Long-standing Gastroesophageal Reflux Disease Research Articles

Transoral incisionless fundoplication and open hiatal hernia repair: A case report

IntroductionTransoral incisionless fundoplication is a new procedure that has recently emerged as a potential alternative to traditional anti-reflux surgeries. It is a less invasive option with fewer complications and reduced recovery time. Hiatal hernia repair is also commonly performed in conjunction with transoral incisionless fundoplication to improve outcomes. In this case, it details a successful transoral incisionless fundoplication and hiatal hernia repair procedure in a patient with long standing gastroesophageal reflux disease (GERD). The case is unique as it involved a patient with an uncharacteristically large hiatal hernia measuring above 5cm, which is a size that is generally not considered suitable for transoral incisionless fundoplication. The hiatal hernia was repaired with a gastrectomy instead of laparoscopically due to the size and adhesions present.Case detailsThis case report presents an 86 year old female patient with a history of long-standing GERD symptoms from the past 10 years who had failed to respond to medical therapy. Endoscopic imaging revealed a hernia of more than 5cm in size, which was confirmed by a bravo study. A DeMeester score of 446 was reported. The patient was referred for surgery and underwent transoral incisionless fundoplication with hiatal hernia repair. Despite the large size of the hiatal hernia, it was decided to proceed with a transoral incisionless fundoplication (TIF) procedure combined with hiatal hernia repair. The gastrectomy was chosen due to significant adhesions and anatomical distortion, making it difficult to continue laparoscopically. The esophagus was fibrosed to the pericardium, and the stomach was stuck in a retrocardiac position. Laparoscopic removal of the adhesions proved difficult since the patient had friable tissues, and there was a high risk of injury to surrounding organs. The surgery was therefore converted to an open approach, and the hernia was repaired with a gastrectomy. The TIF procedure was performed successfully, and the patient had no complications postoperatively.ConclusionThis case details a successful transoral incisionless fundoplication procedure for GERD in a patient with an uncharacteristically large hiatal hernia. Despite the challenges posed by the hernia’s size and anatomical distortion, the TIF procedure combined with hiatal hernia repair was successful in providing relief from GERD symptoms, with no postoperative complications. The case highlights the potential suitability of TIF as an alternative to laparoscopic fundoplication in patients with large hiatal hernias, although gastrectomy may be necessary in cases with significant adhesions or anatomical distortion.

Surgical Treatment of Decompensated Cicatricial Stricture of the Esophagus, Grade III-IV Dysphagia, and Compression Syndrome Caused by Nontoxic Multinodular Goiter: A Case Report

Objective: Long-standing gastroesophageal reflux disease is the most common cause of a cicatricial stricture of the esophagus. The treatment of this pathology involves a wide range of methods including conservative and surgical options. Surgeons can encounter technical difficulties in case of concomitant neck and chest pathology.Clinical case: We report a case of a decompensated cicatricial stricture of the esophagus with concomitant paraesophageal hiatal hernia, refractory gastroesophageal reflux disease, and nontoxic multinodular goiter (166.9 cm3). Selecting the optimal management for such patients is often a challenge. Staged treatment significantly improves postoperative quality of life, but the increased length of hospital stay can negatively impact patient compliance.

Eosinophilic esophagitis, Barrett's esophagus and esophageal neoplasms in the pediatric patient: a narrative review.

There are several esophageal disorders that can occur in the pediatric population. Eosinophilic esophagitis (EoE) is an eosinophil predominant inflammatory disease of the esophagus that was first characterized in the early 1900's. EoE is the most common pediatric esophageal inflammatory condition after gastroesophageal reflux disease (GERD). Longstanding GERD is a known risk factor for the development of Barrett's esophagus (BE) in both children and adults. BE is associated with the development of dysplasia and, if left undiagnosed, may progress to the development of esophageal adenocarcinoma (EAC). EAC and esophageal squamous cell carcinoma (ESCC) comprise the majority of childhood esophageal malignant neoplasms. The prevalence of EoE continues to rise within the pediatric population. On the other hand, both BE and esophageal neoplasms remain extremely rare in children. The relationship between a chronic inflammatory condition like EoE to BE and/or esophageal neoplasms remains unclear. The current research of these disease entities is prioritized to further understanding the disease pathogenesis and disease progression, exploring new diagnostic modalities, and developing novel treatments or less invasive therapeutic options. The focus of the following narrative review is to provide a summary of the current clinical practices, future research and their implications on these various esophageal disorders.

