Assessing the utility, findings, and outcomes of percutaneous transhepatic cholangioscopy with SpyglassTM Direct visualization system: a case series.

Bile duct stones, indeterminate biliary strictures and other biliary duct pathologies represent a significant surgical and endoscopic challenge in patients with altered luminal or biliary anatomy. Traditional endoscopic retrograde cholangiopancreatography (ERCP) is not feasible and alternative approach is usually required. A novel alternative approach of addressing these challenging cases is assessed by this case series. All patients who underwent percutaneous transhepatic cholangioscopy (PTCS) and SpyglassTM Direct visualization system (SDVS) between December 2016 and February 2018 were studied. The indications for procedure, interventions performed, outcomes and complications were reviewed for each case. SpyglassTM marketed by Boston Scientific Corporation, Marlborough, Massachusetts was utilized by interventional endoscopists and radiologists through a 12 French (Fr) percutaneous vascular sheath. Five patients had altered biliary and/or luminal anatomy: two with Roux-en-Y gastric bypass and three with Roux-en-Y hepaticojejunostomy. All patients had unsuccessful previous ERCP attempts. All PTCS with SDVS procedures were technically successful. Indications for this unusual approach were: ascending cholangitis, abnormal liver function tests and biliary dilation on imaging. SDVS was utilized to conduct electrohydraulic lithotripsy (EHL) for biliary stone management in four patients and intraductal biopsies for indeterminate strictures in two of them. PTCS with SDVS can be beneficial for multiple diagnostic and therapeutic indications in patients with altered biliary or luminal anatomy. SDVS allows direct evaluation and management of different biliary pathologies in challenging cases where traditional ERCP is not feasible. Some indications for PTCS with SDVS include evaluation of biliary strictures and biliary stasis, biliary tract biopsy and lithotripsy for management of biliary stones.

Factors Related to Development of Pancreatic Adenocarcinoma in Patients With Chronic Pancreatitis on Long-term Follow-up: A Database Study.

BACKGROUND: Chronic pancreatitis (CP) is a risk factor for pancreatic adenocarcinoma (PA). However, little is known about factors related to development of PA in CP. OBJECTIVE: To evaluate factors associated with PA in CP. METHODS: A national insurance database of 120 million US patients was used. Adults with an International Classification of Diseases, Ninth Revision (ICD-9) code for CP (577.1) from January 1, 2009, to December 31, 20014, were identified. Patients' age, sex, and ICD-9 codes for PA, bile duct obstruction, alcohol use, diabetes mellitus before and after diagnosis of CP, obesity, tobacco use, and type of insurance were obtained. Patients with CP without a unique identification number, missing dates for insurance coverage period, and with duration to end of follow-up or development of PA less than 2 years were excluded. The Cox proportional hazards regression model was used for analysis. RESULTS: The final analysis had 30,555 patients with CP including 219 patients (0.72%) with PA. The Cox proportional hazards regression model showed that in patients with CP age (hazard ratio [HR] = 1.07; 95% Confidence Interval [CI] = 1.03-1.1), male sex (HR = 2.1; 95% CI = 1.25-3.54), tobacco use (HR = 1.88; 95% CI = 1.1-3.23), and having commercial insurance (HR = 4.26; 95% CI = 1.63-11.11) were associated with a subsequent medical claim for PA. Duration of bile duct obstruction (HR = 0.999; 95% CI = 0.998-0.999) and presence of diabetes mellitus before CP (HR = 0.35; 95% CI = 0.19-0.63) were inversely related to subsequent diagnosis of PA. CONCLUSION: PA was diagnosed in 0.72% of the patients with CP at least 2 years after the diagnosis of CP. Increasing age, male sex, tobacco use, having commercial insurance, absence of diabetes mellitus before CP, and shorter duration of bile duct obstruction were associated with a diagnosis of PA in patients with CP.

Anchoring lumen-apposing metal stent with coaxial plastic stent for endoscopic ultrasound-guided drainage of pancreatic fluid collections: any benefit?

