William R. Kessler

Fulminant hepatic failure as the initial presentation of acute autoimmune hepatitis

BACKGROUND & AIMS Autoimmune hepatitis is a common cause of chronic hepatitis, and acute presentation is thought to be uncommon. The aim of this study was to compare clinical, biochemical, and histological features in patients with autoimmune hepatitis presenting with either acute or chronic hepatitis. METHODS Retrospective review of all patients with autoimmune hepatitis presenting to a University medical center from 1993 to 2002. RESULTS One hundred fifteen patients with autoimmune hepatitis were identified. Ten patients with autoimmune hepatitis were identified as having acute presentation (group I), and 20 patients with a classic presentation as chronic hepatitis (group II) served as age- and sex-matched controls. All patients met criteria published by the International Autoimmune Hepatitis Group. Patients with acute presentation differed significantly with regard to encephalopathy, albumin levels, and bilirubin levels. Blinded liver biopsy review demonstrated that those with acute presentation had significantly less fibrosis, and significantly greater interface hepatitis, lobular disarray, lobular hepatitis, hepatocyte necrosis, zone III necrosis, and submassive necrosis. CONCLUSIONS In our study, patients with an acute presentation of autoimmune hepatitis differed from patients with a classical presentation clinically, biochemically, and histologically. In our review, a majority of patients with acute autoimmune hepatitis presented with fulminant hepatic failure. The pattern of zone 3 necrosis may be a specific finding in those with acute autoimmune hepatitis.

High-definition chromocolonoscopy vs. high-definition white light colonoscopy for average-risk colorectal cancer screening.

OBJECTIVES:Flat and depressed colon neoplasms are an increasingly recognized precursor for colorectal cancer (CRC) in Western populations. High-definition chromoscopy is used to increase the yield of colonoscopy for flat and depressed neoplasms; however, its role in average-risk patients undergoing routine screening remains uncertain.METHODS:Average-risk patients referred for screening colonoscopy at four U.S. medical centers were randomized to high-definition chromocolonoscopy or high-definition white light colonoscopy. The primary outcomes, patients with at least one adenoma and the number of adenomas per patient, were compared between the two groups. The secondary outcome was patients with flat or depressed neoplasms, as defined by the Paris classification.RESULTS:A total of 660 patients were randomized (chromocolonoscopy: 321, white light: 339). Overall, the mean number of adenomas per patient was 1.2±2.1, the mean number of flat polyps per patient was 1.4±1.9, and the mean number of flat adenomas per patient was 0.5±1.0. The number of patients with at least one adenoma (55.5% vs. 48.4%, absolute difference 7.1%, 95% confidence interval (−0.5% to 14.7%), P=0.07), and the number of adenomas per patient (1.3±2.4 vs. 1.1±1.8, P=0.07) were marginally higher in the chromocolonoscopy group. There were no significant differences in the number of advanced adenomas per patient (0.06±0.37 vs. 0.04±0.25, P=0.3) and the number of advanced adenomas <10 mm per patient (0.02±0.26 vs. 0.01±0.14, P=0.4). Two invasive cancers were found, one in each group; neither was a flat neoplasm. Chromocolonoscopy detected significantly more flat adenomas per patient (0.6±1.2 vs. 0.4±0.9, P=0.01), adenomas <5 mm in diameter per patient (0.8±1.3 vs. 0.7±1.1, P=0.03), and non-neoplastic lesions per patient (1.8±2.3 vs. 1.0±1.3, P<0.0001).CONCLUSIONS:High-definition chromocolonoscopy marginally increased overall adenoma detection, and yielded a modest increase in flat adenoma and small adenoma detection, compared with high-definition white light colonoscopy. The yield for advanced neoplasms was similar for the two methods. Our findings do not support the routine use of high-definition chromocolonoscopy for CRC screening in average-risk patients. The high adenoma detection rates observed in this study may be due to the high-definition technology used in both groups.

A retrograde-viewing device improves detection of adenomas in the colon: a prospective efficacy evaluation (with videos)

