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Background: Barrett's esophagus (BE) represents the only established precursor to esophageal adenocarcinoma. While endoscopic surveillance is a cornerstone of early detection, it remains limited by interobserver variability, sampling error, and variability in diagnostic yield. In recent years, artificial intelligence (AI) has emerged as a promising tool to improve the detection and characterization of neoplastic lesions in BE.

Summary: This review outlines the current landscape and future potential of AI applications in the endoscopic management of BE. Diagnostic systems employing convolutional neural networks and transformer-based architectures have achieved high performance for both lesion detection (CADe) and characterization (CADx), with several models externally validated in multicenter cohorts. The first CE-certified commercial system, CADU™, has further marked the entry of AI into clinical use. Emerging developments include AI tools for infiltration depth estimation, vessel detection during endoscopic submucosal dissection, post-therapeutic surveillance, and procedural quality assessment. Challenges related to generalizability, human-AI interaction, ethical implementation, and regulatory compliance are discussed in the context of clinical translation.

Key messages: (1) AI systems demonstrate high diagnostic accuracy and enable real-time assistance in BE surveillance. (2) In-domain pretrained models and transformer-based systems may improve robustness and adaptability. (3) Clinical applications are expanding beyond diagnostics to therapeutic guidance and posttreatment monitoring. (4) Successful implementation depends on rigorous validation, explainability, and integration into clinical workflows.

Background: Barrett's esophagus and its malignant progression to Barrett's adenocarcinoma are becoming increasingly prevalent worldwide, yet their underlying mechanisms remain incompletely understood.

Summary: The pathogenesis of Barrett's esophagus and Barrett's adenocarcinoma is multifactorial, involving environmental, genetic, and cellular factors. Chronic acid and bile reflux are well-established contributors, promoting cellular transformation in the esophageal epithelium. Obesity further exacerbates this risk, both indirectly by increasing reflux and directly via proinflammatory adipokines. Recent genetic studies have identified several genetic risk variants, with loss of p53 recognized as critical event in malignant progression. Moreover, the origin of Barrett's esophagus remains under investigation, with proposed sources including cells of esophageal submucosal glands, cells of gastric cardia, and circulating bone marrow-derived cells.

Key messages: The pathophysiological mechanisms underlying Barrett's esophagus and the development of Barrett's adenocarcinoma are still under active investigation. Understanding these mechanisms is essential for developing effective preventive and therapeutic strategies.

Background: With a 50-year delay compared to Europe and the USA, esophageal adenocarcinoma (EAC) began to increase in Japan around 2010, and it is expected to continue rising over the next few decades. This 50-year discrepancy is primarily attributable to variations in the timing of the decline in Helicobacter pylori infection rates across the two regions, with the extent of obesity in Japan also exerting an influence on the projected increase in EAC. Currently, the incidence of EAC in Japan is approximately one-tenth to one-twentieth that observed in Europe and the USA. However, ongoing monitoring is essential to assess the potential for escalation of this cancer. Accurate estimation of the incidence of EAC in Barrett's esophagus (BE), a precancerous condition of EAC, is imperative for the establishment of appropriate endoscopic surveillance for early cancer detection.

Summary: The incidence of EAC in BE is largely determined by its length. In the Japanese population, BE with a length greater than 3 centimeters exhibits a high incidence of EAC and necessitates surveillance, while BE with a length less than 1 centimeter exhibits an exceptionally low incidence of EAC and is considered to require no surveillance. The challenge lies in determining the optimal approach for addressing BE with a length of 1-3 cm, which is observed in 5-15 percent of endoscopic examinees, necessitating careful consideration due to its significance.

Key message: Since the EAC risk of BE varies greatly depending on its length, the need for surveillance and inspection intervals for BE in Japan should be defined by its length.

Introduction: Oesophageal cancer is a leading global health issue, with increasing prevalence of oesophageal adenocarcinoma and its precursor lesion, Barrett's oesophagus (BE). Despite the opportunity to treat dysplasia prior to adenocarcinoma development, rates of missed advanced dysplasia at BE surveillance remain high. This pilot study aimed to assess whether Texture and Colour Enhancement Imaging (TXI), a new advanced mucosal imaging modality, improves dysplasia detection during BE surveillance compared to white light endoscopy (WLE).

Methods: Patients undergoing endoscopy for BE assessment or surveillance at a single centre were included for analysis. Patients were randomized in a 1:1 ratio to examination with WLE then TXI or vice versa, followed by narrow-band imaging (NBI). Targeted biopsies were taken from any suspicious areas and 4-quadrant surveillance biopsies were taken at 1 cm intervals in the entire BE segment.

