Translational gastroenterology and hepatology最新文献

Background: Hepatocellular carcinoma (HCC) surveillance using 6-monthly ultrasonography (US) intervals is recommended. This study investigated the factors associated with early-stage HCC detection.

Methods: All patients with a new HCC diagnosis for the first time between 2019 and 2022 were included. All pre-treatment imaging was independently reviewed according to Liver Imaging Reporting and Data System (LI-RADS) criteria. Early-stage HCC was defined as a single tumour <50 mm or up to 3 tumours all <30 mm. Rate of adherence was expressed as the proportion of the number of 6-monthly surveillance US performed relative to the total number of surveillance US the patient should have undergone over the preceding 5 years or since the diagnosis of cirrhosis, if it was within the preceding 5 years.

Results: The study cohort included 175 patients with new HCC. The median age at diagnosis was 71 years; 78% were males; median body mass index (BMI) was 29.3 kg/m²; 94% were of European ancestry and the most common aetiology was metabolic dysfunction-associated steatotic liver disease (MASLD) (58%). One third (37%) presented through primary surveillance (surveillance group) and the remainder were found to have HCC when investigated for other indications (incidental group). Only the age at presentation [P=0.003; odds ratio (OR) 0.937, 95% confidence interval (CI): 0.899-0.978] and being on HCC surveillance (P<0.001; OR 5.867, 95% CI: 2.533-13.586), but not surveillance adherence were independently associated with early-stage HCC detection.

Conclusions: Being part of primary surveillance, irrespective of adherence rate, is associated with early stage HCC detection. As many patients as possible should be enrolled into primary surveillance programme, even if adherence to recommended frequency is not followed rigorously.

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is a chronic, immune-mediated disorder that impacts the intestinal tract. The gut microbiota, a diverse community of microorganisms, plays a pivotal role in the initiation, development, and progression of IBD by modulating inflammation, and immune responses, and maintaining gut homeostasis. Dysbiosis, or an imbalance in the gut microbiota, is frequently observed in IBD patients and is believed to contribute to the pathogenesis of the disease by disrupting the mucosal immune system. Fecal microbiota transplantation (FMT) involves transferring feces from a healthy donor (HD) into a recipient and has emerged as a promising therapeutic approach for IBD. The primary goal of FMT is to restore microbial balance in the recipient's gut, improving both microbiota composition and immune function. Numerous preclinical and clinical studies have demonstrated varying degrees of success in alleviating IBD symptoms through FMT. The benefits of FMT include modulation of gut bacteria abundance, restoration of microbial diversity, and enhancement of immune system regulation, all of which contribute to reducing IBD-related inflammation. This review presents a comprehensive analysis of animal studies and clinical trials exploring using FMT as a treatment for IBD. Understanding the underlying mechanisms of FMT in IBD is crucial for designing effective therapeutic strategies and optimizing its clinical impact.

Background: Preoperative prediction of laparoscopic surgical difficulty in gallstone patients is crucial for improving surgical outcomes. This study aimed to develop and validate a nomogram based on advanced machine learning algorithms, incorporating key clinical and systemic inflammatory response indicators, such as the C-reactive protein to albumin ratio (CAR).

Methods: A retrospective analysis was conducted on 362 eligible patients who underwent laparoscopic cholecystectomy (LC) for gallstones between 2013 and 2019. A total of 420 patients were initially identified, with 58 excluded based on predefined criteria such as age and incomplete records. The remaining patients were divided into a training set (n=253) and a validation set (n=109). The development of the nomogram involved multiple analytical techniques, including machine learning methods such as least absolute shrinkage and selection operator (LASSO) regression, decision tree analysis, and support vector machine (SVM) models, along with traditional statistical methods like univariate and multivariate logistic regression. Significant predictors, including CAR, white blood cell count (WBC), and gallbladder wall thickness, were integrated into the final predictive model. Model performance was evaluated using receiver operating characteristic (ROC) curve analysis and calibration plots.

Results: The machine learning-based model demonstrated strong predictive capability, with an area under the curve (AUC) of 0.774 in the training set and 0.863 in the validation set. Calibration plots showed good agreement between predicted and actual outcomes, with mean absolute errors of 0.035 and 0.05 for the training and validation sets, respectively.

Conclusions: This study demonstrates the utility of applying machine learning algorithms to develop a robust nomogram for preoperative prediction of laparoscopic surgical difficulty. By integrating key clinical variables and systemic inflammatory markers, the model provides an effective tool for improving surgical planning and enhancing patient outcomes.

Background: Although patients with gastric cancer liver metastases (GCLM) may achieve survival benefits after radical surgery, there is controversy regarding the surgical indications and choice of surgical methods. This study aims to investigate the impact of hepatic resection (HR) on the prognosis of patients with GCLM who have undergone radical resection of the primary tumor.

