Translational gastroenterology and hepatology最新文献

Alcohol-related liver disease (ALD) is the most common indication for liver transplantation (LT) in the United States. The judicious allocation of organs and improvement in outcomes requires identification and monitoring of patients with ALD at high-risk for relapse post-transplantation. The controversial movement toward early LT for severe alcohol-related hepatitis (SAH) has also raised concern for alcohol relapse. While LT cures ALD, treatment of alcohol use disorder (AUD) must be included in the care plan to prevent a return to drinking and subsequent graft ALD. Patients with underlying AUD must be recognized, offered brief interventions and referred for multimodal multidisciplinary treatment that includes medications and psychotherapies along with sober support groups, family engagement, and a new dedication to healthy living in order to help sustain remission. Such comprehensive care will increase LT candidacy in patients with ALD while optimizing clinical outcomes of patients transplanted with AUD.

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.

Liver cirrhosis is the final stage of continuous hepatic inflammatory activity derived by viral, metabolic or autoimmune origin. In the last years, cirrhosis was considered a unique and static condition; recently was accepted some patients subgroups with different liver injury degrees that coexist under the same diagnosis, with implications about the natural disease history. The liver growth factor (LGF) is a potent in vivo and in vitro mitogenic agent and an inducer of hepatic regeneration (HR) through the hepatocytes DNA synthesis. The clinical implications of the LGF levels in cirrhosis, are not clear and even with having a fundamental role in the liver regeneration processes, the studies suggest that it could be a cirrhosis severity marker, in acute liver failure and in chronic hepatitis. Its role as predictor of mortality in fulminant hepatic insufficiency patients has been suggested. HR is one of the most enigmatic and fascinating biological phenomena. The rapid volume and liver function restoration after a major hepatectomy (>70%) or severe hepatocellular damage and its strict regulation of tissue damage response after the cessation, is an exclusive property of the liver. HR is the clinical applications fundament, such as extensive hepatic resections (>70% of the liver parenchyma), segmental transplantation or living donor transplantation, sequential hepatectomies, isolated portal embolization or associated with in situ hepatic transection, temporary artificial support in acute liver failure and the possible cell therapy clinical applications.

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.