Results: A total of 50 patients were included in the study, with 27 suspicious lesions seen in 22 patients. A total 93.3% (n = 14/15) of high-grade dysplasia or early adenocarcinoma was detected as endoscopically visible lesions on TXI and NBI. However, 4 such lesions were not detected on WLE. On per-patient analysis, the sensitivity and NPV of TXI in combination with magnified NBI were both 100% with specificity of 84.6%, surpassing all PIVI thresholds for dysplasia diagnosis in BE.

Conclusion: This pilot study demonstrates the feasibility of TXI as a potential addition to the armamentarium of advanced mucosal imaging available to proceduralists surveilling BE. Further large multi-centre studies would be required to make statistical comparisons with existing imaging modalities.

Background: Barrett's oesophagus (BE) is the sole established precursor to oesophageal adenocarcinoma, with striking contrasts in its epidemiology and management between the East and the West.

Summary: This review, based on a structured literature search, examines the key divergences in endoscopic management: highlighting the Western emphasis on eradication therapy using ablation techniques such as radiofrequency ablation, contrasted with the Eastern expertise in advanced resection techniques including endoscopic submucosal dissection.

Key messages: Despite improving patient outcomes, significant challenges remain, including variable surveillance protocols, controversies regarding non-dysplastic BE and low-grade dysplasia, and optimal strategies for recurrent disease. As gastroesophageal reflux disease and long-segment BE rise in prevalence in the East, and Western proficiency in endoscopic submucosal dissection grows, these once-distinct approaches are poised to converge. As these treatment paradigms align, patients and clinicians alike stand to benefit from more effective, tailored care and better long-term outcomes.

Introduction: Colorectal cancer remains one of the most prevalent gastrointestinal malignancies. This study aims to identify key genes associated with colorectal cancer recurrence, offering novel insights for prognostic assessment and personalized treatment strategies.

Methods: Leveraging the TCGA dataset, we conducted a comprehensive analysis of differentially expressed genes between recurrent and nonrecurrent colorectal cancer patients. We developed a recurrence-associated gene signature (RAGS) model for prognostic evaluation and employed nine machine learning algorithms to predict recurrence risk. Furthermore, we performed extensive functional studies on the most significant genes, examining their expression patterns, prognostic relevance, and effects on cellular proliferation, metastasis, and chemoresistance.

Results: Our analyses identified 45 key genes linked to colorectal cancer recurrence and prognosis. Using LASSO regression, we constructed the RAGS model, incorporating TMEM213, SAP25, POU4F1, RSPO4, and PAGE2B. This model demonstrated exceptional performance in predicting overall prognosis and post-chemotherapy outcomes. Among the machine learning algorithms tested, XGBoost exhibited the highest diagnostic accuracy for recurrence prediction, with POU4F1 emerging as the most significant predictive gene. Functional experiments revealed that POU4F1 knockdown substantially inhibited colorectal cancer cell proliferation and metastasis both in vitro and in vivo, while also reducing resistance to 5-fluorouracil and oxaliplatin.

Conclusion: This study successfully identified crucial genes associated with colorectal cancer recurrence and developed a robust RAGS prognostic model. The XGBoost algorithm underscored the importance of POU4F1 in predicting colorectal cancer recurrence. Our functional analysis of POU4F1 provides fresh insights into colorectal cancer progression mechanisms and informs the development of targeted therapeutic approaches. These findings not only enhance our understanding of colorectal cancer's molecular underpinnings but also establish a solid foundation for advancing precision diagnosis and treatment in clinical practice.

Background: Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder caused by the retrograde flow of gastric contents into the esophagus, leading to bothersome symptoms and complications. Its pathophysiology is complex and multifactorial, and recent research has aimed to explain the heterogeneity of GERD phenotypes, each influenced by different underlying mechanisms that contribute to symptom presentation and disease progression. Summary: GERD arises from an imbalance between defensive mechanisms and disruptive factors. Key pathophysiological contributors include esophageal gastric junction dysfunction, transient lower esophageal sphincter relaxations, esophageal motility abnormalities, delayed gastric emptying, and thoracoabdominal pressure gradients. Mucosal damage is exacerbated by prolonged exposure to acid and bile, pepsin activity, and impaired esophageal volume and chemical clearance. Additionally, central and peripheral neural modulation influences symptom perception, with heightened visceral sensitivity and esophageal hypervigilance playing significant roles in symptom severity and treatment response. Emerging diagnostic techniques such as high-resolution manometry, impedance-pH monitoring, and EndoFLIP® are improving our ability to identify specific pathophysiological abnormalities, leading to more personalized approaches to GERD management. Key Messages: (i) GERD results from a multifactorial interplay between anatomical, functional, and neurophysiological mechanisms. (ii) Esophageal clearance, EGJ structure and function, acid exposure, mucosal resistance, and neural modulation are crucial determinants of symptom severity and disease progression. (iii) The presence of different phenotypes of the reflux disease (e.g., GERD, functional heartburn, and reflux hypersensitivity) underscores the need for individualized diagnostic and therapeutic strategies. (iv) Advances in diagnostic technologies enhance our understanding of GERD pathophysiology, facilitating tailored management approaches beyond acid suppression therapies. Future research should focus on refining GERD phenotyping and integrating mechanistic insights into personalized treatment paradigms.

