Manfred P. Ritter

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.

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.

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 ≤6 mm Hg, the overall length was less than 2 cm, and/or the abdominal length was less than 1 cm. Factors predicting abnormal esophageal acid exposure (composite score >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.

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 (≥3 cm), but little is known about its association with shorter segments. The aim of this study was to evaluate anatomic and physiologic alterations of the cardia and esophageal exposure to gastric and duodenal juice in patients with short and long segments of Barrett’s esophagus. Furthermore, these patients were compared to each other and to patients with erosive esophagitis and those with no mucosal injury. Two hundred sixty-two consecutive patients with foregut symptoms were divided into the following four groups based on endoscopic and histologic findings: group 1, no mucosal injury; group 2, erosive esophagitis; group 3, short-segment Barrett’s esophagus; and group 4, long-segment Barrett’s esophagus. Esophageal exposure time to acid and bilirubin, lower esophageal sphincter characteristics, and endoscopie anatomy of the cardia were compared between the groups. Patients with short-segment Barrett’s esophagus had elevated esophageal acid and bilirubin exposure, decreased lower esophageal sphincter pressure and length, and a high incidence of hiatal hernia. These abnormalities were similar to those in patients with esophagitis and in general less profound than those found in patients with long-segment Barrett’s esophagus. The length of intestinal metaplasia was higher in patients with a defective lower esophageal sphincter. Short-segment Barrett’s esophagus is a complication of severe gastroesophageal reflux disease and is associated with the reflux of both gastric and duodenal juice similar to that seen in patients with long-segment Barrett’s esophagus.

Postprandial gastroesophageal reflux in normal volunteers and symptomatic patients

A structurally intact and competent lower esophageal sphincter in the experimental model shortens and becomes incompetent during gastric distention. The aim of this study was to evaluate postprandial reflux as an indirect measure of this volume-induced sphincter shortening and incompetency. Reflux (pH <4) in the 2-hour period following a meal was retrospectively analyzed from the 24-hour esophageal pH recordings of 94 healthy volunteers and 609 symptomatic patients. Forty-six percent of patients had pathologic postprandial reflux (>95th percentile of normal). The prevalence was lower in patients with a structurally intact compared to a defective lower esophageal sphincter (32% vs. 58%; P <0.001). Pathologic postprandial reflux was greater in patients with abnormal compared to normal findings on 24-hour pH study (76% vs. 21%; P <0.001). Patients with a normal 24-hour pH study and postprandial reflux had shorter sphincter lengths (2.33 vs. 2.82 cm; P <0.001) and lower pressures (10.78 vs. 14.24 mm Hg; P <0.005). A hiatal hernia increased the prevalence of postprandial reflux (P <0.001) in all patients (67% vs. 38%) and in the subgroup with a structurally intact sphincter (75% vs. 27%, P <0.001). Postprandial reflux is a dynamic indicator of sphincter competency, and increases as the structural sphincter characteristics deteriorate and is augmented by a hiatal hernia. (J GASTROINTEST SURG 1998;2:342-349.)

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.

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.

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.

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.