Surgical management of gastroesophageal reflux disease/Barrett's esophagus

Gastroesophageal reflux disease and its complications, such as Barrett's esophagus, are major health problems. In this review, we highlight the critical components of the disease process and surgical considerations relevant to laparoscopic anti-reflux surgery.     

Barrett's esophagus and adenocarcinoma of the esophagus and gastroesophageal junction

Since 1985, 57 patients with adenocarcinoma of the esophagus and gastroesophageal (GE) junction have undergone surgical resection. In this group, 16 of the tumors arose in a Barrett's esophagus. There was a significant predilection toward white men above the age of 55 (15/16; 94%) in this subgroup. The mean proximal extent of abnormal columnar involvement was 5.4 cm above the gastroesophageal junction (range 2.5 to 11 cm). The mean location of the neoplasm centered in the distal esophagus 1.8 +/- 0.5 cm above the gastroesophageal junction. During the same time period, 30 patients with Barrett's esophagus were seen without associated adenocarcinoma. There were no statistical differences in the proximal extent of columnar involvement or the presence of reflux symptoms between the two groups. There were no significant differences in age, smoking history, and alcohol consumption between patients with benign or malignant Barrett's esophagus as compared to those with adenocarcinoma of the gastroesophageal junction not associated with Barrett's mucosa. The marked male predominance seen in the group with malignant Barrett's esophagus was in contrast to the benign cases (16/30; 53%) but was similar to the adenocarcinoma group, without recognized Barrett's esophagus (38/41; 93%). The mean location of the tumor in the latter was 0.9 +/- 1.2 cm above the gastroesophageal junction and was comparable to the location in the group with Barrett's adenocarcinoma. The 4-year survival rate of patients in the non-Barrett's adenocarcinoma group is approximately 30%. Of those with Barrett's adenocarcinoma, the present 4-year survival rate is 60%. The demographic and morphometric similarities between the Barrett's and non-Barrett's adenocarcinoma groups may be of primary importance in determining the true clinical prevalence of Barrett's adenocarcinoma. Our findings suggest that the sensitivity of endoscopic surveillance may be improved if biopsy specimens are concentrated within the distal 3 cm of the esophagus and the esophagogastric junction. Finally, the reason for the current difference in survival between the Barrett's and non-Barrett's adenocarcinoma groups is uncertain but may be related to endoscopic surveillance permitting earlier diagnosis and treatment.     

Length of the esophagus in patients with gastroesophageal reflux disease and Barrett's esophagus compared to controls

BACKGROUND: It is a current opinion among surgeons that the esophagus is shorter in patients with reflux disease and particularly in those with complicated Barrett's esophagus. However, objective evidence of this is scarce. Therefore we attempted to determine the occurrence and magnitude of this phenomenon among our patients. METHODS: One hundred ninety control subjects, 77 patients with severe erosive esophagitis, 74 with Barrett's esophagus, and 29 with complicated Barrett's esophagus (ulcer, stenosis) were grouped according to height. The length of the esophagus was determined by standard manometric study, measuring the distance from the crycopharingeal sphincter to the distal limit of the lower esophageal sphincter. Values were expressed in cm as the mean +/- SD. RESULTS: The esophageal length according to height was 1 to 2 cm shorter in patients compared to controls, but these differences were not significant. CONCLUSIONS: No differences were found between patients with progressive severity of the disease. This study confirms that the presence of a so-called "short esophagus" does not exist or is not relevant in our patients with gastroesophageal reflux disease, including those with complicated Barrett's esophagus.     

