Search

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. 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). 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. 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.

Summary 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.

Protracted dysphagia and bloating are potential troublesome side effects following Nissen fundoplication. The aim of this study was to evaluate the effects of conversion from Nissen to Toupet on dysphagia and bloating. The study used a retrospective chart review of all patients who had undergone conversion from Nissen to Toupet between 2001 and 2014. Endpoints were to determine the effect of conversion on dysphagia, bloating, and reflux control. Twenty-five patients underwent conversion at a median of 3.7 years (1.4–10.5) after initial fundoplication. Indications were dysphagia in 19 (76%) and bloating syndrome in 6 (24%) patients. The median operative time was 104 min (86–146). There were no serious complications or mortality. Median follow-up was 27 months (0.8–130). Dysphagia was relieved in 16 (84%) and bloating in all 6 patients. Two patients developed reflux requiring a redo-Nissen. Two patients had persistent dysphagia and required endoscopic dilation. The GERD-HRQL post-conversion showed a median score of 5 (3–13). Conversion relieved dysphagia in 84% and bloating in 100%. Significant recurrence of GERD was rare. Given the absence of serious complications, conversion should be considered in patients with severe bloating or dysphagia.

SUMMARY Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett's esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291

ObjectivesSurveillance endoscopy has been recommended for patients with Barrett's esophagus; however, recent studies have questioned the importance owing to the new, lower, estimates of the rate of progression of Barrett's esophagus to cancer. The aim of the present study was to compare the tumor stage, survival, and frequency of esophageal preservation in patients who presented with progression of Barrett's esophagus within a surveillance program versus those who presented with prevalent disease.MethodsA retrospective chart review was performed of all patients treated for high-grade dysplasia or esophageal adenocarcinoma from 2005 to 2010. The surveillance group included patients who had had at least 1 endoscopy and biopsy confirming intestinal metaplasia (with or without low-grade dysplasia) 6 months or more before the endoscopy showing progression.ResultsA total of 224 patients were included in the present study, 36 in the surveillance group and 188 in the prevalence group. The surveillance patients had significantly earlier stage tumors (P

Practitioners have noted a striking increase in the number of young patients under the age of 40 years old who develop esophageal adenocarcinoma. The aim of this study was to characterize the presentation, pathology and therapeutic outcome of these young patients. The records of patients who presented to the Foregut Surgical Service at the University of Southern California with esophageal adenocarcinoma between 2000 and 2007 were retrospectively reviewed. The presentation, tumor stage and histology, therapy and outcome of the patients under the age of 40 were compared to those ≥40. Of the 374 patients reviewed, 20 (5 %) were under the age of 40. There were two patients in their second and 18 in their third decade of life. The youngest patient was 25 years old. A history of gastroesophageal reflux disease or Barrett’s esophagus was less common in patients

SUMMARY The necessity of pyloroplasty after esophagectomy and gastric pull-up is debated. Disadvantages of a standard pyloroplasty include the potential for leak, shortening of the length of the graft, and complexity when done during a minimally invasive procedure. The aim of this study is to report our experience with a novel internal pyloroplasty technique using a circular stapler (CS pyloroplasty), which is applicable for both laparoscopic and open esophagectomy. The records of all patients who underwent an esophagectomy with gastric pull-up and pyloroplasty between 2002 and 2007 were reviewed. The CS pyloroplasty was performed through a lesser curve gastrotomy with a 21-mm CS, while the standard pyloroplasty entailed a longitudinal full thickness incision through the pylorus with mucosal closure in the same direction and a Graham patch. A CS pyloroplasty was performed in 144 and a standard pyloroplasty in 133 patients. The median patient age was 66 years, and the median follow-up was 17 months, and was similar for both types of pyloroplasty. Routine postoperative videoesophagram was significantly more likely to show a delay in contrast transit through the pylorus after standard pyloroplasty (16% standard vs. 8% CS pyloroplasty, P= 0.03). Significantly more patients had postoperative endoscopy after standard pyloroplasty (40% standard vs. 24% CS pyloroplasty, P= 0.004), but the frequency of pyloric dilatation was similar. There were no leaks with either technique. A circular stapled pyloroplasty is as efficacious as a standard pyloroplasty after esophagectomy with gastric pull-up. Potential advantages include the ease and simplicity of the procedure along with virtually no risk of a leak and no graft shortening. The technique is amenable to both open and minimally invasive procedures.

The etiology and significance of cardia intestinal metaplasia (CIM) is disputed. CIM may represent a form of Barrett's esophagus due to reflux or could reflect generalized gastric intestinal metaplasia due to Helicobacter pylori. The aim of this study was to utilize gene expression data to compare CIM to Barrett's and gastric intestinal metaplasia. Endoscopic biopsies were classified by endoscopic and histologic criteria as CIM (n= 33), Barrett's (n= 25), or gastric intestinal metaplasia of the antrum or body (n= 18). The squamocolumnar and gastroesophageal junctions were aligned in CIM patients and patients with diffuse gastric intestinal metaplasia were excluded. H. pylori was tested for in the biopsies of all patients. After laser-capture microdissection, quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the mRNA expression of a panel of nine genes that has been shown to differentiate Barrett's from other foregut mucosa. Cluster analysis with linear discriminant analysis of the expression data was used to classify each sample into groups based solely on similarity of gene expression. Cluster analysis was performed for three groups (CIM vs. Barrett's vs. gastric intestinal metaplasia) and two groups (CIM + Barrett's vs. gastric intestinal metaplasia). There was no difference in H. pylori infection among groups (P= 0.66). Clustering into three groups resulted in frequent misclassification between CIM and Barrett's while misclassification of gastric intestinal metaplasia was uncommon. The CIM and Barrett's groups were then combined for two group clustering and linear discriminant analysis correctly predicted 95% of CIM and Barrett's samples and 83% of gastric intestinal metaplasia samples based on gene expression alone. In conclusion, the gene expression profiles of CIM and Barrett's esophagus were similar in 95% of biopsies and differed significantly from that of gastric intestinal metaplasia. The indistinguishable gene expression profile of CIM and BE suggests that they may share a common etiology in the majority of patients with a similar biology, and calls into question the perception that CIM is an innocuous process.

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.

