Barrett's esophagus and adenocarcinoma

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

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

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

Genetic alterations in Barrett's esophagus and esophageal adenocarcinoma

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

Molecular alterations in Barrett's esophagus and adenocarcinoma]

Patients with Barrett's columnar-lined esophagus are at increased risk of developing esophageal adenocarcinoma, the incidence of which has increased rapidly especially in the USA. Although the number of patients with Barrett's adenocarcinoma is fewer in Japan than in the USA, all gastroenterologist should know its multistep carcinogenic process. Tumor suppressor genes (p53, p16), oncogenes (c-erbB-2, H-ras, K-ras, cyclin D1, src), and growth factor/receptor (TGF-alpha, EGFR) seem to cause the malignant transformation of Barrett's esophagus. Because detection of these molecular alterations is feasible, more accurate diagnosis of Barrett's esophageal biopsy specimens should be made by adding the molecular examination to the conventional pathologic examination.     

Limited resection for early adenocarcinoma in Barrett's esophagus

OBJECTIVE: To assess the extent of disease in patients with pT1 esophageal adenocarcinoma and to evaluate the feasibility and outcomes of a limited surgical approach. SUMMARY BACKGROUND DATA: Radical esophagectomy with systematic lymphadenectomy is widely advocated as the treatment of choice in patients with early adenocarcinoma of the distal esophagus. This approach, however, is associated with substantial complications and long-term side effects. The extent of resection necessary to achieve cure in such patients is not clear. METHODS: Seventy-one patients with pT1 adenocarcinoma of the distal esophagus underwent transmediastinal or transthoracic esophagectomy with two-field lymphadenectomy. Twenty-four patients with uT1N0 tumors underwent a limited resection of the distal esophagus and esophagogastric junction, regional lymphadenectomy, and reconstruction by interposition of an isoperistaltic pedicled jejunal segment. The two groups were compared for extent and multicentricity of the primary tumor and associated high-grade dysplasia, pattern of lymph node metastases, complications, deaths, and outcome of surgical treatment. RESULTS: Multicentric tumor growth or associated high-grade dysplasia was observed in 60.6% of the resection specimens. Complete resection of the tumor and the entire segment with intestinal metaplasia was achieved in all patients, irrespective of the surgical approach. Patients undergoing limited resection had fewer complications. Lymph node metastases or micrometastases were present in none of the 38 patients with tumors limited to the mucosa (pT1a) versus 10 of the 56 (17.9%) patients with tumors invading the submucosa (pT1b). Distant lymph node metastases occurred only in patients with more than three positive regional lymph nodes. Lymph node metastases were prognostic, but the pT1a/pT1b category and the surgical approach were not. The mean Gastrointestinal Quality of Life Index after limited resection did not differ from that of healthy controls: 20 of the 24 patients were completely asymptomatic. CONCLUSIONS: In patients with early adenocarcinoma in the distal esophagus, resection of the distal esophagus and esophagogastric junction, with regional lymphadenectomy and jejunal interposition, is an attractive limited surgical alternative to radical esophagectomy.     

Angelchik prosthesis complicates treatment of adenocarcinoma in Barrett's esophagus

Indications for use of the Angelchik prosthesis remain controversial, and many surgeons actively involved in the treatment of reflux disease have not used the device. We describe a case that illustrates difficulties associated with resection of a tumor in the presence of this prothesis. Such experience suggests that patients known to have Barrett's esophagus might be better treated with standard antireflux procedures.     

Esophagectomy without thoracotomy for adenocarcinoma in Barrett's esophagus]

From April 1985 to November 1990, 12 patients with adenocarcinoma in a Barrett's esophagus, all of them men, with a median age of 62 years (range, 46 to 79 years), were operated by transhiatal esophagectomy and were submitted to a periodic follow-up. Dysphagia was the main symptom. Preoperative investigations included esogastroscopy and CT-scan of the abdomen and thorax in all patients. Esophageal endosonography was performed in the last 4 cases and MRI in one case. All patients recovered postoperatively and were discharged from hospital. The resected specimens were staged according to Rosenberg et al.'s classification: stage 1, 3 patients, stage 2, 2 patients, stage 3, 6 patients, stage 4, 1 patient. An anastomotic stricture occurred in 4 patients and was treated successfully by endoscopic dilatation. Five patients died during the follow-up period. Seven patients are alive without evidence of recurrence. Transhiatal esophagectomy appears to be the procedure of choice for adenocarcinoma arising from Barrett's esophagus.     

