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.

Short- and long-term follow-up of patients with non-neoplastic esophageal perforation.

PURPOSE: Esophageal perforation is associated with high morbidity and mortality. In addition to surgical treatment, endoscopic endoluminal stent placement and endoscopic vacuum therapy (EVT) are established methods in the management of this emergency condition. Although health-related quality of life (HRQoL) is becoming a major issue in the evaluation of any therapeutic intervention, not much is known about HRQoL, particularly in the long-term follow-up of patients treated for non-neoplastic esophageal perforation with different treatment strategies. The aim of this study was to evaluate patients' outcome after non-neoplastic esophageal perforation with focus on HRQoL in the long-term follow-up. METHODS: Patients treated for non-neoplastic esophageal perforation at the University Hospital Cologne from January 2003 to December 2014 were included. Primary outcome and management of esophageal perforation were documented. Long-term quality of life was assessed using the Gastrointestinal Quality of Life Index (GIQLI), the Health-Related Quality of Life Index (HRQL) for patients with gastroesophageal reflux disease (GERD), and the European Organization for Research and Treatment of Cancer (EORTC) questionnaires for general and esophageal specific QoL (QLQ-C30 and QLQ-OES18). RESULTS: Fifty-eight patients were included in the study. Based on primary treatment, patients were divided into an endoscopic (n = 27; 46.6%), surgical (n = 20; 34.5%), and a conservative group (n = 11; 19%). Short- and long-term outcome and quality of life were compared. HRQoL was measured after a median follow-up of 49 months. HRQoL was generally reduced in patients with non-neoplastic esophageal perforation. Endoscopically treated patients showed the highest GIQLI overall score and highest EORTC general health status, followed by the conservative and the surgical group. CONCLUSION: HRQoL in patients with non-neoplastic esophageal perforation is reduced even in the long-term follow-up. Temporary stent or EVT is effective and provides a good alternative to surgery, not only in the short-term but also in the long-term follow-up.

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 .

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.

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.

Update on Transumbilical Single-Incision Laparoscopic Assisted Appendectomy (TULAA) - Which Children Benefit and What are the Complications?

BACKGROUND: Transumbilical laparoscopic-assisted appendectomy (TULAA) is fast and cost-effective since no endoloops, staplers or wound protection devices are used. We analyzed the effects of TULAA as first approach for perforated (PA) and non-perforated (NPA) appendicitis in children. PATIENTS: We performed a retrospective analysis of 181 children for whom TULAA was the first approach for appendicitis between October 2010 and March 2016. METHODS: Morbidity, additional laparoscopic instrument insertion (AI), conversions to open extraumbilical appendectomy (OC), and complications were evaluated. RESULTS: TULAA was initiated in 181 (87.4%) children (113 boys: 68 girls). Median age was 10.3 years (3.3-13.9 years) and BMI 16.8 kg/m2 (12.4-30.8). Appendicitis was non-perforated in 157 (86.7%) and perforated in 24 (13.3%) patients. TULAA was finalized in 142 (78.5%) patients, AI were inserted in 20 (11%) and OC were performed in 19 (10.5%) patients. Duration of surgery did not exceed 20 min for 12.8%, and 30 min for 43.6% of patients with TULAA and NPA. The rate of wound infections did not differ between procedures (TULAA 3/142 (2.1%), AI 0 (0%), OC 1/19 (5.3%), P=1.000). Further postoperative course was uneventful in 179 (98.9%) patients. CONCLUSION: TULAA can be used as first approach for appendicitis in all children with a low rate of complications. Extracorporeal appendix stump closure can be safely achieved in the majority of children without using laparoscopic disposable devices.

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.

Long-term quality of life after surgery for adenocarcinoma of the esophagogastric junction: extended gastrectomy or transthoracic esophagectomy?

BACKGROUND: Esophagectomy with gastric tube reconstruction and extended transhiatal gastrectomy with Roux-en-Y reconstruction are alternative procedures in current therapeutic concepts for adenocarcinoma of the esophagogastric junction (AEG). The impact of these operations on long-term health-related quality of life (HRQL) is incompletely understood. METHODS: Patients with cancer-free survival of at least 24 months after esophagectomy (ESO) or extended gastrectomy (GAST) for AEG were identified from a prospectively maintained database. EORTC questionnaires were sent out to assess health-related general (QLQ-C30) and cancer-specific (OG-25) quality of life. Numeric scores were calculated for each conceptual area and compared with those of healthy reference populations. RESULTS: 123 patients (ESO n = 71; GAST n = 52) completed the self-rated questionnaires. HRQL was consistently lower in surgical patients (GAST and ESO) compared with healthy reference populations. Also, there was a general trend for a better HRQL in GAST compared with ESO patients. This trend was statistically significant for physical function (p = 0.04), dyspnea (p = 0.02), and reflux (p = 0.03). Subgroup analysis revealed no significant differences between patients with or without prior neoadjuvant therapy. CONCLUSIONS: After mid- and long-term follow-up, HRQL after extended gastrectomy with Roux-en-Y reconstruction is superior to that after esophagectomy and gastric tube reconstruction. Improved HRQL after gastrectomy is mainly due to less pulmonary and reflux-related symptoms. Our findings may influence the choice of the surgical strategy for patients with AEG.