Methods: This study conducted a retrospective analysis of 120 patients with GCLM who have undergone resection of the primary tumor. The patients were divided into an HR group and a non-hepatic resection (NHR) group. Propensity score matching (PSM) was analyzed and patients' prognoses were followed up and compared.

Results: The PSM analysis included a total of 88 patients. The HR group had a median overall survival (OS) time of 35.0 months [95% confidence interval (CI): 30.7-39.3], with 1-, 2-, and 3-year survival rates of 88.0%, 81.5%, and 46.8% respectively. The NHR group had a median OS time of 16.0 months (95% CI: 10.5-21.5), with 1-, 2-, and 3-year survival rates of 56.8%, 30.8%, and 22.4% respectively. The median OS time was statistically different between the two groups. Extrahepatic metastasis (hazard ratio =2.777; 95% CI: 1.598-5.223; P=0.002) and HR (hazard ratio =0.154; 95% CI: 0.040-0.594; P=0.007) were significant factors for OS. In the HR group, laparoscopic surgery (P=0.004) and extrahepatic recurrence (P=0.008) were significant factors for intrahepatic recurrence-free survival (IHRFS).

Conclusions: HR can significantly improve the prognosis of GCLM with resected primary tumors. Laparoscopic surgery is preferred as the surgical approach. Patients with extrahepatic recurrence have a shorter IHRFS.

Background and objective: Chromogranin A (CgA) is extensively recognized as a biomarker in neuroendocrine neoplasms (NENs) due to its secretion alongside peptide hormones and biogenic amines in neuroendocrine cells. Despite its widespread clinical use, the reliability of CgA as a diagnostic and prognostic tool remains controversial because of its variable expression in various diseases and the influence of factors such as medication and disease characteristics. This review critically examines the role of CgA beyond neuroendocrine contexts, particularly in gastrointestinal conditions where increased levels may mislead clinical diagnostics.

Methods: This review was conducted by performing a search on the PubMed database regarding CgA and both pathological and non-pathological conditions, excluding NENs.

Key content and findings: Conditions such as chronic atrophic gastritis (CAG), proton pump inhibitor usage, and inflammatory bowel diseases (IBDs), among others, can lead to elevated CgA levels, often without any malignant association. Studies reviewed underscore the necessity for cautious interpretation of elevated CgA levels to avoid misdiagnosis and unnecessary anxiety in patients. The review further discusses the implications of non-neuroendocrine diseases contributing to elevated CgA levels, emphasizing the need for improved specificity in testing and a greater awareness among clinicians about the factors influencing CgA levels.

Conclusions: This comprehensive understanding assists in better managing patient outcomes through more accurate diagnosis and appropriate therapeutic interventions.

Background: Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumours of the digestive system and the third leading cause of cancer-related deaths worldwide. As the most common type of primary liver cancer, HCC is associated with poor prognosis despite advancements in treatment options such as radical resection, liver transplantation, and adjuvant therapies. Surgical resection remains the cornerstone of HCC treatment; however, postoperative recurrence and metastasis pose significant challenges to patient survival. Intraoperative factors, including immune suppression and the use of certain anaesthetics, have been implicated in tumour cell dissemination and recurrence. While anaesthetic agents like propofol are known to influence tumour cell proliferation, differentiation, and apoptosis. Ciprofol, a novel intravenous anaesthetic, has demonstrated clinical safety and efficacy, but its potential impact on HCC progression and underlying mechanisms requires further exploration. This study aims to explore how ciprofol affects the behaviour of HCC cells and the underlying mechanisms.

Methods: Hep3B and HCCLM3 HCC cell lines were treated with varying concentrations of ciprofol. The cell numbers were measured at different time points using the Cell Counting Kit-8 (CCK-8) to find the active concentration. Proliferation was assessed by colony formation and 5-ethynl-2'-deoxyuridine (EdU) assays, whereas invasion and migration were tested using Transwell and wound healing assays. Subcutaneous xenograft and orthotopic liver transplantation models were used to study tumour growth in vivo, and a lung metastasis model was created to examine its effects on metastasis. RNA sequencing (RNA-seq) identified transcriptional changes after ciprofol treatment, and western blot and immunofluorescence (IF) validated these findings.

Results: Ciprofol inhibited the proliferation, migration, and invasion of Hep3B and HCCLM3 cells in a manner dependent on both time and dosage. It also reduced tumour growth and lung metastasis in mice. RNA-seq showed that ciprofol affected the MAPK/ERK pathway, which was confirmed by the reduced phosphorylation levels of Raf, MEK, and ERK, without affecting total protein levels.

