Endoscopic full-thickness resection of polyps involving the appendiceal orifice: a multicenter international experience.

BACKGROUND: Endoscopic resection of lesions involving the appendiceal orifice remains a challenge. We aimed to report outcomes with the full-thickness resection device (FTRD) for the resection of appendiceal lesions and identify factors associated with the occurrence of appendicitis. METHODS: This was a retrospective study at 18 tertiary-care centers (USA 12, Canada 1, Europe 5) between November 2016 and August 2020. Consecutive patients who underwent resection of an appendiceal orifice lesion using the FTRD were included. The primary outcome was the rate of R0 resection in neoplastic lesions, defined as negative lateral and deep margins on post-resection histologic evaluation. Secondary outcomes included the rates of: technical success (en bloc resection), clinical success (technical success without need for further surgical intervention), post-resection appendicitis, and polyp recurrence. RESULTS: 66 patients (32 women; mean age 64) underwent resection of colonic lesions involving the appendiceal orifice (mean [standard deviation] size, 14.5 (6.2) mm), with 40 (61 %) being deep, extending into the appendiceal lumen. Technical success was achieved in 59/66 patients (89 %), of which, 56 were found to be neoplastic lesions on post-resection pathology. Clinical success was achieved in 53/66 (80 %). R0 resection was achieved in 52/56 (93 %). Of the 58 patients in whom EFTR was completed who had no prior history of appendectomy, appendicitis was reported in 10 (17 %), with six (60 %) requiring surgical appendectomy. Follow-up colonoscopy was completed in 41 patients, with evidence of recurrence in five (12 %). CONCLUSIONS: The FTRD is a promising non-surgical alternative for resecting appendiceal lesions, but appendicitis occurs in 1/6 cases.

Maximizing success in single-session EUS-directed transgastric ERCP: a retrospective cohort study to identify predictive factors of stent migration.

BACKGROUND AND AIMS: EUS-directed transgastric ERCP (the EDGE procedure) is a simplified method of performing ERCP in Roux-en-Y gastric bypass patients. The EDGE procedure involves placement of a lumen-apposing metal stent (LAMS) into the excluded stomach to serve as a conduit for passage of the duodenoscope for pancreatobiliary intervention. Originally a multistep process, urgent indications for ERCP have led to the development of single-session EDGE (SS-EDGE) with LAMS placement and ERCP performed in the same session. The goal of this study was to identify predictive factors of intraprocedural LAMS migration in SS-EDGE. METHODS: We conducted a multicenter retrospective review that included 9 tertiary medical centers across the United States. Data were collected and analyzed from 128 SS-EDGE procedures. The primary outcome was intraprocedural LAMS migration. Secondary outcomes were other procedural adverse events such as bleeding and perforation. RESULTS: Eleven LAMS migrations were observed in 128 procedures (8.6%). Univariate analysis of clinically relevant variables was performed, as was a binary logistic regression analysis of stent diameter and stent dilation. This revealed that use of a smaller (15 mm) diameter LAMS was an independent predictor of intraprocedural stent migration (odds ratio, 5.36; 95% confidence interval, 1.29-22.24; P = .021). Adverse events included 3 patients who required surgery and 2 who experienced intraprocedural bleeding. CONCLUSIONS: Use of a larger-diameter LAMS is a predictive factor for a nonmigrated stent and improved procedural success in SS-EDGE. Although larger patient cohorts are needed to adequately assess these findings, performance of LAMS dilation and fixation may also decrease risk of intraprocedural LAMS migration and improve procedural success.

Endoscopic ultrasound-directed transgastric ERCP (EDGE): a retrospective multicenter study.

