Daniel S. Mishkin

Complications associated with double balloon enteroscopy at nine US centers.

BACKGROUND & AIMS Double balloon enteroscopy (DBE) was introduced into the US in 2004. Potential complications include perforation, pancreatitis, and gastrointestinal bleeding. Prevalence and risk factors for complications have not been described in a US population. METHODS We conducted a retrospective study of DBE complications in 9 US centers. We obtained detailed information for each complication including patient history, maneuvers performed during the DBE, and presence of altered surgical anatomy. RESULTS We collected data from 2478 DBE examinations performed from 2004 to 2008. The dataset included 1691 (68%) anterograde DBE, 722 (29%) retrograde DBE (including 5 per-stomal DBEs), and 65 (3%) DBE-facilitated endoscopic retrograde cholangiopancreatography ERCP cases. There were a total of 22 (0.9%) major complications including perforation in 11 (0.4%), pancreatitis in 6 (0.2%), and bleeding in 4 (0.2%) patients. One of 6 cases of pancreatitis occurred post retrograde DBE. Perforations occurred in 3/1691 (0.2%) anterograde examinations and 8/719 (1.1%) retrograde DBEs (P = .004). Eight (73%) perforations occurred during diagnostic DBE examinations. Four of 8 retrograde DBE perforations occurred in patients with prior ileoanal or ileocolonic anastomoses. In the subset of 219 examinations performed in patients with surgically altered anatomy, perforations occurred in 7 (3%), including 1/159 (0.6%) anterograde DBE examinations, 6/60 (10%) retrograde DBEs, and 1 of 5 (20%) peristomal DBE examinations (P < .005 compared with patients without surgically altered anatomy). CONCLUSIONS DBE is associated with a higher complication rate compared with standard endoscopic procedures. The perforation rate was significantly elevated in patients with altered surgical anatomy undergoing diagnostic retrograde DBE examinations.

Fructose and Sorbitol Malabsorption in Ambulatory Patients with Functional Dyspepsia Comparison with Lactose Maldigestion/Malabsorption

The aim of this study was to study sugarmaldigestion/malabsorption in patients with functionaldyspepsia using H breath testing. End-expiratory breathH after separate 2 challenges with lactose (25 g), fructose (25 g), and sorbitol (5 g) were usedto determine malabsorption, as well as small boweltransit time (SBTT). Five hundred twenty patients withfunctional dyspepsia received all three challenges. Smaller groups were also tested after lactulose(10 g, N = 36) and glucose (50 g, N = 90) challenges.Fructose and sorbitol were closely linked with respectto absorption and malabsorption status. Only in the case of lactose maldigestion/malabsorption wasthere a greater than random prevalence of malabsorption(P < 0.001) for fructose and sorbitol. In contrast tolactose, ethnic origin did not influence fructose or sorbitol malabsorption, and femalespredominated among fructose and sorbitol malabsorbers.In Jews, the prevalence of lactosemaldigestion/malabsorption decreased in the age group of25-55 and subsequently rose after 55, while fructose and sorbitolmalabsorption decreased progressively with advancingage. With respect to small bowel transit time (SBTT), inthe case of sorbitol and lactulose, it was significantly greater (P < 0.05) than those for fructoseand lactose. Multiple sugar malabsorptions are commonwhen lactose maldigestion/malabsorption ispresent.

Stratifying the Risks of Oral Anticoagulation in Patients With Liver Disease

Background—Chronic liver disease presents a relative contraindication to warfarin therapy, but some patients with liver disease nevertheless require long-term anticoagulation. The goal is to identify which patients with liver disease might safely receive warfarin. Methods and Results—Among 102 134 patients who received warfarin from the Veterans Affairs from 2007 to 2008, International Classification of Diseases-Ninth Revision codes identified 1763 patients with chronic liver disease. Specific diagnoses and laboratory values (albumin, aspartate aminotransferase, alanine aminotransferase, creatinine, and cholesterol) were examined to identify risk of adverse outcomes, while controlling for available bleeding risk factors. Outcomes included percent time in therapeutic range, a measure of anticoagulation control, and major hemorrhagic events, by International Classification of Diseases-Ninth Revision codes. Patients with liver disease had lower mean time in therapeutic range (53.5%) when compared with patients without (61.7%; P<0.001) and more hemorrhages (hazard ratio, 2.02; P<0.001). Among patients with liver disease, serum albumin and creatinine levels were the strongest predictors of both outcomes. We created a 4-point score system: patients received 1 point each for albumin (2.5–3.49 g/dL) or creatinine (1.01–1.99 mg/dL), and 2 points each for albumin (<2.5 g/dL) or creatinine (≥2 mg/dL). This score predicted both anticoagulation control and hemorrhage. When compared with patients without liver disease, those with a score of zero had modestly lower time in therapeutic range (56.7%) and no increase in hemorrhages (hazard ratio, 1.16; P=0.59), whereas those with the worst score (4) had poor control (29.4%) and high hazard of hemorrhage (hazard ratio, 8.53; P<0.001). Conclusions—Patients with liver disease receiving warfarin have poorer anticoagulation control and more hemorrhages. A simple 4-point scoring system using albumin and creatinine identifies those at risk for poor outcomes.

