Felice Schnoll-Sussman

Increasing Incidence of Rectal Cancer in Patients Aged Younger Than 40 Years An Analysis of the Surveillance, Epidemiology, and End Results Database

The incidence of rectal cancer in the United States in young patients is considered to be low. Underestimating this incidence may result in a failure to diagnose younger patients with rectal cancer in a timely manner.

Commercial molecular panels are of limited utility in the classification of pancreatic cystic lesions.

The PathfinderTG biomarker panel is useful in the evaluation of pancreatic cysts that have clinical features suspicious for malignancy, but its utility in classifying fine-needle aspiration biopsies from small pancreatic cystic lesions is yet to be proven. We used morphology to classify 20 pancreatic cyst cytology aspirates, all of which met radiographic criteria for close observation. Cases were cytologically classified as consistent with pseudocyst, serous cystadenoma, or mucinous neoplasm with low-grade, intermediate-grade, or high-grade dysplasia and analyzed for carcinoembryonic antigen. Redpath Integrated Pathology Inc. rendered diagnoses of nonmucinous (reactive/indolent or serous) or mucinous (low-risk or at risk) cyst on the basis of results of the PathfinderTG panel (KRAS mutations, DNA content, and loss of heterozygosity at microsatellites linked to tumor suppressor genes). Cytologic and commercial laboratory diagnoses were concordant in only 7 (35%) cases. Seven cysts classified as mucinous with low-grade dysplasia by cytology were interpreted as nonmucinous on the basis of the PathfinderTG panel, 2 of which were resected mucinous cysts. Two pancreatitis-related pseudocysts were misdiagnosed as low-risk mucinous cysts; 1 mucinous cyst with low-grade dysplasia was considered at risk for neoplastic progression using the PathfinderTG panel. Only 1 cyst misclassified as pseudocyst by cytology, but low-risk mucinous cyst by molecular analysis, proved to be a mucinous cystic neoplasm with low-grade dysplasia after surgical resection. We conclude that the PathfinderTG panel may aid the classification of pancreatic lesions, but is often inaccurate and should not replace cytologic evaluation of these lesions.

Accuracy of First- and Second-Generation Colon Capsules in Endoscopic Detection of Colorectal Polyps: A Systematic Review and Meta-analysis

BACKGROUND & AIMS Colon capsule endoscopy (CCE) is a noninvasive technique used to explore the colon without sedation or air insufflation. A second-generation capsule was recently developed to improve accuracy of detection, and clinical use has expanded globally. We performed a systematic review and meta-analysis to assess the accuracy of CCE in detecting colorectal polyps. METHODS We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and other databases from 1966 through 2015 for studies that compared accuracy of colonoscopy with histologic evaluation with CCE. The risk of bias within each study was ascertained according to Quality Assessment of Diagnostic Accuracy in Systematic Reviews recommendations. Per-patient accuracy values were calculated for polyps, overall and for first-generation (CCE-1) and second-generation (CCE-2) capsules. We analyzed data by using forest plots, the I2 statistic to calculate heterogeneity, and meta-regression analyses. RESULTS Fourteen studies provided data from 2420 patients (1128 for CCE-1 and 1292 for CCE-2). CCE-2 and CCE-1 detected polyps >6 mm with 86% sensitivity (95% confidence interval [CI], 82%-89%) and 58% sensitivity (95% CI, 44%-70%), respectively, and 88.1% specificity (95% CI, 74.2%-95.0%) and 85.7% specificity (95% CI, 80.2%-90.0%), respectively. CCE-2 and CCE-1 detected polyps >10 mm with 87% sensitivity (95% CI, 81%-91%) and 54% sensitivity (95% CI, 29%-77%), respectively, and 95.3% specificity (95% CI, 91.5%-97.5%) and 97.4% specificity (95% CI, 96.0%-98.3%), respectively. CCE-2 identified all 11 invasive cancers detected by colonoscopy. CONCLUSIONS The sensitivity in detection of polyps >6 mm and >10 mm increased substantially between development of first-generation and second-generation colon capsules. High specificity values for detection of polyps by CCE-2 seem to be achievable with a 10-mm cutoff and in a screening setting.