Because of changes in life expectancy, there is an increasing number of elderly patients with esophageal cancer. The aim of this study was to assess the outcome of esophagectomy for cancer in patients 80 years or older. A retrospective review was performed of the records of all patients who underwent esophagectomy for cancer from 1992 to 2007. A cardiac and pulmonary evaluation was obtained on an individual basis in the younger patients and in all octogenarians. Among 560 patients with esophagectomy for cancer, 47 patients (8%) were octogenarians. The median age of the younger group (n= 513) was 63 years (interquartile range 56-71). Octogenarians had significantly more stage III disease (49% vs 31%, P= 0.02) but received less neoadjuvant therapy than younger patients (2% vs 21%, P= 0.0004). In octogenarians, the transhiatal resection was more common than in the younger group (79% vs 36%, P < 0.0001). Weight loss prior to surgery was similar in both groups, but body mass index was significantly lower in octogenarians (25 vs 28 kg/m(2) , P= 0.0002). Major complications occurred in 26% in octogenarians and 31% in the younger group (P= 0.51). Hospital mortality was similar (9% for octogenarians vs 4% in the younger group, P= 0.13). The median postoperative hospital stay was similar at 16 days (P= 0.69). There was no difference in cancer-related survival (median survival 48.9 vs 59.3 months, P= 0.31 log-rank test). Esophagectomy can be performed safely in carefully selected octogenarians with good cardiac and pulmonary function. Patients should not be denied an esophagectomy based only on their age.

Cervical esophageal pH monitoring using a pH threshold of4 in the diagnosis of laryngopharyngeal reflux (LPR) is disappointing. We hypothesized that failure to maintain adequate alkalization instead of acidification of the cervical esophagus may be a better indicator of cervical esophageal exposure to gastric juice. The aim of this study was to define normal values for the percent time the cervical esophagus is exposed to a pH ≥7 and to use the inability to maintain this as an indicator for diagnosis of LPR.Fifty-nine asymptomatic volunteers had a complete foregut evaluation including pH monitoring of the cervical esophagus. Cervical esophageal exposure to a pH4 was calculated, and the records were reanalyzed using the threshold pH ≥7. The sensitivity of these two pH thresholds was compared in a group of 51 patients with LPR symptoms that were completely relieved after an antireflux operation.Compared to normal subjects, patients with LPR were less able to maintain an alkaline pH in the cervical esophagus, as expressed by a lower median percent time pH ≥ 7 (10.4 vs. 38.2, p0.0001). In normal subjects, the fifth percentile value for percent time pH ≥ 7 in the cervical esophagus was 19.6%. In 84% of the LPR patients (43/51), the percent time pH ≥ 7 were below the threshold of 19.6%. In contrast, 69% (35/51) had an abnormal test when the pH records were analyzed using the percent time pH4. Of the 16 patients with a false negative test using pH 4, 11 (69%) were identified as having an abnormal study when the threshold of pH ≥ 7 was used.Normal subjects should have a pH ≥7 in cervical esophagus for at least 19.6% of the monitored period. Failure to maintain this alkaline environment is a more sensitive indicator in the diagnosis of the LPR and identifies two thirds of the patients with a false negative test using pH4.

Factors associated with the risk of progression of Barrett’s esophagus remain unclear, and the impact of therapy on this risk remains uncertain. The aim of this study was to assess patients followed long-term after anti-reflux surgery for Barrett’s esophagus. A retrospective review was performed of all patients with Barrett’s who underwent anti-reflux surgery from 1989 to 2009 and had ≥5 years of follow-up. There were 303 patients and 75 had follow-up ≥5 years. Median follow-up time for the 75 patients was 8.9 years (range 5–18). Regression was seen in 31%. Progression occurred in 8%, and these patients were significantly more likely to have a failed fundoplication (67% vs. 16%, p = 0.0129). The rate of progression from non-dysplastic Barrett’s to high-grade dysplasia or cancer was 0.8% per patient year, and was seven times higher in patients with a failed fundoplication. Compared to the accepted rate of progression of non-dysplastic Barrett’s to high-grade dysplasia or cancer of 1.0% per patient year, anti-reflux surgery reduces this rate during long-term follow-up. The rate of progression was significantly lower in patients with an intact compared to a disrupted fundoplication, further suggesting that anti-reflux surgery can alter the natural history of Barrett’s esophagus.

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.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 pH4) was also measured before and after distension.Progressive gastric distension with air resulted in progressive shortening of LES (R = 0.89, P0.0001). 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).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.

Patients with respiratory and laryngeal symptoms are commonly referred for evaluation of reflux disease as a potential cause. Dual-probe pH monitoring is often performed, although data on normal acid exposure in the proximal esophagus are limited because of the small number of normal subjects and inconsistent placement of the proximal pH sensor in relation to the upper esophageal sphincter. We measured proximal esophageal acid exposure using dual-probe pH and calculated a composite pH score in a large number of asymptomatic volunteers to better define normal values.Eighty-one normal subjects free of reflux, laryngeal, or respiratory symptoms were recruited. All had video esophagraphy to exclude hiatal hernia. Esophageal pH monitoring was performed using 1 of 3 different dual-probe catheters with sensors spaced 10, 15, or 18 cm apart. The standard components of esophageal acid exposure were measured, excluding meal periods. A composite pH score for the proximal esophagus was calculated using these components.The final study population consisted of 59 (49% male) subjects, with a median age of 27 years. All had normal distal esophageal acid exposure and no hiatal hernia. The 95(th) percentile values for the percent time the pH was4 for the total, upright, and supine periods were 0.9%, 1.2%, and 0.4%, respectively. The 95(th) percentile for the number of reflux episodes was 24 and for the calculated proximal esophageal composite pH score was 16.4.In a large population of normal subjects, we have defined the normal values and calculated a composite pH score for proximal esophageal acid exposure. The total percent time pH4 was similar to previously published normal values, but the number of reflux episodes was greater.

Patients with gastroesophageal reflux disease (GERD) often complain of dysphagia and are frequently found to have intraepithelial eosinophils on esophageal biopsy. The aim of this study was to investigate the relationship between dysphagia and the number of intraepithelial eosinophils in patients with GERD. 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. 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). 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.

SUMMARY. It is proposed that epithelial changes induced by gastroesophageal reflux disease are related to the pH environment of the esophageal lumen. We hypothesized that the various types of esophageal epithelium are associated with specific pH environments that induce their formation. The aim of this study was to compare the luminal pH environment to the histology of the distal esophageal epithelium in patients with gastroesophageal reflux disease. A total of 197 symptomatic patients with increased esophageal acid exposure on 24-hour pH monitoring were grouped according to the histology based on biopsies from the distal esophagus: 17 with squamous epithelium, 126 with cardiac epithelium (CE), and 54 with Barrett’s epithelium (BE). All were free of Helicobacter pylori infection and monitored off acid suppression therapy. Acid exposure was expressed as the percent of time the luminal pH was at intervals of 0‐1, 1‐2, 2‐3, 3‐4, 4‐5, 5‐6, and 6‐7 over a 24-hour period. Patients with BE spent significantly more time at pH intervals 2‐3, 3‐4, and 4‐5 than those with CE. This pattern switched at pH interval 5‐6, where patients with cardiac mucosa spent more time than those with BE. Patients with squamous and CE had similar pH exposure at all intervals. Patients with BE have significantly longer exposure time at the pH interval of 2 to 5 compared to those with cardiac and squamous epithelium. This suggests that the exposure of stem cells to a luminal pH between 2 and 5 may trigger the differentiation of CE into intestinalized CE.

