Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Barrett's esophageal cancer is generally considered to be generated through the metaplasia-dysplasia-carcinoma sequence from Barrett's epithelium. We have examined 9 cases of Barrett's esophageal cancer resected in our department, and determined that: 1) The cancer is mainly located in the lower esophagus. 2) Metastases are commonly found in the abdomen and mediastinum in advanced-stage disease. 3) Long-term survival can be expected in patients who undergo radical surgery.
 ...
PMID:[Barrett's esophageal cancer]. 1037 31

Since its description in the 1950s, the definition of Barrett's esophagus has evolved from the macroscopic visualization of gastric-appearing mucosa in the esophagus to the histologic identification of goblet cells confirming the presence of intestinal metaplasia within the esophagus. The length of intestinal metaplasia necessary to be classified as Barrett's, and the relationship between intestinal metaplasia of the esophagus and that limited to the cardia are all areas currently being evaluated. However, any segment of intestinal metaplasia is capable of undergoing dysplastic change and ultimately of becoming a focus of adenocarcinoma. It is logical to expect the degree of risk for developing cancer to be proportional to the amount of intestinal metaplasia present; however, within a population, the low risk to any individual is balanced by the relative frequency of the process. Thus, given the large numbers of people in America with CIM, even a small risk of progression to cancer will result in a large number of patients with adenocarcinoma of the cardia. This is exactly what is occurring today, with the incidence of adenocarcinoma of the cardia and esophagus currently rising faster than any other cancer in the United States. A major risk factor for adenocarcinoma of the esophagus is intestinal metaplasia, which occurs as a consequence of GERD. Patients with Barrett's esophagus usually have more severe reflux disease with significant impairment of LES function and esophageal body motility compared with patients without Barrett's. Furthermore, in patients with Barrett's, the composition of the refluxed juice is different. Patients who reflux both gastric and duodenal juice have a higher prevalence of Barrett's than do those who reflux gastric juice alone. Among patients with Barrett's, a significantly greater esophageal bilirubin exposure has been demonstrated in those with dysplasia. The mechanically defective sphincter and impaired esophageal body function in many patients with Barrett's makes their disease difficult to control medically. In addition, symptoms are unreliable as a guide to successful control of reflux. The hardest symptom to control is regurgitation, and there is concern that this and continued reflux of pharmacologically altered gastric contents, particularly bile acids in their nonpolar form, may contribute to progression of Barrett's. Both medical therapy and failed antireflux surgery are associated with progression of Barrett's to dysplasia and adenocarcinoma. On the other hand, a functioning fundoplication seems to be associated with protection from progression of Barrett's. Intestinal metaplasia of the esophagus is unlikely to regress after antireflux surgery; however, intestinal metaplasia limited to the cardia is perhaps more dynamic and able to regress. Furthermore, low-grade dysplasia frequently regresses after an antireflux procedure. Antireflux surgery is safe, effective, and durable, and often can be performed using minimally invasive techniques. Thus, antireflux surgery should be strongly considered in any patient with intestinal metaplasia of the esophagus or cardia. The possibility of mucosal ablation after an antireflux repair should be considered in patients with low-grade dysplasia. Patients with Barrett's and high-grade dysplasia are at high risk for having a focus of adenocarcinoma present. Even with multiple biopsies, a degree of sampling error exists. Also, adenocarcinoma can develop within the space of several months; and if the cancer is allowed to invade into the submucosa, 50% of these patients will have lymphatic metastases, thereby negating the purpose of surveillance. Although patients with high-grade dysplasia and intramucosal adenocarcinoma on biopsy who do not have an endoscopically visible lesion are unlikely to have lymphatic metastases, 7% do have submucosal invasion. Thus, even in these very early tumors, treatment directed only at the mucosa may be inadequate. (ABSTRACT
 ...
PMID:The diagnosis and management of Barrett's esophagus. 1057 61

