Role of the lower esophageal sphincter and hiatal hernia in the pathogenesis of gastroesophageal reflux disease.

The relative importance of the lower esophageal sphincter (LES) and hiatal hernia in the pathogenesis of gastroesophageal reflux disease is controversial. To identify the role of hiatal hernia and LES in reflux disease, 375 consecutive patients with foregut symptoms and no previous foregut surgery were evaluated. All patients underwent upper endoscopy, stationary manometry, and 24-hour esophageal pH monitoring. Hiatal hernia was diagnosed endoscopically, when the distance between the crural impression and the gastroesophageal junction was >/=2 cm. The LES was considered structurally defective when the resting pressure was 14.7) were analyzed using multivariate analysis. The presence of a hiatal hernia and a defective LES were identified as independent predictors of abnormal esophageal acid exposure. LES pressure and abdominal length were reduced in patients with hiatal hernia by 4 mm Hg and 0.4 cm, irrespective of the presence of gastroesophageal reflux disease. It is concluded that both a structurally defective LES and hiatal hernia are important factors in the pathogenesis of reflux disease. It is hypothesized that in the presence of a structurally normal LES, the altered geometry of the cardia imposed by a hiatal hernia facilitates the ability of gastric wall tension to pull open the sphincter.

Variability in the composition of physiologic duodenogastric reflux.

Duodenogastric reflux has long been associated with various diseases of the foregut. Even though bile is often used as a marker, duodenogastric reflux consists of other components such as pancreatic juice and duodenal secretions. The aim of this study was to investigate the occurrence of duodenogastric reflux, its components, and the variability of its composition in normal subjects. Twenty healthy volunteers (7 men and 13 women) whose median age was 24 years underwent combined 24-hour bilirubin and gastric pH monitoring and intraluminal gastric aspiration. All probes were placed at 5 cm below the lower border of the lower esophageal sphincter. Aspiration was performed hourly and at any time when bilirubin and/or pH monitoring showed signs of duodenogastric reflux. Elastase and amylase were measured in the aspirate. All volunteers had episodes of physiologic duodenogastric reflux. A total of 70 episodes of duodenogastric reflux were registered with a median of three episodes (range 1 to 8) per subject. Most bile reflux occurred separately from pancreatic enzyme reflux. Pancreatic enzyme aspirate was significantly more often associated with a rise in pH in comparison to bile reflux (P <0.01). Duodenogastric reflux is a physiologic event with varying composition. Both bile and pancreatic enzyme reflux frequently occur separately. These findings could explain the disagreement regarding assessment and interpretation of duodenogastric reflux in the past. Thus monitoring of duodenogastric reflux requires more than the detection of just one component.

Duodenoesophageal reflux induces esophageal adenocarcinoma without exogenous carcinogen.

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.

Application of the new classification for cancer of the cardia.

BACKGROUND: Cancer of the cardia is now topographically classified into three types: type I, with the tumor center in the distal esophagus treated with subtotal esophagectomy; type II, arising at the gastroesophageal junction and treated with distal esophagectomy and either proximal or total gastrectomy; and type III, subcardial cancer treated with extended total gastrectomy. Our objective was to review the new classifications and compare the outcomes in patients grouped and treated according to these classifications. METHODS: Seventy-four patients with cancer of the cardia--15 with type I, 30 with type II, and 29 with type III cancer--underwent surgical resection at our institution between 1992 and 1997. Postoperative complications, UICC stages, and survival (Kaplan-Meier) were compared. RESULTS: The majority of patients with type I (73%) or type II (53%) cancer had stage I or II tumors, but only 27% of patients with type III cancer had this tumor stage (P < .05). Overall 30-day mortality was 4% and morbidity was 31%. Curative resections were performed in 73% (54 of 74) of the patients with 3-year survival rates of 72% (type I), 68% (type II), and 61% (type III). CONCLUSION: The recommended therapy for the different types of cancer of the cardia results in acceptable morbidity, mortality, and survival rates.