BACKGROUND: Anchoring double-pigtail plastic stents (DPSs) within lumen-apposing metal stents (LAMSs) has been proposed to prevent adverse events during endoscopic drainage of pancreatic fluid collections (PFCs). We sought to compare the outcomes of patients who received LAMSs alone and those who received both LAMSs and anchoring DPSs for drainage of PFCs. METHODS: A retrospective study was conducted at the University of Kentucky. Patients with PFCs who underwent endoscopic ultrasound-guided drainage using LAMSs, with or without DPSs, between January 2016 and March 2018 were included. Categorical data were analyzed using chi-square tests, and continuous variables using 2-sample t-tests. Adverse events were defined according to the American Society for Gastrointestinal Endoscopy's Lexicon. The primary outcome was to evaluate the efficacy (PFC resolution), and safety (adverse events) of LAMSs with or without DPSs used to drain PFCs. RESULTS: Fifty-seven patients with PFCs were treated by 2 experienced endoscopists over 26 months. Twenty-one (37%) patients received LAMSs alone, and 36 (63%) received LAMSs plus DPSs. Forty-three patients had walled-off pancreatic necrosis, and 14 patients had pancreatic pseudocyst. Clinical success (resolution of PFCs) was achieved in 15 patients (71.4%) in the LAMSs alone group, and 21 patients (58.3%) with LAMSs plus DPSs (P=0.32). In patients with LAMSs alone, 6 patients (28.6%) had adverse events, while in those with LAMSs plus DPSs, 14 (38.9%) patients had adverse events (P=0.43). CONCLUSION: No significant difference was identified in fluid resolution or adverse events between patients with LAMSs alone and those with LAMSs plus DPSs.

Should a fully covered self-expandable biliary metal stent be anchored with a double-pigtail plastic stent? A retrospective study.

BACKGROUND: The migration rate of fully covered self-expandable metal stents (FCSEMSs) has been reported to be between 14% to 37%. Anchoring of FCSEMSs using a double-pigtail plastic stent (DPS) may decrease migration. AIM: To compare stent migration rates between patients who received FCSEMS alone and those who received both an FCSEMS and anchoring DPS. METHODS: We conducted a retrospective analysis of endoscopy reporting system and medical records of 1366 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) with FCSEMS placement at the University of Kentucky health care. Between July 2015 and April 2017, 203 patients with FCSEMS insertion for the treatment of malignant biliary stricture, benign biliary stricture, post-sphincterotomy bleeding, bile leak, and cholangitis drainage were identified. The review and analysis were conducted through our endoscopy reporting system (ProVation® MD) and medical records. Categorical data were analyzed using Chi-Square and Fischer exact test and continuous data using non-parametric tests. A regression analysis was performed to identify factors independently associated with increased risk of stent migration. We determined an FCSEMS migration endoscopically if the stent was no longer visible in the major papilla. RESULTS: 1366 patients had undergone ERCP by three advanced endoscopists over 21-mo period; among these, 203 patients had FCSEMSs placed. 65 patients had FCSEMSs with DPS, and 138 had FCSEMSs alone. 65 patients had FCSEMSs with DPS, and 138 had FCSEMSs alone. 95 patients had a malignant stricture, 82 patients had a benign stricture, 12 patients had bile leak, 12 patients had cholangitis, and nine patients had post-sphincterotomy bleeding. The migration rate in patients with anchored FCSEMSs with DPS was 6%, and those without anchoring DPS was 10% (P = 0.35). Overall, migration was reported in 18 patients with FCSEMSs placement out of 203 patients with an overall migration rate of 9.7%. There was no significant association between anchoring the FCSEMSs with DPS and the risk of stent migration. Only patients with the previous sphincterotomy and begin biliary stricture were found to have a statistically significant difference in the migration rate between patients who had FCSEMS with DPS and FCSEMS alone (P = 0.01). CONCLUSION: The risk of migration of biliary FCSEMS was 9.7 %. Anchoring an FCSEMS with DPS does not decrease the risk of stent migration.

