Clinical outcome after laparoscopic Nissen fundoplication in patients with GERD and PPI refractory heartburn.

Typical reflux symptoms that respond well to proton pump inhibitor (PPI) therapy are key factors predictive of an excellent outcome with antireflux surgery for gastroesophageal reflux disease (GERD). Our aim was to evaluate whether poor preoperative heartburn (HB) relief with PPIs was associated with a worse outcome after Nissen fundoplication. Patients with a main symptom of HB and a positive pH-test who had a laparoscopic Nissen fundoplication between January 2008 and December 2014 were included. Prior to surgery, patients graded how effectively their HB symptoms were relieved by PPIs. Three groups were defined: good response (76-100% relief), partial response (26-75% relief) and poor response (0-25% relief). Outcomes and satisfaction were assessed at a minimum of 1 year after fundoplication. There were 129 patients who met inclusion criteria and 75 agreed to participate. The median follow-up was 48 months. Prior to Nissen fundoplication 13 patients had a good HB response to PPI-therapy, 36 had a partial response and 26 had a poor response. All patients were satisfied with their HB relief after fundoplication (mean satisfaction score: 9.5/10) and there was no difference in satisfaction score or heartburn relief between groups. Heartburn symptoms that respond poorly to PPI therapy are reliably relieved with a Nissen fundoplication in patients with objectively confirmed GERD. Patient satisfaction after Nissen fundoplication was excellent and was similar in patients with poor versus excellent HB relief with preoperative PPI therapy. Therefore, antireflux surgery is an option for patients with HB and confirmed GERD regardless of the degree of relief of HB symptoms provided by PPI medications.

Accuracy of Clinical Staging and Outcome With Primary Resection for Local-Regionally Limited Esophageal Adenocarcinoma.

OBJECTIVE: The aim of this study was to determine the accuracy of clinical staging, to assess survival with surgical resection alone, and to determine factors associated with understaging in patients with esophageal adenocarcinoma thought to have limited local-regional disease. BACKGROUND: Primary surgical resection is the preferred treatment in patients with esophageal adenocarcinoma clinically staged to have limited nodal disease. This approach requires reliable clinical staging. METHODS: A retrospective chart review was performed of all patients who had primary esophagectomy for clinical stage T1-3 N0-1 adenocarcinoma (seventh edition AJCC) from January 2002 to May 2013. Clinical and pathologic stages were compared and overall survival was analyzed. RESULTS: There were 88 patients who met inclusion criteria. Final pathology confirmed appropriate clinical staging (≤T3N1) in 76% of patients (67/88). There were 21 patients who were understaged (>T3N1), and in all cases, understaging was based on the presence of advanced nodal (N2 or N3) disease. Factors independently associated with understaging were the presence of dysphagia, tumor length >3 cm, and poor differentiation. At a median follow-up of 35 months, 63% of all patients (55/88) remain alive. The 5-year survival in correctly staged patients was 67%, compared with 33% for those who were understaged (P < 0.0001). CONCLUSIONS: Modern clinical staging will accurately identify the majority of patients with esophageal adenocarcinoma and limited local-regional disease (≤pT3N1). Survival with surgery alone in correctly staged patients was excellent and unlikely to be improved with neoadjuvant therapy. A combination of dysphagia, poor differentiation, and tumor length >3 cm was associated with understaging in 92% of patients. Patients with these factors are likely to have more advanced disease than clinically suspected and may benefit from neoadjuvant therapy before resection.

Outcome with Primary En-bloc Esophagectomy for Submucosal Esophageal Adenocarcinoma.

