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)

Before the mid-1970s, the most reliable therapy for Zollinger-Ellison syndrome (Z-E syndrome) was total gastrectomy since complete excision of gastrinoma is difficult in many cases due to multifocus and/or metastases. With the advent of H2-blockers gastric acid secretion can be controlled at safe levels (less than 10 mEq/h), and patients with Zollinger-Ellison syndrome can be managed medically. The problem of therapy with H2-blockers however, is that large doses are usually required and that a marked tachyphylaxis is frequently noted during long-term treatment. Treatment with new antisecretory drug, proton pump inhibitor, has been shown to be highly effective with relatively high doses and without tachyphylaxis, although long-term experience is still limited.
 ...
PMID:[Application of proton pump inhibitor to special conditions; Zollinger-Ellison syndrome]. 134 27

The extracellular pH in malignant tumors is known to be lower than in normal tissues and may therefore facilitate extracellular activation of secreted lysosomal cathepsins. We have tested the capability of human mammary cells (continuous cell lines and primary culture) to acidify their extracellular environment, using two techniques. By measuring pH changes through alterations of phenolsulfone phthaleine absorbance, we found that the more aggressive MDA-MB-231 human breast cancer cells were more active in acidifying a non-buffered balanced salt solution than the estrogen receptor positive MCF7 and ZR75 cell lines and than normal mammary epithelial cells in primary culture. Metastatic breast cancer cells from pleural effusions were up to 200-fold more active in acidifying their extracellular milieu than non-malignant mammary cells cultured in the same conditions, strongly suggesting that this difference also occurs in vivo. The use of inhibitors in the presence or absence of glucose showed that both lactate and an ATP-driven proton pump sharing some characteristics of the vacuolar H+ pump were involved. Bafilomycin A1, a specific inhibitor of the vacuolar (V-type) ATP-H+ pump inhibited part of the acidification by MCF7 cells, but not by MDA-MB-231 cells. We also used microelectrodes to measure extracellular pH, in close contact to the MCF7 breast cancer cells. The pH at the free surface of MCF7 cells was lower by 0.33 +/- 0.14 unit than that of the surrounding medium, while insertion of the microelectrode tip beneath the attached surface of the cells showed a greater lowering of pH from 0.3 to 1.7 pH unit as long as cell attachment on the substrate prevented H+ diffusion. We conclude that breast carcinoma cells have a higher capacity for acidifying their extracellular milieu than normal mammary cells, and that both a plasma membrane H(+)-ATPase, and lactic acid production are involved in this acidification. It is therefore possible that the aspartyl and cysteinyl pro-cathepsins secreted in excess by tumor cells may be activated extracellularly in vivo close to the basement membrane.
Clin Exp Metastasis 1997 Jul
PMID:Breast cancer cells have a high capacity to acidify extracellular milieu by a dual mechanism. 921 26

Gastrinoma treatment has evolved considerably in the last 20 years. In particular, the advent of effective acid-reducing pharmacologic agents has changed the primary morbidity of this disease entity from one of acid hypersecretion to one of tumor growth and spread. Thus, while symptoms can be temporized using histamine receptor antagonists, proton pump inhibitors, or somatostatin analogs, cure can be effected only by surgical means. Recent advances in operative techniques and pre- and intra-operative imaging studies, including routine duodenotomy, somatostatin-receptor scintigraphy, and intraoperative ultrasound, have allowed for identification and subsequent resection of more than 95% of gastrinoma tumors. Most experts agree that all sporadic cases of localized gastrinoma should be excised. In addition, debulking of metastatic tumor may improve symptoms and survival when cure cannot be ascertained. There is, however, some controversy as to the surgical approach for gastrinoma found in the setting of multiple endocrine neoplasia, type 1. Because of the usual multiplicity and particular indolence of these tumors, two primary strategies have emerged: aggressive approaches have been advocated in an effort to eradicate all present and potential tumor; and less aggressive, or nonoperative, approaches have been suggested because it is unclear whether intervention offers survival or disease-free benefit in this population. We advocate surgical intervention for patients with gastrinoma and multiple endocrine neoplasia, type 1 when tumors exceed 2.5 cm in size. This tumor size has been associated with a higher likelihood of hepatic metastases, which ultimately affects survival. The role of adjuvant therapies for gastrinoma remains limited.
 ...
PMID:Gastrinoma. 1205 14

