Magnetic sphincter augmentation: paradigm change or just another device in the surgeon's toolbox?

The common denominator for virtually all episodes of gastroesophageal reflux in health and disease is the loss of the barrier that confines the distal esophagus to the stomach. Factors important in maintaining the function of the barrier are its pressure, length and position. In early reflux disease, overeating, gastric distention and delayed gastric emptying led to a transient loss of the barrier. A permanent loss of the barrier occurs from inflammatory injury to the muscle allowing free flow of gastric juice into the esophageal body. Corrective therapy requires augmentation or restoration of the barrier referred to more commonly as the lower esophageal sphincter.

Effect of Increased Intra-abdominal Pressure on the Esophagogastric Junction: A Systematic Review.

With the advent of high-resolution esophageal manometry, it is recognized that the antireflux barrier receives a contribution from both the lower esophageal sphincter (intrinsic sphincter) and the muscle of the crural diaphragm (extrinsic sphincter). Further, an increased intra-abdominal pressure is a major force responsible for an adaptive response of a competent sphincter or the disruption of the esophagogastric junction resulting in gastroesophageal reflux, especially in the presence of a hiatal hernia. This review describes how the pressure dynamics in the lower esophageal sphincter were discovered and measured over time and how this has influenced the development of antireflux surgery.

Propensity score-matched comparison between open and minimal invasive hybrid esophagectomy for esophageal adenocarcinoma.

BACKGROUND: This study compared the outcome between patients who had an open and those who had a hybrid esophagectomy for T1 or T3 esophageal adenocarcinoma (eAC). No clear data are available concerning this question based on T-category. METHODS: Two groups of patients with esophagectomy and high intrathoracic esophagogastrostomy for eAC were analyzed: hybrid (laparoscopy + right thoracotomy) (n = 835) and open (laparotomy + right thoracotomy) (n = 188). Outcome criteria were 30- and 90-day mortality, R0-resection rate (R0), number of resected lymph nodes (rLNs), and 5-year survival rate (5y-SR). For each type of surgery, three patient groups were analyzed: pT1-carcinoma (group-1), cT3Nx and neoadjuvant chemoradiation (group-2), and pT3N0-3 without neoadjuvant therapy (group-3). The comparison was based on a propensity score matching in relation of 1:2 for open versus hybrid. RESULTS: In group-1 (38 open vs 76 hybrid) R0-resection (100%), 30-day mortality (0%), 90-day mortality (2.6% vs 0%), and rLNs (median 29.5 vs 28.5) were not significantly different. The pN0-rate was 76% in the open and 92% in the hybrid group (p = 0.036). Accordingly, the 5y-SR was 69% and 87% (p = 0.016), but the prognosis of the subgroups pT1pN0 or pT1pN+ was not significantly different between open or hybrid. In group-2 (68 open vs 135 hybrid) R0-resection (97%), 30-day (0% vs 0.7%) and 90-day (4%) mortality, rLNs (28.5 vs 26), and 5y-SR (36% vs 41%) were not significantly different. In group-3 (37 open vs 75 hybrid) R0, postoperative mortality, rLNs, and 5y-SR were not significantly different. CONCLUSION: In a propensity score-matched comparison of patients with an open or hybrid esophagectomy for esophageal adenocarcinoma the quality of oncologic resection, postoperative mortality and prognosis are not different.

Rat Reflux Model of Esophageal Cancer and Its Implication in Human Disease.

OBJECTIVES: The epidemiologic shift in esophageal cancer from squamous cell carcinoma to esophageal adenocarcinoma coincided with popularization of proton pump inhibitors and has focused attention on gastroesophageal reflux disease as a causative factor in this shift. The aim of this study is to review the literature on the rat reflux model in an effort to elucidate this phenomenon. METHODS: An extensive online literature review (PubMed) was carried out to identify all seminal contributions to the study of esophageal adenocarcinoma using the rat reflux model. RESULTS: The rat reflux model is a validated reproducible model for the development of Barrett's esophagus and esophageal adenocarcinoma. Esophageal reflux of an admixture of gastric acid and duodenal juice induces Barrett's esophagus followed by adenocarcinoma. A high-pH environment created by surgical gastrectomy or proton pump inhibitor therapy in combination with a high-fat diet seems to potentiate the development of Barrett's esophagus and adenocarcinoma. Early surgical intervention to prevent reflux reduces the progression toward esophageal adenocarcinoma. Anti-inflammatory, antioxidant, and nitrate-trapping agents reduce the incidence of tumorigenesis. CONCLUSIONS: As in the rat so also in humans, reflux of an admixture of gastric acid and duodenal juice in a high-pH environment induces the development of Barrett's esophagus followed by esophageal adenocarcinoma. This has led to the hypothesis that to prevent Barrett's esophagus and subsequent esophageal adenocarcinoma in humans, the reflux of an admixture of acid and bile must be controlled before the development of Barrett's esophagus by methods other than acid-suppression therapy.

