Role of endoscopic retrograde cholangiopancreatography in acute pancreatitis

Endoscopic retrograde cholangiopancreatography (ERCP) is a useful tool in the evaluation and management of acute pancreatitis. This review will focus on the role of ERCP in specific causes of acute pancreatitis, including microlithiasis and gallstone disease, pancreas divisum, Sphincter of Oddi dysfunction, tumors of the pancreaticobiliary tract, pancreatic pseudocysts, and pancreatic duct injury. Indications for endoscopic techniques such as biliary and pancreatic sphincterotomy, stenting, stricture dilation, treatment of duct leaks, drainage of fluid collections and stone extraction will also be discussed in this review. With the advent of less invasive and safer diagnostic modalities including endoscopic ultrasound (EUS) and magnetic retrograde cholangiopancreatography (MRCP), ERCP is appropriately becoming a therapeutic rather than diagnostic tool in the management of acute pancreatitis and its complications.

Feasibility of initial endoscopic common bile duct stone removal in patients with acute cholangitis

AIM To investigate the feasibility of initial endoscopic common bile duct(CBD) stone removal in patients with acute cholangitis(AC).METHODS A single-center,retrospective study was conducted between April 2013 and December 2014 and was approved by the Medical Ethics Committee at our institution.Written informed consent was obtained from each patient prior to the procedure.The cohort comprised 31 AC patients with CBD stones who underwent endoscopic biliary drainage(EBD) for na?ve papilla within 48 h after AC onset.We retrospectively divided the participants into two groups: 19 patients with initial endoscopic CBD stone removal(initial group) and 12 patients with delayed endoscopic CBD stone removal(delayed group).We evaluated the feasibility of initial endoscopic CBD stone removal in patients with AC.RESULTS We observed no significant differences between the groups regarding patient characteristics.According to the assessments based on the Tokyo Guidelines,the AC severity of patients with initial endoscopic CBD stone removal was mild to moderate.The use of antithrombotic agents before EBD was less frequent in the initial group than in the delayed group(11% vs 58%,respectively; P = 0.004).All the patients underwent successful endoscopic CBD stone removaland adverse events did not differ significantly between the groups.The number of endoscopic retrograde cholangiopancreatography procedures was significantly lower in the initial group than in the delayed group [median(interquartile range) 1(1-1) vs 2(2-2),respectively; P < 0.001].The length of hospital stay was significantly shorter for the initial group than for the delayed group [10(9-15) vs 17(14-20),respectively; P = 0.010].CONCLUSION Initial endoscopic CBD stone removal in patients with AC may be feasible when AC severity and the use of antithrombotic agents are carefully considered.

Inhibition of ileal bile acid transporter:An emerging therapeutic strategy for chronic idiopathic constipation

Chronic idiopathic constipation is a common disorder of the gastrointestinal tract that encompasses a wide profile of symptoms. Current treatment options for chronic idiopathic constipation are of limited value; therefore, a novel strategy is necessary with an increased effectiveness and safety. Recently, the inhibition of the ileal bile acid transporter has become a promising target for constipation-associated diseases. Enhanced delivery of bile acids into the colon achieves an accelerated colonic transit, increased stool frequency, and relief of constipationrelated symptoms. This article provides insight into the mechanism of action of ileal bile acid transporter inhibitors and discusses their potential clinical use for pharmacotherapy of constipation in chronic idiopathic constipation.

New serological biomarkers of inflammatory bowel disease

Serological biomarkers in inflammatory bowel disease (IBD) are a rapidly expanding list of non-invasive tests for objective assessments of disease activity, early diagnosis, prognosis evaluation and surveillance. This review summarizes both old and new biomarkers in IBD, but focuses on the development and character-ization of new serological biomarkers (identifi ed since 2007). These include fi ve new anti-glycan antibodies, anti-chitobioside IgA (ACCA), anti-laminaribioside IgG (ALCA), anti-manobioside IgG (AMCA), and antibod-ies against chemically synthesized (∑) two major oligomannose epitopes, Man α-1,3 Man α-1,2 Man (∑Man3) and Man α-1,3 Man α-1,2 Man α-1,2 Man (∑Man4). These new biomarkers serve as valuable complementary tools to existing biomarkers not only in differentiating Crohn's disease (CD), ulcerative colitis (UC), normal and other non-IBD gut diseases, but also in predicting disease involvement (ileum vs colon), IBD risk (as subclinical biomarkers), and disease course (risk of complication and surgery). Interestingly, the prevalence of the antiglycan antibodies, including anti-Saccharomyces cerevisiae antibodies (ASCA), ALCA and AMCA, was found to be associated with single nucleotide polymorphisms (SNPs) of IBD susceptible genes such as NOD2/CARD15, NOD1/CARD4, toll-likereceptors (TLR) 2 and 4, and β-defensin-1. Further-more, a gene dosage effect was observed: anti-glycan positivity became more frequent as the number of NOD2/CARD15 SNPS increased. Other new serum/ plasma IBD biomarkers reviewed include ubiquitination factor E4A (UBE4A), CXCL16 (a chemokine), resistin, and apolipoprotein A-IV. This review also discusses the most recent studies in IBD biomarker discovery by the application of new technologies such as proteomics, fourier transform near-infrared spectroscopy, and mul-tiplex enzyme-linked immunosorbent assay (ELISA)'s (with an emphasis on cytokine/chemokine profiling). Finally, the prospects of developing more clinically use-ful novel diagnostic algorithms by incorporating new technologies in serological biomarker profiling and integrating multiple biomarkers with bioinformatics analysis/modeling are also discussed.

