Michael A. Manfredi

Endoscopic submucosal dissection

ESD is an established effective treatment modality for premalignant and early-stage malignant lesions of the stomach, esophagus, and colorectum. Compared with EMR, ESD is generally associated with higher rates of en bloc, R0, and curative resections and a lower rate of local recurrence. Oncologic outcomes with ESD compare favorably with competing surgical interventions, and ESD also serves as an excellent T-staging tool to identify noncurative resections that will require further treatment. ESD is technically demanding and has a higher rate of adverse events than most endoscopic procedures including EMR. As such,sufficient training is critical to ensure safe conduct and high-quality resections. A standardized training model for Western endoscopists has not been clearly established,but will be self-directed and include courses, animal model training, and optimally an observership at an expert center.Numerous dedicated ESD devices are now available in the United States from different manufacturers. Although the use of ESD in the United States is increasing, issues related to technical difficulty, limited training opportunities and mentors, risk of adverse events, long procedure duration,and suboptimal reimbursement may limit ESD adoption in the United States to a modest number of academic referral centers for the foreseeable future.

Management of Ingested Foreign Bodies in Children: A Clinical Report of the NASPGHAN Endoscopy Committee

Foreign body ingestions in children are some of the most challenging clinical scenarios facing pediatric gastroenterologists. Determining the indications and timing for intervention requires assessment of patient size, type of object ingested, location, clinical symptoms, time since ingestion, and myriad other factors. Often the easiest and least anxiety-producing decision is the one to proceed to endoscopic removal, instead of observation alone. Because of variability in pediatric patient size, there are less firm guidelines available to determine which type of object will safely pass, as opposed to the clearer guidelines in the adult population. In addition, the imprecise nature of the histories often leaves the clinician to question the timing and nature of the ingestion. Furthermore, changes in the types of ingestions encountered, specifically button batteries and high-powered magnet ingestions, create an even greater potential for severe morbidity and mortality among children. As a result, clinical guidelines regarding management of these ingestions in children remain varied and sporadic, with little in the way of prospective data to guide their development. An expert panel of pediatric endoscopists was convened and produced the present article that outlines practical clinical approaches to the pediatric patient with a variety of foreign body ingestions. This guideline is intended as an educational tool that may help inform pediatric endoscopists in managing foreign body ingestions in children. Medical decision making, however, remains a complex process requiring integration of clinical data beyond the scope of these guidelines. These guidelines should therefore not be considered to be a rule or to be establishing a legal standard of care. Caregivers may well choose a course of action outside of those represented in these guidelines because of specific patient circumstances. Furthermore, additional clinical studies may be necessary to clarify aspects based on expert opinion instead of published data. Thus, these guidelines may be revised as needed to account for new data, changes in clinical practice, or availability of new technology.

Increased incidence of urinary matrix metalloproteinases as predictors of disease in pediatric patients with inflammatory bowel disease

Background: Matrix metalloproteinases (MMPs) are a family of metal‐dependent enzymes responsible for the degradation and remodeling of extracellular matrix and basement membrane proteins that occurs during both normal physiologic activity and disease. It has been suggested that MMPs may also play a role in the pathogenesis of inflammatory bowel disease (IBD) by mediating mucosal breakdown in response to an enhanced inflammatory cascade. We previously demonstrated that elevated urinary MMP levels are independent predictors of disease status in cancer patients. Here we demonstrate that elevated urinary MMP levels may be biomarkers of disease activity in patients with IBD. Methods: We analyzed 95 urine samples prospectively collected from 55 children and young adults with known or suspected IBD who presented for evaluation to the Gastrointestinal Procedure Unit at Childrens Hospital Boston. Urinary MMPs were analyzed in patients by zymography and compared to 40 age‐ and sex‐matched controls. Results: Urinary MMP levels were significantly elevated (P < 0.0001) in patients with IBD, as well as in each subgroup (Crohns disease or ulcerative colitis), relative to controls. Multiple logistic regression revealed that urinary MMP‐2 and MMP‐9 NGAL levels were independent predictors of Crohns disease and ulcerative colitis (P < 0.0001). Conclusions: These data are the first to demonstrate that urinary MMPs may represent novel noninvasive biomarkers for use in the evaluation of patients with IBD.

ASGE Technology Committee systematic review and meta-analysis assessing the ASGE Preservation and Incorporation of Valuable Endoscopic Innovations thresholds for adopting real-time imaging–assisted endoscopic targeted biopsy during endoscopic surveillance of Barrett’s esophagus

