Corinne Maydonovitch

Specialized intestinal metaplasia, dysplasia, and cancer of the esophagus and esophagogastric junction: Prevalence and clinical data

BACKGROUND & AIMS Adenocarcinoma of the esophagus and esophagogastric junction (EGJ) is increasing, the earliest lesion being specialized intestinal metaplasia (SIM). This study determined the prevalence and demographic features of patients with SIM, dysplasia, and cancer in the esophagus and EGJ. METHODS Two antegrade biopsy specimens were taken distal to the squamocolumnar junction (SCJ) and any tongues of pink mucosa proximal to the SCJ. Patients were categorized endoscopically and histologically as having long-segment (LSBE) or short-segment Barretts esophagus (SSBE), EGJ-SIM, or a normal EGJ. RESULTS Of 889 patients studied, 56 were undergoing esophagoduodenoscopy screening or surveillance and were not included in the prevalence calculation. The overall prevalence of SIM was 13.2%, with 1.6% LSBE, 6.0% SSBE, and 5.6% EGJ-SIM. Dysplasia or cancer was noted in 31% of LSBE, 10% of SSBE, and 6.4% of EGJ-SIM patients (P </= 0.043). Two cancers were associated with LSBE, 1 with SSBE, and 1 with EGJ-SIM. Patients with LSBE and SSBE were predominantly white (P </= 0.001), male (P </= 0. 009), and smokers (P </= 0.004), with LSBE patients having a longer history of heartburn (P </= 0.009). In contrast, patients with EGJ-SIM were similar in gender and ethnicity to the reference group, tended to be older (P </= 0.05), drank less alcohol (P </= 0.02), and had a higher prevalence of Helicobacter pylori infection (P </= 0.05). CONCLUSIONS The prevalence of SSBE and EGJ-SIM is similar, but each entity is 3.5 times more prevalent than LSBE. However, the prevalence of dysplasia in LSBE is 2 times greater than in SSBE and 4 times greater than in EGJ-SIM. Demographically, EGJ-SIM patients are different from patients with Barretts esophagus and have a higher prevalence of H. pylori infection. These data help to explain the increasing incidence of adenocarcinoma of the distal esophagus and EGJ.

Randomized Controlled Trial Comparing Aerosolized Swallowed Fluticasone to Esomeprazole for Esophageal Eosinophilia

OBJECTIVES:Patients with clinical symptoms of esophageal dysfunction and dense eosinophilic infiltration of the esophageal mucosa are suspected to have eosinophilic esophagitis (EoE). Topical steroids are often used as first-line therapy for EoE, although some patients respond clinically to proton pump inhibitors (PPIs). The purpose of this study was to compare the histological and clinical response of patients with esophageal eosinophilia treated with aerosolized swallowed fluticasone propionate vs. esomeprazole.METHODS:This prospective single-blinded randomized controlled trial enrolled newly diagnosed patients with suspected EoE, defined as having clinical symptoms related to esophageal dysfunction with at least 15 eosinophils/high power field (hpf). Patients underwent 24-h pH/impedance monitoring to establish gastroesophageal reflux disease (GERD). Patients were stratified by the presence of GERD and randomized to receive fluticasone 440 mcg twice daily or esomeprazole 40 mg once daily for 8 weeks followed by repeat endoscopy with biopsies. The primary outcome was histological response of esophageal eosinophilia, defined as <7 eosinophils/hpf. Secondary outcomes included clinical change in symptoms using the validated Mayo dysphagia questionnaire (MDQ) and interval change in endoscopic findings following treatment.RESULTS:Forty-two patients (90% male, 81% white, mean age 38±10 years) were randomized into fluticasone (n=21) and esomeprazole (n=21) treatment arms. In all, 19% (8/42) of patients had coexisting GERD and were equally stratified into each arm (n=4). Overall, there was no significant difference in resolution of esophageal eosinophilia between fluticasone and esomeprazole (19 vs. 33%, P=0.484). In patients with established GERD, resolution of esophageal eosinophilia was noted in 0% (0/4) of the fluticasone group compared with 100% (4/4) of the esomeprazole group (P=0.029). In GERD-negative patients, there was no significant difference in resolution of esophageal eosinophilia between treatment arms with fluticasone and esomeprazole (24 vs.18%, P=1.00). The MDQ score significantly decreased after treatment with esomeprazole (19±21 vs. 1.4±4.5, P<0.001), but not with fluticasone (17±18 vs. 12±16, P=0.162). Improvement in endoscopic findings and other histological markers were similar between treatment groups.CONCLUSIONS:Fluticasone and esomeprazole provide a similar histological response for esophageal eosinophilia. With regard to clinical response, esomeprazole was superior to fluticasone, particularly in patients with established GERD.