High-resolution manometry (HRM) is faster and easier to perform than conventional water perfused manometry. There is general acceptance of its usefulness in evaluating upper esophageal sphincter and esophageal body. There has been less emphasis on the use of HRM to evaluate the lower esophageal sphincter (LES) resting pressure and length, both factors important in LES barrier function. The aim of this study was to compare the resting characteristics of the LES determined by HRM and conventional manometry in the same patients. We performed both HRM and conventional manometry including a slow motorized pull-through technique in 55 patients with foregut symptoms. The characteristics of the LES analyzed were: resting pressure, total length, and abdominal length. Four available modes of HRM analysis were used to assess resting characteristics of the LES: spatiotemporal mode using both abrupt color change and isobaric contour, line tracing, and pressure profile. The values obtained from these four HRM modes were then compared to the conventional manometry measurements. High-resolution manometry and conventional manometry did not differ in their measurement of LES resting pressure. LES overall and abdominal length were consistently overestimated by HRM. A variability up to 4 cm in overall length was observed and was greatest in patients with hiatal hernia (1.8 vs. 0.9 cm, p = 0.027). The current construction of the catheter and software analysis used in high-resolution manometry do not allow precise measurement of LES length. Errors in the identification of the upper border of the sphincter may compromise accurate positioning of a pH probe.

A 75-year-old male with a long history of gastroesophageal reflux symptoms developed adenocarcinoma proximally within a long segment of Barrett's esophagus. He was taken for esophagectomy and gastric pull-up, but intraoperatively, he was found to have a marginal blood supply in the gastric tube. A temporary left-sided esophagostomy was created with the gastric tube sutured to the left sternocleidomastoid muscle in the neck. Pathology showed an intramucosal adenocarcinoma, limited to the muscularis mucosa with surrounding high-grade dysplasia and intestinal metaplasia. The proximal esophageal margin showed no tumor cells, but there was low-grade dysplasia within Barrett's esophagus. He was reconstructed after several months, and 2 years after reconstruction, the patient noticed a nodule at the former esophagostomy site. Biopsy revealed an implant metastasis of esophageal adenocarcinoma. Here, we review the literature and discuss the possible etiology.

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

Identifying gastroesophageal reflux disease as the cause of respiratory and laryngeal complaints is difficult and depends largely on the measurements of increased acid exposure in the upper esophagus or ideally the pharynx. The current method of measuring pharyngeal pH environment is inaccurate and problematic due to artifacts. A newly designed pharyngeal pH probe to avoid these artifacts has been introduced. The aim of this study was to use this probe to measure the pharyngeal pH environment in normal subjects and establish pH thresholds to identify abnormality. Asymptomatic volunteers were studied to define the normal pharyngeal pH environment. All subjects underwent esophagram, esophageal manometry, upper and lower esophageal pH monitoring with a dual-channel pH catheter and pharyngeal pH monitoring with the new probe. Analyses were performed at 0.5 pH intervals between pH 4 and 6.5 to identify the best discriminating pH threshold and calculate a composite pH score to identify an abnormal pH environment. The study population consisted of 55 normal subjects. The pattern of pharyngeal pH environment was significantly different in the upright and supine periods and required different thresholds. The calculated discriminatory pH threshold was 5.5 for upright and 5.0 for supine periods. The 95th percentile values for the composite score were 9.4 for upright and 6.8 for supine. A new pharyngeal pH probe which detects aerosolized and liquid acid overcomes the artifacts that occur in measuring pharyngeal pH with existing catheters. Discriminating pH thresholds were selected and normal values defined to identify patients with an abnormal pharyngeal pH environment.

Introduction Obesity and gastroesophageal reflux disease (GERD) are increasingly important health problems. Previous studies of the relationship between obesity and GERD focus on indirect manifestations of GERD. Little is known about the association between obesity and objectively measured esophageal acid exposure. The aim of this study is to quantify the relationship between body mass index (BMI) and 24-h esophageal pH measurements and the status of the lower esophageal sphincter (LES) in patients with reflux symptoms. Methods Data of 1,659 patients (50% male, mean age 51 ± 14) referred for assessment of GERD symptoms between 1998 and 2008 were analyzed. These subjects underwent 24-h pH monitoring off medication and esophageal manometry. The relationship of BMI to 24-h esophageal pH measurements and LES status was studied using linear regression and multiple regression analysis. The difference of each acid exposure component was also assessed among four BMI subgroups (underweight, normal weight, overweight, and obese) using analysis of variance and covariance. Results Increasing BMI was positively correlated with increasing esophageal acid exposure (adjusted R2 = 0.13 for the composite pH score). The prevalence of a defective LES was higher in patients with higher BMI (p

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. 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. 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

High Intraepithelial Eosinophil Counts in Esophageal Squamous Epithelium Are Not Specific for Eosinophilic Esophagitis in Adults

The molecular pathogenesis of Barrett's esophagus is poorly understood. Evidence suggests that at a phenotypic level, the metaplastic process begins with the transformation of squamous epithelium in the distal esophagus to cardiac mucosa, which subsequently becomes intestinalized. The homeobox gene Cdx-2 has been shown to be an important transcriptional regulator of embryonic differentiation and maintenance of adult intestinal type epithelium. We hypothesized that Cdx-2 gene expression levels increase with the phenotypic transformation of normal squamous mucosa to the intestinalized columnar mucosa of Barrett's esophagus. Endoscopic biopsies were obtained at the gastroesophageal junction in patients with symptoms of gastroesophageal reflux disease and classified according to histology: normal squamous mucosa (n = 62), cardiac mucosa (n = 19), oxynto-cardiac mucosa (n = 14), and intestinal metaplasia (n = 15). Duodenal biopsies (n = 26) served as the columnar control. After laser capture microdissection and RNA isolation, gene expression levels of Cdx-2 were measured in each tissue type by quantitative reverse transcription polymerase chain reaction. Consistent with its known function, Cdx-2 gene expression levels were highest in duodenal mucosa and nearly absent in squamous epithelium. There was a stepwise increase in Cdx-2 gene expression from cardiac to Barrett's epithelium (P < 0.001). Expression levels of Cdx-2 in cardiac and oxynto-cardiac mucosa were 40-70 times higher and Barrett's mucosa 400 times higher than that found in squamous epithelium. Relative expression of the homeobox gene Cdx-2, known to induce differentiation of intestinal type epithelium, increases in a stepwise fashion during the phenotypic transformation of distal esophageal squamous mucosa to cardiac columnar mucosa and to the intestinalized columnar mucosa of Barrett's esophagus. Therefore, Cdx-2 may be a potential biomarker to detect the early transition to Barrett's esophagus.

