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The detection of gastroesophageal reflux (GERD) via pH testing is the key component of the evaluation of patients considered for antireflux surgery. Two common pH testing systems exist, a multichannel, intraluminal impedance-pH monitoring (MII-pH) catheter, and wireless (Bravo®) capsule; however, discrepancies between the two systems exist. In patients with atypical symptoms, MII-pH catheter is often used preferentially. We aimed to elucidate the magnitude of this discrepancy and to assess the diagnostic value of MII-pH and the Bravo wireless capsule in a population of patients with mixed respiratory and typical symptoms. The study population consisted of 66 patients tested with MII-pH and Bravo pH testing within 90 days between July 2009 and 2013. All patients presented with laryngo-pharyngo-respiratory (LPR) symptoms. Patient demographics, symptomatology, manometric and endoscopic findings, and pH monitoring parameters were analyzed. Patients were divided into four comparison groups: both pH tests positive, MII-pH negative/Bravo positive, MII-pH positive/Bravo negative, and both pH tests negative. Nearly half of the patients (44 %) had discordant pH test results. Of these, 90 % (26/29) had a negative MII-pH but positive Bravo study. In this group, the difference in the DeMeester score was large, a median of 29.3. These patients had a higher BMI (28.5 vs. 26.1, p = 0.0357), were more likely to complain of heartburn (50 vs. 23 %, p = 0.0110), to have a hiatal hernia, (85 vs. 53 %, p = 0.0075) and a structurally defective lower esophageal sphincter (LES, 85 vs. 58 %, p = 0.0208). In patients with LPR symptoms, we found a high prevalence of discordant esophageal pH results, most commonly a negative MII-pH catheter and positive Bravo. As these patients exhibited characteristics consistent with GERD (heartburn, defective LES, hiatal hernia), the Bravo results are likely true. A 24-h MII-pH catheter study may be inadequate to diagnose GERD in this patient population.

Background Five-year survival after the surgical treatment of esophageal cancer has traditionally been reported to be as low as 15%. More recently, the improvement of clinical staging involving PET/CT and the introduction of neoadjuvant chemo-radiation have each altered the survival outcomes of patients with this lethal disease. The impact of these factors on survival trends has not been well described in literature. The aim of this study was to analyze the survival trends after esophagectomy for esophageal adenocarcinoma at a high-volume center. Methods The study population consisted of 471 consecutive patients undergoing esophagectomy for esophageal adenocarcinoma at a university-based medical center between January 1, 2000 and July 31, 2017. Clinical variables were collected for three groups based on the date of esophagectomy and were compared (Group 1: 2000–2004, Group 2: 2005–2011, Group 3: 2012–2017). Survival was compared via the Kaplan-Meier (KM) method. Results The 471 patients had a median age of 64.0 years (range 27.0–86.2) and 395/471 (84%) were male. Dysphagia (282/471, 60%), heartburn (63/471, 13%) and chest pain (29/471, 6%) were the most common presenting symptoms. The majority of the patients underwent transhiatal esophagectomy (n = 279, 59.1%) and en-bloc esophagectomy (n = 85, 18.0%). Staging with PET/CT was utilized in 316/471 patients (67%) with 6% of Group 1, 76% of Group 2 and 100% of Group 3, P Conclusion This analysis reveals an improvement in 5-year survival after esophagectomy from 30% to 47% over the past two decades. Similarly, 10-year survival has improved from 23% to 37%. The evolution of better clinical staging and advancements in neoadjuvant therapy likely played a vital role in these trends. In contrast to the earliest cohort, PET/CT is now routinely utilized in the staging of esophageal cancer. Further, other than those with early stage disease, all patients are currently evaluated for neoadjuvant chemo-radiation. Notably, the 5-year survival rate for the most recent cohort (2012–2017) approaches 50% and would likely be higher if patients with esophageal adenocarcinoma treated endoscopically were included. Improvements in staging and treatment paradigms for esophageal adenocarcinoma have resulted in significant progress towards cure. Disclosure All authors have declared no conflicts of interest.

