Endoscopic mucosal resection for early adenocarcinoma arising in Barrett's esophagus

A 58‐year‐old man was diagnosed to have an esophageal adenocarcinoma arising in Barrett's esophagus by screening examination at the previous hospital. Endoscopically, a slightly reddish elevated lesion with a central depressed component was detected in the Barrett's epithelium. Endoscopic ultrasonography showed the thickness of the second layer of the esophagus and no enlarged lymph node. Histological examination of a biopsy specimen revealed well or moderately differentiated adenocarcinoma. From these findings, the lesion was diagnosed as a mucosal esophageal cancer, type IIa + IIc, arising in Barrett's esophagus. As he refused operation, the lesion was resected endoscopically with his informed consent. Histologically, the resected specimens showed moderately differentiated adenocarcinoma arising in Barrett's esophagus. The adenocarcinoma had invaded the superficial muscularis mucosa, but was limited to the deep one with no vessel invasion. Barrett's esophagus often has a double muscularis mucosa. Connective tissues containing vascular and lymphatic vessels exist between them. However, one consideration is whether the existence of vessels between the double muscularis mucosa and the presence of vessel invasion are risk factors for metastasis. In order for a definitive indication for endoscopic mucosal resection, the frequency of lymph node and distant metastasis in cases of early Barrett's cancer needs to be investigated.     

Barrett's esophagus and esophageal adenocarcinoma.

Barrett's esophagus is a condition in which the normal stratified squamous epithelium is replaced by a specialized metaplastic columnar epithelium. It develops as a consequence of chronic gastroesophageal reflux and predisposes to the development of esophageal adenocarcinoma. Adenocarcinoma develops in Barrett's esophagus by a multistep process in which specialized metaplasia progresses to dysplasia, then to early adenocarcinoma, and eventually to deeply invasive and metastatic disease. This neoplastic progression is associated with a process of genomic instability that generates abnormal clones of cells, some of which have aneuploid or increased G2/tetraploid DNA content. A systematic protocol of endoscopic biopsy can detect Barrett's adenocarcinomas at an early stage, when they may be curable.     

Endoscopic findings of adenocarcinoma arising from short-segment Barrett's esophagus

Adenocarcinoma arising from short-segment Barrett's esophagus (SSBE) is rare in Japan, although the incidence of this condition is increasing in Western countries. Four cases of early adenocarcinoma arising from SSBE were diagnosed and treated at Niigata-prefectural Yoshida Hospital. All patients were male, variously 55, 71, 73 and 79 years of age. All four patients had long-term gastroesophageal reflux disease, although one patient had erosive esophagitis and three patients did not have erosive esophagitis. Three patients were diagnosed as having Helicobacter pylori-free stomach. All adenocarcinomas occurred close to the squamocolumnar junction. Patients with SSBE should undergo detailed endoscopic examination of the squamocolumnar junction in order to detect early adenocarcinoma arising from SSBE.     

Advances in Barrett's esophagus and esophageal adenocarcinoma

Despite advances in diagnosis and therapy, esophageal adenocarcinoma remains an aggressive and usually lethal tumor. This review focuses on the epidemiology of esophageal adenocarcinoma and its presumed precursor lesion, Barrett's esophagus; the pathogenesis of the cancer; advances in treatment of adenocarcinoma and Barrett's esophagus; and strategies for cancer prevention. Emphasis is placed on recent literature. Although the absolute number of cases of adenocarcinoma in the United States is still small, the incidence of this cancer has increased dramatically in the last 40 years, and adenocarcinoma is now the predominant form of esophageal cancer in this country. Recent evidence suggests that Barrett's esophagus is more prevalent in asymptomatic individuals than previously appreciated. The pathogenesis of Barrett's esophagus is poorly understood. Given that some subjects will have repeated bouts of severe erosive esophagitis and never develop Barrett's esophagus, host factors must play an important role. The utility of neoadjuvant radiation and chemotherapy in those with adenocarcinoma, although they are widely practiced, is not of clear benefit, and some authorities recommend against it. Ablative therapies, as well as endoscopic mucosal resection, hold promise for those with superficial cancer or high-grade dysplasia. Most series using these modalities feature relatively short follow-up, and longer-term data will be necessary to better describe the effects of these therapies. The value of chemoprevention in subjects with dysplastic Barrett's esophagus by use of cyclooxygenase 2 inhibitors, nonsteroidal anti-inflammatory drugs, or proton pump inhibitors is unknown. Similarly, although endoscopic screening is widely practiced, its value in patients with chronic gastroesophageal reflux disease symptoms is of unproven value, and recommending bodies are divided as to its practice.     

