Current Treatment Options in Gastroenterology

Indications for Single-Operator Cholangioscopy and Pancreatoscopy: an Expert Review Abstract Purpose of review Direct endoscopic visualization of the biliary and pancreatic ducts by single-operator cholangioscopy (SOC) and pancreatoscopy (SOP) is an expanding technique with an increasing number of indications. This review provides technical tips and tricks and a literature update on the usefulness of SOC and SOP in clinical practice. Recent findings SOC has shown a 91.3% and 87.3% diagnostic procedural success in indeterminate strictures and difficult stones respectively, with a 9.4%–16.4% complication rate. Although the interpretation of the images suspected for malignancy can be challenging, new classifications based in mucosal and vascular patterns as well as better devices are in development. A higher sensitivity has been associated to targeted biopsies, compared to brushing and blinded biopsies. Indeed, SOC has recently demonstrated a decrease in the number of procedures and costs when compared with endoscopic retrograde cholangiopancreatography. This technique has also been reported for many other diagnostic and therapeutic indications, such as cholangiocarcinoma staging and foreign body extraction. Similarly, diagnostic and therapeutic SOP in indeterminate strictures or pancreatic stones, and intraductal papillary mucinous neoplasms, has been successfully reported. Summary Research to date supports the use of cholangioscopy as a complementary examination in patients with indeterminate strictures, difficult stones and specific situations. In a near future, there will probably be new established indications, a better understanding of the imaging findings and a place of SOC/SOP as first line in selected scenarios.

The Evolving Role of Thiopurines in Inflammatory Bowel Disease Abstract Purpose of review With the advent of biologic therapies for the treatment of inflammatory bowel disease, the roles of thiopurines have continued to evolve. This review will focus on recent advances in pharmacology and the safety and efficacy of thiopurines as maintenance therapies for steroid-induced remissions and post-surgical maintenance of remission and as combination therapies to reduce immunogenicities of biologic agents. Recent findings Due to pharmacogenetics of thiopurine S-methyltransferase, thiopurine dosing is more effectively based on monitoring of thiopurine metabolites rather than weight-based dosing. Thiopurines continue to have a role as maintenance therapy after steroid-induced remissions and in combination with biologics to induce and maintain remission. Safety monitoring includes measurements of blood counts, liver chemistries, and dermatologic evaluations and protection from sun exposure. Summary Thiopurines appear to be safe during pregnancies and while very uncommon, lymphomas (including hepatosplenic T cell lymphomas) remain a recognized risk, particularly in younger and older males.

The Role of Behind Folds Visualizing Techniques and Technologies in Improving Adenoma Detection Rate Abstract Purpose of review Colorectal cancer is one of the most common malignancies in the Western world and is thought to develop from premalignant polyps. Over the past decade, several behind folds visualizing techniques (BFTs) have become available to improve polyp detection. This systematic review and meta-analysis aims to compare BFTs with conventional colonoscopy (CC). Recent findings In the past five years, 14 randomized controlled trials (RCTs) including 8384 patients comparing different BFTs with CC were published. The overall relative risks for adenoma detection rate, polyp detection rate, and adenoma miss rate comparing BFTs with CC were 1.04 (95% confidence interval [CI] 0.98–1.10; P = 0.15), 1.03 (95% CI 0.98–1.09; P = 0.28), and 0.70 (95% CI 0.46–1.05; P = 0.08), respectively. Other quality metrics for colonoscopy were not significantly different between BFT-assisted colonoscopy and CC either. Summary This meta-analysis of RCTs published in the past five years does not show a significant benefit of BFTs on any of the important quality metrics of colonoscopy. The lack of additional effect of BFTs might be due to improved awareness of colonoscopy quality metrics and colonoscopy skills among endoscopists combined with improvements of conventional colonoscope technology.

