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

The aim of this study was to determine if cyclo-oxygenase-2 (COX-2) expression in adenocarcinoma of the esophagus affects survival outcome in patients undergoing esophagectomy. Ten patients surviving more than 3 years following an esophagectomy for adenocarcinoma of the esophagus were identified from an esophagectomy database maintained by the University of Adelaide Department of Surgery. An additional group of 10 patients, who underwent esophagectomy for adenocarcinoma, but who died within 12 months of surgery due to recurrent disease, were also identified. Pieces of the original formalin fixed carcinoma tissue embedded in paraffin blocks from all of these patients were obtained, and slices of the tumor specimens underwent immunohistochemical staining with COX-2 protein. The extent of staining was then graded by a single 'blinded' pathologist: grade 0, no staining; grade 1 +, limited staining; and grade 2 +, strong staining. Kaplan-Meier survival curves were then constructed and used to determine correlations between survival and COX-2 staining, tumor T-stage, local lymph node metastases, and tumor vascular invasion. Ninety-five percent (19/20) of patients stained positively for COX-2. Patients with grade 2 + staining had a significantly poorer survival outcome compared to grade 1 + patients (P = 0.03). There were also trends towards shorter survival with worsening T-stage, lymph node metastasis and vascular invasion. COX-2 protein appears to be expressed by most esophageal adenocarcinomas. An increased level of expression of COX-2 was associated with a poorer survival outcome in this study. COX-2 protein expression association could be a better prognostic indicator for esophageal adenocarcinoma than traditional histopathological staging.
Dis Esophagus 2004
PMID:Cyclo-oxygenase-2 expression in esophageal adenocarcinoma as a determinant of clinical outcome following esophagectomy. 1523 Jul 26

The purpose of this study was to characterize the spectrum of esophageal pathology at a provincial tertiary care hospital and to evaluate these findings with their respective endoscopic diagnoses. The pathology slides of 183 esophageal biopsies for the year 2000 were reviewed and classified as esophagitis, intestinal metaplasia, low or high grade dysplasia, adenocarcinoma, squamous cell carcinoma or normal. One hundred and fifteen cases (63%) had complete concordant results with respective endoscopic reports. Sixty-eight cases (37%) had discordant results with inaccurate recognition of Barrett's esophagus in 9% and of esophagitis with a false positive in 16% and false negative in 7%. Although esophagoscopy remains a primary investigative tool in gastroesophageal diseases, evaluation of erythema, inflammation and esophagitis can be misleading. Pathologically confirmed esophagitis can occur in a 'normal' esophagus. Accurate endoscopic recognition of short-segment Barrett's remains a diagnostic challenge.
Dis Esophagus 2004
PMID:Pathological validity of esophageal endoscopy. How real is what we see? Myth or reality? 1556 67

Barrett's columnar epithelium with dysplasia is the most important risk factor for adenocarcinoma of the distal esophagus. The molecular mechanisms responsible for progression of columnar metaplasia to dysplasia and invasive carcinoma are mostly unknown. We investigated expression of the tumor suppressor gene p53, E-cadherin expression and cell proliferation in the metaplasia-dysplasia-carcinoma sequence of esophageal adenocarcinoma. In 24 patients with R0-resected adenocarcinomas of the distal esophagus we evaluated the expression of E-cadherin (antibody HECD-1), mutated p53 (antibody DO1) and cell proliferation (antibody MiB1) by immunohistochemistry in sections of adenocarcinoma, columnar metaplasia, with and without dysplasia, and in squamous epithelium of the esophagus. No p53 immunoreactivity was seen in sections of normal squamous epithelium or columnar metaplasia. Fifty per cent of invasive adenocarcinomas stained positive for mutated p53. The p53 expression correlated with the T-category (P = 0.048) and the N-category (P = 0.024). There was a significant decrease in the expression of E-cadherin from columnar metaplasia to dysplasia and to esophageal adenocarcinoma (P < 0.0001). Expression of E-cadherin in columnar metaplasia without dysplasia was similar to that seen in normal squamous epithelium of the esophagus. The Ki-67 proliferation fraction increased significantly from normal squamous epithelium to columnar metaplasia to dysplasia and to invasive carcinoma (P < 0.001), with a marked expansion of the proliferative component. There was no correlation between cell proliferation, E-cadherin expression and the tumor stage. In contrast to the alterations in the p53 expression, a decreased E-cadherin expression and the expansion of the proliferative component represent an early phenomenon in the malignant degeneration of Barrett's esophagus. This might aid in the early detection of esophageal adenocarcinoma.
Dis Esophagus 2004
PMID:Malignant degeneration of Barrett's esophagus: the role of the Ki-67 proliferation fraction, expression of E-cadherin and p53. 1556 71

