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"Name of Journal: World Journal of Gastroenterology Manuscript Type: LETTER TO THE EDITOR Dialister-Associated Succinate Dysregulation in Crohn’s Disease: Clinical and Therapeutic Implications 1Fotios S. Fousekis, 1Konstantinos H. Katsanos, 2Konstantinos Vlachos, 2Georgios D. Lianos 1Department of Gastroenterology, University Hospital of Ioannina, University of Ioannina Ioannina, Greece 2Department of Surgery, University Hospital of Ioannina, University of Ioannina, Greece Corresponding author: Fotios S. Fousekis, MD, PhD, Department of Gastroenterology, University Hospital of Ioannina, University of Ioannina Ioannina, Greece, email: fotisfous@gmail.com Abstract Growing evidence suggests that altered gut microbiota–derived succinate metabolism plays an important role in Crohn’s disease activity and postoperative recurrence. Particular emphasis is placed on Dialister, a gut bacterial genus that consumes succinate inefficiently, potentially leading to its accumulation and increased intestinal inflammation. Elevated succinate may impair immune regulation and enhance inflammatory signaling through SUCNR1 activation and hypoxia-inducible factor-1α stabilization. Recent findings identifying specific Dialister strains associated with postoperative recurrence provide new insight into disease monitoring and risk stratification. Although the study offers an integrative view linking microbial composition, metabolism, and inflammation, further validation using direct metabolomic and shotgun metagenomic approaches is needed. Overall, succinate appears to be a promising biomarker and therapeutic target, supporting future microbiota- and metabolism-based strategies for the management of inflammatory bowel disease. Key words: Crohn’s disease; Inflammatory bowel disease; Gut microbiota; Succinate; Dialister; Postoperative recurrence Core tip Accumulation of the microbial metabolite succinate is increasingly recognized as a key driver of inflammation in Crohn’s disease. Recent evidence links Dialister enrichment to impaired succinate clearance, disease activity, and postoperative recurrence, highlighting succinate as a promising biomarker and therapeutic target in inflammatory bowel disease. To the editor Dialister, an anaerobic Gram-negative genus of the human gut microbiome, has gained clinical interest due to its role in succinate metabolism. While capable of utilizing succinate as a substrate for propionate production, Dialister exhibits relatively slow consumption rates compared with efficient succinate consumers such as Phascolarctobacterium. This inefficiency may result in elevated luminal succinate levels, particularly in the context of inflammatory bowel disease (IBD) (1). Succinate accumulation may disrupt regulatory T cell (Treg) function by promoting FOXP3 degradation, thereby reducing immune tolerance and further amplifying inflammation (2). Furthermore, elevated succinate stabilizes hypoxia-inducible factor-1α (HIF-1α) by inhibiting prolyl hydroxylase activity, which prevents HIF-1α degradation and leads to enhanced inflammatory gene expression and perpetuation of tissue injury, particularly in IBD (3). We read with great interest the recently published article by Boronat-Toscano and colleagues on Dialister-driven succinate accumulation and its association with disease activity and postoperative recurrence in Crohn’s disease (4). This study offers valuable insights into a rapidly growing field of research that links gut microbiota, host metabolism, and inflammation. It positions succinate not just as a metabolic by-product but also as a functional biomarker and potential therapeutic target. One of the major strengths of this work is its integrative, multi-level approach, which combines clinical and biochemical measures of disease activity, such as the Harvey–Bradshaw Index, C-reactive protein, and fecal calprotectin, with gut microbiome profiling using 16S rRNA sequencing and host molecular markers related to succinate signaling, specifically the expression of the succinate receptor SUCNR1 (4). Notably, this study highlights specific Dialister operational taxonomic units (OTUs) in the intestinal mucosa that correlate with the risk and severity of postoperative recurrence. This goes beyond existing knowledge by identifying strain-level microbial signatures with potential predictive value, suggesting that variability within Dialister is vital for patient stratification and disease progression after surgery. The authors also propose a mechanism for succinate accumulation in Crohn's disease, involving the downregulation of NADH dehydrogenase and the upregulation of fumarate reductase and succinate transporters. This metabolic shift enhances succinate production and export by the gut microbiota (4). Despite these strengths, we would like to highlight several issues that merit further discussion. The functional analysis of the gut microbiome is based on predictive approaches (PICRUSt2) rather than on direct measurements of metabolic fluxes or shotgun metagenomic sequencing. Validation of these predictions is essential for robust conclusions. Targeted metabolomic analyses, using mass spectrometry or nuclear magnetic resonance, allow for direct quantification of metabolites as succinate and can confirm the functional activity of predicted pathways (5). In addition shotgun metagenomic sequencing may provide a more comprehensive and direct assessment of the genetic potential for metabolic pathways, including those involved in succinate production and consumption, by sequencing all microbial DNA present in a sample (6). These findings also open important avenues for future research and therapeutic development in inflammatory bowel disease. Given the central role of succinate in promoting intestinal inflammation through SUCNR1 activation and HIF-1α stabilization, strategies aimed at reducing succinate accumulation or blocking its downstream signaling pathways warrant further investigation. Microbiota-targeted interventions, including dietary fiber enrichment, prebiotics, and probiotics designed to enhance the abundance of efficient succinate-consuming bacteria such as Phascolarctobacterium, represent a particularly promising approach, as preclinical studies have demonstrated their ability to lower succinate levels, attenuate inflammatory signaling, and restore epithelial barrier integrity (7). Avoiding supplementation of the diet with refined inulin may be considered, as evidence from mouse models suggests that it can induce abnormal succinate accumulation in the intestinal lumen, thereby contributing to colonic inflammation (8). In parallel, pharmacological inhibition of SUCNR1 using small-molecule antagonists, as well as interventions targeting HIF-1α stabilization, may offer complementary strategies to suppress succinate-driven inflammation (9, 10). Huo et al. demonstrated that the SUCNR1 inhibitor NF-56-EJ40 may suppress glycolysis in intestinal epithelial cells and attenuates Th17-mediated inflammation in a dextran sodium sulfate–induced mouse model of ulcerative colitis. Treatment reduced pro-inflammatory cytokine production, improved epithelial barrier integrity, and alleviated colonic injury, supporting SUCNR1 antagonism as a therapeutic strategy targeting both metabolic and immune pathways (7). Consistently, genetic deletion of SUCNR1 in mice protected against both acute colitis and intestinal fibrosis, while in human fibroblasts derived from Crohn’s disease patients, succinate increased SUCNR1 expression and promoted inflammatory and fibrotic markers that were effectively reversed by SUCNR1 blockade (11). While these approaches are supported by growing mechanistic and translational evidence, well-designed clinical trials will be essential to determine their efficacy and safety in patients with IBD. Conclusion The study conducted by Boronat-Toscano et al. enhances the understanding of how microbiota-driven metabolic dysregulation relates to Crohn’s disease by identifing succinate and Dialister-associated microbial signatures associated as important factors that influence disease activity and the likelihood of postoperative recurrence. These findings support the use of succinate-related biomarkers in future risk assessment and postoperative monitoring strategies. Additionally, they provide a strong biological basis for therapeutic interventions that target succinate metabolism or SUCNR1-mediated signaling. Overall, this study marks a crucial step towards developing metabolically informed, microbiome-based precision medicine for IBD. Author contributions: Fousekis FS wrote the original draft; Lianos GD contributed to conceptualization, writing, reviewing and editing; Katsanos KH and Vlachos K participated in drafting the manuscript; and all authors have read and approved the final version of the manuscript. References 1. Anthamatten L, von Bieberstein PR, Menzi C, Zund JN, Lacroix C, de Wouters T, Leventhal GE. Stratification of human gut microbiomes by succinotype is associated with inflammatory bowel disease status. Microbiome. 2024;12(1):186. PMID: 39350289 PMCID: PMC11441152 DOI: 10.1186/s40168-024-01897-8 2. Wang H, Hu D, Cheng Y, Gao Q, Liu K, Mani NL, Tang AY, Iyer R, Gao B, Zhou Q, Yu Q, Weinberg SE, Zhang X, Cong Y, Dulai PS, Zhang Y, Liu Z, Fang D. Succinate drives gut inflammation by promoting FOXP3 degradation through a molecular switch. Nat Immunol. 2025;26(6):866-80. PMID: 40457062 PMCID: PMC12399925 DOI: 10.1038/s41590-025-02166-y 3. Tannahill GM, Curtis AM, Adamik J, Palsson-McDermott EM, McGettrick AF, Goel G, Frezza C, Bernard NJ, Kelly B, Foley NH, Zheng L, Gardet A, Tong Z, Jany SS, Corr SC, Haneklaus M, Caffrey BE, Pierce K, Walmsley S, Beasley FC, Cummins E, Nizet V, Whyte M, Taylor CT, Lin H, Masters SL, Gottlieb E, Kelly VP, Clish C, Auron PE, Xavier RJ, O'Neill LAJ. Succinate is an inflammatory signal that induces IL-1beta through HIF-1alpha. Nature. 2013;496(7444):238-42. PMID: 23535595 PMCID: PMC4031686 DOI: 10.1038/nature11986 4. Boronat-Toscano A, Queipo-Ortuño MI, Monfort-Ferré D, Suau R, Vañó-Segarra I, Valldosera G, Cepero C, Astiarraga B, Clua-Ferré L, Plaza-Andrade I, Aranega-Martín L, Cabrinety L, Abadia de Barbarà C, Castellano-Castillo D, Moliné A, Caro A, Domènech E, Sánchez-Herrero JF, Benaiges-Fernandez R, Fernández-Veledo S, Vendrell J, Ginés I, Sumoy L, Manyé J, Menacho M, Serena C. Dialister-driven succinate accumulation is associated with disease activity and postoperative recurrence in Crohn's disease. World J Gastroenterol. 2025;31(45):112618. PMID: 41378335 PMCID: PMC12687013 DOI: 10.3748/wjg.v31.i45.112618 5. Han S, Van Treuren W, Fischer CR, Merrill BD, DeFelice BC, Sanchez JM, Higginbottom SK, Guthrie L, Fall LA, Dodd D, Fischbach MA, Sonnenburg JL. A metabolomics pipeline for the mechanistic interrogation of the gut microbiome. Nature. 2021;595(7867):415-20. PMID: 34262212 PMCID: PMC8939302 DOI: 10.1038/s41586-021-03707-9 6. Mitra S, Forster-Fromme K, Damms-Machado A, Scheurenbrand T, Biskup S, Huson DH, Bischoff SC. Analysis of the intestinal microbiota using SOLiD 16S rRNA gene sequencing and SOLiD shotgun sequencing. BMC Genomics. 2013;14 Suppl 5(Suppl 5):S16. PMID: 24564472 PMCID: PMC3852202 DOI: 10.1186/1471-2164-14-S5-S16 7. Huo L, Chen Q, Jia S, Zhang Y, Wang L, Li X, Li Z, Sun B, Shan J, Lin J, Yang L, Sui H. Gut microbiome promotes succinate-induced ulcerative colitis by enhancing glycolysis through SUCNR1/NF-kappaB signaling pathway. Am J Physiol Cell Physiol. 2025;329(2):C440-C54. PMID: 40549551 DOI: 10.1152/ajpcell.00411.2025 8. Tian S, Paudel D, Hao F, Neupane R, Castro R, Patterson AD, Tiwari AK, Prabhu KS, Singh V. Refined fiber inulin promotes inflammation-associated colon tumorigenesis by modulating microbial succinate production. Cancer Rep (Hoboken). 2023;6(11):e1863. PMID: 37489647 PMCID: PMC10644334 DOI: 10.1002/cnr2.1863 9. Haffke M, Fehlmann D, Rummel G, Boivineau J, Duckely M, Gommermann N, Cotesta S, Sirockin F, Freuler F, Littlewood-Evans A, Kaupmann K, Jaakola VP. Structural basis of species-selective antagonist binding to the succinate receptor. Nature. 2019;574(7779):581-5. PMID: 31645725 DOI: 10.1038/s41586-019-1663-8 10. Kim YI, Yi EJ, Kim YD, Lee AR, Chung J, Ha HC, Cho JM, Kim SR, Ko HJ, Cheon JH, Hong YR, Chang SY. Local Stabilization of Hypoxia-Inducible Factor-1alpha Controls Intestinal Inflammation via Enhanced Gut Barrier Function and Immune Regulation. Front Immunol. 2020;11:609689. PMID: 33519819 PMCID: PMC7840603 DOI: 10.3389/fimmu.2020.609689 11. Macias-Ceja DC, Ortiz-Masia D, Salvador P, Gisbert-Ferrandiz L, Hernandez C, Hausmann M, Rogler G, Esplugues JV, Hinojosa J, Alós R; Navarro F, Cosin-Roger J, Calatayud S, Barrachina MD. Succinate receptor mediates intestinal inflammation and fibrosis. Mucosal Immunol. 2019;12(1):178-87. PMID: 30279517 DOI: 10.1038/s41385-018-0087-3 " 
Boronat-Toscano A, Queipo-Ortuño MI, Monfort-Ferré D, Suau R, Vañó-Segarra I, Valldosera G, Cepero C, Astiarraga B, Clua-Ferré L, Plaza-Andrade I, Aranega-Martín L, Cabrinety L, Abadia de Barbarà C, Castellano-Castillo D, Moliné A, Caro A, Domènech E, Sánchez-Herrero JF, Benaiges-Fernandez R, Fernández-Veledo S, Vendrell J, Ginés I, Sumoy L, Manyé J, Menacho M, Serena C. Dialister-driven succinate accumulation is associated with disease activity and postoperative recurrence in Crohn’s disease. World J Gastroenterol 2025; 31(45): 112618 [PMID: 41378335 DOI: 10.3748/wjg.v31.i45.112618]
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"This minireview systematically synthesizes the intricate interplay between depression and gastric cancer (GC), incorporating neuroendocrine, immunological, and psychosocial mechanisms. The authors effectively underscore the bidirectional causality supported by 52 referenced studies, in alignment with the biopsychosocial model. Nonetheless, there are opportunities to enhance methodological rigor and visual communication. Although Figure 1 delineates key components of the bidirectional relationship, its informational density is suboptimal. The figure lacks a hierarchical structuring of pathways (e.g., neuroendocrine versus immune mechanisms) and does not quantify effect sizes (e.g., hazard ratios from cited meta-analyses). It is recommended to incorporate a summary table for comparison." 