Since adenocarcinoma of the esophagus and cardia is increasing at an alarming rate, major efforts are currently oriented to identify patients who may benefit from extensive resection. Between November 1992 and May 1998, 218 patients with histologically proven adenocarcinoma of the distal esophagus or cardia were referred to our Department. In six patients (10.2%) with Barrett's adenocarcinoma, cancer was discovered during endoscopic surveillance program for Barrett's metaplasia. Overall, one hundred-forty-seven patients (67%) underwent resection. Fifty-one underwent an extended mediastinal lymphadenectomy. Median cumulative survival was 25.9+/-3.1 months in patients undergoing resection, and 7+/-1.3 months in patients having palliation (p<0.01). Survival was significantly longer in patients with negative nodes than in those with lymph node metastases (54+/-12.9 versus 17+/-2.8 months, p<0.01). Six of the 51 patients (11.8%) undergoing extended lymphadenectomy had metastatic upper mediastinal nodes. Additional serial sections and immunohistochemistry were performed in 46 patients. In 6 of 18 patients (33.3%) with negative nodes at conventional hematoxylin-eosin examination, immunohistochemistry demonstrated micrometastases in the lesser curve, paracardial, peripancreatic, or lower mediastinal nodes. Early diagnosis remains the prerequisite for curative treatment of adenocarcinoma of the esophagus and cardia. When a curative resection is attempted, extended lymphadenectomy improves tumor staging and may prevent local recurrences. Serial sections and immunohistochemistry provide additional accuracy in the staging of the disease and may prove useful to select patients for adjuvant therapy.
 ...
PMID:Current trends in the surgical treatment of esophageal and cardia adenocarcinoma. 1060 71

To characterize cytogenetic alterations found in Barrett's adenocarcinoma (BA) and, more importantly, its premalignant stages, we studied chromosomal imbalances in various lesions in the histologically proposed metaplasia-dysplasia-carcinoma sequence using comparative genomic hybridization (CGH). Using 30 esophageal adenocarcinoma resection specimens, we were able to study 30 areas of Barrett's adenocarcinoma and 8 lymph node metastases (LN). In addition, we investigated 25 premalignant lesions adjacent to BA derived from a subset of 14 resection specimens including 11 areas of high grade dysplasia (HGD), 8 areas of low grade dysplasia (LGD), and 6 areas of intestinal metaplasia (IM), which were laser-microdissected and studied with CGH. To validate the CGH findings, fluorescence in situ hybridization analysis on 13 BA with probes specific for HER-2/neu and 20q13.2 were performed. The chromosomal alterations most often identified in BA were: gains on 8q (80%), 20q (60%), 2p, 7p and 10q (47% each), 6p (37%), 15q (33%) and 17q (30%). Losses were observed predominantly on the Y-chromosome (76%), 4q (50%), 5q and 9p (43% each), 18q (40%), 7q (33%) and 14q (30%). High-level amplifications were observed on 8q23-qter, 8p12-pter, 7p11-p14, 7q21-31, 17q11-q23. Recurrent chromosomal changes were also identified in metaplastic (gains on 8q, 6p, 10q, losses on 13q, Y, 9p) and dysplastic epithelium (gains on 8q, 20q, 2p, 10q, 15q, losses on Y, 5q, 9p, 13q, 18q). Novel amplified chromosomal regions on chromosomes 2p and 10q were detected in both Barrett's adenocarcinoma and premalignant lesions. An increase of the average number of detected chromosomal imbalances from IM (7.0 +/- 1.7), to LGD (10.8 +/- 2.2), HGD (13.4 +/- 1.1), BA (13.3 +/- 1.4), and LN (22 +/- 1.2) was seen. Although the detection of common chromosomal alterations in premalignant lesions and adjacent carcinomas suggest a process of clonal expansion, the occurrence of several chromosomal changes in an apparently random order relative to one another is striking evidence that clonal evolution is more complex than would be predicted by linear models. This is probably a reflection of the existence of many divergent neoplastic subpopulations and highlights one of the main problems associated with surveillance of Barrett's patients, namely sampling error.
 ...
PMID:Chromosomal imbalances in Barrett's adenocarcinoma and the metaplasia-dysplasia-carcinoma sequence. 1066 85

