Consequence Of Gastroesophageal Reflux Disease Research Articles

Importance of a multidisciplinary approach for the treatment of Barrett’s esophagus

Barrett's esophagus is a consequence of gastroesophageal reflux disease. Today, it is the most common cause of esophageal adenocarcinoma. Cancer is usually the end results of a cascade of events whereby metaplasia changes into low- and high-grade dysplasia and eventually cancer. Today, we have the unique opportunity to block this cascade and avoid the development of esophageal cancer. A multidisciplinary approach with a team composed of radiologists, gastroenterologists, pathologists, and surgeons allows individualization of care and the best results.

Does a melatonin supplement alter the course of gastro-esophageal reflux disease?

Symptomatic gastro-esophageal reflux disease (GERD) is a very common disease. The consequence of GERD is not only erosive esophagitis, but also esophageal stricture, Barrett's esophagus and extra-esophageal damage (including the lungs, throat, sinuses, middle ear and teeth). GERD and Barrett's esophagus are also identified as major risk factors for esophageal carcinoma. Therapy with melatonin prevents esophageal injury from acid-pepsin and acid-pepsin-bile exposure in animals, then further studies are required in humans to establish whether a melatonin supplement is able to protect the patients with GERD from erosions, Barrett's and neoplasia.

Incidence of Use of Acid Suppression Medications in Infants with Oral Clefting

Less than 1% of the general pediatric population needs pharmacologic therapy for reflux symptoms; yet, the co-existence of gastroesophageal reflux disease (GERD) with oral clefting remains unclear. The purpose of this retrospective study was to appreciate the difference in the incidence of anti-GERD pharmacotherapy in a sample population of infants with oral clefting compared to the general pediatric population. One hundred ninety-six consecutive patients diagnosed with cleft lip only, cleft lip and palate, and isolated cleft palate were analyzed through clinical record review. Demographic and clinical information including but not limited to the type of oral cleft present at birth, reported signs and symptoms of GERD, and anti-GERD medications used were compiled for all subjects. Collected data were analyzed using descriptive statistics. Sixty-four (33%) of 196 infants with oral clefts had documented signs and symptoms of GERD. Nine percent (18 of 196) of the subjects received anti-GERD medications. The infant subgroup with treated GERD consisted of 11 out of 62 (18%) patients with isolated cleft palate, 5 of 112 (4.5%) with cleft lip and palate, and 2 of 17 (11%) with cleft lip only. The incidence of anti-GERD pharmacologic therapy among infants with oral clefts (9%) is significantly higher than among the general pediatric population (<1%). Furthermore, palatal clefts impart a greater risk of GERD symptoms than clefts of the alveolus, lip, or nose. In order to minimize the long-term consequences of GERD, a standardized interdisciplinary clinical protocol is necessary for evaluating infants with oral clefts.

On: Laparoscopic fundoplication: Nissen versus Toupet two-year outcome of a prospective randomized study of 200 patients regarding preoperative esophageal motility [Surg Endosc 22(1):21–30