Chen Z, Gong TJ, Zhao L. Bidirectional relationship between depression and the risk and prognosis of gastric cancer. World J Gastrointest Oncol 2025; 17(12): 113272 [DOI: 10.4251/wjgo.v17.i12.113272]
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"I want to congratulate the authors, Zhang et al, for conducting a study and identifying the predictors of refractory GERD. They have identified the disease duration and anxiety as significant risk factors and at least 90 minutes of moderate-intensity physical activity per week as a protective factor for refractory GERD. One of the important findings in this study is the association of significant Overlap DGBI symptoms (such as dyspepsia, constipation, and diarrhoea) in at least 50% of GERD patients. Since most patients had a duration of illness of more than 4 years, complications of GERD and their comparison between the groups were not noted in this study (a limitation). Although hydrogen impedance is used for diagnosis, the comparison of impedance parameters is not provided. H pylori infection is a protective factor for GERD/Barrett's, which is also a limitation. This study has provided a meaningful conclusion regarding the association between long-term symptoms and refractoriness. " 
Zhang N, Wang Y, Fang SS, Han M, Zheng QW, Zhu YY, Zhang MY, Li JJ, Cui LX, Tian JL, Deng YH, Zhu SL, Ni HM, Zhou L, Zuo GL, Huang TS, Liao Q, Li XQ, Shang YY, Wang YJ, Tian Y, Ge LY, Han HQ, Hu WM, Jiang Y, Li YJ, Mao X, Yang LH, Yao JM, Zheng X, Wang HW, Fang SQ. Clinical characteristics and risk factors of refractory gastroesophageal reflux disease: A multicenter cross-sectional study. World J Gastroenterol 2025; 31(45): 113060 [PMID: 41378325 DOI: 10.3748/wjg.v31.i45.113060]
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"The present Letter provides a concise academic response to the article identified by Reader’s code 05354032. The comments focus on several important aspects of the study, including its methodological design, data interpretation, and clinical applicability. The aim is to offer constructive perspectives that may help clarify key issues and support future improvements in related research." 
Ardila CM, Ángel-Estrada S, González-Arroyave D. Robot-assisted vs conventional lumbar interbody fusion: A systematic review and meta-analysis of perioperative, radiographic, and clinical outcomes. World J Orthop 2025; 16(11): 110276 [PMID: 41355831 DOI: 10.5312/wjo.v16.i11.110276]
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"The study title "Comparison of the efficacy of laparoscopic hepatectomy and radiofrequency ablation for small hepatocellular carcinoma: A retrospective study" by Lei et al. aims to compare the long-term survival and perioperative outcomes of Laparoscopic hepatectomy (LH) and radiofrequency ablation (RFA) for small hepatocellular carcinoma (HCC). This retrospective study included 254 patients with small HCC who were collected from Hospital of Chongqing Medical University between December 2022 and March 2025. The results showed that LH was associated with longer operative time, greater blood loss, prolonged recovery, higher costs, and increased complication rates. Consequently, LH, though associated with increased perioperative morbidity, provides superior long-term survival outcomes compared with RFA in patients with small HCC. This study had many limitations such as potential for selection bias and confounding factors that were not controlled for is inherent. The decision to undergo either LH or RFA was made based on clinical judgment and patient-specific factors, which could introduce bias. The sample size was still be insufficient to detect subtle differences in outcomes between the two modalities, especially for subgroups with specific tumor characteristics or comorbidities. Moreover, LH and RFA techniques have evolved over time, and variations in operator experience and institutional protocols could influence outcomes." 
Lei ZL, Tan ZL, Luo YH, Yang M, Wang JL, Qin Z, Liu YY. Comparison of the efficacy of laparoscopic hepatectomy and radiofrequency ablation for small hepatocellular carcinoma: A retrospective study. World J Gastroenterol 2025; 31(45): 111540 [PMID: 41378322 DOI: 10.3748/wjg.v31.i45.111540]
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"We are delighted to read the high-quality review by Zheng et al[1], published in the World Journal of Gastroenterology, which offers insightful perspectives on the neuroimmune mechanisms contributing to the pathogenesis of inflammatory bowel disease (IBD). The intricate interplay between the autonomic nervous system (ANS) and the immune response, particularly involving vagus nerve stimulation (VNS) and its effects on macrophages, provides a promising avenue for future therapeutic interventions in IBD. The review underscores the emerging concept of neuroimmune interactions, particularly the cholinergic anti-inflammatory pathway (CAIP), which regulates inflammation through the vagus nerve and its interaction with intestinal macrophages. This is an exciting area of research, especially in the context of IBD, where inflammation is at the heart of the disease's pathology. Macrophages, as highlighted in the review, play a crucial role in maintaining intestinal homeostasis, but when overactivated, they contribute to the excessive production of proinflammatory cytokines, exacerbating the condition. This review draws attention to how the cholinergic system can modulate macrophage activity, reducing the inflammatory burden through the activation of the α7 nicotinic acetylcholine receptor (α7nAChR). The role of VNS as an approach to activate the cholinergic pathway and regulate inflammation in IBD is a breakthrough concept. Studies showing the beneficial effects of VNS in reducing inflammation and enhancing immune tolerance are promising, offering a potential alternative to conventional treatments, especially in patients with refractory IBD. Furthermore, the use of VNS to modulate the autonomic nervous system offers a unique therapeutic strategy for restoring balance between sympathetic and parasympathetic tones in patients, whose autonomic dysfunction may contribute to disease exacerbation. While the current data on VNS in IBD are promising, the review rightly calls for further research to better establish the clinical applicability of VNS, especially through non-invasive techniques such as transauricular and transcervical VNS. These methods, as highlighted, may offer a safer and more accessible alternative to invasive VNS, which has shown positive effects in treating other inflammatory conditions. The ongoing exploration of VNS in clinical trials, coupled with advancements in understanding the mechanisms of cholinergic signaling in immune cells, opens new avenues for therapeutic interventions in chronic inflammatory diseases. However, as the review mentions, there are still challenges that need to be addressed. The precise mechanisms through which VNS modulates immune responses, particularly in macrophages, are still under investigation. Additionally, while VNS has shown potential in preclinical models, there is a need for larger, well-designed clinical studies to confirm the safety, efficacy, and long-term benefits of VNS in IBD patients. The heterogeneity of IBD, along with differences in patient responses to treatment, further complicates the development of standardized protocols for VNS treatment. In conclusion, the review provides an excellent overview of the current state of research on neuroimmune interactions in IBD, with a special focus on the potential of VNS as a novel therapeutic strategy. The integration of neuroimmune regulation, particularly through the cholinergic pathway, into the treatment of IBD represents an innovative approach that could offer significant improvements in patient outcomes. As we move forward, I hope that the continued research in this field will provide more concrete evidence to support the use of VNS in clinical practice, potentially offering a transformative treatment for IBD patients who have not responded to traditional therapies. LIMITATIONS OF THE REVIEW While the review provides a comprehensive overview of the potential therapeutic role of vagus nerve stimulation (VNS) in inflammatory bowel disease (IBD), there are some limitations that should be addressed in future research. First, while the article highlights the promising effects of VNS, particularly through the cholinergic anti-inflammatory pathway (CAIP), there is a lack of in-depth discussion regarding the specific cellular mechanisms involved. The exact signaling pathways through which VNS modulates macrophage activity and alters immune responses remain unclear, and more detailed mechanistic studies are needed to provide a clearer understanding. Additionally, the review does not fully address the challenges associated with the translation of VNS into clinical practice. For instance, the variability in patient response to VNS, the optimal stimulation parameters (e.g., frequency, duration, and intensity), and the potential side effects of VNS, particularly in IBD patients with coexisting conditions, are aspects that require more attention. Lastly, the review focuses primarily on the autonomic nervous system's role in IBD, but it overlooks other possible neuroimmune interactions that could also influence disease progression. A broader exploration of how other neural pathways or neuropeptides contribute to IBD would provide a more comprehensive view of the neuroimmune mechanisms at play. CONCLUSION The review provides an insightful exploration of the neuroimmune mechanisms involved in inflammatory bowel disease (IBD), particularly focusing on the role of intestinal macrophages and the cholinergic anti-inflammatory pathway. Vagus nerve stimulation (VNS) represents a promising non-invasive therapeutic approach for modulating the immune system and controlling inflammation in IBD. However, further research is needed to fully understand the mechanisms behind VNS and to establish its efficacy in clinical settings for treating chronic inflammatory diseases such as IBD. With the development of non-invasive VNS technologies, future therapies may offer safer and more effective treatments for patients suffering from IBD." 
Zheng L, Duan SL. Neuroimmune interactions in inflammatory bowel disease: Role of intestinal macrophages and the cholinergic pathway. World J Gastroenterol 2025; 31(44): 109440 [PMID: 41356522 DOI: 10.3748/wjg.v31.i44.109440]
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"This editorial provides a comprehensive and insightful overview of self-expandable metal stents (SEMS) in acute colonic obstruction, standing out for its clinical relevance and systematic organization. The authors adeptly synthesize cutting-edge techniques (e.g., fluoroscopy-free stenting, two-person colonoscopy) and critical considerations like stent design selection, backed by high-quality recent evidence, which offers valuable guidance for clinical practice. The discussion of complications and mitigation strategies is pragmatic, while the exploration of future directions (e.g., zero-border stents, multidisciplinary collaboration) reflects a forward-thinking perspective. The academic expression is precise and fluent, with consistent use of professional terminology and clear logical progression. A minor suggestion is to include brief comparative data on cost-effectiveness among different stenting techniques or stent types, which would further assist healthcare institutions in decision-making. Overall, this is a high-quality, clinically impactful piece that serves as an excellent reference for gastroenterologists and surgeons specializing in colorectal disorders." 
Sun HY, Li ZC, Wang HL. Current mechanisms and techniques for placement of self-expandable metal stents in acute colonic obstruction. World J Gastrointest Surg 2025; 17(11): 110512 [PMID: 41357659 DOI: 10.4240/wjgs.v17.i11.110512]
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"The editorial authored by Watanabe presents a timely and clinically pertinent overview of lisocabtagene maraleucel (liso-cel) CAR-T therapy, specifically addressing nodal and gastrointestinal follicular lymphoma (GI-FL). The author skillfully amalgamates essential findings from the TRANSCEND FL trial, emphasizing the extraordinary 97% overall response rate and a 94% complete response rate, alongside a notably reduced toxicity profile where grade ≥3 cytokine release syndrome (CRS) was absent, and grade ≥3 neurotoxicity was observed in merely 3% of patients. This concentrated analysis on the unique advantages of liso-cel—particularly its defined CD4+/CD8+ composition and the feasibility of outpatient treatment—addresses a significant void in the existing literature, especially in light of the historical exclusion of GI-FL from crucial CAR-T trials. The comparative framework juxtaposing lisocabtagene maraleucel with axicabtagene ciloleucel and tisagenlecleucel provides invaluable insights for clinical decision-making. Nevertheless, the editorial's otherwise robust examination fails to explore subtleties regarding the durability of response in high-risk subpopulations. Although the reported 12-month progression-free survival rate exceeding 85% is promising, emerging data indicate that follicular lymphoma patients with specific genomic alterations (e.g., TP53 mutations or 1p36 deletions) display varied responsiveness to CAR-T therapy. This omission is particularly salient for GI-FL, where the biological characteristics of the disease may diverge from those of nodal FL due to influences from the microenvironment. Furthermore, the editorial rightly recognizes cost as a barrier but insufficiently emphasizes how the manufacturing logistics of Liso-Cel disproportionately hinder accessibility in advanced GI-FL cases. Unlike nodal FL, where treatment delays may be manageable, GI-FL frequently presents urgent complications necessitating swift intervention. The three-week manufacturing timeline for liso-cel—despite improvements over previous platforms—remains a challenge for these patients, a difficulty exacerbated by the absence of validated bridging strategies tailored to gastrointestinal involvement. Looking ahead, the integration of endoscopic and molecular staging systems (e.g., Paris classification) with CAR-T therapy response biomarkers emerges as a critical research priority. Real-world studies should specifically investigate GI-FL cohorts to ascertain whether mucosal disease localization influences CAR-T trafficking or persistence. Additionally, the formulation of risk-adapted conditioning regimens could optimize the therapeutic index in patients with gastrointestinal involvement, where organ-specific toxicities remain inadequately characterized. Watanabe's appeal for multicenter collaboration should explicitly encompass these mechanistic and health-services research inquiries to propel personalized CAR-T applications across follicular lymphoma subtypes." 
Watanabe T. Emerging role of lisocabtagene maraleucel chimeric antigen receptor-T cell in nodal and gastrointestinal follicular lymphoma. World J Gastroenterol 2025; 31(45): 112336 [PMID: 41378337 DOI: 10.3748/wjg.v31.i45.112336]
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"This review elevates our understanding of acetaminophen (APAP)-induced acute liver injury from a “single toxic metabolite acting on hepatocytes” model to a dynamic network involving multiple hepatic cell populations. Second, it clearly maps out current and potential therapeutic targets, essentially providing a “cell-type–oriented treatment roadmap” for future translational work. The discussion of CYP2E1/CYP3A4, species differences, and risk factors (such as alcohol use, malnutrition, underlying liver disease, and concomitant enzyme-inducing drugs) helps clinicians better identify high-risk populations and appreciate the limitations of extrapolating from animal models, thereby supporting more individualized risk assessment and dosing. In the treatment section, the authors extend beyond the classical “N-acetylcysteine golden window” and cover emerging strategies such as inhibition of NAPQI formation (e.g. fomepizole), mitochondria-targeted antioxidants (Mito-Tempo, MitoQ), modulation of ferroptosis/ferritinophagy, NLRP3–STING inflammasome pathways, as well as cell-based and hepatocyte transplantation therapies. This allows clinical readers to quickly grasp potential combination or alternative approaches that are entering or approaching clinical trials, while signaling to basic scientists multiple promising cellular pathways and targets for deeper exploration. Overall, the article reads as an up-to-date progress review on the multicellular mechanisms and therapeutic targets of APAP-induced acute liver injury, offering both mechanistic clarity and topic inspiration for those working on drug-induced liver injury, emergency/critical care, and liver transplantation—while also realistically emphasizing that most of the evidence remains at the experimental or early translational stage and is not yet ready to change clinical guidelines." 