BACKGROUND: Intramucosal esophageal adenocarcinoma can be reliably treated endoscopically. Controversy exists about the use of endotherapy versus esophagectomy for submucosal tumors. Increasingly endotherapy is considered for submucosal tumors in part because of the presumed high mortality with esophagectomy and the perceived poor prognosis in patients with nodal disease. This study was designed to assess survival following primary en bloc esophagectomy (EBE) in patients with submucosal esophageal adenocarcinoma (EAC). METHODS: This is a retrospective review of all patients who underwent EBE for submucosal EAC between 1998 and 2015. No patient had neoadjuvant therapy. RESULTS: There were 32 patients (28M/4F; median age 64 years). The median tumor size was 1.5 cm (0.4-8.0), and the median number of resected nodes was 48 (23-85). There was one perioperative death. Lymph node metastases were present in 7 patients (22%). There was one involved node in four patients and 2, 3, and 31 nodes in one patient each. The one N3 patient received adjuvant therapy. The median follow-up was 87 months. Overall survival at 5 and 10 years was 84 and 70% respectively. Disease-specific survival at 10 years was 90%. Eight patients died, but only three deaths (9%) were related to EAC. Disease-specific survival at 10 years in node-positive patients was 71%. CONCLUSIONS: Survival after primary en bloc esophagectomy for submucosal adenocarcinoma was excellent even in node-positive patients. Mortality with esophagectomy was low and far less than the 22% risk of node metastases in patients with submucosal tumor invasion. Esophagectomy should remain the preferred treatment for T1b esophageal adenocarcinoma.

Public perceptions on robotic surgery, hospitals with robots, and surgeons that use them.

OBJECTIVE: The use of robotic-assisted surgery (RS) has rapidly increased, but public perceptions about RS are largely unknown. The aim of this study was to gain insight into public perceptions about RS, hospitals that have robots, and surgeons that use them. METHODS: A Web-based survey was distributed worldwide. Surveys were collected from July to September 2014, and those with 50% or greater completion were used for analysis. RESULTS: There were 789 surveys, and 747 (95%) were used for analysis. The mean age of respondents was 38.5 years. Most (94%) were from the USA. Over half (53%) had a background in health care, and 13% were physicians. The majority of respondents (86%) had previously heard of RS, but almost 25% indicated that RS was like open, laser, or scarless surgery. Over 20% of respondents indicated that the robot had some degree of autonomy during surgery. Most respondents (72%) indicated that RS was safer, faster, and less painful or offered better results, but when asked if they would choose to have RS, 55% would prefer to have conventional minimally invasive surgery. Hospitals with a robot were thought to be better hospitals by 53% of the respondents. Fewer physicians perceived advantages to RS (30% physicians vs 78% non-physicians p < 0.001), and fewer physicians would prefer RS if they needed surgery (30 vs 49% p = 0.001). One-half of respondents would prefer remote RS by a renowned expert they had never met over having RS by a local non-expert surgeon. CONCLUSIONS: Most respondents perceived benefits to RS, but still preferred conventional minimally invasive surgery if necessary. Misperceptions about the robot indicate a need for patient education prior to RS. Interest by 50% of respondents in remote surgery might allow expert surgeons to do complex procedures without necessitating regionalization of care. Issues identified in this survey merit further exploration.

Intraoperative Assessment of Perfusion of the Gastric Graft and Correlation With Anastomotic Leaks After Esophagectomy.

OBJECTIVE: The aim of the study was to evaluate laser-assisted fluorescent-dye angiography (LAA) to assess perfusion in the gastric graft and to correlate perfusion with subsequent anastomotic leak. BACKGROUND: Anastomotic leaks are a major source of morbidity after esophagectomy with gastric pull-up (GPU). In large part, they occur as a consequence of poor perfusion in the gastric graft. METHODS: Real-time intraoperative perfusion was assessed using LAA before bringing the graft up through the mediastinum. When there was a transition from rapid and bright to slow and less robust perfusion, this site was marked with a suture. The location of the anastomosis relative to the suture was noted and the outcome of the anastomosis ascertained by retrospective record review. RESULTS: Intraoperative LAA was used to assess graft perfusion in 150 consecutive patients undergoing esophagectomy with planned GPU reconstruction. An esophagogastric anastomosis was performed in 144 patients. A leak was found in 24 patients (16.7%) and were significantly less likely when the anastomosis was placed in an area of good perfusion compared with when the anastomosis was placed in an area of less robust perfusion by LAA (2% vs 45%, P < 0.0001). By multivariate analysis perfusion at the site of the anastomosis was the only significant factor associated with a leak. CONCLUSIONS: Intraoperative real-time assessment of perfusion with LAA correlated with the likelihood of an anastomotic leak and confirmed the critical relationship between good perfusion and anastomotic healing. The use of LAA may contribute to reduced anastomotic morbidity.

Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression.

Lung cancer is the leading cause of cancer death worldwide, and adenocarcinoma is its most common histological subtype. Clinical and molecular evidence indicates that lung adenocarcinoma is a heterogeneous disease, which has important implications for treatment. Here we performed genome-scale DNA methylation profiling using the Illumina Infinium HumanMethylation27 platform on 59 matched lung adenocarcinoma/non-tumor lung pairs, with genome-scale verification on an independent set of tissues. We identified 766 genes showing altered DNA methylation between tumors and non-tumor lung. By integrating DNA methylation and mRNA expression data, we identified 164 hypermethylated genes showing concurrent down-regulation, and 57 hypomethylated genes showing increased expression. Integrated pathways analysis indicates that these genes are involved in cell differentiation, epithelial to mesenchymal transition, RAS and WNT signaling pathways, and cell cycle regulation, among others. Comparison of DNA methylation profiles between lung adenocarcinomas of current and never-smokers showed modest differences, identifying only LGALS4 as significantly hypermethylated and down-regulated in smokers. LGALS4, encoding a galactoside-binding protein involved in cell-cell and cell-matrix interactions, was recently shown to be a tumor suppressor in colorectal cancer. Unsupervised analysis of the DNA methylation data identified two tumor subgroups, one of which showed increased DNA methylation and was significantly associated with KRAS mutation and to a lesser extent, with smoking. Our analysis lays the groundwork for further molecular studies of lung adenocarcinoma by identifying novel epigenetically deregulated genes potentially involved in lung adenocarcinoma development/progression, and by describing an epigenetic subgroup of lung adenocarcinoma associated with characteristic molecular alterations.

High resolution manometry sub-classification of Achalasia: does it really matter? Does Achalasia sub-classification matter?

BACKGROUND: Three variants of Achalasia have been described using high-resolution esophageal manometry (HRM). While manometrically distinct, their clinical significance has yet to be established. Our objective was to compare the outcome after myotomy in patients with these Achalasia subtypes. METHODS: A retrospective chart review was performed to identify patients with Achalasia who had HRM and who underwent Heller myotomy or Per oral endoscopic myotomy (POEM). Symptoms and esophageal clearance by timed barium study were compared before and after treatment. RESULTS: We identified 49 patients, 21 males and 28 females, with a median age of 52 years. The primary symptom in all patients was dysphagia, with a median duration of 4 years (range 4 months-50 years). By HRM, ten patients (20 %) were classified as Type I, 30 (61 %) as Type II, and 9 (18 %) as Type III. At a median follow-up of 16 months after myotomy (range 1-63 months), the median Eckardt score was zero and was similar across subtypes. Relief of dysphagia was also similar across subtypes (80 % of Type I, 93 % of Type II and 89 % of Type III). On pre-treatment timed barium study, no patient had complete emptying at 1 or 5 min. After myotomy, complete emptying occurred within 1 min in 50 % (20/40) and within 5 min in 60 % (24/40) and was similar across groups. CONCLUSION: Myotomy for Achalasia results in excellent symptomatic outcome and improvement in esophageal clearance. There was no difference among the described HRM Achalasia variants. This calls into question the clinical utility of Achalasia sub-classification and affirms the benefit of myotomy for this disease.

Pharyngeal pH monitoring better predicts a successful outcome for extraesophageal reflux symptoms after antireflux surgery.