Reflux Control After Barrett’s Esophagus Ablation

Esophageal adenocarcinoma (EAC) is difficult to treat and carries a poor prognosis. Barrett’s esophagus, which develops from long-standing gastroesophageal reflux disease, is the only known precursor to EAC. Endoscopic eradication therapy is a major advancement in the treatment of dysplastic Barrett’s esophagus and early EAC; however, failure to eradicate disease and a high rate of recurrence with risk of progression currently remain unacceptably high with the use of acid suppressive medication for reflux. Herein, we describe the physiology of gastroesophageal reflux and review the current literature on endoscopic eradication therapy for Barrett’s esophagus. We summarize that antireflux surgery for reflux control as an adjunct to endoscopic eradication therapy may decrease the need for multiple endoscopic sessions (to achieve eradication), decrease the risk for recurrence/progression, and potentially decrease the need for surveillance.

The Y-chromosome F haplogroup contributes to the development of Barrett’s esophagus-associated esophageal adenocarcinoma in a white male population

SummaryBarrett’s esophagus (BE) is a metaplastic condition of the distal esophagus, resulting from longstanding gastroesophageal reflux disease (GERD). BE predisposes for the highly malignant esophageal adenocarcinoma (EAC). Both BE and EAC have the highest frequencies in white males. Only a subset of patients with GERD develop BE, while <0.5% of BE will progress to EAC. Therefore, it is most likely that the development of BE and EAC is associated with underlying genetic factors. We hypothesized that in white males, Y-chromosomal haplogroups are associated with BE and EAC. To investigate this we conducted a multicenter study studying the frequencies of the Y-chromosomal haplogroups in GERD, BE, and EAC patients. We used genomic analysis by polymerase chain reaction and restriction fragment length polymorphism to determine the frequency of six Y-chromosomal haplogroups (DE, F(xJ,xK), K(xP), J, P(xR1a), and R1a) between GERD, BE, and EAC in a cohort of 1,365 white males, including 612 GERD, 753 BE patients, while 178 of the BE patients also had BE-associated EAC. Univariate logistic regression analysis was used to compare the outcomes. In this study, we found the R1a (6% vs. 9%, P = 0.04) and K (3% vs. 6%, P = 0.035) to be significantly underrepresented in BE patients as compared to GERD patients with an odds ratio (OR) of 0.63 (95% CI 0.42–0.95, P = 0.03) and of 0.56 (95% CI 0.33–0.96, P = 0.03), respectively, while the K haplogroup was protective against EAC (OR 0.30; 95% CI 0.07–0.86, P = 0.05). A significant overrepresentation of the F haplogroup was found in EAC compared to BE and GERD patients (34% vs. 27% and 23%, respectively). The F haplogroup was found to be a risk factor for EAC with an OR of 1.5 (95% CI 1.03–2.19, P = 0.03). We identified the R1a and K haplogroups as protective factors against development of BE. These haplogroups have low frequencies in white male populations. Of importance is that we could link the presence of the predominantly occurring F haplogroup in white males to EAC. It is possible that this F haplogroup is associated to genetic variants that predispose for the EAC development. In future, the haplogroups could be applied to improve stratification of BE and GERD patients with increased risk to develop BE and/or EAC.

Bariatric surgery and gastroesophageal reflux disease.

With the rapidly increasing prevalence of obesity globally, the practice of bariatric surgery is being adopted routinely to prevent the development of chronic conditions as well as some forms of cancers associated with obesity. Gastroesophageal reflux disease (GERD) is one of those chronic conditions. Furthermore, there is accumulating data that obesity is associated with complications related to longstanding GERD such as erosive esophagitis (EE), Barrett’s esophagus (BE), and esophageal adenocarcinoma (EAC). Central obesity, rather than body mass index (BMI), appears to be more closely associated with these complications. It should be expected, therefore, that weight loss procedures should result in improvement in GERD symptoms and its associated complications. However, in reality the different bariatric surgical procedures have unpredictable effects on an established GERD and may even produce GERD symptoms for the very first time (de novo). In this review, we explore the literature studying the effects of bariatric surgical operations on GERD. Roux-en-Y gastric bypass appears to have the most beneficial effect on GERD. On the other hand, laparoscopic sleeve gastrectomy and laparoscopic adjustable gastric banding (LAGB) are linked with long-term increased prevalence of GERD. We argue that GERD is an extremely important preoperative consideration for any patient undergoing bariatric surgery and therefore should be thoroughly investigated objectively (with 24-hour pH study and high-resolution manometry) to select the most suitable bariatric procedure for patients for their long-term success.

