Sex- and gender-specific differences in symptoms and health-related quality of life among patients with gastroesophageal reflux disease.

Gastroesophageal Reflux Disease (GERD) is a common chronic gastrointestinal disorder affecting both men and women. Nonerosive reflux disease generally affects more women, whereas GERD complications such as Barrett's esophagus (BE) or esophageal cancer affect more men. The aim of this study was to evaluate sex- and gender-specific symptoms and health-related quality of life (HRQoL) among men and women with GERD. Patients with clinical signs of reflux and completion of 24-hour pH-Impedance testing at the University Hospital Cologne were included into the study. Evaluation of symptoms and HRQoL included the following validated questionnaires: GERD-Health-Related Quality of Life (GERD HRQL), Gastrointestinal Quality of Life Index (GIQLI), and Hospital Anxiety and Depression Scale (HADS). In all, 509 women and 355 men with GERD were included. Men had a significantly higher DeMeester score (60.2 ± 62.6 vs. 43 ± 49.3, P < 0.001) and a higher incidence of BE (18.6 vs. 11.2%, P = 0.006). Women demonstrated significantly higher levels of anxiety (30.9 vs. 14.5%, P = 0.001), more severely impacting symptoms (45.3 ± 11.3 vs. 49.9 ± 12.3, P < 0.001), as well as physical (14.2 ± 5.7 vs. 16.7 ± 5.6, P < 0.001) and social dysfunction (13.3 ± 4.8 vs. 14.8 ± 4.3, P = 0.002). Women further reported a lower HRQoL (85.3 ± 22.7 vs. 92.9 ± 20.8, P < 0.001). Men and women differ on biological, psychological, and sociocultural levels.

Gastrointestinal function testing model using a new laryngopharyngeal pH probe (Restech) in patients after Ivor-Lewis esophagectomy.

BACKGROUND: There is no established correlation between 24-h esophageal pH-metry (Eso-pH) and the new laryngopharyngeal pH-monitoring system (Restech) as only small case series exist. Eso-pH was not designed to detect laryngopharyngeal reflux (LPR) and Restech may detect LPR better. We have previously published a dataset using the two techniques in a large patient collective with gastroesophageal reflux disease. Anatomically, patients after esophagectomy were reported to represent an ideal human reflux model as no reflux barrier exists. AIM: To use a human reflux model to examine our previously published correlation in these patients. METHODS: Patients after Ivor Lewis esophagectomy underwent our routine follow-up program with surveillance endoscopies, computed tomography scans and further exams following surgery. Only patients with a complete check-up program and reflux symptoms were offered inclusion into this prospective study and evaluated using Restech and simultaneous Eso-pH. Subsequently, the relationship between the two techniques was evaluated. RESULTS: A total of 43 patients from May 2016 - November 2018 were included. All patients presented with mainly typical reflux symptoms such as heartburn (74%), regurgitation (84%), chest pain (58%), and dysphagia (47%). Extraesophageal symptoms such as cough, hoarseness, asthma symptoms, and globus sensation were also present. Esophageal 24-hour pH-metry was abnormal in 88% of patients with a mean DeMeester Score of 229.45 [range 26.4-319.5]. Restech evaluation was abnormal in 61% of cases in this highly selective patient cohort. All patients with abnormal supine LPR were also abnormal for supine esophageal reflux measured by conventional Eso-pH. CONCLUSION: Patients following esophagectomy and reconstruction with gastric interposition can ideally serve as a human reflux model. Interestingly, laryngopharyngeal reflux phases occur mainly in the upright position. In this human volume-reflux model, results of simultaneous esophageal and laryngopharyngeal (Restech) pH-metry showed 100% correlation as being explicable by one of our reflux scenarios.

Simultaneous Laryngopharyngeal and Conventional Esophageal pH Monitoring.

