Gastroenterology Report最新文献

Background: Chronic radiation-induced intestinal injury (CRIII) is the most prevalent condition following radiation therapy in patients with pelvic malignancies. More than 15% of patients with severe CRIII require surgery. The histopathological features and their interactions with clinical presentation and outcomes remain largely unknown. The present study proposed a new pathological categorization of CRIII and investigated its relationship with clinical manifestations and outcomes.

Methods: This retrospective study included 111 patients with CRIII who were treated at the Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between January 2011 and December 2021. The features of ulcers, collagen fibers, and neoangiogenesis were measured via microscopic scoring, Masson's trichrome staining, and immunohistochemistry for CD34. The K-means method was used for cluster analysis based on these three data groups. The Kaplan-Meier method and log-rank test were used to examine the incidence-time curves of severe complications, including intestinal fistula, intestinal obstruction, and anemia, as endpoint events. Cox proportional hazards regression models were used for multivariate analyses.

Results: Four pathological CRIII subtypes were identified: mixed (48.7%), fibrosis (17.1%), telangiectasia (16.2%), and ulcers (18.0%). Patients with the ulcer subtype had a significant probability of developing a recto-intestinal fistula (P = 0.047) and a pathological pattern of deep serosal ulcers, which manifested as fistulas and thrombosis (75%, 15/20). Patients with the telangiectasia subtype consistently exhibited anemia (P = 0.002) and displayed significant arterial dilatation (72.2%, 13/18). Intestinal obstruction occurred more frequently in the fibrosis subtype due to a severe fibrotic pattern (31.6%, 6/19) and sclerotic collagen (57.9%, 11/19) (P = 0.014).

Conclusion: We proposed a new pathological classification for CRIII that better associates with clinical presentations and consequences.

Acute mesenteric ischemia (AMI) is a life-threatening vascular disorder that demands greater clinical and research attention due to its significant morbidity and mortality risks. Clinicians should maintain a high index of suspicion for AMI in patients presenting with severe abdominal pain disproportionate to physical findings, particularly those with atrial fibrillation or recent vasoconstrictor use. In such cases, prompt computed tomography angiography is recommended as the initial diagnostic modality, given its high sensitivity, specificity, efficiency, and favorable safety profile. Multi-disciplinary treatment plays a critical role in elucidating disease etiology and guiding therapeutic decision-making. For confirmed cases of intestinal necrosis, open surgical intervention remains the gold standard. Laparoscopic exploration offers a minimally invasive alternative for assessing bowel viability while reducing unnecessary surgical trauma in equivocal presentations. In the pre-necrotic phase of intestinal ischemia, emerging endovascular therapies demonstrate increasing promise due to their minimally invasive nature and improved clinical outcomes, warranting further investigation. Continuous clinical vigilance is essential throughout management. Persistent abdominal pain or signs of peritonitis may indicate disease progression, necessitating urgent reassessment for possible ischemic necrosis and therapeutic strategy adjustments. This review synthesizes current evidence by examining AMI pathophysiology, anatomical considerations, risk factors, and diagnostic-therapeutic advancements, with an emphasis on optimizing clinical decision-making in this critical condition.

Background: Endoscopic ultrasound (EUS)-guided liver biopsy has been an effective method for acquiring liver tissue. However, currently, there is no consensus on the technical details of biopsy sampling. This study aimed to optimize the EUS-guided liver biopsy techniques to improve specimen quality.

Methods: EUS-guided liver biopsies were performed in four porcine subjects with four technical aspects: negative pressure suction, number of actuations, two puncture manipulations, and two types of puncture needles. The primary outcomes were total specimen length (TSL) and complete portal tracts (CPTs), the secondary outcomes included longest specimen length (LSL), number of specimen pieces, specimen fragmentation, blood contamination, and bleeding.