Background Current diagnostic techniques establishing gastroesophageal reflux disease as the underlying cause in patients with respiratory symptoms are poor. Our aim was to provide additional support to our prior studies suggesting that the association between reflux events and oxygen desaturations may be a useful discriminatory test in patients presenting with primary respiratory symptoms suspected of having gastroesophageal reflux as the etiology. Methods Thirty-seven patients with respiratory symptoms, 26 with typical symptoms, and 40 control subjects underwent simultaneous 24-h impedance–pH and pulse oximetry monitoring. Eight patients returned for post-fundoplication studies. Results The median number (interquartile range) of distal reflux events associated with oxygen desaturation was greater in patients with respiratory symptoms (17 (9–23)) than those with typical symptoms (7 (4–11, p

A 75-year-old male with a long history of gastroesophageal reflux symptoms developed adenocarcinoma proximally within a long segment of Barrett's esophagus. He was taken for esophagectomy and gastric pull-up, but intraoperatively, he was found to have a marginal blood supply in the gastric tube. A temporary left-sided esophagostomy was created with the gastric tube sutured to the left sternocleidomastoid muscle in the neck. Pathology showed an intramucosal adenocarcinoma, limited to the muscularis mucosa with surrounding high-grade dysplasia and intestinal metaplasia. The proximal esophageal margin showed no tumor cells, but there was low-grade dysplasia within Barrett's esophagus. He was reconstructed after several months, and 2 years after reconstruction, the patient noticed a nodule at the former esophagostomy site. Biopsy revealed an implant metastasis of esophageal adenocarcinoma. Here, we review the literature and discuss the possible etiology.

Patients with gastroesophageal reflux disease and Barrett's esophagus can be a management challenge for the treating physician or surgeon. The goals of therapy include relief of reflux symptoms, induction of histologic regression, and prevention of progression of intestinal metaplasia to dysplasia or invasive carcinoma. Antireflux surgery is effective at achieving these end points, although ongoing follow-up and endoscopic surveillance are essential. In cases of dysplasia or early esophageal neoplasia associated with Barrett's esophagus, endoscopic resection and ablation have supplanted esophagectomy as the standard of care in most cases. Esophageal resection continues to have a role, however, in a minority of appropriately selected candidates.

Purpose Screening for esophageal adenocarcinoma (EAC) has not become policy in part over concerns in identifying the high-risk group. It is often claimed that a significant proportion of patients developing EAC do not report preexisting reflux symptoms or prior treatment for gastroesophageal reflux disease (GERD). As such, our aim was to assess the prevalence of GERD symptoms, proton pump inhibitor (PPI) use and Barrett's esophagus (BE) and their impact on survival in patients undergoing esophagectomy for EAC. Methods The study population consisted of 345 consecutive patients who underwent esophagectomy for EAC between 2000 and 2011 at a university-based medical center. Patients with a diagnosis of esophageal squamous cell carcinoma and those who underwent esophagectomy for benign disease were excluded. The prevalence of preoperative GERD symptoms, defined as presence of heartburn, regurgitation or epigastric pain, PPI use (>6 months) and BE, defined by the phrases “Barrett's esophagus,” “intestinal epithelium,” “specialized epithelium,” or “goblet cell metaplasia” in the patients' preoperative clinical notes were retrospectively collected. Overall long-term and stage-specific survival was compared in patients with and without the presence of preoperative GERD symptoms, PPI use, or BE. Results The majority of patients (64%; 221/345) had preoperative GERD symptoms and a history of PPI use (52%; 179/345). A preoperative diagnosis of BE was present in 34% (118/345) of patients. Kaplan–Meier survival analysis revealed a marked survival advantage in patients undergoing esophagectomy who had preoperative GERD symptoms, PPI use or BE diagnosis (P ≤ .001). The survival advantage remained when stratified for American Joint Committee on Cancer stage in patients with preoperative PPI use (P = .015) but was less pronounced in patients with GERD symptoms or BE (P = .136 and P = .225, respectively). Conclusion These data show that the oft-quoted statistic that the majority of patients with EAC do not report preexisting GERD or PPI use is false. Furthermore, a diagnosis of BE is present in a surprisingly high proportion of patients (34%). There is a distinct survival advantage in patients with preoperative GERD symptoms, PPI use, and BE diagnosis, which may not be simply owing to earlier stage at diagnosis. Screening may affect survival outcomes in more patients with EAC than previously anticipated.