In addition to typical reflux symptoms, many patients with gastroesophageal reflux disease (GERD) present with extraesophageal symptoms such as cough, hoarseness or asthma, which can be caused by laryngopharyngeal reflux (LPR). Due to their multifactorial origin, those symptoms can be a great diagnostic and therapeutic challenge. Esophageal pH-monitoring is commonly used to determine abnormal esophageal acid exposure and confirm the diagnosis of GERD. However, for better evaluation of acid exposure above the upper esophageal sphincter, a new laryngopharyngeal pH measurement system is now available and may lead to more reliable results in patients with predominantly extraesophageal symptoms. This article aims to present a standardized protocol for simultaneous pH measurement using esophageal and laryngopharyngeal pH probes in order to obtain acid exposure scores from both measurements.

The CARDIA-trial protocol: a multinational, prospective, randomized, clinical trial comparing transthoracic esophagectomy with transhiatal extended gastrectomy in adenocarcinoma of the gastroesophageal junction (GEJ) type II.

BACKGROUND: Adenocarcinoma of the gastroesophageal junction (GEJ) Siewert type II can be resected by transthoracic esophagectomy or transhiatal extended gastrectomy. Both allow for a complete tumor resection, yet there is an ongoing controversy about which surgical approach is superior with regards to quality of life, oncological outcomes and survival. While some studies suggest a better oncological outcome after transthoracic esophagectomy, others favor transhiatal extended gastrectomy for a better postoperative quality of life. To date, only retrospective studies are available, showing ambiguous results. METHODS: This study is a multinational, multicenter, randomized, clinical superiority trial. Patients (n = 262) with a GEJ type II tumor resectable by both transthoracic esophagectomy and transhiatal extended gastrectomy will be enrolled in the trial. Type II tumors are defined as tumors with their midpoint between ≤1 cm proximal and ≤ 2 cm distal of the top of gastric folds on preoperative endoscopy. Patients will be included in one of the participating European sites and are randomized to either transthoracic esophagectomy or transhiatal extended gastrectomy. The trial is powered to show superiority for esophagectomy with regards to the primary efficacy endpoint overall survival. Key secondary endpoints are complete resection (R0), number and localization of tumor infiltrated lymph nodes at dissection, post-operative complications, disease-free survival, quality of life and cost-effectiveness. Postoperative survival and quality of life will be followed-up for 24 months after discharge. Further survival follow-up will be conducted as quarterly phone calls up to 60 months. DISCUSSION: To date, as level 1 evidence is lacking, there is no consensus on which surgery is superior and both surgeries are used to treat GEJ type II carcinoma worldwide. The CARDIA trial is the first randomized trial to compare transthoracic esophagectomy versus transhiatal extended gastrectomy in patients with GEJ type II tumors. Several quality control measures were implemented in the protocol to ensure data reliability and increase the trial's significance. It is hypothesized that esophagectomy allows for a higher rate of radical resections and a more complete mediastinal lymph node dissection, resulting in a longer overall survival, while still providing an acceptable quality of life and cost-effectiveness. TRIAL REGISTRATION: The trial was registered on August 2nd 2019 at the German Clinical Trials Register under the trial-ID DRKS00016923 .

Software improvement for evaluation of laryngopharyngeal pH testing (Restech) - a comparison between DataView 3 and 4.

