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1
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"In this paper, the tumor indicators of patients with gastric cancer after operation were detected and analyzed. It was found that CEA and AFP were closely related to the recurrence of gastric cancer, which provided a good basis for judging the health level of patients with gastric cancer after operation. But it also needs the support of large-scale clinical data. At the same time, patients with gastric cancer need more tumor indicators to explore a better combination for judging the prognosis of patients with gastric cancer."
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Duan XX, Yu X, Zhou L. Timeliness of postoperative serum carcinoembryonic antigen monitoring for predicting recurrence after gastric cancer surgery. World J Gastrointest Surg 2026; 18(1): 114309 [DOI: 10.4240/wjgs.v18.i1.114309]
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2
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"Dear Editor,
I am writing in response to your invitation to comment on the prospective study by Güneş et al., entitled “Diagnostic value of interleukin-8 in colon cancer,” published in your esteemed journal. The authors provide valuable data reinforcing the role of interleukin-8 (IL-8) as an independent diagnostic biomarker in colon adenocarcinoma. Their work rightly concludes that IL-8 holds promise, particularly as part of a multi-marker panel.
I would like to extend this discussion by contextualizing IL-8 within the current, rapidly evolving biomarker landscape of colorectal cancer (CRC), as recently elaborated in an editorial on this topic. The future of CRC management lies in a dynamic, multi-layered biomarker strategy that integrates three key pillars: 1) Mismatch repair (MMR) status to dictate therapeutic class (chemotherapy vs. immunotherapy); 2) Perioperative carcinoembryonic antigen (CEA) for immediate risk stratification, especially within microsatellite stable (MSS) disease; and 3) Postoperative circulating tumor DNA (ctDNA) as a dynamic tool to guide treatment intensity and de-escalation, as definitively demonstrated by the recent AGITG DYNAMIC-III trial.
In this framework, the findings on IL-8 by Güneş et al. present a compelling opportunity. While its standalone diagnostic accuracy (AUC=0.68) is moderate, its independent predictive value suggests a distinct biological role, likely rooted in its pro-inflammatory and angiogenic functions. This positions IL-8 not as a replacement for the aforementioned pillars, but as a potential complementary element, particularly within the MSS cohort.
Specifically, IL-8 could enhance the second pillar (risk stratification) by providing additional biological granularity. For instance, in MSS patients with normal or borderline CEA levels, an elevated IL-8 might signal a more aggressive tumor biology driven by inflammation, potentially identifying a subset that would benefit from closer surveillance or adjuvant therapy. Furthermore, given its link to angiogenesis and immune modulation, IL-8 merits investigation as a predictive biomarker for responses to anti-angiogenic therapies (e.g., bevacizumab) and possibly immunotherapy, even in MSS/pMMR tumors.
Therefore, I propose that the next logical step for research, as inspired by both this study and the broader editorial perspective, is to evaluate IL-8 within integrated multi-marker panels. Combining IL-8 with CEA, ctDNA, and potentially other inflammatory markers (e.g., CRP) in algorithm-driven models could significantly improve diagnostic sensitivity, prognostic stratification, and predictive accuracy. This approach aligns perfectly with the paradigm of dynamic precision oncology, where multiple data streams are synthesized to guide personalized therapeutic navigation.
I congratulate the authors on their contribution and thank you for the opportunity to share these perspectives, hoping they may stimulate further research into the integrative potential of IL-8 within the modern CRC biomarker ecosystem.
Sincerely,
Pr Nabil Ismaili
Mohammed VI University of Sciences and Health (UM6SS), Mohammed VI Foundation of Sciences and Hrealth (FM6SS), Casablanca, Morocco, nismaili@um6ss.ma, 0000-0001-5786-5134"
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Güneş G, Fırat Oğuz E, Kayılıoğlu I, Dinç T. Diagnostic value of interleukin-8 in colon cancer: Prospective, case-control study. World J Gastrointest Surg 2026; 18(1): 115444 [DOI: 10.4240/wjgs.v18.i1.115444]
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"Systemic antifungal therapy is the backbone of treatment for invasive fungal infections, but it carries an under-recognized burden of endocrine and physiological toxicity. The review by Thakkar et al. (2026) provides an important framework for understanding how these agents affect human cytochrome P450 enzymes and renal function, leading to adrenal insufficiency, mineralocorticoid excess, and electrolyte abnormalities. This review deserves recognition, and adding a global perspective to it could provide new recommendations. If possible, I would like to submit a letter addressing this perspective."