Surgical treatment of adenocarcinoma in Barrett's esophagus and prognosis]

There is no consensus regarding the surgical approach to adenocarcinoma in Barrett's esophagus. From 1980 to 1988, 8 patients with adenocarcinoma in Barrett's esophagus were treated at the National Cancer Center Hospital. Seven patients underwent subtotal esophagectomy with extended lymph node dissection, and one transhiatal esophagogastrectomy with regional lymph node dissection. In 4 patients tumor invasion was limited within the submucosa and in 4 within the muscularis propria. Four of 8 patients had stage I disease. The 5-year survival rate for the 8 patients was 64.3%. Some reports have indicated that endoscopic survey for Barrett's esophagus is important for early diagnosis. We conclude that survival after esophagectomy for adenocarcinoma in Barrett's esophagus is dependent on the method of operation, and that patients with early lesions may expect significantly better survival after extended lymph node dissection.     

Endoscopic diagnosis of Barrett's adenocarcinoma]

Biopsy specimens can reveal that esophageal cancer is an adenocarcinoma but they cannot show that its origin is Barrett's mucosa. Therefore we must show during endoscopy that the tumor exists in Barrett's mucosa. We reported that Barrett's esophagus could be clearly diagnosed at endoscopy as the columnar mucosa lying on the longitudinal vessels in the lower esophagus. We define Barrett's esophagus as "the columnar mucosa in the esophagus which exists continuously more than 2 cm in circumference from the stomach." Short-segment Barrett's esophagus (SSBE) is "the columnar mucosa which exists in the esophagus continuously from the stomach but its length has a part under 2 cm in length." Endoscopically Barrett's adenocarcinoma is visualized as a lesion with a reddish and uneven mucosal surface. Barrett's adenocarcinomas occur in the SSBE as well. Endoscopic observation at periodic intervals is necessary not only for cases with Barrett's esophagus but also with SSBE. A further examination is necessary to determine the application of EMR for superficial Barrett's adenocarcinoma.     

Barrett's esophagus and associated adenocarcinoma in a mouse surgical model

BACKGROUND: The development of Barrett's esophagus (BE) and Barrett's associated adenocarcinoma (BAA) in the rat after experimental inducement of esophageal reflux of gastric, bile, and pancreatic juice has been reported by others. The purpose of this study was to determine whether similar results could be demonstrated in the mouse model. MATERIALS AND METHODS: One hundred eight Swiss-Webster mice were used in this study and were divided into three groups: Group I, 37 mice with esophagojejunostomy; Group II, 39 mice with esophagojejunostomy and the carcinogen N-methyl-N-benzylnitrosamine (MBN); and Group III, 32 mice with MBN alone. The animals were sacrificed after 19 weeks. Macroscopic and histopathologic examinations were performed. RESULTS: One hundred mice survived and were available for pathologic study. Macroscopic evidence suggested esophagitis in 60.6% of mice in Group I, 62.8% of mice in Group II, and 9% of mice in Group III and suggested tumor in 3% of mice in Group I, 51.4% of mice in Group II, and 53.1% of mice in Group III. Histopathologic analysis disclosed BE in 42.4% of mice in Group I, 20% of mice in Group II, and 12.5% of mice in Group III. Cancer was present in 12.2% of mice in Group I, 54.3% of mice in Group II, and 46.9% of mice in Group III. Adenocarcinoma with or without squamous cell carcinoma was present in 6.1% of mice in Group I, 37.1% of mice in Group II, and 12.5% of mice in Group III. CONCLUSIONS: Esophagojejunostomy plus MBN in the mouse results in BE, BAA, or both in 57.1% of animals, consistent with findings in the rat model after similar interventions.     

“Barrett's esophagus” adenocarcinoma: A case report

A case of signet ring cell carcinoma of the lower thoracic esophagus of Barrett type without association of hiatus hernia is reported. The patient is doing well more than five years after esophagectomy combined with esophagogastrostomy. On the base of histological findings of the operative material, this tumor appears to have originated from the gastric type of mucosa with parietal cells, accessory cells and chief cells as it is lining the segment of the esophagus directly distal to the tumor. The basic anomaly in this case is believed to be misdifferentiation of the embryonic columnar epithelium to a gastric fundic type instead of a normal squamous type. Presented at the XI International Cancer Congress, Florence, Italy, October 20–26, 1974.     