BACKGROUND: When gastroesophageal reflux contents reach above the upper esophageal sphincter, patients may, in addition to typical reflux symptoms, present with atypical, extraesophageal symptoms related to laryngopharyngeal reflux (LPR). Surgical treatment of LPR has shown to lead to 70% symptom improvement, however no gold standard for the diagnosis of LPR exists. In 2007, the Restech Dx-pH was released as a valid method to measure acid exposure above the upper esophageal sphincter. Recently, a new software update was introduced for analysis of measured pH data and calculation of composite scores. The effect of the changes applied to the new software version have not yet been analyzed. AIM: To compare results generated by DataView 3 to the most recently released DataView 4. METHODS: All patients with gastroesophageal reflux disease symptoms were seen in a specialized surgical outpatient clinic for gastrointestinal function testing. Retrospective chart review was performed of all patients presenting with suspected gastroesophageal reflux disease and extraesophageal reflux symptoms, who underwent laryngopharyngeal pH monitoring using the Restech Dx-pH system (Respiratory Technology Corp., Houston, TX, United States) and simultaneous esophageal pH monitoring. DataView 3 and DataView 4 were used to evaluate Restech studies obtained. Diary entries such as mealtimes, supine and upright periods, and symptoms were entered manually to ensure accuracy and precise conversion of data between both software versions. Paired t test was performed for statistical analysis of results. RESULTS: A total of 174 patients (63.8% female) met inclusion criteria, all suffering from extraesophageal reflux symptoms as well as typical gastroesophageal reflux disease symptoms. Mean RYAN score upright was 48.77 in DataView 3 compared to 22.17 in DataView 4, showing a significant difference (a P = 0.0001). Similar results were shown for supine period (mean RYAN Score DataView 3 5.29 vs 1.42 in DataView 4, c P = 0.0001). For upright periods 80 patients showed a decrease of value of the RYAN score with a mean of -58.9 (mean 51.1% decrease). For supine position 25 patients showed a decrease of value of the RYAN score with a mean of -15.13 [range (-153.44)-(-0.01)], which equals a mean decrease of value of 44.5%. Ten patients showed no oropharyngeal acid exposure in DataView 3, but mild/moderate (n = 7) or severe (n = 3) acid exposure in DataView 4. Correlation with positive esophageal pH measurement was improved in all 10 patients. CONCLUSION: Results of both software versions cannot be compared to each other. However, our data suggests that DataView 4 may be an improvement of the Restech pH measurement in the evaluation of LPR.

Transdiaphragmatic herniation after transthoracic esophagectomy: an underestimated problem.

Diaphragmatic transposition of intestinal organs is a major complication after esophagectomy and can be associated with significant morbidity and mortality. This study aims of to analyze a large series of patients with this condition in a single high-volume center for esophageal surgery and to suggest a novel treatment algorithm. Patients who received surgery for postesophagectomy diaphragmatic herniation between October 2003 and December 2017 were included. Retrospective analysis of demographic, clinical and surgical data was performed. Outcomes of measure were initial clinical presentation, postoperative complications, in-hospital mortality and herniation recurrence. A total of 39 patients who had surgery for postesophagectomy diaphragmatic herniation were identified. Diaphragmatic herniation occurred after a median time of 259 days following esophagectomy with the highest prevalence between 1 and 12 months. A total of 84.6% of the patients had neoadjuvant radiochemotherapy prior to esophagectomy. The predominantly effected organ was the transverse colon (87.2%) prolapsing into the left hemithorax (81.6%). A total of 20 patients required emergency surgery. Surgery always consisted of reposition of the intestinal organs and closure of the hiatal orifice; a laparoscopic approach was used in 25.6%. Major complications (Dindo-Clavien ≥ IIIb) were observed in 35.9%, hospital mortality rate was 7.7%. Three patients developed recurrent diaphragmatic herniation during follow-up. Postesophagectomy diaphragmatic herniation is a functional complication of the late postoperative course and predominantly occurs in patients with locally advanced adenocarcinoma having chemoradiation before Ivor-Lewis esophagectomy. Due to a high rate of emergency surgery with life-threatening complications not a 'wait-and-see' strategy but early surgical repair may be indicated.

Ultrasound-guided lymphangiography and interventional embolization of chylous leaks following esophagectomy.

OBJECTIVES: Postoperative chylothorax is a serious complication after transthoracic esophagectomy, and is associated with major morbidity due to dehydration and malnutrition. For patients with high-output fistula, re-thoracotomy with ligation of the thoracic duct is the treatment of choice. Radiologic interventional management is an innovative procedure that has the potential to replace surgery in the treatment algorithm. METHODS: Four patients with high-output chylous leaks following esophagectomy are presented. Ultrasound-guided lymphangiography with embolization of the thoracic duct and/or disruption of the cisterna chyli was performed to occlude the leakage site. Radiologic interventions and procedure-related outcomes are described in detail. RESULTS: In all four patients, ultrasound-guided lymphangiography of the groin with injection of Lipiodol was able to detect and visualize the leakage site in the lower mediastinum. In three patients, the leak could be successfully occluded by Lipiodol embolization. In one patient, embolization failed and the disruption technique was successfully performed. No procedure-related complications were observed. CONCLUSIONS: In case of a postoperative chylothorax, radiologic intervention is feasible and safe. The procedure is indicated for high-output chylous fistulas after esophagectomy, and should be applied early after the diagnosis of this postoperative complication.

