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)

The incidence rate of adenocarcinoma of the esophagogastric junction (AEG) is increasing in association with the epidemiologic rise in distal esophageal adenocarcinoma and gastric cardial (AEG type III) tumors. The overall survival rate is poor in most patients with AEG because lymph node or visceral metastases are frequently present at the time patients become symptomatic. A few patients are identified early in the disease because of screening for gastroesophageal reflux and Barrett's esophagus. Early stage AEG (T1N0 or T2NO, carcinoma in situ, or severe dysplasia ) can in many instances be cured with surgery alone. Ablative treatments for early stage AEG, including endoscopic fulguration by cautery and laser or photodynamic therapy, are investigational at this time. Locoregionally advanced AEG (T3, T4, N1, or M1a ) without distant systemic metastases (M1b) has a poor overall survival rate with surgery alone or definitive chemotherapy and radiation therapy without surgery. Analysis of the use of multimodality treatment strategies for locoregionally advanced AEG types I and II have demonstrated improved survival rates in two small phase III trials with preoperative concurrent chemoradiotherapy followed by surgical resection. In contrast, three small phase III trials with preoperative concurrent or sequential chemoradiotherapy in patients with predominantly squamous cell carcinoma did not demonstrate any clear survival advantage. Additionally, a randomized phase III study evaluating preoperative chemotherapy without radiation therapy in esophageal cancer (predominantly adenocarcinoma) has demonstrated no survival benefit. In light of these results, additional large randomized phase III studies are needed to confirm the potential benefit of preoperative concurrent chemoradiotherapy. At the present time, preoperative chemoradiotherapy remains investigational. For locoregionally advanced gastric adenocarcinoma, including AEG type III, postoperative concurrent 5-fluorouracil (5-FU)-based chemoradiotherapy is associated with improved survival as demonstrated in a recently completed random assignment trial (INT 0116). As a result, surgery with postoperative chemoradiotherapy has recently become the standard of care for patients with AJCC stage II and III gastric adenocarcinoma (including patients with AEG type III). Metastatic AEG (M1b) should be treated with palliative chemotherapy (in good performance patients) or supportive care (poor performance) in asymptomatic patients. Radiation therapy and endoscopic stent placement (expandable wire mesh) can be used to palliate dysphagia in patients with M1b disease. The development of expandable stents and improved radiotherapy has obviated surgical bypass to palliate patients with symptomatic, metastatic AEG.
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PMID:Gastroesophageal junction adenocarcinoma. 1205 46

Barrett's metaplasia develops in 6-14% of individuals with gastroesophageal reflux. Barrett's adenocarcinomas are increasing in epidemic proportions for as yet unknown reasons, approximately 0.5-1% of patients with Barrett's will develop adenocarcinoma. Heartburn duration and frequency (but not severity), male gender, and Caucasian 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 propia occurs, the vast majority of patients will 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.
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PMID:Barrett's esophagus: clinical characteristics. 1213 12

