Optimising rapid on-site evaluation-assisted endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal lymph nodes: The real-time cytopathology intervention process.

INTRODUCTION: Lymph node sampling by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the state of art procedure for staging the mediastinum and hilar regions in lung cancer patients. Our experience of implementing the real-time cytopathology intervention (RTCI) process for intraoperative EBUS-TBNAs is presented. This study is aimed to describe in detail the RTCI process for EBUS-TBNAs, and assess its utility and diagnostic yield before and after its implementation in parallel to conventional rapid on-site evaluation (c-ROSE). METHODS: A retrospective review of all EBUS-TBNAs between July 2016 and July 2017 at the University of Rochester Medical Center was performed. Final diagnoses, patient clinical data, and number of non-diagnostic samples (NDS) were reviewed. The numbers of NDS obtained from EBUS-TBNAs with no cytology assistance (NCA), with RTCI and with c-ROSE were analysed. RESULTS: Non-diagnostic lymph node samples were found in 20 out of 116 (17%), three out of 114 (2.6%) and 33 out of 286 (11.5%) cases with NCA, RTCI and c-ROSE, respectively. Application of statistical analysis revealed significant difference in the NDS between the groups of cases in the operating room with NCA and RTCI (P = .005). The different settings and variables between the cases performed using RTCI in the operating room and those assisted with c-ROSE in the bronchoscopy suite preclude legitimate comparison. CONCLUSION: Our results indicate that the use of RTCI could yield a significantly low proportion of NDS when assisting EBUS-TBNA of mediastinal and hilar lymph node for lung cancer patients enhancing the diagnostic efficiency of the procedure.

24-h multichannel intraluminal impedance-pH monitoring may be an inadequate test for detecting gastroesophageal reflux in patients with mixed typical and atypical symptoms.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Tumor differentiation impacts response to neoadjuvant therapy and survival in patients with esophageal adenocarcinoma.

OBJECTIVE: The current staging system for esophageal adenocarcinoma only considers tumor grade in early tumors. The aim of this study was to evaluate the impact of tumor differentiation on response to neoadjuvant chemoradiotherapy and survival in patients with locally advanced esophageal adenocarcinoma. METHODS: This was a multi-institution retrospective review of all patients with esophageal cancer who underwent neoadjuvant chemoradiotherapy followed by esophagectomy from January 2010 to December 2017. Response to neoadjuvant therapy and survival was compared between patients with well- or moderately differentiated (G1/2) tumors versus poorly differentiated (G3) tumors. RESULTS: There were 550 patients, 485 men (88.2%) and 65 women. The median age was 61 years, and the tumor was G1/2 in 288 (52.4%) and G3 in 262 patients. Overall clinical stage before neoadjuvant therapy was similar between groups. Pathologic complete response (pCR) was found in 87 patients (15.8%). The frequency of pCR was similar between groups, but residual disease in the esophagus and lymph nodes was significantly more likely with G3 tumors. Median follow-up was 63 months and absolute survival, overall survival, and disease-free survival were all significantly worse in patients with G3 tumors. Further, even with pCR, patients with G3 tumors had significantly worse survival. CONCLUSIONS: This study showed that response to neoadjuvant therapy was not affected by tumor differentiation. However, poor differentiation was associated with worse survival compared with patients with G1/2 tumors, even among those with pCR. These results suggest that poor differentiation should be considered as an added risk factor for clinical staging in patients with locally advanced esophageal adenocarcinoma.

Bravo catheter-free pH monitoring: normal values, concordance, optimal diagnostic thresholds, and accuracy.

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.

Laparoscopic Nissen fundoplication assessment: task analysis as a model for the development of a procedural checklist.