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Thakkar S, Kantroo V, Nagendra L, Dutta D, Kamrul-Hasan ABM, Kalra S, Bhattacharya S. Endocrine consequences of antifungal therapy: A missed entity. World J Clin Cases 2026; 14(2): 117140 [DOI: 10.12998/wjcc.v14.i2.117140]
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"I read with interest the study comparing the ASGE lexicon and the AGREE classification for adverse events in gastrointestinal endoscopy. The authors are to be commended for their rigorous analysis of a large institutional registry and for highlighting the conceptual differences between two widely used adverse event frameworks.
The high concordance observed between ASGE and AGREE confirms that both systems are robust for capturing clinically significant complications. However, the discordance noted for transient cardiorespiratory and sedation-related events raises an important interpretive issue. The ASGE lexicon intentionally captures such occurrences as “incidents,” supporting quality improvement and preventive strategies, whereas AGREE excludes many of these events by design, prioritising clinical consequence and post-procedural intervention. While this approach improves specificity, it may inadvertently narrow the safety signal.
From a patient-centred perspective, events such as inadequate sedation, procedural discomfort, or transient hypoxia—although self-limiting—can significantly influence patient-reported experience, satisfaction, and trust in endoscopic services. These experiential harms may not require escalation of care yet remain meaningful to patients and may affect willingness for repeat procedures. Their exclusion from adverse event datasets risks underestimating quality concerns that are increasingly relevant in value-based care.
The study also underscores that adverse event classification represents only one dimension of endoscopy quality. Domains such as procedural appropriateness, missed or delayed diagnoses, bowel preparation adequacy, photodocumentation quality, scheduling delays, and patient-initiated procedure termination are not captured by adverse event frameworks but are integral to comprehensive quality assessment.
In summary, while standardised adverse event classification remains essential for benchmarking and safety governance, it should be complemented by patient-reported experience measures and broader quality indicators. A multidimensional framework integrating safety, experience, and appropriateness may better align endoscopy quality metrics with contemporary patient-centred practice."
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Corsi O, Martinez R, Aguirre J, Friedrich I, Galeno V, Jimenez V, Briones P, Díaz LA, Espino A, Vargas JI. Application of a novel adverse event classification scale in a Latin American gastrointestinal endoscopy unit. World J Gastrointest Endosc 2026; 18(1): 111384 [DOI: 10.4253/wjge.v18.i1.111384]
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"This minireview provides a timely and balanced synthesis of the evolving role of endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) in the management of pancreatic neuroendocrine tumors (pNETs). The authors appropriately frame EUS-RFA as a promising yet still selective therapeutic option, and the “lights and shadows” construct is effective in highlighting both its clinical potential and its current limitations
A major strength of the article lies in its comprehensive collation of published clinical experience across functioning and non-functioning pNETs. The tabulated summaries are particularly valuable for readers seeking an overview of technical success, clinical response, and adverse event profiles. Importantly, the authors avoid overstating efficacy and consistently acknowledge the predominance of retrospective series, limited follow-up durations, and heterogeneity in response definitions—an intellectua rigour that strengthens the manuscript.
From a conceptual standpoint, the review highlights a key paradigm shift: EUS-RFA is no longer merely a salvage or palliative modality, but a potential intermediate option within the “grey zone” of small, low-grade pNETs, especially in patients unfit for surgery or those prioritizing minimally invasive approaches. This raises an important clinical question not fully resolved in current guidelines—whether EUS-RFA should eventually be positioned as a disease-modifying therapy rather than an alternative to surveillance.
The discussion on radiological response assessment underscores a critical unmet need in the field. The lack of standardized imaging endpoints, timing of follow-up, and correlation with long-term oncologic outcomes limits meaningful comparison across studies. Future consensus on response metrics—possibly integrating contrast-enhanced harmonic EUS, cross-sectional imaging, and biochemical markers—would significantly enhance interpretability and clinical adoption.
Finally, the article appropriately calls attention to procedural standardization and risk mitigation, particularly regarding pancreatitis prevention and proximity to the main pancreatic duct. These considerations will be central if EUS-RFA is to move beyond expert centers into broader clinical practice.
Overall, this review serves as a valuable reference for gastroenterologists, endosonographers, and multidisciplinary teams managing pNETs. It also clearly delineates the research priorities required before EUS-RFA can be fully integrated into evidence-based treatment algorithms."
