John C. Lipham

High intraepithelial eosinophil counts in esophageal squamous epithelium are not specific for eosinophilic esophagitis in adults.

OBJECTIVESThe histologic criterion of >20 eosinophils per high power field (hpf) is presently believed to establish the diagnosis of idiopathic eosinophilic esophagitis (IEE). This is based on data that the number of intraepithelial eosinophils in gastroesophageal reflux disease (GERD) is less than 20/hpf. This study tests this belief.METHODSPathology records were searched for patients who had an eosinophil count >20/hpf in an esophageal biopsy. This patient population was biased toward adults with GERD who had routine multilevel biopsies of the esophagus. The clinical, radiological, and manometric data and biopsies were studied.RESULTSForty patients out of a total of 3,648 reports examined had an eosinophil count >20/hpf in squamous epithelium of an esophageal biopsy. Analysis of these 40 cases indicated that 6 (15%) patients had IEE, 2 (5%) had coincident IEE and GERD, 28 (70%) had GERD, and 2 (5%) each had achalasia and diverticulum. There was no significant difference among these groups in terms of maximum eosinophil number, biopsy levels with >20 esoinophils/hpf, presence of eosinophilic microabscesses, involvement of surface layers by eosinophils, and severity of basal cell hyperplasia and dilated intercellular spaces.CONCLUSIONAll histologic features presently ascribed to IEE can occur in other esophageal diseases, notably GERD. As such, the finding of intraepithelial eosinophilia in any number is not specific for IEE. When a patient with GERD has an esophageal biopsy with an eosinophil count >20/hpf, it does not mean that the patient has IEE.

Esophageal sphincter device for gastroesophageal reflux disease.

BACKGROUND Patients with gastroesophageal reflux disease who have a partial response to proton-pump inhibitors often seek alternative therapy. We evaluated the safety and effectiveness of a new magnetic device to augment the lower esophageal sphincter. METHODS We prospectively assessed 100 patients with gastroesophageal reflux disease before and after sphincter augmentation. The study did not include a concurrent control group. The primary outcome measure was normalization of esophageal acid exposure or a 50% or greater reduction in exposure at 1 year. Secondary outcomes were 50% or greater improvement in quality of life related to gastroesophageal reflux disease and a 50% or greater reduction in the use of proton-pump inhibitors at 1 year. For each outcome, the prespecified definition of successful treatment was achievement of the outcome in at least 60% of the patients. The 3-year results of a 5-year study are reported. RESULTS The primary outcome was achieved in 64% of patients (95% confidence interval [CI], 54 to 73). For the secondary outcomes, a reduction of 50% or more in the use of proton-pump inhibitors occurred in 93% of patients, and there was improvement of 50% or more in quality-of-life scores in 92%, as compared with scores for patients assessed at baseline while they were not taking proton-pump inhibitors. The most frequent adverse event was dysphagia (in 68% of patients postoperatively, in 11% at 1 year, and in 4% at 3 years). Serious adverse events occurred in six patients, and in six patients the device was removed. CONCLUSIONS In this single-group evaluation of 100 patients before and after sphincter augmentation with a magnetic device, exposure to esophageal acid decreased, reflux symptoms improved, and use of proton-pump inhibitors decreased. Follow-up studies are needed to assess long-term safety. (Funded by Torax Medical; ClinicalTrials.gov number, NCT00776997.).

Vagal-sparing esophagectomy: The ideal operation for intramucosal adenocarcinoma and Barrett with high-grade dysplasia

