Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Barrett's esophagus (BE) patients demonstrate a higher distal esophageal acid exposure profile than other gastroesophageal reflux disease patients. Cellular oxidative stress has been proposed to contribute to the development of BE and esophageal adenocarcinoma. However, a relationship between low esophageal pH and oxidative stress has yet to be elucidated. The aim of this study was to determine the duration of low pH exposure in the esophagus of BE patients compared to those with erosive esophagitis (EE) and to test if brief exposure to low pH leads to the induction of reactive oxygen species (ROS). Seventy-three patients with BE or EE were evaluated by 24-hour esophageal pH monitoring and the percentage of time during which there was exposure to pH < or = 4 and pH < or = 2 was recorded. In vitro, Seg-1 and Het-1A cells were evaluated after brief exposure to pH4 or pH2 by flow cytometry and fluorescent microscopy for the production of ROS. BE patients demonstrated a significantly higher exposure to low pH values (pH < or = 2) than EE patients. The mean percent total time, duration and mean number of reflux episodes at pH < or = 2 were 2.8 +/- 0.53%, 28.8 +/- 3.6 seconds and 79 +/- 11.4 episodes in BE patients, whereas in EE patients they were significantly less, 1.16 +/- 0.3%, 15.6 +/- 1.2 seconds and 48.3 +/- 8.8 episodes, respectively (P < 0.05). In vitro experiments indicate that esophageal cells, when exposed to pH 2, produce ROS. In vitro studies using brief pH 2 exposure are biologically relevant to the clinical situation. Our studies indicate that such exposure induces oxidative stress. This stress may cause DNA damage, mutations and progression to cancer.
Dis Esophagus 2006
PMID:Esophageal acid exposure at pH < or = 2 is more common in Barrett's esophagus patients and is associated with oxidative stress. 1698 34

Oesophageal adenocarcinoma (OA) remains one of the more deadly forms of gastro-intestinal cancer with a mortality rate exceeding 90%. The incidence of OA remains unabated and has a reported fivefold increase since 1970 [Pera M, Cameron AJ, Trastek VF, Carpenter HA & Zinsmeister AR. Increasing incidence of adenocarcinoma of the esophagus and esophagogastric junction. Gastroenterology 1993; 104(2): 510-513]. Gastro-oesophageal reflux disease and its sequelae, Barrett's oesophagus, is one of the principle risk factors in the development of OA, with a 30-fold increased risk in Barrett's patients compared with the general population [Tytgat GNJ. Does endoscopic surveillance in esophageal columnar metaplasia (Barrett's-Esophagus) have any real value. Endoscopy 1995; 27(1): 19-26]. OA is thought to be a microcosm of evolution, developing sequentially along the metaplasia-dysplasia-adenocarcinoma sequence. Progression is attributed to a series of genetic and epigenetic events that ultimately allow for clonal selection of Barrett's cells via subversion of intrinsic control mechanisms regulating cellular proliferation and/or apoptosis. This review will describe the current suppositions of the mechanisms behind the selection and subsequent expansion of Barrett's clones, and focus on some of the principle hallmarks associated with this transition.
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PMID:Molecular biology of Barrett's cancer. 1699 63