Barrett's esophagus and risk of esophageal adenocarcinoma

Barrett's esophagus is most often seen in white men with chronic heartburn who are generally older than 50 years of age. The prevalence of Barrett's esophagus is 10% to 15% in patients who are undergoing endosocopy for gastroesophageal reflux disease and 1% to 2% in asymptomatic American adults. Barrett's esophagus represents metaplastic columnar tissue with specialized intestinal metaplasia, and this condition carries an increased risk of esophageal adenocarcinoma. Patients with Barrett's esophagus have a risk of esophageal adenocarcinoma 30 to 60 times that of the general population with an incidence rate of over 100 times that of the general population. Esophageal adenocarcinoma has increased dramatically over the past few decades with specialized intestinal metaplasia being the most important risk factor for the development of dysplasia and cancer. Barrett's esophagus develops in the presence of persistent gastroesophageal reflux, which is an independent risk factor for adenocarcinoma. Other risk factors for adenocarcinoma in patients with Barrett's esophagus include length of Barrett's epithelium, low-grade dysplasia, and high-grade dysplasia. New data concerning the pathophysiology and biology of Barrett's epithelium may provide answers to prevent or treat esophageal cancer. This article briefly reviews Barrett's esophagus and focuses on the risk factors associated with its progression to adenocarcinoma.     

Preoperative prevalence of Barrett's esophagus in esophageal adenocarcinoma: a systematic review.

BACKGROUND & AIMS: The public health impact of past screening and surveillance practices on the outcomes of Barrett's related cancers has not previously been quantified. Our purpose was to determine the prior prevalence of Barrett's esophagus in reported cases of incident adenocarcinoma undergoing resection, as an indirect measure of impact. METHODS: We performed a systematic review of the literature from 1966 to 2000. Studies were included if they reported: (1) the number of consecutive adenocarcinomas resected, and (2) the number of those resected who had a previously known diagnosis of Barrett's. We generated summary estimates using a random effects model. RESULTS: We identified and reviewed 752 studies. Twelve studies representing a total of 1503 unique cases of resected adenocarcinomas met inclusion criteria. Using a random effects model, the overall percentage of patients undergoing resection who had a prior diagnosis of Barrett's was 4.7% +/- 2.9%. CONCLUSIONS: The low prior prevalence (approximately 5%) of Barrett's esophagus in this study population provides indirect evidence to suggest that recent efforts to identify patients with Barrett's-whether through endoscopic screening or evaluation of symptomatic patients-have had minimal public health impact on esophageal adenocarcinoma outcomes. The potential benefits of endoscopic surveillance seem to have been limited to only a fraction of those individuals at risk. These data thus provide a clear and compelling rationale for the development of effective screening strategies to identify patients with Barrett's esophagus.     

Prevalence of Barrett's esophagus and expression of mucin antigens detected by a panel of monoclonal antibodies in Barrett's esophagus and esophageal adenocarcinoma in Japan

Barrett's esophagus (BE) is an acquired disorder associated with a high incidence of adenocarcinoma of the lower esophagus. Moreover, it has been reported that short-segment BE may be associated with adenocarcinoma of the esophagogastric junction. The objective of this study was to define the prevalence of BE and the mucin profile in BE, including the short-segment type, and to compare the mucin profile in BE with the profiles of Barrett's adenocarcinoma and distal esophageal adenocarcinoma among Japanese. In total, 650 adult subjects underwent endoscopic examination for evaluation of BE. Although the prevalence of traditional (long segment) BE was 0.62%, the overall prevalence of BE including short-segment type was 15.7%. In Barrett's epithelium, the short-segment type predominantly had gastric type mucin, while the middle- and long-segment types possessed intestinal mucin, especially colonic type mucin (sulfo-Lewis^a), with high frequency. In Barrett's epithelium with adenocarcinoma, all Barrett's epithelium adjacent to carcinomas showed a predominance of immunoreactivity to sulfo-Lewis^a. In Barrett's adenocarcinomas, colonic type mucin was detected in 100% by monoclonal antibody (MoAb) 91.9H. Small-intestinal mucin and gastric mucin were stained in 50% and 12.5% of the subjects, respectively. Colonic type mucin was also detected with high frequency (80%) in distal esophageal adenocarcinomas without Barrett's epithelium. These data suggest that the epitope, not of small-intestinal type or gastric type mucin, but of colonic type mucin (sulfo-Lewis^a), may be associated with, at least in part, the malignant phenotype of BE. Received: July 28, 1999 / Accepted: February 25, 2000     

Alteration of the esophageal microbiota in Barrett's esophagus and esophageal adenocarcinoma