Genetic alterations in Barrett's esophagus and esophageal adenocarcinoma

Barrett's esophagus and esophageal adenocarcinoma are increasing health problems in the Western world. The rise in incidence of esophageal adenocarcinoma is greater than that for any other malignancy in Caucasian populations. The social impact of the disease is stressed in addition by the very aggressive nature of esophageal adenocarcinomas with 5-year survival rates of less than 25%. Far more people develop the premalignant condition Barrett's metaplasia than high grade dysplasia and invasive carcinoma. This means that fortunately not all patients with Barrett's metaplasia will make the progression to high grade disease. It is hoped that by unravelling the molecular mechanisms involved in the neoplastic transformation in Barrett's esophagus it will become possible to predict disease progression in the individual patient. This would be a major step forward in the curative treatment of this disease. In addition, identification of the crucial molecular pathways involved in esophageal adenocarcinogenesis would facilitate the development of new treatment strategies. The molecular mechanisms underlying the initiation and progression of this disease are largely unknown. In this review the histological sequence of Barrett's metaplasia via dysplasia to adenocarcinoma is introduced; then the general molecular concepts of carcinogenesis are explained. Furthermore, the most important esophageal neoplasia related genes are described including their possible role in the neoplastic process. The frequent genomic aberrations are put in relation to the different histological entities. Finally, as future prospect, a molecular grading of esophageal adenocarcinogenesis is anticipated.     

Barrett's esophagus: its prevalence and association with adenocarcinoma in patients with symptoms of gastroesophageal reflux

The pathologic reports of all 1,020 esophageal biopsy specimens obtained between 1975 and 1981 in patients with symptoms of gastroesophageal reflux were reviewed. Barrett's esophagus was identified in 84 patients (8 percent). The 362 patients seen between 1980 and 1981 were reviewed in detail. The symptoms in patients with Barrett's esophagus differed from those of the patients without Barrett's esophagus. Dysphagia was more often present in the former group (34 percent versus 16 percent, p less than 0.05) and epigastric distress was less frequent (11 percent versus 27 percent, p less than 0.05). Objective findings of hiatal hernia, esophageal stricture, and esophageal ulcers occurred more commonly in patients with Barrett's esophagus than in those without Barrett's esophagus (70 percent versus 48 percent, 31 percent versus 4 percent, and 14 percent versus 6 percent, respectively, p less than 0.05). Mid esophageal strictures were associated almost exclusively with Barrett's esophagus (five of six patients). At esophagoscopy, erythema was seen more commonly with Barrett's esophagus. The diagnosis was suspected by the endoscopist in only 34 percent of patients subsequently demonstrated histopathologically to have Barrett's esophagus. There was no significant difference in the prevalence of a positive Bernstein test result or gastroesophageal reflux on upper gastrointestinal series in patients with and without Barrett's esophagus. However, a hypotensive lower esophageal sphincter was found more commonly in patients with Barrett's esophagus (100 percent versus 53 percent, p less than 0.05). Thirteen of the 84 patients with Barrett's esophagus (15 percent) had a coexistent adenocarcinoma arising from Barrett's mucosa. These patients, when compared with the patients with Barrett's esophagus without carcinoma, were more often male (77 percent versus 51 percent, p = 0.1), more often had dysphagia (69 percent versus 34 percent, p less than 0.05), and more frequently had a comparatively short duration of symptoms (67 percent versus 36 percent, p less than 0.05). Our findings suggest that patients with Barrett's esophagus have a high risk of development of carcinoma. Because the entity is often not recognized at endoscopy, routine esophageal biopsy should be performed on all patients undergoing esophagoscopy for symptoms of gastroesophageal reflux. Patients with known Barrett's esophagus should be followed closely with repeated endoscopy and biopsy.     

Relationship of gastroesophageal reflux disease with adenocarcinoma of the distal esophagus and cardia

BACKGROUND: Recent studies have suggested that gastroesophageal reflux disease (GERD) increases the risk of developing adenocarcinoma of the distal esophagus and cardia. In order to further define this risk, we studied the relationship of GERD in patients with or without gastroesophageal junction adenocarcinomas. METHODS: The records of all patients with adenocarcinoma of the distal esophagus and cardia treated between 1991 and 1999 were reviewed for the following data: gender, age of diagnosis, presence of GERD, presence of GERD for >4 years, and GERD treatment. A control group of patients without gastroesophageal junction adenocarcinoma were matched for age and gender. Data obtained from the control group included presence of GERD and treatment for GERD. RESULTS: 60 patients with adenocarcinoma of the distal esophagus and cardia were identified. 40% of cancer patients had GERD at the time of diagnosis, (odds ratio 39, p < 0.0001). 27% of cancer patients had GERD for >4 years (odds ratio 21, p < 0.0001). 50% of cancer patients with GERD were being treated with either H(2)-blockers or proton pump inhibitors at the time of cancer diagnosis, with an average duration of treatment of 17 months, compared to none of the patients without GERD (p = 0.006). CONCLUSIONS: Patients with gastroesophageal junction adenocarcinoma had a higher prevalence of GERD-like symptoms compared to age- and gender-matched controls. This supports an association between GERD and gastroesophageal junction cancers. In addition, cancer patients with GERD may be treated for prolonged periods of time with acid-suppression medication prior to the diagnosis of cancer, masking the symptoms of cancer. Patients with long-standing GERD or older patients with new onset GERD may need endoscopy or imaging studies to evaluate for cancer of the distal esophagus or cardia.     