Esophageal squamous cell carcinoma (SCC) remains the leading cause of cancer related deaths in Linzhou (formerly Linxian), the highest incidence area for esophageal cancer (EC) in Henan, northern China. In China, gastric cardia adenocarcinoma (GCA) shares very similar geographic distribution with SCC, suggesting the possibility of similar risk factors involved in SCC and GCA carcinogenesis in these areas. However, the underlying genetic alterations for esophageal and gastric cardia carcinogenesis, especially for the molecular difference between SCC and GCA, are largely unknown. The present study was thus undertaken to determine the difference in chromosomal aberrations in SCC (n = 37) and GCA (n = 31) using the comparative genomic hybridization method (CGH). All the patients were from Linzhou, Henan, a high-risk geographic region for both SCC and GCA. CGH results showed that chromosomal aberrations with different degrees were identified both in SCC and GCA. In SCC, chromosomal profile of DNA copy number was characterized by most frequently detected gains at 8q (29/37, 78%), 3q (24/37, 65%) and 5p (19/37, 51%); and frequently detected losses at 3p (21/37, 57%), 8p and 9q (14/37, 38%). In GCA, the frequently detected gains were identified at 20q (13/31, 42%), 6q (12/31, 39%) and 8q (11/31, 35%); the DNA copy number losses in GCA occurred frequently at 17p (17/31, 55%), 19p (15/31, 48%) and 1p (14/31, 45%). Statistically, there were evident differences between SCC and GCA in DNA copy number gains at 8q, 3q, 5p and 20q (P < 0.05) and in losses at 3p, 8p, 5q, 17p and 18q (P < 0.05). Gains at 8q were frequently observed in both SCC and GCA. Gains at 3q and 8p were frequently observed in TNM stage III of both SCC and GCA. The present CGH results provide candidate regions that may contain specific related genes involved in SCC and GCA in the Linzhou population. Gains at 8q, 3q and 5p and losses at 3p, 8p and 9q were specifically implicated in SCC; gains at 20q, 6q and 8q and losses at 17p, 19p and 1p were specifically implicated in GCA; gains at 8q were implicated in both SCC and GCA.
Dis Esophagus 2006
PMID:Comparative genomic hybridization: comparison between esophageal squamous cell carcinoma and gastric cardia adenocarcinoma from a high-incidence area for both cancers in Henan, northern China. 1706 89

Recent studies indicate that the prevalence of reflux esophagitis (RE) in China is increasing. RE is one of the most common esophageal complications associated with gastroesophageal reflux disease (GERD) and RE-Barrett's esophagus-esophageal adenocarcinoma (EAC) sequence has been considered as an histogenesis model for EAC in Western countries. RE is only present in a subset of patients with GERD, suggesting an altered susceptibility to RE may exist in these GERD individuals. However, the genetic changes related with high susceptibility to RE is largely unknown. The polymorphisms in glutathione S-transferases (GSTs) T1, M1 and P1 have been reported with high susceptibity to esophageal cancer in Chinese people. The present case-control study was thus undertaken to characterize the genetic polymorphisms of GSTs and their correlation with susceptibility to RE. One hundred and nine patients with RE, 97 patients with nonerosive reflux disease (NERD) and 97 normal controls were recruited in this study. All the subjects were from Beijing, China, and received endoscopic examination and questionnaires for RE. Genomic DNA was extracted from the lymphocytes of peripheral blood for each subject. Genotypes of the GSTM1 and GSTT1 genes were analyzed by a multiplex PCR method. A-->G polymorphism of codon 104 of the GSTP1 gene was detected using PCR-based restriction fragment length polymorphisms (RFLP). The variant GSTP1 genotypes (*A/*Bomicron*B/*B) was found with a high frequency in the case with RE (40%), and followed by NERD (25%) and normal control (22%). The differences were statistically significant (P < 0.05). The risk for RE increased 2.42-fold [odds ratio (OR); 95% confidence interval (95% CI), 2.42 (1.22-4.80)] in the subjects with variant GSTP1 genotype. The subjects with positive variant GSTP1 genotypes and negative H. pylori infection showed increasing tendency for risk of RE [OR (95% CI), 2.67 (1.06-6.70)]. However, the subjects with GSTT1 and GSTM1 polymorphisms did not show any correlation with high risk for RE or NERD. No significant interactions were identified between the variant GSTs and cigarette smoking, or alcohol drinking and subtype of RE. The present result suggests that GSTP1 genetic polymorphism may be one of the high susceptibility factors involved in the mechanisms of RE. H. pylori infection may play a protective role against RE.
Dis Esophagus 2006
PMID:Genetic polymorphisms in glutathione S-transferases T1, M1 and P1 and susceptibility to reflux esophagitis. 1706 92