Dear sirs, We read with great interest the recent publication entitled ‘‘Laparoscopic fundoplication: Nissen versus Toupet twoyear outcome of a prospective randomized study of 200 patients regarding preoperative esophageal motility’’ [1]. We already published in 2005 an analysis of our patients operated within the so-called tailored approach on 209 patients with a median follow-up of 52 months [2]. We compared those patients without recurrence regarding their long-term symptoms and their functional results and came to the same conclusion as the authors of the above mentioned publication. The laparoscopic partial posterior (Toupet) fundoplication seems to be the better operative procedure for the treatment of gastroesophageal reflux disease (GERD). It has a lower rate of side effects, nota bene less dysphagia and, given the appropriate technique, it restores the antireflux barrier to the same extent as the Nissen fundoplication [2]. Moreover, in our studies [2, 3] we were even able to demonstrate an improvement of former impaired esophageal motility in the Toupet group, while this was not found in the Nissen group. In our study, there was a strong correlation between postoperative dysphagia and impaired postoperative lower esophageal sphincter (LES) relaxation (Spearman correlation; rs = -0.75 at a p value \0.05) and the same was true for bloating (rs = -0.71), inability to belch (rs = -0.82), inability to vomit (rs = -0.86), and epigastric pain (rs = -0.68). In other words, the Nissen fundoplication may lead to an impairment of the LES relaxation often to an extent like in achalasia, while this was not seen after a Toupet fundoplication; so we concluded that an impaired relaxation could be the main cause of this problem. Unlike mentioned in the discussion of Strate et al.’s paper, patients without symptoms but inflammation of the esophagus or those with pathologic acid exposure of the distal esophagus in 24-h pH monitoring should rather be counted as recurrencies, since we know that heartburn symptoms do not correlate with esophagitis in a large number of patients. Whenever neoplastic consequences of GERD are discussed, a recurrent exposition of the esophagus to refluxate will lead GERD potentially to progress into metaplasia and dysplasia [4]. However, the dissection of the distal esophagus during surgery might lead to an altered sensitivity within the esophagus, thus leading to esophagitis without heartburn when reflux recurs. In the discussion of this publication, it is also stated that there were some discrepancies of manometric results in comparison with findings on 24-h pH monitoring [5]. The statement ‘‘...normal LES pressure due to an intact fundic wrap but still suffer from reflux recurrence due to crural disruption...’’ might probably rather be explained by the technique applied in manometry: the mean LES pressure value may be normal, but often a shortened intra-abdominal length diminishes the overall competency of the antireflux valve. This could be expressed by measuring the intra-abdominal vector volume of the LES [6]. This is supported by the fact that the reported mean intra-abdominal length in this paper is rather at the lower end of the norm. Several small details in operative technique, which are not even mentioned [7], could result in a different method H. Wykypiel (&) Department of General and Transplant Surgery, Medical University Innsbruck, Innsbruck, Austria e-mail: heinz.wykypiel@uibk.ac.at

Inducible nitric oxide synthase, nitrotyrosine and p53 mutations in the molecular pathogenesis of Barrett's esophagus and esophageal adenocarcinoma

Nitric oxide (NO) has been implicated as a potential causative factor for endogenous p53 mutations in gastrointestinal malignancy. To investigate the role of NO in esophageal adenocarcinoma (EADC), we studied patterns of p53 mutations, expression of inducible nitric oxide synthase (iNOS) and the tissue accumulation of nitrotyrosine (NTS), a stable reaction product of NO and a marker for cellular protein damage, in human premalignant and malignant esophageal epithelia. Tissues were obtained from patients with gastroesophageal reflux disease (GERD)-induced esophagitis (n = 76), Barrett's esophagus (BE; n = 119) and primary EADC (n = 54). DNA sequencing was used to characterize p53 mutations, RT-PCR to study iNOS mRNA expression, and immunohistochemistry to study NTS. Relative to self-matched normal epithelia, a progressive increase in iNOS mRNA expression was seen in GERD (30%; 23/76), BE (48%; 57/119), and EADC (63%; 34/54) tissues (P < 0.001). Among patients with EADC, elevated levels of NTS immunoreactivity were more frequent in tumors with p53 mutations (11/21; 52%) compared with tumors with wild-type p53 (9/33; 27%; P = 0.063), and specifically in tumors with p53 mutations at CpG dinucleotides (10/12; 83%) compared with non-CpG p53 mutations (1/9; 11%; P = 0.008). The increasing frequency of iNOS (mRNA) overexpression in GERD, BE and EADC supports the hypothesis that an active inflammatory process, most likely a consequence of GERD, underlies molecular progression to EADC. The highly significant association between NTS, reflecting chronic NO-induced cellular protein damage, and endogenous p53 mutations at CpG dinucleotides, provides further evidence for a molecular link between chronic inflammation and esophageal malignancy.

Barrett's esophagus and its correlation with gastroesophageal reflux in Chinese.