BACKGROUND AND AIMS Endoscopic real-time imaging of Barretts esophagus (BE) with advanced imaging technologies enables targeted biopsies and may eliminate the need for random biopsies to detect dysplasia during endoscopic surveillance of BE. This systematic review and meta-analysis was performed by the American Society for Gastrointestinal Endoscopy (ASGE) Technology Committee to specifically assess whether acceptable performance thresholds outlined by the ASGE Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) document for clinical adoption of these technologies have been met. METHODS We conducted meta-analyses calculating the pooled sensitivity, negative predictive value (NPV), and specificity for chromoendoscopy by using acetic acid and methylene blue, electronic chromoendoscopy by using narrow-band imaging, and confocal laser endomicroscopy (CLE) for the detection of dysplasia. Random effects meta-analysis models were used. Statistical heterogeneity was evaluated by means of I(2) statistics. RESULTS The pooled sensitivity, NPV, and specificity for acetic acid chromoendoscopy were 96.6% (95% confidence interval [CI], 95-98), 98.3% (95% CI, 94.8-99.4), and 84.6% (95% CI, 68.5-93.2), respectively. The pooled sensitivity, NPV, and specificity for electronic chromoendoscopy by using narrow-band imaging were 94.2% (95% CI, 82.6-98.2), 97.5% (95% CI, 95.1-98.7), and 94.4% (95% CI, 80.5-98.6), respectively. The pooled sensitivity, NPV, and specificity for endoscope-based CLE were 90.4% (95% CI, 71.9-97.2), 98.3% (95% CI, 94.2-99.5), and 92.7% (95% CI, 87-96), respectively. CONCLUSIONS Our meta-analysis indicates that targeted biopsies with acetic acid chromoendoscopy, electronic chromoendoscopy by using narrow-band imaging, and endoscope-based CLE meet the thresholds set by the ASGE PIVI, at least when performed by endoscopists with expertise in advanced imaging techniques. The ASGE Technology Committee therefore endorses using these advanced imaging modalities to guide targeted biopsies for the detection of dysplasia during surveillance of patients with previously nondysplastic BE, thereby replacing the currently used random biopsy protocols.

The use of carbon dioxide in gastrointestinal endoscopy

The American Society for Gastrointestinal Endoscopy (ASGE) Technology Committee provides reviews of existing, new, or emerging endoscopic technologies that have an impact on the practice of gastrointestinal endoscopy. Evidence-based methodology is used by performing a MEDLINE literature search to identify pertinent clinical studies on the topic as well as a MAUDE (U.S. Food and Drug Administration Center for Devices and Radiological Health) database search to identify the reported adverse events of a given technology. Both are supplemented by accessing the “related articles” feature of PubMed and by scrutinizing pertinent references cited by the identified studies. Controlled clinical trials are emphasized, but in many cases, data from randomized, controlled trials are lacking. In such cases, large case series, preliminary clinical studies, and expert opinions are used. Technical data are gathered from traditional and Web-based publications, proprietary publications, and informal communications with pertinent vendors. Technology Status Evaluation Reports are drafted by 1 or 2 members of the ASGE Technology Committee, reviewed and edited by the Committee as a whole, and approved by the Governing Board of the ASGE. When financial guidance is indicated, the most recent coding data and list prices at the time of publication are provided. For this review, the MEDLINE database was searched through December 2014 for relevant articles by using the key words “carbon dioxide” and “gastrointestinal endoscopy,” combined with other relevant terms such as “esophagogastroduodenoscopy,” “ERCP,” “balloon enteroscopy,” “colonoscopy,” and “complications or adverse events,” among others. Technology Status Evaluation Reports are scientific reviews provided solely for educational and informational purposes. Technology Status Evaluation Reports are not rules and should not be construed as establishing a legal standard of care or as encouraging, advocating,

Technologies for monitoring the quality of endoscope reprocessing

1 The American Society for Gastrointestinal Endoscopy (ASGE) Technology Committee provides reviews of existing, new, or emerging endoscopic technologies that have an impact on the practice of GI endoscopy. Evidence-based methodology is used, with a MEDLINE literature search to identify pertinent preclinical and clinical studies on the topic, and a MAUDE (U.S. Food and Drug Administration Center for Devices and Radiological Health) database search to identify the reported adverse events of a given technology. Both are supplemented by accessing the “related articles” feature of PubMed and by scrutinizing pertinent references cited by the identified studies. Controlled clinical trials are emphasized, but, in many cases, data from randomized, controlled trials are lacking. In such cases, large case series, preliminary clinical studies, and expert opinions are used. Technical data are gathered from traditional and Web-based publications, proprietary publications, and informal communications with pertinent vendors. For this review, the MEDLINE database was searched through September 2013 by using the keywords “endoscope reprocessing,” “endoscope disinfection,” “endoscope cleaning,” “high-level disinfection,” “surveillance cultures,” and “ATP bioluminescence.” Reports on Emerging Technologies are drafted by 1 or 2 members of the ASGE Technology Committee, reviewed and edited by the committee as a whole, and approved by the governing board of the ASGE. These reports are scientific reviews provided solely for educational and informational purposes. Reports on Emerging Technologies are not rules and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment or payment for such treatment.