BACKGROUND Colonoscopy may fail to detect neoplasia located on the proximal sides of haustral folds and flexures. The Third Eye Retroscope (TER) provides a simultaneous retrograde view that complements the forward view of a standard colonoscope. OBJECTIVE To evaluate the added benefit for polyp detection during colonoscopy of a retrograde-viewing device. DESIGN Open-label, prospective, multicenter study evaluating colonoscopy by using a TER in combination with a standard colonoscope. SETTING Eight U.S. sites, including university medical centers, ambulatory surgery centers, a community hospital, and a physicians office. PATIENTS A total of 249 patients (age range 55-80 years) presenting for screening or surveillance colonoscopy. INTERVENTIONS After cecal intubation, the disposable TER was inserted through the instrument channel of the colonoscope. During withdrawal, the forward and retrograde video images were observed simultaneously on a wide-screen monitor. MAIN OUTCOME MEASUREMENTS The number and sizes of lesions (adenomas and all polyps) detected with the standard colonoscope and the number and sizes of lesions found only because they were first detected with the TER. RESULTS In the 249 subjects, 257 polyps (including 136 adenomas) were identified with the colonoscope alone. The TER allowed detection of 34 additional polyps (a 13.2% increase; P < .0001) including 15 additional adenomas (an 11.0% increase; P < .0001). For lesions 6 mm or larger, the additional detection rates with the TER for all polyps and for adenomas were 18.2% and 25.0%, respectively. For lesions 10 mm or larger, the additional detection rates with the TER for all polyps and for adenomas were 30.8% and 33.3%, respectively. In 28 (11.2%) individuals, at least 1 additional polyp was found with the TER. In 8 (3.2%) patients, the polyp detected with the TER was the only one found. Every polyp that was detected with the TER was subsequently located with the colonoscope and removed. For all polyps and for adenomas, the additional detection rates for the TER were 9.7%/4.1% in the left colon (the splenic flexure to the rectum) and 16.5%/14.9% in the right colon (the cecum to the transverse colon), respectively. LIMITATIONS There was no randomization or comparison with a separate control group. CONCLUSIONS A retrograde-viewing device revealed areas that were hidden from the forward-viewing colonoscope and allowed detection of 13.2% additional polyps, including 11.0% additional adenomas. Additional detection rates with the TER for adenomas 6 mm or larger and 10 mm or larger were 25.0% and 33.3%, respectively. ( CLINICAL TRIAL REGISTRATION NUMBER NCT00657371.).

A quantitative assessment of the risks and cost savings of forgoing histologic examination of diminutive polyps

BACKGROUND AND AIMS Endoscopic prediction of polyp histology is rapidly improving to the point where it may not be necessary to submit all polyps for formal histologic assessment. This study aimed to quantify the expected costs and outcomes of removing diminutive polyps without subsequent pathologic assessment. METHODS Cross-sectional analysis of a colonoscopy database for polyp histology; decision models that quantify effects on guideline-recommended surveillance and subsequent costs and consequences. The database was composed of consecutive colonoscopies from 1999 to 2004 at a single-institution tertiary care center. Patients were those found to have at least one diminutive polyp removed during colonoscopy, irrespective of indication. The main outcome measurements include up-front cost savings resulting from forgoing pathologic assessment; frequency and cost of incorrect surveillance intervals based on errors in histologic assessment; number needed to harm (NNH) for perforation and/or interval cancer. RESULTS Incorrect surveillance intervals were recommended in 1.9% of cases when tissue was submitted for pathologic assessment and 11.8% of cases when it was not. Based on the annual volume of colonoscopy in the US, the annual up-front cost savings of forgoing the pathologic assessment would exceed a billion dollars. An upper estimate on the downstream costs and consequences of forgoing pathology suggests that less than 10% of the up-front savings would be offset and the NNH exceeds 11000. CONCLUSION Endoscopic diagnosis of polyp histology during colonoscopy and forgoing pathologic examination would result in substantial up-front cost savings. Downstream consequences of the resulting incorrect surveillance intervals appear to be negligible.

Treatment of esophageal leaks, fistulae, and perforations with temporary stents: Evaluation of efficacy, adverse events, and factors associated with successful outcomes

BACKGROUND Factors associated with successful endoscopic therapy with temporary stents for esophageal leaks, fistulae, and perforations (L/F/P) are not well known. OBJECTIVES To evaluate the safety, efficacy, and outcomes of esophageal stenting in these patients and identify factors associated with successful closure. DESIGN Retrospective. SETTING Academic tertiary referral center. PATIENTS All patients with attempted stent placement for esophageal L/F/P between January 2003 and May 2012. INTERVENTION Esophageal stent placement and removal. MAIN OUTCOME MEASUREMENTS Factors predictive of therapeutic success defined as complete closure after index stent removal (primary closure) or after further endoscopic stenting (secondary closure). RESULTS Sixty-seven patients with 132 attempted stents for esophageal L/F/P were considered; 13 patients were excluded. Among the remaining 54 patients, 117 stents were placed for leaks (29 patients; 64 stents), fistulae (15 patients; 36 stents), and perforations (10 patients; 17 stents). Procedural technical success was achieved in all patients (100%). Primary closure was successful in 40 patients (74%) and secondary closure in an additional 5 (83% overall). On short-term (<3 months) follow-up, 27 patients (50%) were asymptomatic, whereas 22 (41%) had technical adverse events, including stent migration in 15 patients (28%). Factors associated with successful primary closure include a shorter time between diagnosis of esophageal L/F/P and initial stent insertion (9.03 vs 22.54 days; P = .003), and a smaller luminal opening size (P = .002). LIMITATIONS Retrospective, single-center study. CONCLUSIONS Temporary stents are safe and effective in treating esophageal L/F/P. Defect opening size and time from diagnosis to stent placement appear to be candidate predictors for successful closure.

