Translational gastroenterology and hepatology最新文献

Background: Hepatic ischemia and reperfusion (I/R) injury is a common problem faced by patients undergoing clinical liver transplantation and hepatectomy, but the specific mechanism of liver I/R injury has not been fully elucidated. The protein degradation complex 11S proteasome is involved in apoptosis, proliferation and cell cycle regulation by regulating the 11S proteasome regulatory complex (REG)γ. The main objective of this study is to explore the role and specific mechanism of REGγ in liver I/R.

Methods: By constructing a model of in vivo hepatic I/R injury in mice and a model of hypoxia and reoxygenation (H/R) in isolated hepatocytes. First, the REGγ expression were detected during hepatic I/R in mice. Second, to investigate the effects of REGγ knockout (KO) on liver necrosis, inflammatory response, apoptosis and mitochondrial function. Finally, mouse liver Src homology collagen (p66shc) mitochondrial translocation was detected.

Results: The expression of REGγ was up-regulated during hepatic I/R. REGγ KO had significantly reduced liver tissue infarct size, liver transaminases, inflammatory cells infiltration, inflammatory cytokine and activation of nuclear factor kappa-B (NF-κB) signaling pathway and cell apoptosis. REGγ KO had significantly alleviated the mitochondrial damage, decreased the up-regulated level of cytochrome C, reactive oxygen species (ROS). REGγ KO had significantly reduced p66shc mitochondrial translocation in mice.

Conclusions: The experimental results of this study indicated that REGγ has an important role in preventing liver I/R injury and may play a role through the mitochondrial p66shc signaling pathway.

Background: Liver transplantation (LT) is the most effective and radical treatment for hepatocellular carcinoma (HCC). Most LT criteria are based on the morphological characteristics of tumors, which are not enough to predict the risk of tumor recurrence. It is found that some serological biomarkers can predict tumor recurrence and may be a good indicator for selecting suitable HCC patients for LT. This article aims to evaluate the predictive effect of preoperative serological indicators on long-term overall survival (OS) and tumor recurrence-free survival (TFS) of patients with HCC after LT, and to explore its significance for expanding the Milan criteria.

Methods: Clinical data of 253 patients after LT in HCC were collected retrospectively. The receiver operating characteristic curve was used to calculate the best cut-off value. χ² test was used to analyze the correlation between preoperative serological indicators and tumor pathological features. Univariate and multivariate analyses were used to analyze the risk factors affecting the OS and TFS rates and the predictive values of different LT criteria were compared. Nomogram model was used to predict the OS and TFS rates of patients exceeding Milan criteria.

Results: Independent risk factors for poor OS and TFS rates were alpha-fetoprotein (AFP) >200 ng/mL, gamma-glutamyl transpeptidase (GGT) >80 IU/L, total tumor diameter (TTD) >8 cm and microsatellite lesions. Nomogram model showed patients beyond Milan criteria had better survival when AFP ≤200 ng/mL and GGT ≤80 IU/L or AFP >200 ng/mL, GGT ≤80 IU/L and TTD ≤8 cm. According to Milan criteria, AFP, GGT and TTD, Milan-AFP-GGT-TTD (M-AGT) criteria was established. There was no significant difference in OS and TFS rates among patients in M-AGT, Milan, Hangzhou, Malaya and the University of California at San Francisco (UCSF) criteria.

Conclusions: Preoperative serological indicators AFP and GGT can effectively predict long-term OS and TFS in HCC patients after LT. Establishing M-AGT criteria based on serological indicators is helpful to supplement the Milan criteria.

The rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and its more severe form, metabolic dysfunction-associated steatohepatitis (MASH), is closely linked with a heightened risk of hepatocellular carcinoma (HCC), the fourth leading cause of cancer-related deaths worldwide. Despite the elevated risk of HCC in patients with MASLD, the existing surveillance guidelines are inadequate, particularly for those without cirrhosis. This review evaluates current HCC surveillance practices in patients with MASLD and their shortcomings. It also highlights the critical need for enhanced HCC risk stratification and diagnostic accuracy through new techniques. In this review article, we performed a comprehensive literature review of studies focusing on HCC risk factors in MASLD/MASH patients from 2000 to 2023. We discussed that demographics, comorbidities, liver fibrosis, and genetic markers play critical roles in HCC risk stratification. Additionally, non-invasive tests (NITs) for fibrosis may improve the accuracy for HCC risk stratification and diagnosis. More recently, innovative approaches, such as machine learning techniques and liquid biopsy utilizing extracellular vesicles, cell-free DNA, and circulating tumor cells show promise in redefining early HCC detection. Thus, integrating these various risk factors could optimize early detection of HCC for the growing MASLD/MASH patient population. However, further research is needed to confirm their effectiveness and practical implementation in clinical settings.