Gastric Outlet Obstruction After Esophagectomy: Retrospective Analysis of the Effectiveness and Safety of Postoperative Endoscopic Pyloric Dilatation.

BACKGROUND AND AIMS: Delayed gastric emptying after esophagectomy with gastric replacement can pose a significant postoperative problem, often leading to aspiration and pneumonia. The present study analyzes retrospectively the effectiveness of endoscopic pyloric dilatation for post-surgical gastric outlet obstruction. METHODS: Between March 2006 and March 2010, 403 patients underwent a transthoracic en-bloc esophagectomy and reconstruction with a gastric tube and intrathoracic esophagogastrostomy. In patients with postoperative symptoms of an outlet dysfunction and the confirmation by endoscopy, pyloric dilatations were performed without preference with either 20- or 30-mm balloons. RESULTS: A total of 89 balloon dilatations of the pylorus after esophagectomy were performed in 60 (15.6 %) patients. In 21 (35 %) patients, a second dilatation of the pylorus was performed. 55 (61.8 %) dilatations were performed with a 30-mm balloon and 34 (38.2 %) with a 20-mm balloon. The total redilatation rate for the 30-mm balloon was 20 % (n = 11) and 52.9 % (n = 18) for the 20-mm balloon (p < 0.001). All dilatations were performed without any complications. CONCLUSIONS: Pylorus spasm contributes to delayed gastric emptying leading to postoperative complications after esophagectomy. Endoscopic pyloric dilatation after esophagectomy is a safe procedure for treatment of gastric outlet obstruction. The use of a 30-mm balloon has the same safety profile but a 2.5 lower redilatation rate compared to the 20-mm balloon. Thus, the use of 20-mm balloons has been abandoned in our clinic.

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.

Health-related quality of life after Ivor Lewis esophagectomy.

PURPOSE: Transthoracic Ivor Lewis esophagectomy is a surgical standard therapy for esophageal carcinoma. The aim of this study was to assess health-related quality of life (HRQL) in mid- and long-term survivors. METHODS: Patients with cancer-free survival of at least 12 months after esophageal resection for cancer were identified from a prospectively maintained database. EORTC questionnaires were sent out to assess health-related general (QLQ-C30) and esophageal cancer-specific (QLQ-OES18) quality of life (QOL). A numeric score was calculated in each conceptual area and compared with reference data. RESULTS: One hundred forty-seven patients completed the self-rated questionnaires. They were 121 men and 26 women with a mean age of 63.4 (21-83) years; median FU was 39 (12-139) months. Global health status, functional scales, and symptom scores were significantly reduced compared with healthy reference populations. Also, there was no significant impact of tumor histology, neoadjuvant treatment, minimally invasive approach, or duration of follow-up on HRQL. However, more than half of the patients reported a HRQL similar to that of the healthy reference population. CONCLUSIONS: Despite the major psychosocial and physiological impacts of the disease, more than 50 % of mid- and long-term survivors of the Ivor Lewis procedure for esophageal cancer have a HRQL similar to that of the healthy reference population.

Comparison between endoscopic and surgical resection of mucosal esophageal adenocarcinoma in Barrett's esophagus at two high-volume centers.