Objective:Our aim was to compare outcome of vagal-sparing esophagectomy with transhiatal and en bloc esophagectomy in patients with intramucosal adenocarcinoma or high-grade dysplasia. Summary Background Data:Intramucosal adenocarcinoma and high grade dysplasia have a low likelihood of lymphatic or systemic metastases and esophagectomy is curative in most patients. However, traditional esophagectomy is associated with significant morbidity and altered gastrointestinal function. A vagal-sparing esophagectomy offers the advantages of complete disease removal with the potential for reduced morbidity and a better functional outcome. Method:Retrospective review of outcome in patients with intramucosal adenocarcinoma or high grade dysplasia that had a vagal-sparing (n = 49), transhiatal (n = 39) or en bloc (n = 21) esophagectomy. Results:The length of hospital stay and the incidence of major complications was significantly reduced with a vagal-sparing esophagectomy compared with a transhiatal or en bloc resection. Further, postvagotomy dumping and diarrhea symptoms were significantly less common, and weight was better maintained postoperatively with a vagal-sparing esophagectomy. Recurrent cancer has developed in only 1 patient. Conclusion:Survival with intramucosal adenocarcinoma or Barretts with high-grade dysplasia is independent of the type of resection. A vagal-sparing esophagectomy is associated with significantly less perioperative morbidity and a shorter hospital stay than a transhiatal or en bloc esophagectomy. Further, late morbidity including weight loss, dumping, and diarrhea are significantly less likely after a vagal-sparing approach. Consequently a vagal-sparing esophagectomy is the preferred procedure for patients with intramucosal adenocarcinoma or high grade dysplasia.

Obesity and gastroesophageal reflux: quantifying the association between body mass index, esophageal acid exposure, and lower esophageal sphincter status in a large series of patients with reflux symptoms.

IntroductionObesity and gastroesophageal reflux disease (GERD) are increasingly important health problems. Previous studies of the relationship between obesity and GERD focus on indirect manifestations of GERD. Little is known about the association between obesity and objectively measured esophageal acid exposure. The aim of this study is to quantify the relationship between body mass index (BMI) and 24-h esophageal pH measurements and the status of the lower esophageal sphincter (LES) in patients with reflux symptoms.MethodsData of 1,659 patients (50% male, mean age 51 ± 14) referred for assessment of GERD symptoms between 1998 and 2008 were analyzed. These subjects underwent 24-h pH monitoring off medication and esophageal manometry. The relationship of BMI to 24-h esophageal pH measurements and LES status was studied using linear regression and multiple regression analysis. The difference of each acid exposure component was also assessed among four BMI subgroups (underweight, normal weight, overweight, and obese) using analysis of variance and covariance.ResultsIncreasing BMI was positively correlated with increasing esophageal acid exposure (adjusted R2 = 0.13 for the composite pH score). The prevalence of a defective LES was higher in patients with higher BMI (p < 0.0001). Compared to patients with normal weight, obese patients are more than twice as likely to have a mechanically defective LES [OR = 2.12(1.63–2.75)].ConclusionAn increase in body mass index is associated with an increase in esophageal acid exposure, whether BMI was examined as a continuous or as a categorical variable; 13% of the variation in esophageal acid exposure may be attributable to variation in BMI.

A New Technique for Measurement of Pharyngeal pH: Normal Values and Discriminating pH Threshold

IntroductionIdentifying gastroesophageal reflux disease as the cause of respiratory and laryngeal complaints is difficult and depends largely on the measurements of increased acid exposure in the upper esophagus or ideally the pharynx. The current method of measuring pharyngeal pH environment is inaccurate and problematic due to artifacts. A newly designed pharyngeal pH probe to avoid these artifacts has been introduced. The aim of this study was to use this probe to measure the pharyngeal pH environment in normal subjects and establish pH thresholds to identify abnormality.MethodsAsymptomatic volunteers were studied to define the normal pharyngeal pH environment. All subjects underwent esophagram, esophageal manometry, upper and lower esophageal pH monitoring with a dual-channel pH catheter and pharyngeal pH monitoring with the new probe. Analyses were performed at 0.5 pH intervals between pH 4 and 6.5 to identify the best discriminating pH threshold and calculate a composite pH score to identify an abnormal pH environment.ResultsThe study population consisted of 55 normal subjects. The pattern of pharyngeal pH environment was significantly different in the upright and supine periods and required different thresholds. The calculated discriminatory pH threshold was 5.5 for upright and 5.0 for supine periods. The 95th percentile values for the composite score were 9.4 for upright and 6.8 for supine.ConclusionA new pharyngeal pH probe which detects aerosolized and liquid acid overcomes the artifacts that occur in measuring pharyngeal pH with existing catheters. Discriminating pH thresholds were selected and normal values defined to identify patients with an abnormal pharyngeal pH environment.

