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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.