Carditis: a manifestation of gastroesophageal reflux disease

This series consists of 141 patients in whom cardiac mucosa (CM) was present in biopsy samples from the gastroesophageal junctional region. Inflammation of CM, irrespective of its exact anatomic location, was defined as carditis and classified as acute or chronic based on the number of inflammatory cells present. In all cases, CM showed significant chronic inflammation. One hundred and eleven (79%) of the 141 patients with carditis showed no evidence of gastritis in biopsy samples from the gastric antrum and body. Helicobacter pylori was present in 20 of 141 (14%) patients; of these, 17 had evidence of a pangastritis, with 15 of these patients also showing H. pylori in CM. Patients with severe chronic inflammation in CM had a significantly higher acid exposure of the lower esophagus as quantitated by a 24-hour pH test than those with mild chronic inflammation in CM. Acute inflammation was uncommon in CM; it was present in only 26 of 141 (18.4%) patients. There was no significant difference in acid exposure of the lower esophagus between patients with and without acute inflammation in CM. The presence of acute inflammation in CM was significantly associated with distal gastritis and H. pylori infection. Men with carditis had quantitatively higher acid exposure of the lower esophagus than did women with this disorder. This difference was greatest in men with severe inflammation in CM who had no evidence of distal gastritis. These findings provide evidence that chronic inflammation in CM is strongly associated with acid reflux and that H. pylori is not a significant etiologic factor in carditis. They also show that in patients with CM in whom H. pylori gastritis develops, the infection frequently spreads to involve CM, resulting in acute inflammation with neutrophils that is superimposed on the chronic inflammation already present.     

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.     

Specialized intestinal metaplasia in patients with gastro-oesophageal reflux disease

BACKGROUND: There is an increasing awareness that short (less than 3 cm) segments of Barrett's epithelium and macroscopically normal cardia epithelium may harbour specialized intestinal metaplasia (SIM), a premalignant phenotype. The prevalence of SIM was studied prospectively in an unselected population of patients attending for endoscopy, and the association of SIM with symptoms, lifestyle, medication, endoscopic oesophagitis and carditis was investigated. METHODS: Two hundred consecutive patients underwent endoscopy. Biopsies taken from just below the squamocolumnar junction were stained for SIM, and were analysed for carditis and Helicobacter pylori infection. A detailed questionnaire of symptoms, tobacco consumption and the use of proton pump inhibitors was completed. RESULTS: Forty-two patients (21 per cent) had SIM: 19 (15 per cent) of 126 in an endoscopically normal oesophagus, 15 (24 per cent) of 63 in a short segment of Barrett's epithelium and eight of 11 in classical Barrett's oesophagus. There was a significant association between SIM and carditis (P < 0.0001) and endoscopic oesophagitis (P = 0.03). CONCLUSION: SIM is prevalent in patients undergoing endoscopy, does not correlate with symptoms or H. pylori infection, but is significantly associated with endoscopic and pathological markers of gastro-oesophageal reflux.     

Esophagectomy for gastroesophageal reflux disease.

Failed control of pathologic gastroesophageal reflux leads to irreversible esophageal damage and progressive loss of function. Patients develop severe intractable symptoms, incapacitating dysphagia, and, with end-stage disease, stricture formation or Barrett's esophagus. When medical management and repeated antireflux operations have failed, resection of the diseased esophagus may become the only valid alternative. Careful preoperative evaluation and patient selection are essential to obtain satisfactory long-term functional results with acceptable rates of morbidity and mortality.     

Medical management of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is the most frequent problem seen in the esophageal clinic and laboratory Most patients who have a small hiatal hernia or an occasional reflux require only symptomatic treatment and some lifestyle modifications. However, prolonged medical treatment becomes mandatory in more severe cases, and these patients must significantly modify their lifestyle and try to correct the underlying causes of their condition.     

