Kristen Cox

Endoscopic appearance and location dictate diagnostic yield of biopsies in eosinophilic oesophagitis

Acknowledging that eosinophilic esophagitis (EoE) is a disease with variable involvement throughout the oesophagus, studies have suggested a minimum of five biopsies to diagnose EoE. Although it is accepted that furrows and exudates appear to represent areas of inflammation, no research to date has looked specifically at EoE endoscopic findings to see if eosinophilic infiltrate correlates with specific endoscopic findings.

Clinical Outcomes, Efficacy, and Adverse Events in Patients Undergoing Esophageal Stent Placement for Benign Indications: A Large Multicenter Study.

Introduction:Esophageal stents are commonly used to treat benign esophageal conditions including refractory benign esophageal strictures, anastomotic strictures, fistulae, perforations and anastomotic leaks. Data on outcomes in these settings remain limited. Methods:We performed a retrospective multicenter study of patients who underwent fully or partially covered self-expandable stent placement for benign esophageal diseases. Esophageal stent placements were performed for the following indications: (1) benign refractory esophageal strictures, (2) surgical anastomotic strictures, (3) esophageal perforations, (4) esophageal fistulae, and (5) surgical anastomotic leaks. Results:A total of 70 patients underwent esophageal stent placement for benign esophageal conditions. A total of 114 separate procedures were performed. The most common indication for esophageal stent placement was refractory benign esophageal stricture (48.2%). Global treatment success rate was 55.7%. Treatment success rate was 33.3% in refractory benign strictures, 23.1% in anastomotic strictures, 100% in perforations, 71.4% in fistulae, and 80% in anastomotic leaks. Stent migration was noted in 28 of 70 patients (40%), most commonly seen in refractory benign strictures. Conclusions:This is one of the largest studies to date of esophageal stents to treat benign esophageal diseases. Success rates are lowest in benign esophageal strictures. These patients have few other options beyond chronic dilations, feeding tubes, and surgery, and fully covered self-expandable metallic stent give patients a chance to have their problem fixed endoscopically and still eat by mouth. Perforations, fistulas, and leaks respond very well to esophageal stenting, and stenting should be considered as a first-line therapy in these settings.

Efficacy and safety of therapeutic ERCP in patients with cirrhosis: a large multicenter study.

BACKGROUND AND AIMS Patients with cirrhosis may be less than optimal candidates for ERCP because of underlying ascites, coagulopathy, encephalopathy, and other problems. Although the risks of surgery in patients with cirrhosis are well known, few data are available regarding ERCP in patients with cirrhosis. We performed a retrospective, multicenter study of ERCP in patients with cirrhosis to evaluate outcomes, efficacy, and safety. METHODS Multicenter retrospective study. RESULTS A total of 538 ERCP procedures were performed on 328 patients with cirrhosis. A total of 229 patients had Child-Pugh (CP) class A, 229 patients had CP class B, and 80 patients had CP class C. Thrombocytopenia and coagulopathy were corrected before ERCP. The 30-day, procedure-related adverse events included post-ERCP pancreatitis (n = 25, 4.6%: 21 mild, 3 moderate, 1 severe), hemorrhage (n = 6, 1.1%), cholangitis (n = 15, 2.8%), perforation (n = 2, 0.4%), aspiration pneumonia (n = 5, 0.9%), bile leakage (n = 1, 0.2%), cholecystitis (n = 1, 0.2%), and death (n = 1, 0.2%). There was a higher incidence of adverse events in patients with CP class B and C disease when compared with those with CP class A disease (11.4%, 11.3%, and 6.1%, respectively; P = .048). There was no correlation between the risk of significant hemorrhage and the presence of coagulopathy or CP class, even in those who underwent a sphincterotomy. The presence of poorly controlled encephalopathy correlated with a higher overall adverse event rate (P = .003). Sub-analysis revealed that patients without primary sclerosing cholangitis had a significantly higher overall rate of adverse events, pancreatitis, bleeding, and cardiopulmonary adverse events after ERCP when compared with those with primary sclerosing cholangitis. CONCLUSIONS Our study was performed on a large series of patients with cirrhosis undergoing ERCP. Overall, the adverse events seen in patients with cirrhosis are similar to those seen in the general population of patients undergoing ERCP, although patients with CP classes B and C have higher adverse event rates compared with those with CP class A. Patients with cirrhosis without primary sclerosing cholangitis had significantly greater adverse event rates when compared with patients with primary sclerosing cholangitis.