Gastroesophageal reflux symptoms occur with similar frequency in males and females, yet Barrett's esophagus is less common in females. The reason for this disparity is unknown. The aim of this study was to determine the factors related to Barrett's in females.The records of 796 patients (462 male, 334 female) evaluated from 1990 to 2000 for symptoms of reflux were retrospectively reviewed. Physiologic abnormalities based on results of endoscopic, motility, pH, and Bilitec testing were identified, and factors related to the presence of Barrett's were determined using univariate and multivariate analysis.Females with reflux symptoms were significantly less likely to have a positive 24-h pH test, a defective lower esophageal sphincter, or a hiatal hernia than males with reflux symptoms. Further, females with reflux on the basis of an abnormal 24-h pH test had significantly less esophageal acid exposure than males with reflux. In contrast, esophageal exposure to refluxed acid and bilirubin was similar in females (n = 50) and males (n = 136) with Barrett's. On multivariable analysis increased esophageal bilirubin exposure was the only significant factor associated with the presence of Barrett's in male and female patients with reflux disease.Females with reflux symptoms have less esophageal acid exposure on average than males. However, females and males with Barrett's have a similar severity of reflux, and the female gender does not protect against the development of Barrett's in the setting of advanced reflux disease. Esophageal bilirubin exposure is the major risk factor for the presence of Barrett's in patients with reflux disease.

Endoscopic ultrasound (EUS) is an essential component of preoperative staging for esophageal cancer and is used to determine which patients should proceed to primary surgical resection or receive neoadjuvant therapy prior to surgery. However, when the EUS scope cannot traverse a tumor, the role of pre-dilatation is controversial due to the risk of perforation. A retrospective review was conducted of all patients with esophageal tumor stenosis that could not accommodate the EUS scope who then proceeded with primary esophagectomy. The pathology results were classified based on the revised seventh edition American Joint Committee on Cancer staging system. A total of 27 patients met inclusion criteria. The majority of tumors were T3 (24/27, 89 %). There were no stage I tumors, 15 % (4/27) were stage II, 81 % (22/27) were stage III, and 4 % (1/27) were stage IV due to a resected solitary lung metastasis. Tumors that cannot be assessed with an EUS scope due to tumor stenosis will have locally advanced disease in the majority of cases. In these situations, pre-dilatation of the tumor with EUS staging should be omitted when considering the risk of potential esophageal perforation and the patients should be referred for neoadjuvant therapy.

Proton pump inhibitors are the mainstay of medical management in gastroesophageal reflux disease. Although they provide relief from most symptoms, reflux may persist. We hypothesize that omeprazole does not reduce the total amount of gastroesophageal reflux but simply alters its pH characteristics. Six asymptomatic volunteers had combined 24-hour impedance pH monitoring before and after 7 days of omeprazole (20 mg BID). Multichannel intraluminal impedance was used to identify reflux episodes, which were classified as acid (pH 4 but decrease > 1 pH unit) and nonacid (pH > 4 and decrease < 1 pH unit) by pH measurements 5 cm above the lower esophageal sphincter (LES). A gastric pH sensor located 10 cm below the LES was used to verify the action of omeprazole. Impedance detected a total of 116 reflux episodes before and 96 episodes after omeprazole treatment. The median number of reflux episodes (18 versus 16, P = 0.4), median duration of reflux episodes (4.7 versus 3.6 minutes, P = 0.5), and total duration of reflux episodes (27.2 versus 42.4 minutes, P = 0.5) per subject were similar before and after omeprazole. Acid reflux episodes were reduced from 63% before to 2.1% after omeprazole (P < 0.0001), whereas nonacid reflux episodes increased (15% to 76%, P < 0.0001). Weak acid reflux episodes did not change (22.4% to 21.8%, P = 1.0). The proportion of reflux episodes greater than pH 4 increased from 37% to 98% (P < 0.0001). In normal subjects, omeprazole treatment does not affect the number of reflux episodes or their duration; rather it converts acid reflux to less acid reflux, thus exposing esophagus to altered gastric juice. These observations may explain the persistence of symptoms and emergence of mucosal injury white on proton pump inhibitor therapy.

The objective of this study was to assess the course over time of the Barrett's metaplasia-dysplasia-carcinoma sequence. The method used was a retrospective analysis of the medical records of a patient series with a median follow-up of 25 months. The study was undertaken in a university hospital foregut laboratory. The progress of seven patients was followed through the sequence of Barrett's esophagus, low-grade dysplasia and high-grade dysplasia to cancer. They all underwent subsequent esophagectomy and were found to have intramucosal adenocarcinoma. The main outcome measure was the time from the first diagnosis of intestinal metaplasia to the development of low-grade dysplasia, high-grade dysplasia and adenocarcinoma. Low-grade dysplasia developed in a median of 24 months, high-grade dysplasia after a median of 33 months and cancer after 36 months. All patients underwent esophagectomy with reconstruction and no patient has had a recurrence at a median follow-up of 25 months (range 10-204 months). Patients on Barrett's surveillance who develop early esophageal adenocarcinoma did so within approximately 3 years after the diagnosis of non-dysplastic Barrett's esophagus.