BACKGROUND AND OBJECTIVE: Esophagectomy has previously been the gold standard for patients with mucosal adenocarcinoma in Barrett's esophagus (Barrett's carcinoma, BC). Because of the minimal invasiveness and excellent results obtained with endoscopic resection (ER), the latter has become an accepted alternative. However, few data have so far been published comparing the 2 treatment methods. METHODS: A total of 114 patients with mucosal BC who were treated surgically or endoscopically in 2 high-volume centers were included in this study. Between 1996 and 2009, 38 patients with mucosal BC received transthoracic esophageal resection with 2-field lymphadenectomy (median 29 lymph nodes removed; all pN0) in the Department of Surgery at the University of Cologne. Seventy-six patients with BC treated with ER followed by argon-plasma-coagulation of the remaining non-dysplastic Barrett's esophagus in the Department of Gastroenterology in Wiesbaden were matched according to the following criteria: age, gender, infiltration depth (pT1m1-3), differentiation grade (G1/2 vs. 3) and follow-up period. RESULTS: There were no significant differences between the 2 groups with regard to epidemiologic and tumor criteria. Complete remission (CR) was achieved in all patients in the surgery group and all but 1 patient in the ER group (98.7%; the patient died of other causes before CR was achieved). Major complications after surgery occurred in 32% of the patients, significantly more often than in the ER group (0% major complications, P < 0.001). The 90-day mortality rates were 0% in the ER group and 2.6% in the surgical group (1 of 38; P = 0.333). The median follow-up periods were 4.1 years in the ER group and 3.7 years in the surgical group. During this period, 1 patient in the ER group had a local recurrence and 4 had metachronous neoplasia (overall recurrence rate 6.6%). However, repeat endoscopic treatment was possible in all of the patients, and the long-term CR rates in the surgical and ER groups were 100% and 98.7%, respectively. No tumor-related mortality was observed in either group. CONCLUSIONS: For patients with mucosal BC, both surgery and ER are effective treatment modalities. Surgery is associated with a higher morbidity rate and shows a risk for procedure-related mortality. However, the recurrence rate is higher in patients treated with ER, so that thorough follow-up procedures are mandatory.

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

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.

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.

Botox, dilation, or myotomy? Clinical outcome of interventional and surgical therapies for achalasia.

PURPOSE: Achalasia is a rare, but well-defined primary esophageal motor disorder. Classic therapeutic approaches include botulinum toxin injection, balloon dilation, and surgical myotomy of the lower esophageal sphincter. This report summarizes our experience with different treatment modalities for achalasia. METHODS: Forty-three patients with achalasia treated in our hospital were subdivided according to therapeutic strategy: endoscopic botulinum toxin injection into the lower esophageal sphincter (EBTI; n = 7), endoscopic esophageal balloon dilation (EBD; n = 16), surgical myotomy after failed esophageal balloon dilation (EBD-HM; n = 14), and first-line surgical myotomy (HM; n = 6). Therapeutic efficiency was evaluated comparing standardized symptom scores preoperatively and at follow-up. RESULTS: There was no mortality and no significant difference between the groups for age, sex, or morbidity. The mean follow-up was at 9, 35, 38, and 17 months. At follow-up, recurrent or persistent symptoms were found in 71.4%, 6.3%, 35.7%, and 16.7% in EBTI, EBD, EBD-HM, and HM, respectively. Considering EBD-HM patients as failures of esophageal dilation, the total rate of recurrent or persistent symptoms after EBD was 50%. Poor symptomatic outcome was correlated to a low esophageal sphincter pressure during pretherapeutic manometry (p = 0.03) and to sigmoid-shaped esophageal dilatation (p = 0.06). CONCLUSION: Surgical myotomy is the most reliable first-line therapy for achalasia, particularly in patients with a high sphincter pressure and moderate esophageal dilatation. Botox injection has a high failure rate and should be reserved for exceptional cases. Endoscopic dilation provides about 50% of patients with long-term symptomatic relief; in most cases, failure can be successfully treated surgically.

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.

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.

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.

High prevalence of colonic polyps in white males with esophageal adenocarcinoma.

PURPOSE: There is ongoing discussion regarding Barrett's esophagus and the prevalence of colonic neoplasms. The goal of this investigation was to evaluate colonoscopic findings in patients with esophageal carcinoma. METHODS: In this case-control study, we used the data of patients with esophagectomy. These patients underwent routine preoperative endoscopy of the entire colon to exclude pathologic findings pending the need for colonic bridging graft reconstruction. A total of 171 patients with esophageal cancer (78 adenocarcinomas, 93 squamous-cell carcinomas, and 168 control subjects) who underwent screening colonoscopy were included. Univariate analysis and multinomial logistic regression were used to calculate odds ratios for colonic polyps. RESULTS: The age of the three groups of patients was comparable (median age: adenocarcinoma = 62 years, squamous-cell carcinoma = 58 years, control subjects = 59 years). The male to female ratio differed significantly (adenocarcinoma = 71:7, squamous-cell carcinoma = 65:28, control subjects = 86:82; P < 0.001). Patients with adenocarcinoma had more findings on colonoscopy than patients with squamous-cell carcinoma (45 and 25 percent, respectively; P < 0.01) or control subjects (14 percent; P < 0.001). Analyzing the male data only, the difference was more pronounced. The histologic type of the esophageal tumor significantly impacted the presence of colorectal polyps even with age-adjusted and sex-adjusted data (P < 0.001), with an odds ratio of 4.03 for adenocarcinoma. CONCLUSION: These results demonstrate a significant relationship between the development of Barrett's carcinoma and colonic polyps.