Complications of ERCP in Patients Undergoing General Anesthesia Versus MAC

ERCP is well known to carry risks such as perforation, pancreatitis, and cardiopulmonary adverse events. Cardiopulmonary complications occur in approximately 1 % of cases, with a mortality rate of 0.07 % [1]. In the United States, sedation practices vary widely [2–5]. This retrospective study performed at three academicaffiliated community hospitals in Michigan evaluated whether performing all ERCP procedures under GA reduced the risk of complications when compared to MAC sedation. The hospitals were Providence Hospital, Providence Park Hospital, and St. John Macomb Hospital. A total of 650 procedures (367 procedures performed under MAC sedation and 283 procedures performed under GA) were included in this study. Statistical differences were noted in age, race and BMI when comparing the two groups, with the group receiving MAC sedation being older and having a higher proportion of Caucasian patients and a lower BMI on average. While the Charlson comorbidity index (CCI) was comparable between the two groups (p = 0.13), the patients receiving GA had a higher degree of difficulty with the ERCP (p = 0.01). A total of 89 % of ERCPs were for biliary indications in the GA group and 83 % in the MAC group. In the GA group, one patient had a prolonged weaning from the respirator (2 days). Non-cardiopulmonary complications included two cases of self-limited post-sphincterotomy bleeding and six cases of pancreatitis, five of which were mild and one of which was moderate. In the MAC group, 22 patients experienced cardiopulmonary complications: 13 cases of clinically significant hypoxia, two cases of hypoxia requiring non-invasive positive pressure ventilation and two cases of hypoxia requiring endotracheal intubation. Five patients manifested arrhythmias including bradycardia (2), tachycardia (2), and postprocedure atrial fibrillation (1). The difference in cardio-pulmonary complications between the two groups is statistically significant (p \ 0.0001). Gastrointestinal complications in the MAC group included 19 cases of post-ERCP pancreatitis, 17 of which were mild, one of which was moderate, and one of which was severe (see Table 1). On univariate analysis, the patient’s age, gender, procedure indication, procedure duration, ASA grade and diagnostic ERCP (no intervention) were noted to have a statistically significant effect on complications. On multivariate analysis, diagnostic ERCP and female gender were noted to have a statistically significant effect on complication rates in the MAC group. Multivariate analysis in the GA group did not reveal any significant associations. Overall we noted a statistically significant difference in the rates of cardiopulmonary and overall complications in the MAC group when compared to the GA group at our center. While the majority of general gastrointestinal endoscopic procedures are performed under conscious sedation, a shift toward deep sedation or GA during ERCP has been made in many institutions [6, 7]. We wish to stress that we are not trying to state that any form of sedation for ERCP is S. A. Sorser D. S. Fan E. E. Tommolino R. M. Gamara Department of Gastroenterology, Providence Hospital and Medical Center, Southfield, MI 48075, USA

Self-expanding stent effects on radiation dosimetry in esophageal cancer

It is the purpose of this study to evaluate how self‐expanding stents (SESs) affect esophageal cancer radiation planning target volumes (PTVs) and dose delivered to surrounding organs at risk (OARs). Ten patients were evaluated, for whom a SES was placed before radiation. A computed tomography (CT) scan obtained before stent placement was fused to the post‐stent CT simulation scan. Three methods were used to represent pre‐stent PTVs: 1) image fusion (IF), 2) volume approximation (VA), and 3) diameter approximation (DA). PTVs and OARs were contoured per RTOG 1010 protocol using Eclipse Treatment Planning software. Post‐stent dosimetry for each patient was compared to approximated pre‐stent dosimetry. For each of the three pre‐stent approximations (IF, VA, and DA), the mean lung and liver doses and the estimated percentages of lung volumes receiving 5 Gy, 10 Gy, 20 Gy, and 30 Gy, and heart volumes receiving 40 Gy were significantly lower (p‐values <0.02) than those estimated in the post‐stent treatment plans. The lung V5, lung V10, and heart V40 constraints were achieved more often using our pre‐stent approximations. Esophageal SES placement increases the dose delivered to the lungs, heart, and liver. This may have clinical importance, especially when the dose‐volume constraints are near the recommended thresholds, as was the case for lung V5, lung V10, and heart V40. While stents have established benefits for treating patients with significant dysphagia, physicians considering stent placement and radiation therapy must realize the effects stents can have on the dosimetry. PACS number: 87.55.dk

Elevated Serum Bilirubin Level Correlates With the Development of Cholangiocarcinoma, Subsequent Liver Transplantation, and Death in Patients With Primary Sclerosing Cholangitis.