BACKGROUND: Learning an advanced laparoscopic procedure is a complex process that requires clinical exposure, direct teaching, and deliberate practice. Expert surgeons automate their knowledge, making it difficult to teach incremental steps. Our aim was to deconstruct the steps of a laparoscopic Nissen fundoplication (LNF) and develop a procedural checklist assessment instrument. METHODS: A behavioral task analysis was conducted with five experts using the Delphi technique to identify all steps of a LNF. The Delphi survey included video analysis of expert performance, two electronic iterative rounds and final group interview to reach consensus. The created checklist was then used to assess the performance of 14 general surgery residents. Participants viewed a brief instructional video and performed a LNF on a porcine model. Laparoscope video recordings were evaluated by a blinded investigator using the created LNF checklist. RESULTS: The task analysis produced a 65-step procedural checklist with six major components (patient positioning and port placement, dissection of crura and esophagus, closure of crura, mobilization of fundus, orientation of fundoplication, and creation of fundoplication). Thirteen of 14 participants completed the procedure. Median score for all residents was 31 (range 13-38) with senior residents (36, 34-38) having significantly higher scores than junior residents (30, 13-36) (p = 0.0162). Most residents attempted the major components of the procedure; 13 of 14 dissected the crura and created the fundoplication, 12 closed the crura, and 11 mobilized the fundus. However, residents frequently failed to complete key elements such as protection of the vagus nerve or mediastinal mobilization of the esophagus. CONCLUSIONS: The task analysis and Delphi technique was successful in reaching expert consensus on the procedural steps of a LNF and in creating a valid checklist. By capturing automated knowledge in a checklist form, we can scaffold resident learning and improve feedback for an advanced laparoscopic case.

Measurement of gastric pH in ambulatory esophageal pH monitoring.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Predicting systemic disease in patients with esophageal cancer after esophagectomy: a multinational study on the significance of the number of involved lymph nodes.

OBJECTIVE: The aim of this study was to determine whether the risk of systemic disease after esophagectomy can be predicted by the number of involved lymph nodes. SUMMARY BACKGROUND DATA: Primary esophagectomy is curative in some but not all patients with esophageal cancer. Identification of patients at high risk for systemic disease would allow selective use of additional systemic therapy. This study is a multinational, retrospective review of patients treated with resection alone to assess the impact of the number of involved lymph nodes on the probability of systemic disease. METHODS: The study population included 1,053 patients with esophageal cancer (700 adenocarcinoma, 353 squamous carcinoma) who underwent R0 esophagectomy with > or =15 lymph nodes resected at 9 international centers: Asia (1), Europe (5), and United States (3). To ensure a minimum potential follow-up of 5 years, only patients who had esophagectomy before October 2002 were included. Patients treated with neoadjuvant or adjuvant therapy were excluded. The impact of the number of involved lymph nodes on the risk of systemic disease recurrence was assessed using univariate and multivariate analyses. RESULTS: Systemic disease occurred in 40%. The number of involved lymph nodes ranged from 0 to 26 with 55% of patients having at least 1 involved lymph node. The frequency of systemic disease after esophagectomy was 16% for those without nodal involvement and progressively increased to 93% in patients with 8 or more involved lymph nodes. CONCLUSIONS: This study shows that the number of involved lymph nodes can be used to predict the likelihood of systemic disease in patients with esophageal cancer. The probability of systemic disease exceeds 50% when 3 or more nodes are involved and approaches 100% when the number of involved nodes is 8 or more. Additional therapy is warranted in these patients with a high probability of systemic disease.

The number of lymph nodes removed predicts survival in esophageal cancer: an international study on the impact of extent of surgical resection.

OBJECTIVE: Surveillance, Epidemiology and End Results (SEER) data indicate that number of lymph nodes removed impacts survival in gastric cancer. Our aim was to study this relationship in esophageal cancer. METHODS: The study population included 2303 esophageal cancer patients (1381 adenocarcinoma, 922 squamous) from 9 international centers that had R0 esophagectomy prior to 2002 and were followed at regular intervals for 5 years or until death. Patients treated with neoadjuvant or adjuvant therapy were excluded. RESULTS: Operations consisted of esophagectomy with (1700) and without (603) thoracotomy. Median number of nodes removed was 17 (IQR10-29). There were 508 patients with stage I, 853 stage II, and 942 stage III. Five-year survival was 40%. Cox regression analysis showed that the number of lymph nodes removed was an independent predictor of survival (P < 0.0001). The optimal threshold predicted by Cox regression for this survival benefit was removal of a minimum of 23 nodes. Other independent predictors of survival were the number of involved nodes, depth of invasion, presence of nodal metastasis, and cell type. CONCLUSIONS: The number of lymph nodes removed is an independent predictor of survival after esophagectomy for cancer. To maximize this survival benefit a minimum of 23 regional lymph nodes must be removed.