Treatment of advanced gastroesophageal reflux disease with Collis gastroplasty and Belsey partial fundoplication.

OBJECTIVE: To examine the factors affecting outcome in patients with advanced gastroesophageal reflux disease. DESIGN: Retrospective analysis. SETTING: University tertiary referral center. PATIENTS: Thirty-seven patients with advanced gastroesophageal reflux disease and no previous antireflux surgery. INTERVENTIONS: Thirty patients underwent Collis gastroplasty for esophageal lengthening and Belsey partial fundoplication. Seven patients with esophageal stricture and global loss of esophageal body motility who underwent primary esophagectomy and reconstruction were used as a comparison group. OUTCOME MEASURES: Symptomatic outcome in all 37 patients was assessed by questionnaire at a median of 25 months (range, 5-156 months) after surgery. In a subset of 11 patients undergoing the Collis-Belsey procedure, outcome was measured using 24-hour pH and results of motility studies. RESULTS: The Collis-Belsey procedure was successful in relieving symptoms of gastroesophageal reflux in 21 (70%) of the 30 patients. The outcome was excellent or good in 16 (89%) of 18 patients who presented with symptoms other than dysphagia, but only in 5 (42%) of 12 patients with dysphagia (P = .01). The outcome was particularly poor if dysphagia was associated with a previously dilated esophageal stricture. Persistent or induced dysphagia was the reason for failure in all but 1 patient. Results of 24-hour esophageal pH studies were returned to normal in 8 (73%) of 11 patients undergoing postoperative evaluation. Contraction amplitudes in the distal esophagus and the prevalence of simultaneous contractions in these segments did not change after the operation. All 7 patients who underwent primary esophagectomy were classified as having an excellent or good outcome and were relieved of their reflux symptoms, including dysphagia. Six of these could eat 3 meals per day and enjoyed an unrestricted diet. CONCLUSIONS: The outcome of the Collis-Belsey procedure in patients with advanced gastroesophageal reflux disease without dysphagia is excellent. It is less so in patients with dysphagia as a preoperative symptom. Esophagectomy can provide a good outcome in patients who have a combination of dysphagia stricture and a profound loss of esophageal motility.

Esophagectomy for unsuccessful antireflux operations.

BACKGROUND: Primary antireflux surgery provides excellent symptom relief in most patients. Unfortunately, the results of redo surgery are less predictable. In these patients, esophageal injury from long-standing reflux of gastric contents and operative trauma from previous failed antireflux procedures results in progressive deterioration in esophageal propulsion, poor clearance of reflux episodes, mucosal damage, and, in some cases, stricture formation. For the past 16 years, we have selectively used esophageal resection and replacement instead of another reoperation in these challenging patients. METHODS: Seventeen patients with end-stage esophageal body dysfunction and one or more previously unsuccessful antireflux procedures underwent esophagectomy and reconstruction by colon interposition in 15 patients and jejunum interposition in 2 patients. The indications for esophagectomy rather than a redo antireflux procedure were a global loss of effective esophageal motility in 13 and a nondilatable stricture in four. Their outcome was compared with that of 32 patients with adequate motility and 18 with a similar global loss of motility who had a redo antireflux procedure. Perioperative complications after esophagectomy were recorded, and long-term outcome was assessed by means of a standardized questionnaire at a median of 7 years after the operation. RESULTS: Patients with profound esophageal body dysfunction who underwent esophageal resection had outcomes similar to those with normal motility who underwent a redo antireflux procedure. Those with profound esophageal motility dysfunction who underwent a redo antireflux procedure had a worse outcome than those who underwent resection. Esophageal resection and replacement was performed without mortality or graft failure. All patients who underwent resection stated that their preoperative symptoms were relieved completely (n = 6) or improved (n = 10). Thirteen patients (81%) were able to eat three meals a day, and 12 patients (75%) enjoyed an unrestricted diet. Two thirds of the patients were at or above their ideal body weight, and 88% were fully satisfied with the outcome of the procedure. CONCLUSION: Patients with end-stage esophageal body dysfunction who have had a previous unsuccessful antireflux procedure can be treated by esophageal resection with a high expectation of success.