Introduction:Predicting the clinical course of primary sclerosing cholangitis (PSC) is difficult. There are currently a paucity of studies evaluating serum chemistries as predictors of conventional clinical endpoints. The purpose of this study was to prognosticate key clinical endpoints in patients with PSC who had elevated serum liver chemistries at the time of their initial presentation. Methods:We performed a retrospective cohort study of PSC patients at our institution. The aim of our study was to determine the association between elevated liver chemistries at initial presentation—bilirubin, alanine transaminase, aspartate transaminase, or alkaline phosphatase—with a primary outcome of either cholangiocarcinoma, liver transplantation, death, or composite of the 3. The secondary endpoints examined were development of severe biliary ductal disease and need for biliary stent placement. Results:Eighty-one PSC patients (61 males and 20 females) were included in this study. By univariate analysis, there was a significant association between initial bilirubin elevation >2x the upper limit of normal (ULN) and death (P<0.009). Multivariate regression analysis revealed that an elevated initial serum total bilirubin >2xULN (P<0.017) significantly predicted the composite endpoint. By univariate analysis of pre-endoscopic retrograde cholangiopancreatography labs, serum bilirubin level elevation >2xULN showed an association with severity of biliary ductal disease (P<0.0001). A logistic regression of outcome variables also proved that >2xULN serum bilirubin levels predicted the ductal disease severity (P<0.0001). Conclusions:An initial elevation of serum total bilirubin >2xULN in PSC patients correlates positively with the development of cholangiocarcinoma, subsequent liver transplantation, and death. Elevated bilirubin also correlates positively with the severity of cholangiographic findings.

Prevalence and Relevance of Nonalcoholic Fatty Liver Disease in Patients with Primary Sclerosing Cholangitis

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the United States and encompasses two major histologic entities: simple steatosis and nonalcoholic steatoheaptitis (NASH) [1]. The incidence of NAFLD parallels the continuously growing epidemic of obesity. NAFLD often coexists with other liver diseases and contributes to progression of liver damage. Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic liver disease that is associated with inflammatory bowel disease (IBD), but is rarely linked to metabolic disturbances. The presence of NAFLD in PSC patients has not been previously evaluated. The aim of this study was to identify the prevalence of NAFLD in patients with PSC with or without associated IBD. We performed a retrospective cohort study of subjects with PSC seen at our institution between 2000 and 2012. NAFLD was defined based on evidence of steatosis on imaging (magnetic resonance imaging [MRI] or computed tomography [CT] scan) or if steatosis was present on liver biopsy or liver explant in those patients who underwent liver transplant. None of the patients had a prior diagnosis of liver disease or regular use of alcohol (defined as[30 g/ day for males and[15 g/day for females). All patients had an established diagnosis of PSC. The primary study outcomes were the frequency of, and risk factors for, NAFLD in this cohort. Eighty-one patients with PSC were identified. The mean age was 51.1 ± 16.7 years and 27 % were females. The mean BMI was 25.6 ± 5. Furthermore, 11 % had type 2 diabetes and 63 % had IBD. Thirty-three (40.8 %) patients had liver biopsy available and 74 (93 %) had imaging studies. Most of the patients (70 %) had cirrhosis based on imaging or biopsy. Three patients (3.7 %) had steatosis based on MRI imaging and another four patients (4.9 %) had steatosis based on liver pathology, but none of them had signs of steatohepatitis. Those with steatosis on biopsy or explant had only mild or focal steatosis. There was no association between steatosis and IBD in those with PSC and IBD (p = 0.25). Interestingly, two patients with PSC without concomitant IBD who developed cholangiocarcinoma (CCA) were noted to have focal steatosis on liver explant. Demographics and clinical characteristics of patients with and without NAFLD are presented on Table 1. Overall, our study suggests that NAFLD manifesting as simple steatosis can occur in patients with PSC, but rarely does. In our cohort of 81 patients with PSC, only 8.6 % had steatosis based on MRI imaging or liver pathology. This is lower than the reported 30 % prevalence of NAFLD in the general US population [2]. Traditional metabolic risk factors, such as obesity and diabetes, likely play a major role in steatosis development in PSC patients with no other obvious specific contributors. In accord with a recent study which found that IBD patients have a lower risk for NAFLD [3], we did not note an increased risk for NAFLD in patients with PSC and IBD. An additional important question that our study raises is whether steatosis may be a sign of comorbid CCA in patients with PSC. We found two patients with dominant I. Doycheva K. Cox D. G. Adler (&) Division of Gastroenterology and Hepatology, University of Utah School of Medicine, Salt Lake City, UT, USA e-mail: douglas.adler@hsc.utah.edu

Insufflation with carbon dioxide reduces pneumoperitoneum after percutaneous endoscopic gastrostomy (PEG): a randomized controlled trial