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Tringali A, Caiazzo A. Role of endoscopic ultrasound in the treatment of pancreatic neuroendocrine tumors: Lights and shadows of endoscopic ultrasound-guided radiofrequency ablation. World J Gastrointest Endosc 2026; 18(1): 113617 [DOI: 10.4253/wjge.v18.i1.113617]
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"Commentary: Clinical Considerations in Immunocompromised Patients With Edwardsiella tarda–Associated Spontaneous Bacterial Peritonitis
The case report by Usuda et al., recently published in the World Journal of Clinical Cases, represents a notable contribution to clinical microbiology by documenting, to the best of current knowledge, the first reported case of spontaneous bacterial peritonitis (SBP) caused by Edwardsiella tarda in an immunocompromised patient undergoing dialysis [1].This report substantially expands the recognized infectious spectrum in patients with end-stage renal disease (ESRD) and underscores the need for heightened clinical awareness of atypical and opportunistic pathogens in this vulnerable population.
One particularly commendable aspect of this report is the authors’ detailed discussion of the virulence mechanisms of E. tarda. The organism’s capacity to survive and replicate within macrophages plays a pivotal role in its pathogenicity, especially in hosts with compromised cellular immunity [2,3]. In the present case, the coexistence of diabetic nephropathy and long-term dialysis likely created a permissive immunological milieu that facilitated this opportunistic infection. Such intracellular persistence provides a plausible explanation for the severe and insidious clinical course observed, even in the absence of classical epidemiological exposures such as raw seafood consumption or contact with freshwater environments.
Equally noteworthy is the authors’ adherence to principles of antimicrobial stewardship. The stepwise transition from empirical broad-spectrum therapy with cefmetazole to targeted, de-escalated treatment using cefalexin—guided by comprehensive antimicrobial susceptibility testing (Table 3)—offers a valuable therapeutic reference for clinicians managing similarly rare infections.
Nevertheless, building on the authors’ insightful acknowledgment of the limitations surrounding “ascites culture conversion,” I would like to propose a more structured and rigorous framework for defining treatment endpoints in such high-risk cases. While clinical and symptomatic improvement remains an essential marker of response, it may be insufficient when dealing with pathogens such as E. tarda, which possess the ability to persist intracellularly [4,5]. Accordingly, I suggest an integrated “imaging-to-microbiology” strategy prior to antibiotic discontinuation.
First, advanced imaging modalities—such as abdominal computed tomography or high-resolution ultrasonography—should be systematically incorporated to objectively assess the resolution of ascites. Complete radiological absorption of ascitic fluid would substantially strengthen the clinical justification for treatment cessation. Conversely, if residual ascites is detected, even in minimal or loculated forms, reliance on systemic inflammatory markers such as C-reactive protein or leukocyte counts alone may be misleading. Given the organism’s persistence potential [3], repeat diagnostic paracentesis should be strongly considered to confirm microbiological eradication. This dual confirmation—radiological and microbiological—would provide a more robust and evidence-based rationale for terminating antimicrobial therapy [6], thereby reducing the risk of relapse in immunocompromised patients.
In conclusion, while this case report fills an important gap in the current literature, it also highlights the need to refine discharge and treatment-completion criteria for rare causes of SBP. Adoption of an imaging-guided microbiological confirmation strategy may enhance the precision of clinical decision-making and ultimately improve long-term outcomes in patients with complex comorbidities.
参考文献
[1]Usuda D , Furukawa D, Imaizumi R et al. Spontaneous bacterial peritonitis due to Edwardsiella tarda in an immuno-compromised dialysis patient: A case report and review of literature. World J Clin Cases 2026,6; 14(1): 115102.