The glucose breath test: A diagnostic test for small bowel stricture(s) in Crohn's disease

The aim of this study was to determine whether an indirect noninvasive indicator of proximal bacterial overgrowth, the glucose breath test, was of diagnostic value in inflammatory bowel disease. Twenty four of 71 Crohns disease patients tested had a positive glucose breath test. No statistical conclusions could be drawn between the Crohns disease activity index and glucose breath test status. Of patients with radiologic evidence of small bowel stricture(s), 96.0% had a positive glucose breath test, while only one of 46 negative glucose breath test patients had a stricture. The positive and negative predictive values for a positive glucose breath test as an indicator of stricture formation were 96.0% and 97.8%, respectively. This correlation was not altered in Crohns disease patients with fistulae or status postresection of the terminal ileum. The data in ulcerative colitis were nondiagnostic. In conclusion, the glucose breath test appears to be an accurate noninvasive inexpensive diagnostic test for small bowel stricture(s) and secondary bacterial overgrowth in Crohns disease.

Conception soon after discontinuing interferon/ribavirin therapy: a successful outcome

1. Tokumine F, Sunagawa T, Shiohira Y, et al. Drug-associated cholelithiasis: A case of sulindac stone formation and the incorporation of sulindac metabolites into the gallstones. Am J Gastroenterol 1999;94:2285–8. 2. Shen TY, Witzel BE, Jones H, et al. Synthesis of a new antiinflammatory agent, cis-5-fluoro-2-methyl-1-[p-(methylsulfinyl)benzylidenyl]-indene-3-acetic acid. Fed Proc 1972;31: 577. 3. Duggan DE, Hare LE, Ditzler CA, et al. The disposition of sulindac. Clin Pharmacol Ther 1977;21:326–35. 4. Rare complication with sulindac. FDA Drug Bull 1989;Feb 4. 5. Sugerman HJ. Sulindac-induced acute pancreatitis mimicking gallstone pancreatitis. Am Surg 1989;55:536–8.

Re: Pimentel et al.--Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome.

TO THE EDITOR: The article by Pimentel et al. in the December issue (1) concludes that 78% of irritable bowel syndrome (IBS) patients have evidence of small intestinal bacterial overgrowth (SIBO) and that 48% of subjects whose SIBO was eradicated no longer met the Rome criteria for IBS symptoms. Our experience and data do not support the very high prevalence of SIBO quoted in this article. We conducted multiple hydrogen breath tests on IBS patients, such as lactose, fructose, and sorbitol for symptom management, but also glucose and lactulose challenges for their diagnostic potential (2, 3). Our hypothesis was that although IBS patients have a constellation of symptoms, they have no identifiable organic pathology on routine testing. Therefore, the presence of a positive glucose breath test (GBT) or lactulose hydrogen breath test would indicate SIBO, which should be “pathological.” Our data showed that 28% of 100 consecutive patients with functional dyspepsia/IBS had positive lactulose hydrogen breath tests according to the criteria of Pimentelet al. (1). The bulk of our experience relates to the use of the GBT as an indirect test for SIBO (4) in 350 patients. Thirteen percent were GBT 1. The prevalence rose to 22.2% and 25.6% in the presence of elevated fasting hydrogen and methane, respectively (high background

Downhill Esophageal Varices Caused by Catheter-Related Thrombosis

15 ppm on at least three sugar challenges). Twenty-seven of a total of 60 GBT1 patients were treated with short courses of antibiotics. Symptomatic improvement and reversal of GBT positive to negative occurred in 92.6% and 74.1%, respectively. In our data, the patients who were GBT 1 were re-evaluated regarding possible explanations for this indirect evidence of abnormal SIBO. Etiologies such as diabetes mellitus with complications and history of previously treated and untreated GI infections were the most common. In the majority of patients we were able to suggest or hypothesize one of these clinical scenarios, but approximately 20% remained unexplained. These data did not support using GBT to exclude functional dyspepsia/IBS by identifying SIBO. From our study and interpretation of Pimentel’s data, there appears to be a subgroup of IBS patients who have SIBO on indirect testing and would benefit from a course of antibiotics. More patients need to be tested to help define this specific patient population. In the absence of more objective data and lack of a true gold standard test of SIBO, we believe that this will be a dynamic field that still needs to be explored.