Endoscopic resection and ablation versus esophagectomy for high-grade dysplasia and intramucosal adenocarcinoma

BACKGROUND Esophagectomy has been the traditional therapy for high-grade dysplasia and intramucosal adenocarcinoma. New endoscopic approaches allow treatment of these lesions with esophageal preservation. The aim of this study was to compare the outcome of endoscopic therapy with esophagectomy for high-grade dysplasia and intramucosal cancer. METHODS A retrospective review was performed of all patients treated for high-grade dysplasia or intramucosal adenocarcinoma from 2001 to April 2010. RESULTS Endoscopic therapy was performed in 40 patients (high-grade dysplasia = 22, intramucosal cancer = 18) and esophagectomy in 61 patients (high-grade dysplasia = 13, intramucosal cancer = 48). Endotherapy consisted of 102 endoscopic resections and 79 mucosal ablations (median 3 interventions per patient). In the endotherapy group, intramucosal cancer was completely resected in all patients. At last assessment, 10 patients have been converted to intestinal metaplasia without dysplasia and 21 to no residual intestinal metaplasia. Five patients have follow-up biopsy procedures pending after recent ablation, and esophagectomy was performed in 3 patients for failed endotherapy. A laparoscopic Nissen fundoplication has been performed in 8 patients after eradication of intestinal metaplasia. Esophagectomy resected the mucosal disease with negative margins in all patients. Compared with esophagectomy, endotherapy was associated with significantly lower morbidity (39% vs 0; P < .0001) and similar survival (94% at 3 years in both groups; median follow-up 34 months after esophagectomy vs 17 months after endotherapy; P = .0026). CONCLUSIONS Endoscopic therapy for high-grade dysplasia or intramucosal cancer has lower morbidity than an esophagectomy and similar survival during short-term follow-up, but required multiple procedures in most patients. Both therapies are appropriate options, but preservation of the esophagus allows the option of a fundoplication for reflux control, perhaps further improving long-term quality of life.

Laparoscopic sphincter augmentation device eliminates reflux symptoms and normalizes esophageal acid exposure: one- and 2-year results of a feasibility trial.

Objectives:One- and 2-year evaluation of a feasibility trial (clinicaltrials.gov registration numbers NCT01057992, NCT01058070, and 01058564) to assess the safety and efficacy of a laparoscopically implanted sphincter augmentation device for the treatment of gastroesophageal reflux disease (GERD). Methods:A sphincter augmentation device (LINX Reflux Management System; Torax Medical, Shoreview, MN), designed to prevent reflux due to abnormal opening of the lower esophageal sphincter (LES), was laparoscopically implanted at the gastroesophageal junction in 44 patients. At baseline, all patients had abnormal esophageal acid exposure on 24-hour pH monitoring and improved, but persistent, typical GERD symptoms while on acid suppression therapy with proton pump inhibitors (PPIs). The device comprises a miniature string of interlinked titanium beads, with magnetic cores, placed around the gastroesophageal junction. The magnetic bond between adjacent beads augments sphincter competence. The beads temporarily separate to accommodate a swallowed bolus, allow belching or vomiting, and reapproximate to augment the LES in the closed position. Patients were evaluated after surgery by GERD Health-Related Quality of Life symptom score, PPI usage, endoscopy, esophageal manometry, and 24-hour esophageal pH monitoring. Results:The total mean GERD Health-Related Quality of Life symptom scores improved from a mean baseline value of 25.7 to 3.8 and 2.4 at 1- and 2-year follow-up, representing an 85% and 90% reduction, respectively (P < 0.0001). Complete cessation of PPI use was reported by 90% of patients at 1 year and by 86% of patients at 2 years. Early dysphagia occurred in 43% of the patients and self-resolved by 90 days. One device was laparoscopically explanted for persistent dysphagia without disruption of the anatomy or function of the cardia. There were no device migrations, erosions, or induced mucosal injuries. At 1 and 2 years, 77% and 90% of patients had a normal esophageal acid exposure. The mean percentage time pH was less than 4 decreased from a baseline of 11.9% to 3.1% (P < 0.0001) at 1 year and to 2.4% (P < 0.0001) at 2 years. Patient satisfaction was 87% at 1 year and 86% at 2 years. Conclusions:The new laparoscopically implanted sphincter augmentation device eliminates GERD symptoms without creating undue side effects and is effective at 1 and 2 years of follow-up.

