World Journal of Gastroenterology最新文献

Background: Esophageal stricture ranks among the most significant complications following endoscopic submucosal dissection (ESD). Excessive fibrotic repair is a typical pathological feature leading to stenosis after ESD.

Aim: To examine the effectiveness and underlying mechanism of Kangfuxin solution (KFX) in mitigating excessive fibrotic repair of the esophagus post-ESD.

Methods: Pigs received KFX at 0.74 mL/kg/d for 21 days after esophageal full circumferential ESD. Endoscopic examinations occurred on days 7 and 21 post-ESD. In vitro, recombinant transforming growth factor (TGF)-β1 (5 ng/mL) induced a fibrotic microenvironment in primary esophageal fibroblasts (pEsF). After 24 hours of KFX treatment (at 1.5%, 1%, and 0.5%), expression of α-smooth muscle actin-2 (ACTA2), fibronectin (FN), and type collagen I was assessed. Profibrotic signaling was analyzed, including TGF-β1, Smad2/3, and phosphor-smad2/3 (p-Smad2/3).

Results: Compared to the Control group, the groups treated with KFX and prednisolone exhibited reduced esophageal stenosis, lower weight loss rates, and improved food tolerance 21 d after ESD. After treatment, Masson staining revealed thinner and less dense collagen fibers in the submucosal layer. Additionally, the expression of fibrotic effector molecules was notably inhibited. Mechanistically, KFX downregulated the transduction levels of fibrotic functional molecules such as TGF-β1, Smad2/3, and p-Smad2/3. In vitro, pEsF exposed to TGF-β1-induced fibrotic microenvironment displayed increased fibrotic activity, which was reversed by KFX treatment, leading to reduced activation of ACTA2, FN, and collagen I. The 1.5% KFX treatment group showed decreased expression of p-Smad 2/3 in TGF-β1-activated pEsF.

Conclusion: KFX showed promise as a therapeutic option for post-full circumferential esophageal ESD strictures, potentially by suppressing fibroblast fibrotic activity through modulation of the TGF-β1/Smads signaling pathway.

Background: Laparoscopic liver resection (LLR) can be challenging due to the difficulty of establishing a retrohepatic tunnel under laparoscopy. Dissecting the third hepatic hilum before parenchymal transection often leads to significant liver mobilization, tumor compression, and bleeding from the short hepatic veins (SHVs). This study introduces a novel technique utilizing the ventral avascular area of the inferior vena cava (IVC), allowing SHVs to be addressed after parenchymal transection, thereby reducing surgical complexity and improving outcomes in in situ LLR.

Aim: To introduce and evaluate a novel LLR technique using the ventral avascular area of the IVC and compare its short-term outcomes with conventional methods.

Methods: The clinical cohort data of patients with pathologically confirmed hepatocellular carcinoma or intrahepatic cholangiocarcinoma who underwent conventional LLR and novel LLR between July 2021 and July 2023 at the First Affiliated Hospital of Chongqing Medical University were retrospectively analyzed. In novel LLR, we initially separated the caudate lobe from the IVC using dissecting forceps along the ventral avascular area of the IVC. Then, we transected the parenchyma of the left and right caudate lobes from the caudal side to the cephalic side using the avascular area as a marker. Subsequently, we addressed the SHVs and finally dissected the root of the right hepatic vein or left hepatic vein. The short-term postoperative outcomes and oncological results of the two approaches were evaluated and compared.

Results: A total of 256 patients were included, with 150 (58.59%) undergoing conventional LLR and 106 (41.41%) undergoing novel LLR. The novel technique resulted in significantly larger tumor resections (6.47 ± 2.96 cm vs 4.01 ± 2.33 cm, P < 0.001), shorter operative times (199.57 ± 60.37 minutes vs 262.33 ± 83.90 minutes, P < 0.001), less intraoperative blood loss (206.92 ± 37.09 mL vs 363.34 ± 131.27 mL, P < 0.001), and greater resection volume (345.11 ± 31.40 mL vs 264.38 ± 31.98 mL, P < 0.001) compared to conventional LLR.

Conclusion: This novel technique enhances liver resection outcomes by reducing intraoperative complications such as bleeding and tumor compression. It facilitates a safer, in situ removal of complex liver tumors, even in challenging anatomical locations. Compared to conventional methods, this technique offers significant advantages, including reduced operative time, blood loss, and improved overall surgical efficiency.