Yang D, Kim B, Kim JW. Mechanistic insights into hepatic cell type-specific contributions to acetaminophen-induced acute liver injury. World J Gastroenterol 2025; 31(45): 112720 [PMID: 41378327 DOI: 10.3748/wjg.v31.i45.112720]
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"this review provides a clear and systematic overview of the interactions among intestinal macrophages, the enteric nervous system, and the cholinergic anti-inflammatory pathway in inflammatory bowel disease (IBD). By closely linking basic mechanistic insights with the potential clinical application of vagus nerve stimulation (VNS)—especially low-frequency, non-invasive VNS—the paper offers a fresh “neuroregulation–immune modulation” angle on IBD treatment, which is currently dominated by immunosuppressants and biologics. In terms of clinical practicality, the authors emphasize the promise of non-invasive VNS as a safer and more tolerable approach, while frankly acknowledging that current evidence still largely comes from animal models and a few pilot clinical studies, with a lack of large-scale randomized controlled trials. This “promising yet cautious” tone is valuable for clinical readers. On the one hand, the paper helps gastroenterologists and basic scientists understand why heart rate variability (HRV), emotional status, and autonomic imbalance may be linked to IBD course and relapse; on the other hand, it reminds readers that VNS and α7nAChR-targeted agents are still at the stages of proof-of-concept and early translation. In the short term, their main value lies in inspiring new research designs (for example, clinical trials stratified by HRV, combined with intestinal macrophage phenotype analysis), rather than immediately changing standard treatment pathways. Overall, this work reads like a forward-looking “blueprint” for neuro-immune therapies in IBD and is particularly thought-provoking for readers interested in IBD mechanisms and novel therapeutic strategies." 
Zheng L, Duan SL. Neuroimmune interactions in inflammatory bowel disease: Role of intestinal macrophages and the cholinergic pathway. World J Gastroenterol 2025; 31(44): 109440 [PMID: 41356522 DOI: 10.3748/wjg.v31.i44.109440]
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"Commentary on "Large Language Models and Large Concept Models in Radiology: Present Challenges, Future Directions, and Critical Perspectives" The transition from LLMs to LCMs, aiming for enhanced semantic reasoning, is fundamentally challenged by the necessity of building these sophisticated models upon historical data streams polluted by human cognitive biases [1]. Diagnostic interpretation errors are often not perceptual misses but interpretive errors driven by faulty reasoning [2,3]. These biases include Anchoring Bias, where a radiologist becomes fixated on an initial impression despite contradictory evidence, often coupled with Confirmation Bias, the inclination to seek information only to affirm that initial theory [2,4,5]. Similarly, Availability Bias, or availability heuristics, predisposes the interpreter to recall recently seen or memorable diagnoses regardless of the actual prevalence [3,4,6]. When AI learns its "concepts" or "relationships" from millions of reports generated under the influence of these specific biases, it may normalize or amplify flawed reasoning patterns, potentially leading to widespread, systemic diagnostic vulnerabilities that mirror rather than correct human limitations [3]. For instance, an AI trained primarily on reports that exhibit Zebra Retreat—the avoidance of accurate but rare diagnoses due to lack of confidence—will systematically underreport uncommon but critical findings, reducing the diagnostic sensitivity for edge cases [2,6]. The core strength of future AI systems must therefore lie not just in conceptual depth but in active debiasing, mitigating the human errors that underpin the training corpus [4,5]. If AI recommendations are opaque, clinicians may fall prey to Blind Obedience or Premature Closure by accepting the machine's initial diagnosis without critical Type 2 analysis [2,6]. To counter this, AI must incorporate the same cognitive forcing strategies used by human interpreters, demanding metacognition ("thinking about thinking") to identify susceptibility to bias [3,4]. Furthermore, AI must specifically address the Hindsight Bias that plagues retrospective quality review [2,6], by ensuring its decision pathways are fully auditable and transparent, allowing for objective assessment of whether an error resulted from inherent data contamination or algorithmic failure. As AI integrates deeper into clinical workflows, its ability to enhance safety hinges on proactively resisting the transfer and propagation of predictable human cognitive limitations [6]. References 1. Merchant SA, Merchant N, Varghese SL, Shaikh MJS. Large language models and large concept models in radiology: Present challenges, future directions, and critical perspectives. World J Radiol. 2025;17(11):114754. [DOI: 10.4329/wjr.v17.i11.114754] 2. Onder O, Yarasir Y, Azizova A, Durhan G, Onur MR, Ariyurek OM. Errors, discrepancies and underlying bias in radiology with case examples: a pictorial review. Insights Imaging. 2021;12:51. [PMID: 33877458. DOI: 10.1186/s13244-021-00986-8] 3. Chen J, Gandomkar Z, Reed WM. Investigating the impact of cognitive biases in radiologists' image interpretation: A scoping review. Eur J Radiol. 2023;166:111013. [PMID: 37541180. DOI: 10.1016/j.ejrad.2023.111013] 4. Busby LP, Courtier JL, Glastonbury CM. Bias in Radiology: The How and Why of Misses and Misinterpretations. Radiographics. 2018;38:236–247. [PMID: 29194009. DOI: 10.1148/rg.2018170107] 5. Gunderman RB. Biases in radiologic reasoning. AJR Am J Roentgenol. 2009;192:561–564. [PMID: 19234247. DOI: 10.2214/AJR.08.1220] 6. Yoon SY, Lee KS, Bezuidenhout AF, Kruskal JB. Spectrum of Cognitive Biases in Diagnostic Radiology. Radiographics. 2024;44:e230059. [PMID: 38843094. DOI: 10.1148/rg.230059] " 
Merchant SA, Merchant N, Varghese SL, Shaikh MJS. Large language models and large concept models in radiology: Present challenges, future directions, and critical perspectives. World J Radiol 2025; 17(11): 114754 [PMID: 41356761 DOI: 10.4329/wjr.v17.i11.114754]
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"The authors present a clinically important case highlighting the coexistence of mixed connective tissue disease (MCTD) and tuberculosis (TB), a scenario that poses substantial diagnostic challenges in TB-endemic regions. The manuscript is well structured and clearly describes the sequence of clinical events, laboratory workup, and therapeutic decisions. The discussion appropriately emphasizes the overlap between autoimmune manifestations and infectious etiologies, particularly when both present with pulmonary involvement. From an academic standpoint, the case is relevant and contributes meaningfully to the limited global literature examining MCTD–TB coexistence. The authors successfully integrate immunological findings with epidemiological considerations, underscoring the need for high clinical suspicion and comprehensive autoimmune evaluation in complex presentations. The reference list is current and well selected, drawing from both rheumatology and infectious disease literature. The language is generally clear and understandable, although a few sections may benefit from stylistic tightening to improve flow, particularly in the discussion where multiple concepts are presented in close succession. Minor grammatical refinements could enhance readability. The inclusion of comprehensive tables and immunological profiles strengthens the diagnostic clarity of the case. For future research and case documentation, the authors may consider: 1. Providing a more detailed longitudinal follow-up, especially regarding TB status, autoimmune markers, and treatment tapering, as long-term outcomes for MCTD-TB coexistence are not well described in the literature. 2. Elaborating on radiologic findings, given the central role of imaging in differentiating pulmonary TB from autoimmune lung involvement. 3. Discussing possible immunopathological links between chronic infections and autoimmune flare, which could enrich the mechanistic understanding of such overlap syndromes. 4. Addressing medication safety monitoring, particularly concerning hepatotoxicity in the context of ATT combined with corticosteroids and hydroxychloroquine. Overall, this is a valuable clinical contribution that highlights key diagnostic considerations in resource-limited, TB-endemic settings. The manuscript is academically sound, clinically relevant, and will be informative for physicians managing complex autoimmune presentations. " 
Sial F, Basit A, Ghafoor N, Sial W, Basil AM. Mixed connective tissue disease and tuberculosis coexistence as a diagnostic dilemma: A case report. World J Clin Cases 2025; 13(33): 109866 [PMID: 41356082 DOI: 10.12998/wjcc.v13.i33.109866]
13
"The review by Nian et al. offers a thorough and thoughtfully articulated overview of current insights into Osteopontin (OPN)–mediated PI3K/AKT signaling and its pivotal influence on gastrointestinal cancer progression, metastatic behavior, and therapeutic resistance. The authors skillfully synthesize mechanistic and translational findings, underscoring how OPN-driven activation of the PI3K/AKT pathway promotes epithelial–mesenchymal transition, metabolic adaptation, immune escape, and chemoresistance. Their discussion of OPN splice variants, tumor microenvironment interactions, and biomarker-informed therapeutic strategies provides meaningful guidance for advancing precision oncology. A major strength of the review is its emphasis on the inherent complexity and compensatory nature of OPN–PI3K/AKT signaling, which helps explain the challenges associated with single-agent therapeutic approaches. The recommendation to pursue combination strategies—such as pairing PI3K/AKT inhibitors with immune checkpoint blockade or OPN-targeted antibodies—is timely and supported by accumulating preclinical data. Furthermore, the manuscript’s focus on PIK3CA mutation subsets and OPN expression as potential predictive biomarkers may enable more refined patient stratification in future clinical trials. Despite these promising avenues, clinical translation remains constrained. Current trials evaluating PI3K/AKT inhibitors in gastrointestinal malignancies have yielded limited efficacy and notable toxicity, highlighting the need for more rigorous biomarker-driven study designs. Although the review acknowledges these issues, a deeper appraisal of the reasons underlying clinical shortcomings—and the specific contribution of OPN signaling to these obstacles—would further strengthen its clinical impact. In sum, this review provides a valuable contribution by elucidating the diverse oncogenic roles of OPN and outlining strategic paths toward overcoming therapeutic resistance. Continued research into isoform-specific activity, tumor microenvironmental dynamics, and rational combinatorial regimens will be crucial for realizing the therapeutic potential of targeting the OPN–PI3K/AKT axis in gastrointestinal cancers." 
Nian H, Bai Y, Wang HY, Yu H, Zhang ZL, Shi RH, Zhang S, Wu YB, Zhou DH, Du QC. Targeting the Osteopontin-regulated PI3K/AKT signaling pathway: A molecular approach to overcome drug resistance and metastasis in gastrointestinal tumors. World J Gastrointest Oncol 2025; 17(11): 109923 [PMID: 41281471 DOI: 10.4251/wjgo.v17.i11.109923]
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"This article presents an interesting retrospective study involving a substantial cohort of patients, highlighting the role of total neoadjuvant therapy (TNT), specifically the RAPIDO protocol, compared to conventional long-course chemoradiotherapy (LCCRT) in the management of locally advanced rectal cancer (LARC). The study focuses on early surgical outcomes, a topic of significant clinical relevance. The cornerstone of LARC treatment remains optimal surgical resection via total mesorectal excision (TME). To reduce locoregional failure, preoperative concurrent chemoradiotherapy has long been the standard of care. However, as noted in the article and supported by prior evidence (e.g., Fokas et al.), the efficacy of this approach is primarily confined to local control, while distant metastases continue to be a major cause of treatment failure and compromised survival. The intensification of neoadjuvant therapy through TNT addresses this limitation by achieving early systemic control, significant tumor downstaging, and higher rates of pathological complete response, all without compromising early surgical outcomes compared to LCCRT, as demonstrated in this study. Moreover, the authors report that TNT is associated with a shorter total stoma duration and a lower permanent stoma rate, which are meaningful benefits for patients' quality of life. Recent landmark trials, such as RAPIDO and PRODIGE 23, have provided robust evidence supporting the use of TNT, showing improved pathological complete response, better treatment compliance, and reduced distant metastases compared to LCCRT. This study adds valuable real-world data to the growing body of literature affirming the safety and feasibility of TNT from a surgical perspective. We commend the authors for their contribution and agree that further prospective studies with longer follow-up are warranted to evaluate long-term oncological outcomes. (By Prof Sanaa El Majjaoui and Pr Nabil Ismaili)" 
Jabbar SAA, Choo ALE, Wong NW, Ngu JCY, Teo NZ. Comparing early surgical outcomes between total neoadjuvant therapy and standard long course chemoradiotherapy for rectal cancer. World J Gastrointest Oncol 2025; 17(11): 111250 [PMID: 41281487 DOI: 10.4251/wjgo.v17.i11.111250]
15
"This minireview describes the important role of 0steopontin (OPN)-regulated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in gastrointestinal tumor proliferation, metastasis, chemoresistance, and immune evasion. Targeting osteopontin-regulated PI3K/AKT signaling pathway with PI3K/AKT inhibitors or OPN neutralizing antibodies may reverse drug resistance and suppress metastasis. Further research should be needed to find combination therapies which have the potential to provide more effective anti-tumor activity towards refractory cancers." 