BACKGROUND: Gastroesophageal reflux disease can be associated with extraesophageal symptoms (hoarseness, cough, asthma, and globus). However, these symptoms may have a multifactorial etiology. Proximal pH monitoring has been proposed as a means of identifying patients where reflux is the cause of the extraesophageal symptoms. The aim of this study was to determine whether proximal esophageal or pharyngeal pH monitoring better identified patients with extraesophageal symptoms that improved after antireflux surgery. METHODS: A retrospective chart review was performed to identify all patients who had esophageal and pharyngeal pH monitoring before an antireflux operation. A composite score was used to define an abnormal result with each test. A successful outcome was defined as improvement or resolution of extraesophageal symptoms. RESULTS: There were 20 patients identified. Antireflux surgery led to a successful outcome in 14 patients (70 %). Restech better identified patients with extraesophageal symptoms who had a successful outcome with antireflux surgery (12 of 14 [86 %] based on abnormal Restech versus 5 of 10 [50 %] based on abnormal proximal probe, p = 0.06). Comparing only the 15 patients who had both proximal esophageal and pharyngeal pH monitoring, Restech again better identified those who had a successful outcome with antireflux surgery (9 of 10 [90 %] based on abnormal Restech versus 5 of 10 [50 %] based on abnormal proximal probe, p = 0.05). The positive and negative predictive values for symptomatic improvement after a fundoplication were better for an abnormal Restech score than for an abnormal proximal esophageal score (80 vs. 71 % and 60 vs. 38 %, respectively). In two patients with a successful outcome, Restech was the only positive test. CONCLUSIONS: In patients with extraesophageal reflux symptoms, proximal esophageal pH monitoring failed to identify half of the patients who had a successful outcome after antireflux surgery. In contrast, an abnormal Restech pH test was present in 90 % of patients with a successful outcome. Further, a negative Restech study more reliably indicated the absence of reflux-induced extraesophageal symptoms. Our results indicate that Restech pharyngeal pH monitoring should be utilized in the evaluation of patients with extraesophageal symptoms that may be associated with reflux disease.

Diaphragmatic relaxing incisions during laparoscopic paraesophageal hernia repair.

BACKGROUND: Laparoscopic paraesophageal hernia (PEH) repair is associated with an objective recurrence rate exceeding 50% at 5 years. Minimizing tension is a critical factor in preventing hernia recurrence. This study aimed to evaluate the outcomes of crural relaxing incisions in patients undergoing PEH repair. METHODS: Records were reviewed to identify patients who received a relaxing incision during laparoscopic PEH repair. The patients were followed by chest X-ray and videoesophagram at 3 months and then annually. RESULTS: From November 2010 to March 2013, 58 patients underwent PEH repair, and 15 patients received a relaxing incision to accomplish crural closure. The median age of the patients was 72 years (range 58-84 years). The relaxing incision was right-sided in 13 patients, left-sided in one patient, and bilateral in one patient. All the procedures were completed laparoscopically and included a fundoplication. Collis gastroplasty for a short esophagus was performed for 40% of the patients. No major complications occurred. During a median follow-up period of 4 months, one patient had an asymptomatic mildly elevated left hemidiaphragm, and one patient had a trivial recurrent hernia, as shown on esophagogastroduodenoscopy (EGD). CONCLUSION: Crural tension likely contributes to the high recurrence rate noted with laparoscopic PEH repair. Relaxing incisions are safe and allow crural approximation. Advanced laparoscopic surgeons should be aware of this option when faced with a large hiatus in a patient with PEH.

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

Day-to-day discrepancy in Bravo pH monitoring is related to the degree of deterioration of the lower esophageal sphincter and severity of reflux disease.

BACKGROUND: The Bravo capsule allows monitoring of esophageal acid exposure over a two-day period. Experience has shown that 24-32% of patients will have abnormal esophageal acid exposure detected on only one of the 2 days monitored. This variation has been explained by the effect of endoscopy and sedation. The aim of this study was to assess the day-to-day discrepancy following transnasal placement of the Bravo capsule without endoscopy or sedation and to determine factors related to this variability. METHODS: Bravo pH monitoring was performed by transnasal placement of the capsule in 310 patients. Patients were divided into groups based on the composite pH score: both days normal, both days abnormal and only one of the 2 days abnormal. Lower esophageal sphincter (LES) characteristics were compared between groups. RESULTS: Of the 310 patients evaluated, 60 (19%) showed a discrepancy between the 2 days. A total of 127 patients had a normal pH score on both days and 123 had an abnormal pH score on both days. Of the 60 patients with a discrepancy, 27 were abnormal the first day and 33 (55%) were abnormal the second day. Patients with abnormal esophageal acid exposure on both days had higher degrees of esophageal acid exposure and were more likely to have a defective LES compared to those with an abnormal score on only one day (35 vs. 83%, p=0.027). CONCLUSION: Patients with a discrepancy between days of Bravo pH monitoring have lower esophageal acid exposure. Variability between the 2 days represents early deterioration of the gastroesophageal barrier and indicates less advanced reflux disease.