Barrett's metaplasia develops in 6% to 14% of individuals with gastroesophageal reflux. Barrett's adenocarcinomas are increasing in epidemic proportions for, as yet unknown, reasons; approximately 0.5% to 1% of patients with Barrett's metaplasia develop adenocarcinoma. Heartburn duration and frequency (but not severity), male gender, and white race are major risk factors for developing cancer. Obesity and smoking are weak risk factors. Survival is determined by depth of tumor invasion (stage). Once invasion of the muscularis propria occurs, most patients have developed widespread metastasis, even when clinical staging studies are negative. No currently available therapy results in prolonged survival once metastases develop. Thus, the more widespread use of effective surveillance strategies is the only currently available means for reducing the morbidity and mortality associated with Barrett's adenocarcinoma.
 ...
PMID:Barrett's esophagus. Reducing the risk of progression to adenocarcinoma. 1069 10

In the past, adenocarcinomas were thought to occur rarely in the esophagus and to comprise a small percentage of the tumors. In recent years the incidence has risen so that they represent 25% to 35% of all esophageal tumors. Epidemiological studies have shown that the tumor is more common in men than women ( approximately 8:1) and in whites than non-whites ( approximately 7:1). The most common associated condition is Barrett's esophagus, but the evaluation is clouded by the inconsistent definition of Barrett's esophagus in the gastroenterology literature. The diagnosis of Barrett's esophagus requires the identification of metaplastic glandular epithelium with goblet cells in the esophagus. The management of adenocarcinomas of the esophagus is difficult to evaluate because the tumors are frequently included with squamous carcinomas of the esophagus or adenocarcinomas of the gastric cardia. Esophageal adenocarcinomas are associated with a high rate of local recurrence when treated with surgery or radiation alone. Their pattern of spread is different from that of gastric carcinomas in that peritoneal seeding is uncommon and liver and pulmonary parenchymal metastases are less common, whereas pleural and bony metastases are more common. This would suggest that they should be analyzed as a separate clinical entity. In the absence of prospective trials, the reported experience suggests that these patients should be considered for combined surgery and preoperative or postoperative chemotherapy and radiation. Patients who are not candidates for surgery can receive effective and durable palliation from chemosensitized radiation. There are theoretical advantages to both preoperative and postoperative therapy and the selection of treatment programs should be individualized.
 ...
PMID:Controversies in the Management of Adenocarcinoma of the Esophagus and Esophagogastric Junction. 1071 5

A retrospective study of surgically resectable esophageal cancers was undertaken to determine the relationship between angiogenesis score and growth factor expression with tumor size, histology, degree of differentiation, depth of invasion, nodal disease, and the presence of Barrett's esophagus. The office and hospital charts of 27 patients who had esophageal resection for carcinoma between 1990 and 1995 at Rush-Presbyterian-St. Luke's Medical Center were reviewed. Data collection included patient demographics, survival, tumor size, histology, differentiation, depth of invasion, nodal metastases, and the presence of Barrett's esophagus. The pathology specimens were immunostained for von Willebrand factor (factor VIII-related antigen). Immunostaining was also performed for vascular endothelial growth factor and transforming growth factor alpha. Twenty normal esophageal specimens served as controls. Angiogenesis score was determined by counting vessels under conventional light microscopy at x200 magnification, and growth factor expression was graded on a scale of 1 to 4. Cancers had higher angiogenesis and growth factor expression than controls (P = 0.01). Patient age, tumor size, histology, differentiation, depth of invasion, and Barrett's esophagus did not correlate with angiogenesis score or tumor growth factor expression. Lymph node status did correlate with both angiogenesis score and growth factor expression (P < or = 0.02). We conclude that high angiogenesis score and growth factor expression correlate with the presence of lymph node metastases. This may help select patients for preoperative radiation and chemotherapy or determine the extent of surgery performed for esophageal carcinoma.
 ...
PMID:Do angiogenesis and growth factor expression predict prognosis of esophageal cancer? 1077 79