Endoscopic intrapyloric injection of botulinum toxin A in the treatment of children with gastroparesis: a retrospective, open-label study

BACKGROUND Botulinum toxin A has been used in children to treat spastic disorders and recently for GI conditions. Open-label studies in adults with gastroparesis have reported an improvement in symptoms and gastric emptying after endoscopic intrapyloric botulinum injections (IPBIs), although placebo-controlled trials have shown conflicting results. Only a single case report of IPBI is available in children. OBJECTIVE To determine the long-term clinical outcomes and predictive factors for IPBI response in children with gastroparesis refractory to medical therapy. DESIGN Retrospective review. SETTING Single tertiary care center. PATIENTS Children with refractory gastroparesis symptoms undergoing IPBIs. INTERVENTIONS IPBIs. MAIN OUTCOME MEASUREMENTS Clinical improvement and predictive factors for response. RESULTS A total of 70 injections were given to 47 patients (mean age 9.98 ± 6.5 years; 23 female patients) with follow-up in 45 patients. IPBI failed in 15 patients and was successful in 30 patients. The median duration of response to the first IPBI was 3.0 months (95% CI, 1.2-4.8). A total of 29 patients received a single IPBI, and 18 received multiple IPBIs. Older age and vomiting predicted response to initial IPBI, and male sex predicted response to repeat IPBI. Only 1 patient reported exacerbation of vomiting after IPBI resolving within a week. LIMITATIONS The open-label and retrospective nature of the study. CONCLUSION IPBI is safe and may be effective in the management of children with symptoms of gastroparesis. Subgroups identifying who responded to the first IPBI include older patients and those presenting with vomiting, whereas male patients responded better to repeat IPBIs.

Foker process for the correction of long gap esophageal atresia: Primary treatment versus secondary treatment after prior esophageal surgery

PURPOSE The Foker process (FP) uses tension-induced growth for primary esophageal reconstruction in patients with long gap esophageal atresia (LGEA). It has been less well described in LGEA patients who have undergone prior esophageal reconstruction attempts. METHODS All cases of LGEA treated at our institution from January 2005 to April 2014 were retrospectively reviewed. Patients who initially had esophageal surgery elsewhere were considered secondary FP cases. Demographics, esophageal evaluations, and complications were collected. Median time to esophageal anastomosis and full oral nutrition was estimated using the Kaplan-Meier method. Multivariate Cox-proportional hazards regression identified potential risk factors. RESULTS Fifty-two patients were identified, including 27 primary versus 25 secondary FP patients. Median time to anastomosis was 14 days for primary and 35 days for secondary cases (p<0.001). Secondary cases (p=0.013) and number of thoracotomies (p<0.001) were identified as significant predictors for achieving anastomosis and the development of a leak. Predictors of progression to full oral feeding were primary FP cases (O.R.=17.0, 95% CI: 2.8-102, p<0.001) and patients with longer follow-up (O.R.=1.06/month, 95% CI: 1.01-1.11, p=0.005). CONCLUSIONS The FP has been successful in repairing infants with primary LGEA, but the secondary LGEA patients proved to be more challenging to achieve a primary esophageal anastomosis. Early referral to a multidisciplinary esophageal center and a flexible approach to establish continuity in secondary patients is recommended. Given their complexity, larger studies are needed to evaluate long-term outcomes and discern optimal strategies for reconstruction.

A recurrent craniopharyngioma illustrates the potential usefulness of urinary matrix metalloproteinases as noninvasive biomarkers: case report.

OBJECTIVEMatrix metalloproteinases (MMPs) are a class of enzymes involved in angiogenesis, tumor growth, and metastasis. Recent reports indicate that urinary MMPs predict the presence of several types of tumors, including those of the breast, prostate, and bladder. Ongoing protocols at our institution are evaluating the efficacy of urinary MMPs as diagnostic markers for brain tumors and gastrointestinal disease. CLINICAL PRESENTATIOnAn 8-year-old girl underwent transsphenoidal resection of a craniopharyngioma at the age of 6 years with radiographic gross total resection. Two years later, her urine was analyzed for MMPs as part of an evaluation for gastrointestinal complaints. Despite normal gastrointestinal evaluation results, her urinary MMP levels were markedly elevated. She subsequently sought treatment for recurrent craniopharyngioma. INTERVENTIONThe craniopharyngioma was resected again. Approximately 1 year after surgery, no sources of the elevated MMPs have been found other than the recurrent craniopharyngioma. Follow-up analysis of urinary MMPs demonstrated clearing of markers concordant with tumor treatment. CONCLUSIONWe report the finding of elevated urinary MMPs in the setting of a recurrent craniopharyngioma. These biomarkers correlate with the presence of disease, clear with treatment, and can be tracked from source tissue to urine. The findings of this case support the hypothesis that urinary MMPs may be a useful predictor of the presence or recurrence of brain tumors. To our knowledge, this is the first report supporting the proof-of-principle concept that urinary MMPs may have potential usefulness in predicting the presence of brain tumors, expanding the spectrum of tumors capable of being diagnosed with this technique.

Bowel Preparation for Pediatric Colonoscopy: Report of the NASPGHAN Endoscopy and Procedures Committee

ABSTRACT Pediatric bowel preparation protocols used before colonoscopy vary greatly, with no identified standard practice. The present clinical report reviews the evidence for several bowel preparations in children and reports on their use among North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition members. Publications in the pediatric literature for bowel preparation regimens are described, including mechanisms of action, efficacy and ease of use, and pediatric studies. A survey distributed to pediatric gastroenterology programs across the country reviews present national practice, and cleanout recommendations are provided. Finally, further areas for research are identified.