Restoration of Completely Transected Common Bile Duct Continuity Using Single Operator Cholangioscopy.

Common bile duct (CBD) injury, ranging from a partial tear to a complete transection, is a major surgical complication of cholecystectomy with significant morbidity and mortality. Proper management of these complex injuries depends on the type and extent of injury and time of recognition. Identifying and repairing injuries during cholecystectomy can prevent development of complications, but this only occurs in about one-third of cases. We report a novel technique to reconnect a transected CBD with assistance of single-operator cholangioscopy.

The efficacy of endoscopic therapy for pancreas divisum: a meta-analysis.

BACKGROUND: The purpose of this study was to perform a meta-analysis assessing the efficacy and predictors of success of endoscopic therapy in the management of patients with pancreas divisum. METHODS: An electronic database search (PubMed and ScienceDirect) was performed for relevant studies. Studies were selected based on predefined criteria and data were extracted on patient population, follow up, endotherapy methods, success rates and complication rates. A random-effect model was used to pool the effect size across studies. Heterogeneity testing and publication bias assessment were performed. Multivariate regression analysis was performed to identify predictors of successful endoscopic therapy. RESULTS: Of 381 articles reviewed, 23 studies with 874 patients met the inclusion criteria. All were case series with suboptimal quality. Endoscopic therapy included minor papilla sphincterotomy, minor papilla sphincteroplasty and dorsal duct stenting. Mean follow-up duration was 37 months. The rate of "improvement" as defined by authors after endoscopic therapy varied significantly across studies, ranging from 31-96%: 589/874 patients were reported to have improved, corresponding to a pooled efficacy rate of 67.5% (95% confidence interval [CI] 0.610-0.734; P=0.0001). The pooled rate of pancreatitis after endoscopic retrograde cholangiopancreatography was 10.1% (95%CI 0.084-0.124; 2-sided P=0.0001). On subgroup analysis, patients with recurrent acute pancreatitis had better endoscopic outcomes (pooled efficacy rate 76%, 95%CI 0.712-0.803, P=0.0001). Dorsal duct stenting and longer follow up were the only parameters predictive of successful endotherapy. Significant heterogeneity was observed within and across studies. CONCLUSIONS: Endoscopic efficacy in pancreas divisum is estimated at 67.5%. Available studies are of poor quality with significant heterogeneity. Comparative studies with rigorous methodology are needed.

Fenofibrate is effective adjunctive therapy in the treatment of primary biliary cirrhosis: A meta-analysis.

BACKGROUND AND AIM: Fenofibrate is a potential novel therapy for primary biliary cirrhosis (PBC). We performed a systematic review and a meta-analysis of studies of fenofibrate in PBC. METHODS: Electronic database search was performed for relevant studies. A search of abstracts presented in the main scientific meetings in the field and articles in press was also performed. Random effect model was used to pool the effect size across studies for changes in alkaline phosphatase, GGT, bilirubin and IgM levels before and after treatment and the overall rate of complete response to fenofibrate therapy. RESULTS: Six studies with 102 patients met the inclusion criteria. All studies were case series and in all, patients who had no or incomplete response to UDCA had fenofibrate added at a dose of 100-200mg daily. Treatment duration ranged from 8-100weeks. Treatment with fenofibrate was associated with a significant decrease in alkaline phosphatase (-114IU/L, 95% CI: -152 to -76, P<0.0001); a significant decrease in GGT level (-92IU/L, 95% CI: -149 to -43; P=0.0004); significant decrease in total bilirubin (-0.11mg/dL, 95% CI: -0.18 to -0.08; P=0.0008); and a significant decrease in IgM level (-88mg/dL, 95% CI: -119 to -58; P<0.0001). The complete response rate was 69% (95% CI: 53-82%) with an odds ratio of 82.8 (95% CI: 21.6-317.2; P=0.024) while on fenofibrate. CONCLUSIONS: Fenofibrate at doses of 100-200mg daily appears to be effective adjunctive therapy in PBC patients who had no or incomplete response to UDCA. There is a critical need for larger scale randomized trials to determine its effect on liver-related morbidity and mortality (or progression towards end-stage disease).