Background Reports of esophageal anastomotic complications often involve more gastric than colonic reconstructions and are incomplete because of fragmented followup by physicians unfamiliar with the surgical procedure. Study design Three hundred ninety-three consecutive esophagectomy patients had prevalence and risk factors determined for graft ischemia and anastomotic leak; 363 of these patients followed for more than 1 month (median 15 months) had prevalence and risk factors determined for anastomotic stricture. Results Conduit ischemia occurred in 36 (9.2%) and anastomotic leak in 43 patients (10.9%). Risk factor for ischemia was comorbid conditions requiring therapy (Odds ratio [OR]: 2.2 [95% CI 1.1–4.3]), and for leak were ischemia (OR: 5.5 [95% CI 2.5–12.1]), neoadjuvant therapy (OR: 2.2 [95% CI 1.1–4.5]), and comorbid conditions (OR: 2.1 [95% CI 1.1–3.9]). A stricture developed in 80 patients (22.0%). Risk factors were ischemia (OR: 4.4 [95% CI 2.0–9.6]), anastomotic leak (OR: 3.8 [95% CI 1.9–7.6]), and increasing preoperative weight (p = 0.022). The prevalence of ischemia was similar after gastric (10.4%) versus colonic (7.4%) reconstruction; leak and stricture were more common (14.3% versus 6.1%, p=0.013, 31.3% versus 8.7%, p Conclusions After esophagectomy 10% of patients will develop conduit ischemia or an anastomotic leak and 22% will develop anastomotic stricture. Anastomotic leak and strictures are more common and the strictures are more severe after gastric pull-up compared with colon interposition. Dilatation is a safe and effective treatment.

Hypertensive lower esophageal sphincter (LES) is an uncommon manometric abnormality found in patients with dysphagia and chest pain, and is sometimes associated with gastroesophageal reflux disease (GERD). Preventing reflux by performing a fundoplication raises concerns about inducing or increasing dysphagia. The role of myotomy in isolated hypertensive LES is also unclear. The aim of this study was to determine the outcome of surgical therapy for isolated hypertensive LES and for hypertensive LES associated with GERD. Sixteen patients (5 males and 11 females), ranging in age from 39 to 89 years, with hypertensive LES (>26 mm Hg; i.e., >95th percentile of our control population) who had surgical therapy between 1996 and 1999 were reviewed. Patients with a diagnosis of achalasia and diffuse esophageal spasm were excluded. All patients had dysphagia or chest pain. Eight of 16 patients had symptoms of GERD, four had a type III hiatal hernia, and four had isolated hypertensive LES pain. Patients with hypertensive LES and GERD or type III hiatal hernia had a Nissen fundoplication, and those with isolated hypertensive LES had a myotomy of the LES with partial fundoplication. Outcome was assessed as follows: excellent if the patient was asymptomatic; good if symptoms were present but no treatment was required; fair if symptoms were present and required treatment; and poor if symptoms were unimproved or worsened. All patients were contacted by telephone for symptom assessment at a median of 3.6 years (range 3 to 6.1 years) after surgery. Patients with hypertensive LES and GERD or type III hiatal hernia had significantly lower LES pressure than those with isolated hypertensive LES (29.9 vs. 47.4 mm Hg; P = 0.013). Dysphagia and chest pain were relieved in all patients at long-term follow up. Outcome was excellent in 10 of 16, good in 3 of 16, and fair in 3 of 16. All patients but one were satisfied with their outcome. Patients with hypertensive LES are a heterogeneous group in regard to symptoms and etiology. Treatment of patients with hypertensive LES should be individualized. A Nissen fundoplication for hypertensive LES with GERD or type III hiatal hernia relieves dysphagia and chest pain suggesting reflux as an etiology. A myotomy with partial fundoplication for isolated hypertensive LES relieves dysphagia and chest pain suggesting a primary sphincter dysfunction.

Background: Intestinal metaplasia occurs in the esophagus as a consequence of gastroesophageal reflux disease and in the stomach secondary to H. pylori infection. The etiology of intestinal metaplasia limited to the gastroesophageal junction or cardia (CIM) is disputed. We hypothesized that CIM has dual etiologies: gastroesophageal reflux in some, H. pylori infection in others, and that cytokeratin immunostaining can help to differentiate between these two etiologies. Methods: We defined CIM as the presence of intestinal metaplasia within cardiac mucosa on biopsy from an endoscopically normal-appearing gastroesophageal junction. Thirty patients with CIM who had multiple biopsy specimens taken from the esophagus, gastroesophageal junction, and stomach were identified. Tissue blocks from biopsy specimens taken at the gastroesophageal junction were sectioned and immunostained for cytokeratins 7 and 20. The cytokeratin 7/20 staining of the CIM in each patient was determined to be either a Barrett's or non-Barrett's pattern. H. pylori infection was assessed by Giemsa staining of antral biopsy specimens. Results: H. pylori infection was present in 16 patients. A Barrett's cytokeratin 7/20 staining pattern in the CIM was present in only 46% of the H. pylori–positive patients, as compared to 86% in the 14 patients with CIM and no H. pylori (p = 0.025). Objective evidence of reflux disease was present in 71% of patients with CIM and no H. pylori, as compared to 31% of patients with H. pylori. Conclusions: The two different patterns of cytokeratin 7/20 staining found in patients with CIM support the concept of dual etiologies for CIM. A Barrett's staining pattern was associated with objective evidence of gastroesophageal reflux and the absence of H. pylori, suggesting that cytokeratin 7/20 immunostaining is useful to determine the likely etiology of CIM.

The purpose of this study was to evaluate the interindividual and intraindividual variability of slow motorized pull-through lower esophageal sphincter (LES) manometry compared to standard station pull-through LES manometry to measure LES overall length, abdominal length, and pressure and to report normal values for the slow motorized pull-through method. The slow motorized pull-through had significantly smaller coefficient of variation, indicating closer agreement between different examiners in analyzing a given tracing. The correlation coefficients for each parameter in normal subjects and symptomatic patients was significantly higher when using slow motorized pull-through for both patients and normal subjects for all three parameters. The 5th percentile of normal values obtained from 41 volunteers for LES overall length, abdominal length, and pressure was 2.7 cm, 1.4 cm, 5.1 mm Hg, respectively. The results indicate that the slow motorized pull-through method is more reproducible than the standard station pull-through method both between different observers and when the same examiner measures the same tracing on two different occasions.