The University of Chicago contribution to the treatment of gastroesophageal reflux disease and its complications: a tribute to David B. Skinner 1935-2003.

OBJECTIVE: To highlight the contributions from the University of Chicago under the leadership of Dr David B. Skinner to the understanding of gastroesophageal reflux disease (GERD) and its complications. BACKGROUND: The invention of the esophagoscope confirmed that GERD was a premorbid condition. The medical world was divided between those who believed in a morphological lower esophageal sphincter (LES) and those who did not. Those who did not believe attempted to rearrange the anatomy of the foregut organs to stop reflux with minimal success. The discovery of the LES focused attention on the sphincter as the main deterrent to reflux and the hope that measurement of a low LES pressure would mark the presence of GERD. This turned out not to be so. In July 1973, with this history of confusion, Dr Skinner at the age of 36 assumed the chair of surgery at the University of Chicago. METHODS: The publications of the University of Chicago's esophageal group were collected from private and public (PubMed) databases, reviewed, and seminal contributions selected. RESULTS: Twenty-four-hour esophageal pH monitoring led to the understanding of the LES, its contribution to GERD, and the complication of Barrett's esophagus. The relationship of Barrett's to adenocarcinoma was clarified. The rising incidence of esophageal adenocarcinoma led to contributions in the staging of esophageal cancer and its treatment with an en bloc resection. CONCLUSIONS: Ten years after the death of Dr Skinner, we can appreciate the monumental contributions to benign and malignant esophageal disease under his leadership.

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.

Laparoscopic wedge fundectomy for collis gastroplasty creation in patients with a foreshortened esophagus.

OBJECTIVE: To assess the outcome of a laparoscopic wedge-fundectomy Collis gastroplasty for a short esophagus during fundoplication and hiatal hernia repair. BACKGROUND: The Collis gastroplasty provides a surgical solution for a foreshortened esophagus but has been associated with postoperative dysphagia and esophagitis. METHODS: We identified 150 patients who underwent a Collis gastroplasty from 1998 to 2012, and of these, 85 patients underwent laparoscopic procedures using the wedge-fundectomy technique. RESULTS: The median age of the 85 patients (42 men/43 women) was 66 years (range, 37-84 years). A Nissen fundoplication was added to the Collis gastroplasty in 56 patients (66%) and a Toupet fundoplication in 29 patients. No patient had a staple line leak or abscess, and the median hospital stay was 3.5 days (interquartile range, 3-4.5 days). At a median follow-up of 12 months, 93% of patients were free of heartburn. Dysphagia was significantly less common after surgery (preoperative: 58% vs postoperative: 16%; P < 0.0001). New-onset dysphagia developed in only 2 patients. An upper endoscopy was performed in 54 patients at a median of 6 months after surgery, and erosions above the fundoplication were seen in 6 patients (11%). A small (1-2 cm) recurrent hernia was seen in 2 patients (2.4%). CONCLUSIONS: The laparoscopic wedge-fundectomy Collis gastroplasty can be performed safely and is associated with a low prevalence of new-onset dysphagia and esophagitis. The addition of a Collis gastroplasty to an antireflux operation is an effective strategy in patients with short esophagus, and its more liberal use is encouraged.

Insights gained from symptom evaluation of esophageal motility disorders: a review of 4,215 patients.