BACKGROUND: Endoscopic ultrasound-directed transgastric endoscopic retrograde cholangiopancreatography (ERCP; EDGE) is an alternative to enteroscopy- and laparoscopy-assisted ERCP in patients with Roux-en-Y gastric bypass anatomy. Although short-term results are promising, the long-term outcomes are not known. The aims of this study were: (1) to determine the rates of long-term adverse events after EDGE, with a focus on rates of persistent gastrogastric or jejunogastric fistula; (2) to identify predictors of persistent fistula; (3) to assess the outcomes of endoscopic closure when persistent fistula is encountered. METHODS: This was a multicenter retrospective study involving 13 centers between February 2015 and March 2019. Adverse events were defined according to the ASGE lexicon. Persistent fistula was defined as an upper gastrointestinal series or esophagogastroduodenoscopy showing evidence of fistula. RESULTS: 178 patients (mean age 58 years, 79 % women) underwent EDGE. Technical success was achieved in 98 % of cases (175/178), with a mean procedure time of 92 minutes. Periprocedural adverse events occurred in 28 patients (15.7 %; mild 10.1 %, moderate 3.4 %, severe 2.2 %). The four severe adverse events were managed laparoscopically. Persistent fistula was diagnosed in 10 % of those sent for objective testing (9/90). Following identification of a fistula, 5 /9 patients underwent endoscopic closure procedures, which were successful in all cases. CONCLUSIONS: The EDGE procedure is associated with high clinical success rates and an acceptable risk profile. Persistent fistulas after lumen-apposing stent removal are uncommon, but objective testing is recommended to identify their presence. When persistent fistulas are identified, endoscopic treatment is warranted, and should be successful in closing the fistula.

Increasing Prevalence of Hepatitis C among Hospitalized Children Is Associated with an Increase in Substance Abuse.

OBJECTIVE: To evaluate the impact of substance abuse on pediatric hepatitis C virus (HCV) prevalence, we examined geographic and demographic data on inpatient hospitalizations in children with HCV. STUDY DESIGN: We examined hospitalizations in children using the Kids' Inpatient Database, a part of the Healthcare Cost and Utilization Project. We identified cases using the International Classification of Diseases, 9th edition, codes for HCV infection during 2006, 2009, and 2012. Nonparametric tests for trend were used to calculate trend statistics. RESULTS: From 2006 to 2012 nationally, the number of hospitalizations of children with HCV increased 37% (2.69 to 3.69 per 10 000 admissions; P < .001). The mean age of children hospitalized was 17.6 years (95% CI, 17.4-17.8). HCV cases among those 19-20 years of age represented 68% of the total HCV diagnoses, with a 54% increase over the years sampled (P < .001 for trend). The burden of HCV in children was highest in whites, those in the lowest income quartile, and in the Northeast and Southern regions of the US (all P < .0001). The prevalence of substance use among children with HCV increased from 25% in 2006 to 41% in 2012 (P < .001). CONCLUSION: The increases of HCV in hospitalized children are largely in teenagers, highly associated with substance abuse, and concentrated in Northeast and Southern states. These results strongly suggest that public health efforts to prevent and treat HCV will also need to include adolescents.

Cost Utility Analysis of Topical Steroids Compared With Dietary Elimination for Treatment of Eosinophilic Esophagitis.

BACKGROUND & AIMS: Topical corticosteroids or dietary elimination are recommended as first-line therapies for eosinophilic esophagitis, but data to directly compare these therapies are scant. We performed a cost utility comparison of topical corticosteroids and the 6-food elimination diet (SFED) in treatment of eosinophilic esophagitis, from the payer perspective. METHODS: We used a modified Markov model based on current clinical guidelines, in which transition between states depended on histologic response simulated at the individual cohort-member level. Simulation parameters were defined by systematic review and meta-analysis to determine the base-case estimates and bounds of uncertainty for sensitivity analysis. Meta-regression models included adjustment for differences in study and cohort characteristics. RESULTS: In the base-case scenario, topical fluticasone was about as effective as SFED but more expensive at a 5-year time horizon ($9261.58 vs $5719.72 per person). SFED was more effective and less expensive than topical fluticasone and topical budesonide in the base-case scenario. Probabilistic sensitivity analysis revealed little uncertainty in relative treatment effectiveness. There was somewhat greater uncertainty in the relative cost of treatments; most simulations found SFED to be less expensive. CONCLUSIONS: In a cost utility analysis comparing topical corticosteroids and SFED for first-line treatment of eosinophilic esophagitis, the therapies were similar in effectiveness. SFED was on average less expensive, and more cost effective in most simulations, than topical budesonide and topical fluticasone, from a payer perspective and not accounting for patient-level costs or quality of life.