Gastroesophageal reflux disease and mucosal injury with emphasis on short-segment Barrett's esophagus and duodenogastroesophageal reflux.

Gastroeosphageal reflux disease has been associated with long segments of Barrett's esophagus

Outcome after laparoscopic fundoplication is not dependent on a structurally defective lower esophageal sphincter.

With the advent of laparoscopic surgery and the recognition that gastroesophageal reflux disease often requires lifelong medication, patients with normal resting sphincter characteristics are now being considered for surgery. The outcome of these patients after fundoplication is unknown and formed the basis of this study. The study population consisted of 123 patients undergoing laparoscopic Nissen fundoplication between 1992 and 1996. All patients had increased esophageal acid exposure on 24-hour esophageal pH monitoring. Patients were divided into those with a normal (n = 36) and those with a structurally defective (n = 87) lower esophageal sphincter (LES), based on LES resting pressure (normal >6 mm Hg), overall length (normal >2 cm), and abdominal length (normal >1 cm), and their outcomes were assessed. Each group was subsequently divided into patients presenting with a primary symptom that was "typical" (heartburn, regurgitation, or dysphagia) or "atypical" (gastric, respiratory, or chest pain) of gastro-esophageal reflux, and outcome was assessed. Median duration of follow-up was 18 months after surgery. Overall, laparoscopic fundoplication was successful in relieving symptoms of gastroesophageal reflux in 90% of patients. Patients with a typical primary symptom had an excellent outcome irrespective of the resting status of the LES (95% and 97%, respectively). Atypical primary symptoms were significantly more common in patients with a normal LES (29%) than in those with a structurally defective LES (10%; P <0.05), and these symptoms were less likely (50%) to be relieved by antireflux surgery. Laparoscopic antireflux surgery is highly successful and not dependent on the status of the resting LES in patients with increased esophageal acid exposure and primary symptoms "typical" of gastroesophageal reflux. Antireflux surgery should be applied cautiously in patients with atypical primary symptoms.

Isolated upright gastroesophageal reflux is not a contraindication for antireflux surgery.

BACKGROUND: Patients with gastroesophageal reflux disease who reflux only in the upright position are thought to have a less severe abnormality. Controversy exists over whether these patients should be considered candidates for antireflux surgery. METHODS: A total of 224 consecutive patients with increased esophageal acid exposure on 24-hour pH monitoring were classified as having upright (n = 54), supine (n = 72), or bipositional (n = 98) reflux and were evaluated by manometry and endoscopy. Of these, 116 patients had a laparoscopic Nissen fundoplication. Their clinical outcome at a median of 12 months (range 4 to 44 months) was compared. RESULTS: Patients with upright reflux had a lower prevalence of a structurally defective lower esophageal sphincter, fewer hiatal hernias, and less esophageal injury when compared to those with bipositional reflux (p < 0.005). Excellent (asymptomatic) or good outcome (minor symptoms not requiring acid suppression therapy) was achieved in 86% of the patients with upright reflux, 90% of those with supine reflux, and 89% of those with bipositional reflux. CONCLUSIONS: Patients with upright reflux have less complicated, earlier disease and have results equivalent to those patients with supine and bipositional reflux after antireflux surgery.

Inflammation and specialized intestinal metaplasia of cardiac mucosa is a manifestation of gastroesophageal reflux disease.

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.

Can the combination of symptoms and endoscopy confirm the presence of gastroesophageal reflux disease?