Current Status and Future Perspective in Cholangiopancreatoscopy Abstract Purpose of review With the rapid growth of cholangiopancreatoscopy, several platforms of cholangiopancreatoscopy have been currently available. Since the introduction of digital single-operator cholangiopancreatoscopy, there have been several reports describing its efficacy for long-standing and novel applications. The purpose of this review is to show the current status and future perspective of cholangiopancreatoscopy. Recent findings Meta-analysis of cholangiopancreatoscopy have demonstrated good diagnostic yield for visual impression; however, it should be noted that there is no standardized classification system used for distinguishing benign from malignant lesions. In contrast, utility of tissue sampling under direct vision for cholangiopancreatic disorders is inconclusive. This could be explained by the fact that available devices (e.g., biopsy forceps) are limited by the small diameter of accessory channel. Regarding therapeutic applications, several studies demonstrated efficacy and feasibility of electrohydraulic lithotripsy or laser lithotripsy for difficult bile duct stone and pancreatic duct stone under cholangiopancreatoscopic guidance. Additionally, ablation of tumors, selective guidewire placement, retrieval of migrated stents, and anterograde cholangioscopy-guided procedure by using cholangiopancreatoscopy have been reported. Summary The recent development of digital single-operator cholangiopancreatoscopy enables easy access to the bile duct and pancreatic duct, contributing to expanding indications for cholangiopancreatoscopy. Improvement of devices or development of innovative devices is required to overcome the remaining problems of cholangiopancreatoscopy.

Hepatitis C elimination: a Public Health Perspective Abstract Purpose of review Hepatitis C virus (HCV) infection is a principal cause of morbidity, mortality, and economic burden, and the global elimination of HCV is now considered a public health objective. Globally, an estimated 71 million have chronic HCV infection with an estimated annual mortality of 3,99,000. Recent findings The 69th World health Assembly has endorsed the global HCV elimination strategy by 2030, which is made possible because of all oral, cost-effective, efficacious, generic direct-acting antivirals. The public health strategy targets not only diagnosed chronic hepatitis C patients but also asymptomatic undiagnosed HCV-infected individuals, persons living with human immunodeficiency virus (HIV), post-transplant, thallasemia, persons who inject drugs, and the pediatric population. Summary Mobilization of state-sponsored HCV elimination programs in a global coalition against HCV has taken root in Egypt, India, Georgia, Mongolia, China, Australia, and Brazil. This review summarizes current HCV elimination initiatives in terms of medical progress, barriers to HCV elimination, and current gaps in knowledge and social outreach from the public health perspective.

Endoscopic Methods for Gallbladder Drainage Abstract Purpose of review Acute cholecystitis is conventionally managed with cholecystectomy; however, when this occurs in the non-operative patient, it requires consideration for alternative means of gallbladder drainage (GBD). Recent findings Suitable endoscopic methods for GBD include transpapillary cystic duct stent or endoscopic ultrasound (EUS)-guided transmural stent placement. Importantly, patients who undergo endoscopic GBD have comparable outcomes to those who undergo placement of percutaneous transhepatic catheters by interventional radiology (IR). Summary There is evolving evidence to support endoscopic gallbladder drainage by EUS or ERCP with transpapillary stenting for patients who are non-operative candidates. There appear to be advantages over percutaneous drainage in terms of lower rates of recurrent cholecystitis, faster clinical resolution of symptoms, and omission of external drain-related complications. However, careful consideration of individual characteristics is warranted in the care of these complicated patients. The technical and clinical considerations for endoscopic methods of GB drainage are discussed in this review article.

Epigenetic Mechanisms of Pancreatobiliary Fibrosis Abstract Purpose of review The goal of this manuscript is to review the current literature related to fibrogenesis in the pancreatobiliary system and how this process contributes to pancreatic and biliary diseases. In particular, we seek to define the current state of knowledge regarding the epigenetic mechanisms that govern and regulate tissue fibrosis in these organs. A better understanding of these underlying molecular events will set the stage for future epigenetic therapeutics. Recent findings We highlight the significant advances that have been made in defining the pathogenesis of pancreatobiliary fibrosis as it relates to chronic pancreatitis, pancreatic cancer, and the fibro-obliterative cholangiopathies. We also review the cell types involved as well as concepts related to epithelial-mesenchymal crosstalk. Furthermore, we outline important signaling pathways (e.g., TGFβ) and diverse epigenetic processes (i.e., DNA methylation, non-coding RNAs, histone modifications, and 3D chromatin remodeling) that regulate fibrogenic gene networks in these conditions. Summary We review a growing body of scientific evidence linking epigenetic regulatory events to fibrotic disease states in the pancreas and biliary system. Advances in this understudied area will be critical toward developing epigenetic pharmacological approaches that may lead to more effective treatments for these devastating and difficult to treat disorders.

