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

Once a rare tumor, adenocarcinoma of the esophagus is currently the cancer with the fastest rising incidence in America. In addition to the increasing prevalence of the disease, surveillance programs for patients with Barrett's have led to the identification of increasing numbers of patients with high-grade dysplasia or early-stage esophageal adenocarcinomas. Although traditional esophagectomy is curative in the majority of these patients, associated morbidity and mortality remains a hurdle for patient acceptance of the procedure. New endoscopic and surgical therapies offer the potential of decreased morbidity, but do not include a lymphadenectomy, and consequently, are not appropriate in patients that have a significant risk of lymph node metastases. Endoscopic mucosal resection allows precise determination of the depth of tumor invasion and facilitates accurate local staging of early esophageal cancers. A vagal-sparing esophagectomy accomplishes the goal of removing the diseased esophagus while minimizing the physiologic impact of an esophagectomy in patients with early-stage esophageal cancer.
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PMID:Endoscopic mucosal resection and vagal-sparing esophagectomy for high-grade dysplasia and adenocarcinoma of the esophagus. 1642 38

Endoscopic surveillance is recommended for patients with Barrett's esophagus to detect high-grade dysplasia (HGD) or cancer. We studied the outcome of esophagectomy in a cohort of patients who developed HGD or cancer between 1995 and 2003 while under surveillance for Barrett's. Outcomes were measured by analysis of clinical records, symptom questionnaire, and SF-36 (version 2). In 34 patients, mean surveillance time was 48 months (range, 4-132); the mean number of endoscopies was 10 (range, 3-30). Preoperative diagnosis was HGD in 9 patients (26.5%), carcinoma in situ in 16 (47%), and adenocarcinoma in 9 (26.5%). There was no esophagectomy-related mortality; 10 patients (29%) had complications. At mean follow-up of 46 months (range, 13-108), SF-36 (version 2) results showed quality of life scores equal to or better than those of healthy individuals. Incidence and severity scores (VAS 1-10) for postoperative symptoms were reflux, 59% (2.8); dysphagia, 28% (3.7); bloating, 45% (2.6); nausea, 28% (2.1); and diarrhea, 55% (2.5). Twenty-nine patients (85%) have no clinical, radiographic, or endoscopic evidence of recurrent esophageal cancer or metastasis. One patient has metastatic disease. Endoscopic surveillance in Barrett's patients yields malignant lesions at an early, generally curable, stage. Esophagectomy is curative in the great majority and can be accomplished with minimal mortality and excellent quality of life.
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PMID:Long-term outcome of esophagectomy for high-grade dysplasia or cancer found during surveillance for Barrett's esophagus. 1650 78

Claudins are components of tight junctions important in intercellular barriers and cell polarity. The authors identified upregulation of Claudins 3, 4, and 7 in gastric adenocarcinoma using Affymetrix U-133 oligonucleotide microarrays and immunohistochemistry (IHC). While normal gastric mucosa lacked Claudin 3, 4, and 7 expression, intestinal metaplasia and dysplasia showed these proteins. The authors hypothesized that Claudins would be similarly overexpressed in Barrett's esophagus (BE)/adenocarcinoma. Claudins 3, 4, and 7 gene expression was analyzed by Affymetrix U-133 microarrays in three esophageal adenocarcinomas, one case of BE, and three normal esophagi. IHC validation was performed using tissue microarrays constructed from esophageal resection specimens containing squamous (44 cases), gastric (40 cases), and non-dysplastic BE (16 cases), low-grade and high-grade dysplasia (16 and 26 cases), adenocarcinoma (58 cases), and nodal metastases (27 cases). IHC staining was scored semiquantitatively (0+ to 4+). By microarray analysis, Claudin 3 showed a marked increase in mRNA expression compared with normal esophagus (approximately 100-fold). Claudins 4 and 7 were modestly increased (2.2- and 1.3-fold). By IHC, Claudin 3 expression was 1+ in most (>95%) normal squamous or gastric tissues and 2+ to 4+ in more than 80% of high-grade dysplasia, adenocarcinoma, and metastases specimens. Claudin 4 protein expression was 2+ or less in most squamous and gastric mucosa (>90%) but 3+ or 4+ in BE, low- and high-grade dysplasia, adenocarcinoma, and metastases specimens (>90%). Claudin 7 expression was minimal in squamous and gastric mucosa but strong (3+ to 4+) in BE and low-grade dysplasia. In high-grade dysplasia, adenocarcinoma, and metastases, Claudin 7 was less intense, with 60% to 70% staining 3+ or 4+ and 30% to 40% staining weakly (1+ or 2+). The findings suggest that alterations in Claudin proteins are an early event in tumorigenesis and may provide targets for diagnosis and directed therapy for esophageal adenocarcinoma and its precursors.
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PMID:Overexpression of claudin proteins in esophageal adenocarcinoma and its precursor lesions. 1654 Jul 26