Trends in incidence and prevalence of specialized intestinal metaplasia,barrett's esophagus,and adenocarcinoma of the gastroesophageal junction

Most available information on the epidemiology of Barrettacute;s esophagus (BE) relates to patients with long segments (> 3 cm) of specialized intestinal metaplasia (SIM). Its prevalence is 3% in patients undergoing endoscopy for reflux symptoms and 1% in those undergoing endoscopy for any clinical indication. The latter prevalence is similar to the 1% found in autopsy series. A "silent majority" with BE remain unrecognized in the general population. BE is more common in men, and the prevalence rises with age. Recent endoscopic series document a rise in the diagnosis of endoscopically apparent short segments (< 3 cm) of BE (SSBE). The prevalence of SSBE in both unselected and reflux patients is 8% to 12%. Specialized intestinal metaplasia at the cardia, below a normal-appearing squamocolumnar junction, has been reported to vary from 6% to 25% in patients presenting for upper endoscopy. Unlike patients with long segment Barrett's esophagus (LSBE), the role of gastroesophageal reflux disease in the pathogenesis of SSBE and SIM of the cardia is controversial. Recent data suggest that the etiology of SIM of the cardia might be secondary to Helicobacter pylori infection, although the role of other environmental factors cannot be ruled out. The incidence of adenocarcinoma of the esophagus and esophagogastric juction (EGJ) has been increasing over the past 15 years in Western countries. Surgical series and population-based studies show that by 1994 adenocarcinomas of the esophagus accounted for half of all esophageal cancer among white men. LSBE and SSBE predispose to the development of adenocarcinoma of the esophagus and EGJ. The role of SIM of the cardia as a precursor lesion for EGJ adenocarcinoma is still unclear. The prevalences of dysplasia in LSBE and SSBE are around 6% and 8%, respectively. The incidence of adenocarcinoma in patients with LSBE is about 1 in 100 patient-years. Cancer risk for SSBE and SIM at the cardia is unknown. Smoking and obesity increase the risk for esophageal and EGJ adenocarcinomas.     

Etiology of intestinal metaplasia at the gastroesophageal junction

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.     

Laparoscopic Nissen fundoplication is an effective treatment for gastroesophageal reflux disease.

OBJECTIVE: The open Nissen fundoplication is effective therapy for gastroesophageal reflux disease. In this study, the outcomes in 198 patients treated with the laparoscopic Nissen fundoplication was evaluated for up to 32 months after surgery to ascertain whether similar positive results could be obtained. SUMMARY BACKGROUND DATA: To ensure surgical success, patients were required to have mechanically defective sphincters on manometry and increased esophageal acid exposure on 24-hour pH monitoring. The patients either had severe complications of gastroesophageal reflux disease or had failed medical therapy. These requirements have been found to be necessary to ensure a successful surgical outcome. METHODS: The disease was complicated by ulceration (46), stricture (25) and Barrett's esophagus (33). Patients underwent standard Nissen fundoplications identical in every detail to open procedures except that the procedures were carried out by the laparoscopic route. RESULTS: Perioperative complications included gastric or esophageal perforation (3), pneumothorax (2), bleeding (2), breakdown of crural repair (2) and periesophageal abscess (1). The only mortality occurred from a duodenal perforation. Six patients required conversion to the open procedure. The median hospital stay was 3 days. One hundred patients were observed for follow-up for 6 to 32 months (median 12 months), with outcomes similar to the open Nissen fundoplication. Further surgery was required for two patients who had recurrent gastroesophageal reflux and one who developed an esophageal stricture. Ninety-seven percent are satisfied with their decision to have the operation. CONCLUSIONS: The laparoscopic Nissen fundoplication can be carried out safely and effectively with similar positive results to the open procedure and with all of the advantages of the minimally invasive approach.     

腹腔镜手术治疗胃食管反流病和贲门失弛缓症

目的:探索三种腹腔镜胃底折叠术治疗胃食管反流病及Heller肌切开术治疗贲门失弛缓症的安全性与可行性。方法:1995年12月至2004年9月,经腹腔镜手术治疗了胃食管反流病人45例和贲门失弛缓病人5例。术前常规行胃镜与上消化道钡餐检查者50例,加行食管测酸、测压检查者39例。腹腔镜单纯胃底折叠术10例(Nissen式1例,Toupet式9例);腹腔镜食管裂孔疝修补加胃底折叠术35例(Nissen式11例,Toupet式24例)。Heller肌切开术加Dor胃底折叠术5例。结果:全组病人的平均手术时间为120(60～360)min,术中平均出血量15(10～100)ml,术后日平均引流量20(10～100)ml,平均住院7(5～12)d。其中前10例使用电刀者平均用时210(180～360)min,中转开腹1例;后40例使用超声刀者平均用时100(60～180)min。术中脾被膜划破出血2例,12例Nissen式胃底折叠术后有1例出现吞咽困难,1月后缓解。42例获随访的病人中40例不再需要服药。其中5例Heller肌切开术Dor胃底折叠术病人术后第2天即可顺畅进食,且无反流。结论:与传统的经胸或经腹手术相比,腹腔镜抗反流手术治疗胃食管反流病和Heller肌切开贲门失弛缓症的病人具有心肺干扰小、麻醉难度低、创伤小、痛苦轻、并发症少、住院时间短、康复快、疗效好等突出优点。经过不断改进手术设计和加强训练可使?     