Esophageal dilation with either bougie or balloon technique as a treatment for eosinophilic esophagitis: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Esophageal dilation is a now recognized to be an important therapeutic modality in eosinophilic esophagitis (EoE). We aimed to evaluate the safety of esophageal dilation in EoE, especially regarding perforation risk, and to examine perforation risk by dilator type. METHODS: We conducted a systematic review of the published literature from January 1, 1950 to June 30, 2016 using PubMed, EMBASE, and Web of Science. Studies were included if they described patients with EoE who underwent elective esophageal dilation and also reported the presence or absence of at least 1 adverse event (eg, perforation, bleeding, pain, or hospitalization). We used random-effects meta-analysis to estimate the frequency of each adverse event. RESULTS: Of 923 identified articles, 37 met inclusion criteria and represented 2034 dilations in 977 patients. On meta-analysis, postprocedure hospitalization occurred in .689% of dilations (95% confidence interval [CI], 0%-1.42%), clinically significant GI hemorrhage in .028% (95% CI, 0%-.217%), and clinically significant chest pain in 3.64% (95% CI, 1.73%-5.55%). Nine perforations were documented, at a rate of .033% (95% CI, 0%-.226%) per procedure after meta-analysis. None of the perforations resulted in surgical intervention or mortality. Most (5/9) were reported before 2009 (rate, .41% [95% CI, 0%-2.75%]); from 2009 forward the rate was .030% (95% CI, 0%-.225%). Dilation method was described in 30 studies (1957 dilations), in which 4 perforations were detected. The estimated perforation rate for bougies was .022% (95% CI, 0%-.347%) and for balloons was .059% (95% CI, 0%-.374%). CONCLUSIONS: Perforation from esophageal dilation in EoE is rare, and there is no evidence of a significant difference in perforation risk related to dilator type. Esophageal dilation should be considered a safe procedure in EoE.

Causes and Outcomes of Esophageal Perforation in Eosinophilic Esophagitis.

GOALS: To characterize patients who suffer perforation in the context of eosinophilic esophagitis (EoE) and to identify predictors of perforation. BACKGROUND: Esophageal perforation is a serious complication of EoE. MATERIALS AND METHODS: We conducted a retrospective cohort study of the University of North Carolina EoE clinicopathologic database from 2001 to 2014. Subjects were included if they had an incident diagnosis of EoE and met consensus guidelines, including nonresponse to a PPI trial. Patients with EoE who had suffered perforation at any point during their course were identified, and compared with EoE cases without perforation. Multiple logistic regression was performed to determine predictors of perforation. RESULTS: Out of 511 subjects with EoE, 10 (2.0%) had experienced an esophageal perforation. Although those who perforated tended to have a longer duration of symptoms before diagnosis (11.4 vs. 7.0 y, P=0.13), a history of food impaction (odds ratio, 14.9; 95% confidence interval, 1.7-129.2) and the presence of a focal stricture (odds ratio, 4.6; 95% confidence interval, 1.1-19.7) were the only factors independently associated with perforation. Most perforations (80%) occurred after a prolonged food bolus impaction, and only half of individuals (5/10) carried a diagnosis of EoE at the time of perforation; none occurred after dilation. Six patients (60%) were treated with nonoperative management, and 4 (40%) required surgical repair. CONCLUSIONS: Esophageal perforation is a rare but serious complication of eosinophilic esophagitis, occurring in ∼2% of cases. Most episodes are due to food bolus impaction or strictures, suggesting that patients with fibrostenotic disease due to longer duration of symptoms are at increased risk.

Association Between Body Mass Index and Clinical and Endoscopic Features of Eosinophilic Esophagitis.