Modular step-up approach to robot-assisted transthoracic esophagectomy-experience of a German high volume center.

BACKGROUND: The use of robotic technology in general surgery is rapidly increasing in Europe. Aim of this study is to evaluate the introduction of new robotic technologies in a center of excellence for upper gastrointestinal surgery. METHODS: A standardized teaching protocol of a complete OR team was performed in simulation and animal models at the Center for the Future of Surgery (San Diego CA, USA) and IRCAD (Strasbourg, France) to receive certification as console surgeons. Starting 02/2017 the daVinci Xi and Stryker ICG laparoscopy systems were introduced at our academic center (certified center of excellence for surgery of the upper gastrointestinal tract, n>300 upper gastrointestinal cases/year). After simple training procedures based on our minimally invasive expertise were performed, difficulty was increased based on a modular step up approach to finally perform robotic assisted transthoracic Ivor Lewis esophagectomy. RESULTS: A total of 70 patients (9 females) fulfilled inclusion criteria to our study. Robotic assisted esophagectomy was divided into six modules. Level of difficulty was increased based on our modular step up approach without quality compromises. There were no intraoperative complications and no unplanned conversions to open surgery. Two surgeons were able to sequentially train and perform a completely robotic transthoracic esophagectomy using this modular approach without a substantial learning curve. A total of ten esophagectomies per surgeon were necessary to complete all modules in one case. CONCLUSIONS: The standardized training protocol and the University of Cologne modular step up approach allowed safe introduction of the new technology used. All cases were performed safely without operation-associated complications.

Endoscopic Treatment of Transesophageal Echocardiography-Induced Esophageal Perforation.

BACKGROUND: Perforation of the esophagus is the most severe complication of transesophageal echocardiography (TEE) and can lead to mediastinitis, pleural empyema, or peritonitis. Currently, the majority of patients receive operative treatment with only 6% treated endoscopically. We report our experience with endoscopic and conservative approaches. METHODS: We retrospectively reviewed all patients treated for esophageal perforation and included all patients with perforation caused by TEE. All patients with perforation of the esophagus by TEE probe underwent conservative or endoscopic treatment, drainage of pleural and mediastinal retentions, and adjusted to antibiotic therapy. RESULTS: From January 2004 to December 2014 a total of 109 patients were treated for esophageal perforation in our department. In 6 patients (5.5%) the perforation was caused by TEE. Location was cervical and midthoracic in 2 and 4 cases, respectively. All patients underwent successful endoscopic treatment and no further surgical procedure, such as esophageal suture or resection was necessary. The mean time between TEE and therapy of the perforation was 7.3 days. In all patients closure of the leakage could be achieved within 30 days. Mortality rate was 0%. CONCLUSIONS: Esophageal perforations caused by TEE are typically small, in the cervical and mid esophagus, and minimally contaminated. These are good prognostic factors for successful endoscopic treatment with preservation of the esophagus. Operative treatment should only be considered in cases of failed endoscopic treatment.

Results of endoscopic vacuum-assisted closure device for treatment of upper GI leaks.

