Kumar Krishnan

The incidence of oesophageal adenocarcinoma in non-dysplastic Barrett's oesophagus: a meta-analysis

Introduction The risk of oesophageal adenocarcinoma (OAC) in non-dysplastic Barretts oesophagus (BO) may have been overestimated. The objective was to estimate the incidence of OAC in patients with BO without dysplasia. Methods The authors searched MEDLINE and EMBASE from 1966 to 2011 and performed a bibliographic review of previous publications, excluding abstracts, non-peer-reviewed publications and those not published in English, for prospective or retrospective studies of the incidence of OAC in patients with BO. They excluded patients with any degree of dysplasia at baseline and those without documented intestinal metaplasia. Studies were independently reviewed by two individuals. 57 of 3450 studies were included. The authors extracted information on number of patients with BO, length of follow-up, incident cases of OAC, mean age of patients, country of origin, whether prospective or retrospective, mean length of BO segments and mortality from causes other than OAC. Study quality was assessed by the Ottawa Newcastle criteria. Results The 57 included studies comprised 11 434 patients and 58 547 patient-years of follow-up. The pooled annual incidence of OAC was 0.33% (95% CI 0.28% to 0.38%). Among 16 studies that provided appropriate information on mortality, there were 56 incident cases of OAC but 684 deaths from apparently unrelated causes. Among 16 studies that provided information on patients with short-segment BO, the annual incidence of OAC was only 0.19%. Conclusions The incidence of OAC in non-dysplastic BO is around 1 per 300 patients per year. The incidence of OAC in short-segment BO is under 1 per 500 patients per year.

Intestinal growth factors: Potential use in the treatment of inflammatory bowel disease and their role in mucosal healing

Background: A key feature of inflammatory bowel disease (IBD) is impaired epithelial repair. Human growth factors comprise an array of signaling molecules that lead to ligand‐specific signal transduction. Their downstream effects are associated with several cellular functions including epithelial healing in response to injury. Several studies have described specific growth factor deficiencies in patients with IBD, implicating their role in disease pathophysiology. The aim of this review was to describe currently known enterocyte‐targeted growth factors, their mechanisms of action, and their potential therapeutic utility. Methods: The National Library of Medicine (http://www.pubmed.gov) and meeting abstracts were searched using the following terms: growth factor, intestine, colon, inflammatory bowel disease, Crohns disease, ulcerative colitis, colitis, animal model, transforming growth factor, bone morphogenetic protein, activins, growth hormone, fibroblast growth factor, epidermal growth factor (EGF), keratinocyte growth factor (KGF), glucagon‐like peptide II, granulocyte macrophage colony–stimulating factor (GM‐CSF), granulocyte colony–stimulating factor (G‐CSF), vascular endothelial growth factor (VEGF) inhibitors, and trefoil factors. Results: Several growth factors are therapeutic candidates in IBD. Growth hormone, KGF, EGF, teduglutide, GM‐CSF/G‐CSF have entered early clinical trials, whereas others are currently in preclinical evaluation. Conclusions: There are several growth factors responsible for epithelial repair. Preliminary studies using recombinant growth factors seem promising in IBD preclinical and clinical trials. (Inflamm Bowel Dis 2011;)

Increased Risk for Persistent Intestinal Metaplasia in Patients With Barrett's Esophagus and Uncontrolled Reflux Exposure Before Radiofrequency Ablation

BACKGROUND & AIMS Radiofrequency ablation (RFA) is a safe alternative to esophagectomy for patients with dysplastic Barretts esophagus (BE). Although some studies have indicated that RFA is effective at eradicating dysplasia, most have found that RFA is not as effective in eradicating intestinal metaplasia. We investigated whether uncontrolled reflux is associated with persistent intestinal metaplasia after RFA. METHODS Thirty-seven patients with BE underwent RFA, high-resolution manometry, and 24-hour impedance-pH testing; they received proton pump inhibitors twice daily. Patients returned every 2 months for repeat treatment or standard surveillance. Patients were classified as complete responders (CRs) if all intestinal metaplasia was eradicated in fewer than 3 ablation sessions. We analyzed clinical parameters to identify factors associated with a CR or incomplete responder (ICR). RESULTS Among the 37 patients, 22 had a CR and 15 had an ICR. Mann-Whitney U tests revealed that length of BE, size of hiatal hernia, and frequency of reflux, but not acid reflux, differed between CRs and ICRs. CRs had fewer weakly acidic events than ICRs (29.5 vs 52; P < .05) and total reflux events (33.5 vs 60; P < .05), and a trend toward fewer weakly alkaline events (1.0 vs 5.0; P = .06). No other clinical or manometric features differed between groups. CONCLUSIONS Uncontrolled, predominantly weakly acidic reflux despite twice-daily proton pump inhibitor therapy before RFA increases the incidence of persistent intestinal metaplasia after ablation in patients with BE. Length of BE and size of hiatal hernia also were associated with persistent intestinal metaplasia after RFA.