To study the prevalence of Barrett's esophagus in Chinese and its correlation with gastroesophageal reflux. This study was carried out in a large prospective series of 391 patients who had undergone upper endoscopy. The patients were divided into 3 groups according to the position of squamocolumnar junction (SCJ). Reflux esophagitis (RE) and its degree were recorded. Intestinal metaplasia (IM) in biopsy specimen was typed according to histochemistry and HE and alcian blue (pH2.5) staining separately. Results correlating with clinical, endoscopic, and pathological data were analysed. The prevalence of IM endoscopically appearing Long-segment Barrett's Esophagus (LSBE) was 26.53%, Short-segment Barrett's Esophagus (SSBE) was 33.85% and gastroesophageal junction (GEJ) was 34.00%. IM increased with age of above 40 years old and no difference was found between male and female. Twelve were diagnosed as dysplasia (7 low-grade, 5 high-grade), 16 were diagnosed as cardiac adenocarcinoma and 1 as esophageal adenocarcinoma. The more far away the SCJ moved upward above GEJ, the higher the prevalence and the more severe the RE were. There was no difference of the prevalence of IM in different places of SCJ, and IM increased with age of above 40 years old. It is important to pay attention to dysplasia in the distal esophagus and gastro-esophageal junction, and adenocarcinoma is more common in cardia than in esophagus. BE is a consequence of gastroesophageal reflux disease.

Etiology of intestinal metaplasia at the gastroesophageal junction.

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. 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. 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. 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.

Inflammation in the cardia.

The detection of chronic inflammation and intestinal metaplasia at the gastric side of a normal-appearing esophagogastric junction started active research on gastric cardia pathology. The main causes for this interest have been the increasing incidence of gastroesophageal reflux disease (GERD) and cardia adenocarcinoma. Many controversies still exist. It is even controversial whether noninflamed gastric cardia epithelium is a normal structure present at birth or an acquired lesion as a consequence of GERD. Similarly, the pathogenesis of chronic inflammation and intestinal metaplasia of gastric cardia are a matter of debate. Some researchers consider these lesions to be a consequence of Helicobacter pylori infection, whereas others think that chronic cardia inflammation and intestinal metaplasia are consequences of GERD. In this paper we review recent published studies in this field.

Short-segment Barrett's Esophagus: a prevalent complication of gastroesophageal reflux disease with malignant potential

The significance of finding specialized intestinal epithelium localized to the region of the gastroesophageal junction is unclear. We tested the hypothesis that short segments of specialized intestinal epithelium are a consequence of gastroesophageal reflux disease and are premalignant. Two hundred forty-one patients with reflux symptoms underwent gastroscopy with rigorous biopsy. Barrett's esophagus was diagnosed when specialized intestinal epithelium was present on biopsy. Patients with Barrett's esophagus were subdivided according to the length of Barrett's mucosa: short-segment Barrett's (<3 cm) and extended Barrett's (≥3 cm). Esophageal function was evaluated by manometry and 24-hour pH monitoring. In another 16 patients with small noncircumferential adenocarcinomas, the endoscopic length of Barrett's mucosa was recorded. Thirty-three patients (14%) had short-segment Barrett's and 37 (15%) had extended Barrett's esophagus. Patients with short-segment Barrett's esophagus had significantly more acid exposure than patients without specialized intestinal epithelium. Eighty-one percent of patients with short-segment Barrett's esophagus had increased esophageal acid exposure as did 100% of those with extended Barrett's esophagus. All lengths of Barrett's mucosa were associated with poor esophageal sphincter function and reduced contraction amplitudes in the distal esophagus. Twelve percent of patients with short-segment Barrett's esophagus had dysplasia. The length of Barrett's mucosa was ≤3 cm in 25% (4 of 16) of patients with early Barrett's adenocarcinoma. Short-segment Barrett's esophagus is commonly associated with gastroesophageal reflux disease. Further, short segments of specialized intestinal epithelium are premalignant in nature.