Results: Forty-four biopsy samplings were performed. In Phase I, specimens obtained with 1-mL suction demonstrated significantly superior TSL, CPTs, and LSL compared with other suction techniques according to multiple comparisons. In Phase II, median TSL and CPTs with fewer than three actuations were significantly higher compared with those with at least three actuations (P < 0.05). In Phase III, the modified "click-puncture" yielded superior median CPTs, TSL, and LSL in comparison with conventional puncture (P < 0.05). In Phase IV, a fine-needle aspiration (FNA) needle was effective with a low risk of bleeding and foreign-tissue embedding (P < 0.05).

Conclusions: Optimal techniques for specimen quality in EUS-guided liver biopsy include using 1-mL suction, no more than three actuations, and employing a modified "click-puncture" manipulation. While FNA and fine-needle biopsy needles achieved comparable specimen quality, the FNA needle demonstrated the prevention of bleeding and foreign-tissue embedding.

Background: The association between delayed surgery and survival outcomes in locally advanced rectal cancer patients with a poor response to neoadjuvant chemoradiotherapy (nCRT) remains unclear. This study aimed to determine the optimal timing of surgery following nCRT in these patients and to explore the association between delayed surgery and survival outcomes.

Methods: Restricted cubic spline curves were used to determine the optimal timing of surgery for patients with a poor response to nCRT (ypT2-4N0 or ypTxN+). The patients were divided into two groups: the early surgery group and the delayed surgery group. Propensity score matching (PSM) analysis was employed to reduce the selection bias and survival analysis was conducted to assess the survival differences. Immunostaining of post-operative specimens was performed to investigate whether the difference in survival was associated with the CD8⁺ T-cell density in the tumor.

Results: A total of 583 patients were enrolled in this study. The optimal timing for surgery was determined to be 9 weeks after nCRT. In PSM analysis, delayed surgery was associated with worse disease-free survival (63.0% vs 76.3% at 5 years, 53.0% vs 76.3% at 10 years; P = 0.003) and cancer-specific survival (72.9% vs 85.5% at 5 years, 60.1% vs 81.8% at 10 years; P = 0.001). Immunostaining analysis showed that longer waiting times were associated with decreased CD8⁺ T-cell density in tumors (P = 0.017).

Conclusions: Patients who had a poor tumor response after nCRT, detected by using magnetic resonance imaging restaging or other assessments, need timely radical surgery without delay.

Distal malignant biliary obstruction (dMBO) is a common complication of advanced malignancies, particularly pancreatic cancer and biliary tract cancer, requiring biliary drainage to relieve symptoms. Endoscopic drainage using self-expandable metal stents (SEMS) is widely preferred due to improved long-term patency compared with plastic stents. However, the choice between fully covered SEMS (FCSEMS) and uncovered SEMS (UCSEMS) remains controversial, primarily due to migration risks associated with FCSEMS. Recent advances in stent design, such as anchoring flaps, flared ends, and anti-migration coatings, have been developed to improve FCSEMS stability. Additionally, techniques incorporating double-pigtail plastic stents as internal or external anchors have demonstrated significant reductions in migration rates. This review examines the current literature and evaluates various anti-migration strategies for FCSEMS, highlighting the clinical efficacy and challenges associated with each approach. Understanding these innovations is crucial for optimizing stent selection and improving patient outcomes in dMBO.

Background: Ulcerative colitis (UC) is a chronic disease that induces colon tissue damage. Previous studies have shown the clinical benefit of New Baitouweng Decoction (NBD). Here, we aimed to investigate the effects of NBD on dextran sodium sulfate (DSS)-induced UC and the underlying mechanisms in a mouse model.

Methods: UC was induced in mice by using DSS for 7 days. The efficacy of NBD was determined by analysing the pathological appearance and the expression of inflammatory factors and tight junction proteins. 16S rDNA sequencing was used to describe the gut microbiota. Gas chromatography-mass spectrometry was employed to quantify bile acid (BA) levels. Spearman's correlation analysis was conducted to determine the relationship between gut microbiota composition and BA profiles. Western blot was used to detect the amounts of farnesoid X receptor (FXR), Nod-like receptor (NLR) family pyrin domain containing 3 (NLRP3), caspase-1, and cleaved caspase-1.