Clinical Implications of Emerging Data on the Safety of Proton Pump Inhibitors

Opinion statementProton pump inhibitors (PPI) are among the safest class of drugs used by all care providers, including gastroenterologists. They are the mainstay in treatment of acid-related disease, in particular, gastroesophageal reflux disease. Without them, many patients would experience a major decrement in their quality of life. However, no drug is without side effects or adverse events. In the past decade, numerous reports, principally case control studies and meta-analyses, have raised questions about important adverse events related to the use of PPIs. This has affected not only physicians’ prescribing habits but patients’ concerns about using these medications, particularly long term. Several FDA warnings are listed including those related to long bone fractures, interaction with clopidogrel, enteric infections, and hypomagnesaemia. More recently, concerns regarding PPIs and cardiovascular events have resurfaced as have issues related to kidney disease and dementia. The methodology of these studies allows us to find an association with these events but does not provide us with sufficient evidence to determine causality. In general, the findings of the available studies do not fit with our clinical experience nor is the magnitude of the association sufficient to result in a major change in our practice. Nevertheless, the recent literature has resulted in our careful reevaluation of PPI use across both FDA indications and in general. This article will critically review the literature regarding potential PPI adverse events and attempt to place them in perspective for the practicing physician.

Identification of Quality Measures for Performance of and Interpretation of Data From Esophageal Manometry

BACKGROUND & AIMS Esophageal manometry is the standard for the diagnosis of esophageal motility disorders. Variations in the performance and interpretation of esophageal manometry result in discrepant diagnoses and unnecessary repeated procedures, and could have negative effects on patient outcomes. We need a method to benchmark the procedural quality of esophageal manometry; as such, our objective was to formally develop quality measures for the performance and interpretation of data from esophageal manometry. METHODS We used the RAND University of California Los Angeles Appropriateness Method (RAM) to develop validated quality measures for performing and interpreting esophageal manometry. The research team identified potential quality measures through a literature search and interviews with experts. Fourteen experts in esophageal manometry ranked the proposed quality measures for appropriateness via a 2-round process on the basis of RAM. RESULTS The experts considered a total of 29 measures; 17 were ranked as appropriate and were as follows: related to competency (2), assessment before the esophageal manometry procedure (2), the esophageal manometry procedure itself (3), and interpretation of data (10). The data interpretation measures were integrated into a single composite measure. Eight measures therefore were found to be appropriate quality measures for esophageal manometry . Five other factors also were endorsed by the experts, although these were not ranked as appropriate quality measures. CONCLUSIONS We identified 8 formally validated quality measures for the performance and interpretation of data from esophageal manometry on the basis of RAM. These measures represent key aspects of a high-quality esophageal manometry study and should be adopted uniformly. These measures should be evaluated in clinical practice to determine how they affect patient outcomes.

Development of Quality Measures for the Care of Patients with Gastroesophageal Reflux Disease

BACKGROUND & AIMS Gastroesophageal reflux disease (GERD) is a common and costly disorder. Symptoms attributed to GERD have a wide spectrum of presentations and complications that have led to complex diagnostic and management algorithms. As such, there is considerable variation in clinical approaches to GERD. In contrast to multiple published guidelines for the management of GERD, there are few validated GERD quality measures. The objective of this study was to use a well-described, formal methodology to develop valid, physician-led quality measures for all aspects of care for patients with GERD. METHODS Quality measures were identified from the literature, consensus guidelines, and GERD experts. Eight clinical experts ranked potential measures for validity on the basis of the RAND/University of California, Los Angeles Appropriateness Methodology. RESULTS Of the 52 proposed quality measures, 24 were rated as valid, and 1 new measure was developed. These valid measures were related to initial diagnosis and management (9), monitoring (3), further diagnostic testing (4), proton pump inhibitor refractory symptoms (2), symptoms of chest pain (1), erosive esophagitis (3), esophageal stricture or ring (1), and surgical therapy (2). Fifteen of these measures were ranked with the highest validity. Twenty-seven measures were determined to be equivocal; 89% of these were extracted from guidelines that were based on low or moderate level evidence. CONCLUSIONS We used RAND/University of California, Los Angeles Appropriateness Methodology to develop quality measures for GERD care. By examining performance on these valid, formally developed quality measures, clinical practices and individual providers can assess their adherence with them and direct quality improvement efforts accordingly.