BACKGROUND: Because eosinophilic esophagitis (EoE) causes dysphagia, esophageal narrowing, and strictures, it could result in low body mass index (BMI), but there are few data assessing this. AIM: To determine whether EoE is associated with decreased BMI. METHODS: We conducted a prospective study at the University of North Carolina from 2009 to 2013 enrolling consecutive adults undergoing outpatient EGD. BMI and endoscopic findings were recorded. Incident cases of EoE were diagnosed per consensus guidelines. Controls had either reflux or dysphagia, but not EoE. BMI was compared between cases and controls and by endoscopic features. RESULTS: Of 120 EoE cases and 297 controls analyzed, the median BMI was lower in EoE cases (25 vs. 28 kg/m2, p = 0.002). BMI did not differ by stricture presence (26 vs. 26 kg/m2, p = 0.05) or by performance of dilation (26 vs. 27 kg/m2 for undilated; p = 0.16). However, BMI was lower in patients with narrow caliber esophagus (24 vs. 27 kg/m2, p < 0.001). EoE patients with narrow caliber esophagus also had decreased BMI compared to controls with narrow caliber esophagi (24 vs. 27 kg/m2, p = 0.001). On linear regression after adjustment for age, race, and gender, narrowing decreased BMI by 2.3 kg/m2 [95% CI -4.1, -0.6]. CONCLUSIONS: BMI is lower in EoE cases compared to controls, and esophageal narrowing, but not focal stricture, is associated with a lower BMI in patients with EoE. Weight loss or low BMI in a patient suspected of having EoE should raise concern for esophageal remodeling causing narrow caliber esophagus.

NAFLD and liver transplantation: Current burden and expected challenges.

Because of global epidemics of obesity and type 2 diabetes, the prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing both in Europe and the United States, becoming one of the most frequent causes of chronic liver disease and predictably, one of the leading causes of liver transplantation both for end-stage liver disease and hepatocellular carcinoma. For most transplant teams around the world this will raise many challenges in terms of pre- and post-transplant management. Here we review the multifaceted impact of NAFLD on liver transplantation and will discuss: (1) NAFLD as a frequent cause of cryptogenic cirrhosis, end-stage chronic liver disease, and hepatocellular carcinoma; (2) prevalence of NAFLD as an indication for liver transplantation both in Europe and the United States; (3) the impact of NAFLD on the donor pool; (4) the access of NAFLD patients to liver transplantation and their management on the waiting list in regard to metabolic, renal and vascular comorbidities; (5) the prevalence and consequences of post-transplant metabolic syndrome, recurrent and de novo NAFLD; (6) the alternative management and therapeutic options to improve the long-term outcomes with particular emphasis on the correction and control of metabolic comorbidities.

Distribution and Characteristics of Colonic Diverticula in a United States Screening Population.

BACKGROUND & AIMS: Colonic diverticula are the most common finding from colonoscopy examinations. Little is known about the distribution of colonic diverticula, which are responsible for symptomatic and costly diverticular disease. We aimed to assess the number, location, and characteristics of colonic diverticula in a large US screening population. METHODS: We analyzed data from a prospective study of 624 patients (mean age, 54 years) undergoing screening colonoscopy at the University of North Carolina Hospital from 2013 through 2015. The examination included a detailed assessment of colonic diverticula. To assess the association between participant characteristics and diverticula, we used logistic regression to estimate odds ratios and 95% confidence intervals. RESULTS: Of our population, 260 patients (42%) had 1 or more diverticula (mean number, 14; range, 1-158). Participants with diverticula were more likely to be older, male, and have a higher body mass index than those without diverticula. The distribution of diverticula differed significantly by race. Among white persons, 75% of diverticula were in the sigmoid colon, 11% in the descending splenic flexure, 6% in the transverse colon, and 8% were in the ascending colon or hepatic flexure. In black persons 64% of diverticula were in the sigmoid colon, 8% in the descending colon or splenic flexure, 7% in the transverse colon, and 20% in the ascending colon or hepatic flexure (P = .0008). The proportion of patients with diverticula increased with age: 35% were 50 years or younger, 40% were 51-60 years, and 58% were older than 60 years. The proportion of patients with more than 10 diverticula increased with age: 8% were 50 years or younger, 15% were 51-60 years, and 30% were older than 60 years. CONCLUSIONS: Older individuals not only have a higher prevalence of diverticula than younger individuals, but also a greater density, indicating that this is a progressive disease. Black persons have a greater percentage of their diverticula in the proximal colon and fewer in the distal colon compared with white persons. Understanding the distribution and determinants of diverticula is the first step in preventing diverticulosis and its complications.

Burden of Gastrointestinal, Liver, and Pancreatic Diseases in the United States.