An evidence-based guideline for the diagnosis and treatment of oesophageal carcinoma was developed on the initiative of the Netherlands Society of Gastroenterohepatology in cooperation with the Dutch Institute for Healthcare Improvement (CBO) and the Dutch Association of Comprehensive Cancer Centres. If a patient with oesophageal carcinoma is eligible for treatment with curative intent, they should undergo thoracic and abdominal CT, ultrasound investigation of the supraclavicular region and endoscopic ultrasonography for staging purposes. Endoscopic therapy is the preferred treatment for high-grade dysplasia or early cancer in Barrett's oesophagus confined to the mucosa. Surgical resection is indicated if the tumour invades the submucosa. If resection of the oesophageal carcinoma is performed with curative intent, one should aim for radical resection. The type and extent of the resection depends on the location of the tumour. There is evidence that the mortality rate following surgery can be reduced by performing it in centres with ample experience with oesophageal cancer surgery. Preoperative chemotherapy and radiotherapy may improve survival in patients with oesophageal carcinoma. Palliative treatment for oesophageal carcinoma should be considered in cases of local invasion of surrounding organs, metastases, poor physical condition of the patient or recurrent disease after previous curative treatment. Psychosocial support is an important element in the follow-up of patients with oesophageal carcinoma.
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PMID:[Guideline 'Diagnosis and treatment of oesophageal carcinoma']. 1697 9

A relatively young patient with chronic gastroesophageal reflux disease (GERD), obesity, smoking, and alcohol intake presented with widespread metastatic disease in lymph nodes, liver and lungs from a lower esophageal adenocarcinoma extending into the gastroesophageal junction associated with Barrett's mucosa and dysplasia.A complete response was achieved with six cycles of chemotherapy that sustained for more than 4 years without further recurrence. Unfortunately, there was presence of esophageal metaplasia after complete response which eventually converted to low to high grade dysplasia and ultimately to a second primary localized lower esophageal adenocarcinoma that was treated with thoracoabdominal esophagectomy and lymphadenectomy. No evidence of disease recurrence was seen 2 years later. The pathogenesis of a recent increase in the incidence of GERD, Barrett's esophagus and lower esophageal adenocarcinoma are discussed. Surgery, radiotherapy and combination chemotherapy are effective in the early stages leading to tumor shrinkage and prolongation of life and even cure in some cases. Lower esophageal adenocarcinoma is frequently associated with Barrett's high-grade dysplasia. Since there has been a dramatic increase in the incidence of Barrett's dysplasia, appropriate surveillance with upper gastrointestinal endoscopy and preventive strategies, such as the use of aspirin, cyclo-oxygenase II inhibitors and other nonsteroidal antiinflammatory drugs known to be chemopreventive agents against colon, esophagus, gastric and bladder cancers, need to be studied.
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PMID:Esophageal adenocarcinoma arising from Barrett's dysplasia: a case report of double occurrence and prolonged survival after chemotherapy. 1698 98