[2][2]Qin L, Li F, Wang X, Sun Y, Bi K, Gao Y. Proteomic analysis of macrophage in response to Edwardsiella tarda-infection. Microb Pathog, 2017; 111: 86-93 [RCA] [PMID: 28826764 DOI: 10.1016/j.micpath.2017.08.028]
[3]Zhang L, Ni C, Xu W, Dai T, Yang D, Wang Q, Zhang Y, Liu Q. Intramacrophage Infection Reinforces the Virulence of Edwardsiella tarda. J Bacteriol 2016; 198: 1534-1542 [RCA] [PMID: 26953340 DOI: 10.1128/JB.00978-15]
[4]An L, Chan JL, Nguyen M, Yang S, Deville JG. Case Report: Disseminated Edwardsiella tarda infection in an immunocompromised patient. Front Cell Infect Microbiol 2023; 13: 1292768 [RCA] [PMID: 38053529 DOI: 10.3389/fcimb.2023.1292768]
[5]Matsukawa H, Usuda D, Takami H, Nomura T, Sugita M. A Case of Edwardsiella tarda Infection With Iliopsoas Abscess Following Acute Pyelonephritis. Cureus 2024; 16: e58868 [RCA] [PMID: 38800258 DOI: 10.7759/cureus.58868]
[6]A Rimola , G García-Tsao, M Navasa, L J Piddock, R Planas, B Bernard, J M Inadomi. Diagnosis, treatment and prophylaxis of spontaneous bacterial peritonitis: a consensus document. International Ascites Club. J Hepatol, 2000; 32(1):142-53[RCA][PMID: 10673079 DOI: 10.1016/s0168-8278(00)80201-9]"
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Usuda D, Furukawa D, Imaizumi R, Ono R, Kaneoka Y, Nakajima E, Kato M, Sugawara Y, Shimizu R, Inami T, Kawai K, Matsubara S, Tanaka R, Suzuki M, Shimozawa S, Hotchi Y, Osugi I, Katou R, Ito S, Mishima K, Kondo A, Mizuno K, Takami H, Komatsu T, Nomura T, Sugita M. Spontaneous bacterial peritonitis due to Edwardsiella tarda in an immuno-compromised dialysis patient: A case report and review of literature. World J Clin Cases 2026; 14(1): 115102 [PMID: 41551684 DOI: 10.12998/wjcc.v14.i1.115102]
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" This paper presents a systematic retrospective analysis of the incidence and clinical significance of gallstones and gallbladder wall thickening in patients with liver cirrhosis, offering valuable clinical observations for practitioners. The study clearly indicates that the prevalence of gallbladder abnormalities—including gallstones and asymptomatic wall thickening—is significantly higher in patients with cirrhosis, especially in the decompensated stage, compared to the general population. This finding aligns with previous research and further supports the pivotal role of portal hypertension and hepatic dysfunction in the development of gallbladder pathology.
Notably, the authors emphasize that these imaging findings are often related to cirrhosis itself rather than being indicators of acute cholecystitis. This distinction is clinically important, as it can help prevent unnecessary interventions—such as misdiagnosis and surgery for presumed acute cholecystitis—particularly in asymptomatic individuals. Moreover, the study suggests that gallbladder abnormalities correlate more strongly with the decompensated state of cirrhosis than with its etiology, providing a fresh perspective on the mechanisms underlying gallbladder changes in these patients.
However, several limitations should be acknowledged. First, the retrospective design and single-center sample may limit the generalizability of the results. Second, the study lacks in-depth analysis of subgroups based on the etiology of cirrhosis, leaving it unclear whether findings differ notably in non-alcoholic liver disease patients. Finally, potential influencing factors such as gallbladder motility and medication use were not systematically evaluated, even though they may contribute to wall thickening and stone formation.
Overall, this paper offers practical clinical insights into the imaging assessment of the gallbladder in cirrhotic patients. Future prospective, multicenter studies incorporating more pathophysiological parameters—such as gallbladder motility and bile composition—could help further elucidate the complex relationship between cirrhosis and gallbladder disorders and contribute to optimized clinical decision-making."
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Tsankof A, Protopapas AA, Kyritsi V, Gogou C, Kyziroglou M, Papathanasiou E, Chatzikosma C, Michalopoulos A, Savopoulos C, Protopapas AN. Gallstones and gallbladder wall thickening in patients with cirrhosis: Prevalence and clinical impact. World J Clin Cases 2026; 14(1): 114043 [PMID: 41551687 DOI: 10.12998/wjcc.v14.i1.114043]
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8
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"This meta-analysis systematically retrieved and synthesized evidence from 30 randomized controlled trials (RCTs) involving nearly 17,000 patients, providing the most comprehensive assessment to date on the efficacy of indomethacin for preventing post-ERCP pancreatitis (PEP). It offers valuable, up-to-date evidence-based references for clinical practice, and the authors' efforts are highly commendable. Nevertheless, while acknowledging its contributions, two critical methodological limitations must be highlighted, which may compromise the interpretation and generalizability of its findings.