OBJECTIVE: The normal histology at the gastroesophageal junction, and in particular the nature of cardiac mucosa, remains in dispute. Likewise, the relationship of intestinal metaplasia at the gastroesophageal junction (CIM) to Barrett’s and intestinal metaplasia of the stomach (GIM) is unclear. The aim of this study was to assess the immunostaining characteristics of cardiac mucosa and CIM and compare their staining pattern with that of other foregut mucosal types. We hypothesized that the immunostaining patterns of these foregut tissues would provide insight into the nature and etiology of cardiac mucosa and CIM. METHODS: Paraffin-embedded biopsy specimens from 50 patients with normal antral or fundic mucosa, cardiac mucosa, squamous mucosa, CIM, GIM, or Barrett’s were obtained and immunostained with a panel of monoclonal antibodies including those for cytokeratins 7 and 20 (CK7/ CK20) and DAS-1. RESULTS: Biopsies from normal gastric antral and fundic mucosa and squamous esophageal mucosa all showed a non-Barrett’s type CK7/CK20 immunostaining pattern, whereas in 85% of patients, cardiac mucosa had a Barrett’s type CK7/CK20 pattern (p 0.001). A Barrett’s type CK7/ CK20 staining pattern was seen in 100% of Barrett’s, 78% of CIM, and 0% of GIM patients. Likewise, DAS-1 staining was similar in patients with CIM and Barrett’s and significantly different in patients with GIM. CONCLUSIONS: Cytokeratin immunostaining of cardiac mucosa demonstrates significant differences from recognized normal gastric and esophageal mucosa but a similarity to Barrett’s. This suggests that cardiac mucosa, like Barrett’s, may be acquired. Likewise, immunostaining similarities between CIM and Barrett’s biopsies point to the possibility of a reflux etiology for CIM in some patients. (Am J Gastroenterol 2002;97:2514 –2523. © 2002 by Am. Coll. of Gastroenterology)

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. 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. 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. 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.

Objective To assess the long-term outcome of antireflux surgery in patients with Barrett's esophagus. Summary background data The prevalence of Barrett's esophagus is increasing, and its treatment is problematic. Antireflux surgery has the potential to stop reflux and induce a quiescent mucosa. Its long-term outcome, however, has recently been challenged with reports of poor control of reflux and the inability to prevent progression to cancer. Methods The outcome of antireflux surgery was studied in 97 patients with Barrett's esophagus. Follow-up was complete in 88% (85/97) at a median of 5 years. Fifty-nine had long-segment and 26 short-segment Barrett's. Patients with intestinal metaplasia of the cardia were excluded. Fifty patients underwent a laparoscopic procedure, 20 a transthoracic procedure, and 3 abdominal Nissen operations. Nine had a Collis-Belsey procedure and three had other partial wraps. Outcome measures included relief of reflux symptoms (all), patients' perception of the result (all), upper endoscopy and histology (n = 79), and postoperative 24-hour pH monitoring (n = 21). Results At a median follow-up of 5 years, reflux symptoms were absent in 67 of 85 patients (79%). Eighteen (20%) developed recurrent symptoms; four had returned to taking daily acid-suppression medication. Seven patients underwent a secondary repair and were asymptomatic, increasing the eventual successful outcome to 87%. Recurrent symptoms were most common in patients undergoing Collis-Belsey (33%) and laparoscopic Nissen (26%) procedures and least common after a transthoracic Nissen operation (5%). The results of postoperative 24-hour pH monitoring were normal in 17 of 21 (81%). Recurrent hiatal hernias were detected in 17 of 79 patients studied; 6 were asymptomatic. Seventy-seven percent of the patients considered themselves cured, 22% considered their condition to be improved, and 97% were satisfied. Low-grade dysplasia regressed to nondysplastic Barrett's in 7 of 16 (44%), and intestinal metaplasia regressed to cardiac mucosa in 9 of 63 (14%). Low-grade dysplasia developed in 4 of 63 (6%) patients. No patient developed high-grade dysplasia or cancer in 410 patient-years of follow-up. Conclusions After antireflux surgery, most patients with Barrett's enjoy long-lasting relief of reflux symptoms, and nearly all patients consider themselves cured or improved. Mild symptoms recur in one fifth. Importantly, dysplasia regressed in nearly half of the patients in whom it was present before surgery, intestinal metaplasia disappeared in 14% of patients, and high-grade dysplasia and adenocarcinoma were prevented in all.

The aim of this study was to test the hypothesis that gastric bacterial overgrowth is a side effect of acid suppression therapy in patients with gastroesophageal reflux disease (GERD) and that the bacteria-contaminated gastric milieu is responsible for an increased amount of deconjugated bile acids. Thirty patients with GERD who were treated with 40 mg of omeprazole for at least 3 months and 10 patients with GERD who were off medication for at least 2 weeks were studied. At the time of upper endoscopy, 10 ml of gastric fluid was aspirated and analyzed for bacterial growth and bile acids. Bacterial overgrowth was defined by the presence of more than 1000 bacteria/ml. Bile acids were quantified via high-performance liquid chromatography. Eleven of the 30 patients taking omeprazole had bacterial overgrowth compared to one of the 10 control patients. The median pH in the bacteria-positive patients was 5.3 compared to 2.6 in those who were free of bacteria and 3.5 in the control patients who were off medication. Bacterial overgrowth only occurred when the pH was >3.8. The ratio of conjugated to unconjugated bile acids changed from 4:1 in the patients without bacterial overgrowth to 1:3 in those with bacterial growth greater than 1000/ml. Proton pump inhibitor therapy in patients with GERD results in a high prevalence of gastric bacterial overgrowth. The presence of bacterial overgrowth markedly increases the concentration of unconjugated bile acids. These findings may have implications in the pathophysiology of gastroesophageal mucosal injury.

Laparoscopic Nissen flmdoplication has been applied with increasing frequency in the treatment of gastroesophageal reflux disease. The aim of this study was to determine the variables that predict outcome of laparoscopic Nissen fundoplication. A multivariate analysis was performed on data from 199 consecutive patients undergoing laparoscopic Nissen fundoplication. Variables included age, sex, body mass index, primary symptoms, clinical response to acid suppression therapy, erosive esophagitis, 24-hour esophageal pH score, and the percentage of time the esophageal pH was less than 4 on 24-hour pH monitoring, lower esophageal sphincter competence, status of the esophageal body motility, hiatal hernia, carditis, intestinal metaplasia of cardiac epithelium limited to the gastroesophageal junction, and Barrett's esophagus of any length. Clinical outcome was obtained from all patients at a median follow-up of 15 months (range 6 to 74 months) after surgery. One hundred seventy-three patients had an excellent or good outcome (87%) and 26 had a fair or poor outcome. Three factors were significantly predictive of a successful outcome: an abnormal 24-hour pH score (odds ratio = 5.4; 95% confidence interval [CI] = 1.9-15.3), a typical primary symptom (odds ratio = 5.1; 95% CI = 1.9-13.6), and a clinical response to acid suppression therapy (odds ratio = 3.3; 95% CI = 1.3-8.7). We conclude that 24-hour pH monitoring provides the strongest outcome predictor of laparoscopic Nissen fundoplication and that outcome is based more on the correct identification of the disease than on its severity. (J GASTROINTEST SURG 1999;3:292-300.)