Background: Esophagogastroduodenoscopy is often performed as an initial examination in patients with symptoms such as dysphagia or chest pain, which may suggest esophageal motility disorders. However, its current role is largely limited to ruling out organic diseases.

Summary: High-resolution manometry (the gold standard for diagnosing primary esophageal motility disorders such as achalasia) along with esophagography is extremely useful for diagnosis. In recent years, however, several new endoscopic findings - esophageal rosette, gingko leaf sign, champagne glass sign, corona appearance, and pinstripe pattern - have been reported, making it increasingly possible to strongly suspect achalasia through endoscopy. Additionally, the presence of multiple annular contractions, spiral (corkscrew) contractions, or narrowing (poor distensibility) in the esophageal body during endoscopy may suggest abnormal motility of the esophageal body.

Key messages: When performing endoscopic examinations in patients with symptoms such as dysphagia or chest pain, it is important to consider the possibility of esophageal motility disorders. Careful endoscopic observation may allow for the suspicion of such disorders during the examination itself.

Background: The incidence of Barrett's esophagus-related neoplasia is increasing worldwide, with a growing number of cases reported in Japan. While early stage lesions are suitable for endoscopic resection, accurate endoscopic detection, and histological assessment remain difficult, particularly in long-segment Barrett's esophagus (LSBE), where lesions often exhibit flat morphology and indistinct margins. These characteristics reduce endoscopic visibility and are associated with lower endoscopic R0 resection rates compared with short-segment Barrett's neoplasias. In Japan, image-enhanced magnifying endoscopy with targeted biopsy is the preferred diagnostic approach, whereas Western guidelines recommend random biopsies according to the Seattle protocol. This review discusses current diagnostic approaches and challenges from a Japanese perspective. Summary: Current diagnostic strategies for superficial Barrett's esophagus-related neoplasia (SBERN) incorporate high-resolution modalities such as white-light endoscopy and magnifying narrow-band imaging with or without acetic acid enhancement. The Japan Esophageal Society Barrett's Esophagus (JES-BE) classification provides a standardized framework for evaluating mucosal and vascular patterns in magnifying endoscopy, thereby improving diagnostic consistency. Nevertheless, histological interpretation, particularly for SBERNs arising in LSBE, poses major challenges due to interobserver variability in differentiating true dysplasia from inflammation-associated atypia and in grading dysplasia, even among expert gastrointestinal pathologists. In Japan, immunohistochemical markers such as p53 and Ki-67 are widely used in routine practice to support histological assessment, particularly for lesions indefinite for dysplasia. Key Messages: Given the increasing clinical burden of SBERN, further standardization of endoscopic criteria and histological assessment is expected to establish more reliable surveillance strategies tailored to segment extent of BE.

Introduction: Conventional endoscopic mucosal resection (EMR) is widely accepted for 6-20 mm superficial non-ampullary duodenal epithelial tumors (SNADETs); however, its en bloc and R0 resection rates remain suboptimal. Modified techniques, such as underwater EMR (UEMR) and cap-assisted EMR (EMRC), have been introduced to improve outcomes; nevertheless, comparative data are limited despite both techniques being increasingly utilized.

Methods: This retrospective two-center study included patients with 6-20 mm SNADETs treated with either UEMR or EMRC between April 2016 and May 2024 at Kobe University Hospital and the International Clinical Cancer Research Center. Clinicopathologic characteristics, therapeutic outcomes, and adverse events were compared. Multivariate logistic regression analysis was conducted to identify risk factors for non-R0 and piecemeal resection.

Results: A total of 155 SNADETs (51 UEMR, 104 EMRC) were included. The EMRC group achieved significantly higher R0 resection rates (86.5% vs. 62.7%; p < 0.001) and en bloc resection rates (94.2% vs. 78.4%; p = 0.003) without increasing adverse events. Multivariate analysis identified UEMR, lesion size ≥10 mm, and anterior or lateral wall involvement as independent risk factors for non-R0 resection. Lesion size ≥10 mm was the only independent risk factor for piecemeal resection.

Conclusion: In SNADETs measuring 6-20 mm, EMRC demonstrated higher en bloc and R0 resection rates than UEMR with a comparable safety profile, suggesting EMRC may be a useful option for achieving complete resection in selected cases. Prospective studies are needed to refine techniques to minimize complications while maintaining efficacy and to clarify long-term outcomes and recurrence.