Vagal-sparing esophagectomy.

The vagal-sparing esophagectomy is associated with low mortality, reduced morbidity, and improved long-term gastrointestinal functional outcome compared with standard esophagectomy. It is the ideal operation for the management of intramucosal cancers, Barrett's with high-grade dysplasia and end-stage benign esophageal disease.

Primary Esophageal Melanoma with Aberrant CD56 Expression: A Potential Diagnostic Pitfall.

Primary esophageal malignant melanoma (MM) is rare and extremely aggressive. For pathologists, it can be challenging to diagnose and differentiate from other poorly differentiated malignant neoplasms in the esophagus. Complicating this fact, MM can have divergent differentiation and express nonmelanocytic immunohistochemical markers including epithelial markers (cytokeratins) and rarely neuroendocrine markers. Lack of awareness of this fact by a pathologist can lead to an erroneous diagnosis and delay treatment for an already aggressive disease. Herein, we report a case of primary esophageal malignant melanoma with aberrant CD56 expression without accompanying synaptophysin or chromogranin expression.

Surgical Management of Barrett's Esophagus.

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.

Neoadjuvant treatment response in negative nodes is an important prognosticator after esophagectomy.

BACKGROUND: The current American Joint Committee on Cancer Seventh Edition (AJCC7) pathologic staging for esophageal adenocarcinoma (EAC) is derived from data assessing the outcomes of patients having undergone esophagectomy without neoadjuvant treatment and has unclear significance in patients who have received multimodality therapy. Lymph nodes with evidence of neoadjuvant treatment effect without residual cancer cells may be observed and are not traditionally considered in pathologic reports, but may have prognostic significance. METHODS: All patients who underwent esophagectomy after completing neoadjuvant therapy for EAC at our institution between 2006 and 2012 were reviewed. Slides of pathologic specimens were reexamined for locoregional treatment-response nodes lacking viable cancer cells but with evidence of acellular mucin pools, central fibrosis, necrosis, or calcifications suggesting prior tumor involvement. Kaplan-Meier survival functions were estimated, and Cox proportional hazards regression models were used to compare staging models. RESULTS: Ninety patients (82 men) underwent esophagectomy after neoadjuvant therapy for EAC (mean age, 61.8 ± 8.9 years). All patients received preoperative chemotherapy, and 50 patients also underwent preoperative radiotherapy. Median Kaplan-Meier survival was 55.6 months, and 5-year survival was 35% (95% confidence interval, 19% to 62%). A total of 100 treatment-response nodes were found in 38 patients. For patients with limited nodal disease (62 ypN0-N1), the presence of treatment-response nodes was associated with significantly worse survival (p = 0.03) compared with patients lacking such nodes. Adjusting for patient age and AJCC7 pathologic stage showed the presence of treatment-response nodes significantly increased the risk of death (hazard ratio, 2.7; 95% confidence interval, 1.1 to 6.9; p = 0.04). When stage-adjusted survival was modeled, counting treatment-response nodes as positive nodes offered a better model fit than ignoring them. CONCLUSIONS: Treatment-response lymph nodes detected from esophagectomy specimens in patients having undergone neoadjuvant chemotherapy or combined chemoradiation for EAC provide valuable prognostic information, particularly in patients with limited nodal disease. The current practice of considering lymph nodes lacking viable cancer cells, but with evidence of tumor necrosis, as pathologically negative likely results in understaging. Future efforts at revising the staging system for EAC should consider incorporating treatment-response lymph nodes in the analysis.

Unusual cases of jaundice secondary to non-neoplastic bile duct obstruction.

