Translational gastroenterology and hepatology最新文献

Background: Radiofrequency ablation (RFA) has been used to treat various abdominal tumors including pancreatic tumors. Multiple approaches such as laparoscopic, open, and percutaneous have been used for pancreatic tissue ablation. More recently, endoscopic ultrasound (EUS)-guided RFA has emerged as a new technique for pancreatic tissue ablation. The role of EUS-RFA in management of pancreatic lesions is still not well-established. In this study, our aim is to assess efficacy and safety of EUS-RFA for management of pancreatic lesions.

Methods: MEDLINE, Scopus, and Cochrane Library databases were searched to identify studies reporting EUS-RFA of pancreatic lesions with outcomes of interest. Studies with <5 patients were excluded. Clinical success was defined as symptom resolution, decrease in tumor size, and/or evidence of necrosis on radiologic imaging. Efficacy was assessed by the pooled clinical response rate whereas safety was assessed by the pooled adverse events rate. Heterogeneity was assessed using I². Pooled estimates and the 95% CI were calculated using random-effect model.

Results: Ten studies (5 retrospective and 5 prospective) involving 115 patients with 125 pancreatic lesions were included. 152 EUS-RFA procedures were performed. The lesions comprised of 37.6% non-functional neuroendocrine tumors (NFNETs), 15.4% were insulinomas, 26.5% were pancreatic cystic neoplasms (PCNs), and 19.7% were pancreatic adenocarcinomas. The majority were present in the pancreatic head (40.2%), 38.3% in the body, 11.2% in the tail, and 10.3% in the uncinate process. Pooled overall clinical response rate was 88.9% (95% CI: 82.4-93.7, I²=38.1%). Pooled overall adverse events rate was 6.7% (95% CI: 3.4-11.7, I²=34.0%). The most common complication was acute pancreatitis (3.3%) followed by pancreatic duct stenosis, peripancreatic fluid collection, and ascites (2.8%) each. Only one case of perforation was reported with pooled rate of (2.1%).

Discussion: This study demonstrates that EUS-RFA is an effective treatment modality for pancreatic lesions, especially functional neuroendocrine tumors such as insulinomas.

Along with the worldwide increase in obesity and metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) and its more severe subset, non-alcoholic steatohepatitis (NASH), are on path to become the leading cause of liver transplantation in the United States. NAFLD, as well as obesity, create an inflammatory milieu via the release of adipocytokines. In turn, the inflammatory environment can trigger an increase in prothrombotic factors. Independent of inflammation, the severity of NASH is associated with a graded increase in hypercoagulability such as an increase in factor VIII, increase in plasminogen activator inhibitor-1, and decrease in protein C. Ultimately, this environment creates an increase in thrombotic risk, leading to higher rates of pre-transplant portal vein thrombosis (PVT) in patients with NASH cirrhosis vesus other causes of cirrhosis. Many studies have shown worse outcomes in liver transplant recipients with PVT as it complicates anastomotic reconstruction which can negatively affect portal blood supply needed for adequate liver functioning. Management and treatment of PVT is not standardized, but from a pharmacologic standpoint, multiple classes of anticoagulants have shown to be successful in recanalization of the portal vein and preventing recurrence of clot with minimal bleeding complications. The increasing prevalence of NASH cirrhosis and subsequent increase in PVT require further research for improved outcomes.

Frailty manifesting as sarcopenia is an independent risk factor for mortality in cirrhosis, and often presents in low model for end-stage liver disease (MELD) patients. Its etiology is multifactorial, but key physiologic changes culminate in altered energy utilization in the fasting state, preferentially utilizing muscle amino acids for gluconeogenesis thereby promoting sarcopenia. Hyperammonemia alters the circulating amino acid profile, diminishing pro-muscle branched-chain amino acids like leucine. The metabolic syndrome worsens sarcopenia through multi-tissue insulin resistance. Alcohol also exacerbates sarcopenia as a direct muscle toxin and inhibitor of growth signaling. Therapy is aimed at alcohol cessation, frequent high-protein meals, branched-chain amino acid supplementation, and diminished time spent fasting. Moderate exercise can improve muscle mass and muscle quality, though precise exercise regimens have not yet been explicitly determined. Studies are ongoing into the effects of myostatin antagonists and insulin sensitizers. The Liver Frailty Index can predict patients most at risk of poor outcome and should be considered in the management of all cirrhotic patients. Specialty testing like dual-energy X-ray absorptiometry (DEXA) scanning and cross-sectional estimates of muscle mass are areas of active research and may play a future role in clinical risk-stratification.