Role of gastrointestinal endoscopy in the screening of digestive tract cancers in Europe: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.

In Europe at present, but also in 2040, 1 in 3 cancer-related deaths are expected to be caused by digestive cancers. Endoscopic technologies enable diagnosis, with relatively low invasiveness, of precancerous conditions and early cancers, thereby improving patient survival. Overall, endoscopy capacity must be adjusted to facilitate both effective screening programs and rigorous control of the quality assurance and surveillance systems required. 1 : For average-risk populations, ESGE recommends the implementation of organized population-based screening programs FOR COLORECTAL CANCER: , based on fecal immunochemical testing (FIT), targeting individuals, irrespective of gender, aged between 50 and 75 years. Depending on local factors, namely the adherence of the target population and availability of endoscopy services, primary screening by colonoscopy or sigmoidoscopy may also be recommendable. 2 : In high-risk populations, endoscopic screening FOR GASTRIC CANCER: should be considered for individuals aged more than 40 years. Its use in countries/regions with intermediate risk may be considered on the basis of local settings and availability of endoscopic resources. 3 : For esophageal and pancreatic cancer, endoscopic screening may be considered only in high-risk individuals:- FOR SQUAMOUS CELL CARCINOMA: , in those with a personal history of head/neck cancer, achalasia, or previous caustic injury; - FOR BARRETT'S ESOPHAGUS (BE)-ASSOCIATED ADENOCARCINOMA: , in those with long-standing gastroesophageal reflux disease symptoms (i. e., > 5 years) and multiple risk factors (age ≥ 50 years, white race, male sex, obesity, first-degree relative with BE or esophageal adenocarcinoma [EAC]). - FOR PANCREATIC CANCER SCREENING: , endoscopic ultrasound may be used in selected high-risk patients such as those with a strong family history and/or genetic susceptibility.

Update on the Durability and Performance of Collis Gastroplasty For Chronic GERD and Hiatal Hernia Repair At 4-Year Post-Intervention

BackgroundCollis gastroplasty (CG) remains an important procedure to lengthen the esophagus when indicated in patients undergoing fundoplication for longstanding refractory gastroesophageal reflux disease (GERD) or large hiatal hernias. Concerns over potential sequelae of CG such as dysphagia and worsening heartburn as well as questions regarding the durability of the procedure remain a subject of debate. In this study, 3 and 4-year postoperative data is presented assessing patient quality of life (QOL) measures for those undergoing laparoscopic antireflux surgery (LARS) with and without CG. MethodsComparative review of a prospectively maintained GERD patient database was conducted between patients undergoing LARS with CG versus non-CG (NC) at two institutions between October 2004 and February 2019. Patient demographic, perioperative, and QOL data was analyzed at 3 and 4 years postoperatively using four validated instruments: the Reflux Symptom Index (RSI), Laryngopharyngeal Reflux QOL (LPR-QOL), Swallowing QOL (SWAL), and Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQOL) surveys. ResultsA total of 214 CG and 798 NC patients were included in this study. The CG group was older (66.1±12.9 vs. 59.0 ± 14.1, p < 0.001), had a higher frequency of ASA class 3 patients (39.7% vs. 29.7%), and had greater proportion of comorbid disease compared to NG. The groups were parallel in BMI (Collis 28.4±5.2 kg/m2 vs. non-Collis 28.6±5.3 kg/m2, p = 0.673). Subset analysis revealed persistent benefits through 4 years reflected by survey results in both groups. There were no statistically significant differences in QOL outcomes between CG and NC. A majority of patients in both groups reported discontinuation of antireflux medications and satisfaction with surgical outcomes and symptom control. ConclusionLong-term QOL outcomes after laparoscopic CG are comparable to patients treated with fundoplication alone in cases of long-standing GERD and hiatal hernias. Furthermore, CG patients enjoyed equivalent durability of the procedure without risk of subsequent dysphagia. Collis gastroplasty remains an important tool in the armamentarium of foregut surgeons.

Retrospective Analysis of Eosinophilic Esophagitis in Patients with Refractory Gastroesophageal Reflux Disease.