BACKGROUND: Esophageal perforations and postoperative leakage of esophagogastrostomies are considered to be life-threatening conditions due to the potential development of mediastinitis and consecutive sepsis. Vacuum-assisted closure (VAC) techniques, a well-established treatment method for superficial infected wounds, are based on a negative pressure applied to the wound via a vacuum-sealed sponge. Endoluminal VAC (E-VAC) therapy as a treatment for GI leakages in the rectum was introduced in 2008. E-VAC therapy is a novel method, and experience regarding esophageal applications is limited. In this retrospective study, the experience of a high-volume center for upper GI surgery with E-VAC therapy in patients with leaks of the upper GI tract is summarized. To our knowledge, this series presents the largest patient cohort worldwide in a single-center study. METHODS: Between October 2010 and January 2017, 77 patients with defects in the upper gastrointestinal tract were treated using the E-VAC application. Six patients had a spontaneous perforation, 12 patients an iatrogenic injury, and 59 patients a postoperative leakage in the upper gastrointestinal tract. RESULTS: Complete restoration of the esophageal defect was achieved in 60 of 77 patients. The average duration of application was 11.0 days, and a median of 2.75 E-VAC systems were used. For 21 of the 77 patients, E-VAC therapy was combined with the placement of self-expanding metal stents. CONCLUSION: This study demonstrates that E-VAC therapy provides an additional treatment option for esophageal wall defects. Esophageal defects and mediastinal abscesses can be treated with E-VAC therapy where endoscopic stenting may not be possible. A prospective multi-center study has to be directed to bring evidence to the superiority of E-VAC therapy for patients suffering from upper GI defects.

Percutaneous Endoscopic Gastrostomy in Direct Puncture Technique: When, Why and How?

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) placed in the pull through (PT) technique is a common procedure to restore enteral feeding in patients with swallowing disorders. Limitations of this technique are patients with obstruction of the pharynx or esophagus or with an esophageal stent. We report our experience with the direct puncture (DP) PEG device. METHODS: We included 154 patients (55 women). One hundred forty patients had cancer. After passing the endoscope into the stomach, 4 gastropexies were performed with a gastropexy device and the PEG was placed with the introducer method. After 1 month, the sutures were removed and a constant gastrocutaneous fistula had been created and the new catheter could be placed safely. RESULTS: The DP PEG was successfully placed in all patients. Overall complication rate was 11% (minor: 6%, major: 5%). The most common event was tube dislocation (40 cases). In 5 cases of dislocation, this resulted in a major complication with injuring the gastric wall and the necessity for surgical treatment. CONCLUSIONS: The DP PEG system is safe, and can be used in cases in which a standard PT PEG is not feasible. To avoid dislocation, strict adherence to a post-interventional protocol is highly recommended.

Incidence and management of chylothorax after Ivor Lewis esophagectomy for cancer of the esophagus.

OBJECTIVE: Chylothorax is a major complication after esophagectomy. As recent studies refer to heterogeneous patient cohorts and surgical procedures, this study was conducted to report the incidence and evaluate the optimal management of chylous fistula in patients treated with transthoracic esophagectomy and 2-field lymphadenectomy for esophageal cancer. METHODS: From January 2005 to December 2013, a total of 906 patients underwent transthoracic esophageal resection for esophageal carcinoma at our institution. En bloc esophagectomy was performed with routine supradiaphragmatic ligation of the thoracic duct. The incidence of chylothorax, and associated morbidity and mortality, were analyzed, and subsequent therapeutic management was reviewed. RESULTS: Chylothorax after Ivor Lewis esophagectomy was observed in 17 (1.9%) patients. Fifteen patients required surgical intervention with rethoracotomy and repeat duct ligation. Thoracic duct ligation was successful in all patients. Two patients died within 90 days after primary esophageal resection. The median time between initial tumor resection and rethoracotomy was 13 days. Average daily chest-tube output at time of reoperation was 1900 mL. In 2 patients, pleural effusion did not exceed 1000 mL per day. In these cases, conservative management with additional thoracic drainage and total parenteral nutrition led to complete resolution of chylous fistula. CONCLUSIONS: Occurrence of chylothorax after prophylactic thoracic duct ligation during transthoracic esophagectomy for esophageal cancer is rare. In patients with high-output chylous fistula, an early rethoracotomy with repeat ligation of the thoracic duct is safe and helps to shorten recovery time. In cases of low-volume drainage, a conservative approach is feasible.

Effect of laparoscopic antireflux surgery on esophageal motility.