Racial Differences in the Prevalence of Celiac Disease in the US Population: National Health and Nutrition Examination Survey (NHANES) 2009-2012.

AIM: To provide an estimate of the prevalence of celiac disease by race/ethnic origin in large sample of US population. METHODS: Data from the 2009-2010 and 2011-2012 NHANES were combined and analyzed. The NHANES is a nationally representative survey with oversampling of certain minorities. Sample-based frequencies were reported and weighted frequencies were used to estimate prevalence. RESULTS: A total of 14,701 participants were checked for tissue transglutaminase (tTG) and endomysial (EMA) IgA antibodies. Seventy-four participants had positive tTG and/or EMA corresponding to prevalence of 0.79 % (95 % CI 0.54-1.04 %). Non-Hispanic white were more likely to be positive for both compared with other races (72.0 vs 31.7 %; p = 0.010) and less likely to be weakly positive for tTG but positive for EMA (3.6 vs 26.4 %; p = 0.03). The prevalence of positive serology according to race was as follows: 1.08 % (95 % CI 0.70-1.45 %) in non-Hispanic white, 0.23 % (95 % CI 0.03-0.43 %) in Mexican, 0.22 % (95 % CI 0.01-0.44 %) in non-Hispanic black, 0.38 % (95 % CI 0.00-0.89 %) in "other Hispanic," and 0.15 % (95 % CI 0.00-0.34 %) in other races including multiracial and undeterminable in non-Hispanic Asian due to the presence of only one positive EMA test. 0.9 % of the NHANES sample participants followed gluten-free diet. Of this group of participants, 85 % were never diagnosed with celiac disease and 99 % of them had negative celiac disease serology. CONCLUSIONS: Potentially 0.79 % of the general US population demonstrate serologic evidence of celiac disease autoimmunity. The prevalence is 4-8 times higher among non-Hispanic white compared with other races. Close to 1 % of the population is electively following gluten-free diet despite having little evidence of the disease.

Probiotic mix VSL#3 is effective adjunctive therapy for mild to moderately active ulcerative colitis: a meta-analysis.

BACKGROUND: VSL#3 is a probiotic mix preparation reported to be effective in the treatment of mild to moderately active ulcerative colitis. We aimed to perform a systematic review of the literature and a meta-analysis of studies on its efficacy. METHODS: The searched databases included PubMed, Scopus, and ScienceDirect. The Mantel-Haenszel method was used to pool the effect- ize across studies, and the odds ratios (ORs) and 95% confidence intervals (CIs) of experiencing a specific outcome were calculated. RESULTS: Five studies with 441 patients were identified. The pooled remission rate was 49.4% (95% CI, 42.7-56.1). Only 3 low risk of bias studies with 319 patients met the inclusion criteria for further analysis. A total of 162 patients received 3.6 × 10 CFU/d VSL#3, and 157 patients received placebo. A total of 95% of patients received concomitant therapies with 5-ASA and/or immunomodulators. The Ulcerative Colitis Disease Activity Index was used to define response and remission. A >50% decrease in the Ulcerative Colitis Disease Activity Index was achieved in 44.6% of the VSL#3-treated patients versus 25.1% of the patients given placebo (P = 0008; OR, 2.793; 95% CI, 1.375-5.676; number needed to treat = 4-5). The response rate was 53.4% in VSL#3-treated patients versus 29.3% in patients given placebo (P < 0001; OR, 3.03; 95% CI, 1.89-4.83; number needed to treat = 3-4). The remission rate was 43.8% in VSL#3-treated patients versus 24.8% in patients given placebo (P = 0007; OR, 2.4; 95% CI, 1.48-3.88; number needed to treat = 4-5). No serious side effects were reported. CONCLUSIONS: VSL#3, when added to conventional therapy at a daily dose of 3.6 × 10 CFU/d, is safe and more effective than conventional therapy alone in achieving higher response and remission rates in mild to moderately active ulcerative colitis.