Impact of bending section length on insertion and retroflexion properties of pediatric and adult colonoscopes

BACKGROUND:Colonoscopes with short bending sections facilitate retroflexion but their effect on other aspects of colonoscope insertion are unknown. We sought to determine the impact of short bending on cecal insertion, terminal ileal intubation, and proximal colon retroflexion.METHODS:Two studies were performed. In study 1, we randomized 104 adult patients with intact colons to undergo colonoscopy with a standard pediatric colonoscope (Olympus PCF-160), a prototype pediatric colonoscope with short bending in four directions (PCF-AYL), or a prototype pediatric colonoscope with short bending in two directions, and normal bending in two directions (PCF-AY3L). In study 2, we randomized 70 patients with intact colons to undergo colonoscopy with a prototype 170° wide angle colonoscope (CFQ160-WL) with a standard bending section length or to a prototype 170° colonoscope with a short bending section (CFQ160-W2L).RESULTS:In study 1, the cecum was reached in all patients. Using the AYL, the cecal intubation time (4.08 min) was significantly longer when compared to both the PCF-160 (2.62 min; p= 0.0001) and the AY3L (3.25 min; p= 0.02). The AYL required the application of abdominal pressure (79%) and activation of the variable stiffness device (70%) more frequently when compared to both the PCF-160 (32%; p= 0.0001 and 41%; p= 0.02, respectively) and the AY3L (34%; p= 0.0003 and 41%; p= 0.02, respectively). Successful cecal retroflexion was possible less often with the PCF-160 (57%) when compared to either the AYL (94%; p= 0.005) or AY3L (91%; p= 0.001). The ability to intubate the terminal ileum was similar in all three groups (PCF-160 and AY3L 100%; AYL 94%) as was the time needed to intubate (p= 0.73). Depth of ti intubation was deeper for the PCF-160 when compared to the AYL (p= 0.0002) or AY3L (p= 0.02). There was a trend toward deeper ileal intubation with the AY3L compared to AYL (p= 0.09).In study 2, no difference was noted in cecal intubation time (p= 0.1) or in frequency of application of abdominal pressure (p= 0.28), position change (p= 0.15), or activation of the stiffening device (p= 0.46). Cecal retroflexion was successful more often when using the W2L when compared to the WL (p= 0.00001).CONCLUSIONS:Short bending sections facilitate proximal colon retroflexion for both pediatric and adult colonoscopes, but can negatively impact cecal insertion and terminal ileal intubation in pediatric colonoscopes. A pediatric colonoscope with short bending in only two directions had good function for both cecal insertion and proximal colon retroflexion.

Outcomes of submucosal (T1b) esophageal adenocarcinomas removed by endoscopic mucosal resection

AIM To investigate the outcomes and recurrences of pT1b esophageal adenocarcinoma (EAC) following endoscopic mucosal resection (EMR) and associated treatments. METHODS Patients undergoing EMR with pathologically confirmed T1b EAC at two academic referral centers were retrospectively identified. Patients were divided into 4 groups based on treatment following EMR: Endoscopic therapy alone (group A), endoscopic therapy with either chemotherapy, radiation or both (group B), surgical resection (group C) or no further treatment/lost to follow-up (< 12 mo) (group D). Pathology specimens were reviewed by a central pathologist. Follow-up data was obtained from the academic centers, primary care physicians and/or referring physicians. Univariate analysis was performed to identify factors predicting recurrence of EAC. RESULTS Fifty-three patients with T1b EAC underwent EMR, of which 32 (60%) had adequate follow-up ≥ 12 mo (median 34 mo, range 12-103). There were 16 patients in group A, 9 in group B, 7 in group C and 21 in group D. Median follow-up in groups A to C was 34 mo (range 12-103). Recurrent EAC developed overall in 9 patients (28%) including 6 (38%) in group A (median: 21 mo, range: 6-73), 1 (11%) in group B (median: 30 mo, range: 30-30) and 2 (29%) in group C (median 21 mo, range: 7-35. Six of 9 recurrences were local; of the 6 recurrences, 5 were treated with endoscopy alone. No predictors of recurrence of EAC were identified. CONCLUSION Endoscopic therapy of T1b EAC may be a reasonable strategy for a subset of patients including those either refusing or medically unfit for esophagectomy.