The incidence of esophageal adenocarcinoma(EAC) has increased in recent decades, and its 5-year survival rate is less than 20%. As a well-established precursor, patients with Barrett's esophagus(BE) have a persistent risk of progression to EAC. Many researchers have already identified some factors that may contribute to the development of BE and EAC, and the identified risks include gastroesophageal reflux(GER), male sex, older age, central obesity,tobacco smoking, Helicobacter pylori(H. pylori) eradication, and the administration of proton pump inhibitors(PPIs) and antibiotics. The human gut harbors trillions of microorganisms, the majority of which are bacteria. These microorganisms benefit the human host in many ways, such as helping in digestion, assisting in the synthesis of certain vitamins, promoting the development of the gastrointestinal immune system, regulating metabolism and preventing invasion by specific pathogens. In contrast, microbial dysbiosis may play important roles in various diseases, such as inflammation and cancers. The composition of the microbiota located in the normal esophagus is relatively conserved without distinct microbial preferences in the upper, middle and lower esophagus. Six major phyla constitute the esophageal microbiota, including Firmicutes,Bacteroides, Actinobacteria, Proteobacteria, Fusobacteria and TM7, similar to the oral microbiota. Streptococcus dominates the esophageal microbiota. However, the microbiota varies in different esophageal diseases compared to that in the healthy esophagus. The type Ⅰ microbiota, which is primarily composed of gram-positive bacteria, is closely associated with the normal esophagus, while type Ⅱ microbiota has enriched gram-negative bacteria and is mainly associated with the abnormal esophagus. These increased gram-negative anaerobes/microaerophiles include Veillonella, Prevotella, Haemophilus, Neisseria, Granulicatella and Fusobacterium, many of which are associated with BE. The microbial diversity in the esophagus is decreased in EAC patients, and Lactobacillus fermentum is enriched compared to that in controls and BE patients. Furthermore, the microbiota may be associated with BE and EAC by interacting with their risk factors, including central obesity, GER, H. pylori, administration of PPIs and antibiotics. Therefore, a large gap in research must be bridged to elucidate the associations among these factors. Some studies have already proposed several potential mechanisms by which the microbiota participates in human carcinogenesis by complicated interactions with the human host immune system and signaling pathways. The activation of the LPS-TLR4-NF-κB pathway may contribute to inflammation and malignant transformation. This exciting field of gastrointestinal microbiota allows us to unravel the mystery of carcinogenesis from another perspective. Further studies are needed to explore whether the microbiota changes before or after disease onset, to improve our understanding of the pathogenesis, and to find novel targets for prevention, diagnosis and therapy, which could offer more cost-effective and relatively safe choices.     

MicroRNAs, development of Barrett’s esophagus, and progression to esophageal adenocarcinoma

Barrett's esophagus is a premalignant condition caused by gastroesophageal reflux. Once developed, it can progress through varying grades of dysplasia to esoph-ageal adenocarcinoma. Whilst it is well accepted that Barrett's esophagus is caused by gastroesophageal reflux, the molecular mechanisms of its pathogenesis and progression to cancer remain unclear. MicroRNAs (miRNAs) are short segments of RNA that have been shown to control the expression of many human genes. They have been implicated in most cellul...     

From reflux esophagitis to Barrett's esophagus and esophageal adenocarcinoma

The occurrence of gastroesophageal reflux disease is common in the human population.Almost all cases of esophageal adenocarcinoma are derived from Barrett's esophagus,which is a complication of esophageal adenocarcinoma precancerous lesions.Chronic exposure of the esophagus to gastroduodenal intestinal fluid is an important determinant factor in the development of Barrett's esophagus.The replacement of normal squamous epithelium with specific columnar epithelium in the lower esophagus induced by the chronic exposure to gastroduodenal fluid could lead to intestinal metaplasia,which is closely associated with the development of esophageal adenocarcinoma.However,the exact mechanism of injury is not completely understood.Various animal models of the developmental mechanisms of disease,and theoretical and clinical effects of drug treatment have been widely used in research.Recently,animal models employed in studies on gastroesophageal reflux injury have allowed significant progress.The advantage of using animal models lies in the ability to accurately control the experimental conditions for better evaluation of results.In this article,various modeling methods are reviewed,with discussion of the major findings on the developmental mechanism of Barrett's esophagus,which should help to develop better prevention and treatment strategies for Barrett's esophagus.     