Background and study aims: Pneumoperitoneum following PEG placement has been reported in up to 60 % of cases, and while usually benign and self-limited, it can lead to evaluation for suspected perforation. This study was designed to determine whether using CO2 compared to ambient air for insufflation during PEG reduces post-procedure pneumoperitoneum. Patients and Methods: Prospective, double-blind, randomized trial of 35 consecutive patients undergoing PEG at a single academic medical center. Patients were randomized to insufflation with CO2 or ambient air. The primary outcome was pneumoperitoneum determined by left-lateral decubitus abdominal x-rays 30 minutes after PEG placement. Secondary endpoints included abdominal distention, pain, and bloating. Results: PEG was successfully placed in 17 patients using CO2 and 18 patients using ambient air. Three patients in each arm were unable or declined to have x-rays completed and were excluded. Pneumoperitoneum was identified in 2/14 (14.3 %) using CO2 and 8/15 (53.3 %) using ambient air (P = 0.05). There was no significant difference in abdominal distention, visual analog scale (VAS) scores for pain or bloating between CO2 and ambient air. Conclusion: Utilizing CO2 significantly reduces the frequency of post-procedural pneumoperitoneum compared to use of ambient air during PEG placement, with no difference in waist circumference, pain or bloating between CO2 and ambient air. CO2 appears to be safe and effective for use and may be the insufflation agent of choice during PEG.

Primary Sclerosing Cholangitis in the Setting of Normal Liver Chemistries Can Be Associated with Severe Ductal Disease and Dominant Strictures

Primary sclerosing cholangitis (PSC) is commonly associated with abnormal laboratory studies. A subset of PSC patients will present with normal laboratory studies. We conducted a retrospective study of PSC patients with normal liver chemistries to evaluate their clinical course, endoscopic, and pathologic findings. There were 102 patients in our PSC database from 2000 to 2013. Of these, 11 patients (8 M, 3 F, mean age 47.1 years) had normal liver chemistries at the time of their clinical presentation. Patients were evaluated for suspected PSC despite normal labs given a history of IBD, abdominal pain, symptoms such as pruritis, and abnormal imaging studies suggesting bile duct disease. Five patients had IBD: 3/5 had Crohn’s disease (only one of whom had colitis), 2/5 had ulcerative colitis. On CT scan, 8/11 patients had evidence of cirrhosis. 8/11 patients underwent MRI/MRCP, and 5 of these patients had ductal findings suggestive of PSC. One patient had an MRI/MRCP that was suggestive of PSC and cholangiocarcinoma. All 11 patients underwent ERCP which confirmed the diagnosis of PSC. All patients had intrahepatic ductal disease manifesting as innumerable strictures and pruning. Four patients were felt to have dominant strictures-three of these dominant strictures were in the common hepatic duct and one was in the common bile duct. Four patients were felt to have mild PSC, five were felt to have moderate PSC, and two were felt to have severe PSC. There were no complications following ERCP (Fig. 1). Eight patients underwent tissue sampling by brushings and/or biopsy during ERCP. Three patients were not felt to warrant tissue sampling. One patient had a mass lesion at the common hepatic duct that to date has yielded only benign brushing, histology, and FISH results and is being closely monitored. The patient with the dominant CBD stricture had a brushing that showed atypical cells suspicious for malignancy and a positive FISH study. This patient underwent a pancreaticoduodenectomy for presumed cholangiocarcinoma. His final pathology showed evidence of high grade dysplasia but no cancer. None of the remaining patients who underwent tissue sampling had positive FISH testing or positive brushings for malignancy (Fig. 1). Overall, this study shows that patients with PSC can have cirrhosis and significant ductal disease, including dominant strictures and abnormal tissue samples, in the setting of normal liver chemistries. Patients with PSC and normal liver chemistries were less likely to have IBD and colitis than were patients with PSC and abnormal labs [1]. All patients tolerated their ERCP exams without difficulty and had no complications: this may be explained, at least in part, by undergoing ERCP by experienced operators [2]. No patient has had significant progression of disease over a mean follow up period of 50 months. This is in contrast to most PSC patients who can be expected to have progression when followed over the same timeframe [3]. This small study demonstrates that patients with PSC who have normal liver chemistries may have slower progression of disease but can still have significant ductal and pathologic findings. T. Queen K. Cox D. G. Adler (&) Gastroenterology and Hepatology, Huntsman Cancer Center, University of Utah School of Medicine, 30N 1900E 4R118, Salt Lake City, UT 84312, USA e-mail: douglas.adler@hsc.utah.edu

Evaluation of TNM Status Changes Between the First Two CT Scans in Patients With Pancreatic Cancer

Evaluation of TNM Status Changes Between the First Two CT Scans in Patients With Pancreatic Cancer