The new developments in the management of Barrett's esophagus in 2005 result in refinements of decision making. New techniques including magnification endoscopy have been used for real-time recognition of intestinal metaplasia but are not yet validated. The finding of BE in patients lacking GERD symptoms highlights the problems of developing screening criteria for the general population. Many experimental optical techniques are pushing the optical recognition of dysplasia to real time. Availability, cost and validation remain barriers to clinical application. Endoscopic mucosal resection is being more widely applied resulting in more accurate staging of patients with early adenocarcinoma of the esophagus and helping to define patients amenable to endoscopic therapy. The approval of photodynamic therapy for the treatment of high grade dysplasia adds to the non-operative therapeutic arsenal. The impact of medical therapy of GERD and anti-reflux surgery on the development of esophageal adenocarcinoma is disappointing. Technological developments and emerging efforts in chemoprevention offer promise for the future.
Dis Esophagus 2005
PMID:Managing Barrett's esophagus: what is new in 2005? 1577 36

Initial treatment of locally advanced esophageal and gastroesophageal junction (GEJ) malignancies for selected patients at some institutions has recently changed from surgical resection to neoadjuvant therapy. The aim of this study is to evaluate the impact of this change in treatment strategy on both the overall disease profile and locoregional endoscopic ultrasound (EUS) staging accuracy for a cohort of patients managed with primary surgical resection over a 10-year period at our institution. All subjects at our institution who underwent primary esophagectomy from 1993 to 2002 following preoperative EUS for known or suspected esophageal and/or GEJ cancers were identified. Patients with dysplasia alone, prior upper gastrointestinal tract surgery, preoperative neoadjuvant therapy, cancer of the gastric cardia or recurrent malignancy were excluded. EUS findings and staging results were compared to surgical pathology following resection. The impact of the gradually increased use of primary chemoradiation during the second half of the study was assessed. Of the 286 operations performed, 184 subjects were excluded. The remaining 102 underwent primary surgical resection a median of 18 days following EUS staging for adenocarcinoma (88%) or squamous cell carcinoma (12%) of the esophagus (69%) or GEJ (31%). Overall EUS locoregional T and N staging accuracy was 72% and 75% respectively; accuracy for T1, T2, T3 and T4 cancer was 42%, 50%, 88% and 50% respectively. Despite an increased frequency of pathologically confirmed T1 and T2 cancers (P = 0.005) and an insignificant trend toward increased N0 malignancy (P = 0.05) during the second half of the study period, no statistically significant changes in T (P = 0.07) or N (P = 0.82) staging accuracies for EUS or disease characteristics were noted between the first and second half of the study period. Despite both inaccurate radial EUS staging and increased relative use of primary surgery for early cancers, recent increased use of primary neoadjuvant therapy did not change overall disease characteristics and accuracy of locoregional EUS staging of esophageal and GEJ cancers managed with primary surgical resection.
Dis Esophagus 2005
PMID:Endoscopic ultrasound for esophageal and gastroesophageal junction cancer: Impact of increased use of primary neoadjuvant therapy on preoperative locoregional staging accuracy. 1577 37

SUMMARY. Esophageal cancer is one of the most deadly forms of gastrointestinal cancer with a mortality rate exceeding 90%. The major risk factors for esophageal adenocarcinoma are gastroesophageal reflux disease (GERD) and its sequela, Barrett's esophagus. GERD commonly leads to esophagitis. In a minority of patients however, ongoing GERD leads to replacement of esophageal squamous mucosa with metaplastic, intestinal-type Barrett's mucosa. In the setting of continued peptic injury, Barrett's mucosa can give rise to esophageal adenocarcinoma. Despite the widespread use of potent acid suppressive therapies for patients with GERD, the incidence of esophageal adenocarcinoma, among white men in the USA, the UK and Europe has continued to rise. Cancers in Barrett's esophagus arise through a sequence of genetic events that endow the cells with six essential physiologic hallmarks of cancer as described by Hanahan and Weinberg in 2000. These cancer hallmarks include the ability to proliferate without exogenous stimulation, to resist growth-inhibitory signals, to avoid triggering the programmed death mechanism (apoptosis), to resist cell senescence, to develop new vascular supplies (angiogenesis), and to invade and metastasize. While the acquisition of these essential attributes is not specific to the neoplastic progression of Barrett's esophagus, this review will focus on the genetic alterations that occur in Barrett's cells that contribute to the acquisition of each of the hallmarks. Moreover, potential diagnostic and therapeutic strategies for Barrett's patients aimed at each of these cancer hallmarks will be reviewed.
Dis Esophagus 2005
PMID:Molecular targets for treatment of Barrett's esophagus. 1605 81