Central endoscopy reads in inflammatory bowel disease clinical trials: The role of the imaging core lab

3 55-year-old woman with end-stage renal disease on hemodialysis presented with hematemesis and melena after a routine dialysis session. wo months prior she had been diagnosed with a non–catheter-related left pper-extremity deep vein thrombosis and was placed on anticoagulation with arfarin. Her past medical history was significant for human immunodefiiency virus (last CD4 cell count, 168/mm3) and ischemic cardiomyopathy ejection fraction, 40%). On examination, she was hemodynamically unstable. he had a swollen face with puffy eyes, bulging neck veins, and an edematous ight breast and right arm that had developed over the previous 3 months. A unneled right internal jugular central venous catheter was in place since 5 onths prior. Laboratory testing revealed a hemoglobin level of 7.4 g/dL, ecreased from 12.5 g/dL, and an international normalized ratio of 2.29. An esophagogastroduodenoscopy showed grade III varices in the proximal sophagus with an overlying protuberant blood clot (Figure A). The rest of the sophagus was normal. Endoscopic variceal ligation was performed with placeent of 3 bands, resulting in successful hemostasis and decompression of the arices. Magnetic resonance angiography and venography revealed an abrupt ut off in the superior vena cava (SVC) with an intraluminal obstructing hrombus, likely related to her central venous catheter (Figure B). Radiographic vidence of numerous breast and abdominal collaterals suggested a chronic bstruction. The patient underwent angiography, which confirmed the abence of blood flow beyond the thrombus. Balloon dilation with stent placeent was performed with successful recannulization of the SVC, shown by eturn of physiologic blood flow from the SVC to the right atrium on angioram (Figure C). Her internal jugular central venous catheter was removed. ecovery was uneventful and the patient was discharged home off anticoaglation. Downhill varices form in the proximal esophagus and provide an alternate oute for blood flow when systemic flow is obstructed. Obstruction of the SVC bove the level of the azygous vein causes blood to return toward the heart via he azygous vein and mediastinal collaterals, resulting in the formation of arices in the upper third of the esophagus. This leads to the downward irection of blood flow along the esophagus, hence the name downhill varices. n contrast, obstruction of the SVC below the level of the azygous vein causes lood to return to the heart via the inferior vena cava through the hemiazygos, sophageal, and portal veins and results in formation of varices along the ntire length of the esophagus. Downhill varices are less common than uphill istal esophageal varices caused by portal hypertension. Downhill varices rarely leed and it is estimated that 7.6% are associated with hemorrhage.1,2 Downhill varices are associated most often with upper-body venous obtruction from a variety of causes including primary and metastatic mediastial tumors, mediastinal fibrosis, substernal goiters, venulitis, indwelling cathters, muscular constriction of the hypopharyngeal veins, and, rarely, astleman disease.3 Diagnosis should be suspected when patients present with pper gastrointestinal bleeding and symptoms of SVC syndrome, including yspnea, facial swelling, and head fullness. Management of downhill varices hould be targeted at obtaining hemostasis through endoscopic therapy and reatment of the underlying vascular occlusion. At the 3-month follow-up evaluation this patient had significant improveent in her facial swelling and breast and arm edema, and no further bleeding fter removal of her central venous catheter and recannulization of her SVC.

Pregnancy outcomes in liver transplant patients, a population-based study

Clinical trials in inflammatory bowel disease (IBD) are evolving at a rapid pace by employing central reading for endoscopic mucosal assessment in a field that was, historically, largely based on assessments by local physicians. This transition from local to central reading carries with it numerous technical, operational, and scientific challenges, many of which can be resolved by imaging core laboratories (ICLs), a concept that has a longer history in clinical trials in a number of diseases outside the realm of gastroenterology. For IBD trials, ICLs have the dual goals of providing objective, consistent assessments of endoscopic findings using central-reading paradigms whilst providing important expertise with regard to operational issues and regulatory expectations. This review focuses on current approaches to using ICLs for central endoscopic reading in IBD trials.

Sorbital H2 breath testing when screening for malabsorption/intolerance and untreated celiac disease: Understanding the dose and concentration issues

Abstract Objective: To determine the incidence of pregnancy in liver transplant (LT) patients in a large population-based cohort and to determine the maternal and fetal risks associated with these pregnancies. Methods: We conducted an age-matched cohort study using the US Healthcare and Utilization project–Nationwide Inpatient Sample from 2003–2011. We used unconditional logistic regression, adjusted for baseline characteristics, to estimate the likelihood of common obstetric complications in the LT group compared with age-matched nontransplant patients. Results: There were 7 288 712 deliveries and an estimated incidence of 2.1 LTs/100 000 deliveries over the nine-year study period. LT patients had higher rates of maternal complications including hypertensive disorders (OR 6.5, 95% CI: 4.4–9.5), gestational diabetes (OR 1.9, 95% CI: 1.0–3.5), anemia (OR 3.2, 95% CI: 2.1–4.9), thrombocytopenia (OR 27.5, 95% CI: 12.7–59.8) and genitourinary tract infections (OR 4.2, 95% CI: 1.8–9.8). Deliveries among women with LT had higher risks of cesarean section (OR 2.9, 95% CI: 2.0–4.1), postpartum hemorrhage (OR 3.2, 95% CI: 1.7–6.2) and blood transfusion (OR 18.7, 95% CI: 8.5–41.0). Fetal complications in LT patients included preterm delivery (OR 4.7, 95% CI: 3.2–7.0), intrauterine growth restriction (OR 4.1, 95% CI: 2.1–7.7) and congenital anomalies (OR 6.0, 95% CI: 1.1–32.0). Conclusion: Although pregnancies in LT recipients are feasible, they are associated with a high rate of maternal and fetal morbidities. Close antenatal surveillance is recommended.