Parasites have coexisted with humans throughout history, forming either symbiotic relationships or causing significant morbidity and mortality. The liver is particularly vulnerable to parasitic infections, which can reside in, pass through, or be transported to the liver, leading to severe damage. This editorial explores various parasites that infect the liver, their clinical implications, and diagnostic considerations, as discussed in the article "Parasites of the liver: A global problem?". Parasites reach the liver primarily through oral ingestion, mucosal penetration, or the bloodstream, with some larvae even penetrating the skin. Hepatic parasites such as cestodes (Echinococcus), trematodes (Clonorchis, Opisthorchis), nematodes (Ascaris), and protozoa (Entamoeba histolytica) can also cause systemic infections like visceral leishmaniasis, malaria, cryptosporidiosis, and toxoplasmosis. Chronic infections like clonorchiasis and opisthorchiasis are linked to persistent hepatobiliary inflammation, potentially progressing to cholangiocarcinoma, a fatal bile duct cancer, particularly prevalent in Southeast Asia. The global nature of liver parasite infestations is alarming, with hundreds of millions affected worldwide. However, control over treatment quality remains suboptimal. Given the significant public health threat posed by these parasites, international medical organizations must prioritize improved diagnosis, treatment, and preventive measures. Strengthening educational efforts and enhancing healthcare provider training are critical steps toward mitigating the global impact of parasitic liver diseases.

The global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is estimated at 32.4%, reflecting its growing clinical significance. MASLD, which includes MASLD and metabolic dysfunction-associated steatohepatitis (MASH) has been linked to increased metabolic, cardiovascular, and malignant morbidity. Progression into fibrotic stages of MASLD is also strongly associated with liver-related mortality. The past few years have seen a heightened focus on creating innovative therapeutic strategies for MASH management. GLP-1 receptor agonists (RA) have also emerged as a potential treatment option. Studies on GLP-1 agonists, such as liraglutide and semaglutide, have demonstrated efficacy in MASH management, albeit with limited histological improvement of fibrosis. However, recent investigations into GLP-1/GIP RA (tirzepatide) and Glucagon/GLP-1 RA (survodutide) have shown even more encouraging results, with higher rates of MASH resolution and fibrosis improvement. The tolerability of these medications due to their gastrointestinal side effects remains a major concern. Future research should focus on optimizing drug regimens, identifying patients most likely to benefit, and balancing efficacy with tolerability. The evolving landscape of MASH therapeutics suggests a bright future, with the potential for combination therapies to further enhance patient outcomes.

Background: Wireless capsule endoscopy (WCE) has become an important noninvasive and portable tool for diagnosing digestive tract diseases and has been propelled by advancements in medical imaging technology. However, the complexity of the digestive tract structure, and the diversity of lesion types, results in different sites and types of lesions distinctly appearing in the images, posing a challenge for the accurate identification of digestive tract diseases.

Aim: To propose a deep learning-based lesion detection model to automatically identify and accurately label digestive tract lesions, thereby improving the diagnostic efficiency of doctors, and creating significant clinical application value.

Methods: In this paper, we propose a neural network model, WCE_Detection, for the accurate detection and classification of 23 classes of digestive tract lesion images. First, since multicategory lesion images exhibit various shapes and scales, a multidetection head strategy is adopted in the object detection network to increase the model's robustness for multiscale lesion detection. Moreover, a bidirectional feature pyramid network (BiFPN) is introduced, which effectively fuses shallow semantic features by adding skip connections, significantly reducing the detection error rate. On the basis of the above, we utilize the Swin Transformer with its unique self-attention mechanism and hierarchical structure in conjunction with the BiFPN feature fusion technique to enhance the feature representation of multicategory lesion images.

Results: The model constructed in this study achieved an mAP50 of 91.5% for detecting 23 lesions. More than eleven single-category lesions achieved an mAP50 of over 99.4%, and more than twenty lesions had an mAP50 value of over 80%. These results indicate that the model outperforms other state-of-the-art models in the end-to-end integrated detection of human digestive tract lesion images.

Conclusion: The deep learning-based object detection network detects multiple digestive tract lesions in WCE images with high accuracy, improving the diagnostic efficiency of doctors, and demonstrating significant clinical application value.