SUMMARY. Patients with inoperable esophageal malignancy often undergo palliative self-expanding metal stent insertion. This analysis of cases shows that although such stents provide good palliation of dysphagia, complications frequently occur. Complications reported were pain after insertion, bleeding, food bolus impaction, stent migration and increased gastroesophageal reflux. Furthermore, in patients with esophageal adenocarcinoma, survival was less if the distal end of the stent entered the stomach, rather than lying entirely within the esophagus. Reduced survival, in this group with gastroesophageal junction tumors, may be a result of increased gastroesophageal reflux leading to pulmonary aspiration. Stents incorporating an antireflux valve have been shown to reduce symptomatic gastroesophageal reflux. It may be that such valves offer a survival advantage where stent insertion ablates the function of the lower esophageal sphincter. Further studies are needed to assess the role of antireflux stents on survival in patients with gastroesophageal junction tumors.
Dis Esophagus 2005
PMID:Self-expanding metal stents in the palliation of malignant dysphagia: outcome analysis in 100 consecutive patients. 1605 83

SUMMARY. Neoadjuvant chemoradiotherapy is often administered to patients with esophageal carcinoma in the belief that this will improve survival. However, its role in the management of esophageal carcinoma remains controversial. In this study we evaluated our experience with neoadjuvant chemoradiotherapy for the treatment of esophageal carcinoma. The study group was 115 patients who underwent esophagectomies between January 1999 and January 2004. Eighty-nine patients had adenocarcinoma and 26 had squamous cell carcinoma. Fifty-six patients underwent neoadjuvant chemoradiotherapy (two cycles of cisplatin and 5-fluorouracil with 45 Gy radiation) followed by esophagectomy. The other 59 patients proceeded directly to esophagectomy. Outcomes were determined prospectively, and follow-up was available for all patients. Neoadjuvant chemoradiotherapy achieved down-staging of the esophageal cancer in 43%, 43% and 46% of patients, according to T, N and TNM classifications, respectively. Neoadjuvant chemoradiotherapy resulted in a complete pathological response in seven (13%) patients. The surgical morbidity rate was 37% (42/115), and in-hospital mortality was 5% (6/115). There were no differences between patients who did and did not undergo neoadjuvant chemoradiotherapy in regard to completeness of resection, perioperative mortality and postoperative morbidity. Four-year survival was 33% following neoadjuvant chemoradiotherapy, compared with 19% for patients undergoing surgery alone. The administration of neoadjuvant chemoradiotherapy in patients with esophageal carcinoma down-staged nearly 50% of tumors, and a complete pathological response occurred in some of these patients. It was not associated with any increase in postoperative morbidity or perioperative mortality. In this non-randomized study, it was also associated with a trend towards a better survival outcome.
Dis Esophagus 2005
PMID:Neoadjuvant chemoradiotherapy for esophageal carcinoma. 1605 85

There have been recent advances in the surgical approach to respectable esophageal cancer. In addition, despite the paucity of level 1 data, regardless of histology (squamous cell or adenocarcinoma), neo-adjuvant chemoradiotherapy has evolved into a de facto standard of care for resectable disease. Pathologic response rate is a surrogate for a more favorable outcome. In addition, there are a number of molecularly targeted agents that may have clinical utility for these patients. Current clinical trials have been designed with a translational research component to define which patients may benefit from the incorporation of these novel agents alongside standard combined-modality approaches.
Dis Esophagus 2005
PMID:Current and ongoing progress in the therapy for resectable esophageal cancer. 1612 75

We examined the epidemiology of esophageal cancer in Finland and the role of the surveillance of Barrett's esophagus (BE) in detecting esophageal adenocarcinoma (EA) in our own hospital referral area. We observed that the incidence of EA in men has increased tenfold from the 1970s and was 1.10/100,000/year in 1998-2002. In women, a 4.5-fold increase was observed (incidence 0.11/100,000/year). In 1998-2002, the mean annual number of new EA cases was 57.4 (79.8% men) in Finland with a population of 5.2 million. In our hospital referral area with a mean population of 261 349, 11 EAs were observed in 1996-2001. Of them, two (18.2%) had BE. One EA was detected during surveillance. EA comprised 0.05% of all causes of deaths in our hospital referral area. We conclude that EA incidence has increased significantly in men in Finland, but still EA is seldom detected on BE surveillance. EA is an uncommon cause of death in our hospital referral area.
Dis Esophagus 2005
PMID:The changing epidemiology of esophageal cancer in Finland and the impact of the surveillance of Barrett's esophagus in detecting esophageal adenocarcinoma. 1612 77


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