The aim of this study was to evaluate the accuracy of symptomatology and esophagogastroduodenoscopy (EGD) in the diagnosis of proven gastroesophageal reflux disease (GERD). We evaluated the symptoms and EGD findings of 100 consecutive patients presenting with symptoms suggestive of GERD. Patients' symptoms were scored at their first visit with a standardized symptom scoring system (grades 0-3). Grade 3 symptoms were the most severe. EGD findings were classified according to the modified Savary-Miller scale. Esophageal acid exposure was quantified using 24-hour esophageal pH monitoring; a positive composite score was considered evidence of GERD. Fifty-seven patients had positive pH scores, and 43 were negative. The combination of grade 2 or 3 heartburn and/or regurgitation with erosive esophagitis or Barrett's esophagus on EGD had a 97 per cent specificity and 64 per cent sensitivity for accurately diagnosing GERD. It is concluded that, in the presence of moderate to severe symptoms and endoscopic injury, the diagnosis of GERD can be made without further studies. However, 24-hour esophageal pH monitoring is still indicated in patients with mild typical symptoms, atypical symptoms, or when the combination of heartburn and regurgitation, regardless of their severity, occurs in the absence of severe mucosal damage.

Duodenogastric reflux potentiates the injurious effects of gastroesophageal reflux.

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, in fact, 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.

Static and dynamic function of the lower esophageal sphincter before and after laparoscopic Nissen fundoplication.

The means by which fundoplication protects against reflux is disputed. We studied the resting and dynamic features of the lower esophageal sphincter (LES) and 24-hour pH monitoring in 26 patients before and after laparoscopic Nissen fundoplication. Resting features were LES pressure, abdominal length, and total length. Dynamic function was assessed by the residual pressure in the LES during a swallow measured as the bolus flowed though the LES. All patients experienced near-total relief of heartburn and all but one had normal postoperative acid scores. Resting LES characteristics were restored to normal. Mean residual pressure on swallowing was 7.1+/-3.2 mm Hg in the patients postoperatively compared with 1.2+/-1 mm Hg preoperatively and 4.0+/-2.4 mm Hg in normal subjects. Eighteen of 26 patients had residual LES pressure within the normal range (<8.2 mm Hg). There was a tendency for residual pressures to be lower as experience with the procedure was gained. Incomplete LES relaxation is not necessary for effective functioning of a Nissen fundoplication. In construction of a Nissen fundoplication, creating a large retroesophageal window and deliberate dissection of the back of the posterior fundus from the left crus allows the creation of an effective antireflux procedure with restoration of static LES parameters to normal and minimal limitation of LES relaxation.

Outcome of respiratory symptoms after antireflux surgery on patients with gastroesophageal reflux disease.

OBJECTIVE: To investigate factors predictive of relief of respiratory symptoms associated with gastroesophageal reflux disease (GERD). DESIGN: A case series of patients with GERD and respiratory symptoms undergoing fundoplication from 1987 to 1994 at a tertiary care university hospital. PATIENTS: Of 118 patients undergoing fundoplication for cardinal symptoms of GERD, 63 had respiratory symptoms. Postoperative follow-up information was available in 50 patients at a median of 3 years. INTERVENTIONS: The presence of GERD was documented on the basis of barium swallow, esophagoscopy, esophageal manometry, and 24-hour pH studies. A standardized questionnaire was used to score symptoms. A Nissen fundoplication was performed in 39 patients, a Collis-Belsey fundoplication in 3 patients. MAIN OUTCOME MEASURES: A repeat standardized questionnaire was used to evaluate the response to surgery for each symptom experienced. Univariate analysis was performed to evaluate factors influencing outcome. RESULTS: Respiratory symptoms were present in 53% (63/118) of patients with GERD. Fundoplication relieved the respiratory symptoms in 76% (38/50) of the patients. Reflux symptoms were relieved in 86% (43/50) of the patients. Abnormalities of esophageal motility were present in 34% (17/50) of the patients, and these were significantly more common in patients who did not experience relief of their respiratory symptoms (9/12 vs 8/38, chi 2 = 9.54, P = .002). CONCLUSIONS: Respiratory symptoms are common in patients with GERD. Unlike classic reflux symptoms, the beneficial effects of antireflux surgery on respiratory symptoms are less predictable. The probability of relief of these respiratory symptoms with antireflux surgery is directly dependent on esophageal motor function.