IntroductionEosinophilic esophagitis (EoE) is not a common differential diagnosis in patients with longstanding refractory gastroesophageal reflux disease (GERD). The aim of this retrospective analysis was to assess the prevalence of EoE in patients with refractory GERD.MethodsThis retrospective analysis was performed in the Gastroenterology Department of a tertiary care institute in Karachi, Pakistan. Records of esophagogastroduodenoscopy (EGD) with esophageal biopsy from January 2016 till December 2018 were included.ResultsThere were 16 (7.7%) patients of refractory GERD diagnosed with EoE. There were more females than males (5:3). The median age was 58 years (range: 41-63 years). Dysphagia was the chief complaint leading to EGD followed by food impaction and heartburn. The median duration of symptoms was 46.5 months (range: 22-65 months). Erosive esophagitis, white plaques, and friability are common endoscopic findings; however, strictures are also not uncommon.ConclusionEosinophilic esophagitis is not uncommon in patients with refractory GERD. It may present with dysphagia, heartburn, and food impaction. Old patients with longstanding GERD, positive for atopy, not responding to gastric acid inhibitors must be considered for EoE screening via EGD and esophageal biopsy.

Аденокарцинома пищевода: факторы риска и современные стратегии скрининга

Aim of review. To present the modern concepts on epidemiological pattern and risk factors of esophageal adenocarcinoma (EAC) and analyze the modern screening approach. Summary. In developed countries EAC is characterized by rapid increase of mobidity, as well as by high mortality level. As a rule, EAC is diagnosed at the late stage: diagnosis is often made at the 3rd or 4th stage of the tumor that is a major contributing factor for high mortality as treatment options at these stages are significantly limited. The basic established risk factor for EAC is the gastroesophageal reflux disease (GERD). EAC develops usually as a complication of the Barret's esophagus (BE) being a consequence of the long-standing GERD. Male gender, Caucasian race, obesity and metabolic syndrome, tobacco smoking, and series of genetic markers are considered to be significant EAC risk factors. A main goal of EAC screening programs is the early diagnosis that allows to improve patient survival. Conclusion. Only GERD patients develop EAC, with the highest risk in males, Caucasians, smokers, overweight patients and those with uncontrolled symptoms. Timely diagnosis of GERD, its effective treatment and follow-up of BE cases can prevent EAC development.

Multiple recurrences of esophageal adenocarcinoma after esophagectomy.

We present a patient with an unusual course of late and multiple recurrences of esophageal adenocarcinoma (EAC) after esophagectomy. A 57-year-old man with longstanding gastroesophageal reflux disease (GERD) underwent screening upper endoscopy in September 2004 and was found to have a 6 cm mass in a 7 cm segment of Barrett’s esophagus (BE). Endoscopic ultrasound (EUS) showed a T2N0 mass and positron emission tomography (PET) scan revealed no distant metastases. Biopsies showed a poorly differentiated EAC of the distal esophagus. He underwent total esophagectomy (post-operatively restaged T3N1M0) followed by adjuvant chemoradiation therapy completed in February 2005

Fatal Aortoesophageal Fistula Following Neoadjuvant Chemoradiation and Robot-Assisted Esophagectomy for Stage IIIa Esophageal Adenocarcinoma

Esophageal cancer is the sixth leading cause of cancer death worldwide, with an estimated 15,500 yearly death total in the US alone. Management guidelines advocate neoadjuvant chemoradiation followed by esophagectomy for T1-T3, and regional T4 disease. Depending on malignancy location, various surgical resection techniques can be utilized, including more recently the robot assisted minimally invasive esophagectomy (RAMIE). 54 year-old female with longstanding gastroesophageal reflux disease (GERD) presented to an outside medical center with progressive dysphagia. Esophagogastroduodenoscopy (EGD) revealed a circumferential ulcerated mass at the GE junction. Biopsies, endoscopic ultrasound and positron emission tomography (PET) scan revealed a stage IIIa (T3N1M0) esophageal adenocarcinoma. Neoadjuvant chemoradiation was initiated, and at 5 months post cancer diagnosis, RAMIE with mediastinal drain placement was performed. Post-operative day 11, patient developed acute chest pain, computerized tomography (CT) chest scan noted an esophageal perforation. EGD confirmed a 3 cm anastomotic dehiscence, 23cm from the incisors, communicating with the mediastinum. Defect closure with the Apollo overstitch device (Apollo EndoSurgery, Austin, TX) was attempted; however, the sutures could not fasten the thin ulcerated tissue. A fully covered esophageal stent was placed, however the stent eventually migrated and was replaced with a partially covered stent. Post-operative day 32, patient suffered acute massive hematemesis with hemodynamic compromise. Repeat EGD with esophageal stent removal revealed active arterial bleeding at the anastomotic dehiscence site. Massive hematemesis intermittently recurred despite epinephrine injection therapy. Subsequent interventional radiology (IR) angiography was performed revealing the presence of an aortoesophageal fistula (AEF). During angiography, the patient coded and shortly thereafter was pronounced dead, autopsy was declined. AEF formation post esophagectomy is an exceedingly rare and often fatal complication that arises from an anastomotic leakage or peptic ulceration. The nidus dehiscence is often attributed to postsurgical ischemia, neoadjuvant chemoradiation and/or mediastinitis. In this particular case, mediastinitis was the likely underlying factor for AEF formation. Ultimately, it is important to recognize that AEF is a potential complication in patients with a documented post-esophagectomy anastomotic dehiscence.