We reviewed two cases of adenocarcinoma of the gastric tube used for reconstruction after esophagectomy for cancer. The first case gastric cancer was detected during follow-up by endoscopic examination. Total resection of the gastric tube and reconstruction by Roux-en-Y was performed each time. The patient was alive and disease-free 1 year after surgery. In the second case the tumor was revealed via thoracic pain. Chemotherapy, using carboplatin-5-fluorouracil, was performed because of lung metastasis but the patient died 1 year later. The incidence of gastric tube cancer after esophagectomy has recently increased in conjunction with the lengthening of survival of esophageal cancer patients. The clinical symptoms related to tumors are associated with short-term survival, whereas the cancers detected by routine endoscopy screening have occasional long-term survival. Gastrectomy is proposed for surgical treatment but the operating procedure is complex with a high morbidity rate. Lesions detected at an early stage could be treated by minimally invasive surgery such as endoscopic mucosal resection.
Dis Esophagus 2006
PMID:Metachronous cancer of gastroplasty after esophagectomy. 1706 98

Epidermal growth factor receptor is over-expressed in several tumors and is the target for the tyrosine kinase inhibitor gefitinib. This receptor is also over-expressed in esophageal adenocarcinomas. In non-small cell lung cancer, specific somatic mutations residing in the epidermal growth factor receptor tyrosine kinase in the activation loop and the glycine-rich P-loop, are responsible for an enhanced sensitivity toward gefitinib. We analyzed exons 19 and 21 coding for the receptor tyrosine kinase of the epidermal growth factor gene in 105 samples of esophageal (Barrett's) adenocarcinoma by denaturing high-pressure liquid chromatography. We found only one silent mutation in exon 19 of adenine to guanine in codon 754 leading to a substitution of K to K, the rest of the sample being wild-type genotype. In conclusion, mutations within the tyrosine kinase domain of EGFR associated with sensitivity of non-small cell lung cancer patients to gefitinib are not present in esophageal (Barrett's) adenocarcinoma.
Dis Esophagus 2007
PMID:Lack of EGFR gene mutations in exons 19 and 21 in esophageal (Barrett's) adenocarcinomas. 1722 3

After esophagectomy, pleural drainage is performed to ensure complete drainage of the pleural cavities. The aim of this study was to detect predisposing factors for prolonged drainage. Patients who underwent transhiatal or extended transthoracic esophagectomy for adenocarcinoma of the distal esophagus or gastroesophageal junction were included. Patients who underwent esophagectomy produced a median total drainage volume of 2477 mL (range 30-14,908). Seventy-five patients needed chest drainage = 7 days (short drainage) while 57 patients needed chest drainage > 7 days (prolonged drainage). Factors associated with prolonged drainage were a transthoracic approach (P < 0.001), a higher volume of blood loss (P = 0.027), a higher number of resected lymphnodes (P = 0.046) and a radical dissection (P = 0.033). Prolonged pleural drainage is associated with a transthoracic approach and is seen more often in patients after a microscopically radical dissection. Prolonged drainage is a sign of adequate dissection on the site of the primary tumor, probably due to the more extensive trauma to the lymphatic vessels in the mediastinum.
Dis Esophagus 2007
PMID:Predictive factors associated with prolonged chest drain production after esophagectomy. 1722 6