Background: While single organ metastases generally present a more optimistic prognosis compared to multiple metastases, the influence of the specific organ site for single organ metastases on prognosis remains undetermined. This retrospective study aimed to investigate the prognostic differences in late-stage gastric cancer with single organ metastasis.

Methods: Data for patients diagnosed with gastric cancer were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database for survival analysis, covering years spanning from 2010 to 2016. Furthermore, Kaplan-Meier survival curves and Cox regression were utilized to analyze overall survival (OS) and disease-specific survival (DSS). Additionally, given the impact of confounders and bias on the results, prognosis was further analyzed using propensity score matching (PSM) and floating absolute risk methods.

Results: A cohort comprising 4,297 patients diagnosed with gastric cancer and exhibiting single organ metastasis was hereby enrolled. Liver metastasis was the most common (71% of the total), while brain metastasis accounted for the least (1.7% of the total). Compared to other metastases, patients with bone metastasis presented the worst OS [hazard ratio (HR), 1.319; 95% confidence interval (CI): 1.207-1.442; P<0.001], and this remained consistent even upon the application of floating absolute risk (HR, 1.10; 95% CI: 1.01-1.20) and PSM methods (HR, 1.187; 95% CI: 1.053-1.339; P=0.005). In addition, subgroup analysis and interaction tests of OS revealed an interaction between age (P=0.02), histological type (P=0.002), and bone metastasis.

Conclusions: In patients with single organ metastasis of gastric cancer, the prognosis varies by the metastatic site, with bone metastasis presenting the poorest outcome. Overall, this study forges a foundation for further research on the mechanisms and patterns of different metastatic sites in gastric cancer and informs treatment strategies.

Background: Crohn's disease continues to be a major component of inflammatory bowel disease with increasing incidence and prevalence. Increasing publications of surgery in Crohn's disease have significantly expanded the research scope. The aim of this study is to characterize main topics and a full landscape of surgery in Crohn's disease.

Methods: Studies of surgery in Crohn's disease from 2000 to 2020 were screened and retrieved from the Web of Science Core Collection database. Latent Dirichlet allocation (LDA), one of machine-learning algorithms for natural language processing, was employed for topic modeling. All the studies were processed, analyzed and visualized by R software, CiteSpace and Gephi.

Results: A total of 3,697 original publications were identified from the database. USA was the leading country with the most top institutions such as Cleveland Clin Florida and Mayo Clinic and Mayo Foundation. Increasing impact of institutions from Korea and China was also noticed. Bo Shen was the leading author in publication. A machine learning based topic modeling identified major clusters, including disease assessment, surgical treatment and complications, risk factors and epidemiology, disease development and diagnosis, target treatment and recurrence. Three topics attracted continuous high research attention, including expression of intestinal cell, perianal fistula and laparoscopic and open operation.

Conclusions: This study identified key topics relating to the development of surgery in Crohn's disease, and provided bibliometric insights and perspectives for future development in the field of surgery in Crohn's disease.

Background and objective: This narrative review addresses idiopathic acute pancreatitis (IAP) and its epidemiology, diagnosis, clinical course and treatment during the last decade. As there is no previously validated protocol for finding the aetiology of acute pancreatitis (AP), the primary aim of this study is to find, describe and unify evidence about the diagnostic work-up of AP to diagnose the true IAP. By finding the aetiology with the highest possible yield it may be possible to reduce recurrent AP (RAP) episodes and related morbidity and thereby decrease health care costs and possibly improve patients' quality of life.

Methods: This narrative review includes articles retrieved from PubMed search with publications from 2013-2023. Cross references were used when found relevant.