Nian H, Bai Y, Wang HY, Yu H, Zhang ZL, Shi RH, Zhang S, Wu YB, Zhou DH, Du QC. Targeting the Osteopontin-regulated PI3K/AKT signaling pathway: A molecular approach to overcome drug resistance and metastasis in gastrointestinal tumors. World J Gastrointest Oncol 2025; 17(11): 109923 [PMID: 41281471 DOI: 10.4251/wjgo.v17.i11.109923]
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"I want to congratulate the authors for conducting this excellent study on the impact of PAD in PEP. This study has demonstrated that PAD, particularly Type B, has a Significant risk of PEP. This subgroup analysis of PAD is important for advancing efforts to prevent PEP. This study included predominantly older patients, where the prevalence of PAD is higher. Whether the presence of only PAD increases the risk of pancreatitis is still difficult to interpret. As PAD increases the difficulty of CBD cannulation, requiring advanced cannulation techniques which itself may increase the risk of PEP, furthermore indication of ERCP is also analysed in both groups " 
Shu J, Liao YS, Zhang YJ, Zhou WL, Zhang H. Impact of periampullary diverticulum on the incidence of post-endoscopic retrograde cholangiography pancreatitis. World J Gastrointest Endosc 2025; 17(11): 111243 [PMID: 41256294 DOI: 10.4253/wjge.v17.i11.111243]
17
"The study by Li Lin et al., “Early vs conventional initiation of adjuvant chemotherapy in advanced gastric cancer: A propensity-matched outcomes study,” addresses a clinically relevant question; however, several issues limit the strength and applicability of its conclusions. First, the analysis does not demonstrate any clear advantage of early versus conventional initiation of adjuvant chemotherapy in terms of either overall survival or disease-free survival. A possible benefit is suggested with respect to the rate of peritoneal recurrence, but this signal is difficult to interpret in the absence of any comparison with currently available intraperitoneal treatment strategies. Moreover, the study does not provide robust selection criteria to clearly identify which patients might be optimal candidates for an earlier initiation of adjuvant therapy. Given the well-known short-term physiological impact of gastrectomy, there is a concrete risk that patients starting chemotherapy very early after surgery may actually receive a suboptimal treatment—most notably through dose reductions—precisely in the first cycles, when dose intensity may be most critical. Finally, the heterogeneity of the adjuvant chemotherapy regimens, which persists even after propensity score matching, further complicates interpretation of the results and limits the ability to draw firm conclusions regarding the true effect of treatment timing per se. " 
Lin L, Zhang P, Wang YY, Cai YF, Wen LB, Chen WP, Xiao YF, Li ZK, Liu GY. Early vs conventional initiation of adjuvant chemotherapy in advanced gastric cancer: A propensity-matched outcomes study. World J Gastroenterol 2025; 31(42): 110069 [PMID: 41278157 DOI: 10.3748/wjg.v31.i42.110069]
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"Long-term prognosis of HBV-cirrhosis hepatocellular carcinoma recurrence and mortality rates post-treatment with antivirals TDF, TAF, ETV and curative radiofrequency ablation is still controversial Dina Johar* Department of Biochemistry and Nutrition, Faculty of Women for Arts, Sciences and Education, Ain Shams University, Heliopolis, Cairo, Egypt *Dina Johar, PhD Department of Biochemistry and Nutrition Faculty of Women for Arts, Sciences, and Education Ain Shams University, Cairo, Egypt Phone:+2 01060782045 Email: dinajohar@gu.edu.eg • To whom correspondence should be addressed Abstract The efficiency of antiviral agents for hepatitis B cirrhosis-related hepatocellular carcinoma (HCC) is still an important clinical challenge with high recurrence rates. In this commentary, we focus on recent findings from Xu et al. We highlight the potential benefit of studying HBV genotypes and subgenotypes as possible mechanisms behind different responses to antivirals. Mechanisms of viral reactivation that parallel HCC recurrence remain uncovered. The commentary is a significant step forward in understanding the nuanced approach to managing HCC recurrence and mortality rate in HBV-cirrhosis patients, offering valuable insights for clinical decision-making. Keywords HBV-related HCC, TDF, TAF, ETV, recurrence, mortality Core Tip A similar virological response to TDF, TAF, and ETV treatment in the first 6-12 months may require further investigation to understand early treatment dynamics. Understanding how HBV genotypes and subgenotypes influence chronic active HBV infection is crucial. Investigating potential molecular mechanisms that explain recurrence rate differences helps develop predictive models for individualized treatment selection. Background The paper entitled “Effect of antiviral therapy on 3-year recurrence and prognosis of hepatocellular carcinoma after curative radiofrequency ablation” by Xu et al. (1) is a robust retrospective cohort study that comprehensively evaluates long-term prognostic effects of advanced nucleos(t)ide analogs (NAs): ETV, TDF, and TAF on HBV-cirrhosis HCC patients post-RFA outcomes. The study identified four independent predictors of post-RFA HCC recurrence. The study findings recommend TDF or TAF as preferred antiviral agents for the long-term management of such patients. The three antiviral agents had a similar impact on the three-year mortality rate. The study used a substantial sample size (n=319) with a follow-up period of 144 weeks, across multiple time points (6, 12, 24, 36 months), although the sample sizes in the TDF (n=76) and TAF (n=52) groups are relatively small. Two of the major determinants of the outcome of chronic HBV infection are the HBV genotypes and subgenotypes. While Xu et al. adhered to established diagnostic guidelines, there are at least ten different confirmed HBV genotypes (A-J). There is limited knowledge about how different genotypes and subgenotypes of HBV affect the risk of HCC recurrence in patients with HBV-cirrhosis related HCC. The best way to find out is through long-term, population-based studies. These studies should compare people with different genotypes and follow them over time. For example, there is a substantial homogeneity of HBV subtypes found in Egypt, a country with a comparably high HBV-cirrhosis-related HCC, mostly genotype D, subgenotype D3, hepatitis B surface antigen (HBsAg) subtype ayw2, with a prevalence of the Major Hydrophilic Region (MHR) mutations (2). Genotype D is related to more advanced liver disease, i.e., HCC, than other genotypes (3) and is an independent risk for Fulminant Hepatitis (FH) (4). Whether new classes of drugs are needed to manage chronic HBV, whether a cure is possible, or even necessary, has not been addressed. The goal of new therapies for chronic hepatitis B should be to achieve a virological cure. Current NAs can slow down HBV replication and help improve liver damage. However, they rarely fully clear chronic HBV infections. There is an urgent need for new drugs and more effective strategies to combat the virus, which eventually will help get rid of the cancer. Still, more research is needed to find clear links between specific genotypes and risks like cirrhosis or HCC. Some research has been carried out in areas such as Asia and Alaska, but many genotypes, including A1 and D, have not been studied in long-term, prospective research. Data is missing for some genotypes and subgenotypes, such as A3, E, F4, and H, regarding their impact on health. Collaboration between multiple institutions from different countries enhances the strength of these studies. Retrospective and prospective studies examined serum HBV DNA levels, liver function, complication rates, and hospital stay duration (5, 6). A study looked at whether high-dose TDF therapy can stop HBV-related HCC recurrence. They designed a study where everyone received the same treatment, with no comparison group. The goal was to determine if using high-dose TDF is practical in real-world settings. They enrolled 10 patients in September 2015 and monitored their progress for three months or until they had to discontinue treatment early. They found that high doses of TDF, up to five times the recommended amount, are poorly tolerated by many patients. These doses also do not effectively stop HBV from replicating as HCC progresses (7). In 2018, a study looked at 607 patients with HBV-related HCC who had surgery or RFA. They divided them into three groups based on their antiviral drugs. The first group, with 261 patients, did not get antiviral treatment. The second group, with 90 patients, received low-strength NAs. The last group, with 256 patients, was treated with high-strength NAs. The main goal was to see how long patients stayed free of cancer recurrence. Patients on ETV and TDF had fewer recurrences than those on other antivirals (8). Another study followed 1,695 patients who had surgery for HBV-related HCC at Korea’s Barcelona Clinic Liver Cancer stage 0 or A between 2010 and 2018. Of these, 813 patients received ETV while 882 took TDF. The study compared cancer recurrence and overall survival between the two groups, using statistical methods to match patients’ backgrounds and adjust for other confounding factors. The analysis started from the day of their liver surgery. Results showed that patients on TDF had a notably lower chance of their HCC recurrence and survived longer overall than those on ETV (9). Between 2013 and 2017, three hospitals enrolled patients with HBV-related HCC who had surgery or ablation as their first treatment. A 421 patients had part of their liver removed, and 305 received RFA. All of these patients started antiviral medication using either ETV or TDF. The study examined HCC recurrence and mortality rates. Researchers adjusted for factors such as HBV DNA levels, tumour characteristics, and patient demographics. The results showed no significant difference in cancer recurrence or death rates between patients treated with ETV and TDF (10). Patients with HCC who go beyond the Milan criteria tend to have a high chance of HCC recurrence post-surgery. When comparing treatments, TDF significantly reduces the risk of HCC recurrence more than ETV therapy (11). Using propensity score matching from the date of liver resection for HCC, TDF showed better overall survival. It also offered stronger protection of liver function. However, in another study, there was no difference in the rate of HCC recurrence between TDF and ETV treatments (12). Other research shows that TDF works better than ETV for eliminating hepatitis B symptoms after RFA treatment. It helps reduce serum HBV DNA levels and improves the albumin-bilirubin (ALBI) grade more effectively (13) (14). A study in 2024 looked at how TDF and ETV affect long-term health in patients with HCC, fatty liver disease, and HBV. The researchers analyzed patient data using a multivariate Cox proportional hazards model and applied a propensity score matching method. They then compared survival outcomes with Kaplan-Meier survival curves. The results showed that TDF helped improve long-term prognosis for patients (15). The latter discovery was confirmed in 2025 in patients with high HBsAg levels after they had their liver removed (16). A study looked back over ten years, finishing in 2025. It included 1,396 patients with HBV-related cirrhotic HCC who had surgery. The patients were divided into two groups: those who took antiviral medicine and those who did not. The research focused on HCC recurrence, taking into account when the antiviral treatment was started, how well the virus was kept under control, and the levels of HBV DNA. Recurrences were labelled as early if they occurred within two years and late if they occurred after that. The study found that long-term antiviral therapy helped prevent late recurrence after surgery, regardless of whether it was started pre- or post-operation. Patients who responded well to the virus treatment saw the biggest benefit (17). Given such controversial results, in Xu et al. study, being a single-center study, there is potential for selection bias inherent in the retrospective study design. The uneven baseline characteristics across treatment groups, potential need for larger sample size to validate findings, and limited exploration of potential mechanisms are behind the differential recurrence rates achieved with TDF, TAF versus ETV, or even behind the similar impact that the three NAs had on the three-year mortality rate. The study will benefit from extending the follow-up period to provide more comprehensive long-term insights. Considering propensity score matching to reduce potential selection bias. Expanding the research scope through multi-center collaborative study enhances external validity and generalizability. Exploring potential interaction effects between NAs and the molecular mechanisms underlying the differential efficacy of TDF and TAF is insightful. Including more diverse patient populations enhances analytical approach, provides a nuanced understanding of anti-HBV agent effectiveness and contributes to a personalized medicine approach in hepatology. Including sensitivity analyses helps validate findings. Declarations Funding This commentary did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The author declare that no honorarium, grant, or other form of payment was given to anyone to produce the manuscript. Conflict of interest The author declares no conflict of interest exists. Consent to publish Not applicable. Availability of data and materials All data generated or analyzed during this study are included in this published article. Acknowledgment N/A References 1. Xu B, Zhang X, Liu F, Li F, Zhang X, Xiang H, et al. Effect of antiviral therapy on 3-year recurrence and prognosis of hepatocellular carcinoma after curative radiofrequency ablation. World J Gastrointest Oncol 2025;17: 112689. 2. Abu Zeid WA RD, Shemis MA,. Prevalence of mutations within major hydrophilic region of hepatitis B virus and their correlation with genotypes among chronically infected patients in Egypt. Arab Journal of Gastroenterology 2016 17 (2016) 34–40. 3. Thakur V, Guptan RC, Kazim SN, Malhotra V, SK. S. Profile, spectrum and significance of HBV genotypes in chronic liver disease patients in the Indian subcontinent. . J Gastroenterol Hepatol. 2002;17:165-70. 4. Wai CT, Fontana RJ, Polson J, Hussain M, Shakil AO, Han SH, et al. US Acute Liver Failure Study Group. Clinical outcome and virological characteristics of hepatitis B-related acute liver failure in the United States. J Viral Hepat. 2005 12:192-8. 5. Yuan B, Li R, Yuan W, Xiang B, Zheng M, Yang T, et al. Perioperative entecavir for patients with HBV-related hepatocellular carcinoma and low levels of viral DNA: analysis using propensity score matching. Oncotarget. 2017 16(31):51810-6. 6. Yoo S, Jang J, Kwon J, Jung S, Jang B, Choi J. Preemptive antiviral therapy with entecavir can reduce acute deterioration of hepatic function following transarterial chemoembolization. . Clin Mol Hepatol. 2016 22:458-65. 7. Hwang S, Song G, Jung D, Yoon Y, Yoo H, Tak E. High-dose tenofovir is not effective in suppressing hepatitis B virus replication in patients with hepatocellular carcinoma progression: a preliminary result. Korean J Hepatobiliary Pancreat Surg.2016(1). 8. Cho H, Ahn H, Lee DH, Lee JH, Jung YJ, Chang Y, et al. Entecavir and tenofovir reduce hepatitis B virus-related hepatocellular carcinoma recurrence more effectively than other antivirals. . Journal of viral hepatitis. 2018;25:707–17. 9. Choi J, Jo C, Lim YS. Tenofovir Versus Entecavir on Recurrence of Hepatitis B Virus-Related Hepatocellular Carcinoma After Surgical Resection. Hepatology (Baltimore, Md). 2021 73(661–673). 10. Lee JH, Kim BK, Park SY, Tak WY, Park JY, Kim DY, et al. The efficacies of entecavir and tenofovir in terms of enhancing prognosis after curative treatment of hepatitis B virus-related hepatocellular carcinoma. . Eur J Intern Med.2021:48-55. 11. Shen J, Qi W, Dai J, Leng S, Jiang K, Zhang Y, et al. Tenofovir vs. entecavir on recurrence of hepatitis B virus-related hepatocellular carcinoma beyond Milan criteria after hepatectomy. . Chinese medical journal. 2021;135:301–8. 12. Wang XH, Hu ZL, Fu YZ, Hou JY, Li WX, Zhang YJ, et al. Tenofovir vs. entecavir on prognosis of hepatitis B virus-related hepatocellular carcinoma after curative resection. . Journal of gastroenterology. 2022;57:185–98. 13. Hu Z, Zeng H, Hou J, Wang J, Xu L, Zhang Y, et al. Tenofovir vs. Entecavir on Outcomes of Hepatitis B Virus-Related Hepatocellular Carcinoma after Radiofrequency Ablation. Viruses. 2022;14(656). 14. Giri S, Agrawal D, Afzalpurkar S, Gopan A, Angadi S, Sundaram S. Tenofovir versus entecavir for tertiary prevention of hepatocellular carcinoma in chronic hepatitis B infection after curative therapy: A systematic review and meta-analysis. . Journal of viral hepatitis. 2023;30:108–15. 15. Kong Q GQ, Li W, Chen Z. Effect of tenofovir versus entecavir on the long-term prognosis in hepatocellular carcinoma patients with concurrent metabolic dysfunction-associated steatotic liver disease and hepatitis B. Asian J Surg. 2024 Nov;47(11):4725-4734. doi: 10.1016/j.asjsur.2024.03.147. Epub 2024 Sep 16. PMID: 39289060. 16. Qiu Z XY, Qi W, Shen J, Wen T, Li C. Tenofovir vs Entecavir on the Prognosis of Patients With Hepatitis B Virus-Related Hepatocellular Carcinoma After Liver Resection: The Role of HBsAg Levels. Clin Transl Gastroenterol. 2025 Mar 1;16(3):e00814. doi: 10.14309/ctg.0000000000000814. PMID: 39791573; PMCID: PMC11932590. 17. Liu J BS, Shi X, Yuan T, Yu Y, Lin J, Dai C, Wu Y, Cui L, Zhu B, Fu X, Wang K, Yu W, Li J. Benefits of entecavir therapy in HBV-related hepatocellular carcinoma patients with compensated cirrhosis after hepatectomy: A ten-year retrospective cohort study. Eur J Surg Oncol. 2025 May;51(5):109621. doi: 10.1016/j.ejso.2025.109621. Epub 2025 Jan 23. PMID: 39919509. " 
Xu BG, Zhang X, Liu F, Li FH, Zhang X, Xiang HL, Liang J. Effect of antiviral therapy on 3-year recurrence and prognosis of hepatocellular carcinoma after curative radiofrequency ablation. World J Gastrointest Oncol 2025; 17(11): 112689 [PMID: 41281477 DOI: 10.4251/wjgo.v17.i11.112689]
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"This study has provided a combined method including ultrasound and endoscopic examination to present the clinical features of pancreatic cancer in patients with old age. The lifestyles of these patients can be analyzed to perform the potential relationship in the prognosis of pancreatic cancer. In addition, the important features in malignant level as this study displayed may be summarized by author's efforts to indicate significantly and meaningfully in the prognosis of pancreatic cancer in patients. " 
Zignani N, Balzarini M, Dabizzi E, Fracas E, Millefanti L, Segato S, Vecchi M, Cengia G, Missale G, Tontini GE, Moneghini D, Cavallaro F. Endoscopic ultrasound features of pancreatic solid lesions: Descriptive and predictive analysis on a multicenter sample. World J Gastrointest Endosc 2025; 17(11): 112487 [PMID: 41256295 DOI: 10.4253/wjge.v17.i11.112487]
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"The comprehensive review by Professor Elsayed offers a timely and insightful overview of a critical clinical challenge: the management of recurrent hepatocellular carcinoma (RHCC). As a clinician actively managing HCC patients, I find this synthesis of evidence exceptionally valuable. RHCC indeed lacks standardized guidance, and this review effectively consolidates fragmented data across surgical, locoregional, and systemic modalities, offering pragmatic approaches tailored to recurrence patterns (intrahepatic vs. extrahepatic), liver functional reserve, and prior interventions. RHCC complexity demands collaboration between hepatologists, surgeons, interventional radiologists, and oncologists—highlighted here as essential for optimizing outcomes. The candid discussion on limitations—such as the reduced functional liver remnant post-resection/transplant, donor shortages for salvage LT (SLT), and the aggressive biology of RHCC—grounds the review in clinical reality. Coverage of emerging strategies—like combination therapies (TACE + sorafenib), novel ICIs (e.g., atezolizumab/bevacizumab), and AI-driven recurrence prediction—provides hope and direction for ongoing research. While ther are some points for further discussion. In practice, SLT candidates often face adverse factors (e.g., time to recurrence <1 year, vascular invasion), potentially skewing survival. Could risk-stratified SLT criteria enhance patient selection? The review notes mixed evidence comparing TACE/RFA with surgical re-resection. Further emphasis on tumor-specific factors (e.g., size ≤3 cm, subcapsular location) could clarify which patients benefit most from minimally invasive options versus surgery. The brief mention of TKIs (sorafenib/lenvatinib) and ICIs for RHCC post-LT warrants caution. Safety data on immune checkpoint inhibitors in transplant recipients (graft rejection risk) remains limited. How might immunosuppression regimens be optimized alongside systemic therapy? Overall, this review masterfully navigates the evolving landscape of RHCC management. The proposed treatment algorithm—rooted in individualized patient assessment—will serve as a vital reference. There is an urgent need for prospective randomized trials validating combination regimens and SLT protocols. As AI algorithms mature, their integration into recurrence surveillance and prediction models could revolutionize early intervention strategies." 