Radiofrequency ablation for refractory gastric antral vascular ectasia (with video)

BACKGROUND Gastric antral vascular ectasia (GAVE) is a cause of upper GI bleeding and chronic anemia. Although upper endoscopy with argon plasma coagulation (APC) is an accepted therapy for GAVE, many patients continue to bleed and remain transfusion dependent after therapy. Radiofrequency ablation (RFA) may provide an alternative therapeutic option for GAVE. OBJECTIVE To determine the efficacy and safety of RFA for patients with GAVE who remain transfusion dependent after APC treatment. DESIGN Open-label prospective cohort study of patients with GAVE refractory to APC. SETTING Academic tertiary referral center. PATIENTS GAVE patients with previous failed APC therapy, chronic anemia, and transfusion dependence. INTERVENTIONS Endoscopic RFA to the gastric antrum using the HALO(90) ULTRA ablation catheter until transfusion independence is achieved or a maximum of 4 sessions are performed. MAIN OUTCOME MEASUREMENTS Transfusion requirements before and after RFA. Secondary outcomes are hemoglobin before and 6 months after RFA completion, number of RFA sessions, and complications. RESULTS Twenty-one patients underwent at least 1 RFA session with ablation of GAVE lesions. At 6 months after completion of the course of RFA therapy, 18 of 21 patients (86%) were transfusion independent. Mean hemoglobin increased from 7.8 to 10.2 in responders (n = 18). Two adverse events occurred (minor acute bleeding and superficial ulceration); both resolved without intervention. LIMITATIONS Single-center, single-operator, and nonrandomized design. CONCLUSIONS RFA is safe and effective for treating patients with refractory GAVE after attempted APC.

Endoscopic ultrasound as an adjunctive evaluation in patients with esophageal motor disorders subtyped by high-resolution manometry

Esophageal motor disorders are a heterogeneous group of conditions identified by esophageal manometry that lead to esophageal dysfunction. The aim of this study was to assess the clinical utility of endoscopic ultrasound (EUS) in the further evaluation of patients with esophageal motor disorders categorized using the updated Chicago Classification.

Do Endoscopic Antireflux Procedures Fit in the Current Treatment Paradigm of Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is a common condition requiring considerable medical resources. The mainstay of therapy is proton pump inhibitors (PPIs), which are effective at reducing acid reflux. In patients who have refractory acid reflux and esophagitis despite high-dose PPI, or are intolerant of the side effects of PPI therapy, surgical fundoplication is the primary therapy. The risk and cost gap between medical therapy and surgery has resulted in substantial interest in less-invasive endoscopic therapies. In this review, we discuss the underlying physiology of GERD along with the anatomic hurdles that must be overcome to develop an effective antireflux procedure. We also review the current published literature and assess the clinical efficacy of the devices that have been studied or currently are being investigated. Despite promising early studies, many of the devices fall short in high-quality randomized controlled trials. Furthermore, the physiologic aberration resulting in GERD oftentimes is addressed inadequately. Although there is certainly a need for less-invasive, safe, and effective therapy for reflux, therapy will need to withstand the established clinical efficacy of both PPI and surgical fundoplication. At present, we have the luxury of time to wait for such a device to become available.

Recurrence of Barrett’s Esophagus is Rare Following Endoscopic Eradication Therapy Coupled With Effective Reflux Control

Objectives:Recent data suggest that effective control of gastroesophageal reflux improves outcomes associated with endoscopic eradication therapy (EET) for Barrett’s esophagus (BE). However, the impact of reflux control on preventing recurrent intestinal metaplasia and/or dysplasia is unclear. The aims of the study were: (a) to determine the effectiveness and durability of EET under a structured reflux management protocol and (b) to determine the impact of optimizing anti-reflux therapy on achieving complete eradication of intestinal metaplasia (CE-IM).Methods:Consecutive BE patients referred for EET were enrolled and managed with a standardized reflux management protocol including twice-daily PPI therapy during eradication. Primary outcomes were rates of CE-IM and IM or dysplasia recurrence.Results:Out of 221 patients enrolled (46.0% with high-grade dysplasia/intramucosal carcinoma, 34.0% with low-grade dysplasia, and 20.0% with non-dysplastic BE) an overall CE-IM of 93% was achieved within 11.6±10.2 months. Forty-eight patients did not achieve CE-IM in 3 sessions. After modification of their reflux management, 45 (93.7%) achieved CE-IM in a mean of 1.1 RFA sessions. Recurrence occurred in 13 patients (IM in 10(4.8%), dysplasia in 3 (1.5%)) during a mean follow-up of 44±18.5 months. The only significant predictor of recurrence was the presence of a hiatal hernia. Recurrence of IM was significantly lower than historical controls (10.9 vs. 4.8%, P=0.04).Conclusions:The current study highlights the importance of reflux control in patients with BE undergoing EET. In this setting, EET has long-term durability with low recurrence rates providing early evidence for extending endoscopic surveillance intervals after EET.