Goblet cells in Barrett’s esophagus (BE) vary in their density within the Barrett’s segment. Exposure of Barrett’s epithelium to bile acids is a major stimulant for goblet cell formation. The dissociation of bile acids into forms that penetrate Barrett’s epithelium is known to be pH dependent. We hypothesized that variations in the esophageal luminal pH environment explains the variability in goblet cell density. The aim of this study was to correlate esophageal luminal pH with goblet cell density in patients with BE. A customized six-sensor pH catheter was positioned with the most distal sensor in the stomach and the remaining sensors located 1 cm below and 1, 3, 5, and 8 cm above the upper border of the lower esophageal sphincter in five normal subjects and six patients with long-segment BE. The luminal pH was measured by each sensor for 24-h and expressed as median pH. Patients with BE had four quadrant biopsies at levels corresponding to the location of the pH sensors. Goblet cell density was graded from 0 to 3 based on the number per high-power field. In normal subjects, the median pH values recorded in the sensors within the lower esophageal sphincter (LES) and esophageal body were all above 5. In patients with BE, the median pH recorded by the sensor within the LES was 2.8 and increased progressively to 4.7 in the sensor at 8 cm above the LES. Goblet cell density was significantly lower in the distal Barrett’s segment exposed to a median pH of 2.2 and increased in the proximal Barrett’s segment exposed to a median pH of 4.4 (p = 0.003). Patients with BE have a goblet cell gradient that correlates directly with an esophageal luminal pH gradient. This suggests that goblet cell differentiation is pH dependent and likely due to the effect of pH on bile acid dissociation.

Background & Aims The Bravo pH capsule is a catheter-free intraesophageal pH monitoring system that avoids the discomfort of an indwelling catheter. The objectives of this study were as follows: (1) to obtain normal values for the first and second 24-hour recording periods using a Bravo capsule placed transnasally 5 cm above the upper border of the lower esophageal sphincter determined by manometry and to assess concordance between the 2 periods, (2) to determine the optimal discriminating threshold for identifying patients with gastroesophageal reflux disease (GERD), and (3) to validate this threshold and to identify the recording period with the greatest accuracy. Methods Normal values for a manometrically positioned, transnasally inserted Bravo capsule were determined in 50 asymptomatic subjects. A test population of 50 subjects (25 asymptomatic, 25 with GERD) then was monitored to determine the best discriminating thresholds. The thresholds for the first, second, and combined (48-hour) recording periods then were validated in a separate group of 115 patients. Results In asymptomatic subjects, the values measured using a manometrically positioned Bravo pH capsule were similar between the first and second 24-hour periods of recording. The highest level of accuracy with Bravo was observed when an abnormal composite pH score was obtained in the first or second 24-hour period of monitoring. Conclusions Normal values for esophageal acid exposure were defined for a manometrically positioned, transnasally inserted, Bravo pH capsule. An abnormal composite pH score, obtained in either the first or second 24-hour recording period, was the most accurate method of identifying patients with GERD.

Ambulatory esophageal pH monitoring is the method used most widely to quantify gastroesophageal reflux. The degree of gastroesophageal reflux may potentially be underestimated if the resting gastric pH is high. Normal subjects and symptomatic patients undergoing 24-h pH monitoring were studied to determine whether a relationship exists between resting gastric pH and the degree of esophageal acid exposure. Normal volunteers (n = 54) and symptomatic patients without prior gastric surgery and off medication (n = 1,582) were studied. Gastric pH was measured by advancing the pH catheter into the stomach before positioning the electrode in the esophagus. The normal range of gastric pH was defined from the normal subjects, and the patients then were classified as having either normal gastric pH or hypochlorhydria. Esophageal acid exposure was compared between the two groups. The normal range for gastric pH was 0.3–2.9. The median age of the 1,582 patients was 51 years, and their median gastric pH was 1.7. Abnormal esophageal acid exposure was found in 797 patients (50.3%). Hypochlorhydria (resting gastric pH >2.9) was detected in 176 patients (11%). There was an inverse relationship between gastric pH and esophageal acid exposure (r = −0.13). For the patients with positive 24-h pH test results, the major effect of gastric pH was that the hypochlorhydric patients tended to have more reflux in the supine position than those with normal gastric pH. There is an inverse, dose-dependent relationship between gastric pH and esophageal acid exposure. Negative 24-h esophageal pH test results for a patient with hypochlorhydria may prompt a search for nonacid reflux as the explanation for the patient’s symptoms.

In the 1940s, Dragstedt reported a 20% to 25% frequency of delayed gastric emptying after truncal vagotomy alone for peptic ulcer disease. A similarly high frequency of delayed gastric emptying was reported by Bergin in 1959 in a series of 32 patients. Based on this experience, it seemed reasonable, as many authorities have, to expect prolonged gastric emptying after esophagectomy and reconstruction by gastric pullup — an operation in which bilateral truncal vagotomy is inevitable — unless a pyloroplasty or pyloromyotomy is performed.