Key content and findings: The rates of aetiologies of AP and the diagnostics performed behind these numbers vary widely between different studies, time periods and different geographical regions, as there is no unified algorithm in diagnostic work-up of IAP. In this study, we describe an up-to-date summary of epidemiology, diagnostic course and treatment of IAP, and propose an algorithm of IAP diagnostics in light of recent scientific studies and their outcomes and address possible treatments of IAP.

Conclusions: Although aetiology is key for AP management, there is still no validated protocol for aetiological diagnosis. IAP is relevant due to its recurrence rate and possible evolution to chronic pancreatitis. We still need more studies addressing this topic and evaluating new diagnostic protocols with advanced tests and treatment strategies in true IAP.

Background and objective: Hepatobiliary diseases are a longstanding and significant medical challenge which, despite advances in surgical techniques, still carry risks for postoperative complications such as anastomotic leaks (ALs), which can include both postoperative pancreatic fistula (POPF) and bile leaks (BL). These complications incur significant human and economic costs on all those involved, including the patient, healthcare providers, and hospital systems. The aim of this study was to construct a narrative review of literature surrounding definitions and grading systems for ALs in the context of hepato-pancreato-biliary (HPB) procedures, and consequences of POPF and BL.

Methods: A literature review was conducted by examining databases including PubMed, Web of Science, OVID Embase, Google Scholar, and Cochrane library databases. Searches were performed with the following search criteria: (((((((anastomosis) OR (anastomotic leak*)) OR (postoperative pancreatic fistula)) OR (bile leak*)) OR (pancreaticoduodenectomy)) OR (whipple)) AND ((hepatobiliary) OR (hepato-pancreato-biliary)) AND ((definition) OR (grading system*) OR (consequences) OR (outcomes) OR (risk factor*) OR (morbidity) OR (mortality))). Publications that were retrieved underwent further assessment to ensure other relevant publications were identified and included.

Key content and findings: A universally accepted definition and grading system for POPF and BL continues to be lacking, leading to variability in reported incidence in the literature. Various groups have worked to publish guidelines for defining and grading POPF and BL, with the International Study Group in Pancreatic Surgery (ISGPS) and International Study Group for Liver Surgery (ISGLS) definitions the current most recommended definitions for POPF and BL, respectively. The burden of AL on patients, healthcare providers, and hospitals is well documented in evidence from leak consequences, such as increased morbidity and mortality, higher reoperation rates, and increased readmission rates, among others.

Conclusions: AL remains a significant challenge in HPB surgery, despite medical advancements. Understanding the progress made in defining and grading leaks, as well as the range of negative outcomes that arise from AL, is crucial in improving patient care, reduce surgical mortality, and drive further advancements in earlier detection and treatment of AL.

Background: Primary hepatic angiosarcoma (PHA) is a rare hepatic malignancy primarily observed in the elderly. It carries a poor prognosis as a result of the characteristics of rapid progression, high aggressiveness, and resistance to traditional chemo- and radiotherapies. Its nonspecific clinical manifestations, along with the lack of laboratory features and various imaging findings, make it hard to recognize in clinic, especially among non-high-risk populations. Hence, pathological diagnosis is essential to establish an accurate diagnosis.

Case description: In the present report, a young male presented with right upper quadrant abdominal pain and hemoperitoneum was eventually diagnosed as hepatic angiosarcoma based on the immunohistochemical staining results of a liver needle biopsy. Contrast-enhanced ultrasound (CEUS) effectively improved the accuracy of the liver needle biopsy in this case. This report describes the epidemiology, presentation, laboratory tests, imaging findings, and pathological features of a rare hepatic angiosarcoma seen in this young male. The patient rapidly developed severe abdominal hemorrhage. Transcatheter hepatic artery embolization, blood transfusions, and symptomatic treatments were administered. The family members abandoned treatment because the patient was in critical condition and could not receive antitumor therapy.

Conclusions: This case emphasizes the significance of pathological findings in the diagnosis of PHA especially in non-high-risk individuals, and the supportive role of CEUS in guiding the liver needle biopsy. Abdominal hemorrhage is one of the serious complications of PHA and transarterial embolization (TAE) should be considered for controlling life-threatening bleeding from ruptured tumor. Further investigation is required to early diagnosis and to improve the prognosis of patients with PHA.