OBJECTIVE: The aim of this study was to determine whether antireflux surgery is more effective in producing loss of intestinal metaplasia located only at the gastroesophageal junction than it has been in patients with intestinal metaplasia extending up into the distal esophagus. SUMMARY BACKGROUND DATA: Biopsies of a normal appearing gastroesophageal junction will demonstrate cardiac mucosa containing goblet cells--the hallmark of intestinal metaplasia--in 10% to 15% of patients who are evaluated for symptoms of gastroesophageal reflux. The incidence of adenocarcinoma of the esophagus and cardia is rising faster than any other cancer in America, and most of these cancers are found adjacent to areas of intestinal metaplasia. Antireflux surgery in patients with Barrett's esophagus may provide protection from progression to dysplasia and cancer; however, it does not reliably cause regression of the intestinal metaplasia. Less is known about the potential for intestinal metaplasia limited to the cardia (CIM) to regress. METHODS: Sixty patients with intestinal metaplasia of the esophagus or cardia had antireflux surgery. Patients in the intestinal (CIM) group (n = 15) had no endoscopically visible segment of columnar epithelium. Patients in the Barrett's group (n = 45) had columnar epithelium visible within the esophagus. Median follow-up was 25 months in each group. RESULTS: Postoperative biopsies showed complete loss of intestinal metaplasia in 73% of the patients with CIM compared with 4.4% of the patients with Barrett's. Low-grade dysplasia, present in 10 patients preoperatively, regressed in 7 patients (70%). No patient progressed to high-grade dysplasia or cancer. CONCLUSIONS: Loss of intestinal metaplasia after antireflux surgery is rare in patients with Barrett's, but occurred in most patients with CIM. This suggests that cardiac epithelium is dynamic and that microscopic areas of intestinal metaplasia are able to regress much more frequently than longer, visible segments of intestinal metaplasia.

In the rat model, esophageal adenocarcinoma reproducibly develops following surgically induced duodenal reflux into the esophagus and administration of nitrosamine. In addition, decreasing gastric acid via partial or total gastrectomy increases the prevalence of adenocarcinoma in this model. We questioned whether carcinogen was necessary for cancer development in the gastrectomized model and whether esophageal acidification could reverse the effect of gastrectomy. Three groups of 26 rats each were randomized to a surgical procedure to produce one of the following reflux models: gastroduodenal reflux by esophagojejunostomy, duodenal reflux by total gastrectomy and esophagojejunostomy, or no reflux by Roux-en-Y reconstruction. In a second experiment, 42 rats were operated on to induce duodenal reflux. One week following surgery, they were randomized to receive acidified water (pH 1.8) or tap water. The animals were killed at 24 weeks of age, and the esophagus was evaluated histologically. All animals with reflux had severe esophagitis and 87% developed columnar lining of the distal esophagus. Nearly half (48%) developed adenocarcinoma at the anastomotic site 16 weeks postoperatively and without carcinogen administration. Cancer prevalence did not differ between animals with gastroduodenal or duodenal reflux but tended to be lower in animals receiving acidified water. Duodenoesophageal reflux is carcinogenic in the rat model. Exogenous carcinogen is not necessary for cancer development in gastrectomized rats.

OBJECTIVE: The purpose of the study was to test the hypothesis that cardiac mucosa, carditis, and specialized intestinal metaplasia at an endoscopically normal-appearing cardia are manifestations of gastroesophageal reflux disease. SUMMARY BACKGROUND DATA: In the absence of esophageal mucosal injury, the diagnosis of gastroesophageal reflux disease currently rests on 24-hour pH monitoring. Histologic examination of the esophagus is not useful. The recent identification of specialized intestinal metaplasia at the cardia, along with the observation that it occurs in inflamed cardiac mucosa, led the authors to focus on the type and condition of the mucosa at the gastroesophageal junction and its relation to gastroesophageal reflux disease. METHODS: Three hundred thirty-four consecutive patients with symptoms of foregut disease, no evidence of columnar-lined esophagus, and no history of gastric or esophageal surgery were evaluated by 1) endoscopic biopsies above, at, and below the gastroesophageal junction; 2) esophageal motility; and 3) 24-hour esophageal pH monitoring. The patients were divided into groups depending on the histologic presence of cardiac epithelium with and without inflammation or associated intestinal metaplasia. Markers of gastroesophageal reflux disease were compared between groups (i.e., lower esophageal sphincter characteristics, esophageal acid exposure, the presence of endoscopic erosive esophagitis, and hiatal hernia). RESULTS: When cardiac epithelium was found, it was inflamed in 96% of the patients. The presence of cardiac epithelium and carditis was associated with deterioration of lower esophageal sphincter characteristics and increased esophageal acid exposure. Esophagitis occurred more commonly in patients with carditis whose sphincter, on manometry, was structurally defective. Specialized intestinal metaplasia at the cardia was only seen in inflamed cardiac mucosa, and its prevalence increased both with increasing acid exposure and with the presence of esophagitis. CONCLUSION: The findings of cardiac mucosa, carditis, and intestinal metaplasia in an endoscopically normal-appearing gastroesophageal junction are histologic indicators of gastroesophageal reflux disease. These findings may be among the earliest signs of gastroesophageal reflux and contribute to the authors understanding of the pathophysiology of the disease process.

Experimental studies have shown that the severity of esophageal mucosal injury in gastroesophageal reflux disease is related to the reflux of both gastric and duodenal juice. The purpose of this study was to determine whether duodenal juice potentiates esophageal injury in patients with reflux disease or, inf act, causes no harm allowing acid and pepsin to do the damage. A total of 148 consecutive patients who had no previous gastric or esophageal surgery underwent endoscopy and biopsy, manometry, and 24-hour esophageal pH and bilirubin monitoring. Esophageal injury was defined by the presence of erosive esophagitis, stricture, or biopsy-proved Barrett's esophagus. Exposure to duodenal juice, identified by the absorbance of bilirubin, was defined as an exposure time exceeding the ninety-fifth percentile measured in 35 volunteers. To separate the effects of gastric and duodenal juice, patients were stratified according to their acid exposure time. One hundred patients had documented acid reflux on pH monitoring, and in 63 of them it was combined with reflux of duodenal juice. Patients with combined reflux (50 of 63) were more likely to have injury than patients without combined reflux (22 of 37; P < 0.05). When the acid exposure time was greater than 10%, patients with injury (n = 40) had a greater exposure to duodenal juice (median exposure time 17.2% vs. 1.1%, P = 0.006) than patients without injury (n = 5), but there was no difference in their acid exposure (16.9% vs. 13.4%). Patients with dysplasia of Barrett's epithelium (n = 9) had a greater exposure to duodenal juice (median exposure time 30.2% vs. 7.2%, P = 0.04) compared to patients without complications (n = 25), whereas acid exposure was the same (16.4% vs. 15%). Duodenal juice adds a noxious component to the refluxed gastric juice and potentiates the injurious effects of gastric juice on the esophageal mucosa.