Addition of Endoscopic Ultrasound (EUS)-Guided Fine Needle Aspiration and On-Site Cytology to EUS-Guided Fine Needle Biopsy Increases Procedure Time but Not Diagnostic Accuracy

Background/Aims Although the diagnostic accuracy of endoscopic ultrasound with fine needle aspiration (EUS-FNA) in pancreas adenocarcinoma is high, endoscopic ultrasound with fine needle biopsy (EUS-FNB) is often required in other lesions; in these cases, it may be possible to forgo initial EUS-FNA and rapid on-site cytology evaluation (ROSE). The aim of this study was to compare the diagnostic accuracy of EUS-FNB alone (EUS-FNB group) with a conventional sampling algorithm of EUS-FNA with ROSE followed by EUS-FNB (EUS-FNA/B group) in nonpancreas adenocarcinoma lesions. Methods Retrospective cohort study of subjects who underwent EUS sampling of nonpancreatic adenocarcinoma lesions between February 2011 and May 2013. Results Over the study period, there were 43 lesions biopsied in 41 unique patients in the EUS-FNB group and 53 patients in the EUS-FNA/B group. Overall diagnostic accuracy was similar between the EUS-FNB and EUS-FNA/B groups (83.7% vs. 84.9%; p=1.0). In the subgroup of subepithelial mass lesions, diagnostic accuracy remained similar in the EUS-FNB and EUS-FNA/B groups (81.0% and 70.6%; p=0.7). EUS-FNB procedures were significantly shorter than those in the EUS-FNA/B group (58.4 minutes vs. 73.5 minutes; p<0.0001). Conclusions EUS-FNB without on-site cytology provides a high diagnostic accuracy in nonpancreas adenocarcinoma lesions. There appears to be no additive benefit with initial EUS-FNA but this requires further study in a prospective study.

EUS-guided choledochoduodenostomy with use of a lumen-apposing metal stent: the freehand technique

re 1. A, Distorted ampullary orifice secondary to infiltrative pancreatic-head carcinoma. Despite several attempts, guidewire access could not be ved for retrograde stent placement. B, EUS revealing a markedly dilated bile duct secondary to known pancreatic head mass. Advancement of ry-enhanced lumen-apposing metal stent (LAMS) to the duodenal wall. C, Advancement of LAMS catheter into the bile duct under EUS guidance. proximal flange is deployed and visible on EUS. D, Deployment of proximal end of the LAMS under endoscopic guidance. Bile can be seen draining the stent. E, Malignant duodenal obstruction, which will not allow passage of a duodenoscope to perform standard retrograde cholangiography. F, ncement of cautery enhanced LAMS into dilated bile duct by the use of pure cut current. G, Deployment of distal flange under endoscopic guidance. sive biliary drainage is noted through the stent. H, Fluoroscopic image revealing LAMS to be positioned. No extraluminal contrast material is seen. mobilia is noted, with some residual contrast material in the bile duct.

S1481: A Novel Biopsy Protocol for Assessment of Neosquamous Epithelium After Radiofrequency Ablation of Barrett's Esophagus With High Grade Dysplasia

Radiofrequency ablation (RFA) has altered the management paradigm of Barrett’s esophagus with high grade-dysplasia (HGD). However, three specific dilemmas remain regarding tissue sampling technique after ablative therapy: 1. accurate determination of the original extent of intestinal metaplasia (IM) 2. achieving adequate depth, inclusive of muscularis mucosa (MM), to ensure proper specimen orientation and inclusion of the lamina propria for assessment of buried glands, 3. differentiating post-ablative IM at the squamocolumnar junction (SCJ) from IM of the gastric cardia.. Toward these ends, we implemented a novel biopsy protocol with jumbo biopsy forceps for identification of neosquamous epithelium (NE) after ablative therapy for dysplastic BE.