Nutritional modulation of the inflammatory response in inflammatory bowel disease-From the molecular to the integrative to the clinical

Nutrient deficiencies are common in patients with inflammatory bowel disease (IBD). Both total parenteral and enteral nutrition provide important supportive therapy for IBD patients, but in adults these are not useful for primary therapy. Dietary intervention with omega-3 polyunsaturated fatty acids contained in fish oil may be useful for the care of IBD patients, and recent studies have stressed the role of PPAR on NFκB activity on the potential beneficial effect of dietary lipids on intestinal function.

Geographic differences in low-dose aspirin-associated gastroduodenal mucosal injury

Aspirin, even at low doses, has been known to cause upper gastro-intestinal complications, such as gastroduodenal ulcers, despite the definite benefits from its antithrombotic effects. Helicobacter pylori(H. pylori) is major pathogen responsible for gastroduodenal ulcerformation. There have been conflicting results about the potential interaction between these two ulcerogenic factors and the geographic areas involved. In Western countries, the prevalence of gastroduodenal ulcers is consistently higher in H. pylori-positive low-dose aspirin(LDA) users than in H. pylori-negative ones, suggesting that H. pylori infection exacerbates LDA-induced gastroduodenal mucosal injury in these geographic areas. Meanwhile, previous studies from Japan have generally reported a similar prevalence of LDA-induced gastroduodenal mucosal injury regardless of the presence of H. pylori infection, indicating that the infection is not an overall exacerbating factor for drug-induced injury. H. pylori infection could have a synergistic or antagonistic interaction with LDA use in adverse gastroduodenal events depending on gastric acid secretion. It is wellrecognized that the net effect of H. pylori infection on gastric acid secretion shows considerable geographic variation at the population level. While gastric acid secretion levels were not decreased and were wellpreserved in most patients with H. pylori infection from Western countries, the majority of Japanese patients with H. pylori infection exhibited decreased gastric acid secretion. Such large geographic differences in the net effect of H. pylori infection on gastric acid secretion could be at least partly responsible for the geographically distinct interaction between LDA use and H. pylori infection on adverse gastroduodenal lesions.

Effects of probiotic bacteria on gastrointestinal motility in guinea-pig isolated tissue

AIM: To evaluate the intestinal motility changes evoked by 8 bacterial strains belonging to Bifidobacterium , Lactobacillus and Streptococcus genera within the probiotic preparation VSL#3. METHODS: Ileum and proximal colon segments isolated from guinea-pigs were used as a study model. Entire cells and cell fractions (cell debris, cell wall fraction, cytoplasmatic fraction, proteinaceous and non- proteinaceous cytoplasmatic components) of VSL#3 strains and, as controls, Escherichia coli, Salmonella aboni and Bacillus licheniformis were tested in this in vitro model. RESULTS: Among the bacterial cell fractions tested, only the cytoplasmatic fraction modified intestinal motility. Lactobacillus strains stimulated the contraction of ileum segment, whereas all probiotic strains tested induced proximal colon relaxation response. The non-proteinaceous cytoplasmatic components were responsible for the colon relaxation. CONCLUSION: The results obtained in this study suggest that the proximal colon relaxation activity showed by the probiotic bacteria could be one of the possible mechanisms of action by which probiotics exert their positive effects in regulating intestinal motility.

Novel ATP8B1 mutation in an adult male with progressive familial intrahepatic cholestasis

Progressive familial intrahepatic cholestasis type 1 is a rare disease that is characterized by low serum γ-glutamyltransferase levels due to mutation inATP8B1.We present a 23-year-old male who experienced persistent marked pruritus for eighteen years and recurrent jaundice for thirteen years,in addition to cholestasis that eventually became fatal.Genetic sequencing studies of the entire coding(exon) sequences of ATP8B1 and ABCB11 uncovered a novel heterozygous missense 3035G>T mutation(S1012I) and a synonymous 696T>C mutation in ATP8B1.The patient's progression was associated with not only impaired familial intrahepatic cholestasis 1(FIC1) function but also impaired bile salt export pump expression due to the impaired FIC1 function.Our findings show that patients with intermittent cholestasis can develop progressive liver disease even after several decades and require regular follow up.