Elsayed MOK. Treatment of recurrent hepatocellular carcinoma: The current standards and future perspectives. World J Gastrointest Oncol 2025; 17(11): 110735 [PMID: 41281491 DOI: 10.4251/wjgo.v17.i11.110735]
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"The study provides strong evidence that circulating GDF15 levels are elevated in IBD patients, with a clear correlation to markers of inflammation and intestinal permeability. This relationship could offer a new avenue for monitoring disease progression and assessing the severity of IBD. The results showing that GDF15 impacts the intestinal barrier function by modulating tight junctions such as ZO-1 and claudin 1 are especially intriguing. From a clinical standpoint, understanding how GDF15 contributes to barrier dysfunction could lead to new therapeutic targets aimed at preventing the "leaky gut" phenomenon, which is a key feature in IBD. One of the most interesting aspects is the suggestion that GDF15 could be a potential biomarker for intestinal permeability, which could be valuable in both clinical diagnosis and disease monitoring. However, as a clinician, I’d like to see more clarity on how these findings might translate into practical treatment strategies. For instance, how could we use this information to develop therapies targeting GDF15 or its signaling pathways in patients with IBD? Additionally, while the in vitro findings are compelling, clinical trials will be essential to confirm whether modulating GDF15 can indeed improve clinical outcomes for IBD patients." 
Ruiz-Malagón AJ, Herraiz-Vilela M, Serrano-Pino R, García-Ávila P, Díaz-Suárez L, Carmona-Segovia AD, Becerra-Munoz VM, Jiménez-Navarro M, Arranz-Salas I, López-Villodres JA, Fernández-Castañer A, Gutiérrez-Martínez F, Rodríguez-González FJ, Camargo-Camero R, Alcaín-Martínez G, Rodríguez-Díaz C, García-Fuentes E, Sánchez-Quintero MJ, López-Gómez C. Growth differentiation factor 15 alters intestinal barrier and increases permeability: A new molecular target in inflammatory bowel disease. World J Gastroenterol 2025; 31(41): 110955 [PMID: 41257277 DOI: 10.3748/wjg.v31.i41.110955]
22
"As a clinician, I found this study highly relevant and practical. The use of VCTE to assess liver fibrosis in PBC patients offers a non-invasive, reliable alternative to liver biopsies, which is a huge advantage in daily practice. The dual cut-off approach for diagnosing advanced fibrosis seems useful, providing clear thresholds that can guide treatment decisions without the need for invasive procedures. However, the grey area (10-14.5 kPa) remains a challenge, and it would be helpful to have additional tools or markers for better decision-making in these cases. Overall, this study offers a valuable, non-invasive method for fibrosis assessment, but more research on managing patients in the grey zone would be beneficial." 
Chen JL, Hou YX, Liu Y, Jiang YY, Wang XB. Real-world performance of transient elastography in assessing advanced fibrosis in Chinese patients with primary biliary cholangitis. World J Gastroenterol 2025; 31(41): 111256 [PMID: 41257279 DOI: 10.3748/wjg.v31.i41.111256]
23
"Transient Elastography is an easy, bedside, non-invasive test for assessing liver fibrosis. PBC is a condition for which earlier diagnosis and treatment are associated with a better prognosis. So, evaluating Fibrosis has important diagnostic and therapeutic implications in PBC. However, studies on TE in PBC are limited to Asian settings, and the study by Jia-Liang Chen provides important data in this subset. In this retrospective study, they compared TE with the gold-standard findings of liver biopsy. They showed that TE is highly accurate for diagnosing Advanced fibrosis, and LSM has outperformed other fibrotic markers in ROC curves. Furthermore, they have classified patients with LSM into early, indeterminate, and late stages based on the LSM cut-off; these stages may have future prognostic significance. Future Prospective observational studies can be conducted to assess changes in LSM with treatment, disease progression, or complications. " 
Chen JL, Hou YX, Liu Y, Jiang YY, Wang XB. Real-world performance of transient elastography in assessing advanced fibrosis in Chinese patients with primary biliary cholangitis. World J Gastroenterol 2025; 31(41): 111256 [PMID: 41257279 DOI: 10.3748/wjg.v31.i41.111256]
24
"The authors presented a case of pancreatic tuberculosis and provided a detailed analysis of the diagnostic process, which holds significant reference value for the diagnosis of similar cases. However, the report lacks an in-depth discussion and evaluation of the treatment approach and therapeutic strategy employed in this case, thereby limiting its applicability in guiding clinical management of analogous conditions. Consequently, the inclusion of a comprehensive treatment plan would substantially enhance the clinical utility and overall contribution of this case report." 
Nima CL, Wang HG, Zhou Q. Pancreatic tuberculosis: A case report and review of literature. World J Gastroenterol 2025; 31(41): 110398 [PMID: 41257270 DOI: 10.3748/wjg.v31.i41.110398]
25
"This study has compared several computational methods to be used in the predication of prognosis for acute variceal bleeding in cirrhosis patients. Author claimed that the convolution network by their efforts displayed the best effect in the outcomes analysis rather than another methods. However, the specific features in different subgroups with data presentations using AI or other computational methods lacked in the full analysis to be performed in the compared computation process. This means that this study only provides the end result for supporting their analysis as they wanted. In addition, the standard between high and low risk group presented to differ significantly without clinical parameters in this study. " 
Xiang Y, Yang N, Zheng TL, Huang YF, Liu TY, Ma DQ, Hu SJ, Zhang WH, Xiang HL, Zhang LY, Yuan LL, Wang X, Dang T, Zhang G, Wu B, Peng LJ, Gao M, Xia DL, Liu ZB, Li J, Song Y, Zhou XQ, Qi XS, Zeng J, Tan XY, Deng MM, Fang HM, Qi SL, He S, He YF, Ye B, Wu W, Shao JB, Wei W, Hu JP, Yong X, He CH, Bao JL, Zhang YN, Ji R, Bo Y, Yan W, Li HJ, Li SL, Geng S, Zhao L, Liu B, Qi XL. Development of a deep learning model for guiding treatment decisions of acute variceal bleeding in patients with cirrhosis. World J Gastroenterol 2025; 31(41): 111361 [PMID: 41257275 DOI: 10.3748/wjg.v31.i41.111361]
26
"This article is a well-conducted clinical study that elucidates the psychological profiles of patients undergoing esophagectomy for esophageal cancer. Its core contributions lie in: 1. Demonstrating a significant negative correlation among anxiety, depression, and mindfulness, advancing understanding of the mind–body interaction in surgical oncology; 2. Identifying key demographic and clinical risk factors that shape postoperative emotional outcomes, thereby guiding individualized psychological assessment and intervention. By linking psychometric evaluation with perioperative management, this study offers a valuable reference for integrating mindfulness-based strategies into holistic recovery pathways. " 
Deng X, Hu YH, Xiong YJ, Mao N, Hong B, He G. Correlation of anxiety and depression with mindfulness in esophageal cancer patients undergoing esophagectomy and analysis of risk factors. World J Psychiatry 2025; 15(9): 104813 [PMID: 40933162 DOI: 10.5498/wjp.v15.i9.104813]
27
"The article is well-written and demonstrates a clear and logical flow from the introduction to the conclusion. The research objectives are clearly stated, and the study design appropriately addresses the research questions. The literature review is comprehensive and up to date, providing a strong theoretical foundation for the study. The methodology is well-described, enabling replication, and the data analysis is appropriate and rigorous. The discussion effectively interprets the findings in relation to existing studies, and the conclusions are supported by the results. Overall, this is a good-quality manuscript that makes a valuable contribution to the field. " 
Yanti L, Surtiningsih, Ardiyani FHN, Sekarini NNAD, Susanti D, Mustaan, Murniati, Supriyadi, Santosa A. Long-term consequences of unintended pregnancy: Impacts on early childhood growth and development in a multicenter study. World J Clin Pediatr 2025; 14(4): 107346 [PMID: 41255691 DOI: 10.5409/wjcp.v14.i4.107346]
28
"The retrospective study by Huang and colleagues provides valuable insights into the prevalence and clinicopathological significance of HER2 expression in upper tract urothelial carcinoma. Their finding that HER2 overexpression is strongly associated with high tumor grade but not with conventional markers of disease progression underscores the distinct biological behavior of UTUC compared to bladder cancer. This work is particularly relevant as it highlights a potential therapeutic target in a disease with limited treatment options. However, the clinical implications of HER2 expression in UTUC must now be reinterpreted in light of the practice changing results presented at the ESMO Congress 2025. The phase 3 RC48 C016 trial demonstrated for the first time that a combination of the anti HER2 antibody drug conjugate disitamab vedotin and the anti PD1 immunotherapy toripalimab significantly outperforms standard platinum based chemotherapy in the first line treatment of HER2 expressing locally advanced or metastatic urothelial carcinoma. The results are striking: Progression free survival was nearly doubled (13.1 months versus 6.5 months; HR = 0.36); Overall survival showed a remarkable improvement (31.5 months versus 16.9 months; HR = 0.54); Benefits were consistent across all HER2 expression levels (IHC 1+, 2+, and 3+); and The combination also exhibited a more favorable safety profile. These findings represent a paradigm shift. For the first time, a biomarker directed strategy has proven superior to chemotherapy in the first line setting for advanced UC. Given that HER2 expression is found in up to 70% of urothelial carcinomas, this new regimen could benefit a majority of patients. In this context, the work by Huang et al gains even greater importance. Their observation that nearly half of UTUC tumors (46.2%) show HER2 positivity especially in high grade disease suggests that a substantial proportion of UTUC patients may be candidates for this novel, highly effective combination therapy. The authors call for clinical trials evaluating HER2 targeted therapies in high grade, HER2 positive UTUC is now more urgent than ever. Future studies should urgently validate the efficacy of disitamab vedotin plus toripalimab in UTUC specific cohorts and explore its potential in earlier disease stages. The era of biomarker driven therapy for urothelial carcinoma has arrived, and HER2 is firmly at its center. Reference: Sheng X, He Z, Zhang G, et al. Primary results from the phase 3 RC48 C016 trial: Disitamab vedotin plus toripalimab versus chemotherapy as first line treatment for HER2 expressing locally advanced or metastatic urothelial carcinoma. Annals of Oncology 2025;36(Supplement 3):S1573 S1574." 
Huang L, He J. Human epidermal growth factor receptor 2 overexpression is associated with high-grade tumors in upper tract urothelial carcinoma. World J Clin Oncol 2025; 16(10): 110047 [PMID: 41178915 DOI: 10.5306/wjco.v16.i10.110047]
29
"This review on the gut-liver axis provides a highly insightful and comprehensive exploration of the evolving role of the microbiome in liver diseases. It successfully ties together mechanisms of microbiome dysbiosis with the pathogenesis of various hepatic conditions, including metabolic dysfunction-associated liver disease, cirrhosis, and cholangiopathies. The authors delve into how imbalances in gut microbiota disrupt bile acid metabolism, increase intestinal permeability, and promote inflammation, which in turn drives liver injury. The article's coverage of emerging treatment options, including bacteriophage therapy and genetic engineering of gut microbes, is particularly noteworthy, reflecting a growing understanding of the microbiome's potential as a therapeutic target. This forward-thinking approach adds substantial clinical relevance, making the article valuable for researchers and clinicians looking to integrate microbiome-based therapies into practice." 