Introduction: Accurate and complete identification of patients with symptoms secondary to gastroesophageal reflux disease has been a clinical challenge. This has led to the classification, perhaps erroneously, of some patients as "functional heartburn". 48-hour wireless pH monitoring has been shown to increase the diagnostic yield of reflux detection. We hypothesize that 96-hour monitoring would further increase reflux detection rate. Methods: The study population consisted of 31 patients who underwent 96-hour wireless pHmonitoring between February 2012 and October 2013.Patients with incomplete studies due to capsule dislodgement or failed signal transmission, achalasia, previous antireflux or gastric bypass surgery were excluded. Patient demographics, presenting symptoms, manometric and pHmonitoring parameters were collected and compared. Patients were divided into pH negative, single day positive or multiple day positive groups for comparison. All studies were done off PPI medications for at least 7 days. A positive study was defined by DeMeester score >14.72 on any day. Results: Eighteen (58%) of the 31 patients were negative on all 4 days, 7 (23%) were positive on a single day and 6 (19%) were positive on multiple days. Thirteen percent of the patients (4/31) were only positive on day 3 or day 4 and would have been considered normal on a 48 hour study. Lower esophageal sphincter (LES) parameters correlated with the number of pH positive days including LES overall length ( σ=-0.43, p=0.02), IBP (σ=0.41, p=0.02) and IRP (σ=-0.54, p=0.003). Mean axial separation between the LES and CD, 0.16cm in pH negative, 0.66cm in patients with one day positive and 0.26 in patients with multiple days positive (p=0.1506). Conclusions: 96 hour wireless pH monitoring identified pathologic esophageal acid exposure in 13% of patients who would have been considered normal on 48 hour study. These patients are more likely to have less profound alteration in characteristics of the gastroesopahgeal barrier including LES length and axial crural diaphragm separation. Prolonged 96-hour pH monitoring may be necessary before classifying patients as GERD negative or functional heartburn.

INTRODUCTION: As pre-operative chemoradiation followed by esophagectomy has become standard therapy in patients with resectable esophageal adenocarcinoma (EAC), traditional pathological staging has become a less useful prognostic tool. The 7th edition of the American Joint Commission on Cancer (AJCC7) staging system for EAC is derived from data on patients undergoing esophagectomy without neoadjuvant therapy and classifies lymph node status by the number of involved lymph nodes. Lymph node harvest (LNH) and lymph node positivity ratio (LNPR) have been suggested to be prognostic indicators but have not found widespread support. In an effort to develop a valid staging model in the era of neoadjuvant therapy, we compared the predictive value of LNH and LNPR to AJCC7 staging in a large cohort of patients undergoing resection for EAC. METHODS: The study population consisted of 316 patients who underwent R0 esophagectomy for EAC from 1/00 to 12/11 (86% male; mean age 64.0±10.3 years). Survival functions were estimated using the KaplanMeier method. Classification thresholds for both LNPR and LNH were derived by recursive partitioning using conditional inference trees comparing survival functions. Based on these analyses, LNPR was stratified and Cox proportional hazards regression models were used to compare predictive value of lymph node categorization strata. RESULTS: Median lymph node harvest was 12 (IQR 7-20). 51% of patients were N0, 29% N1, 13% N2. Median overall survival was 63.4 months (95%CI 40.6 92.3) and 5-year overall survival was 50.7% (95%CI 45.0 57.2). Eighty-three patients (26%) received neoadjuvant chemotherapy, radiation therapy or both. In patients who received neoadjuvant therapy and had no lymph node metastasis identified (40/83; 48%), recursive partitioning analysis yielded a LNH threshold of 15 for discrimination of survival functions. LNH ≥ 15 was associated with a significant survival advantage (3-year survival 95 vs. 38%; p = 0.000022). Similarly, recursive partitioning analysis yielded LNPR categories of less than 20%, 20-40%, or greater than 40% as significantly discriminant of survival functions. In patients who received neoadjuvant therapy, LNPR was more predictive of survival than number of positive lymph nodes as categorized by AJCC7 (p=0.00018 vs. 0.033). In the 256 patients who received no neoadjuvant therapy, LNH was not a significant predictor of survival after node negative resection, although LNPR was a stronger predictor of survival than the current nodal staging system (p-value 0.000015 vs. 0.05). CONCLUSION: For patients receiving neoadjuvant therapy, both LNH and LNPR are more predictive of survival than the number of lymph node metastases detected in esophagectomy specimens. A minimum LNH of 15 is necessary to establish reliable N0 staging in this cohort.