BACKGROUND/AIMS: Achalasia (Ach), diffuse esophageal spasm (DES), nutcracker esophagus (NE), and nonspecific motility disorder (NSMD) are described primary esophageal body motility disorders; however, their clinical symptom correlation is poorly understood. The aim of this study is to examine the association between a patient's presenting symptoms and their manometric diagnosis. METHODS: Manometric findings and reported symptoms of all patients undergoing esophageal manometry at the Creighton University Medical Center were prospectively entered in a database. Twenty-four-year data from 1984 through 2008 were accessed and analyzed. RESULTS: Of the 4,215 patients, 130 (3.1%) had Ach, 192 (4.6%) had DES, 290 (6.9%) had NE, 508 (12.1%) had NSMD, and 3,095 (73.4%) had normal esophageal body motility. There was significant symptom overlap between the groups. Ach and DES had a similar symptom distribution, with dysphagia being the predominant symptom. Patients with NE, normal body motility, and NSMD presented predominantly with reflux symptoms. There was an increasing prevalence of esophageal dysmotility (DES and NSMD) with age, and women were found to be more likely to have NE than men. CONCLUSION: In an individual, reported symptoms do not correlate with their manometric diagnosis in a predictable fashion, and a thorough physiological assessment should be obtained to understand and diagnose the disease process. Esophageal motility deteriorates with age.

The LINX® reflux management system: confirmed safety and efficacy now at 4 years.

BACKGROUND: Sphincter augmentation with the LINX® Reflux Management System is a surgical option for patients with chronic gastroesophageal disease (GERD) and an inadequate response to proton pump inhibitors (PPIs). Clinical experience with sphincter augmentation is now available out to 4 years. METHODS: In a multicenter, prospective, single-arm study, 44 patients underwent a laparoscopic surgical procedure for placement of the LINX System around the gastroesophageal junction (GEJ). Each patient's baseline GERD status served as the control for evaluations post implant. Long-term efficacy measures included esophageal acid exposure, GERD quality-of-life measures, and use of PPIs. Adverse events and long-term complications were closely monitored. RESULTS: For esophageal acid exposure, the mean total % time pH < 4 was reduced from 11.9 % at baseline to 3.8 % at 3 years (p < 0.001), with 80 % (18/20) of patients achieving pH normalization (≤ 5.3 %). At ≥ 4 years, 100 % (23/23) of the patients had improved quality-of-life measures for GERD, and 80 % (20/25) had complete cessation of the use of PPIs. There have been no reports of death or long-term device-related complications such as migration or erosion. CONCLUSIONS: Sphincter augmentation with the LINX Reflux Management System provided long-term clinical benefits with no safety issues, as demonstrated by reduced esophageal acid exposure, improved GERD-related quality of life, and cessation of dependence on PPIs, with minimal side effects and no safety issues. Patients with inadequate symptom control with acid suppression therapy may benefit from treatment with sphincter augmentation.

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.

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.

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.

Validation of a rodent model of Barrett's esophagus using quantitative gene expression profiling.

BACKGROUND: A rodent model of gastroduodenal-esophageal reflux can result in replacement of squamous esophageal mucosa with intestinal-type columnar mucosa and carcinoma. The validity of this model is debated, as it is unproven whether this mucosa is intestinal metaplasia due to reflux or represents migration of adjacent jejunal mucosa above the anastomosis. The aim of this study was to evaluate the esophageal intestinal-type mucosa in these animals by measuring expression of trefoil factor genes (TFF-1, -2, -3) and comparing it with adjacent jejunum in order to determine its etiology. METHODS: Twenty-five rats underwent esophagojejunostomy at the ligament of Treitz to induce reflux of gastric and duodenal contents. The animals were sacrificed at 16 weeks (n = 14) and 30 weeks (n = 11). After sacrifice, the distal esophagus, jejunum, and colon were obtained. RNA was isolated, reverse transcribed, and messenger RNA (mRNA) expression of TFF-1, -2, and -3 was measured with real-time polymerase chain reaction (PCR). Linear discriminant analysis classified samples based on gene expression. RESULTS: Esophageal intestinal-type mucosa was present at sacrifice in 18 animals. Compared to jejunum, the expression of TFF-1 and TFF-2 mRNA in the intestinal mucosa of the distal esophagus was increased (p = 0.0007 and p < 0.0001, respectively). Expression of TFF-3 was also increased in esophageal intestinal mucosa compared with jejunum (p = 0.0002), but there was significant overlap in expression between these tissues for this gene. Linear discriminant analysis misclassified esophageal intestinal-type mucosa as jejunum in only one case. In no cases was jejunum misclassified as esophageal intestinal-type mucosa. CONCLUSION: The gene expression profile of esophageal intestinal-type mucosa following surgically induced reflux in a rodent model indicates that this represents intestinal metaplasia, not proximal migration of jejunum. This validates this model for studying the pathogenesis of Barrett's esophagus. Use of this model has potential for assessment of the impact of various therapies on the natural history of reflux disease.