BACKGROUND & AIMS: Gastrointestinal (GI), liver, and pancreatic diseases are a source of substantial morbidity, mortality, and cost in the United States. Quantification and statistical analyses of the burden of these diseases are important for researchers, clinicians, policy makers, and public health professionals. We gathered data from national databases to estimate the burden and cost of GI and liver disease in the United States. METHODS: We collected statistics on health care utilization in the ambulatory and inpatient setting along with data on cancers and mortality from 2007 through 2012. We included trends in utilization and charges. The most recent data were obtained from the Centers for Disease Control and Prevention, the Agency for Healthcare Research and Quality, and the National Cancer Institute. RESULTS: There were 7 million diagnoses of gastroesophageal reflux and almost 4 million diagnoses of hemorrhoids in the ambulatory setting in a year. Functional and motility disorders resulted in nearly 1 million emergency department visits in 2012; most of these visits were for constipation. GI hemorrhage was the most common diagnosis leading to hospitalization, with >500,000 discharges in 2012, at a cost of nearly $5 billion dollars. Hospitalizations and associated charges for inflammatory bowel disease, Clostridium difficile infection, and chronic liver disease have increased during the last 20 years. In 2011, there were >1 million people in the United States living with colorectal cancer. The leading GI cause of death was colorectal cancer, followed by pancreatic and hepatobiliary neoplasms. CONCLUSIONS: GI, liver and pancreatic diseases are a source of substantial burden and cost in the United States.

Outcomes of Esophageal Dilation in Eosinophilic Esophagitis: Safety, Efficacy, and Persistence of the Fibrostenotic Phenotype.

OBJECTIVES: Esophageal dilation is commonly performed in eosinophilic esophagitis (EoE), but there are few long-term data. The aims of this study were to assess the safety and long-term efficacy of esophageal dilation in a large cohort of EoE cases, and to determine the frequency and predictors of requiring multiple dilations. METHODS: We conducted a retrospective cohort study in the University of North Carolina EoE Clinicopathological Database from 2002 to 2014. Included subjects met consensus diagnostic criteria for EoE. Clinical, endoscopic, and histologic features were extracted, as were dilation characteristics (dilator type, change in esophageal caliber, and total number of dilations) and complications. Patients with EoE who had undergone dilation were compared with those who did not and also stratified by whether they required single or multiple dilations. RESULTS: Of 509 EoE patients, 164 were dilated a total of 486 times. Those who underwent dilation had a longer duration of symptoms before diagnosis (11.1 vs. 5.4 years, P<0.001). Ninety-five patients (58%) required >1 dilation (417 dilations total, mean of 4.4±4.3 per patient). The only predictor of requiring multiple dilations was a smaller baseline esophageal diameter. Dilation was tolerated well, with no major bleeds, perforations, or deaths. The overall complication rate was 5%, primarily due to post-procedural pain. Of 164 individuals dilated, a majority (58% or 95/164) required a second dilation. Of these individuals, 75% required repeat dilation within 1 year. CONCLUSIONS: Dilation in EoE is well-tolerated, with a very low risk of serious complications. Patients with long-standing symptoms before diagnosis are likely to require dilation. More than half of those dilated will require multiple dilations, often needing a second procedure within 1 year. These findings can be used to counsel patients with fibrostenotic complications of EoE.

The extremely narrow-caliber esophagus is a treatment-resistant subphenotype of eosinophilic esophagitis.

BACKGROUND AND AIMS: Some patients with eosinophilic esophagitis (EoE) have an extremely narrow esophagus, but the characteristics of this group have not been extensively described. We aimed to characterize the narrow-caliber phenotype of EoE, determine associated risk factors, and identify differences in treatment response in this subgroup of patients. METHODS: This retrospective cohort study from 2001 to 2014 included subjects with a new diagnosis of EoE per consensus guidelines. Demographic, endoscopic, histologic, and treatment response data were extracted from medical records. An extremely narrow-caliber esophagus was defined when a neonatal endoscope was required to traverse the esophagus due to the inability to pass an adult endoscope. Patients with and without an extremely narrow-caliber esophagus were compared. Multivariable logistical regression was performed to assess treatment outcomes. RESULTS: Of 513 patients with EoE, 46 (9%) had an extremely narrow-caliber esophagus. These patients were older (33 vs 22 years; P < .01), had longer symptom duration (11 vs 3 years; P < .01), more dysphagia (98% vs 66%; P < .01), and food impactions (53% vs 31%; P < .01). Dilation was more common with extreme narrowing (69% vs 17%; P < .01). Patients with a narrow-caliber esophagus were more refractory to steroid treatment, with lower symptom (56% vs 85%), endoscopic (52% vs 76%), and histologic (33% vs 63%) responses (P < .01 for all), and these differences persisted after multivariate analysis. CONCLUSION: The extremely narrow-caliber esophagus is a more treatment-resistant subphenotype of EoE and is characterized by longer symptom duration and the need for multiple dilations. Recognition of an extremely narrow-caliber esophagus at diagnosis of EoE can provide important prognostic information.