Neuroendocrine differentiation is common in adenocarcinomas of the stomach and colon and may be associated with a slightly better prognosis in gastric adenocarcinoma. We studied neuroendocrine differentiation in esophageal adenocarcinomas and associated Barrett's esophagus (BE) to determine association with patient outcome. Fifty-eight cases of esophageal adenocarcinoma (15 biopsies, 43 resections) from 52 patients were stained with a monoclonal antibody to chromogranin (CG). Medical records were reviewed for tumor stage, response to therapy, and patient survival. Thirty-two patients received radiation and chemotherapy, and four received radiation. Twelve of 58 (20.7%) esophageal adenocarcinomas contained scattered CG-positive cells. Tumors with CG-positive cells were moderately to poorly differentiated, and many consisted of large cribriform glands, similar to intestinal-type adenocarcinomas. One case of small cell carcinoma of the esophagus was weakly CG positive; another was negative. Neuroendocrine differentiation was retained in lymph node metastases in two cases but lost in three other cases. In 10 CG-negative primary tumors, lymph node metastases were also negative. For five of six patients with paired biopsy/resection specimens, no CG-positive cells were seen in either specimen; one patient had CG-positive cells only in the resection. There was no difference in tumor stage at surgery or survival time between CG-positive and CG-negative tumors. BE was present in 34 cases and contained CG-positive cells in 21 of 34 (61.8%). Low-grade dysplasia contained CG-positive cells in 11 of 14 cases (78.6%) and high-grade dysplasia in 3 of 6 cases. Fourteen of 21 (66.7%) adenocarcinomas associated with CG-positive BE were negative for CG. In summary, neuroendocrine differentiation is common in BE and is retained in low- and high-grade dysplasia but is usually lost in esophageal adenocarcinoma. The presence of scattered neuroendocrine cells does not affect patient outcome.
 ...
PMID:Prevalence and prognostic significance of neuroendocrine cells in esophageal adenocarcinoma. 1082 17

Lymph node metastasis is one of the strongest negative prognostic factors for patients with Barrett's adenocarcinoma (BCA). However, despite the importance of the metastatic process in BCA, the molecular basis of it remains poorly understood. To search for cytogenetic events associated with metastasis in regional or distant lymph nodes in BCA, we investigated 8 primary BCA and their lymph node metastases and compared them with 18 nonmetastatic BCA. In metastatic primary BCA, we observed significantly more DNA gains on 3q (P = .013), 17q (P = .019), and 22q (P = .021) compared with nonmetastatic primary BCA. No statistically significant correlation could be observed between DNA copy number changes and the histopathologic stage, grade, or survival (P > .05). The most frequent alteration observed only in lymph node metastases but not in the related primary tumor was loss of 2q (5 of 8). Coamplification of 7p and chromosome 17 was found in 6 of 8 lymph node metastases. A comparison of DNA copy number changes between primary tumors and their corresponding metastases indicated a high degree of genetic heterogeneity. Fluorescence in situ hybridization analysis demonstrated the involvement of the Her-2/neu gene in primary BCA and its related lymph node metastases. Each of the investigated primary tumors and related lymph node metastases also showed striking heterogeneity with respect to Her-2/neu, with several areas displaying different levels of amplification. In summary, our data indicate that DNA copy number changes on 2q, 3q, 7p, 17q, and 22q may be involved in the metastatic process in BCA. Furthermore, the striking genetic heterogeneity that we found between primary BCA and its lymph node metastases may underlie BCA's poor responsiveness to therapy and could help explain why prognostic biomarkers measured exclusively in primary tumors give an incomplete view of the biologic potential of BCA.
 ...
PMID:Molecular genetic changes in metastatic primary Barrett's adenocarcinoma and related lymph node metastases: comparison with nonmetastatic Barrett's adenocarcinoma. 1091 43

Adenocarcinoma of the esophagus and gastric cardia are the most rapidly increasing cancers in developed countries. Adenocarcinoma of the esophagus is associated with chronic gastroesophageal reflux, and Barrett's esophagus is a precursor. This disease most frequently affects middle-aged white men. Endoscopic surveillance should be performed on patients with Barrett's esophagus, and esophagectomy is often performed on persons with high-grade dysplasia. Ablation of Barrett's esophagus has been proposed to prevent cancer but the outcomes are unproven. Squamous carcinoma of the esophagus most often affects black men and is associated with alcohol and tobacco use. The diagnosis of esophageal cancer is made by endoscopy with biopsy. Optimal staging is with endoscopic ultrasonography for depth of invasion and regional nodes and CT scanning for distant metastases. Neoadjuvant chemotherapy and radiation therapy followed by surgery is widely practiced, but survival benefits remain to be proven. Palliation of dysphagia may be achieved with surgery, radiation therapy, or endoscopic means, with the latter having fewer complications.
 ...
PMID:Esophageal cancer prevention, cure, and palliation. 1095 Apr 58


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>