Esophageal Adenocarcinoma Masquerading as Hyperplastic Polyps

Introduction: We report a case with the rare occurrence of hyperplastic polypoid lesions in the background of Barrett's esophagus in associated with invasive adenocarcinoma of the esophagogastric junction (EGJ). Case Report: A 65 year old Caucasian male with chronic acid reflux presented with progressive dysphagia and weight loss. Exam was unremarkable except for a body mass index of 37. Lab studies showed mild anemia with hemoglobin of 12.5 gm/dl. Esophagogastroduodenoscopy (EGD) revealed a diffuse, polypoid growth involving the distal 14 cm of the esophagus. Histological exam revealed glandular mucosa with elongated hyperplastic foveolar epithelium and cystic changes, consistent with hyperplastic polyp. EGD was repeated and tissue specimen collected with cold snare as well as multiple 4 quadrant biopsies every 1 cm, histology revealed hyperplastic polyps in the background of intestinal metaplasia without dysplasia. Endoscopic ultrasonography (EUS) showed that the growth was limited to the mucosal layer, positron emission test (PET) scan showed increased uptake only in the distal esophagus. Patient was referred to surgery and underwent esophagectomy with proximal gastrectomy. Esophago-gastric continuity could not be achieved, thus a left sided esophageal spit fistula was created. Surgical specimen showed moderately differentiated adenocarcinoma with tumor invasion through muscularis propria into the serosal fat at the EGJ and multiple lymph nodes involvement. Discussion: Epithelial polypoid lesions of the esophagus and EGJ are uncommon. Most of these lesions reportedly occur at the EGJ (67%) followed by distal esophagus (30%). Among these lesions, hyperplastic polyps are quite rare and usually occur in the setting of long-standing gastro esophageal reflux disease. In the largest reported case series by Abraham et al., among 27 patients with hyperplastic esophageal and EGJ polyps, only 15% had concomitant Barrett's esophagus. There have been only two cases reported of hyperplastic polyps at EGJ where subsequent endoscopic mucosal resection showed foci of high grade dysplasia and adenocarcinoma. Our case is unique due to the presence of long segment Barrett's esophagus with concomitant circumferential, villiform polypoid growth where multiple repeat mucosal biopsies showed reactive changes. Due to the diffuse extensive nature of the lesion it was not amenable to safe endoscopic resection and thus required surgical resection which revealed an invasive adenocarcinoma of the EGJ. This case highlights the extremely rare occurrence of the hyperplastic polyps in the setting of Barrett's esophagus and invasive adenocarcinoma of the EGJ. It also underscores the fact that malignancy in this setting should always be suspected even when mucosal biopsies are negative.Figure 1Figure 2Figure 3

Animal Models of Barrett's Esophagus and Esophageal Adenocarcinoma-Past, Present, and Future.