The present commentary aims to identify two key methodological flaws in this meta-analysis that seriously undermine the statistical validity and clinical interpretability of its results. First, the authors inappropriately disaggregated seven multi-arm randomized controlled trials into multiple independent pairwise comparisons for inclusion in the analysis. This practice directly violates the core assumption of data independence in meta-analyses: different comparison groups derived from the same trial are correlated due to the shared control arm. Treating these as independent samples artificially inflates the total sample size, misestimates the weight of each study, and leads to an inappropriate narrowing of confidence intervals, thereby increasing the risk of Type I or Type II errors. Second, the definition of the "control group" in the study encompasses interventions with extremely high clinical heterogeneity, including placebo, normal saline, other active medications (e.g., diclofenac, somatostatin), and invasive procedures (e.g., pancreatic duct stenting). Pooling these controls with vastly different mechanisms of action and therapeutic efficacies renders the reported pooled relative risk (RR = 0.85) clinically meaningless. Furthermore, the high heterogeneity observed (I² = 79%) is most likely attributable to this flawed methodological design. In summary, the aforementioned issues cast doubt on the statistical credibility of the primary conclusion—that "indomethacin does not significantly reduce the incidence of PEP"—and also make it difficult to provide a reasonable clinical interpretation for practice.
Given that this review incorporates multiple interrelated interventions for comparison, network meta-analysis would represent a more appropriate methodological framework. It can rigorously integrate data from multi-arm trials and simultaneously evaluate the relative efficacy of all relevant preventive strategies."
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Tian F, Huang ZC, Khizar H, Qiu K. Efficacy of indomethacin for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: A comprehensive meta-analysis of randomized controlled trials. World J Gastroenterol 2026; 32(1): 113232 [PMID: 41551526 DOI: 10.3748/wjg.v32.i1.113232]
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9
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"This meta-analysis systematically retrieved and synthesized evidence from 30 randomized controlled trials (RCTs) involving nearly 17,000 patients, providing the most comprehensive assessment to date on the efficacy of indomethacin for preventing post-ERCP pancreatitis (PEP). It offers valuable, up-to-date evidence-based references for clinical practice, and the authors' efforts are highly commendable. Nevertheless, while acknowledging its contributions, two critical methodological limitations must be highlighted, which may compromise the interpretation and generalizability of its findings.
The present commentary aims to identify two key methodological flaws in this meta-analysis that seriously undermine the statistical validity and clinical interpretability of its results. First, the authors inappropriately disaggregated seven multi-arm randomized controlled trials into multiple independent pairwise comparisons for inclusion in the analysis. This practice directly violates the core assumption of data independence in meta-analyses: different comparison groups derived from the same trial are correlated due to the shared control arm. Treating these as independent samples artificially inflates the total sample size, misestimates the weight of each study, and leads to an inappropriate narrowing of confidence intervals, thereby increasing the risk of Type I or Type II errors. Second, the definition of the "control group" in the study encompasses interventions with extremely high clinical heterogeneity, including placebo, normal saline, other active medications (e.g., diclofenac, somatostatin), and invasive procedures (e.g., pancreatic duct stenting). Pooling these controls with vastly different mechanisms of action and therapeutic efficacies renders the reported pooled relative risk (RR = 0.85) clinically meaningless. Furthermore, the high heterogeneity observed (I² = 79%) is most likely attributable to this flawed methodological design. In summary, the aforementioned issues cast doubt on the statistical credibility of the primary conclusion—that "indomethacin does not significantly reduce the incidence of PEP"—and also make it difficult to provide a reasonable clinical interpretation for practice.
Given that this review incorporates multiple interrelated interventions for comparison, network meta-analysis would represent a more appropriate methodological framework. It can rigorously integrate data from multi-arm trials and simultaneously evaluate the relative efficacy of all relevant preventive strategies."
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Ding Y, Wang CY, Pan YT, Wang YJ, Zhao AG, Wen HZ. Scutellaria baicalensis Georgi as a potential therapeutic drug intervention in ulcerative colitis: Mechanisms of action and clinical trials. World J Gastroenterol 2026; 32(1): 114558 [PMID: 41551522 DOI: 10.3748/wjg.v32.i1.114558]
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"I read the excellent paper by Rajak et al.
The review is organized and precisely addresses the role of microplastics in inducing metabolic-associated steatotic liver disease and its progression.
The review raises a growing emergency: the relationship between air pollution and human health.