Introduction: The identification of esophagogastric junction (EGJ) outflow obstruction via high resolution manometry (HRM) is increasingly common and of unclear clinical significance. The objective of this study was to review the HRM characteristics of EGJ outflow obstruction and to assess how this diagnosis translates into clinical practice. Methods: A retrospective review was conducted of 1105 symptomatic patients who underwent HRM between 9/09 and 8/12. EGJ outflow obstruction was defined as an elevated 4 second lower esophageal sphincter integrated relaxation pressure (IRP). Patients with elevated IRP were divided into 3 groups: achalasia, mechanical obstruction (large hiatal hernia, postoperative and neoplasia) and functional obstruction (no obvious underlying cause). Clinical and demographic data, presenting symptoms, upper endoscopic findings, treatment and posttreatment outcomes were compared among the groups. Results: Of the 1105 patients studied, 237 (21%) had an elevated IRP. Sixty four percent were female with a mean age of 56.8±15.4 years. Mechanical causes of obstruction were most common (100/237, 42%) including postoperative in 50, large hiatal hernia in 48 and esophageal cancer in 2. Achalasia was present in 75 patients (32%). The remaining 62 (26%) had an elevated IRP without evidence of mechanical obstruction. Dysphagia was the primary presenting symptom in 85% of patients in the achalasia group, 31% of the mechanical group and 13% of the functional group (p,0.009). Interestingly, upper respiratory symptoms were significantly more common in patients with functional outflow obstruction (26% vs. 1% achalasia and 4% mechanical, p,0.001). The mean IRP also varied amongst the clinical groups, highest in achalasia 31.0±11.7mmHg, intermediate in mechanical obstruction (23.5 ±8.6 mmHg) and lowest in the functional group (18.7±3.8 mmHg) p,0.001. A similar pattern was seen in the mean intra-bolus pressures 28.6±15.0 mmHg, 20.1±7.4 mmHg and 14.9±4.0 mmHg, respectively. Nearly 40% (22/57) of the patents with functional outflow obstruction parameters were pH positive suggesting GE barrier failure despite the manometric findings. Fundoplication was performed in 9 of these 22 patients (41%) with good response. Five of the remaining functional patients underwent treatment; myotomy in one and Botox in 4. Conclusions: The predominant etiologies of EGJ outflow obstruction are mechanical obstruction and achalasia. Mechanical causes should be excluded before functional outflow obstruction is diagnosed and treated. HRM parameters of functional outflow obstruction may be present in a subset of patients with pH positive GERD. The ideal management of patients with symptomatic functional obstruction remains unclear.

Introduction: Prospective randomized trials document long term relief of gastro-esophageal reflux (GERD) symptoms in 85% of patients following antireflux surgery. One of the key challenges, in the decision to pursue antireflux surgery, is assuring that the patients symptoms are actually caused by GERD. Mathematical calculations of the relationship of reflux events to the occurrence of symptoms have been proposed as a mechanism to support GERD as the underlying cause of both typical and atypical reflux symptoms. The symptom index (SI) and Symptom Association Probability (SAP) are the most commonly calculated measures in clinical use. The clinical utility of these measures is unclear and unexplored with respect to antireflux surgery. Methods: The study population included 66 patients (mean age 52.6 years; 58% female) undergoing laparoscopic fundoplication fromNovember 2006 to October 2011. All were pH-positive (DeMeester Score >14.72) with either cough, heartburn and/or regurgitation, in which SI (positive ≥50%) and SAP (positive ≥95%) were calculated preop. Symptom outcome after surgery was categorized as ‘improvement', ‘no change' and ‘worsening' in their symptoms. All available data were logged into SPSS (version 18) for statistical analyses. Results: At the time of pH testing heartburn was recorded in 51 (84%), regurgitation in 22 (33%) and cough in 21 (32%) patients. One or both symptom indices were positive in 85% (56/66) and both negative in 15% (10/66) of the patients. Cough was significantly less associated with positive SI and/or SAP when compared to heartburn and regurgitation (SI 19% vs. 72.5% and 81.8%; p