Anis MA, Shahid Y, Majeed AA, Abid S. Microbiome and gut-liver interactions: From mechanisms to therapies. World J Gastroenterol 2025; 31(40): 111409 [PMID: 41180995 DOI: 10.3748/wjg.v31.i40.111409]
30
"This study offers a compelling and innovative exploration of colonoscopy quality, addressing the critical interplay between insertion time and withdrawal duration to optimize adenoma detection rate (ADR). The proposed "insertion-to-withdrawal" paradigm marks a significant departure from fixed withdrawal time standards, advocating for a personalized approach—a novel and practical advancement. The development of a Shiny app to deliver real-time, individualized guidance further enhances its clinical relevance, providing endoscopists with a valuable tool to improve outcomes. Several aspects warrant deeper consideration. First, the hybrid SVM-XGBoost model's modest discriminative performance (AUC ≈ 0.64) suggests limitations in its current predictive power, likely due to unaddressed variables such as bowel preparation nuances, insertion difficulty, or segment-specific inspection times. Expanding the dataset with multicenter inputs and incorporating these factors could refine its accuracy. Second, while insertion time serves as a proxy for procedural complexity, its validation against objective difficulty scales or video analysis would bolster the mechanistic basis of the findings. Third, the personalized strategy’s generalizability remains untested; prospective multicenter validation across diverse demographics, endoscopist expertise, and regions is essential. Finally, evaluating real-world app adoption and its impact on ADR adherence would provide critical evidence of its efficacy. Overall, this study lays a robust foundation for data-driven personalization in endoscopy, moving beyond uniform metrics. With further refinement and validation, it has the potential to transform clinical practice significantly." 
Xu BX, Xu CZ, Zhang HY, Chen XJ, Wei BN, Yang C. Personalizing withdrawal time by insertion time to achieve target adenoma detection rate in colonoscopy. World J Gastroenterol 2025; 31(38): 111364 [PMID: 41112006 DOI: 10.3748/wjg.v31.i38.111364]
31
"I want to congratulate Yang-Yang Xiong for publishing an excellent study comparing Endoscopic Clip or EUS Coil-assisted glue for gastric varices. The authors have shown that EUS-guided therapy is more costly and involves high operating time; however, it has similar technical eradication of gastric varices and re-bleeding rates even in larger varices > 4 cm. The size comparison may not be uniform, as the Endoscopic group measured by endoscopic appearance, which may be as accurate as EUS measurement. The Authors have shown only a 5-day rebleeding rate; adding delayed rates could have been more impactful. There is a discrepancy in the table and image regarding post-injection ulcer; the Image shows a post-glue ulcer in both groups, whereas in the table, it was zero; these typographical errors could have been avoided. The eradication time frame is not mentioned; whether it is immediately or 5 days, as the rebleeding rate or any other time frame is not clear. The Follow up endoscopy data is not given; if done even after CT showing eradication of varices or for other GI Bleeding, the time at which it was done was not mentioned, and the procedure done when eradication is not established is also not given. Despite these limitations the study has provided a meaning ful comparison and can change my practice " 
Xiong YY, Li DW, Zhou TY, Ma H, Gao JG, Shen Z, Xu CF, Yu CH. Clip-assisted endoscopic cyanoacrylate injection vs endoscopic ultrasound-guided coil and cyanoacrylate injection for gastric varices: A propensity score-matched study. World J Gastroenterol 2025; 31(38): 111363 [PMID: 41112012 DOI: 10.3748/wjg.v31.i38.111363]
32
"This article provides a timely and valuable overview of emerging therapeutic strategies for managing IBD. The integration of physical exercise and VNS as adjuncts to traditional pharmacological treatments is particularly relevant, as clinicians are increasingly seeking non-invasive and complementary approaches to help manage chronic inflammatory diseases. The article does an excellent job of explaining how these interventions may improve autonomic regulation, reduce inflammation, and promote gut health, which are all essential factors in managing the symptoms and progression of IBD. The focus on the vagus nerve’s role in regulating the immune system through the cholinergic anti-inflammatory pathway presents an interesting potential for VNS as a therapeutic tool. The idea that VNS could restore normal immune function, protect the intestinal barrier, and improve the composition of the gut microbiota is compelling, especially for patients who do not respond adequately to conventional treatments. This could open new avenues for clinical practice, offering patients a holistic approach to managing IBD. However, one of the challenges noted in the article is the variability in response to these non-pharmacological interventions. The review highlights how factors such as exercise intensity, duration, and individual patient factors can influence outcomes. This reflects a common issue in clinical practice, where personalized approaches are often required to determine the best intervention for a given patient. While the evidence for the benefits of physical exercise and VNS in IBD is promising, further studies are needed to establish standardized protocols and validate these therapies in diverse patient populations. The inclusion of vagotomy as a counterpoint to VNS and exercise also brings an important clinical consideration into focus. The article explains how vagotomy, by disrupting the vagal pathway, may exacerbate intestinal inflammation and worsen IBD symptoms. This serves as a reminder of the delicate balance between parasympathetic and sympathetic nervous system function and the potential risks of interfering with this balance in patients with chronic inflammatory conditions." 
da Silva ACA, Severo JS, dos Santos BLB, Soares HS, Martins JA, Lima RSP, Gadelha KKL, Torres-Leal FL, Correia-de-Sá P, Magalhães PJC, Santos AA, da Silva MTB. Role of physical exercise, vagal nerve stimulation, and vagotomy in inflammatory bowel disease. World J Gastroenterol 2025; 31(38): 111252 [PMID: 41112001 DOI: 10.3748/wjg.v31.i38.111252]
33
"This article offers a thorough and insightful overview of the transformative potential of multimodal AI in gastroenterology and hepatology. The application of AI across various clinical areas—from early diagnosis to precision treatment—holds great promise. However, the limitations in current AI models—such as lack of data standardization, poor model interpretability, and the need for large-scale, multi-center trials to validate findings—are all issues that would resonate with healthcare professionals. It is crucial for the clinical community to address these issues to ensure that AI technologies can be seamlessly integrated into practice without compromising patient safety or clinical outcomes." 
Wu YM, Tang FY, Qi ZX. Multimodal artificial intelligence technology in the precision diagnosis and treatment of gastroenterology and hepatology: Innovative applications and challenges. World J Gastroenterol 2025; 31(38): 109802 [PMID: 41112005 DOI: 10.3748/wjg.v31.i38.109802]
34
"Gestational diabetes (GD) is a complex disorder with metabolic, inflammatory, genetic, and fetoplacental unit display. The screening is based on oral glucose tolerance tests (OGTT) (one-step and two-step), OGTT is limited by low sensetivity. I addition, it is combersome test and the recommendations and cut-off varied significantly between International Organization. GD is common and is associated with poor maternal and fetal outcomes and the development of type 2 diabetes. The intergration of metabolic, inflammatory, genetic, urinary, and placental biomarkers is highly relevant for the personalized approach among various women. The article is of great interset worldwide, I am very thrilled to write and editorial on this interesting manuscript. Hyder Mirghani, Professor of Internal Medicine and Endocrine, University of Tabuk, Saudi Arabia " 
Kaymak D, Ozgu-Erdinc AS. Advances in gestational diabetes mellitus screening: Emerging trends and future directions. World J Diabetes 2025; 16(10): 111309 [PMID: 41113482 DOI: 10.4239/wjd.v16.i10.111309]
35
"Hu et al. (World J Gastroenterol. 2025;31:109528) presented a multicenter study evaluating image-guided thermal ablation (IGTA) for oligometastatic colorectal cancer (CRC) with lung involvement. Among 336 patients treated between 2014 and 2022, the 3- and 5-year overall survival rates were 59.5% and 41.0%, respectively, demonstrating meaningful long-term benefit. Extrapulmonary metastases, particularly in the bone and abdominal cavity, significantly worsened outcomes, whereas patients with liver-only metastases had comparatively favorable survival. Elevated tumor markers (CEA, CA19-9), greater tumor burden, and absence of systemic therapy were adverse prognostic factors. Notably, combining IGTA with systemic therapy improved overall survival. This study underscores IGTA as a viable, minimally invasive treatment for patients with oligometastatic CRC and highlights the prognostic relevance of metastatic distribution in guiding personalized therapy." 
Hu XF, Dong XJ, Gu XY, Hu JH, Li XH, Zhao FH, Xia XW, Fan HJ, Xu SF. Extrapulmonary metastases impact survival outcomes of thermal ablation for colorectal lung oligometastases: A multicenter study. World J Gastroenterol 2025; 31(38): 109528 [PMID: 41112004 DOI: 10.3748/wjg.v31.i38.109528]
36
"Hyperuricemia and high density lipoproteins are imprortant metabolic and inflammatory biomarkers, they are easy to obtain. In addition, they are among the cardiovascular risk factors (among other ) and are component of the metabolic syndrome. Depression and tpe 2 diabetes are common health disorders with significant burden on the patients, healthcare system, and the community. When the above diseases present together they exacerbate each other serious consequences. Assessing the uric acid-to-high-density lipoprotein cholesterol ratio in diabetes and psychological disease is highly relevant because they are attainable and the literature on these important parameters is scarce. Thank you very much for the invitation and I would like to publish a letter to the Editor on this interesting topic. " 
Xu H, He DJ, Luo C, Yu XM, Duan CZ, Sun D, Wu DJ, Mao XQ, Jiang WF. Association between uric acid to high-density lipoprotein ratio and mental health symptoms in people with type 2 diabetes. World J Diabetes 2025; 16(10): 110211 [PMID: 41113500 DOI: 10.4239/wjd.v16.i10.110211]
37
"Cong et al. deliver a thorough and insightful overview of stem cell–driven cartilage regeneration, addressing the interdisciplinary progress achieved across biomaterials, cellular therapies, and translational research. Their review integrates recent developments in scaffold engineering, stem cell selection, and in vivo regeneration strategies, making it a valuable guide for researchers in this developing field. However, a few key aspects require more in-depth discussion to fully analyse the field’s complexity and clinical translation. For instance, extracellular vesicles—emerging as central mediators of regenerative signaling—warrant more detailed explanation regarding their standardization and underlying mechanisms. Expanding coverage of these areas would improve the depth of the review and strengthen its guidance toward improving reproducibility, safety, and durability in hyaline cartilage repair strategies based on stem cells. Overall, this comprehensive review by Cong et al. highlights that stem cell-based cartilage regeneration is a rapidly advancing and highly promising field, successfully bridging biological strategies and innovative engineering to offer definitive clinical solutions for challenging joint and cartilage defects." 
Cong B, Zhang FH, Zhang HG. Stem cell-based cartilage regeneration: Biological strategies, engineering innovations, and clinical translation. World J Stem Cells 2025; 17(9): 108523 [PMID: 41025101 DOI: 10.4252/wjsc.v17.i9.108523]
38
"This manuscript is well-written and well-prepared. The previous history of adjuvant chemotherapy might have an impact on the oligometastatic disease, particularly in colorectal cancer patients.For the long-term follow-up, this current modality of treatment should be considered as one of the options in giving the multimodality treatment in this case. The methods is already clear." 
Hu XF, Dong XJ, Gu XY, Hu JH, Li XH, Zhao FH, Xia XW, Fan HJ, Xu SF. Extrapulmonary metastases impact survival outcomes of thermal ablation for colorectal lung oligometastases: A multicenter study. World J Gastroenterol 2025; 31(38): 109528 [PMID: 41112004 DOI: 10.3748/wjg.v31.i38.109528]
39
"This study explored that the method of thermal therapy displayed a beneficial role in the prognosis of oligometastatic colorectal lung metastases in patients. It should present the histology features including clinical tumor formation and CT images especially in the determination of different tumor size and outcomes under patients after treatment as author mentioned in this study. In addition, the numbers of distinct groups used for comparison performed a large difference in the statistical analysis. " 
Hu XF, Dong XJ, Gu XY, Hu JH, Li XH, Zhao FH, Xia XW, Fan HJ, Xu SF. Extrapulmonary metastases impact survival outcomes of thermal ablation for colorectal lung oligometastases: A multicenter study. World J Gastroenterol 2025; 31(38): 109528 [PMID: 41112004 DOI: 10.3748/wjg.v31.i38.109528]
40
"Recent research has uncovered fascinating insights into how a protein called FLOT1 drives liver cancer growth. Scientists found that FLOT1 disrupts normal cellular processes by triggering stress in the Golgi apparatus, essentially giving cancer cells the green light to grow and spread more aggressively. While these findings are exciting and point to FLOT1 as a promising target for new cancer treatments, we still need clinical trials to validate them in patients. Despite this limitation, the study represents a meaningful step forward in our understanding of liver cancer and how we might fight it more effectively in the future." 