Calculus bovis (C. bovis) is widely used in traditional Chinese medicine due to its anti-tumor effects. C. bovis shifts liver cancer tumor microenvironment towards regression by hindering tumor-associated macrophages polarization. Huang et al have demonstrated in their study that C. bovis inhibits M2-tumour-associated macrophages (TAM) polarization by halting the Wnt/β-catenin pathway. The mechanism of action by which C. bovis exerts its anti-tumor effects is multifaceted and includes network pharmacology, transcriptomics and molecular docking. In vitro assays demonstrated that C. bovis-containing serum inhibited M2-TAMs polarization in human hepatocellular carcinomas cells. C. bovis was found to have 22 active components of which 11 were detected in the bloodstream. The anti-neoplastic activity of C. bovis lies in suppressing M2-TAM polarization by modulation of the Wnt/B-catenin pathway. In vitro and in vivo experiments have shown that C. bovis suppresses M2-TAM polarization and halts the Wnt signaling pathway. The inhibitory effect of C. bovis on M2-TAM was reversed by SKL2001, a Wnt agonist, which highlights C. bovis's selectivity and specificity. C. bovis inhibits M2-TAM polarization by modulating the Wnt/ β-catenin pathway, thus impeding liver cancer growth. Owing to the "cross-talk" between transforming growth factor-β (TGF-β) signaling pathways, this paper highlights the potential significance of C. bovis in controlling the tumor microenvironment not only through hindering the polarization of M2-TAMs via the Wnt signaling pathway, but also by downregulating TGF-β. Therefore, C. bovis serves as an igniter to fuel a cascade of signaling events that culminates in the regression of the tumor microenvironment by compromising oncogenesis and angiogenesis. TGF-β is also known for its pro-fibrotic properties. Therefore, C. bovis may play a pivotal role in treating liver fibrosis by downregulating TGF-β, thus hindering oncogenesis, angiogenesis and liver fibrosis. Hence, the "domino effect".

Small cell lung carcinoma metastatic to the stomach, whether synchronous or metachronous, is a rare phenomenon accounting for < 0.5% of lung cancers. Hence it can be overlooked by clinicians resulting in delayed diagnosis. This manuscript comments on Yang et al's article which reported 3 such cases. The main diagnostic features are based on routine morphology comprised of small cells with hyperchromatic nuclei, scant cytoplasm, brisk mitoses and necrosis. This can be supplemented by immunohistochemistry demonstrating positivity for cytokeratin, thyroid transcription factor-1 and neuroendocrine markers as well as a high Ki-67 labelling index. Imaging modalities such as positron emission tomography/contrast computed tomography help to confirm lung origin and rule out the possibility of extra-pulmonary small cell carcinoma. The predominant mechanism of spread is most likely hematogeneous. Prognosis is generally poor since this represents stage 4 disease but survival can be improved by chemo/radiotherapy and palliative surgery in select cases. Though outcomes have not changed much in the last several decades, the recent Food and Drug Administration approval of immune checkpoint inhibitors was a significant milestone as was the delineation of small cell lung carcinoma molecular subtypes. Liquid biopsies are increasingly being used for biomarker studies in clinical trials to assess treatment response and prognosis.

Background: Hepatocellular carcinoma (HCC) is a prevalent and aggressive tumor. Sorafenib is the first-line treatment for patients with advanced HCC, but resistance to sorafenib has become a significant challenge in this therapy. Cancer stem cells play a crucial role in sorafenib resistance in HCC. Our previous study revealed that the long non-coding RNA (lncRNA) KIF9-AS1 is an oncogenic gene in HCC. However, the role of KIF9-AS1 in drug resistance and cancer stemness in HCC remains unclear. Herein, we aimed to investigate the function and mechanism of the lncRNA KIF9-AS1 in cancer stemness and drug resistance in HCC.

Aim: To describe the role of the lncRNA KIF9-AS1 in cancer stemness and drug resistance in HCC and elucidate the underlying mechanism.

Methods: Tumor tissue and adjacent non-cancerous tissue samples were collected from HCC patients. Sphere formation was quantified via a tumor sphere assay. Cell viability, proliferation, and apoptosis were evaluated via Cell Counting Kit-8, flow cytometry, and colony formation assays, respectively. The interactions between the lncRNA KIF9-AS1 and its downstream targets were confirmed via RNA immunoprecipitation and coimmunoprecipitation. The tumorigenic role of KIF9-AS1 was validated in a mouse model.