Obstructive jaundice secondary to common bile duct stricture is most commonly attributed to malignancy. Here we present three unusual cases that mimicked carcinoma in presentation but were histologically diagnosed as benign inflammatory processes during operative care. The first case was attributed to obstruction-induced chronic pancreatitis secondary to Crohn's disease of the head of the pancreas, the second was due to sarcoidosis within periportal and extrahepatic biliary lymph nodes and distal common bile duct, and the third case was due to tuberculosis of biliary lymph nodes. All were successfully managed surgically, but potentially these patients may have been effectively treated pharmacologically, without the need for invasive surgical intervention, if an earlier diagnosis were available to the clinicians. A retrospective and comparative review of the data of each case demonstrated subtle clues such as multiple enlarged biliary lymph node involvement and only moderately elevated bilirubin levels that pointed toward possible nonmalignant processes.

Surgical management of complicated hydatid disease of the liver.

Increased worldwide travel and immigration have led to an increase in the incidence of hepatic hydatid disease outside of endemic areas. In nonendemic areas lack of familiarity with the disease may lead to a delay in diagnosis with increased risk for development of complicated disease. Complicated disease is defined as: infected cysts, cysts with a hyperechoic solid pattern or calcified walls, or cysts with biliary rupture. Over a 6-month period six patients with complicated hydatid disease were referred to our institution. All six patients were immigrants from endemic areas and were found to have complicated hepatic hydatid disease including cholangitis and intrabiliary rupture. Patients were treated with oral albendazole for 3 weeks before operation and oral praziquantel for 2 days preoperatively. Surgical therapy consisted of subtotal cystectomy, cholecystectomy in all patients, and cystic duct biliary decompression-drainage in five patients. The one patient without biliary drainage developed a postoperative bile leak that resolved with endoscopic biliary stenting. All patients received albendazole for 3 months postoperatively and were free of disease at 6 to 24 months follow-up. We conclude that although nonoperative management with percutaneous drainage or medical management alone may be successful in patients with uncomplicated disease operation remains the therapy of choice for complicated hydatid disease.

Eliminating a need for esophagectomy: endoscopic treatment of Barrett esophagus with early esophageal neoplasia.

Over the past several years, endoscopic ablation and resection have become a new standard of care in the management of Barrett esophagus (BE) with high-grade dysplasia (HGD) or intramucosal adenocarcinoma (IMC). Risk factors for failure of endoscopic therapy and the need for subsequent esophagectomy have not been well elucidated. The aims of this study were to determine the efficacy of radiofrequency ablation (RFA) with or without endoscopic mucosal resection (EMR) in the management of BE with HGD or IMC, to discern factors predictive of endoscopic treatment failure, and to assess the effect of endoscopic therapies on esophagectomy volume at our institution. Data were obtained retrospectively for all patients who underwent endoscopic therapies or esophagectomy for a diagnosis of BE with HGD or IMC in our department between January 1, 2004, and December 31, 2012. Complete remission (CR) of BE or HGD or IMC was defined as 2 consecutive biopsy sessions without BE or HGD or IMC and no subsequent recurrence. Recurrence was defined by the return of BE or HGD or IMC after initial remission. Progression was defined as worsening of HGD to IMC or worsening of IMC to submucosal neoplasia or beyond. Overall, 57 patients underwent RFA with or without EMR for BE with HGD (n = 45) or IMC (n = 12) between 2007 and 2012, with a median follow-up duration of 35.4 months (range: 18.5-52.0 months). The 57 patients underwent 181 ablation sessions and more than half (61%) of patients underwent EMR as a component of treatment. There were no major procedural complications or deaths, with only 2 minor complications including 1 symptomatic stricture requiring dilation. Multifocal HGD or IMC was present in 43% (25/57) of patients. CR of IMC was achieved in 100% (12/12) at a median of 6.1 months, CR of dysplasia was achieved in 79% (45/57) at a median of 11.5 months, and CR of BE was achieved in 49% (28/57) at a median of 18.4 months. Following initial remission, 28% of patients (16/57) had recurrence of dysplasia (n = 12) or BE (n = 4). Progression to IMC occurred in 7% (4/57). All patients without CR continue endoscopic treatment. No patient required esophagectomy or developed metastatic disease. Overall, 6 patients died during the follow-up interval, none from esophageal cancer. Factors associated with failure to achieve CR of BE included increasing length of BE (6.0 ± 0.6 vs 4.0 ± 0.6cm, P = 0.03) and shorter duration of follow-up (28.5 ± 3.8 months vs 49.0 ± 5.8 months, P = 0.004). Shorter surveillance duration (17.8 ± 7.6 months vs 63.9 ± 14.4 months, P = 0.009) and shorter follow-up (21.1 ± 6.1 months vs 43.2 ± 4.1 months) were the only significant factors associated with failure to eradicate dysplasia. Our use of esophagectomy as primary therapy for BE with HGD or IMC has diminished since we began using endoscopic therapies in 2007. From a maximum of 16 esophagectomies per year for early Barrett neoplasia in 2006, we performed only 3 esophageal resections for such early disease in 2012, all for IMC, and we have not performed an esophagectomy for HGD since 2008. Although recurrence of BE or dysplasia/IMC was not uncommon, RFA with or without EMR ultimately resulted in CR of IMC in all patients, CR of HGD in the majority (79%), and CR of BE in nearly half (49%). No patient treated endoscopically for HGD or IMC subsequently required esophagectomy. In patients with BE with HGD or IMC, RFA and EMR are safe and highly effective. The use of endoscopic therapies appears justified as the new standard of care in most cases of BE with early esophageal neoplasia.

