Liam Zakko

B-cell count and survival: differentiating chronic lymphocytic leukemia from monoclonal B-cell lymphocytosis based on clinical outcome

The diagnosis of chronic lymphocytic leukemia (CLL) in asymptomatic patients has historically been based on documenting a characteristic lymphocyte clone and the presence of lymphocytosis. There are minimal data regarding which lymphocyte parameter (absolute lymphocyte count [ALC] or B-cell count) and what threshold should be used for diagnosis. We analyzed the relationship of ALC and B-cell count with clinical outcome in 459 patients with a clonal population of CLL phenotype to determine (1) whether the CLL diagnosis should be based on ALC or B-cell count, (2) what lymphocyte threshold should be used for diagnosis, and (3) whether any lymphocyte count has independent prognostic value after accounting for biologic/molecular prognostic markers. B-cell count and ALC had similar value for predicting treatment-free survival (TFS) and overall survival as continuous variables, but as binary factors, a B-cell threshold of 11 x 10(9)/L best predicted survival. B-cell count remained an independent predictor of TFS after controlling for ZAP-70, IGHV, CD38, or fluorescence in situ hybridization (FISH) results (all P < .001). These analyses support basing the diagnosis of CLL on B-cell count and retaining the size of the B-cell count in the diagnostic criteria. Using clinically relevant criteria to distinguish between monoclonal B-cell lymphocytosis (MBL) and CLL could minimize patient distress caused by labeling asymptomatic people at low risk for adverse clinical consequences as having CLL.

Breath Testing for Barrett’s Esophagus Using Exhaled Volatile Organic Compound Profiling With an Electronic Nose Device

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Jacques Bergman and Patrick Yachimski, Section Editors 61 62 63 64 65 Breath Testing for Barrett’s Esophagus Using Exhaled Volatile Organic Compound Profiling With an Electronic Nose Device 66 67 68 69 70 71 Daniel K. Chan, Liam Zakko, Kavel H. Visrodia, Cadman L. Leggett, Lori S. Lutzke, Magdalen A. Clemens, James D. Allen, Marlys A. Anderson, and Kenneth K. Wang

No Benefit From Platelet Transfusion for Gastrointestinal Bleeding in Patients Taking Antiplatelet Agents

BACKGROUND & AIMS: Antiplatelet agents decrease cardiovascular events but increase gastrointestinal bleeding (GIB). Guidelines propose platelet transfusion for patients who take antiplatelet agents and have serious GIB. We investigated whether such patients are at decreased risk for rebleeding or increased risk for cardiovascular events after platelet transfusion. METHODS: We performed a retrospective cohort study of patients with GIB admitted to Yale‐New Haven Hospital from 2008 to 2013 who were taking antiplatelet agents and had platelet counts higher than 100 × 109/L. Cases (patients who received platelet transfusion, n = 204) were matched with controls (no platelet transfusions, n = 204) for sex, age, and GIB location. The primary outcome was recurrent GIB. Multivariable regression analyses were performed to adjust for differences in baseline characteristics. RESULTS: Cases and controls had similar proportions of GIB due to non‐variceal upper GIB (117 of 204, 57% vs 115 of 204, 56%) and colonic GIB (80 of 204, 39% vs 81 of 204, 40%). Cases had more severe GIB than controls, which was based on lower blood pressure and hemoglobin levels and higher heart rates and the proportion admitted to intensive care. Univariate analyses showed that higher proportions of cases had major cardiovascular events (23% vs 13% for controls), died (7% vs 1% for controls), or had hospital stay longer than 4 days (47% vs 33% for controls). However, multivariable analyses showed a significant difference between cases and controls in only risk of death (odds ratio, 5.57; 95% confidence interval, 1.52–27.1). The adjusted odds ratio for recurrent bleeding was 1.47 (95% confidence interval, 0.73–3.05) for cases vs controls. CONCLUSIONS: The use of platelet transfusions in patients with GIB who are taking antiplatelet agents without thrombocytopenia did not reduce rebleeding but was associated with higher mortality. At least some of the increase in mortality could be due to the residual bias of an observational study, but because of the lack of benefit, we do not support the use of platelet transfusions in patients with GIB who are taking antiplatelet agents.