Boceprevir or telaprevir in hepatitis C virus chronic infection:The Italian real life experience

AIM: To check the safety and efficacy of boceprevir/telaprevir with peginterferon/ribavirin for hepatitis C virus(HCV) genotype 1 in the real-world settings. METHODS: This study was a non-randomized, observational, prospective, multicenter. This study involved 47 centers in Italy. A database was prepared for the homogenous collection of the data, was used by all of the centers for data collection, and was updated continuously. All of the patients enrolled in this study were older than 18 years of age and were diagnosed with chronic infection due to HCV genotype 1. The HCV RNA testing was performed using COBAS-Taq Man2.0(Roche, LLQ 25 IU/m L). RESULTS: All consecutively treated patients were included. Forty-seven centers enrolled 834 patients as follows: Male 64%; median age 57(range 18-78), of whom 18.3% were over 65; mean body mass index 25.6(range 16-39); genotype 1b(79.4%); diagnosis of cirrhosis(38.2%); and fibrosis F3/4(71.2%). The following drugs were used: Telaprevir(66.2%) and PEG-IFN-alpha2a(67.6%). Patients were na?ve(24.4%), relapsers(30.5%), partial responders(14.8%) and null responders(30.3%). Overall, adverse events(AEs) occurred in 617 patients(73.9%) during the treatment. Anemia was the most frequent AE(52.9% of cases), especially in cirrhotic. The therapy was stopped for 14.6% of the patients because of adverse events or virological failure(15%). Sustained virological response was achieved in 62.7% of the cases, but was 43.8% in cirrhotic patients over 65 years of age. CONCLUSION: In everyday practice, triple therapy is safe but has moderate efficacy, especially for patients over 65 years of age, with advanced fibrosis, nonresponders to peginterferon + ribavirin.

Combination therapy for inflammatory bowel disease

Biologic therapies such as infliximab and adalimumab have become mainstays of treatment for inflammatory bowel disease. Early studies suggested that combination therapy(CT) with infliximab and an immunomodulator drug such as azathioprine may help optimize biologic pharmacokinetics, minimize immunogenicity, and improve outcomes. The landmark SONIC trial in Crohn's disease and the UC SUCCESS trial in ulcerative colitis demonstrated CT with infliximab and azathioprine to be superior to monotherapy with either agent alone at inducing clinical remission in treatment na?ve patients with moderate to severe disease. However, many unanswered questions linger. The role of CT in non-naive patients as well as the optimal duration of CT remains unknown. The effectiveness of CT with alternate biologics and/or alternate immunomodulators is not as clear, and it is unknown whether SONIC's conclusions can be extrapolated beyond infliximab and azathioprine. Also looming are the risks of CT including opportunistic infection and malignancy; specifically, lymphoma. This review lays out the evidence as it pertains to the risks and benefits of CT as well as the areas that require further research. With this information in hand, the practitioner may develop a treatment strategy that best suits each individual patient.

Lumen-apposing metal stents for benign gastrointestinal tract strictures: An international multicenter experience

AIM To investigate technical feasibility, outcomes and adverse events of the lumen-apposing metal stent(LAMS) for benign gastrointestinal(GI) tract strictures.METHODS Between July 2015 and January 2017, patients undergoing treatment by LAMS for benign GI strictures at three tertiary referral centers were included in this study. Primary outcomes included technical success, shortterm clinical success, long-term clinical success, and adverse events. Short-term clinical success was defined as symptom resolution at 30 d after stent placement. Longterm clinical success was defined by symptom resolution at 60 d in patients who continued to have indwelling stent, or continued symptom resolution at 30 d after elective stent removal.RESULTS A total of 21 patients(mean age 62.6 years, 47.6% males) underwent placement of LAMS for benign GI strictures. A 15 mm × 10 mm LAMS was placed in 16 patients, a 10 mm × 10 mm LAMS was placed in 2 patients, and a 16 mm × 30 mm LAMS was placed in 3 patients. Technical success was obtained in all cases. Short-term clinical success was achieved in 19 out of 21 cases(90.5%), and long-term clinical success was achieved in 12 out of 18(66.7%). Mean(range) stent indwell time was 107.2(28-370) d. After a mean(range) dwell time of 104.3(28-306) d, 9 LAMSs were removed due to the following complications: ulceration at stent site(n = 1), angulation(n = 2), migration(n = 4) and stricture overgrowth(n = 2). Migration occurred in 4 cases(19.0%), and it was associated with stricture resolution in one case. Median(range) follow-up period was 119(31-422) d. CONCLUSION Utilization of LAMS for benign strictures has shown to be technically feasible and safe, but adverse events highlight the need for further study of its indications.