This can be a stimulus for policymakers and international organizations to take concrete action.
However, it should be remembered that a proper lifestyle can mitigate the negative impact of microplastics on the liver and human health in general.
While waiting for long-term measures, this is information that can yield short-term results.
On this issue, it will be my concern to send a letter to the editor.
Sincerely, Gianni Testino"
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Rajak S, Shahi A, Yadav A, Medhe P, Sinha RA. Microplastics in metabolic dysfunction-associated steatotic liver disease: An emerging threat to liver health. World J Hepatol 2025; 17(12): 111198 [PMID: 41479513 DOI: 10.4254/wjh.v17.i12.111198]
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"1.The article does not cover the temporal and spatial dynamic changes of inflammatory cytokines during the development of NSCLC, as well as how these changes affect the occurrence and development of drug resistance. For instance, are there any differences in the expression levels of inflammatory cytokines in the early stage, progression stage, and resistance stage of the tumor? Are their distributions different in various parts of the tumor (such as the primary lesion and metastatic lesion)?
It is suggested to utilize techniques such as in situ hybridization and immunohistochemistry, combined with single-cell sequencing and spatial transcriptomics, to study the temporal and spatial dynamic changes of inflammatory cytokines in different development stages and different locations of NSCLC. By analyzing longitudinal samples of patients (such as before treatment, during treatment, and after resistance), the dynamic change patterns of inflammatory cytokines during the process of drug resistance can be revealed.
2. Although IL-6R blockade shows the effect of reversing drug resistance, single-target therapy may have limitations in efficacy or the risk of drug resistance escape. It is suggested to explore IL-6/IL-8 dual-target inhibition in preclinical models, or to combine it with downstream pathway inhibitors (such as JAK/STAT, PI3K/AKT, NF-κB inhibitors) or immune checkpoint inhibitors to evaluate its synergistic anti-tumor effect and its remodeling effect on the tumor microenvironment, in order to provide theoretical basis for future clinical trials of combination therapy."
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Calibasi-Kocal G. Inflammatory cytokine-associated cisplatin resistance in non-small cell lung cancer and re-sensitization through interleukin-6 receptor blockade. World J Clin Oncol 2025; 16(12): 114275 [PMID: 41480163 DOI: 10.5306/wjco.v16.i12.114275]
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"Author:
Priya Hazrah
Professor, Department of Surgery, Lady Hardinge Medical College, New Delhi.
Email: priyahazrah@gmail.com, ORCID ID 0009-0008-1915-3978
Deborshi Sharma
Director Professor Department of Surgey ABVIMS, New Delhi.
Email: drdeborshi@gmail.com, ORCID ID 0000-0001-8251-8484
Sonali Mittal
Assistant professor, Lady Hardinge Medical College, New Delhi
Email: sonali.prachi@gmail.com, ORCID 0000-0002-6289-7656
Corresponding Author:
Priya Hazrah
Professor Department of Surgery, Lady Hardinge Medical College, New Delhi.
Email: priyahazrah@gmail.com
We read with tremendous interest your article entitled “Mastering the third space: Innovations in intramural endoscopic surgery for gastrointestinal disorders.” It was a very apt and concise review of commonly performed third space endoscopy (TSE) procedures, namely the C, Z, E, and G POEM (per oral endoscopic myotomy). Here, we would like to highlight other evolving procedures related to third space endoscopy and also the emerging concept of “fourth space endoscopy.”
POETRE, peroral esophageal tunnelling for restoration of the esophagus, based on the principle of TSE, is an innovative technique of submucosal tunnelling proposed to be a useful therapeutic option in long-segment complete esophageal luminal obstruction in a few case series [1, 2]. PREM/PAEM (per rectal/per anal myotomy) is another novel use of TSE with limited exploration in patients with Hirschsprung’s disease [3]. STER (submucosal tunnelling endoscopic resection) and POET (peroral endoscopic excision of tumor) have been reported to be safe procedures for resection of extramucosal tumors in the upper gastrointestinal tract with acceptable complication rates vouched for in recent meta-analyses [4-7]. Further, TSE can be used to gain peritoneal access, as seen in POEM+F (POEM with fundoplication).
Building upon the model of third space endoscopy is a forthcoming concept of fourth space endoscopy based on the technique of sub-serosal dissection for excision of extramucosal tumors in the upper gastrointestinal tract, like gastrointestinal stromal tumors, leiomyoma, hamartoma, etc., published in a limited case series [8]. The feasibility of using the principle of the fourth-space endoscopy procedure for vagotomy is investigational and has been reported currently in an anecdotal non-human study [9]. The fourth space is also utilized at times in POEM to enable a full-thickness myotomy [10].