Minimally invasive surgery for esophageal cancer.

Minimally invasive surgery has revolutionized the surgical management of benign foregut disease, as well as pulmonary and other gastrointestinal malignancies. With the potential to reduce operative morbidity and increase patient satisfaction, minimally invasive esophagectomy for the management of esophageal cancer is gaining in popularity. It is unclear, however, whether the minimally invasive approach to esophageal cancer resection has comparable long-term oncologic results. This article discusses the rationale for minimally invasive esophagectomy, describes the surgical technique, and reviews the published results.

Reflux-associated oxygen desaturations: usefulness in diagnosing reflux-related respiratory symptoms.

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 < 0.001)) or control subjects (3 (2-6, p < 0.001)). A similar relationship was found for the number of proximal reflux-associated desaturations. Repeat study in seven post-fundoplication patients showed marked improvement, with reflux-associated desaturations approaching those of control subjects in five patients; 20 (9-20) distal preoperative versus 3 (0-5, p = 0.06) postoperative; similar results were identified proximally. CONCLUSIONS: These data provide further proof that reflux-associated oxygen desaturations may discriminate patients presenting with primary respiratory symptoms as being due to reflux and may respond to antireflux surgery.

Gastroesophageal reflux disease, proton-pump inhibitor use and Barrett's esophagus in esophageal adenocarcinoma: Trends revisited.

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.

Dysphagia postfundoplication: more commonly hiatal outflow resistance than poor esophageal body motility.

BACKGROUND: Historically, risk assessment for postfundoplication dysphagia has been focused on esophageal body motility, which has proven to be an unreliable prediction tool. Our aim was to determine factors responsible for persistent postoperative dysphagia. METHODS: Fourteen postfundoplication patients with primary dysphagia were selected for focused study. Twenty-five asymptomatic post-Nissen patients and 17 unoperated subjects served as controls. Pre- and postoperative clinical and high-resolution manometry parameters were compared. RESULTS: Thirteen of the 14 symptomatic patients (92.9%) had normal postoperative esophageal body function, determined manometrically. In contrast, 13 of 14 (92.9%) had evidence of esophageal outflow obstruction, 9 of 14 (64.3%) manometrically, and 4 of 14 (28.6%) on endoscopy/esophagram. Median gastroesophageal junction integrated relaxation pressure was significantly greater (16.2 mm Hg) in symptomatic than in asymptomatic post-Nissen patients (11.1 mm Hg, P = .05) or unoperated subjects (10.6 mm Hg, P = .02). Sixty-four percent (9/14) of symptomatic patients had an increased mean relaxation pressure. Dysphagia was present in 9 of 14 (64.3%) preoperatively, and elevated postoperative relaxation pressure was independently associated with dysphagia. CONCLUSION: These data suggest that postoperative alterations in hiatal functional anatomy are the primary factors responsible for post-Nissen dysphagia. Impaired relaxation of the neo-high pressure zone, recognizable as an abnormal relaxation pressure, best discriminates patients with dysphagia from those without symptoms postfundoplication.

Intraluminal pH and goblet cell density in Barrett's esophagus.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.