Lifetime risk of esophageal adenocarcinoma in patients with Barrett's esophagus

AIM: To investigate the lifetime risk of development of esophageal adenocarcinoma and/or high-grade dysplasia in patients diagnosed with Barrett’s esophagus.METHODS: Data were extracted from the United Kingdom National Barrett’s Oesophagus Registry on date of diagnosis, patient age and gender of 7877 patients from who had been registered from 35 United Kingdom centers. Life expectancy was evaluated from United Kingdom National Statistics data based upon gender and age at year at diagnosis. These data were then used with published estimates of annual adenocarcinoma and high-grade dysplasia incidences from meta-analyses and large population-based studies to estimate overall lifetime risk of development of these study endpoints.RESULTS: The mean age at diagnosis of Barrett’s esophagus was 61.6 years in males and 67.3 years in females. The mean life expectancy at diagnosis was 23.1 years in males, 20.7 years in females and 22.2 years overall. Using data from published meta-analyses, the lifetime risk of development of adenocarcinoma was between 1 in 8 and 1 in 14 and the lifetime risk of high-grade dysplasia or adenocarcinoma was 1 in 5 to 1 in 6. Using data from 3 large recent population-based cohort studies the lifetime risk of adenocarcinoma was between 1 in 10 and 1 in 37 and of the combined end-point of high-grade dysplasia and adenocarcinoma was between 1 in 8 and 1 in 20. Age at Barrett’s esophagus diagnosis is reducing and life expectancy is increasing, which will partially counter-balance lower annual cancer incidence.CONCLUSION: There is a significant lifetime risk of development of high-grade dysplasia and adenocarcinoma in Barrett’s esophagus.     

Photodynamic therapy for mucosal esophageal adenocarcinoma and dysplastic Barrett's esophagus

Photodynamic therapy is a novel endoscopic technique that combines a photosensitizer and laser light to destroy target cells. Photodynamic therapy has been used in Europe, North Africa and Japan to treat esophageal neoplasms and dysplastic Barrett's esophagus. This paper summarizes the available published experience of photodynamic therapy for the treatment of each esophageal cancer and Barrett's esophagus. These studies suggest that photodynamic therapy is a promising modality for esophageal mucosal disease. More long-term studies, however, are needed to document the efficacy of photodynamic therapy in reducing the morbidity and mortality from esophageal cancer for patients with high-grade dysplasia and early adenocarcinoma in Barrett's esophagus.     

Australian clinical practice guidelines for the diagnosis and management of Barrett's esophagus and early esophageal adenocarcinoma

Barrett's esophagus (BE), a common condition, is the only known precursor to esophageal adenocarcinoma (EAC). There is uncertainty about the best way to manage BE as most people with BE never develop EAC and most patients diagnosed with EAC have no preceding diagnosis of BE. Moreover, there have been recent advances in knowledge and practice about the management of BE and early EAC. To aid clinical decision making in this rapidly moving field, Cancer Council Australia convened an expert working party to identify pertinent clinical questions. The questions covered a wide range of topics including endoscopic and histological definitions of BE and early EAC; prevalence, incidence, natural history, and risk factors for BE; and methods for managing BE and early EAC. The latter considered modification of lifestyle factors; screening and surveillance strategies; and medical, endoscopic, and surgical interventions. To answer each question, the working party systematically reviewed the literature and developed a set of recommendations through consensus. Evidence underpinning each recommendation was rated according to quality and applicability.     

Risk factors for the development of esophageal adenocarcinoma in Barrett's esophagus

OBJECTIVE: To identify risk factors for esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE). METHODS: A hospital-based case-control study was performed in which 91 cases with EAC and 244 controls with histologically confirmed BE (>2 cm) with no dysplasia or low-grade dysplasia were included. Information on demographic, anthropometric, and lifestyle characteristics, physical activity levels, working posture, family history, gastroesophageal reflux disease (GERD) symptoms, and medication use was collected by questionnaire. RESULTS: Cases more often were current smokers (odds ratio 3.7, 95% confidence interval 1.4-9.9), more often had a body mass index >25 assessed at age 20 (2.6, 1.2-5.5), and more frequently had been working in a stooped posture at age 20 (2.0, 1.1-3.9), compared to controls. In addition, cases less often experienced symptoms of heartburn (0.3, 0.2-0.5) and less frequently used proton pump inhibitors (0.1, 0.05-0.2), compared to controls, whereas use of nonsteroidal anti-inflammatory drugs/aspirin was more common among cases (1.8, 1.1-3.2). Cases more often were men, compared to controls (91%vs 67%, p < 0.001). CONCLUSION: In patients with BE, the risk of EAC is related to risk factors for GERD, which is, however, asymptomatic. As these risk factors are common in Western countries, they are probably not helpful in individualization of surveillance intervals.