the Frequency Scale for the Symptoms of GERD (FSSG) questionnaire.

Results: Of the 192 patients with PPI-/P-CAB-refractory GERD, 41 (21.4%) were diagnosed with abnormal acid reflux. Among them, 30 (7 in the SRA-positive group and 23 in the SRA-negative group) underwent symptom assessments before and after treatment. The SRA-positive group had a significantly greater symptom improvement after treatment compared with the SRA-negative group (FSSG score changes: -13.0 ± 6.5 vs. -5.4 ± 8.2, p = 0.016).

Conclusions: SRA evaluation is effective in predicting secondary treatment outcomes in patients with abnormal acid reflux.

Introduction: We investigated the importance of skin microbiota in functional dyspepsia (FD) based on the skin-gut axis theory and revealed potential mechanisms. This study also validates recent popular FD treatments.

Methods: We used mendelian randomization (MR) to analyze 418 gut bacteria and 145 skin bacteria, identifying key symbionts in FD development. Bibliometric keyword analysis was conducted on current FD therapies. Finally, we used a mouse model of FD to assess body weight, food intake, gastric residue rate, small intestine transit rate, and fecal water content after interventions with skin-gut symbionts and treatment methods. Hematoxylin-eosin staining observed gastric antrum tissue morphology. RhoA and ROCK1 protein and mRNA levels in gastric antrum tissue were detected by western blot and real-time PCR. Fluorescence immunoassay observed ROCK1 and vesicular acetylcholine transporter (VAChT) protein expression.

Results: Streptococcus has a causal relationship with FD. Bibliometric analysis highlighted electroacupuncture as a research hotspot. Skin Streptococcus colonization reduced food intake, body weight, small intestine transit rate, and increased gastric residue rate in FD mice, decreasing RhoA, ROCK1, and VAChT protein and mRNA levels. Antibiotics reversed these effects. Electroacupuncture improved weight, appetite, gastrointestinal motility, and RhoA, ROCK1, and VAChT protein, and mRNA levels in FD mice.

Conclusion: The study confirmed the pathogenic role of skin Streptococcus in FD and the therapeutic value of electroacupuncture at Tianshu acupoint, potentially via RhoA/ROCK1 signaling pathway regulation.

Introduction: Esophageal squamous cell carcinoma (ESCC) is a highly fatal cancer with unclear molecular underpinnings. This study utilized bioinformatics to uncover key genes and pathways associated with ESCC and to identify prognostic markers.

Methods: We identified the differentially expressed genes (DEGs) using three datasets (GSE53625, GSE67269, and GSE23400-GPL96). Meanwhile, weighted gene co-expression network analysis (WGCNA) constructed gene co-expression networks based on the GSE23400-GLP97 dataset. Machine-learning algorithms further identified the most critical genes. Additionally, we validated the expression and diagnostic potential of the hub genes using the GSE161533 and GSE38129 datasets. Survival analysis and Gene Set Enrichment Analysis (GSEA) revealed the prognostic value and potential functions of the hub genes, respectively.

Results: The study identified 240 DGEs (103 upregulated and 137 downregulated). Concurrently, WGCNA pinpointed 209 genes associated with ESCC. Subsequently, machine-learning algorithms identify four hub genes, including KIF14, GALNT12, MGLL, and EMP1. Moreover, their expression differences and potential as diagnostic biomarkers for ESCC were validated. Survival analysis indicated that elevated GALNT12 expression was associated with a poor prognosis for ESCC patients. GSEA delineated the involvement of GALNT12 in critical biological pathways.

Conclusion: Our results identified GALNT12 as a novel potential diagnostic and prognostic marker for ESCC.

Background: Colorectal cancer (CRC) is a significant global health issue, ranking as the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths. Countries with a high Human Development Index (HDI) report the highest incidence rates, driven by dietary and lifestyle factors. In contrast, low-to-middle HDI countries are experiencing rising CRC rates due to urbanization and westernization. Japan exemplifies this shift, with increasing CRC incidence linked to the adoption of westernized diets. Despite advances in screening and treatment, CRC-related mortality remains substantial, with 53,088 deaths reported in Japan.

Summary: This review examines global and regional CRC trends, focusing on incidence, mortality, and risk factors such as genetic predispositions, diet, and lifestyle influences. The review highlights the growing burden of CRC in Japan and other regions where dietary changes and urbanization are prevalent. Key findings include the significant impact of processed foods, sugary beverages, obesity, alcohol, and smoking on CRC risk, as well as the protective effects of vitamin D, calcium, and fermented foods. The role of inflammatory bowel disease and diabetes in CRC risk is also discussed. Furthermore, the review emphasizes the importance of public health initiatives, including organized screening programs, in mitigating the CRC burden.

Key messages: Understanding the interplay between genetic, lifestyle, and environmental factors is crucial for developing effective prevention strategies. Enhancing CRC screening, early detection, and public health interventions can significantly reduce CRC-related mortality. Continued research and collaboration are essential for advancing CRC prevention and improving global health outcomes.