Adenocarcinoma of the oesophagus and gastro-oesophageal junction are rapidly increasing in incidence and have a well described sequence of carcinogenesis: the Barrett's metaplasia-dysplasia-adenocarcinoma sequence. During recent years there have been changes in the knowledge surrounding disease progression, cancer management and histopathology specimen reporting. Tumours around the gastro-oesophageal junction (GOJ) pose several specific challenges. Numerous difficulties arise when the existing TNM staging systems for gastric and oesophageal cancers are applied to GOJ tumours. The issues facing the current TNM staging and GOJ tumour classification systems are reviewed in this article. Recent evidence regarding the importance of several histopathologically derived prognostic factors, such as circumferential resection margin status and lymph node metastases, have implications for specimen reporting. With the rising use of multimodal treatments for oesophageal cancer it is important that the response of the tumour to this therapy is carefully documented pathologically. In addition, several controversial and novel areas such as endoscopic mucosal resection, lymph node micrometastases and the sentinel node concept are being studied. We aim to review these aspects, with special relevance to oesophageal and gastro-oesophageal cancer specimen reporting, to update the surgical oncologist with an interest in upper gastrointestinal cancer.
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PMID:Emerging aspects of oesophageal and gastro-oesophageal junction cancer histopathology - an update for the surgical oncologist. 1711 94

A 62-year-old woman with Barrett's esophageal cancer was hospitalized. Abdominal CT confirmed metastases to the liver and lymph nodes, for which surgical excision and radiotherapy were not indicated. We started chemotherapy with a course of daily oral S-1 at a dose of 80 mg/m(2) for 21 days, with a 2-hour drip of cisplatin at 60 mg/m(2) on day 8. Breaks of 14 drug-free days were given between courses. After two courses, a repeat CT confirmed that the liver and lymph node metastases had disappeared; after three courses, another CT confirmed that the metastatic foci were still absent, so we judged the disease to be in complete remission. Endoscopy and upper GI series confirmed that the primary tumor was reduced, and endoscopic mucosal resection performed using the strip biopsy method. The excision specimen was well differentiated adenocarcinoma, and mucosal invasion, and the excision stump was negative. After two more courses of S-1 + cisplatin, chemotherapy has been suspended with the patient's consent, and in the 21 months after endoscopic mucosal resection, no recurrence has been observed. This is a rare case of metastatic Barrett's esophageal cancer in which the metastases were eradicated by S-1 + cisplatin, and the primary tumor successfully excised by endoscopic mucosal resection after downstaging.
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PMID:Successful treatment of S-1 + CDDP followed by salvage EMR for a case with metastatic Barrett's esophageal cancer. 1743 3

Depth of invasion is one of the most important prognostic indicators in esophageal adenocarcinoma. Unlike other regions of the gastrointestinal tract, the esophagus in Barrett metaplasia frequently develops duplication of the muscularis mucosae (MM), but this feature is underrecognized, and its effect on appropriate staging of superficially invasive adenocarcinoma is unclear. We first randomly selected 50 esophageal resections for high-grade dysplasia or T1 adenocarcinoma in Barrett esophagus (BE) to evaluate the sensitivity and specificity of MM duplication for BE and its histologic characteristics, including percentage of the Barrett segment involved by MM duplication, origin of the duplicated muscle layer, and appearance of the tissue between duplicated MM. Twenty esophageal resections for squamous cell carcinoma served as controls. Next, to study the clinical significance of MM duplication, we evaluated 30 resections for BE that had superficial adenocarcinoma confined to regions of duplicated MM. Each case was classified as: depth of invasion (inner MM, space between duplicated MM, or outer MM), angiolymphatic invasion, and rate of lymph node metastasis. We observed MM duplication in 46 of 50 (92%) BE resections, involving 5% to >90% of the Barrett segment, in contrast to none in 20 (0%) resected squamous cell carcinoma, P<0.0001. In 5 (10%) cases, the MM was focally triplicated. The outer MM was continuous with the single MM beneath squamous epithelium, suggesting that outer MM represents the "original" muscle layer. The space between duplicated MM predominantly consisted of loose fibrovascular tissue similar to submucosa; in 15 (30%) cases, there were also areas of fibrosis or thin muscle strands joining the 2 MM layers. Of 30 adenocarcinomas invading duplicated MM, 10 (33%) invaded only inner MM, 12 (40%) invaded the space between MM, and 8 (27%) invaded the outer MM. Angiolymphatic invasion was present in 5 (17%) cases, and nodal metastases in 3 (10%, 1 case each of invasion into inner MM, between MM, and outer MM). These data show that MM duplication is a characteristic finding in BE, but it can pose difficulty in proper staging of superficial adenocarcinomas. The 17% rate of angiolymphatic invasion and 10% rate of lymph node metastases in our patients with invasion into duplicated MM suggest that these tumors can behave aggressively despite their technically intramucosal location.
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PMID:Duplication of the muscularis mucosae in Barrett esophagus: an underrecognized feature and its implication for staging of adenocarcinoma. 1882 91