Teduglutide in intestinal adaptation and repair: light at the end of the tunnel.

BACKGROUND: Malabsorption of nutrients, fluids and electrolytes is a key finding in patients with short bowel syndrome. If not compensated for by increased intake, it leads to diminished body stores and subclinical, and eventually clinical, deficiencies. Until recently, management options were limited to interventions aimed at provision of adequate macro- and micronutrients and fluids to prevent malnutrition, nutrient deficiencies and dehydration, treatment of associated infections and correction and prevention of acid-base disturbances. Identification of novel gut hormones, combined with the growing understanding of their pivotal role in intestinal adaptation, has provoked interest in developing more specific therapies. AIM: To provide an update on the recent advances on the use of teduglutide in patients with short bowel syndrome. METHODS: A comprehensive Medline search using the terms teduglutide, ALX-0600, dipeptidyl peptidase IV (DPP-IV) and glucagon like peptide-2 (GLP-2). RESULTS: Teduglutide (GATTEX, ALX-0600; NPS Allelix Corp) is a synthetic DPP-IV-resistant recombinant human GLP-2 analog that differs from GLP-2 only by an N-terminus substitution of glycine for alanine in position 2 of the peptide that renders the component resistant to enzymatic degradation. Based on the results of the few Phase II studies and the preliminary results of a Phase III trial, teduglutide at doses of 0.05 or 0.10 mg/kg/day may improve many clinical, laboratory and histologic abnormalities in short bowel syndrome patients. It appears to be safe and well tolerated. CONCLUSION: Teduglutide is a first-in-class therapy with the potential to create a new standard of care for patients suffering from short bowel syndrome. Future studies to address the appropriate initial and maintenance dosage and optimal duration of treatment are needed.

Wireless capsule endoscopy indication as a predictor of study quality.

PURPOSE: The aim of the study was to assess whether specific indications are associated with poor visualization during wireless capsule endoscopy (WCE) studies . Four hundred consecutive WCE studies performed at our institute were analyzed retrospectively. RESULTS: Data was available on cases involving 176 males and 224 females. About 23 capsules failed to exit the stomach (excluded from the study). Poor visualization was reported in 66 (17%) WCE studies. The most common indications were gastrointestinal (GI) blood loss (271 cases; 72%), abdominal pain and/or diarrhea (73 cases; 19%), and suspected inflammatory bowel disease (46 cases; 12%). Of the 271 patients suffering GI bleeding, visualization was reported to be poor in 53 (19%) patients; among those showing other indications, visualization was poor in 13 (11%) patients (P = 0.02). After controlling for secondary indications and age, GI bleeding was associated with a higher rate of poor visualization compared to all other indications (odds ratio 2.6; 95% confidence interval 1.4-6.8). CONCLUSIONS: Gastrointestinal bleeding as study indication for WCE is associated with a higher rate of poor visualization.

Treatment of Perianal Fistula and Abscess: Crohn's and Non-Crohn's.

The management of perianal abscesses and fistulas is relatively straightforward in most cases and based on a sound knowledge of the anatomy of the anorectum and adherence to established medical and surgical principles. Asymptomatic fistulas should not be treated, whereas abscesses require surgical drainage under general anesthesia. Fistula treatment includes drainage of any associated sepsis and eradication of the fistula track to prevent recurrence while preserving sphincter integrity. A small percentage of anal abscesses and fistulas are complex and very challenging to manage, particularly in conditions such as rectovaginal fistulas and abscesses and/or fistulas complicating Crohn's disease. Treatment strategies in these situations rely on an accurate clinical assessment of the degree of rectal inflammation and perianal pathology. Treatment should combine aggressive medical therapy (antibiotics, immunomodulators, and anti-tumor necrosis factor antibody treatment) and minimal surgical interventions. Patients with proctitis have a significantly lower healing rate and a significantly higher complication rate with aggressive surgical interventions.

An instrument to predict endoscopy tolerance: a prospective randomized study.