The Z-line appearance and prevalence of intestinal metaplasia among patients without symptoms or endoscopical signs indicating gastroesophageal reflux

BACKGROUND: A four-graded classification of the Z-line appearance (ZAP) has been proposed, which was shown to correlate with the prevalence of intestinal metaplasia (IM) among patients with gastroesophageal reflux disease (GERD). The aim of this study was to determine the ZAP grade and the prevalence of IM among patients without GERD. METHODS: In this study, 53 consecutive patients without signs or symptoms of GERD were included. RESULTS: A normal Z-line (ZAP grade 0) was found in 26 patients (51%), and this group had a lower prevalence of Helicobacter pylori infection and atrophy in the cardia than ZAP grade patients. The non-GERD patients in this study had less ZAP pathology than the GERD patients in our previous study. Intestinal metaplasia at the Z-line, observed in 17% of the patients, was found to associate with peptic ulcer and carditis. CONCLUSION: The normal Z-line is feasibly defined as ZAP grade 0.     

Pathophysiology of gastroesophageal reflux disease

From a pathophysiologic viewpoint, GERD results from the excessive reflux of gastric contents into the distal esophagus. Under normal conditions, this is prevented as a function of the antireflux barrier at the EGJ, the integrity of which is dependent on the delicate interplay of a host of anatomic and physiologic factors, including the integrity of the LES, TLESR, and anatomic degradation of the EGJ inclusive of but not limited to hiatus hernia. Considerable investigative focus is aimed at describing the subtle aberrations of the EGJ that may contribute to the root causes of GERD. The net result is an increased number of reflux events, an increasing diversity of potential mechanisms of reflux, and a diminished ability of the stomach to selectively vent gas, as opposed to gas and gastric juice, during TLESR. Once reflux occurs, the duration of resultant esophageal acid exposure is determined by the effectiveness of esophageal acid clearance, the dominant determinants of which are peristalsis, salivation, and, again, the anatomic integrity of the EGJ. Approximately half of patients who have GERD have abnormal acid clearance and the major contributor to this is hiatus hernia. Abnormalities of acid clearance probably are the major determining factor influencing which patients who have GERD are most prone to developing esophagitis as opposed to symptomatic GERD. In summary, GERD is a multifactorial process involving physiologic and anatomic abnormalities. These abnormalities exhibit a complicated interplay that degrades the ability of the EGJ to contain gastric juice within the stomach and to clear the esophagus of gastric juice effectively once reflux has occurred.     

Evaluation of gastroesophageal reflux disease

Patients with gastroesophageal reflux disease (GERD) may present with a variety of symptoms, including heartburn, regurgitation, dysphagia, chronic cough, laryngitis, or even asthma. Therefore, the clinical presentation of GERD varies among individuals and conversely symptoms not always correspond to the presence of actual reflux. For that reason, the diagnosis poses certain challenges to the physician. To overcome these challenges, a thorough clinical examination followed by objective functional testing could improve diagnostic accuracy. In addition, a proper evaluation of patients with GERD can help in identifying those who will likely benefit the most from an antireflux procedure. The diagnostic work-up of these patients should include: symptomatic evaluation, upper endoscopy, barium swallow, high-resolution manometry, and ambulatory pH monitoring. Once a proper diagnosis of GERD is achieved, antireflux surgery is an excellent option for patients with partial control of symptoms with medication, for patients who do not want to be on long-term medical treatment (compliance/cost), or when complications of medical treatment occur.     

Patterns of gastroesophageal reflux in health and disease.