Conclusions: Ciprofol inhibited the MAPK/ERK pathway by reducing the phosphorylation of Raf, MEK, and ERK, which may explain its inhibitory effects on HCC. The results of this study could guide the use of anaesthetic drugs in HCC surgery.

Background: Sarcopenia is an important prognostic factor for chronic liver disease (CLD), and systemic inflammation, which contributes to sarcopenia, is also a potent exacerbator of cirrhosis. This study introduces the novel concept of inflammatory sarcopenia (I-SP) and clarifies its clinical profile.

Methods: This single-center retrospective study included 762 CLD patients with liver stiffness (LS) measured by magnetic resonance elastography (MRE). I-SP was defined as patients with C-reactive protein (CRP) ≥0.5 mg/dL and low muscle mass assessed by magnetic resonance imaging (MRI), compared with non-sarcopenia (non-SP) and non-I-SP (NI-SP). Prognostic analysis for advanced CLD (ACLD) was conducted using a Cox proportional hazards model, with ACLD defined as LS ≥3 kPa.

Results: In CLD, 534, 168, and 60 patients had non-SP, NI-SP, and I-SP, respectively. I-SP patients had a higher complication rate of hepatocellular carcinoma (HCC), which correlated with increased LS and worsening albumin-bilirubin (ALBI) scores (P<0.01 for each). Multivariate logistic regression identified LS (≥3 kPa), ALBI score, alcohol-related liver disease (ALD), and HCC as associated with I-SP (P<0.05 for each). In the follow-up of NI-SP patients (median 36 months), 13% progressed to I-SP and none of the patients had LS <3 kPa. In the ACLD study (n=306), patient survival was stratified into non-SP, NI-SP, and I-SP groups [hazard ratio (HR) reference, 3.4, 15.0, P<0.01 for each]. Multivariate analysis identified ALBI score, HCC, and I-SP as independent prognostic factors (P<0.05 for each).

Conclusions: Our study provides a novel perspective on sarcopenia in CLD and advocates a two-step treatment strategy focused on preventing sarcopenia in ACLD and controlling its progression to I-SP.

Background: Early-onset colorectal cancer (EO-CRC), defined as being diagnosed before the age of 50 years, is becoming increasingly prevalent. Among these patients, synchronous early-onset colorectal liver metastases (EO-CRLM) have emerged as a leading cause of mortality. This study aims to investigate the epidemiology, clinicopathological characteristics, and survival outcomes related to synchronous EO-CRLM to provide a clearer understanding of the challenges faced by patients with synchronous EO-CRLM.

Methods: The National Cancer Database was queried for patients with synchronous CRLM diagnosed from 2010 to 2019. Patients were then stratified by age of onset: EO-CRLM (younger than 50 years old) and late-onset colorectal liver metastases (LO-CRLM) (50 years old or older). The incidence, limited-duration prevalence rates (over a 10-year period), clinicopathological characteristics and overall survival (OS) were assessed.

Results: Among 115,422 patients with CRLM, EO-CRLM and LO-CRLM were observed in 17,536 (15.2%) patients and in 97,886 (84.8%) patients, respectively. The annual age-adjusted incidence of EO-CRLM increased from 0.48 to 0.69 per 100,000 population from 2010 to 2019 [average annual percentage change (AAPC): 5.1, 95% confidence interval (CI): 4.1 to 6.1], significantly faster than that of LO-CRLM (AAPC difference: 3.5, 95% CI: 2.5 to 4.5; P<0.001). The 10-year limited-duration prevalence for EO-CRLM increased from 0.0004% in 2010 to 0.0020% in 2019 (AAPC: 15.7, 95% CI: 10.2 to 21.5). A comparison of the clinicopathological features revealed that, compared with LO-CRLM, EO-CRLM patients were more likely to reside in urban areas, have higher rates of high school completion, have higher income, and be covered by private insurance/managed care. Genetic analysis revealed EO-CRLM with microsatellite instability (MSI)-high had the largest increase of AAPC of 28.7 (95% CI: 13.1 to 46.3) compared to MSI-low and microsatellite stability (MSS) (P<0.001). Similarly, EO-CRLM patients had a rapid rise in Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations with AAPC of 10.6 (95% CI: 8.8 to 12.5). Compared with LO-CRLM, EO-CRLM was associated with improved OS in inverse probability of treatment weighting-adjusted Cox proportional hazards regression analysis (hazard ratio: 0.876, 95% CI: 0.838 to 0.915; P<0.001).

Conclusions: The incidence of EO-CRLM has increased rapidly, and represents a distinct population in terms of socioeconomic and clinicopathological characteristics. Among this cohort, the prognosis of patients with EO-CRLM was favorable compared to that of patients with LO-CRLM.