The importance of symptom assessment in the surgical treatment of gastroesophageal reflux disease and Barrett's esophagus

The "art" and science of symptom assessment in the evaluation of patients with gastroesophageal reflux disease has been under emphasized. In fact, it is critical to judgements regarding surgical versus non-surgical therapy and is much more difficult than meets the eye. Many symptoms thought to be secondary to gastroesophageal reflux are not, and some, such as asthma cough and chest pain, which are commonly thought secondary to other causes, are indeed symptoms of reflux. Diagnostic studies are helpful but far from perfect, ultimately requiring the clinician's expert judgement as the key factor in determining a successful outcome. The following outlines both an approach to the assessment of symptoms and when possible, clinical studies shedding light on their cause and interpretation.     

The relationship between gastroesophageal reflux, intestinal metaplasia and adenocarcinoma of the esophagus

Currently available data indicate a clear and probably causal relationship between long-lasting gastroesophageal reflux disease, the development of long segments with specialized intestinal metaplasia in the distal esophagus and subsequent progression to adenocarcinoma. To a lesser degree, this also appears to be the case for short segments of specialized intestinal metaplasia in the distal esophagus. In contrast, epidemiological data and classic parameters for the diagnosis of gastroesophageal reflux disease do not currently support a causal role of gastroesophageal reflux in the pathogenesis of specialized intestinal metaplasia at the gastric cardia. Despite its high prevalence and malignant potential, many questions about the prevention and management of intestinal metaplasia in the distal esophagus remain unsolved. In patients with chronic gastroesophageal reflux, current modes of medical therapy do not appear to prevent the development of intestinal metaplasia, while effective anti-reflux surgery seems to have a protective effect. Formal studies with adequate follow-up are, however, still lacking. Neither acid-suppression therapy nor anti-reflux surgery, with or without mucosal ablation, can reliably prevent the malignant degeneration of established intestinal metaplasia of the esophagus. Close endoscopic surveillance with extensive biopsies, therefore, remains mandatory in such patients, irrespective of the treatment modality.     

Barrett's esophagus and adenocarcinoma

Sixty-two cases of Barrett's esophagus were observed among 707 patients with hiatal hernia (8.7%). The symptomatology of this condition is described. An additional 10 adenocarcinomas were associated with a Barrett's esophagus--a carcinoma prevalence of 13.8%. Differences in pathology and clinical manifestations of nonmalignant and malignant cases were determined. Fifty-one patients with nonmalignant Barrett's esophagus were operated upon conservatively, while 11 underwent resection. Our results favor conservative surgery via an abdominal approach. The patients with adenocarcinomas underwent esophageal resection with six apparent cures from 6 months to 5 years. Histological study showed specialized epithelium in 8 of 10 cases and severe dysplasia in 5. Our clinical study of Barrett's esophagus shows an incidence of malignancy equal to 1 new case per 274 patient-years (1.72%). It is still not firmly established whether correction of reflux will influence the level of columnar epithelium in the esophagus, esophageal dysplasia, and the risk of malignancy.     