Interplay of Liver Disease and Gut Microbiota in the Development of Colorectal Neoplasia Abstract Purpose of the review Liver disease, colon cancer, and the gut microbiome are intimately interrelated; however, the connections linking liver disease and colorectal neoplasia via the gut microbiota remain poorly understood and rarely addressed in a single space. The goal of this review is to take a broad perspective on the clinical problem of colorectal neoplasia in the liver disease population, recognize the significance of the clinical study findings, and delve into the evidence supporting putative molecular mechanisms connecting dysbiosis in the progression of liver disease to the development of colorectal neoplasia. Recent findings Clinical studies have recently reported increased risk of colorectal neoplasia in patients with fatty liver disease, and risk increases with liver disease severity. Concurrently, the evolution of -omics technology has shown dysregulation of the gut microbial community, termed dysbiosis, in the progression of liver disease. Specific microbes enriched in the gut flora of liver disease patients have been linked to colon cancer and adenomatous precursor lesions. Summary The gut microbiome of liver disease patients generates a pro-neoplastic environment, mediated via altered bile acid signaling and a dysregulated inflammatory response that suppresses immune surveillance. Research focused on the mechanisms linking liver disease to colorectal neoplasia via the gut microbiome is needed to help us prepare for the rising tide of colon cancer in young patients with an increasing prevalence of liver disease.

Endoscopic Bariatric Therapies: Intragastric Balloons, Tissue Apposition, and Aspiration Therapy Abstract Purpose of review Endoscopic bariatric therapies (EBTs) have been identified as a group of procedures that can bridge the treatment gap between bariatric surgical procedures and non-procedural treatments such as pharmacotherapy and lifestyle therapy. We will review the recent progress that has been made in this important area in the past several years. Recent findings Traditional intragastric balloons (IGB) that are both placed and removed endoscopically have been the fixture of IGB therapy. They have been shown to be safe and effective, when kept in place for 6 months. Newer IGBs, both currently FDA approved and those in clinical trials, have unique features. The Obalon gastric balloon system is gas filled and does not require endoscopy for placement. The Elipse balloon system that is in clinical trials neither requires endoscopy for placement nor removal. The Spatz3 balloon is in clinical trials and can be adjusted endoscopically by adding or subtracting volume to titrate balloon volume to symptoms and weight loss. In addition to IGBs, several other promising therapies have continued to evolve. Endoscopic sleeve gastroplasty (ESG) is a promising gastric restriction technique that has efficacy and durability. POSE is a gastric plication technique that is available in Europe and in clinical trials in the USA. Aspiration therapy is a novel approach to weight loss that requires patient compliance but can be very effective and used long term. Summary EBTs are an evolving effective and safe approach for patients who do not qualify for or do not want bariatric surgery. There are multiple EBTs currently FDA approved as well as prospective endoscopic therapies in clinical trials that appear promising.

Contemporary Epidemiology of Cirrhosis Abstract Purpose of Review We sought to review the contemporary epidemiology of cirrhosis, focusing on the relative burden of the most common chronic liver diseases. Recent Findings The key findings in the review highlight the increasing prevalence and impact of alcohol-related liver disease, particularly among young people, and the epidemic of nonalcoholic fatty liver commensurate with rising rates of obesity. We also contrast recent advances in the care of persons with hepatitis C with the lamentable rise in new infections associated with intravenous drug use. Finally, we highlight the impact of both conventional complications of cirrhosis (namely hepatic encephalopathy) but also the host of patient-reported outcomes adversely impacted by the symptoms of cirrhosis. Summary Cirrhosis is associated with an expanding footprint in contemporary public health. In order to improve global outcomes, we must not only focus on the identifying and treating persons with viral hepatitis but also preventing the rise of alcohol-related liver disease and nonalcoholic fatty liver disease while attending to the urgent patient-centered needs posed by the symptoms of cirrhosis.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
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6948891480

alsfakia@gmail.com