Benign strictures of the colon and rectum affect a sizable portion of patients who have an underlying inflammatory disease or who have undergone recent surgery. Etiologies include inflammatory bowel disease (IBD), post-surgical ischemia, anastomotic strictures, non-steroidal anti-inflammatory drugs (NSAIDs), and complicated diverticulitis. Refractory colorectal strictures are very difficult to manage and often require repeated and different treatment options. We report a novel technique using argon plasma coagulation (APC) with endoscopic balloon dilation (EBD) as a safe and effective treatment modality for refractory benign colorectal strictures. Four patients with symptomatic benign colorectal strictures were referred for endoscopic treatment. In all cases (two females and two males; average age 62 years), the endoscopic and radiographic assessment showed significant strictures (diameter, 4-13 mm). The stricture was secondary to Crohn's disease in one patient and anastomotic strictures in the other three patients. Endoscopic stricturotomy through fulguration and tissue destruction using argon plasma at 1.5 liters/minute, effect 2, and 40 watts was performed, followed by EBD. All patients were treated by one advanced endoscopist. The primary outcomes were the efficiency and safety of endoscopic stricturotomy with pulsed argon plasma and balloon dilation. The resolution of stricture was achieved in all patients. No complications were reported. We believe that combined APC with EBD is a safe and effective technique in the treatment of benign colonic stricture.

Pancreatic fluid collections (PFCs) are frequent complications in severe acute pancreatitis that are the result of damage to the pancreas to include but not limited to trauma, surgery, autoimmune diseases, alcohol abuse, infections, medications, gallstones, metabolic disorders, and premalignant or malignant conditions. The majority of these collections resolve spontaneously; however, if the collection is infected or causes symptoms to include abdominal pain, nausea, vomiting, diarrhea, fevers, and tachycardia, drainage is indicated. Drainage of PFCs can be accomplished surgically, percutaneously, or endoscopically and should be approached in a multidisciplinary fashion for best overall patient care and outcomes. Before the introduction of endoscopic procedures, surgical and percutaneous drainage was the preferred modality. Today a minimally-invasive "step-up" approach is generally accepted depending upon the specific characteristics of the PFC and clinical presentation. Endoscopic ultrasound-guided PFC drainage is favored due to high success rates, shorter hospital stays, and lower cost. Direct debridement of walled-off pancreatitis can now be performed endoscopically with higher success rates with larger caliber fully covered metal stents. At large, the field of endoscopic techniques has evolved, and more specifically, the management of PFCs continues to evolve with increasing experience and with the advent of new stents and accessories, leading to increased efficacy with less adverse events.

Background: Pathophysiology of gastroesophageal reflux disease (GERD) shows a multifactorial background. Different anatomical and functional alterations can be determined such as weakness of the lower esophageal sphincter (LES), changes in anatomy by a hiatal hernia (HH), an impaired esophageal motility (IEM), and/or an associated gastric motility problem with either duodeno-gastro-esophageal reflux (DGER) or delayed gastric emptying (DGE). The purpose of this study is to assess a large GERD-patient population to quantitatively determine different pathophysiologic factors contributing to the disease.

Methods: For this analysis only patients with documented GERD (pathologic esophageal acid exposure) were selected from a prospectively maintained databank. Investigations: history and physical, body mass index, endoscopy, esophageal manometry, 24 h-pH-monitoring, 24 h-bilirbine-monitoring, radiographic-gastric-emptying or scintigraphy, gastrointestinal quality of life index (GIQLI).

Results: In total, 728 patients (420 males; 308 females) were selected for this analysis. Mean age: 49.9 years; mean BMI: 27.2 kg/m² (range, 20-45 kg/m²); mean GIQLI of 91 (range: 43-138; normal level: 121); no esophagitis: 30.6%; minor esophagitis (Savary-Miller type 1 or Los Angeles Grade A): 22.4%; esophagitis [2-4]/B-D: 36.2%; Barrett's esophagus 10%. Presence of pathophysiologic factors: HH 95.4%; LES-incompetence 88%, DGER 55%, obesity 25.6%, IEM 8.8%, DGE 6.8%.

Conclusions: In our evaluation of GERD patients, the most important pathophysiologic components are anatomical alterations (HH), LES-incompetence and DGER.

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.