References
1. Wagh MS, Draganov PV. Per-oral endoscopic tunneling for restoration of the esophagus: a novel endoscopic submucosal dissection technique for therapy of complete esophageal obstruction. Gastrointest Endosc. 2017 Apr;85(4):722-727. doi: 10.1016/j.gie.2016.08.035. Epub 2016 Sep 7. PMID: 27612924.
2. Félix C, Barreiro P, Rodrigues Azevedo J, Maia L, Küttner-Magalhães R, Pedroto I, Chagas C. Per-oral endoscopic tunneling for restoration of the esophagus (POETRE) in the management of a complete esophageal obstruction. Endosc Int Open. 2021 Jul;9(7):E1084-E1085. doi: 10.1055/a-1463-3059. Epub 2021 Jun 17. PMID: 34222634; PMCID: PMC8211479.
3. Bapaye A, Dashatwar P, Biradar V, Biradar S, Pujari R. Initial experience with per-rectal endoscopic myotomy for Hirschsprung's disease: medium and long term outcomes of the first case series of a novel third-space endoscopy procedure. Endoscopy. 2021 Dec;53(12):1256-1260. doi: 10.1055/a-1332-6902. Epub 2021 Mar 2. PMID: 33291158.
4. Onimaru M, Inoue H, Bechara R, Tanabe M, Abad MRA, Ueno A, Shimamura Y, Sumi K, Ikeda H, Ito H. Clinical outcomes of per-oral endoscopic tumor resection for submucosal tumors in the esophagus and gastric cardia. Dig Endosc. 2020 Mar;32(3):328-336. doi: 10.1111/den.13471. Epub 2019 Jul 22. PMID: 31234231.
5. Peng W, Tan S, Huang S, Ren Y, Li H, Peng Y, Fu X, Tang X. Efficacy and safety of submucosal tunneling endoscopic resection for upper gastrointestinal submucosal tumors with more than 1-year' follow-up: a systematic review and meta-analysis. Scand J Gastroenterol. 2019 Apr;54(4):397-406. doi: 10.1080/00365521.2019.1591500. Epub 2019 Mar 29. PMID: 30925071.
6. Song S, Wang X, Zhang S, Li Y, Zhang X, Chu X. Efficacy and complications of submucosal tunneling endoscopic resection for upper gastrointestinal submucosal tumors and exploration for influencing factors. Z Gastroenterol. 2018 Apr;56(4):365-373. English. doi: 10.1055/s-0043-123765. Epub 2018 Jan 18. PMID: 29346827.
7. Cao B, Lu J, Tan Y, Liu D. Efficacy and safety of submucosal tunneling endoscopic resection for gastric submucosal tumors: a systematic review and meta-analysis. Rev Esp Enferm Dig. 2021 Jan;113(1):52-59. doi: 10.17235/reed.2020.6989/2020. PMID: 33222480.
8. Liu F, Zhang S, Ren W, Yang T, Lv Y, Ling T, Zou X, Wang L. The fourth space surgery: endoscopic subserosal dissection for upper gastrointestinal subepithelial tumors originating from the muscularis propria layer. Surg Endosc. 2018 May;32(5):2575-2582. doi: 10.1007/s00464-017-5985-z. Epub 2017 Dec 20. PMID: 29264757.
9. Kadkhodayan K, Irani S. Endoscopic truncal vagotomy. Exploring the fourth space. A technical feasibility study in a porcine model. VideoGIE. 2025 Mar 4;10(7):340-344. doi: 10.1016/j.vgie.2025.02.012. PMID: 40642399; PMCID: PMC12237756.
10. Jiang T, Yang Y, Luo W. Application of the fourth space in peroral endoscopic myotomy (POEM) surgery for achalasia. Rev Esp Enferm Dig. 2025 Jun 27. doi: 10.17235/reed.2025.11331/2025. Epub ahead of print. PMID: 40575899.