Thoraco-abdominal pressure gradients during the phases of respiration contribute to gastroesophageal reflux disease.

BACKGROUND AND AIMS: Exaggerated pressure fluctuation between the thorax and abdomen during exercise or with pulmonary disease may challenge the gastroesophageal barrier and allow reflux of gastric juice into the esophagus. The aim of this study was to investigate the pressure differentials in the region of the gastroesophageal junction to better understand the relationship between the thoraco-abdominal pressure gradient and the lower esophageal sphincter (LES) barrier function. METHODS: We reviewed the esophageal motility and 24-h pH studies in 151 patients with a manometrically normal lower esophageal sphincter who did not have pulmonary disease, history of anti-reflux surgery, hiatal hernia, or ineffective esophageal motility (IEM). Intra-abdominal gastric and intra-thoracic esophageal pressure fluctuations with respiration were measured and the thoraco-abdominal pressure gradients were calculated during both inspiratory and expiratory phases of the respiratory cycle. Predictive factors for an abnormal composite pH score were identified by multivariable analysis. RESULTS: An inspiratory thoraco-abdominal pressure gradient that was higher than the resting LES pressure was found in 27 patients. In 23 of these patients (85.2%) there was increased esophageal acid exposure (OR 13.5, 95% CI 4.4-41.8). An abnormal composite pH score was predicted by a high inspiratory thoraco-abdominal pressure gradient (P < 0.001), greater fluctuation between inspiratory and expiratory thoracic pressure (P = 0.023), lower LES resting pressure (P = 0.049) and a decreased residual pressure after a swallow induced relaxation (P = 0.002). CONCLUSIONS: The gastroesophageal barrier function of the LES can be overcome during times when the inspiratory thoraco-abdominal pressure gradient is increased, leading to reflux of gastric juice into the esophagus. This implies that exaggerated ventilatory effort, as occurs with exercise or in respiratory disease, can result in gastroesophageal reflux.

Adequacy of EGD Reporting: a Review of 100 Reports from 100 Endoscopists.

INTRODUCTION: Esophagogastroduodenoscopy (EGD) is commonly performed in patients with gastroesophageal reflux disease (GERD). An EGD report should document pertinent findings such as esophagitis, a columnar-lined esophagus (CLE), the location of the squamo-columnar and gastroesophageal junctions, the size and type of a hiatal hernia and the number and location of any biopsies. The aim of this study was to evaluate how commonly these findings were noted in the EGD reports of patients referred for antireflux surgery. METHODS: A retrospective review was performed of patient charts from 2012 to 2015 to identify 100 consecutive EGD reports from different endoscopists in different patients. Each EGD report was reviewed for pertinent findings and the use of a classification system for esophagitis (Savory-Miller or Los Angeles) and for reporting a CLE (Prague). RESULTS: In 100 EGD reports, esophagitis was noted in 33 patients, but was graded in only 14 (42%). A CLE was noted in 28 patients, but the length was reported in only 16 (57%) and no report used the Prague classification system. A hiatal hernia was noted in 61 patients, measured in 31 (51%) and the type classified in 26%. A biopsy was taken in 93 patients and the location noted in 86 patients (93%). The number of biopsies was recorded in only 20 patients (22%). In 12 patients the EGD was for Barrett's surveillance, yet a Seattle biopsy protocol was reported to be used in only 3 patients. CONCLUSION: Endoscopy reports frequently do not include the use of a grading system for esophagitis or the Prague system for CLE. This hampers the assessment of change with therapy or over time. The size of a hiatal hernia was typically reported in a subjective fashion and only infrequently was the type specified. Lack of clarity about the presence of a paraesophageal hernia can impede evaluation of acute symptoms. In patients with Barrett's esophagus a standard biopsy protocol was infrequently reported to be used. These findings raise concern about the quality of upper endoscopy, both in the performance of the procedure and the documentation of findings. A consistent reporting system is recommended for routine use with upper endoscopy.