Alkaline gastroesophageal reflux: implications in the development of complications in Barrett's columnar-lined lower esophagus

Barrett's esophagus is a common finding in patients with gastroesophageal reflux and is associated with a high incidence of serious complications (stricture, ulceration, and carcinoma). The reason that only a portion of patients with reflux develop Barrett's esophagus and why some are prone to develop complications is unknown. Twenty-three patients with Barrett's esophagus underwent endoscopy, 24-hour esophageal pH monitoring, and manometry. Nine of these patients with gastritis underwent 24-hour gastric pH monitoring, and three with symptoms of duodenogastric reflux underwent 99mTc-labeled hepato-iminodiacetic acid scanning. Patients with complicated (n = 12) and uncomplicated (n = 11) Barrett's esophagus were compared with each other and with patients with reflux esophagitis (n = 53) and normal volunteers (n = 50). Patients with Barrett's esophagus showed an increased exposure to acid and alkaline gastric juice compared with patients with esophagitis and normal volunteers. In the patients with Barrett's esophagus with and without complications, there was no significant difference in age, incidence of defective lower esophageal sphincter, incidence of defective peristalsis, extent of the Barrett's epithelium, or percent time the esophageal pH was less than 4. In contrast, the percent time the esophageal pH was greater than 7 was significantly greater in patients with complications. This alkaline exposure is likely to be related to duodenogastric reflux. This was supported by positive gastric pH scores for duodenogastric reflux and 99mTc-labeled hepato-iminodiacetic acid scans in patients with Barrett's complications. These findings suggest that the development of complications in Barrett's esophagus is the result of the damaging effect of refluxed duodenal juice.     

Factors affecting esophageal motility in gastroesophageal reflux disease

BACKGROUND: There are conflicting data concerning the effect of gastroesophageal reflux disease (GERD) on esophageal motor function. HYPOTHESIS: Duration of GERD might affect severity of symptoms, grade of esophageal mucosal injury, and esophageal motor behavior. DESIGN: Retrospective study of a defined cohort. SETTINGS: Two referral centers, one of them academic, for esophageal gastrointestinal motility disorders. PATIENTS: One hundred forty-seven patients with documented GERD. MAIN OUTCOME MEASURES: Symptoms, grade of mucosal injury on esophagoscopy, esophageal manometry, ambulatory esophageal pH monitoring, and esophagogram. RESULTS: Patients with GERD had significantly decreased lower esophageal sphincter resting pressure (P =.02), lower amplitude of esophageal peristalsis at all levels of measurement (P<.001), and more delayed esophageal transit (P =.007) compared with control subjects. Patients with dysphagia, severe esophagitis, and Barrett esophagus presented with a longer history of the disease, significantly worse esophageal motor function (P<.01), and more prolonged esophageal transit than patients without the above features of the disease. Impairment of esophageal peristalsis and lower esophageal sphincter resting pressure were significantly inversely related to the duration of the disease (P<.001). Also, delay of esophageal transit was significantly related to the duration of the disease (P =.002) and inversely related to the amplitude of esophageal peristalsis (P<.001). Unlike the manometric variables, the extent of reflux, as assessed by ambulatory 24-hour esophageal pH monitoring, was not related to the duration of the disease. CONCLUSION: A long history of GERD is more commonly associated with presence of dysphagia, delayed esophageal transit, severe esophagitis, presence of Barrett esophagus, and impaired esophageal motility.     

Medical treatment of gastroesophageal reflux disease does not prevent the development of Barrett's metaplasia and poor esophageal body motility

Objective: Duodenal contents refluxing into the esophagus may be involved in the pathophysiology of gastroesophageal reflux disease (GERD). This study was performed to investigate whether medical treatment of GERD aimed at suppression of gastric acid production can prevent the development of complications, such as Barrett's metaplasia or poor esophageal body motility.Design: Retrospective study.Setting: University hospital.Patients: 138 GERD patients were analyzed regarding the development of Barrett's metaplasia or poor esophageal body motility, despite intermittent or continuous treatment with H₂ blockers or omeprazole.Main outcome measures: The rate of patients with Barrett's metaplasia or poor esophageal body motility with or without effective medical treatment.Results: Barrett's metaplasia was found in 33.8% of patients receiving medical treatment, although it was not present when treatment was induced. This rate was 21.9% among patients who were not receiving therapy (not significant). In all, 41.9% of patients with medication had impaired esophageal body motility compared with 59.3% of patients not receiving treatment (P<0.05), but these patients had a significantly shorter history of GERD.Conclusions: Medical treatment with H₂ blockers or omeprazole does not prevent the development of Barrett's metaplasia or poor esophageal body motility.     