Esophageal adenocarcinoma is the fastest rising cancer in the United States. It develops from long-standing gastroesophageal reflux disease which affects >20% of the general population. It carries a very poor prognosis with 5-year survival <20%. The disease is known to sequentially progress from reflux esophagitis to a metaplastic precursor, Barrett's esophagus and then onto dysplasia and esophageal adenocarcinoma. However, only few patients with reflux develop Barrett's esophagus and only a minority of these turn malignant. The reason for this heterogeneity in clinical progression is unknown. To improve patient management, molecular changes which facilitate disease progression must be identified. Animal models can provide a comprehensive functional and anatomic platform for such a study. Rats and mice have been the most widely studied but disease homology with humans has been questioned. No animal model naturally simulates the inflammation to adenocarcinoma progression as in humans, with all models requiring surgical bypass or destruction of existing antireflux mechanisms. Valuable properties of individual models could be utilized to holistically evaluate disease progression. In this review paper, we critically examined the current animal models of Barrett's esophagus, their differences and homologies with human disease and how they have shaped our current understanding of Barrett's carcinogenesis.

Acute Coronary Syndrome: An Unusual Consequence of GERD.

We report a case of an 83-year-old man with history of coronary artery disease and gastroesophageal reflux disease (GERD) who presented with sudden onset nocturnal dyspnea. He was diagnosed with non-ST elevation myocardial infarction based on the electrocardiographic changes and cardiac biomarker elevation. Cardiac catheterization revealed chronic three-vessel coronary artery disease, with 2 patent grafts and 2 chronically occluded grafts. While at the hospital, the patient experienced a similar episode of nocturnal dyspnea, prompting a barium esophagram, which was suggestive of a stricture in the distal esophagus from long-standing GERD. We hypothesized that he had myocardial ischemia due to increased oxygen demand from uncontrolled GERD symptoms. He had no further ischemic episodes after increasing the dose of antireflux medication over a 6-month follow-up. After presenting our case, we review the literature on this atypical presentation of GERD causing acute coronary syndrome and discuss potential mechanisms.

Immunohitochemical study of p53 protein expression in gastroesophageal reflux disease

ObjectiveThis study aimed to determine p53 protein expression by immunohistochemistry in the esophageal mucosa of patients with gastroesophageal reflux disease (GERD).BackgroundGERD is a common clinical disorder that can significantly impact the patient's quality of life and pose a significant burden on healthcare systems worldwide. The incidence of esophageal adenocarcinoma has been increasing rapidly over the past few decades. The major risk factors predisposing to the development of adenocarcinoma are long-standing GERD and Barrett's esophagus. P53 protein expression in esophageal carcinogenesis is still being studied. The identification of tumor markers in patients with GERD may enable recognition of subgroups of patients who are more at risk of developing dysplasia and/or cancer.Patients and methodsThis study was carried out on 200 patients with symptoms of GERD. They were recruited from the endoscopy unit of Menoufia University Hospital between August 2010 and March 2013, and were included in group 1. According to the results of upper endoscopy and histopathology, they were subdivided as follows: group 1a included patients with GERD with erosive esophagitis ( n = 180), group 1b included patients with GERD and Barrett's esophagus ( n = 20), and group 2 included 20 patients with other GIT symptoms with no reflux and normal esophageal squamous epithelium; this was the control group. Written valid consent was obtained from every patient for examination and upper endoscopy; the clinical sheet for every case was completed, including assessment of history, examination, and the investigations required.ResultsWe found negative reactivity for p53 in 20 histologically normal patients (0%), and positive p53 protein expression in 76 patients (40%) in the esophagitis group and in 14 patients (70%) with Barrett's metaplasia ( n = 20). According to the Los Angeles classification grade, p53 was overexpressed in 33.3% ( n = 24) of esophagitis grade A (mild esophagitis) patients, 46.3% ( n = 32) of esophagitis grade B (moderate esophagitis) patients, 56.4% ( n = 22) of esophagitis grade C patients, and 60% ( n = 12) of esophagitis grade D (severe esophagitis) patients.ConclusionGERD grades C and D were more prevalent in Barrett's esophagus. P53 expression was higher in Barrett's esophagus than in erosive esophagitis compared with the normal group. P53 protein expression increases gradually with the severity of esophagitis caused by GERD.