Consensus for Thoracoscopic Left Upper Lobectomy-Essential Components and Targets for Simulation.

BACKGROUND: Simulation-based training is a valuable component of cardiothoracic surgical education. Effective curriculum development requires consensus on procedural components and focused attention on specific learning objectives. Through use of a Delphi process, we established consensus on the steps of video-assisted thoracoscopic surgery (VATS) left upper lobectomy and identified targets for simulation. METHODS: Experienced thoracic surgeons were randomly selected for participation. Surgeons voted and commented on the necessity of individual steps comprising VATS left upper lobectomy. Steps with greater than 80% of participants in agreement of their necessity were determined to have established "consensus." Participants voted on the physical or cognitive complexity of each, or both, and chose steps most amenable to focused simulation. RESULTS: Thirty thoracic surgeons responded and joined in the voting process. Twenty operative steps were identified, with surgeons reaching consensus on the necessity of 19. Components deemed most difficult and amenable to simulation included those related to dissection and division of the bronchus, artery, and vein. CONCLUSIONS: Through a Delphi process, surgeons with a variety of practice patterns can achieve consensus on the operative steps of left upper lobectomy and agreement on those most appropriate for simulation. This information can be implemented in the development of targeted simulation for VATS lobectomy.

The impact of gastric distension on the lower esophageal sphincter and its exposure to acid gastric juice.

BACKGROUND AND AIMS: The lower esophageal sphincter (LES) in patients with gastroesophageal reflux disease often has a low resting pressure and a short abdominal length. The mechanism by which this occurs is unknown. We hypothesize that gastric distension causes progressive effacement of the abdominal portion of the LES, exposing it to acid injury resulting in mucosal and sphincter damage. Our aim was to assess in normal subjects the effect of gastric distension on the LES length and pressure and its exposure to acid gastric juice. METHODS: Eleven asymptomatic volunteers had their LES length and pressure measured before and during gastric distension. The location of the pH step-up point (shift from gastric pH to a pH >4) was also measured before and after distension. RESULTS: Progressive gastric distension with air resulted in progressive shortening of LES (R = 0.89, P < 0.0001). After infusion of 750 cc of air there was a significant reduction in the median LES length from 4 to 2.6 cm (P = 0.001). This change occurred in the abdominal length of the LES (2.6-1.4 cm [P = 0.001]) and not in the thoracic length. At rest the pH step-up point was 0.5 cm above the lower border of the LES and with distension moved a median of 1 cm cephalad within the LES. Simultaneously with the loss of length there was a reduction in LES pressure (27.4-23.4 mm Hg, P = 0.02). CONCLUSIONS: Gastric distension causes progressive shortening of the abdominal length of the LES and a reduction in its pressure. The process exposes the effaced mucosa and sphincter to acid gastric juice.

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.

Esophageal intraepithelial eosinophils in dysphagic patients with gastroesophageal reflux disease.

BACKGROUND: Patients with gastroesophageal reflux disease (GERD) often complain of dysphagia and are frequently found to have intraepithelial eosinophils on esophageal biopsy. AIM: The aim of this study was to investigate the relationship between dysphagia and the number of intraepithelial eosinophils in patients with GERD. METHODS: Review of all patients studied in our esophageal function laboratory from 1999 to 2007 identified 1,533 patients with increased esophageal acid exposure. Patients who complained of dysphagia without mechanical or motor causes were identified and divided into three groups based on whether dysphagia was their primary, secondary or tertiary symptom. A control group consisted of randomly selected GERD patients with no dysphagia. The highest number of intraepithelial eosinophils per high-power field (HPF) in biopsies from the squamocolumnar junction (SCJ) and esophageal body was compared across groups. RESULTS: There were 71 patients with unexplained dysphagia. Dysphagia was the primary symptom in 13 (18%), secondary symptom in 34 (48%), and tertiary symptom in 24 (34%) patients. The number of eosinophils differed between the four groups, with the highest number in those with dysphagia as the primary symptom (P = 0.0007). This relationship persisted whether biopsies were from the SCJ (P = 0.0057) or esophageal body (P = 0.0096). CONCLUSION: An association exists between the number of intraepithelial eosinophils and dysphagia in GERD patients, with the highest number of eosinophils in those with the primary symptom of dysphagia.