Screening and Preventive Strategies in Esophagogastric Cancer

Gastric adenocarcinoma, esophageal adenocarcinoma, and esophageal squamous cell carcinoma are among the most prevalent and deadly of malignancies worldwide. Screening and prevention programs will be critical to finally improving outcomes in these diseases. For gastric adenocarcinoma, screening in high-risk populations has significantly reduced mortality. More research is needed on screening high-risk individuals in low-risk populations. For esophageal adenocarcinoma, work is needed to develop efficient and effective techniques in mass screening programs. For most Western populations, current screening is not cost effective. Avoiding environmental risk factors is critical to reducing the incidence of this deadly illness.

Screening for Barrett's Esophagus.

Barretts esophagus is the only known esophageal precursor for the development of esophageal adenocarcinoma. However, screening for Barretts esophagus remains controversial. Although screening is advocated in selected populations, it is unclear how it should be implemented. In this review, the current definition of Barretts esophagus will be discussed. There will be a review of the emerging evidence supporting the cost-effectiveness of screening and surveillance for Barretts esophagus in preventing esophageal adenocarcinoma. The known risk factors for Barretts esophagus and the development of esophageal adenocarcinoma, currently utilized to determine the appropriate populations to screen, will be reviewed. Finally we will review the standard techniques utilized to screen for Barretts esophagus and examine new technologies that might improve the efficacy and availability of Barretts esophagus screening.

Radiofrequency Ablation of Barrett’s Esophagus: Efficacy, Complications, and Durability

In the last decade, radiofrequency ablation in combination with endoscopic mucosal resection has simplified and improved the treatment of Barretts esophagus. These treatments not only reduced the progression of dysplastic Barretts esophagus to esophageal adenocarcinoma but also decreased treatment-related complications. More recent data from larger series with extended follow-up periods are emerging to refine expectations in patients treated with radiofrequency ablation. Although most patients achieve eradication of neoplasia and intestinal metaplasia, in the long-term a substantial portion of patients develop recurrent disease. This article provides an updated review of radiofrequency ablation efficacy, complications, and durability.

Genetically linking chronic gastroesophageal reflux disease: Barrett’s esophagus and esophageal adenocarcinoma

Esophageal adenocarcinoma remains a devastating disease with incidence and mortality rates that are nearly equivalent. The most well known risk factor is gastroesophageal reflux (GERD) (1). Recent guidelines from multiple gastroenterology societies (American College of Gastroenterology, American Gastroenterology Association and British Society of Gastroenterology) now recommend selected screening primarily based on symptomatic GERD in patients with other known risk factors such as obesity, age, and Caucasian race. About 10–15% of those with GERD develop Barrett’s esophagus (BE) or intestinal metaplasia of the esophageal mucosa (2). Those with BE then undergo regular surveillance endoscopy. The hope is this will result in early detection and treatment of EA to improve outcomes.

Volumetric laser endomicroscopy interpretation and feature analysis in dysplastic Barrett's esophagus: Barrett's Esophagus Endomicroscopy

Volumetric laser endomicroscopy (VLE) is used to identify Barretts esophagus (BE) dysplasia. Selection of a dysplastic region of interest (ROI) can be challenging due to feature variability across a large amount of data. The degree of agreement among VLE users in selecting a ROI has not been studied.

Mucosal Ablation in Patients with Barrett’s Esophagus: Fry or Freeze?

The management of Barrett’s esophagus and early esophageal adenocarcinoma has shifted away from esophagectomy and toward endoscopic techniques, including endoscopic resection and ablative therapies. The most commonly used ablative therapies are radiofrequency ablation and cryotherapy. Radiofrequency ablation has risen to the top of the management algorithm due to its favorable safety profile and established track record of efficacy in patients with dysplastic Barrett’s. Cryotherapy offers early promise as an alternatively safe and effective ablative modality. We review radiofrequency ablation and cryotherapy techniques, and updated data regarding their efficacy and safety as well as their roles in the management of Barrett’s esophagus.

Editorial: The Effect of Bias on Estimation of Improved Survival after Diagnosis of Barrett's Esophagus

Abstract: Adjustments for lead and length time bias has been used when examining apparent survival advantages from screening procedures. However, these estimates depend on several assumptions and are modeled from malignancies that are fairly common and large cohorts are available. In smaller retrospective cohorts, adjustments themselves may be based on estimates that may not be biological nor statistically accurate, which can lead to divergent results as has been found in several recent studies of screening in Barrett’s esophagus. Only a prospective randomized controlled trial can really determine the benefit though this may not feasible.