Twenty-four pH monitoring the distal esophagus quantitates gastroesophageal reflux in a near physiologic setting by measuring the frequency and duration of acid exposure to the esophageal mucosa. Fifteen asymptomatic volunteers were studies with 24-hour pH and esophageal manometry. The normal cardia was more competent supine than in the upright position. Physiologic reflux was unaffected by age, rarely occurred during slumber, and was the rule after alimentation. One hundred symptomatic pateitns with an abnormal 24-hour pH record (2 S.D. above the mean of controls) could be divided into three patterns of pathological reflux: those who refluxed only in the upright position (9), only in the supine position (37), and in both positions (54). Upright differed from supine refluxers by excessive aerophagia causing reflux episodes by repetitive belching. Compared to controls, they had excessive post-prandial reflux, lower DES pressure, and less DES exposed to the positive pressure of the abdomen. Supine differed from upright refluxers by having a higher incidence of esophagitis and an inability to clear the esophagus of acid after a supine reflux episode. Compared to controls, they had only a lower DES pressure. Combined refluxers had a higher incidence of esophagitis than supine refluxers. Stricture (15%) was seen only in this group. They were similar to supine refluxers in their inability to clear a supine reflux episode. Compared to controls, they had a lower DES pressure and less DES exposed to the positive pressure of the abdomen. Forty of the 100 patients had an antireflux procedure (4 upright, 8 supine, 28 combined). The most severe postoperative flatus and abdominal distention was seen in the upright refluxers. It is concluded that minimal reflux is physiological. Patients with pathological reflux all have lower DES pressure. Patients with upright reflux have less of their DES exposed to the positive pressure environment of the abdomen. Patients with supine reflux have an inability to clear the esophagus of reflux acid and are prone to develop esophagitis. Patients with both upright and supine reflux have the most severe disease and are at risk in developing strictures. In patients with only upright reflux, aerophagia and delayed gastric emptying may be an important etiological factor.     

Helicobacter pylori is not associated with the manifestations of gastroesophageal reflux disease.

HYPOTHESIS: Helicobacter pylori is not associated with gastroesophageal reflux disease and its complications, including adenocarcinoma of the esophagus and the gastroesophageal junction (GEJ). DESIGN: Retrospective analysis. SETTING: University tertiary referral center. PATIENTS: Two hundred twenty-nine patients with symptoms suggestive of foregut disease underwent esophageal manometry, 24-hour pH monitoring, and upper gastrointestinal tract endoscopy, with biopsy specimens obtained from the gastric antrum, the GEJ, and the distal esophagus. In these and in an additional 114 patients with adenocarcinoma of the esophagus and the GEJ, the presence of H. pylori was determined by Giemsa stain. The presence of gastroesophageal reflux disease, defined by abnormal esophageal acid exposure, and its manifestations (carditis, erosive esophagitis, intestinal metaplasia limited to the GEJ, Barrett esophagus, and adenocarcinoma of the esophagus and GEJ) were correlated with the presence of H. pylori. RESULTS: Helicobacter pylori was found on the biopsy specimens of the gastric antrum in 14.0% (32/229) of the patients with benign disease. It was not related to the features of gastroesophageal reflux disease, including abnormal esophageal acid exposure, erosive esophagitis, or Barrett esophagus. The presence of inflamed cardiac mucosa at the GEJ or carditis was inversely related to H. pylori infection and strongly associated with increased esophageal acid exposure. There was no association between the presence of intestinal metaplasia and H. pylori infection. Helicobacter pylori was found in 22 (19.3%) of the 114 patients with esophageal adenocarcinoma, which was not different from the prevalence of H. pylori in patients with benign disease. CONCLUSION: Helicobacter pylori plays no role in the pathogenesis of gastroesophageal reflux disease or its complications.     

Esophageal dysmotility and gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) produces a spectrum of symptoms ranging from mild to severe. While the role of the lower esophageal sphincter in the pathogenesis of GERD has been studied extensively, less attention has been paid to esophageal peristalsis, even though peristalsis governs esophageal acid clearance. The aim of this study was to evaluate the following in patients with GERD: (1) the nature of esophageal peristalsis and (2) the relationship between esophageal peristalsis and gastroesophageal reflux, mucosal injury, and symptoms. One thousand six consecutive patients with GERD confirmed by 24-hour pH monitoring were divided into three groups based on the character of esophageal peristalsis as shown by esophageal manometry: (1) normal peristalsis (normal amplitude, duration, and velocity of peristaltic waves); (2) ineffective esophageal motility (IEM; distal esophageal amplitude < 30 mm Hg or >30% simultaneous waves); and (3) nonspecific esophageal motility disorder (NSEMD; motor dysfunction intermediate between the other two groups). Peristalsis was classified as normal in 563 patients (56%), IEM in 216 patients (21%), and NSEMD in 227 patients (23%). Patients with abnormal peristalsis had worse reflux and slower esophageal acid clearance. Heartburn, respiratory symptoms, and mucosal injury were all more severe in patients with IEM. These data show that esophageal peristalsis was severely impaired (IEM) in 21% of patients with GERD, and this group had more severe reflux, slower acid clearance, worse mucosal injury, and more frequent respiratory symptoms. We conclude that esophageal manometry and pH monitoring can be used to stage the severity of GERD, and this, in turn, should help identify those who would benefit most from surgical treatment.     