Extraesophageal Malignancies Among Patients With Barrett Esophagus

To evaluate the incidence of extraesophageal malignancies among patients with Barrett esophagus (BE). Gastroesophageal reflux disease has been reported to be associated with upper aerodigestive malignancies. BE is considered a consequence of long-standing gastroesophageal reflux disease; however, the association of BE with extraesophageal malignancies is controversial. The database of the largest health service provider in Israel was queried for all patients diagnosed with BE between 2000 and 2010. Data regarding medical background and diagnosis of malignancy were recorded. Malignancy rates were compared with subjects without BE or malignancy and matched for age, sex, and smoking status (1:4 ratio). Patients in whom a malignancy was diagnosed within 1 year of BE diagnosis were excluded. A total of 3669 patients with BE and 14,676 controls were included. Several nonesophageal malignancies were significantly more prevalent among BE patients: colorectal cancer (relative risk 1.98, P<0.001) and prostate cancer (relative risk 1.99, P<0.001), but not cancer of the upper aerodigestive tract. Multivariate analysis revealed that Jewish origin and the presence of BE were associated with higher malignancy risk [hazard ratio (HR) 1.83, HR 1.41, respectively; P<0.001]; body mass index was inversely associated with malignancy risk (HR 0.98; P<0.005). BE seems to be associated with colorectal and prostate cancer. Further research is necessary to determine whether this is a causative relationship and, consequently, whether a change in the screening policy for colorectal cancer in patients with BE is warranted.

Prolonged exposure to acid and bile induces chromosome abnormalities that precede malignant transformation of benign Barrett’s epithelium

Barrett’s esophagus (BE) is an asymptomatic, pre-malignant condition of the esophagus that can progress to esophageal adenocarcinoma (EAC). BE arises typically in individuals with long-standing gastroesophageal reflux disease (GERD). The neoplastic progression of BE has been extensively studied histologically and defined as a metaplasia- dyplasia- carcinoma sequence. However the genetic basis of this process is poorly understood. It is conceived that preclinical models of BE may facilitate discovery of molecular markers due to ease of longitudinal sampling. Clinical markers to stratify the patients at higher risk are vital to institute appropriate therapeutic intervention since EAC has very poor prognosis. We developed a dynamic in-vitro BE carcinogenesis (BEC) model by exposing naïve Barrett’s epithelium cell line (BAR-T) to acid and bile at pH4 (B4), 5min/day for a year. The BEC model acquired malignant characteristics after chronic repeated exposure to B4 similar to the sequential progression of BE to EAC in vivo.AimTo study cytogenetic changes during progressive transformation in the BEC model.ResultsWe observed that the BAR-T cells progressively acquired several chromosomal abnormalities in the BEC model. Evidence of chromosomal loss (-Y) rearrangements [t(10;16) and dup (11q)] and clonal selection appeared during the early stages of the BEC model. Clonal selection resulted in a stabilized monoclonal population of cells that had a changed morphology and formed colony in soft agar. BAR-T cells grown in parallel without any exposure did not show any of these abnormalities.ConclusionsProlonged acid and bile exposure induced chromosomal aberrations and clonal selection in benign BAR-T cells. Since aneuploidy preceded morphological/dysplastic changes in the BEC model, chromosomal aberrations may be an early predictor of BE progression. The [t(10;16) and dup(11q)] aberrations identified in this study harbor several genes associated with cancer and may be responsible for neoplastic behavior of cells. After further validation, in-vivo, they may be clinically useful for diagnosis of BE, progressing to dysplasia/esophageal adenocarcinoma.

Management of High-Grade Dysplasia and Intramucosal Adenocarcinoma in Barrett's Esophagus

A 62-year-old Caucasian male with chronic long-standing gastroesophageal reflux disease and a history of nondysplastic Barrett's esophagus (BE) undergoes surveillance upper endoscopy with biopsies at an outside facility. Biopsies revealed high-grade dysplasia (HGD) and the patient is referred to a tertiary care referral center for endoscopic eradication therapy (EET). His symptoms are adequately controlled on twice daily proton pump inhibitor therapy, and he denies any alarm symptoms. His physical examination is unremarkable with the exception of mild obesity.

Effect of medical and surgical treatment of Barrett’s metaplasia

Barrett's esophagus (BE) is a change in the esophageal mucosa as a result of long-standing gastroesophageal reflux disease. The importance of BE is that it is the main risk factor for the development of esophageal adenocarcinoma, whose incidence is currently growing faster than any other cancer in the Western world. The aim of this review was to compare the common treatment modalities of BE, with the focus on proton pump inhibitors and operative fundoplication. We performed a literature search on medical and surgical treatment of BE to determine eligible studies for this review. Studies on medical and surgical treatment of BE are discussed with regard to treatment effect on progression and regression of disease. Although there is some evidence for control of reflux with either medical or surgical therapy, there is no definitive evidence that either treatment modality decreases the risk of progression to dysplasia or cancer. Even though there is a trend toward antireflux surgery being superior, there are no definitive studies to prove this.