Sarcoidosis remains a fascinating illness that almost always affects the respiratory tract but often involves many other organs as well. Although many patients seem to have only an intrathoracic illness, with perhaps one other site or organ involved, others can experience a severe multi-organ disease. The inciting stimulus, even if unknown, can elicit an immunologic host response-the non-caseating granuloma-in almost every organ. It is intriguing that this stimulus can be so widespread throughout the body, while the biology of the disease can be so variable. Many series of patients with sarcoidosis have reported the multiple organs involved and the clinical presentation. Our series of 67 patients (40 female, 27 male, mean age 38.7 years +/- 13.2 (SD) at time of diagnosis) generally mirrors the clinical pattern found in five comparison series that span the past 60 years. However, more emphasis is given in this series to associated medical conditions that can complicate the presentation of sarcoidosis, as well as to co-morbid illnesses that must be managed in addition to the patient's sarcoidosis. Although most patients had intrathoracic sarcoidosis diagnosed at initial evaluation (40%), many had other organs or bodily sites involved in addition (or subsequently) as the illness evolved. Confounding the initial patient evaluation were two factors: (1) the presence of an occupational respiratory exposure(s) (n = 25 or 37% of patients); (2) a previously diagnosed malignancy (n = 6 or 9%) that heightened the possibility of a primary malignancy presenting in the chest, or the reactivation of a prior malignancy (breast, thyroid, and lymphoma) that could metastasize to the lung. Symptoms present when a patient's diagnosis was established usually differentiated respiratory and/or abdominal organ involvement. Although respiratory symptoms could be absent (n = 18 or 27%) for many patients with incidental thoracic findings, most had typical ones, including exertional dyspnea. For patients with an abdominal presenting illness (n = 11 or 16%), nonspecific digestive and abdominal symptoms were experienced as well as arthralgias. Almost every patient had at least one important other illness that factored significantly into the management of their sarcoidosis. Older patients had more illnesses, such as cardiovascular illness, diabetes mellitus, neurologic problems, and functional gastrointestinal symptoms. Depression affected all ages and was probably underrecognized; more emphasis on this illness is needed. Obesity was associated with disordered sleep syndromes, but not invariably so, as half the subjects had a good body habitus. Thus, many of the other illnesses experienced by sarcoidosis patients are common problems that middle-aged people develop. However, digestive and gastroenterological symptoms seemed disproportionately frequent in this series. This is a component of multi-organ sarcoidosis that has not received extensive coverage in the literature. Approximately one-third of sarcoidosis patients had one of two very common problems-gastroesophageal reflux or irritable bowel syndrome. But these are common problems, and it is thus necessary to separate these symptoms from those associated with abdominal visceral involvement of sarcoidosis. Although liver and/or splenic involvement with sarcoidosis do not cause organ dysfunction or insufficiency, they can contribute to abdominal symptoms. Finally, it remains of interest whether inflammatory bowel disease-Crohn's disease in particular-is another organ manifestation of sarcoidosis, or is it unrelated?
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PMID:Sarcoidosis: impact of other illnesses on the presentation and management of multi-organ disease. 1248 22

The frequency, symptoms, and complication rate of PUD seem to decrease during pregnancy. Yet clinicians often have to treat dyspepsia or pyrosis of undetermined origin during pregnancy because the frequency of pyrosis significantly increases during pregnancy, and clinicians reluctantly perform EGD during pregnancy for pyrosis to differentiate reliably between GERD and PUD. Dyspepsia or pyrosis during pregnancy is initially treated with dietary and lifestyle modifications. If the symptoms do not remit with these modifications, sucralfate or antacids, preferably magnesium-containing or aluminum-containing antacids, should be administered. Histamine2 receptor antagonists are recommended when symptoms are refractory to antacid or sucralfate therapy. Ranitidine seems to be a relatively safe H2 receptor antagonist. If symptoms continue despite H2 receptor antagonist therapy, the patient should be evaluated for possible EGD or PPI therapy. Pregnant women with hemodynamically significant upper gastrointestinal bleeding or other worrisome clinical findings should undergo EGD. Indications for surgery include ulcer perforation, ongoing active bleeding from an ulcer requiring transfusion of six or more units of packed erythrocytes, gastric outlet obstruction refractory to intense medical therapy, and a malignant gastric ulcer without evident metastases.
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PMID:Gastric and duodenal ulcers during pregnancy. 1263 19

Esophageal carcinoma is a highly lethal disease with increasing prevalence and an equally dramatic epidemiologic shift. Its causal association with gastroesophageal reflux disease and adenocarcinoma of the esophagus is well established, and the molecular events underlying this progression from mucosal injury to metaplasia to dysplasia to carcinoma are now becoming clear. Current diagnostic modalities and preoperative staging systems have significant limitations. The extent of surgical resection for esophageal carcinoma remains controversial. Disease confined to the mucosa and submucosa is more common, and endoscopic ablative techniques have been proposed. However, preoperative evaluation of tumor depth and regional nodal metastases remains inadequate in these very early lesions and urges caution before adoption of therapies that may compromise cure. Patients with disease confined to the mucosa or submucosa should undergo resectional therapy aimed at removing the entire esophageal wall, including the periesophageal and perihiatal lymph nodes. For disease penetrating the submucosa, the extent of surgical therapy must be tailored to the objectives of treatment (cure vs palliation) and preoperative stage. Although data from seven prospective, randomized trials are encouraging, no clear survival benefit has been documented for neoadjuvant combined-modality therapy. Surgical resection remains the standard of care and best chance for cure in the treatment of esophageal malignancy, with combined-modality therapy reserved for prohibitive surgery candidates.
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PMID:Surgical management of esophageal malignancy. 1273 40