BACKGROUND/AIMS: The effect of laparoscopic antireflux surgery on esophageal motility is incompletely understood, and any indication for this procedure in patients with motility disorder is disputed in literature. We evaluated the influence of laparoscopic Nissen fundoplication on impaired esophageal motility. METHODS: In this pathological manometric study, we divided the patients into two groups preoperatively: the hypomotility group (mean amplitude of esophageal contraction wave <40 mm Hg; HYPO group, n = 11) and the normal group (mean amplitude of esophageal contraction wave >40 mm Hg; NORM group, n = 43). The amplitudes of esophageal contraction waves 3 and 8 cm above the lower esophageal sphincter and the percentage of peristaltic contraction waves of the tubular esophagus were analyzed pre- and postoperatively. RESULTS: In total, 54 patients with GERD underwent esophageal manometry before and 6 months after Nissen fundoplication. The length and pressure of the lower esophageal sphincter were increased in both groups postoperatively (p < 0.01). Patients in the HYPO group (n = 11) showed a statistically significant increase of mean amplitude of esophageal contraction (32.8 vs. 57.3 mm Hg; p < 0.01), while no change was found in the NORM group (n = 43). A total of 72% of patients with preoperative motility disorder showed normal postoperative manometry. CONCLUSION: Nissen fundoplication normalizes esophageal motility, especially in patients with preoperative hypomotility. Patients with impaired esophageal motility should not per se be excluded from antireflux surgery.

Effect of aging on esophageal motility in patients with and without GERD.

BACKGROUND/AIMS: The impact of aging on esophageal motility is not completely understood. This study aims at assessing 1) whether degeneration of esophageal body motility occurs with age and 2) whether this development is influenced by gastroesophageal reflux disease (GERD). METHODS: 326 consecutive patients with symptoms of GERD underwent a diagnostic work-up including a water-perfused esophageal manometry. Patients were divided by age: 17-39 years (group 1, n=75), 40-49 years (group 2, n=79), 50-59 years (group 3, n=64), 60-69 years (group 4, n=74), and >70 years (group 5, n=34). GERD was diagnosed if patients had erosive esophagitis at endoscopy, a positive pH-metry, or both. The amplitude of esophageal contraction waves 3 cm and 8 cm above the lower esophageal sphincter and the percentage of peristaltic contraction waves of the tubular esophagus were analyzed and correlated to GERD. RESULTS: A normal esophageal manometry was found in 86.7%, 73.4%, 67.2%, 58.1%, and 55.9% (p<0.01) in groups 1-5, respectively. Esophageal contraction wave amplitudes were affected by age in patients positive for GERD only (p<0.01). Esophageal body peristalsis was affected by age (p<0.01) independent of the diagnosis of GERD. CONCLUSION: Aging is correlated to esophageal motor abnormalities. GERD has a significant impact on esophageal contraction wave amplitude, but not on peristalsis.

The prevalence of lymph node metastases in patients with T1 esophageal adenocarcinoma a retrospective review of esophagectomy specimens.

UNLABELLED: Knowledge of the risk of lymph node metastases is critical to planning therapy for T1 esophageal adenocarcinoma. This study retrospectively reviews 75 T1a and 51 T1b tumors and correlates lymph node metastases with depth of tumor invasion, tumor size, presence of lymphovascular invasion, and tumor grade. OBJECTIVES: Increasingly, patients with superficial esophageal adenocarcinoma are being treated endoscopically or with limited surgical resection techniques. Since no lymph nodes are removed with these therapies, it is critical to have a clear understanding of the risk of lymph node metastases in these patients. The aim of this study was to define the risk of lymph node metastases for intramucosal and submucosal (T1) esophageal adenocarcinoma and to analyze factors potentially associated with an increased risk of lymph node involvement. METHODS: We reanalyzed the pathology specimens of all patients that had primary esophagectomy for T1 adenocarcinoma of the distal esophagus or gastroesophageal junction from January 1985 to December 2008. The prevalence of lymph node metastases was correlated with tumor size, depth of invasion, presence of lymphovascular invasion, and degree of tumor differentiation. RESULTS: There were 126 patients, 102 men (81%) and 24 women (19%), with a mean age of 64 (± 10) years. Tumor invasion was limited to the mucosa (T1a) in 75 patients (60%), whereas submucosal invasion (T1b) was present in 51 patients (40%). Tumors that had poor differentiation, lymphovascular invasion, and size ≥2 cm were significantly more likely to be invasive into the submucosa. Lymph node metastases were rare (1.3%) with intramucosal tumors but increased significantly with submucosal tumor invasion (22%)[P = 0.0003]. Lymph node metastases were also significantly associated with poor differentiation (P = 0.0015), lymphovascular invasion (P < 0.0001), and tumor size ≥2 cm (P = 0.01). Division of the submucosa into thirds did not show a layer with a significantly decreased prevalence of node metastases. CONCLUSIONS: Adenocarcinoma invasive deeper than the muscularis mucosa is associated with a significant increase in the prevalence of lymph node metastases,and there is no "safe" level of invasion into the submucosa. Lymphovascular invasion, tumor size ≥2 cm, and poor differentiation are associated with an increased risk of submucosal invasion and lymph node metastases and should be factored into the decision for endoscopic therapy or esophagectomy