Results: Compared with that in normal controls, the expression of the lncRNA KIF9-AS1 was upregulated in HCC tissues. Knockdown of KIF9-AS1 inhibited stemness and attenuated sorafenib resistance in HCC cells. Mechanistically, N6-methyladenosine modification mediated by methyltransferase-like 3/insulin-like growth factor 2 mRNA-binding protein 1 stabilized and increased the expression of KIF9-AS1. Additionally, KIF9-AS1 increased the stability and expression of short stature homeobox 2 by promoting ubiquitin-specific peptidase 1-induced deubiquitination. Furthermore, depletion of KIF9-AS1 alleviated sorafenib resistance in a xenograft mouse model of HCC.

Conclusion: The N6-methyladenosine-modified lncRNA KIF9-AS1 promoted stemness and sorafenib resistance in HCC by upregulating short stature homeobox 2 expression.

Background: Diagnosing laryngopharyngeal reflux (LPR) is challenging due to overlapping symptoms. While proton pump inhibitors (PPIs) are commonly prescribed, reliable predictors of their responsiveness are unclear. Reflux monitoring technologies like dual potential of hydrogen (pH) sensors and multichannel intraluminal impedance-pH (MII-pH) could improve diagnosis. Research suggests that a composite pH parameter, defined by ≥ 2 pharyngeal acid reflux (PAR) episodes and/or excessive esophageal acid reflux (EAR), predicts PPI efficacy. The criteria for PAR episodes, a pharyngeal pH drop of ≥ 2 units to < 5 within 30 seconds during esophageal acidification, showed strong interobserver reliability. We hypothesized that PAR episodes alone might also predict PPI responsiveness.

Aim: To investigate whether PAR episodes alone predict a positive response to PPI therapy.

Methods: Patients suspected of having LPR were prospectively recruited from otolaryngologic clinics in three Taiwanese tertiary centers. They underwent a 24-hour esophagopharyngeal pH test using either 3-pH-sensor or hypopharyngeal MII-pH catheters while off medication, followed by a 12-week esomeprazole course (40 mg twice daily). Participants were categorized into four groups based on pH results: PAR alone, EAR alone, both pH (+), and both pH (-). The primary outcome was a ≥ 50% reduction in primary laryngeal symptoms, with observers blinded to group assignments.

Results: A total of 522 patients (mean age 52.3 ± 12.8 years, 54% male) were recruited. Of these, 190 (mean age 51.5 ± 12.4 years, 61% male) completed the treatment, and 89 (47%) responded to PPI therapy. Response rates were highest in the PAR alone group (73%, n = 11), followed by EAR alone (59%, n = 68), both pH (+) (56%, n = 18), and both pH (-) (33%, n = 93). Multivariate analysis adjusting for age, sex, body mass index, and endoscopic esophagitis showed that participants with PAR alone, EAR alone, and both pH (+) were 7.4-fold (P = 0.008), 4.2-fold (P = 0.0002), and 3.4-fold (P = 0.03) more likely to respond to PPI therapy, respectively, compared to the both pH (-) group. Secondary analyses using the definition of ≥ 1 PAR episode were less robust.

Conclusion: In the absence of proven hypopharyngeal predictors, this post-hoc analysis found that baseline ≥ 2 PAR episodes alone are linked to PPI responsiveness, suggesting the importance of hypopharyngeal reflux monitoring.

The study by López-Gómez et al, reports a significantly low prevalence (4.5%) of Helicobacter pylori (H. pylori) infection in esophageal cancer patients, contrasting sharply with the general population's infection rate. This finding challenges the established negative association between H. pylori and gastric malignancies, suggesting a potential protective role of H. pylori against esophageal carcinoma, particularly in the context of widespread proton pump inhibitor use. However, the study's retrospective nature, single-center design, and small sample size limit the generalizability of the findings and raise concerns about selection bias and statistical power. Diagnostic methods primarily based on histology may not detect all cases, especially those with prior antibiotic or proton pump inhibitor use. Additionally, the study does not account for various confounding factors such as dietary habits, socio-economic status, and genetic predispositions that could affect the association between H. pylori and esophageal carcinoma. Further research with larger, more diverse cohorts and comprehensive data collection is necessary to clarify the complex relationship between H. pylori and esophageal carcinoma and substantiate these preliminary findings.