Our purpose in this study was to determine if the use of an instrument developed by our group to direct sedation choice improves patient satisfaction with endoscopy sedation compared to standard sedation practice. After 200 enrollments, data were available for 194 patients who completed the study. There were nine cases of dissatisfaction: five (5%) in the control group and four (4%) in the intervention group (P = 0.78). The 95% confidence intervals (1%-10%) were almost identical, indicating no difference between groups. The study was stopped after an interim analysis showed no significant difference in satisfaction between the groups. This could have been because the assumption that patients with increased risk of dissatisfaction do better with deeper sedation is incorrect. Another explanation could be the increased awareness of the value of benzodiazepines in endoscopy. Consistent with our findings, nervousness rather than pain predicted dissatisfaction, and the optimal use of anxiolytics with amnesic properties may be comparable to that of propofol.

Development of an instrument to assess and predict satisfaction and poor tolerance among patients undergoing endoscopic procedures.

We aimed to test the reliability of a developed questionnaire that measures and predict aversive endoscopic experience. Two questionnaires (pre- and postprocedure) were given to patients presenting for routine endoscopy. The first questionnaire elicited demographics, prior endoscopic experience, history of drug or alcohol use, patient expectations, and levels of anxiety and nervousness before procedure. After endoscopy, tolerance and willingness to repeat the examination were determined. The primary outcome of "adverse endoscopic experience" (AEE) was defined as a score of > or =5 on the postprocedure overall level of satisfaction or unwillingness to repeat endoscopy. Thirteen of 148 subjects reported an AEE. Items measuring the primary outcome were internally validated by reliability analysis which significantly correlated with measures of aversive experience like pain, nervousness, and suffering during the procedure. Preprocedure factors that were associated with AEE in the univariate analysis and multivariate analysis were nervousness (P = 0.02) and chronic use of psychotropic drugs or alcohol (P = 0.03). In conclusion, we have developed a questionnaire that reliably measures aversive endoscopic experience. Nervousness before procedure and chronic use of psychotropic drugs are reliable predictors of such experience.

Gastroduodenal Crohn's disease is associated with NOD2/CARD15 gene polymorphisms, particularly L1007P homozygosity.

Limited data exist on the specific association between gastroduodenal Crohn's disease (GDCD) and NOD2/CARD15 gene polymorphisms. The aim of this study was to assess the association between NOD2 polymorphisms and GDCD, and to assess the specific association between each of the 3 major allelic variants G908R, L1007P, and R702W and the clinical features of Crohn's disease. We retrospectively reviewed the records of 202 patients with confirmed Crohn's disease and complete data was performed. Seventy-one patients (35%) had at least 1 allelic variant: 55 had 1 variant, 4 were homozygous for L1007fs, 2 homozygous for R702W, and 10 were compound heterozygous. Eighteen patients with confirmed GDCD were identified; 10 (56%) had wild type, 4 (22%) had 1 variant, and 4 (22%) had 2 allelic variants (2 were L1007P homozygous and 2 compound heterozygous). Compared to patients without gastroduodenal involvement, those with GDCD were more likely to have 2 allelic variants (22% vs. 6%; odds ratio [OR] 2.7; 95% confidence interval [CI] 1.6-7.3) and to be homozygous for L1007P (11% vs. 1%; OR 5.2; 95% CI 2.5-9.4). G908R heterozygosity was associated with ileal involvement (OR 1.4; 95% CI 1.1-2.9) and smoking habits (OR 2.4; 95% CI 1.2-3.8), whereas L1007P homozygosity was associated with GDCD (OR 5.8; 95% CI 2.6-10.8). L1007P variation was associated with younger age at diagnosis as well. There was no specific association between R702W homo- or heterozygosity and any of the characteristics examined. In conclusion, GDCD is associated with double dose of the NOD2/CARD15 gene variants, particularly L1007P homozygosity. There is evidence of specific variant-phenotype associations. G908R heterozygosity is associated with ileal involvement and smoking, whereas L1007P homozygosity is strongly associated with GDCD and younger age at diagnosis.