The aim of this study was to determine the role of body mass index (BMI) in a Western population on outcomes after esophagectomy for cancer. Two hundred and fifteen consecutive patients undergoing esophagectomy for esophageal cancer of any cell type were studied prospectively. Patients with BMIs > 25 kg/m were classified as overweight and compared with control patients with BMIs below these reference values. Ninety-seven patients (45%) had low or normal BMIs, 86 patients (40%) were overweight, and a further 32 (15%) were obese. High BMIs were associated with a higher incidence of adenocarcinoma versus squamous cell carcinoma (83%vs. 14%, P = 0.041). Operative morbidity and mortality were 53% and 3% in overweight patients compared with 49% (P = 0.489) and 8% (P = 0.123) in control patients. Cumulative survival at 5 years was 27% for overweight patients compared with 38% for control patients (P = 0.6896). In a multivariate analysis, age (hazard ratio [HR] 1.492, 95% CI 1.143-1.948, P = 0.003), T-stage (HR 1.459, 95% CI 1.028-2.071, P = 0.034), N-stage (HR 1.815, 95% CI 1.039-3.172, P = 0.036) and the number of lymph node metastases (HR 1.008, 95% CI 1.023-1.158, P = 0.008), were significantly and independently associated with durations of survival. High BMIs were not associated with increased operative risk, and long-term outcomes were similar after R0 esophagectomy.
Dis Esophagus 2007
PMID:Prognostic significance of body mass indices for patients undergoing esophagectomy for cancer. 1722 7

Adenocarcinoma of the distal esophagus and gastroesophageal junction are believed to arise in Barrett's esophagus with intestinal metaplasia. Whether adenocarcinoma can arise in columnar lined esophagus without intestinal metaplasia is in doubt. Whether adenocarcinoma of the gastric cardia arises in intestinal metaplasia of the gastric cardia is also in doubt. We aim to evaluate the relationship of size and stage of adenocarcinoma of the distal esophagus, gastroesophageal junction and gastric cardia to intestinal metaplasia and other types of columnar epithelium. Seventy-four patients who had esophagogastrectomy for adenocarcinomas in this region were examined histologically to assess the frequency of residual intestinal metaplasia in the surrounding epithelium. Tumors without residual intestinal metaplasia were evaluated for the presence of other columnar epithelia and correlated with tumor size and stage. Cardiac mucosa was present around all tumors. Residual intestinal metaplasia was present in 48 (65%) tumors, including 33/38 (87%) distal esophageal, 10/25 (45%) junctional and 5/11 (45%) gastric cardia tumors. The prevalence of intestinal metaplasia was 100% in all tumors that were less than 1 cm in maximum diameter and all intramucosal tumors. The prevalence of residual intestinal metaplasia decreased with increasing tumor size and stage. These data strongly support the contention that adenocarcinomas of this region, including those in the gastric cardia, arise in intestinal metaplastic epithelium. The absence of residual intestinal metaplasia in larger tumors is the result of tumor overgrowing the intestinal metaplasia from which it arose.
Dis Esophagus 2007
PMID:Is intestinal metaplasia a necessary precursor lesion for adenocarcinomas of the distal esophagus, gastroesophageal junction and gastric cardia? 1722 8

We reported four families with familial Barrett's esophagus (FBE) in 1993. This follow-up study includes an additional 16 families with FBE, gastroesophageal reflux disease (GERD) and BE-related adenocarcinoma (BEAC) highlighting the familial trends of inheritance. A retrospective survey of endoscopic and histopathological reports on 95 confirmed cases of BE from 1975 to 2005 was performed and a detailed family history was obtained. Five representative pedigrees from a total of 20 are discussed here. These 20 families represent one of the largest cohorts studied over three decades from a single institution. Familial BE is more common than previously thought and the prevalence of GERD, BE and BEAC in these families is distinctly higher than with sporadic cases. The conditions appear to be inherited in an autosomal dominant fashion with incomplete penetrance. Hence diligence in taking family history with BE patients is critical since the endoscopic screening of relatives is warranted in FBE. Earlier diagnosis and surveillance of FBE should hopefully improve outcomes.
Dis Esophagus 2007
PMID:Familial trends of inheritance in gastro esophageal reflux disease, Barrett's esophagus and Barrett's adenocarcinoma: 20 families. 1722 11


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