Cleavage of E-Cadherin Contributes to Defective Barrier Function in Neosquamous Epithelium.

BACKGROUND: After ablation of Barrett's esophagus (BE), the esophagus heals with neosquamous epithelium (NSE). Despite normal endoscopic appearance, NSE exhibits defective barrier function with similarities to defects noted in the distal esophageal epithelium in patients with gastroesophageal reflux disease (GERD). AIM: To determine whether patients with NSE, unlike patients with healthy esophageal epithelium, have C-terminal fragments (CTFs) of e-cad detectable on tissue biopsy. Secondly, to determine whether patients with NSE have elevated levels of N-terminal fragments (NTFs) of e-cad in the serum. METHODS: Fifteen patients with ablated long-segment BE, who had healing with formation of NSE, were enrolled in this pilot study. Western blots for CTFs and NTFs were performed on biopsies of NSE. Venous blood was obtained to assess levels of NTFs. Endoscopic distal esophageal biopsies from patients without esophageal disease served as tissue controls. Control blood samples were obtained from healthy subjects. RESULTS: Blots of NSE were successful in 14/15 patients, and all 14 (100 %) had a 35-kD CTF of e-cad, while CTFs were absent in healthy control tissues. Despite CTFs in NSE, serum NTFs of e-cad in NSE were similar to controls, p > 0.05. However, unlike healthy controls, blots of NSE also showed NTFs with molecular weights of 70-90 kD. CONCLUSIONS: Cleavage of e-cad, as evidenced by the presence of CTFs and NTFs on biopsy, contributes to defective barrier function in NSE. However, unlike findings reported in GERD patients, serum NTFs are not elevated in NSE patients. This difference may reflect poor absorption with tissue entrapment of NTFs in previously ablated areas with poorly perfused NSE.

Renal safety of intravenous gadolinium-enhanced magnetic resonance imaging in patients awaiting liver transplantation.

Renal dysfunction in cirrhosis carries a high morbidity and mortality. Given the potential risk of contrast-induced nephropathy associated with iodinated intravenous contrast used in computed tomography (CT), alternate contrast modalities for abdominal imaging in liver transplant candidates need to be examined. The purpose of this study was to examine the renal safety of magnetic resonance imaging (MRI) with gadolinium in patients awaiting liver transplantation. The study involved a retrospective analysis of 352 patients of abdominal MRI with low-dose gadobenate dimeglumine (MultiHance) (0.05 mmol/kg) in patients with cirrhosis and without renal replacement therapy at a single center during the period from 2007 to 2013. For each case, serum creatinine before and within a few days after the MRI were compared. In addition, the patients were analyzed for the development of nephrogenic systemic fibrosis (NSF), a reported complication of gadolinium in chronic kidney disease. The pre-MRI serum creatinine values ranged from 0.36 to 4.86 mg/dL, with 70 patients (20%) having values ≥ 1.5 mg/dL. A comparison of the pre- and post-MRI serum creatinine values did not demonstrate a clinically significant difference (mean change = 0.017 mg/dL; P = 0.38), including those patients with a pre-MRI serum creatinine ≥ 1.5 mg/dL. In addition, no cases of NSF were noted. In conclusion, our findings suggest that MRI with low-dose gadobenate dimeglumine (MultiHance) is a nonnephrotoxic imaging modality in liver transplant candidates, and its use can be cautiously expanded to liver transplant candidates with concomitant renal insufficiency.