Genetic variations in angiogenesis pathway genes predict tumor recurrence in localized adenocarcinoma of the esophagus.

OBJECTIVE: The aim of this study was to determine whether the risk of systemic disease after esophagectomy could be predicted by angiogenesis-related gene polymorphisms. SUMMARY BACKGROUND DATA: Systemic tumor recurrence after curative resection continues to impose a significant problem in the management of patients with localized esophageal adenocarcinoma (EA). The identification of molecular markers of prognosis will help to better define tumor stage, indicate disease progression, identify novel therapeutic targets, and monitor response to therapy. Proteinase-activated-receptor 1 (PAR-1) and epidermal growth factor (EGF) have been shown to mediate the regulation of local and early-onset angiogenesis, and in turn may impact the process of tumor growth and disease progression. METHODS: We investigated tissue samples from 239 patients with localized EA treated with surgery alone. DNA was isolated from formalin-fixed paraffin-embedded normal esophageal tissue samples and polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism and 5'-end [gamma-P] ATP-labeled polymerase chain reaction methods. RESULTS: PAR-1 -506 ins/del (adjusted P value=0.011) and EGF +61 A>G (adjusted P value=0.035) showed to be adverse prognostic markers, in both univariate and multivariable analyses. In combined analysis, grouping alleles into favorable versus nonfavorable alleles, high expression variants of PAR-1 -506 ins/del (any insertion allele) and EGF +61 A>G (A/A) were associated with a higher likelihood of developing tumor recurrence (adjusted P value<0.001). CONCLUSION: This study supports the role of functional PAR-1 and EGF polymorphisms as independent prognostic markers in localized EA and may therefore help to identify patient subgroups at high risk for tumor recurrence.

Clinical characteristics, biologic behavior, and survival after esophagectomy are similar for adenocarcinoma of the gastroesophageal junction and the distal esophagus.

OBJECTIVE: The Siewert classification system differentiates between adenocarcinoma of the gastroesophageal junction and that of the distal esophagus. The purpose of this study was to evaluate whether there were differences in the location and prevalence of lymph node metastases, type of recurrence, and survival with these tumors that warrant distinguishing between them in clinical practice. METHODS: Records of all patients who underwent resection for adenocarcinoma of the distal esophagus or gastroesophageal junction from 1987 to 2007 were retrospectively reviewed. Based on the endoscopic location of the epicenter of the tumor in relation to the gastroesophageal junction, tumors were categorized in 301 patients as being of the distal esophagus and in 208 as being of the gastroesophageal junction. RESULTS: There were no significant differences in age, sex, or body mass index between patients with adenocarcinoma of the distal esophagus or gastroesophageal junction. Patients with adenocarcinoma of the distal esophagus were more likely to have reflux symptoms (75% vs 53%, P < .0001) and peritumoral intestinal metaplasia (73% vs 51%, P < .0001) and be in a surveillance program (54% vs 9%, P = .0005) compared with patients with adenocarcinoma of the gastroesophageal junction. However, the prevalence and location of nodal metastases was similar, and in node-positive patients mediastinal node involvement was present in more than 40% of the patients in each group (distal esophageal adenocarcinoma, 47%; gastroesophageal junction adenocarcinoma, 41%). Survival was similar (5 years: distal esophageal adenocarcinoma, 45%; gastroesophageal junction adenocarcinoma, 38%; P = .14), as was the prevalence and type of recurrence. CONCLUSION: The prevalence and distribution of lymph node metastases in patients with adenocarcinoma of the distal esophagus and gastroesophageal junction were similar, and after esophagectomy, there was no difference in overall survival or recurrence. Efforts to differentiate between these tumors are unnecessary, and both are effectively treated with esophagectomy.