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.

Background : Detection of subclinical recurence after surgical resection of esophageal cancer would allow earlier treatment of recurrent disease and potentially offer a better outcome for rescue therapy. Methods : The utility of serum carcinoembryonic antigen (CEA) assay was evaluated in the management of patients with esophageal cancer. Results : Serum carcinoembryonic antigen was measured preoperatively in 74 patients. Elevation of the CEA level (>5 ng/mL) was present in 14 patients (19%). There was no relationship between preoperative CEA elevation and the stage of the tumor or the patients' survival. Eighty-three patients had CEA assay at regular follow-up intervals after resection. Objective evidence of recurrent disease was determined at similar intervals by chest radiography and abdominal and thoracic computed tomography scans. During follow-up, 53 of 83 patients developed recurrence. Postoperative elevation of CEA levels occurred in 32 patients, resulting in a sensitivity of 55% for detecting recurrent disease. Twenty-nine of the 32 patients who developed CEA elevation had objective evidence of metastatic disease. In 13 patients, the rise in CEA levels predated objective evidence of recurrence by a median of 4 months (range 3 to 35), and in 16 patients, it occurred concomitantly. The specificity with which an elevated postoperative CEA level indicated recurrence was high, 90%, with a positive predictive value of 91%. Conclusions : Postoperative CEA elevation is highly predictive of recurrent disease. In 16% of patients, elevation of CEA was the earliest objective sign of recurrence; such elevation should prompt consideration of adjuvant therapy.

The outcome of Nissen fundoplication in patients with a nonspecific motility abnormality compared with the outcome in patients with normal motility is unknown. One hundred consecutive patients who underwent primary Nissen fundoplication were evaluated before and a median of 50 months after operation, with emphasis on the presence of a preoperative motility disorder and its relationship to preoperative and postoperative symptoms. Compared with patients who had normal motility, patients with a nonspecific motility abnormality had a greater prevalence and severity of heartburn and regurgitation before operation. These patients also had a greater esophageal exposure to gastric juice on pH monitoring as.a result of poorer esophageal clearance function. The prevalence and severity of preoperative dysphagia was not related to the presence of a motility disorder. A 90 % or a 95 actuarial success rate was achieved in the relief of heartburn and regurgitation over a 96-month period in patients with and without a motility abnormality. The overall actuarial success rate was 93%. bysphagia was rarely caused or made more severe by the procedure; if present before the operation, it was relieved in most patients. The prevalence of persistent postoperative dysphagia was similar in patients with and without a motility abnormality. The success of Nissen fundoplication in properly selected patients is not affected by the presence of a nonspecific motility disorder.

Present management algorithms for patients with gastroesophageal reflux disease (GERD) limit endoscopy to patients with advanced disease. When endoscopy is performed, biopsy is limited to patients who have a visible columnar-lined esophagus. Biopsy is not recommended for patients whose endoscopy is normal. This algorithm results in the failure to evaluate patients with early stages of GERD at a pathologic level. We report 714 patients with normal endoscopic findings irrespective of symptoms who had adequate biopsies taken from the squamocolumnar junction and the area 1-cm distal to this from mucosa that had rugal folds. Concurrent biopsies were also taken from the gastric body and/or antrum. All patients had a gap between their esophageal squamous epithelium and gastric oxyntic mucosa in the junctional region composed of oxyntocardiac ± cardiac ± intestinal epithelia. A total of 643 (90.1%) patients had no significant pathology in the gastric antrum and/or body, indicating that the squamooxyntic gap was an isolated abnormality in this region in all but 71 (9.9%) patients. The gap contained only oxyntocardiac epithelium in 71 (9.9%) patients, cardiac mucosa without intestinal metaplasia in 482 (67.5%) patients, and intestinal metaplasia in 161 (22.6%) patients. The pathologic interpretation of biopsies taken from the gastroesophageal junction is confusing and has significant interobserver variation. This results from lack of agreement as to whether these biopsies originate in the proximal stomach ("gastric cardia") or in the esophagus. We provide evidence that the presence of oxyntocardiac ± cardiac ± intestinal epithelia in biopsies from patients who are endoscopically normal is diagnostic of a dilated GERD-damaged distal esophagus. The dilated distal esophagus is the pathologic manifestation of destruction of the abdominal segment of the lower esophageal sphincter. Its presence is the pathologic basis of early GERD, which is missed if patients who are endoscopically normal are not biopsied, as is the present recommendation. Its recognition allows for accurate and evidence-based interpretation of biopsies from this region and removes the present confusion and permits the development of a reproducible pathologic diagnostic method.

Goblet cells in Barrett’s esophagus (BE) vary in their density within the Barrett’s segment. Exposure of Barrett’s epithelium to bile acids is a major stimulant for goblet cell formation. The dissociation of bile acids into forms that penetrate Barrett’s epithelium is known to be pH dependent. We hypothesized that variations in the esophageal luminal pH environment explains the variability in goblet cell density. The aim of this study was to correlate esophageal luminal pH with goblet cell density in patients with BE. A customized six-sensor pH catheter was positioned with the most distal sensor in the stomach and the remaining sensors located 1 cm below and 1, 3, 5, and 8 cm above the upper border of the lower esophageal sphincter in five normal subjects and six patients with long-segment BE. The luminal pH was measured by each sensor for 24-h and expressed as median pH. Patients with BE had four quadrant biopsies at levels corresponding to the location of the pH sensors. Goblet cell density was graded from 0 to 3 based on the number per high-power field. In normal subjects, the median pH values recorded in the sensors within the lower esophageal sphincter (LES) and esophageal body were all above 5. In patients with BE, the median pH recorded by the sensor within the LES was 2.8 and increased progressively to 4.7 in the sensor at 8 cm above the LES. Goblet cell density was significantly lower in the distal Barrett’s segment exposed to a median pH of 2.2 and increased in the proximal Barrett’s segment exposed to a median pH of 4.4 (p = 0.003). Patients with BE have a goblet cell gradient that correlates directly with an esophageal luminal pH gradient. This suggests that goblet cell differentiation is pH dependent and likely due to the effect of pH on bile acid dissociation.