"
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Restrepo-Rodas G, Rodriguez J. Mastering the third space: Innovations in intramural endoscopic surgery for gastrointestinal disorders. World J Gastrointest Endosc 2025; 17(12): 111206 [PMID: 41479932 DOI: 10.4253/wjge.v17.i12.111206]
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"This article addresses an important and timely topic: differentiation-based strategies for colorectal cancer (CRC) therapy using natural products. The authors present a comprehensive in vitro study suggesting that Ferula assafoetida (FA) induces differentiation and apoptosis in Caco-2 colon cancer cells, potentially via activation of the JNK/MAPK pathway. As a reader, the work is interesting, methodologically broad, and conceptually aligned with current interests in natural compound–based cancer therapeutics, although certain conceptual and interpretative gaps limit its translational impact.
As a reader, I would regard this article as a useful exploratory study that justifies further mechanistic, protein-level, and in vivo investigations, rather than a conclusive demonstration of FA as a differentiation therapy for CRC."
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Abdelsalam HM, Abdelghany AM, Ahmed WA, Diab AA, Abdellateif MS. Ferula assafoetida induced colon cancer cells differentiation through JNK/MAPK signalling pathway activation. World J Exp Med 2025; 15(4): 110757 [PMID: 41497690 DOI: 10.5493/wjem.v15.i4.110757]
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"his retrospective study by Cooper et al. provides a valuable comparison of endoscopic band ligation (EBL) and endoscopic thermal therapy (ETT) as initial treatments for nodular gastric antral vascular ectasia (GAVE), a rare and challenging subtype. The analysis of 37 patients demonstrates that EBL outperforms ETT, with significantly higher clinical remission rates (90% vs. 69%, P=0.041), shorter treatment intervals (172 vs. 928 days, P=0.013), and fewer required endoscopic sessions (1.95 vs. 5.56, P=0.009), supported by improved hemoglobin levels and reduced transfusions. The findings robustly advocate for EBL as a first-line approach due to its efficiency and lower treatment burden. However, limitations include the small sample size, single-center design, and retrospective nature, which may affect generalizability. Despite this, the study fills a critical gap in nodular GAVE management and underscores the need for prospective multicenter trials to validate EBL's superiority and optimize clinical protocols."
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Cooper JA, Statham E, Holyfield A, Shoreibah MG, Peter S. Initial treatment approaches for nodular gastric antral vascular ectasia: A comparison of endoscopic band ligation and thermal therapies. World J Gastrointest Endosc 2025; 17(12): 111872 [PMID: 41479935 DOI: 10.4253/wjge.v17.i12.111872]
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"The minireview by El Dada et al. offers a timely synthesis of endoscopic ultrasound (EUS)-guided coil embolization for gastric varices (GVs), highlighting its potential as a safer, precise alternative to traditional therapies like cyanoacrylate injection. Strengths include systematic comparisons with meta-analytic data (e.g., 96.7% obliteration rate for EUS-coil/cyanoacrylate vs. 70.6% for cyanoacrylate alone), practical technical details (coil selection, Doppler confirmation), real-world case illustrations, and cost-effectiveness analysis (1,831vs.11,000 hospitalization). However, limitations persist: reliance on retrospective/single-center data, absence of randomized controlled trials (RCTs) against TIPS/BRTO, and lack of long-term (>5 years) rebleeding/complication data (e.g., coil migration). The authors appropriately call for multicenter RCTs to standardize protocols, explore material combinations, and integrate predictive biomarkers. Despite gaps, the review compellingly argues for EUS-coil’s inclusion in GV guidelines, serving as a valuable reference for advancing therapeutic endoscopy with balanced analysis of efficacy, safety, and accessibility."
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El Dada A, El Khoury M, Stephan P, Nehme F. Endoscopic ultrasound-guided coil embolization for gastric varices: A promising alternative to traditional therapies. World J Gastrointest Endosc 2025; 17(12): 110168 [PMID: 41479939 DOI: 10.4253/wjge.v17.i12.110168]
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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
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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
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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."
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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 [PMID: 41480211 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.
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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."
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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."
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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."
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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."
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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."
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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."
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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."
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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]
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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.
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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]
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"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."
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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)"
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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]
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"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."
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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 "
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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]
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"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.
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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.
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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. "
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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."
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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."
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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]
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"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."
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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]
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38
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"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.
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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]
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"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."
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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]
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40
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"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. "
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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]
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41
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"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.
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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]
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42
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"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. "
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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]
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"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."
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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]
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"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."
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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]
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"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."
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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]
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46
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"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 "
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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]
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"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."
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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]
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48
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"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."
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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]
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"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
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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]
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"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."
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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]
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