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.

INTRODUCTION: Obesity 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. METHODS: Data 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. RESULTS: Increasing BMI was positively correlated with increasing esophageal acid exposure (adjusted R (2) = 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)]. CONCLUSION: An 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.

Survival in lymph node negative adenocarcinoma of the esophagus after R0 resection with and without neoadjuvant therapy: evidence for downstaging of N status.

BACKGROUND: After esophagectomy, many patients who received neoadjuvant therapy have no evidence of lymph node involvement (N0 disease). Whether lymph nodes were initially involved and eradicated by the neoadjuvant therapy (down-staged) or if the nodes were never involved is a subject of debate. To address this issue, we compared clinical outcomes in N0 patients treated with neoadjuvant therapy with outcomes in patients treated with surgery alone. STUDY DESIGN: We reviewed records of 100 consecutive patients who underwent R0 esophagectomy for adenocarcinoma with pathologic N0 status. Seventy-five patients were treated by operation alone and 25 received neoadjuvant therapy. Tumor characteristics including length, depth, lymphovascular invasion, and degree of differentiation were compared and longterm survival was assessed by Kaplan-Meier analysis at a median of 46 months (interquartile range 26 to 77 months). RESULTS: Tumor characteristics were similar between groups. Recurrence was more common in patients who received neoadjuvant therapy compared with those treated with surgery alone (10 of 25 versus 10 of 75, p=0.0063). Patients with N0 disease after neoadjuvant therapy had a significantly worse survival than patients treated by surgery alone (49% versus 85%, p=0.005). CONCLUSIONS: Although neoadjuvant therapy may eradicate lymph node metastases, it does not result in the same outcomes as those achieved in patients with N0 disease treated with surgery alone. The poor clinical outcomes observed in N0 patients after neoadjuvant therapy suggest that they initially had node involvement and were downstaged by eradication of lymph node disease.

Delayed esophagogastrostomy: a safe strategy for management of patients with ischemic gastric conduit at time of esophagectomy.

BACKGROUND: Ischemia of the gastric conduit remains an important complication of esophagectomy and is associated with an increased risk of anastomotic leak and sepsis. We report a group of patients with multiple comorbid conditions and an ischemic gastric conduit that was successfully managed by a delayed esophagogastrostomy. STUDY DESIGN: Between 2000 and 2007, esophagectomy with gastric pullup was performed in 554 patients. In 37 patients (7%), the combination of an ischemic graft and substantial comorbid conditions prompted delayed reconstruction to avoid an immediate esophagogastrostomy. In these patients, the gastric conduit was brought up and secured in the neck, and a cervical esophagostomy was constructed. Subsequently, a delayed esophagogastrostomy was performed through neck incision. Outcomes were analyzed at a median of 22 months (interquartile range [IQR], 13 to 30 months). RESULTS: There were 29 male and 8 female patients, with a median age of 65 years (IQR, 58 to 75 years). Thirty-one patients had malignant disease; 12 received neoadjuvant therapy. All 37 patients recovered from their esophagectomy without evidence of ischemic necrosis or fistula from their gastric conduit. In 35 patients, a delayed esophagogastrostomy was performed at a median of 98 days (IQR, 89 to 110 days). At the time of reconstruction, all had well-perfused gastric conduits, and the anastomoses healed without leak, wound infection, or sepsis. A stricture developed in three patients and was treated with dilation. Delayed esophagogastrostomy was never performed in two patients because of development of recurrent malignant disease. CONCLUSIONS: Delayed esophagogastrostomy is a safe strategy for management of patients with comorbidities and an ischemic gastric conduit at the time of esophagectomy.