Laryngopharyngeal reflux symptoms better predict the presence of esophageal adenocarcinoma than typical gastroesophageal reflux symptoms

OBJECTIVE: To determine whether the presence of laryngopharyngeal reflux symptoms is associated with the presence of esophageal adenocarcinoma (EAC). BACKGROUND: Most patients diagnosed with EAC have incurable disease at the time of detection. The majority of these patients are unaware of the presence of Barrett's esophagus prior to cancer diagnosis and many do not report typical symptoms of gastroesophageal reflux disease (GERD). This suggests that the current GERD symptom-based screening paradigm may be inadequate. Data support a causal relation between complicated GERD and laryngopharyngeal reflux symptoms. We theorize that laryngopharyngeal reflux symptoms are not recognized expeditiously, resulting in chronic esophageal injury and an unrecognized progression of Barrett's esophagus to EAC. METHODS: This is a case-comparison (control) study. Cases were patients diagnosed with EAC (n = 63) between 1997 and 2002. Three comparison groups were selected: 1) Barrett's esophagus patients without dysplasia (n = 50), 2) GERD patients without Barrett's esophagus (n = 50), and 3) patients with no history of GERD symptoms or antisecretory medication use (n = 56). The risk factors evaluated included demographics, medical history, lifestyle variables, and laryngopharyngeal reflux symptoms. Typical GERD symptoms and antisecretory medication use were recorded. Multivariate analysis of demographics, comorbid risk factors, and symptoms was performed with logistic regression to provide odds ratios for the probability of EAC diagnosis. RESULTS: The prevalence of patients with laryngopharyngeal reflux symptoms was significantly greater in the cases than comparison groups (P = 0.0005). The prevalence of laryngopharyngeal reflux symptoms increased as disease severity progressed from the non-GERD comparison group (19.6%) to GERD (26%), Barrett's esophagus (40%), and EAC patients (54%). Symptoms of GERD were less prevalent in cases (43%) when compared with Barrett's esophagus (66%) and GERD (86%) control groups (P < 0.001). Twenty-seven percent (17 of 63) of EAC patients never had GERD or laryngopharyngeal reflux symptoms. Fifty-seven percent of EAC patients presented without ever having typical GERD symptoms. Chronic cough, diabetes, and age emerged as independent risk factors for the development of EAC. CONCLUSIONS: Symptoms of laryngopharyngeal reflux are more prevalent in patients with EAC than typical GERD symptoms and may represent the only sign of disease. Chronic cough is an independent risk factor associated with the presence of EAC. Addition of laryngopharyngeal reflux symptoms to the current Barrett's screening guidelines is warranted.     

Outcome of esophageal adenocarcinoma detected during endoscopic biopsy surveillance for Barrett's esophagus

BACKGROUND: In an attempt to reduce mortality from esophageal adenocarcinoma, it has been recommended to enroll patients with Barrett's esophagus in endoscopic surveillance programs in order to detect malignant degeneration at an early and possibly curable stage. The aim of this study was to assess the impact of endoscopic biopsy surveillance on outcome of Barrett's adenocarcinoma. METHODS: Between November 1992 and June 2000, 312 patients with histologically proven esophageal adenocarcinoma were referred to our department. Ninety-seven of these patients had Barrett's adenocarcinoma. In 12 (12.2%) patients, cancer was discovered during endoscopic surveillance for Barrett's metaplasia. RESULTS: The prevalence of gastroesophageal reflux disease in the Barrett's group was 38.8% versus 8% (p < 0.01) in non-Barrett's patients. In the surveyed group, there were 9 (75%) early stage tumors (Tis-1/N0) versus 9 (10.6%, p < 0.01) in the nonsurveyed patients. Three of 5 surveyed patients operated on for high-grade dysplasia proved to have invasive carcinoma in the esophagectomy specimen. All surveyed patients were alive at a median follow-up of 48 months; the median survival in the nonsurveyed group was 24 +/- 3 months (p < 0.01). CONCLUSION: Endoscopic surveillance of Barrett's esophagus provides early detection of malignant degeneration and a better long-term survival than in nonsurveyed patients.