Mazziotta C, Rotondo JC. Unraveling the role of flotillin-1 in driving hepatocellular carcinoma progression through transcription factor E3-mediated Golgi stress response. World J Gastroenterol 2025; 31(38): 112489 [PMID: 41112003 DOI: 10.3748/wjg.v31.i38.112489]
41
"Machine Learning in Surgical Decision-Making and Non-Surgical Treatment of Alveolar Echinococcosis Fengying liu,Yongfang Xie Introduce Alveolar Echinococcosis (AE) is a chronic, progressive liver disease caused by the ingestion of Echinococcus multilocularis larvae, with foxes and wild dogs as definitive hosts and rodents as intermediate hosts1. It typically centers in the liver, slowly spreading and metastasizing, with an incubation period lasting 5 to 15 years. Due to early non-specific symptoms such as fever and weight loss, patients are often difficult to diagnose in the early stages. In the later stages, continuous asexual reproduction of Echinococcus multilocularis and severe inflammatory granulomatous infiltration around the parasite lead to widespread fibrosis and necrosis. Without timely treatment, the mortality rate of patients can reach 90% within 10 years1. Currently, radical surgery combined with adjuvant chemotherapy is the only curative treatment method2. However, most patients are diagnosed at advanced stages, missing the optimal timing for liver resection. Ex vivo liver resection and liver autotransplantation (ELRA)3 offer hope for these patients, but traditional surgical decision-making often relies on the clinical experience of surgeons, which can be subjective and prone to bias. In recent years, machine learning has made significant progress in the medical field, especially in disease prediction, treatment selection, and clinical diagnosis, showing tremendous potential for development. By processing large amounts of clinical data, machine learning uncovers complex underlying relationships and assists doctors in making more accurate and objective decisions. Against this backdrop, I carefully reviewed the study published by Da-Long Zhu et al., and found that in the treatment of Alveolar Echinococcosis (HAE), machine learning not only aids in surgical decision-making but also provides valuable support for patients undergoing non-surgical treatments, driving the development of precision medicine4. 1.The Advantages and Challenges of Machine Learning in the Explainability of Surgical Decision-Making for HAE 1.1 Innovative Analysis of Machine Learning Da-Long Zhu et al. conducted a retrospective cohort study based on data from the First Affiliated Hospital of Xinjiang Medical University, including 710 patients, of whom 545 underwent liver resection and 165 underwent ex vivo liver resection and ELRA. The authors innovatively applied three feature selection techniques—recursive feature elimination, minimum redundancy maximum relevance, and LASSO regression—with cross-validation to enhance the model. Ultimately, they identified 10 key features from the extensive clinical data, including lesion size, vascular invasion type, bile duct invasion degree, white blood cell count, platelet count, hemoglobin, indirect bilirubin, serum creatinine, γ-glutamyl transferase, and prothrombin time. These features are closely related to the prognosis of HAE and provide important data support for surgical decision-making. Da-Long Zhu et al. systematically compared the performance and explainability of 11 machine learning models, ultimately selecting the XGBoost model and using Bayesian optimization for hyperparameter tuning.XGBoost5,as an efficient ensemble learning algorithm, demonstrates strong predictive ability in various classification and regression tasks. Model evaluation showed an AUC of 0.935 for the training set and 0.734 for the validation set, with a sensitivity of 93.6% and a specificity of 90.9%. Both the calibration curve and decision curve displayed good clinical utility, effectively predicting whether a patient is suitable for liver resection or ELRA. Furthermore, XGBoost, with its ensemble learning characteristics, reduces the risk of overfitting, providing a stable decision-making tool. To improve the interpretability of the model, Da-Long Zhu et al. employed the SHAP analysis method5 to explain the contribution of each feature to the prediction. Further analysis of the results revealed that vascular invasion type is a key factor in choosing ELRA, while indicators such as platelet count, prothrombin time, and hemoglobin reflect the patient's coagulation function, liver reserve, and inflammatory status. For instance, when significant invasion of the hepatic vein and inferior vena cava is present, the choice of ELRA is more likely, whereas for patients with no vascular invasion or only portal vein involvement, liver resection is preferred. Through SHAP analysis, the model's prediction process became more transparent, enhancing clinicians' trust in the model. 1.2 Limitations and Challenges of the Model It is commendable that Da-Long Zhu et al. accurately identified the clinical decision-making challenges in the surgical treatment of AE and achieved satisfactory results. However, the model still has some limitations. First, the sample size is relatively small, and the data comes from a single source, which may not fully represent patients from different regions or healthcare settings. Secondly, imaging examinations, such as CT scans, are an important tool for diagnosing HAE. However, the study did not conduct a deeper analysis and evaluation of the quantitative features extracted from imaging omics data, such as tumor morphology, texture, and other imaging features6. According to the research by Yener Aydin et al7, HAE often presents with characteristics such as pulmonary nodules, lesions, cavities, and metastatic tumors in imaging. In clinical practice, small solid nodules are easily confused with malignant tumors. Machine learning can help identify the differences and make accurate judgments. In addition to the XGBoost model used by Da-Long Zhu et al., other machine learning models also have their advantages in clinical prediction tasks. To facilitate the rational selection and comparison of models in this field, the following summary is provided (Table 1). Table 1 Model Advantages Limitations XGBoost8 Robust performance, accurate predictions, and comprehensive functionality, suitable for medium-sized data Slower training speed; risk of overfitting, requires regularization control LightGBM9 Extremely fast training speed, high memory efficiency, suitable for large-scale data Higher risk of overfitting on small datasets CatBoost10 Excellent handling of categorical features, high prediction accuracy, fast training speed, strong anti-overfitting ability Lower model flexibility TabNet11 Attention-based deep learning framework, high performance potential, built-in interpretability Requires large datasets and computational power Therefore, future research should focus on multi-center, large-sample validation to improve the external validity and generalizability of the model. Additionally, extracting quantitative features from imaging omics should be prioritized to enhance the clinical relevance and application value of the model. 2. The Prospects of Machine Learning in Non-Surgical Treatment of HAE 2.1 Current Non-Surgical Treatment Methods for HAE The non-surgical treatment of HAE relies on albendazole-based medications12, which interfere with microtubule formation by binding to β-tubulin, thereby impairing nutrient absorption and parasite growth. However, albendazole does not kill the parasite and has significant hepatotoxicity. Therefore, although the medication can improve patient survival rates, its effectiveness remains limited, especially for patients who cannot undergo surgery. In such cases, prevention and continuous monitoring become crucial treatment strategies. In addition to conventional drug therapy, the development of new drugs is also an important direction for non-surgical treatment. Mefloquine12 has shown certain advantages in terms of its anti-parasitic effect and lower hepatotoxicity.Furthermore, progress has been made in vaccine development, such as the recombinant Tetraspanin 3 vaccine13 , which induces strong local and systemic immune responses, effectively protecting humans from infections of Echinococcus multilocularis in the intestine, bloodstream, and liver. However, these studies have not yet undergone large-scale clinical trials and face challenges regarding individual variations in efficacy. 2.2 The Prospects of Machine Learning in HAE Non-Surgical Treatment Through Imaging and Multi-Omics Data Machine learning also shows great potential in the non-surgical treatment of HAE. By deeply analyzing patients' imaging features and multi-omics data, machine learning can provide precise analysis in early disease diagnosis, treatment processes, and prognosis assessment. Since early symptoms of HAE are often atypical, making early detection difficult, machine learning can significantly enhance the accuracy of early intervention, treatment effectiveness, and prognosis prediction through the deep analysis of imaging features and multi-omics data. CT scans and MRI images, as the most commonly used imaging tools, help doctors make judgments by analyzing features such as lesion size and shape. Machine learning can extract characteristics such as tumor morphology, size, density, and texture, allowing it to identify potential lesions even before clear clinical symptoms appear. By analyzing features like irregular tumor borders and vascular invasion, machine learning can alert clinicians to high-risk patients without obvious symptoms, assisting in decisions about whether to proceed with surgery or opt for non-surgical treatment. Additionally, features such as cavitation and cystic changes in imaging can reflect the prognosis of the disease. In conjunction with imaging data, integrated multi-omics analysis (Table 2) can also help identify early biomarkers for HAE. Machine learning can extract features from miRNA1,lncRNAs14, transcriptomics15 and metabolomics , revealing molecular-level changes in the liver of HAE patients. The significant expression of certain miRNAs in HAE, as well as changes in the expression of liver fibrosis-related genes and immune factors, not only aid in early diagnosis but also allow for the detection of treatment responses, helping clinicians assess treatment efficacy and adjust treatment plans (Table 3). Table 2 Application Methods/Techniques Imaging Features U-Net16,SVM Surgical Decision XGBoost,LightGBM,CatBoost Multi-Omics Data SNF17,DeepProg17,FM Table 3 Application Area Traditional Methods Machine Learning Diagnosis Relies on imaging examinations and subjective judgment Automatically extracts imaging features, improving diagnostic accuracy and reducing subjective bias Surgical Decision Relies on the experience and clinical judgment of surgeons Provides objective, data-driven decision support based on extensive clinical data Personalization Lacks personalization Analyzes multi-omics and imaging data to revise treatment plans Early Diagnosis Relies on clinical symptoms Combines imaging and omics data to identify potential lesions early Summary The study by Da-Long Zhu et al. applies machine learning to surgical decision-making in HAE, providing a more objective and accurate approach to disease treatment. By using various feature selection methods and the XGBoost model, the study successfully identified key features from a large amount of clinical data. The use of SHAP analysis enhanced the model's interpretability, increasing clinicians' trust in the machine learning model. These findings play a crucial role in surgical decision-making and provide strong data support for HAE treatment decisions. By combining imaging and multi-omics analysis, machine learning can play a significant role in both surgical and non-surgical treatment of HAE. However, current research still faces challenges, such as small sample sizes and single-source data, which affect the external validity and generalizability of the model. Additionally, there is still a lack of feature extraction and in-depth analysis of imaging omics and multi-omics data. Future research should focus on multi-center, large-sample validation to further improve the model's interpretability and clinical relevance. In conclusion, machine learning demonstrates enormous potential in the surgical and non-surgical treatment of HAE. In the future, it will provide data support and objective analysis for early diagnosis, treatment effectiveness evaluation, and long-term prognosis of HAE patients. Citation 1. Boubaker, G. et al. Regulation of hepatic microRNAs in response to early stage Echinococcus multilocularis egg infection in C57BL/6 mice. PLoS Negl Trop Dis 14, e0007640 (2020). 2. Liu, H. et al. Induced hepatocyte-like cells derived from adipose-derived stem cells alleviates liver injury in mice infected with Echinococcus Multilocularis. Sci Rep 14, 26296 (2024). 3. McManus, D. P., Gray, D. J., Zhang, W. & Yang, Y. Diagnosis, treatment, and management of echinococcosis. BMJ 344, (2012). 4. Tang, T. et al. Interpretable machine learning model for predicting post-hepatectomy liver failure in hepatocellular carcinoma. Sci Rep 15, 15469 (2025). 5. Liang, D. et al. Perspective: Global Burden of Iodine Deficiency: Insights and Projections to 2050 Using XGBoost and SHAP. Adv Nutr 16, 100384 (2025). 6. Wang, Z. et al. Multiclassification of Hepatic Cystic Echinococcosis by Using Multiple Kernel Learning Framework and Ultrasound Images. Ultrasound Med Biol 50, 1034–1044 (2024). 7. Aydin, Y. et al. Relevance of Pulmonary Alveolar Echinococcosis. Arch Bronconeumol (Engl Ed) 56, 779–783 (2020). 8. Ellmann, S. et al. Tumor grade-titude: XGBoost radiomics paves the way for RCC classification. Eur J Radiol 188, 112146 (2025). 9. Yanagawa, R. et al. LightGBM outperforms other machine learning techniques in predicting graft failure after liver transplantation: Creation of a predictive model through large-scale analysis. Clin Transplant 38, e15316 (2024). 10. Han, Y. et al. Early prediction of sepsis associated encephalopathy in elderly ICU patients using machine learning models: a retrospective study based on the MIMIC-IV database. Front Cell Infect Microbiol 15, 1545979 (2025). 11. Jin, Y. et al. Classification of Alzheimer’s disease using robust TabNet neural networks on genetic data. Math Biosci Eng 20, 8358–8374 (2023). 12. Rufener, R. et al. Activity of mefloquine and mefloquine derivatives against Echinococcus multilocularis. Int J Parasitol Drugs Drug Resist 8, 331–340 (2018). 13. Dang, Z. et al. A Pilot Study on Developing Mucosal Vaccine against Alveolar Echinococcosis (AE) Using Recombinant Tetraspanin 3: Vaccine Efficacy and Immunology. PLoS Negl Trop Dis 6, e1570 (2012). 14. Nian, X. et al. Understanding pathogen–host interplay by expression profiles of lncRNA and mRNA in the liver of Echinococcus multilocularis-infected mice. PLoS Negl Trop Dis 16, e0010435 (2022). 15. Zhang, X. et al. Transcriptomic Profiling Reveals Gene Expression Changes in Mouse Liver Tissue During Alveolar Echinococcosis. Genes (Basel) 16, 839 (2025). 16. Yousef, R. et al. U-Net-Based Models towards Optimal MR Brain Image Segmentation. Diagnostics (Basel) 13, 1624 (2023). 17. Poirion, O. B., Jing, Z., Chaudhary, K., Huang, S. & Garmire, L. X. DeepProg: an ensemble of deep-learning and machine-learning models for prognosis prediction using multi-omics data. Genome Med 13, 112 (2021). " 
Zhu DL, Tulahong A, Liu C, Aierken A, Tan W, Ruze R, Yuan ZD, Yin L, Jiang TM, Lin RY, Shao YM, Aji T. Identification of key factors and explainability analysis for surgical decision-making in hepatic alveolar echinococcosis assisted by machine learning. World J Gastroenterol 2025; 31(37): 111038 [PMID: 41025013 DOI: 10.3748/wjg.v31.i37.111038]
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"The quality of evidence is really poor in this article. Besides, there is a real conflict of interest: the author works as a speaker for the laboratory in Mexico, and this is an ethical issue. The conclusion is not valid without the statistical analysis. The sample size is very small, and readers should not believe that sylimarine is useful in MASLD" 
Martínez-Sánchez FD, Martínez-Vázquez SE, Gutiérrez-Monterrubio R, Muñoz-Martínez S, Garcia-Juarez I. Silymarin-alpha lipoic acid and metabolic dysfunction-associated steatotic liver disease: Insights and methodological considerations. World J Hepatol 2025; 17(9): 110162 [PMID: 41024889 DOI: 10.4254/wjh.v17.i9.110162]
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"Great subject, it is very difficult to define when autoimmune hepatitis is refractory and when we should change therapy to a second line. Most of the time, patients receive steroids for long periods, and that is unnecessary. It is very important to switch patients as soon as possible, instead of repeating steroid treatments for long periods, and second- and third-line options are safe and effective treatments, and hepatologists should not be afraid to use them" 
Malakar S, Shamsul Hoda U, Giri S, Samanta A, Roy A, Gupta R, Kumar SR, Agarwal M, Pawar A, Rungta S, Ghoshal UC. Difficult to treat and refractory autoimmune hepatitis: Recent advances in pharmacological management. World J Hepatol 2025; 17(9): 110264 [PMID: 41024881 DOI: 10.4254/wjh.v17.i9.110264]
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"After reading with great interest the recent article by Liu et al. (2025) comparing the safety and efficacy of 40 mg/day and 80 mg/day initial doses of lurasidone in acute schizophrenia. The study addresses a clinically relevant question regarding optimal dosing strategies, particularly in Chinese populations where approved doses may differ from international guidelines. The authors should be commended for their pragmatic trial design, which incorporated a one-week fixed-dose period followed by flexible dosing—a approach that closely mirrors real-world clinical practice. The finding of no significant difference in discontinuation rates due to adverse events (3.03% vs 5.10%, P=0.707) between the two dosing strategies provides valuable evidence supporting the safety of initiating treatment at 80 mg/day. Several aspects of the results deserve particular attention. The early advantage in PANSS positive subscale improvement observed in the 80 mg/day group at weeks 1 and 2 (P<0.05) suggests that higher initial dosing may offer more rapid control of psychotic symptoms—a potentially important consideration in acute care settings. Equally noteworthy was the paradoxical finding regarding weight change, with the 40 mg/day group showing significant weight gain (0.83 kg, P<0.01) compared to minimal change in the 80 mg/day group (-0.08 kg). This observation challenges conventional dose-response expectations and warrants further investigation. However, some limitations should be considered when interpreting these findings. The open-label design, while pragmatic, introduces potential for assessment bias. Additionally, the relatively short 6-week duration limits understanding of long-term outcomes, and the sample size, though adequate for safety endpoints, may be underpowered for certain efficacy comparisons. Despite these limitations, this study makes a valuable contribution to the literature by demonstrating that 80 mg/day initiation appears to be a viable and safe option that may offer early symptomatic benefits without increased metabolic risk. These findings should encourage clinicians to consider individual patient needs when selecting initial doses, particularly when rapid symptom control is prioritized. Future research with longer follow-up and broader dose ranges would help further elucidate the optimal dosing strategies for lurasidone in diverse clinical populations." 