Extracolonic Findings on CT Colonography Increases Yield of Colorectal Cancer Screening

OBJECTIVE The purpose of this study is to evaluate the impact of extracolonic findings when screening is undertaken by CT colonography (CTC). MATERIALS AND METHODS We performed a retrospective cohort study of patients completing a screening CTC from August 2003 to June 2006 at Walter Reed Army Medical Center. Extracolonic findings were categorized using a CTC reporting and data system that classifies findings as highly significant, likely significant, and insignificant. All final diagnoses, surgeries, malignancies, and costs of diagnostic radiology procedures were calculated for each category. RESULTS Of 2,277 patients (mean +/- SD age, 59 +/- 11 years; 60% white; 56% male) undergoing CTC, extracolonic findings were identified in 1,037 (46%) patients, with 787 (34.5%) insignificant and 240 (11.0%) significant findings. Evaluation of significant findings generated 280 radiology procedures and 19 surgeries over a mean follow-up time of 19 +/- 10 months. The total cost of the radiology studies was

CT Colonography May Improve Colorectal Cancer Screening Compliance

113,179; the studies added approximately

A Randomized Comparison of Methylene Blue-Directed Biopsy Versus Conventional Four-Quadrant Biopsy for the Detection of Intestinal Metaplasia and Dysplasia in Patients With Long-Segment Barrett's Esophagus

50 extra per patient. Seven high-risk lesions were identified (six extracolonic malignancies and one large aortic aneurysm) in patients with significant findings. CTC also identified six intracolonic malignancies and three adenomas with high-grade dysplasia. When considering extracolonic findings, CTC increased the odds of identifying high-risk lesions by 78% (nine intracolonic lesions vs 16 intracolonic plus extracolonic lesions; p = 0.0156). Of the 16 intracolonic and extracolonic high-risk lesions, 11 (69%) underwent curative resection, and 5 of 11 (44.4%) were extracolonic. CONCLUSION CTC increased the odds of identifying high-risk lesions by 78%. CTC should be considered as an alternative to optical colonoscopy for colorectal cancer screening or as a onetime procedure to identify significant treatable intracolonic and extracolonic lesions.

Normalization of intestinal metaplasia in the esophagus and esophagogastric junction: incidence and clinical data.

OBJECTIVE While colonoscopy is currently the preferred test for colorectal cancer (CRC) screening, the invasive and time-consuming characteristics of the test are often cited as reasons for noncompliance with screening. CT colonography (CTC) is a less invasive screening method that is comparable to colonoscopy for the detection of advanced neoplasia. The aim of this project was to assess patient preferences between colonoscopy and CTC in an open access system. MATERIALS AND METHODS Two hundred fifty consecutive average-risk patients undergoing CRC screening completed a survey that assessed reasons for choosing CTC in lieu of colonoscopy, compliance with CRC screening if CTC was not offered, and which of the two tests they preferred. RESULTS The most common reasons for undergoing CTC included convenience (33.6%), recommendation by referring provider (13.2%), and perceived safety (10.8%). Had CTC not been an available option, 91 of the 250 patients (36%) would have foregone CRC screening. Among the 57 patients who had experienced both procedures, 95% (n = 54) preferred CTC. CONCLUSION These findings show the importance of providing CTC as an alternative screening option for CRC at our institution, which may increase CRC adherence screening rates.

The effect of terbutaline sulfate, nitroglycerin, and aminophylline on lower esophageal sphincter pressure and radionuclide esophageal emptying in patients with achalasia.

OBJECTIVES:Methylene blue (MB) selectively stains specialized intestinal metaplasia (SIM) and may assist in surveying a columnar-lined esophagus for Barretts esophagus associated dysplasia.METHODS:This is a prospective, randomized crossover study comparing 4-quadrant random biopsies (4QB) versus MB-directed biopsies for the detection of SIM and dysplasia in 48 patients with long segment Barretts esophagus (LSBE). Patients randomly underwent two endoscopies over a 4-wk time period with either 4QB or MB-directed biopsies as their first or second exam. Our aim was to correlate stain intensity with histology.RESULTS:The sensitivity of MB for SIM and dysplasia was 75.2% and 83.1%, respectively. The yield of 4QB for identifying nondysplasia SIM was 57.6% (523/917) and for dysplasia was 12% (111/917). Dark staining was significantly associated with histologic grade (P < 0.007). The final diagnosis was correct in 43 (90%) patients using MB and in 45 (94%) using 4QB. The 4QB technique missed dysplasia in 3 of 21 patients while MB biopsies missed dysplasia in 5 of 21 patients. The discordance between the two techniques was not significant (P = 0.727, McNemars test). The mean number of biopsies taken during 4QB was 18.92 ± 6.36 and with MB was 9.23 ± 2.89 (P < 0.001).CONCLUSION:MB requires significantly fewer biopsies than 4QB to evaluate for SIM and dysplasia. Dark staining correlates more with HGD than LGD in our experience. While MB is not more accurate than 4QB, MB may help to define areas to target for biopsy during surveillance endoscopy in patients with LSBE.