A simplified technique for intrathoracic stomach repair: laparoscopic fundoplication with Vicryl mesh and BioGlue crural reinforcement.

BACKGROUND: Laparoscopic repair of an intrathoracic stomach has been associated with a high recurrence rate. The use of biologic or synthetic mesh to reinforce the crural repair has been shown to reduce recurrence. This study aimed to assess a simplified technique for reinforcing the crural repair using absorbable Vicryl mesh secured with BioGlue during laparoscopic repair of an intrathoracic stomach. METHODS: The charts of all patients who underwent laparoscopic repair of an intrathoracic stomach from June 2006 to March 2009 using the described technique were retrospectively reviewed. Intrathoracic stomach was defined as more than 50% of the stomach herniated into the chest. Follow-up assessment was routinely performed 1 year or more after surgery and included endoscopy, video esophagram, Bravo 48-h pH monitoring, and a gastroesophageal reflux disease (GERD)-health-related quality-of-life (HRQL) questionnaire. RESULTS: A total of 35 patients (male:female = 10:25) with a mean age of 70 years (48-89 years) and a mean body mass index (BMI) of 30.4 kg/m(2) (20.4-44.8 kg/m(2)) underwent repair using this technique. The median operating time was 144 min (101-311 min), and the median hospital stay was 2 days (1-21 days). There were three conversions (8.6%) and one intraoperative complication (2.9%). Three patients (8.6%) experienced postoperative complications. No mesh-related complications occurred. Follow-up assessment 1 year or more after surgery was available for 21 of the 25 eligible patients [median follow-up period, 14 months (11-34 months)]. There were two recurrences (9.5%), one of them asymptomatic. The median GERD-HRQL score was 5 (2-28). Nearly all the patients (91.3%) were satisfied with the operation, and 96% would have it again. CONCLUSION: Vicryl mesh secured with BioGlue is a simple and easy method for reinforcing the crural closure during laparoscopic repair of an intrathoracic stomach. The recurrence rate at 1 year is low and comparable with that of other series using biologic mesh secured with sutures or tacks.

Detection of gastric conduit ischemia or anastomotic breakdown after cervical esophagogastrostomy: the use of computed tomography scan versus early endoscopy.

BACKGROUND: Concern over potential injury to the anastomosis has limited the use of early postoperative endoscopy to diagnose conduit ischemia or anastomotic breakdown. Alternatively, a computed tomography (CT) scan has been suggested as a noninvasive means for identifying these complications. This study aimed to compare CT scan with early endoscopy for diagnosing gastric conduit ischemia or anastomotic breakdown after esophagectomy with cervical esophagogastrostomy. METHODS: Between 2000 and 2007, 554 patients underwent an esophagectomy and gastric pull-up with cervical esophagogastrostomy at the University of Southern California. Records were reviewed to identify patients who had undergone endoscopy and CT scan within 24 h of each other during the first three postoperative weeks for suspicion of an ischemic conduit or anastomotic breakdown. The accuracies of CT scan and endoscopy in diagnosing an ischemic conduit were compared. RESULTS: A total of 76 patients had endoscopy and CT scan for clinical suspicion of conduit ischemia or anastomotic breakdown. Endoscopy was performed without complications in all 76 patients. The postoperative endoscopic findings were normal in 24 of the patients, and none subsequently experienced an ischemic conduit or anastomotic breakdown. Evidence of ischemia was present in 28 patients, 7 of whom had black mucosa throughout the gastric conduit with the anastomosis still intact and required removal of their conduit. The remaining 24 patients had partial or complete anastomotic breakdown. On the CT scan, 23 of the 76 patients showed evidence of conduit ischemia (n = 9) or anastomotic breakdown (n = 14). There was no evidence of ischemia or anastomotic breakdown on CT scan for the 24 patients with normal endoscopy or for 3 of the 7 patients who had their conduit removed for graft necrosis. CONCLUSION: A normal CT scan does not rule out the possibility of an ischemic gastric conduit after esophagectomy. Early endoscopy is a safe and accurate method for assessing conduit ischemia.