Because of effective surveillance programs in patients with known Barrett's esophagus, adenocarcinoma of the distal esophagus is increasingly diagnosed at early stages. With the introduction of limited surgical and endoscopic treatment modalities, the need for radical esophagectomy and extensive lymphadenectomy in such patients has been questioned. When selecting the approach to early Barrett's cancer, the precancerous nature of the underlying Barrett's esophagus, the frequent multicentricity of neoplastic alterations within the Barrett mucosa, the inaccuracy of current staging modalities, and the presence of lymph node metastases should be taken into account. Invasiveness and morbidity of the procedures, as well as quality of life aspects, should also be considered. From an oncologic point of view the minimum extent of a resection for early Barrett's cancer should include a full-thickness removal of the entire segment of the distal esophagus covered by intestinal metaplasia together with a regional lymphadenectomy. In appropriately selected patients this can be achieved by a limited surgical procedure involving transhiatal resection of the distal esophagus, but not by endoscopic mucosal ablation or endoscopic mucosa resection. Our experience with 49 limited surgical resections with regional lymphadenectomy indicates that this procedure is oncologically adequate and safe. Reconstruction with an interposed jejunal loop prevents postoperative gastroesophageal reflux and is associated with good quality of life. In contrast, endoscopic interventions are plagued by a high tumor recurrence rate, probably from persistence of Barrett's mucosa and gastroesophageal reflux.
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PMID:Approach to early Barrett's cancer. 1291 59

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.
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PMID:Molecular targets for treatment of Barrett's esophagus. 1605 81

Surgery for cancer carries concerns of tumor dissemination related to tumor manipulation, tumor violation, and wound seeding. Minimally invasive surgery is now standard for several benign conditions, such as symptomatic cholelithiasis and surgical therapy of gastroesophageal reflux. With the minimally invasive surgery explosion of the 1990s, virtually every procedure traditionally performed via laparotomy has been performed successfully with laparoscopic methods, including pancreaticoduodenectomy for cancer. Shortly after the first descriptions of laparoscopic-assisted colectomy, reports of port-site tumor recurrences surfaced, raising concerns of usingpneumoperitoneum-based surgery for malignancy. This review covers the development of laparoscopic surgery for cancer. Historical perspectives elucidate factors that helped shape the current state of the art. Theoretical concerns are discussed regarding surgery-induced immune suppression and its potential effects on tumor recurrence with both open and laparoscopic approaches. The concerns of laparoscopic port-site wound metastases are addressed, with a critical evaluation of the literature. Finally, a technical discussion of laparoscopic-assisted resections of hepatic and pancreatic tumors details patient selection, operative approach, and existing data for these operations.
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PMID:Laparoscopic surgery for cancer: historical, theoretical, and technical considerations. 1692 61

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

Esophageal carcinoma remains a highly lethal disease that has shown a recent profound increase in prevalence and an equally dramatic epidemiologic shift. There is a well recognized causal association between gastroesophageal reflux disease and adenocarcinoma of the esophagus, and the molecular events underlying this progression from mucosal injury, to metaplasia, to dysplasia, to carcinoma are now becoming clear. Current diagnostic modalities and preoperative staging systems all have significant limitations. Fortunately, chemoprevention strategies and the identification of clinically useful molecular biomarkers that may be used to stage disease and select appropriate therapy are on the horizon. The extent of surgical resection for esophageal carcinoma remains an area of great controversy. Disease that is confined to the mucosa is being diagnosed more commonly, and endoscopic ablative techniques have been proposed. To date, however, preoperative discrimination of tumor depth and presence of regional nodal metastases remains inadequate in these very early lesions, and caution is urged before adopting therapies that may compromise cure. For disease penetrating the mucosa, the extent of surgical therapy must be tailored by the objectives of treatment (cure vs palliation) and preoperative stage. Surgical resection is the current standard of care, with combined-modality therapy reserved for prohibitive surgical candidates. No clear survival benefit has been documented for neoadjuvant radiotherapy or chemotherapy alone. The results of preoperative combined-modality therapy, including three prospective, randomized trials, are encouraging but to date have not shown a definite benefit.
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PMID:Surgery, radiotherapy, and chemotherapy in carcinoma of the esophagus. 1703 Nov 7


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