Possibilities of chromoesophagoscopy for diagnosis of Barrett's esophagus

When the distal esophagus is covered with columnar gastric mucosa up to 2 cm from the esophagogastric junction it is considered normal. If the distal esophagus is covered with columnar epithelium more than 2 cm from the esophagogastric junction, it is called Barrett's esophagus. We have developed a new chromoesophagoscopic method to improve diagnostic testing for Barrett's esophagus. The distinctive feature of this method is that 4 to 5 ml of a 1% solution of neutral red is administered intravenously, after which excretion of the stain by the esophageal mucosa is examined by endoscopy. Chromoesophagoscopy has been carried out in 11 patients with reflux esophagitis. It revealed Barrett's esophagus in four patients, which was proved by histologic evaluation of biopsy specimens obtained from the stained zone of the esophageal mucosa. These observations suggest that chromoesophagoscopy is an effective, accessible, feasible, safe method for diagnosing Barrett's esophagus. It allows us to determine the length of the metaplastic epithelium and the topography of gastric glands; it also allows us to examine parietal cells in the esophagus and estimate the functional activity of these parietal cells in metaplastic epithelium.     

Cdx2与食管炎、Barrett's食管及腺癌的关系

同源异型盒转录因子2是新发现的尾相关同源异型盒转录因子家旅中的一个成员,特异地表达于从十二指肠至肛管齿状线的肠道绒毛上皮,在其他空腔脏器黏膜上皮异位表达时可诱导相应部位的肠化生或腺癌发生.在胃十二指肠反流-食管炎- Barrett's食管-食管腺癌演化过程中,同源异型盒转录因子2起着重要的调控作用,并与p63基因、维甲酸、MUC2、骨形态发生蛋白4等多因素共同作用促进了这一过程的发展.     

Histopathologic evaluation of an animal model for Barrett's esophagus and adenocarcinoma of the distal esophagus

INTRODUCTION: Barrett's esophagus and adenocarcinoma of the esophagus are related to long-standing duodeno-gastroesophageal reflux. The development of an animal model in which Barrett's esophagus and/or carcinoma is induced by duodeno-(gastro-)esophageal reflux could provide better understanding of the pathogenesis of the metaplasia-dysplasia-carcinoma sequence and would create the possibility of investigating new treatment strategies for this aggressive disease. MATERIALS AND METHODS: Two rat models were analyzed. In the first experiment, 44 male Sprague Dawley rats underwent end-to-side esophagojejunostomy with gastric resection, to ensure duodenoesophageal reflux without gastric acid. In the second experiment a side-to-side esophago-gastrojejunostomy was performed in 30 rats, ensuring duodeno-gastroesophageal reflux. In both experiments animals were not exposed to any exogenous carcinogens during the experiment. Sequential morphological changes (i.e., esophagitis, intestinal metaplasia, dysplasia, and carcinoma) were studied after 4, 6, and 12 months. To analyze histopathologic characteristics, evaluation of the hematoxylin and eosin specimens was combined with immunohistochemical stainings for high-iron diamine-alcian blue, alcian blue/periodic acid-Schiff, the proliferation marker PCNA, and mutations in the tumor suppressor gene p53. RESULTS: In the first experiment, only 11 animals survived the postoperative period. These animals had to be sacrificed at a median of 11 weeks due to persistent weight loss and failure to thrive. Severe ulcerative esophagitis was seen in all animals, with a 2-mm segment of metaplastic epithelium found at the anastomosis. In four animals a large, well-differentiated, mucinous tumor without malignant characteristics was observed. In the second experiment, eight animals died postoperatively. Twelve animals were sacrificed according to protocol at 4 or 6 months. In these animals, extensive esophagitis with squamous cell hyperplasia was found. In addition, a short (2 mm) segment of metaplastic epithelium was observed, without dysplasia. The remaining animals survived 1 year. After 1 year, 9 of the 10 animals had developed a glandular metaplastic segment (median length, 10 mm), which was histologically and immunohistologically characteristic for the specialized columnar epithelium of Barrett's esophagus without signs of dysplasia. Finally, in seven animals a mucinous tumor with cytologic characteristics of a well-differentiated mucinous adenocarcinoma was found without infiltrative growth. These tumors were always found at the site of the anastomosis, originated in the submucosa, and did not reach either the luminal surface or the muscular layer. The mucinous lesions were not positive for p53, and PCNA was only slightly increased. Although they showed cytological characteristics of malignancy, histopathologic evaluation was more suggestive of a reactive mucous producing lesion fitting the diagnosis "esophagitis cystica profunda." CONCLUSION: This study demonstrates the development of a long Barrett's segment in an animal duodeno-gastroesophageal reflux model. Although mucinous tumors resembling adenocarcinomas develop around the anastomosis, these are probably not reflux induced and are more likely to be reactive lesions. However, the true nature of these tumors remains to be elucidated.