Translational gastroenterology and hepatology最新文献

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer in the world. Clinical and laboratory evaluation of a cirrhotic patient with a liver nodule may show alterations suggesting malignancy. There is a lack of questions related to diagnosis of HCC and evaluation of liver imaging reporting and data system (LI-RADS) could be a tool for early diagnosis of HCC. This aims to confirm an association between clinical and laboratory characteristics in cirrhotic patients with hepatic nodule after LI-RADS categorization.

Methods: A cross-sectional retrospective study was performed with 62 patients grouped according to LI-RADS algorithm. Differences between groups were confirmed using association tests and the Kappa test was employed to provide further confirmation.

Results: Associations were observed after univariate analysis with higher values of aspartate aminotransferase (AST) (P=0.008), alanine aminotransferase (ALT) (P=0.019), alkaline phosphatase (ALP) (P=0.0052), gamma glutamyl transferase (GGT) (P=0.0023), alpha-fetoprotein (AFP) (P=0.0001), nodule size (P=0.0001) and age (P=0.007) in LR 5 group compared to LR 3. Univariate analysis also revealed higher levels for the LR5 group of ALP (P=0.0228), AFP (P=0.022) and age (P=0.046) in relation to LR 1+2 group. AFP also had higher serum levels in the LR 4 group compared to LR 1+2 (P=0.004). After multivariate analysis, higher levels in LR5 group of nodule size (P=0.047) and ALP (P=0.027) were observed in relation to LR3, and were therefore considered predictors of HCC diagnosis.

Conclusions: The study suggests that the combination of clinical-laboratory and radiological factors, such as heightened serum levels of ALP and hepatic nodule size, may support the screening of HCC in cirrhotic patients with hepatic nodules using the LI-RADS algorithm.

Computer-aided diagnosis (CAD) for colonoscopy with use of artificial intelligence (AI) is catching increased attention of endoscopists. CAD allows automated detection and pathological prediction, namely optical biopsy, of colorectal polyps during real-time endoscopy, which help endoscopists avoid missing and/or misdiagnosing colorectal lesions. With the increased number of publications in this field and emergence of the AI medical device that have already secured regulatory approval, CAD in colonoscopy is now being implemented into clinical practice. On the other side, drawbacks and weak points of CAD in colonoscopy have not been thoroughly discussed. In this review, we provide an overview of CAD for optical biopsy of colorectal lesions with a particular focus on its clinical applications and limitations.

Background: Since human fetal liver progenitor cells (hFLPC) can differentiate into multiple liver cell types in vitro and in vivo, hFLPC may be a suitable source for cell therapy and regeneration strategies. Imperative for effective clinical applications of hFLPC is the enhanced knowledge of growth factors that mediate and improve migration and proliferation. The canonical wingless/int-1 (Wnt) signal transduction pathway is known to play a key role in proliferation and migration of stem cells. So, we investigated a role for Wnt3a and Wnt5a ligands in regulating the proliferation and migration of hFLPC.

Methods: We used alamarBlue assay and transwell migration assay and examined proliferation and migration of hFLPC to Wnt3a and Wnt5a. In addition, the target genes of Wnt signal transduction pathway was identified using microarray analysis and validated by quantitative real-time polymerase chain reaction (qPCR).

Results: We found that Wnt3a or Wnt5a independently significantly increased migration and proliferation in a dose-dependent manner which was significantly inhibited by Wnt inhibitors Wnt-C59 or KN-62. Addition of Wnt3a to hFLPC resulted in increased mRNA expression of the known Wnt target genes Axin-2, DKK2, while Wnt5a increased CXCR7, all of which are closely associated with an enhanced proliferation capacity of stem cells.

Conclusions: Thus, we report that Wnt3a and Wnt5a may play an important role in the proliferation and migration of hFLPC by possibly regulating key target genes-involved in these processes. Incorporating recombinant human Wnt3a and Wnt5a in regenerative strategies using liver stem/progenitor cells might improve the process of liver regeneration.

Background: Post-cholecystectomy syndrome (PCS) is a group of heterogeneous signs and symptoms, predominately consisting of right upper quadrant abdominal pain, dyspepsia, and/or jaundice, manifesting after undergoing a cholecystectomy. According to some studies, as many as 40% of post-cholecystectomy patients are in fact, affected by this syndrome. This study aims to determine the demographics, aetiology, average length of hospital stay, and health care burden associated with PCS.

Methods: We queried the National Inpatient Sample (NIS) database to determine inpatient admissions of PCS between 2011 and 2014 using the ICD-9 primary diagnosis code 576.0.

Results: From 2011 to 2014, the number of inpatient admissions with a principal diagnosis of PCS totally 275. The average length of hospital stay was 4.28±4.28, 3.42±2.73, 3.74±1.84, and 3.79±2.78 days in 2011, 2012, 2013, and 2014, respectively. The total yearly charges were $32,079±$24,697, $27,019±$22,633, $34,898.21±$24,408, and $35,204±$32,951 in 2011, 2012, 2013, and 2014, respectively. Notably, the primary cause of PCS in our patient sample between the year 2011 and 2014, was biliary duct dysfunction, followed by Peptic ulcer disease.

Conclusions: In conclusion, there is a strong need to examine for and treat the underlying aetiology when approaching a post-cholecystectomy patient. We found that longer hospital stays, were associated with a greater health care burden, and visa versa. Furthermore, our findings help identify at-risk populations which can contribute to improving surveillance of this costly disease.