751c Effectiveness of the Third Eye Retroscope for Detecting Polyps in the Right Colon

Background & Aims: Lysophosphatidic acid (LPA), a naturally produced phospholipid, mediates multiple effects that are vital to disease process, including cancer and inflammation. The expression of LPA receptor 2 (LPA2) is up-regulated in several types of cancer, including ovary and colon cancer (CC), but the importance of LPA and LPA2 in the development and progression of CC is unclear. Chronic inflammation is also a risk factor for CC. In this study, we sought to determine whether LPA and LPA2 regulate the progression of CC using animal models of CC. Methods: We examined the potential effects of LPA in CC progression by administering LPA to ApcMin/+ mice. We determined the role of LPA2 in colon tumorigenesis by examining the loss of LPA2 function. We treated LPA2-/mice with azoxymethane (AOM) and dextran sulfate sodium (DSS). Furthermore, we examined the role of LPA2 in modulating intestinal adenoma formation by crossing LPA2-/mice with ApcMin/+ mice. Results: We found that LPA treatment by gavage increased the number of adenomas in small intestine in Apcmin/+ mice. The difference in body weight and mortality suggested that the absence of LPA2 protected animals from the AOM/DSS treatment. LPA2-/mice treated with AOM/DSS showed significantly fewer and smaller tumors in the colon than wild-type (WT) mice. There was no difference in number and size of tumors between LPA2+/and WT mice. We observed reduced epithelial cell proliferation and decreases in β-catenin, Kruppel-like factor 5 (KLF5), and cyclooxygenase-2 (COX-2) expression in LPA2-/mice compared to WT. Compared to WT mice, induction of monocyte chemoattractant protein-1 (MCP-1) and macrophage migration inhibitory factor (MIF) was significantly abrogated in LPA2-/mice with reduced infiltration by macrophages. The absence of LPA2 expression in ApcMin/ + mice resulted in a significant decrease in adenomas. At 5 month, ApcMin/+/LPA2-/mice developed an average of 22 adenomas in the small intestine compared with 38 in ApcMin/ +/LPA2+/+ and 43 in ApcMin/+/LPA2+/mice. Consistently, the average number of adenomas in the colon was 2.67, 1.75, and 0.64 for ApcMin/+/LPA2+/+, ApcMin/+/LPA2+/-, and ApcMin/ +/LPA2-/respectively. Adenomas larger than 2 mm accounted for 18% for ApcMin/+/LPA2-/mice in contrast to 38% for ApcMin/+/LPA2+/+. Conclusion: The absence of LPA2 attenuates several effects that may contribute to tumorigenesis In Vivo. Hence, our studies identify LPA2 as a modulator of intestinal tumorigenesis.

Impact of the development of an endoscopic eradication program for Barrett’s esophagus with high grade dysplasia or early adenocarcinoma on the frequency of surgery

Background and aims  The impact of the advent of an institutional endoscopic eradication therapy (EET) program on surgical practice for Barrett’s esophagus (BE)-associated high grade dysplasia (HGD) or suspected T1a esophageal adenocarcinoma (EAC) is unknown. The aims of this study are to evaluate the different endoscopic modalities used during development of our EET program and factors associated with the use of EET or surgery for these patients after its development. Methods  Patients who underwent primary endoscopic or surgical treatment for BE-HGD or early EAC at our hospital between January 1992 and December 2014 were retrospectively identified. They were categorized by their initial modality of treatment during the first year, and the impact over time for choice of therapy was assessed by multivariable logistic regression. Results  We identified 386 patients and 80 patients who underwent EET and surgery, respectively. EET included single modality therapy in 254 (66 %) patients and multimodal therapy in 132 (34 %) patients. Multivariable logistic regression showed that, for each subsequent study year, EET was more likely to be performed in patients who were older ( P  = 0.0009), with shorter BE lengths ( P  < 0.0001), and with a pretreatment diagnosis of HGD ( P  = 0.0054) compared to surgical patients. The diagnosis of EAC did not increase the utilization of EET compared to surgery as time progressed ( P  = 0.8165). Conclusion  The introduction of an EET program at our hospital increased the odds of utilizing EET versus surgery over time for initial treatment of patients who were older, had shorter BE lengths or the diagnosis of BE-HGD, but not in patients with EAC.

Stenting of Esophageal Perforation in the Setting of Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is a chronic, immunemediated inflammatory condition of the esophagus that often presents with food bolus impaction requiring endoscopic therapy. The incidence of EoE has increased significantly over the last few decades [1–3]. The disease is characterized by dense eosinophilic infiltration of the esophageal epithelium, and its endoscopic appearance is classically described as concentric rings with linear furrowing [4]. Since eosinophilic infiltration leads to esophageal wall remodeling, the mucosa is extremely friable and easily torn during routine endoscopy and in particular during retrieval of an impacted food bolus [5, 6]. While there are a number of reports of esophageal perforations in the setting of EoE [6–17], none have described the use of an esophageal stent for short-term treatment of the perforation and for palliation of dysphagia. We present two cases of esophageal perforation in patients with EoE who were managed with short-term esophageal stents.