Liu Q, Qian MC, Liu ZF, Dong F, Liu DT, Li ML, Ning YP, Wang XP, Liu TB, Wu Q, Li T, Yu X. Safety and efficacy of different initial doses of lurasidone in the schizophrenia treatment: A multi-center, randomized, open-label study. World J Psychiatry 2025; 15(10): 110968 [PMID: 41112599 DOI: 10.5498/wjp.v15.i10.110968]
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"This study addresses a key technical challenge in the treatment of rectal neuroendocrine tumors (NETs) by innovatively evaluating the advantages of pretraction-assisted endoscopic submucosal dissection (p-ESD) over conventional endoscopic submucosal dissection (c-ESD). The encouraging findings provide valuable evidence for clinical practice. Through a rigorous retrospective cohort study, the authors demonstrated that the p-ESD technique significantly shortens dissection time, improves the R0 resection rates, and reduces the risk of intraoperative bleeding and muscularis propria injury. These results strongly align with the fundamental principle of traction-assisted endoscopic submucosal dissection: enhancing safety and efficiency by improving exposure of the submucosal plane. The concept of "pretraction" – establishing traction before mucosal incision – is particularly commendable. Compared to methods applying traction after incision, this approach may provide earlier and more sustained visualization, potentially representing the key innovation leading to the superior outcomes. While fully acknowledging the value of this study, we offer the following suggestions for consideration to strengthen the manuscript further: 1. Technical standardization and learning curve: The article notes that all procedures were performed by a single expert endoscopist, ensuring consistency but raising an important question. What is the learning curve for the p-ESD technique? For less experienced operators, how challenging is it to master the timing of device placement and tension control? Future studies involving operators with varying experience levels or providing standardized procedural videos and schematic diagrams would greatly promote the dissemination of this technique. 2. Comparison with other traction techniques: the discussion appropriately cites studies where other traction methods showed less pronounced benefits for rectal lesions. This highlights the potential uniqueness of the p-ESD technique described. A more in-depth comparison of the similarities and differences between various traction methods, in terms of mechanical principles and application scenarios, would help readers better understand why the pre-traction strategy employed in this study achieves such significant results. Overall, the study by Guo et al. presents a safer and more efficient option for the minimally invasive treatment of rectal NETs. We look forward to further prospective studies from this team and other centers to validate the broad applicability of this technique and explore its standardized training protocols." 
Guo XX, Zhang SH, Chen AJ, Chen YL, Chen FL. Efficacy and safety of pretraction-assisted endoscopic submucosal dissection for treating rectal neuroendocrine tumors. World J Gastrointest Endosc 2025; 17(9): 111734 [PMID: 40979064 DOI: 10.4253/wjge.v17.i9.111734]
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"Working towards improving transarterial chemoembolization (TACE) outcomes for hepatocellular carcinoma Eduardo Segovia-Vergara, Arturo Alonso, Rodrigo Mansilla-Vivar Abstract: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, and transarterial chemoembolization (TACE) is a cornerstone therapy for patients with intermediate or advanced disease. However, TACE outcomes are influenced by multiple clinical, imaging, and psychosocial factors. Recent studies highlight the value of a multidisciplinary approach to optimize post-TACE management. This includes assessing immune, coagulation, and biomarker responses to predict prognosis, applying magnetic resonance imaging bias field correction to improve tumor evaluation, and identifying risk factors for post-procedural complications such as infections. Together, these strategies work towards improving TACE results for HCC, emphasizing the need for integrated care that combines technological, clinical, and supportive interventions. Dear Editor, We read with great interest the recent articles addressing transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC), including the works by Song et al., Liu et al., Fu et al., and Shan et al. These studies provide valuable insights into the clinical, imaging, and systemic aspects of TACE, highlighting its therapeutic potential as well as the challenges in optimizing patient outcomes. Taken together, these studies emphasize the value of integrating clinical, imaging, and systemic considerations to improve outcome prediction and manage complications in HCC patients undergoing TACE, and they motivate a discussion on strategies aimed at enhancing TACE efficacy through a multidisciplinary approach. Although these studies provide important insights, some are limited by retrospective designs, small sample sizes, among other limitations. Nevertheless, these findings underscore the need for coordinated, multidisciplinary strategies in HCC patients undergoing TACE. Building on this evidence, this letter aims to discuss potential approaches to enhance TACE outcomes by integrating clinical evaluation, advanced imaging, complication management, and supportive care. " 
Wei LL, Lai YL, Qiu KH, He X, Yang T. Clinical efficacy of neoadjuvant chemotherapy combined with radical gastrectomy in elderly patients with advanced gastric cancer. World J Gastrointest Surg 2025; 17(9): 106995 [PMID: 41024826 DOI: 10.4240/wjgs.v17.i9.106995]
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"This guideline is a powerful and practical tool for the pluralistic management of inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. This interesting tool, appropriate for making clinical decisions about IBD management in the United Arab Emirates, may be useful for addressing those chronic disorders elsewhere. The content is insightful. The work is interesting, and the text is well written." 
Al Awadhi S, Al Hassani A, El Ouali S, Alam MB, Azar C, Georgopoulos F, Jazzar AN, Khassouan AM, Koutoubi Z, Nathwani RA, Quraishi MN. Second United Arab Emirates consensus guidance on the diagnosis and management of inflammatory bowel disease. World J Gastroenterol 2025; 31(35): 109882 [PMID: 41024766 DOI: 10.3748/wjg.v31.i35.109882]
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"Reader Comments on “Cystatin C–based equations: Enhancing accuracy in kidney function tests for type 2 diabetes” World Journal of Nephrology. 2025; 14(3): 102756. DOI: 10.5527/wjn.v14.i3.102756 Dear Editor, Diabetic kidney disease (DKD) remains the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) worldwide, I read with great interest this topic, which highlights the role of cystatin C–based equations in improving the accuracy of renal function assessment in patients with type 2 diabetes mellitus (T2DM). Strengths of the article: The paper clearly underscores the limitations of creatinine-based estimated glomerular filtration rate (eGFR), especially in diabetic patients where muscle mass may distort results. The authors’ emphasis on cystatin C as a more reliable biomarker, along with advocacy for combined creatinine–cystatin C equations as recommended by KDIGO, reflects current evidence-based practice. The discussion on integrating cystatin C into precision medicine approaches, particularly alongside artificial intelligence (AI), is forward-thinking and aligns with global efforts toward individualized care. While cystatin C reduces creatinine-related biases, factors such as thyroid dysfunction, systemic inflammation, and corticosteroid use may also influence its levels. Table 1 offers a concise and summary of the main methods for estimating GFR. Points for further consideration: Role of renal biopsy: The article notes the underutilization of renal biopsy in DKD diagnosis. Expanding on how cystatin C may complement, but not replace, biopsy in complex diagnostic scenarios could be useful. Outcome validation: Future studies should demonstrate whether cystatin C–based eGFR translates into better clinical outcomes (e.g., reduced DKD progression, lower cardiovascular events, delayed dialysis initiation) beyond improved diagnostic precision. AI applications: The proposed integration of cystatin C into AI-driven models is exciting. Specific examples or pilot studies where biomarker–AI integration has improved predictive accuracy would strengthen this vision. Conclusion: This editorial makes an important contribution by advocating for more accurate renal assessment in patients with T2DM. The call for cystatin C integration, particularly in high-risk populations, is well-justified and aligned with evolving guidelines. Broader validation, cost-effectiveness studies, and exploration of biomarker–AI synergy will be critical steps toward translating these insights into standard nephrology practice. Sincerely, [Rabie M Ibrahim, MD in urology] Urology department, Faculty of medicine Beni-Suef University, Beni-Suef, Egypt. " 
Gembillo G, Sessa C, Santoro D. Cystatin C-based equations: Enhancing accuracy in kidney function tests for type 2 diabetes. World J Nephrol 2025; 14(3): 102756 [PMID: 41024961 DOI: 10.5527/wjn.v14.i3.102756]
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"This systematic review and meta-analysis highlight the importance of prehabilitation in patients undergoing hepatobiliary and pancreatic cancer resections by providing a comprehensive analysis of randomized controlled trials (RCTs). It concluded that prehabilitation was associated with fewer postoperative complications compared to no prehabilitation, with a risk ratio (RR) of 0.79 (95% CI: 0.66-0.95, P = 0.01). Also there is tendency towards shorter hospital stay. No statistically significant differences were found between prehabilitation and no prehabilitation groups for postoperative readmission rates (RR: 1.31, 95% CI: 0.79-2.17, P = 0.29), major complications (RR: 1.08, 95% CI: 0.61-1.92, P = 0.78), length of stay (standardized mean difference: -0.11, 95% CI: -0.31 to 0.1, P = 0.29), or mortality (RR: 0.28, 95% CI: 0.01-6.51, P = 0.43). The study highlights that hepatobiliary and pancreatic cancers are highly lethal, and surgical intervention, though central to treatment, often leads to postoperative complications. Prehabilitation is proposed as a tool to optimize patients preoperatively, thereby reducing morbidity and improving recovery. Despite its findings, the authors acknowledge limitations, such as the relatively small sample size due to strict inclusion criteria of only RCTs, which may limit the generalizability. We found that the article does not explicitly address pulmonary complications, which are common in patients undergoing major abdominal surgeries, including hepatobiliary and pancreatic resections. This omission leaves a gap in understanding the full spectrum of prehabilitation's impact. The article notes that postoperative rehabilitative care varied between included trials, introducing heterogeneity. This makes it challenging to clearly differentiate between a 'prehabilitation' group and a 'standard care' group, especially since elements like nutritional support and pulmonary exercises are often considered standard preoperative care for these patients. The varied prehabilitation protocols (multimodal, nutritional, or exercise-based) further complicate this distinction. In conclusion, while this article provides valuable evidence that prehabilitation can reduce overall postoperative complications in hepatobiliary and pancreatic cancer resections, its limitations regarding sample size, protocol heterogeneity, lack of long-term data, and unaddressed specific complications like pulmonary issues highlight the need for more focused and standardized research in this critical area." 
Lubbad O, Mahmood WU, Shafique S, Singh KK, Khera G, Sajid MS. Effect of prehabilitation in patients undergoing hepatobiliary and pancreatic cancer resections: A systematic review and meta-analysis. World J Gastrointest Endosc 2025; 17(9): 109029 [PMID: 40979053 DOI: 10.4253/wjge.v17.i9.109029]
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"Colorectal Strictures in Ulcerative Colitis To the Editor, I read with great interest the article by Shao et al., titled “Risk Factors and Long-Term Prognosis for Colorectal Strictures in Ulcerative Colitis” (1). The authors have provided valuable insights into the natural history and risk stratification of stricture formation in ulcerative colitis (UC). I would like to offer several comments and pose a few questions for further clarification and discussion. First, Figure 1 in the article clearly illustrates that the risk of stricture formation increases with disease duration in UC. The graph appears to show a near-linear progression, with an estimated annual risk of approximately 1.2% per year post-diagnosis. This finding reinforces the understanding that strictures are a time-dependent complication of UC. Second, stricture formation is generally considered a marker of chronic and progressive disease. Therefore, the increased frequency of certain clinical features—such as anemia and extraintestinal manifestations—among patients with strictures may reflect prolonged disease activity rather than being directly caused by the strictures themselves. Similarly, higher rates of corticosteroid use and steroid resistance could also be secondary to a more advanced disease state. In this context, the reported risk factors (older age, elevated ESR and CRP, prior steroid use) may be better interpreted as indirect indicators of disease chronicity rather than primary etiologic factors. Third, it is not surprising that strictures most commonly occur in the sigmoid colon, given its status as the narrowest anatomical segment of the large intestine. Wall thickening in this region is more likely to result in significant luminal narrowing, potentially predisposing this site to stricture formation. Fourth, the relationship between UC and cigarette smoking remains one of the more intriguing and paradoxical findings in inflammatory bowel disease research (2). While smoking is generally associated with a reduced risk of developing UC, the absence of a significant difference in smoking status between patients with and without strictures in this study is noteworthy (3). Further exploration of this finding may yield important mechanistic insights. Fifth, the higher incidence of bowel obstruction in patients with strictures is expected. However, the increased frequency of toxic megacolon in this group is particularly interesting. This could be explained either by the long-standing disease course or possibly by obstruction-induced colonic distension acting as a trigger for toxic megacolon. In light of these observations, I would like to pose the following questions: 1. Is it feasible to classify colonic strictures in UC patients based on clinical parameters such as disease severity, prognosis, or response to treatment? Would such a classification have therapeutic or prognostic value? 2. Are there notable clinical differences between patients with solitary versus multiple strictures? For instance, do patients with multiple strictures have a longer disease duration or higher risk of complications such as colorectal cancer or toxic megacolon? 3. Among the eight patients in whom strictures resolved during follow-up, what were their clinical characteristics? Was remission attributed to specific therapies, or could patient-related factors (e.g., genetic or immunological profiles) have contributed? Furthermore, was the possibility of pseudo-strictures or diagnostic misclassification considered? I commend the authors for their important contribution to our understanding of this complex and clinically relevant complication of UC and would appreciate any additional insights they may offer in response. Sincerely, Cuneyt Kayaalp MD, Professor, Istanbul Atlas University, Department of General Surgery, Istanbul, Turkiye cuneytkayaalp@gmail.com, +90 533 4757434 Reference 1. Shao YP, Han TT, Lv H, Yang ST, Zhu QL, Li J, Li JN. Risk factors and long-term prognosis for colorectal strictures in ulcerative colitis. World J Gastroenterol. 2025 Sep 7;31(33):109938. doi: 10.3748/wjg.v31.i33.109938. PMID: 40933463; PMCID: PMC12417941. 2. Alperen CC, Soydas B, Serin E, Erbayrak M, Savas NA, Unler GK, Meral CE, Toprak U, Boyacioglu AS, Dagli U. Role of Environmental Risk Factors in the Etiology of Inflammatory Bowel Diseases: A Multicenter Study. Dig Dis Sci. 2024 Aug;69(8):2927-2936. doi: 10.1007/s10620-024-08491-w. Epub 2024 Jun 5. PMID: 38837110. 3. Harmandar F, Çekin AH. Preventive care in inflammatory bowel disease. Turk J Gastroenterol. 2017 Jul;28(4):307-310. doi: 10.5152/tjg.2017.190617. PMID: 28699605. " 
Shao YP, Han TT, Lv H, Yang ST, Zhu QL, Li J, Li JN. Risk factors and long-term prognosis for colorectal strictures in ulcerative colitis. World J Gastroenterol 2025; 31(33): 109938 [PMID: 40933463 DOI: 10.3748/wjg.v31.i33.109938]
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