The effect of oral decontamination with clindamycin palmitate on the incidence of bacteremia after esophageal dilation: a prospective trial

BACKGROUND:Attention has focused on whether normalization, regression, and development of dysplasia and cancer in specialized intestinal metaplasia (SIM) differ among long-segment Barretts esophagus (LSBE), short-segment BE (SSBE), and esophagogastric junction SIM (EGJSIM). We prospectively followed a cohort of SIM patients receiving long-term antisecretory medications to determine: (a) histologic normalization (no evidence of SIM on biopsy), (b) change in SIM length, (c) incidence of dysplasia and cancer, and (d) factors associated with normalization.METHODS:One hundred forty-eight patients with SIM were identified in our original cohort. Of these, 60.5% (23/38) LSBE, 69.8% (44/63) SSBE, and 72.3% (34/47) EGJSIM patients underwent repeat surveillance over a mean 44.4 ± 9.7 months. Demographic, clinical, and endoscopic data were obtained.RESULTS:(a) With long-term, antisecretory therapy, normalization occurred in 0/23 LSBE, 30% (13/44) of SSBE, and 68% (23/34) of EGJSIM (P < 0.001). (b) Normalization was more likely with EGJSIM (odds ratio [OR] 6.7, CI 2.3–19.3, P = 0.005), female gender (OR 7.3, CI 2.3–23.1, P = 0.001), or absence of hiatal hernia (OR 2.9, CI 1.02–8.06, P = 0.002). (c) A significant decrease in mean SIM length was noted for the entire population (2.5 ± 0.3 to 2.13 ± 0.3 cm, P = 0.004). (d) Follow-up incidence of dysplasia and cancer was 26.1% (3 indefinite, 2 low-grade dysplasia [LGD], 1 cancer) for LSBE, 6.8% (2 indefinite, 1 LGD) for SSBE, and none for EGJSIM (P < 0.004).CONCLUSIONS:(a) Normalization of SIM occurs most frequently in EGJSIM>SSBE>LSBE. (b) Factors associated with normalization favor less severe GER and shorter segments of SIM. (c) Surveillance of LSBE results in the greatest yield for identifying dysplasia and cancer.

The effect of simethicone on colonic visibility after night-prior colonic lavage: a double-blind randomized study

We studied the effects of three smooth muscle relaxants on lower esophageal sphincter (LES) pressure and radionuclide esophageal emptying in 15 untreated patients with achalasia. LES pressures were determined before and after the administration of normal saline subcutaneously, terbutaline sulfate subcutaneously, nitroglycerin sublingually, and aminophylline intravenously. All smooth muscle relaxants significantly decreased LES pressures when compared with normal saline controls and pretreatment baseline pressures (p less than 0.01). However, in normal saline controls, LES pressure actually increased over time (p less than 0.01). Control radionuclide esophageal emptying studies were performed in all patients. Subsequent esophageal emptying studies were carried out only in patients responding to smooth muscle relaxants by decreasing LES pressures by greater than or equal to 25% (terbutaline sulfate, n = 8; nitroglycerin, n = 7; and aminophylline, n = 4). Significant improvement in esophageal emptying was observed after nitroglycerin and terbutaline sulfate (p less than 0.05) but not after aminophylline. We conclude that in patients with achalasia (a) terbutaline sulfate, nitroglycerin, and aminophylline can significantly decrease LES pressure; (b) resting LES pressures vary over time; and (c) terbutaline sulfate and nitroglycerin significantly improve esophageal emptying in some subjects.

Early Comparison of Inflammatory vs. Fibrostenotic Phenotype in Eosinophilic Esophagitis in a Multicenter Longitudinal Study

BACKGROUND Antibiotic prophylaxis to prevent bacterial endocarditis is recommended in high-risk patients undergoing esophageal dilation, a high-risk procedure. Some studies suggest that the oropharynx is the source of bacteremia. A topical antibiotic mouthwash, which reduces bacterial colonization of the oral flora, might decrease bacteremia rates and would be an attractive alternative to systemic administration of antibiotics. METHODS Adults undergoing outpatient bougienage for a benign or malignant esophageal stricture were randomized in a clinician-blinded fashion to either pre-procedure clindamycin mouthwash or no treatment. Subjects were stratified by type of dilator used. Blood cultures were obtained immediately after the first esophageal dilation and 5 minutes after the last dilation. RESULTS Fifty-nine patients were enrolled: 30 in the treatment arm and 29 in the no-treatment arm. There were 7 positive blood cultures: 5 in the treatment arm and 2 in the no-treatment arm. The identified organisms were Streptococcus viridans (2), Staphylococcus mucilaginous (2), Lactobacillus (2), and Actinomyces odontolyticus (1). Patients with bacteremia reported greater subjective difficulty with dysphagia (p = 0.01) irrespective of stricture diameter, procurement of biopsies, or dilator type. CONCLUSIONS The percentage of cases with bacteremia for all dilations performed in this manner was 12% (95% CI [5.3, 23.6]), much lower than previously cited. All organisms in this study were oral commensals. There appears to be no effect of a clindamycin mouthwash on reducing bacteremia after esophageal dilation.