Phase Ib Randomized, Double-Blinded, Placebo-Controlled, Dose Escalation Study of Polyphenon E in Patients with Barrett's Esophagus

This study was conducted to determine the safety and efficacy of the green tea–derived Polyphenon E (Poly E) in patients with Barretts Esophagus (BE). Subjects were randomized to a 6-month, twice daily (BID) oral treatment of placebo or Poly E (200, 400, or 600 mg). Endoscopic evaluation, including biopsies, was performed before and after treatment. The primary objective was to demonstrate safety; secondary objectives investigated catechin accumulation and effects in clinical specimens. Of the 44 enrolled subjects, 11 received placebo, and 33 received Poly E. No dose-limiting toxicities were encountered, and a maximum tolerated dose (MTD) was not reached. The recommended phase II dose was 600 mg twice daily. The most common treatment-related adverse events (AE) in Poly E–treated subjects were grade I and II nausea, grade I belching, and grade I lactate dehydrogenase (LDH) elevation. No treatment-related AEs were reported in placebo-treated subjects, aside from grade I laboratory abnormalities. Pill counts and subject diaries were not consistently collected, and compliance was difficult to determine. However, on the basis of an intention-to-treat analysis, there was a significant relationship between Poly E dose and esophageal EGCG level—mean changes (pmol/g) of 0.79 (placebo), 6.06 (200 mg), 35.67 (400 mg), and 34.95 (600 mg); P = 0.005. There was a possible relationship between Poly E dose and urine PGE-M concentration. In conclusion, Poly E was well-tolerated, and treatment with Poly E (400 and 600 mg) but not Poly E (200 mg) or placebo resulted in clinically relevant and detectable EGCG accumulation in the target organ, esophageal mucosa. Cancer Prev Res; 8(12); 1131–7. ©2015 AACR.

Peroral endoscopic myotomy as salvation technique post‐Heller: International experience

Treatment for achalasia has traditionally been Heller myotomy (HM). Despite its excellent efficacy rate, a number of patients remain symptomatic post‐procedure. Limited data exist as to the best management for recurrence of symptoms post‐HM. We present an international, multicenter experience evaluating the efficacy and safety of post‐HM peroral endoscopic myotomy (POEM).

New York Citywide Colon Cancer Control Coalition: A public health effort to increase colon cancer screening and address health disparities

Although screening for colorectal cancer (CRC) is a widely accepted concept nationally and screening rates are increasing, there are differences in screening rates between states and within states.

Capsule Endoscopy: Can It Replace Upper Endoscopy to Screen for Barrett's?

Capsule Endoscopy: Can It Replace Upper Endoscopy to Screen for Barretts? Felice Schnoll-Sussman, Adam B. Hernandez, Toral Shah Aim: To compare the utility of capsule endoscopy (CE) versus upper endoscopy (EGD) in evaluation of the esophagogastric junction. Background: Barrett’s esophagus (BE) is a premalignant condition in which an abnormal columnar epithelium replaces the esophageal stratified squamous epithelium. It is a known risk factor for the development of esophageal adenocarcinoma. The gold standard to screen for BE is EGD. BE can appear as erythematous tongues extending from the squamocolumnar junction or as discrete islands within normal appearing mucosa. An abnormally appearing gastroesophageal junction (GEJ) necessitates a biopsy. CE is a novel, noninvasive means of evaluating the gastrointestinal tract. A small capsule containing a camera is swallowed and transmits images to an external recording device. In this study, we evaluated CE in the diagnosis of Barrett’s-like changes of the esophagus. Methods: The capsule exams of 53 consecutive patients who presented to New York Presbyterian Hospital were retrospectively reviewed by one physician (FS). The reviewer was blinded to the findings on the patient’s previous EGD. All esophageal findings, specifically an abnormal or normal EGJ and the presence or absence of a hiatal hernia, were documented. These findings were then compared to any esophageal abnormalities seen on EGD. The sensitivity, specificity, positive and negative predictive value of detecting Barrett’s-like changes on a CE in comparison to a standard EGD were calculated. Findings: The average number of esophageal images per patient recorded by capsule endoscopy was 11. Sensitivity of CE in detecting Barrett’s-like changes = 67% Specificity of CE in detecting Barrett’s-like changes = 75% Positive predictive value = 35% Negative predictive value = 92% Fifty four percent (6/11) of patients with a false positive finding at CE had a hiatal hernia in comparison to 26% of the remaining patients. There were no capsule associated complications. Conclusions: BE is a premalignant condition which is associated with the development of esophageal adenocarcinoma. There are characteristic changes of the esophageal mucosa which to date have only been easily detectable on EGD. CE is a noninvasive means of evaluating the esophageal mucosa. The high negative predictive value of a CE in diagnosing Barrett’s-like changes of the esophagusmakes it a promising new tool in the screening for BE. The false positive rate may be improved if patients with a known hiatal hernia are excluded.