Recurrence after Esophagectomy for Adenocarcinoma: Defining Optimal Follow-Up Intervals and Testing

BACKGROUND To determine the optimal follow-up strategy after esophagectomy for adenocarcinoma of the esophagus or gastroesophageal junction by evaluating the timing of recurrence and the method that first detected the recurrence. STUDY DESIGN Between 1991 and 2007, 590 patients had an esophagectomy for adenocarcinoma. Recurrence occurred in 233 (40%) and, of those, 174 had complete follow-up at our center with a protocol that consisted of an office visit with CT scans and laboratory studies every 3 months for 3 years, every 6 months for 2 years, and then annually. A subset of patients had PET annually. RESULTS Recurrence in the 174 patients with complete follow-up was systemic in 104 (60%), locoregional/nodal in 51 (30%), and both in 19 (10%). Recurrence was first suspected by symptoms and/or physical examination in 29 patients (17%), by CT scan in 105 (60%), PET in 32 (18%), and by elevated CEA in 8 (5%). Recurrence was detected at a median of 11 months (range 3 to 72 months) and occurred later after esophagectomy alone compared with patients who received neoadjuvant therapy (12 versus 8 months; p = 0.01), but the pattern of recurrence was similar. More than 90% of recurrences were detected within 2 years after neoadjuvant therapy, compared with 3 years after esophagectomy alone. Median survival after recurrence was 7 months and was significantly longer in patients treated for the recurrence (9 versus 3 months; p = 0.001). CONCLUSIONS Frequent early follow-up is appropriate after esophagectomy for adenocarcinoma because >90% of recurrences will occur by 3 years after esophagectomy alone and by 2 years following neoadjuvant therapy. Beyond these time periods, 2% to 3% of recurrences were detected each year, suggesting that annual follow-up is adequate. Survival after recurrence was improved with therapy, confirming the use of careful follow-up in these patients.

Predictive factors of coexisting cancer in Barrett’s high-grade dysplasia

BackgroundIdentification of high-grade dysplasia (HGD) in Barrett’s esophagus has been considered an indication for esophagectomy because of the high risk for coexisting cancer. However, rigorous endoscopic surveillance programs recently have been recommended, reserving esophagectomy for patients whose cancer is identified on biopsy. This approach risks continued surveillance for patients who already have cancer unless reliable markers for the presence of occult cancer are identified. This study aimed to determine the endoscopic, histologic, and demographic features associated with the presence of occult cancer in patients with HGD.MethodsEndoscopic, histologic, and demographic findings for 31 patients who underwent esophagectomy for HGD were reviewed. The presence of an ulcer, nodule, stricture, or raised area on preoperative endoscopy was noted. The results of endoscopic biopsies taken before resection every 1 to 2 cm along the Barrett’s segment were reviewed. The HGD was categorized as unilevel if the dysplasia was limited to one level of biopsy and as multilevel if more than one level was involved. Patients were divided into two groups according to the presence or absence of cancer in the resected specimens, and these variables were compared.ResultsThe prevalence of coexisting cancer in patients with HGD was 45% (14/31). Of the 31 patients in this study, 9 had a visible lesion. Cancer was found in the resected specimens from 7 (78%) of 9 patients with a visible lesion and 7 (32%) of 22 patients without a visible lesion (p = 0.019). Of 22 patients without a visible lesion, 10 had multilevel and 12 had unilevel HGD. The findings showed that 6 (60%) of 10 patients with multilevel HGD and 1 (8.3%) of 12 patients with unilevel HGD had cancer in the resected esophagus (p = 0.009).ConclusionFor patients with HGD, a lesion visible on endoscopy and/or HGD at multiple biopsy levels is associated with an increased risk for coexisting cancer. These patients should be considered for early esophagectomy.

Intraoperative Assessment of Perfusion of the Gastric Graft and Correlation With Anastomotic Leaks After Esophagectomy.

Anastomotic complications are a major source of morbidity after esophagectomy with gastric pull-up and are often related to poor graft perfusion. The aim of this study was to evaluate the use of laser-assisted fluorescent-dye angiography to assess perfusion in gastric grafts and determine the relationship between perfusion and anastomotic leaks.