New endoscopic treatments for gastroesophageal reflux disease.

This article reviews the available endoscopic treatments for gastroesophageal reflux disease (GERD). Plicating gastric folds methods, like Bard's EndoCinch method (Endoscopic Gastroplication, ELGP method), NDO Surgical's Full-thickness Plicator method, and Wilson-Cook Medical's Endoscopic Suturing Device (ESD) method, are used to form new plications in the cardia. Alternatively, thermal tissue remodeling/neurolysis methods, like Curon Medical's Stretta System, can be used to denature the muscular layer of the lower esophageal sphincter (LES) region. Finally, bulking injection methods, like Boston Scientific's Enteryx Procedure and Medtronic's Gatekeeper Reflux Repair System, can be used to insert a foreign body into the LES region. All six methods resulted in the improvement of symptoms and acid reflux, but only the bulking injection methods caused an improvement of the manometric findings. Nevertheless, the improvement of symptoms and acid reflux seems to be much more important than the improvement of the manometric findings. The overall discontinuation of proton-pump inhibitor (PPI) use was about 70%. Thus, endoscopic treatments for GERD are still in the development phase. The efficacy, safety, durability, cost-effectiveness, indications, and possible combination with other treatments must be thoroughly assessed in randomized controlled trials. If the usefulness of endoscopic treatment is confirmed, however, a new minimally invasive treatment strategy for GERD will have been established.     

Surgical treatment of gastroesophageal reflux disease

Background

Gastroesophageal reflux disease is by far the most prevalent disorder of the foregut. For a long time during the twentieth century, surgical therapy was the mainstay of treatment and the only chance for cure for patients with severe symptoms. Later, after introduction of proton pump inhibitor therapy in the early 1990s, surgical therapy was considered widely a second choice option due to its potential morbidity and side effects. More recently, however, there is growing evidence that long-term antisecretory therapy might be associated to a number of adverse effects such as osteoporosis and increased risk of cardiovascular events. This is the rationale why interventional and surgical options are coming back into focus.

Purpose

The purpose of this review is to analyze and to discuss the current spectrum of surgical therapy of gastroesophageal reflux disease.     

Laparoscopic repair of gastroesophageal reflux disease

Summary This report describes our preliminary experience with two surgical laparoscopic fundoplication procedures, the Nissen technique and the Toupet operation, in which the fundal wrap is reduced from 360° to 180–200°. Fourteen patients with symptomatic gastroesophageal reflux disease who were refractory to pharmacologic and medical therapy underwent a laparoscopic Nissen fundoplication; in an additional 14 patients, we performed a laparoscopic Toupet partial fundoplication. Our laparoscopic approach to the two procedures does not differ significantly from the traditional open methods and the effectiveness of the laparoscopic fundoplication procedures appears similar to that of the same conventional techniques. Oral feedings can be resumed on the first postoperative day and patients typically are discharged on the second day after surgery. Operative time for performing the Toupet procedure averaged just approximately 1.6 h and was shorter than that for the Nissen fundoplication, due to the use of a stapler to secure the fundal wrap. Confirming earlier observations, the laparoscopic Toupet 180–200° fundoplication was associated with a lower incidence of postoperative digestive complications, such as dysphagia, than was the laparoscopic Nissen operation. The laparoscopic fundoplication approach offers the advantages of clear visualization, adequate dissection and precise repair, along with the benefits associated with endoscopic surgery: diminished postoperative pain and discomfort, reduced hospitalization, and quicker return to normal activities. Our experience indicates that the Toupet fundoplication may be preferable to the Nissen technique for many patients requiring surgical treatment of their reflux disease.