Results: NBD reduced the disease activity index scores, ameliorated colonic pathological damage, inhibited colon inflammation, and repaired the intestinal barrier. In addition, 16S rDNA sequencing showed that NBD enhanced the relative abundance of beneficial bacteria such as Lactobacillus and Akkermansia, known to be involved in fecal BA metabolism. Furthermore, BA metabolomics analysis indicated that NBD elevated the concentrations of lithocholic acid and deoxycholic acid, thereby linking to the activation of the FXR pathway to inhibit NLRP3-mediated inflammation. Inhibiting FXR activation by using Z-guggulsterone impeded the protective function of NBD in DSS-induced UC.

Conclusion: NBD had a therapeutic effect on DSS-induced UC in a mouse model by regulating the gut microbiota, BAs, and subsequent FXR-NLRP3 pathway for decreasing the release of pro-inflammatory factors and repairing the intestinal barrier to preserve the equilibrium.

Dysregulation of bone morphogenetic protein 6 (BMP6) is found to be associated with gastric cancer development. Here, we further explored the functions of BMP6 in gastric cancer cell malignant behaviors, ferroptosis, and doxorubicin sensitivity and the mechanism driving BMP6 dysregulation. BMP6 mRNA detection was performed by quantitative polymerase chain reaction, and protein expression was tested by immunoblotting and immunohistochemistry. Subcutaneous xenograft studies were used to analyze in vivo effects. Cell growth was evaluated by CCK-8 and EdU assays. Cell invasiveness and motility were tested by transwell assay. Cell apoptosis was detected by flow cytometry. Cell ferroptosis was assessed by detecting related markers. Cytotoxicity assay was used to evaluate doxorubicin sensitivity. The relationship of the E3 ubiquitin ligase SMURF1 with BMP6 protein was predicted by UbiBrowser algorithm and verified by co-immunoprecipitation experiment and stability analysis. BMP6 expression was downregulated in gastric cancer, and its overexpression acted for in vitro suppression of gastric cancer cell growth, invasiveness, and migration. Increased BMP6 expression sensitized gastric cancer cells to doxorubicin therapy and enhanced cell ferroptosis. Mechanistically, SMURF1 mediated the ubiquitination and degradation of BMP6. Moreover, BMP6 reduction reversed sh-SMURF1-driven in vitro alterations of cell phenotypes and ferroptosis and in vivo enhancement of doxorubicin efficacy. Our study indicates that SMURF1-mediated BMP6 ubiquitination underlies the underexpression of BMP6 in gastric cancer. BMP6 upregulation induces gastric cancer cell ferroptosis and sensitizes cells to doxorubicin therapy. Our findings provide a therapeutic strategy in gastric cancer.

Background: Colorectal cancer (CRC) is one of the most lethal malignancies worldwide. Early diagnosis is critical in CRC treatment. More convenient and accurate biomarkers for early diagnosis are needed. However, whether circular RNAs (circRNAs) participate in colorectal tumorigenesis and their role in early diagnosis of CRC remain unknown.

Methods: We investigated the deregulated circRNAs and CRC-specific blood exosomal circRNAs in the Gene Expression Omnibus database and exoRBase. Functional assays were performed to evaluate the effects of hsa_circ_0004771 (circNRIP1) on proliferation and tumorigenesis both in vitro and in vivo. RNA pull-down, proteomic analysis, and RNA immunoprecipitation-polymerase chain reaction were performed to explore the underlying biological functions of circNRIP1 in CRC tumorigenesis.

Results: circNRIP1 was significantly downregulated in tumor tissues and increased in the blood exosomes of CRC patients. Knockdown of circNRIP1 significantly promoted CRC-cell proliferation and colony-forming ability in vitro and increased the tumor-formation ability in the xenograft mouse model. Mechanistically, circNRIP1 interacted with the K homology_1/2 domain of IGF2BP1 and blocked its m⁶A reader activity, and further reduced the stability of NACC1 mRNA and inhibited colorectal tumorigenesis.

Conclusions: circNRIP1 is an important tumor suppressor in CRC tumorigenesis and blood exosomal circNRIP1 could be an early diagnostic biomarker for CRC.