A well-known type of mesenchymal/epithelial interaction occurs in Barrett esophagus (BE) characterized by the formation of a new, superficially located, muscularis mucosae (MM), which results in the division of the lamina propria (LP) into a superficial and deep compartment. The vascular and lymphatic properties of these 2 regions of LP are unknown. The risk of metastases of carcinomas that infiltrate these 2 anatomic areas also remains unclear. The aim of this study was to evaluate the density of blood vessels and lymphatic spaces within the superficial and deep LP and submucosa in patients with BE, and to compare the results to normal squamous-lined esophagus. Thirty esophago-gastrectomy specimens were stained immunohistochemically with CD31 (stains blood vessel and lymphatic endothelium) and D2-40 (stains lymphatic endothelium only). The density of CD31+ blood and lymphatic vessels (per 20 x field) in BE (superficial LP=37 and deep LP=38) was significantly lower compared with the LP of squamous-lined esophagus (68; P<0.001). However, the total number of blood and lymphatic vessels in the superficial and deep LP in BE was statistically similar to the LP of squamous-lined esophagus. The density of CD31+ blood and lymphatic vessels (per 20x field) in the submucosa of BE (21) was not significantly different from the submucosa of squamous-lined esophagus (23; P>0.05). We conclude that in BE, the "native" LP in squamous-lined esophagus is separated into 2 LP compartments (superficial and deep) by the formation of a new MM. These findings suggest that carcinomas that invade through the superficial MM into the deep LP should be considered "intramucosal" rather than "submucosal." Further outcome studies are needed to evaluate the risk of vascular/lymphatic metastasis in BE patients with different levels of LP invasion.
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PMID:Vascular and lymphatic properties of the superficial and deep lamina propria in Barrett esophagus. 1868 88

Esophageal adenocarcinoma arises in the backdrop of Barrett metaplasia-dysplasia sequence, with the vast majority of patients presenting with late-stage malignancy. Mesothelin, a glycophosphatidylinositol-anchored protein, is aberrantly overexpressed on the surface of many solid cancers. Mesothelin expression was assessed in esophageal tissue microarrays encompassing the entire histological spectrum of Barrett-associated dysplasia and adenocarcinoma. Mesothelin expression was observed in 24/84 (29%) of invasive adenocarcinomas and in 5/34 (15%) lymph node metastases. In contrast, normal squamous and cardiac mucosa, as well as noninvasive Barrett lesions, failed to label with mesothelin. Mesothelin was expressed in the esophageal adenocarcinoma cell line JH-EsoAd1 but not in primary human esophageal epithelial cells. Anti-mesothelin antibody-conjugated CdSe/CDS/ZnS quantum rods were synthesized, and confocal bioimaging confirmed robust binding to JH-EsoAd1 cells. Anti-mesothelin antibody-conjugated nanoparticles can be useful for the diagnosis and therapy of mesothelin-overexpressing esophageal adenocarcinomas.
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PMID:Mesothelin is a specific biomarker of invasive cancer in the Barrett-associated adenocarcinoma progression model: translational implications for diagnosis and therapy. 1869 48


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