The management of Barrett's esophagus (BE) has evolved as newer technologies and novel methods are developed. Endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) are the initial interventions of choice for nodular BE, with ESD reserved for endoscopists highly trained in the technique and for larger lesions that would warrant en bloc resection. Resection should then be followed by ablative therapy, which remains first line in the treatment of BE with dysplasia. Although there is a myriad of ablation techniques available to the endoscopist, this review has found that radiofrequency ablation (RFA) continues to have the most robust safety and efficacy data to support its use despite a relatively high rate of recurrence. Cryotherapy and Hybrid-APC appear to be safe and effective as RFA alternatives, but further trials are still needed to directly compare their outcomes to RFA and ultimately guide changes in treatment decisions.

Nonalcoholic steatohepatitis (NASH) is the most common cause of chronic liver disease today, and it has now emerged as the leading etiology of end-stage liver disease requiring liver transplantation. It is a progressive form of non-alcoholic fatty liver disease which can not only progress to cirrhosis of liver and hepatocellular carcinoma (HCC), but is associated with increased cardiovascular risks too. Despite all the advances in the understanding of the risk factors and the pathogenetic pathways involved in the pathogenesis and progression of NASH, an effective therapy for NASH has not been developed yet. Although lifestyle modifications including dietary modifications and physical activity remain the mainstay of therapy, there is an unmet need to develop a drug or a combination of drugs which can not only reduce the fatty infiltration of the liver, but also arrest the development and progression of fibrosis and advancement to cirrhosis of liver and HCC. The pharmacologic therapies which are being developed target the various components believed to be involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD)/NASH which includes insulin resistance, lipid metabolism oxidative stress, lipid peroxidation, inflammatory and cell death pathways, and fibrosis. In this review, we summarize the current state of knowledge on pharmacotherapy of NASH, and also highlight the recent developments in the field, for optimizing the management and treatment of NASH.

Cholangiocarcinoma, a malignancy of the epithelial cells in the intrahepatic or extrahepatic biliary tree, is often diagnosed at later stages. Median survival duration ranges from 3 to 9 months with a less than ten percent 5-year survival rate. Thus, often treatment strategies are aimed more towards palliation instead of cure. With the majority of patients presenting with unresectable disease at the time of diagnosis, surgical intervention is not feasible, making less invasive endoscopic therapies more suitable. Initially, biliary stents were utilized for biliary decompression to mitigate cholestatic symptoms and prevent cholangitis; however, this strategy did not prove to provide significant survival benefit. Therefore, efforts to treat the tumor burden itself in addition to maintaining biliary patency became a focus of innovation and research in the endoscopic field. This study has led to the advent of therapies such as photodynamic therapy, radiofrequency ablation, and intraluminal brachytherapy. These options combined with biliary stenting have shown to not only offer the benefit of biliary decompression, but also to potentially improve stent patency and survival. Further, there is an anti-tumor effect of each of these modalities, portending an additional benefit in this subset of patients. Despite numerous retrospective and prospective studies assessing these ablative therapies, there is still a paucity of appropriately powered randomized controlled trials, and further research has yet to be done in the field. This review details the current literature entailing endobiliary ablative strategies.

The global pandemic of coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is predominantly a respiratory illness, but gastrointestinal (GI) manifestations of variable severity have been reported. In patients with COVID-19 pneumonia, observational studies have demonstrated the elevation of pancreatic enzymes as surrogate markers for pancreatic injury without evidence of acute pancreatitis (AP). We report a case of AP in a patient with COVID-19 with SARS-CoV-2 as possible etiological agent with imaging evidence of pancreatitis. We hypothesize a causal relationship of SARS-CoV-2 in this patient with an otherwise unexplained presentation of AP after excluding the common causes. We postulate that AP in COVID-19 could be related to the abundant expression of angiotensin converting enzyme 2 (ACE 2) receptors in the pancreas which serve as viral entry binding receptors for SARS-CoV-2 or due to direct viral involvement of the pancreas. Although there seems to be an association between diabetes and AP, the available data regarding the etiological role of diabetes in causing AP is very limited. We also propose that imaging studies such as computerized tomography (CT) scan of the abdomen should be considered in the diagnosis of AP in patients with COVID-19 infection to exclude the false positive amylase and lipase.

Background: Blood-borne tumour markers in the form of circulating tumour cells (CTCs) are of intense research interest in the diagnostic and prognostic work-up of hepatocellular carcinoma (HCC).

Methods: This is a meta-analysis. Using a PICO strategy, adults with HCC was the population, with the individual CTCs as the intervention and comparators. The primary outcome was the sensitivity and specificity of HCC detection with tumour specific single gene methylation alteration. Secondary outcomes were the comparison using specific assay methods and the effect of early vs. late stages on CTC positivity. We included patients with HCC who had samples taken from peripheral blood and had sufficient data to assess the outcome data. ASSIA, Cochrane library, EMbase, Medline, PubMed and the knowledge network Scotland were systematically searched with appropriate Mesh terms employed. The quality assessment of diagnostic accuracy studies (QUADAS) was used to ensure quality of data. Statistical analysis was performed using the 'Rev Man' meta-analysis soft ward for Windows.

Results: The review included 36 studies, with a total of 5,853 patients. Here, we found that AFP has the highest overall diagnostic performance. The average Youden index amongst all CTC was 0.46 with a mode and median of 0.5 with highest of 0.87 and lowest of 0.01.

Conclusions: The available literature provides weak evidence that there is potential in the use of CTC, however the lack of a standardised procedure in the study of CTC contribute to the lack of consensus of use. Future research should include large scaled, standardized studies for the diagnostic accuracy of CTCs.