Effective medical therapy of gastric hypersecretion in Zollinger-Ellison syndrome may delay the diagnosis of gastrinoma. To examine the impact of effective medical therapy on the surgical treatment of gastrinoma we reviewed the records of 108 patients diagnosed between 1948 and 1998 at a single institution. Minimum follow-up was 5 years. The experience was divided into four periods: I, 1955-1965-initial recognition, n = 11; II, 1966-1975-increasing recognition, n = 27; III, 1976-1985-widespread application of gastrin radioimmunoassay, n = 21; and IV, 1986-1998-widespread use of effective medical therapy, n = 49. There was no significant difference in age or sex in the groups. Gastric surgery was less common in period IV (37% compared with 86% to 100% in previous periods) as was total gastrectomy (6% compared with 43% to 78%; P <0.0001). Tumor resection was attempted in a similar percentage of patients in each group (57% to 67%). The incidence of metastatic disease in period III was 19% (P = 0.034 versus period I, 45%, period II, 56%, and period IV, 55%). The 5-year disease-free survival increased in period III to 29% (P = 0.001 versus period I, 0%, period II, 4%, and period IV, 2%). The results support the effectiveness of acid suppressive therapy by H2 antagonists and proton pump inhibitors as evidenced by the decrease in gastric surgery. However, in the era of effective medical therapy, the surgeon sees the patient with more advanced disease and 5-year cure is less likely. Physicians must maintain a high index of suspicion for this disease and not mask a potential malignancy with prolonged control of acid-related symptoms without taking steps to diagnose gastrinoma.
 ...
PMID:Zollinger-Ellison syndrome in the era of effective acid suppression: are we unknowingly growing tumors? 1294 26

Zollinger-Ellison syndrome is characterised by refractory peptic ulcer disease, severe diarrhoea and gastric acid hypersecretion associated with an islet-cell tumour of the pancreas (gastrinoma). The true incidence and prevalence of this rare disease is unknown; in the US, the frequency is one per one million people and the age at presentation varies from 7 to 90 years. Zollinger-Ellison syndrome is sporadic in 62-80% of cases and in 20-38% of cases is associated with multiple endocrine neoplasia type 1 (MEN 1). The diagnosis of Zollinger-Ellison syndrome is certain when the plasma gastrin is >1000 pg/mL and the basal acid output is >15 mEq/h in patients with an intact stomach, >5 mEq/h in gastrectomised patients, or when this hypergastrinemia is associated with a pH <2. The treatment is based on control of gastric acid hypersecretion and of the malignant tumour and its possible metastases. Proton pump inhibitors are the most effective antisecretory drugs and can be administered in the elderly at high dosages without drug-related adverse effects. As an initial therapy, daily dosages of omeprazole 80-100 mg or pantoprazole 40-160 mg are employed. In long-term treatment the doses can be greatly reduced once effective control of the gastric output has been established. Intravenous proton pump inhibitors may be administered when patients cannot take oral therapy, particularly in acute conditions. All sporadic localised gastrinomas should be excised if possible. When liver metastases are also present, their debulking may improve symptoms and survival, and facilitate medical treatment. There is some controversy as to the surgical approach for gastrinomas associated with MEN 1. Somatostatin analogues can be useful in reducing gastric acid hypersecretion, serum gastrin and gastric enterochromaffin-like (ECL) cells and can thus contribute to treating the disease more effectively. Their antiproliferative effect can be used in treating liver metastases. Chemotherapy is not the therapy of choice in patients with gastrinomas and is indicated only in those with malignant progressive disease; interferon alpha, embolisation and chemoembolisation are not advisable for the elderly. The treatment of elderly Zollinger-Ellison syndrome patients, similarly to all elderly oncological patients, should be based on the use of comprehensive geriatric assessment. This will enable the clinician to define the functional status of the elderly person, to decide whether the patient can tolerate surgery and/or the stress of antineoplastic therapy, and finally, to determine whether this patient can tolerate an aggressive treatment for Zollinger-Ellison syndrome or whether the only possible choice is palliative relief of symptoms.
 ...
PMID:Optimal treatment of Zollinger-Ellison syndrome and related conditions in elderly patients. 1465 42

Gastrinomas of the stomach are extremely rare endocrine tumors producing Zollinger-Ellison syndrome. We report here the case of a patient with gastrinoma of the stomach who presented regional and hepatic metastases at the time of diagnosis. The endocrine tumor was discovered incidentally 8 yr after the onset of symptoms related to peptic ulcer, which responded to medical treatment with a proton pump inhibitor. Surgery did not cure the patient, as demonstrated by provocative tests showing serum gastrin responses indicative of residual disease. A long-term treatment with the somatostatin analog lanreotide induced a biochemical response and was associated with a substantially stable disease.
 ...
PMID:Gastrinoma of the stomach: a case report. 1611 Jan 23

Zollinger-Ellison syndrome (ZES) is characterised by refractory peptic ulcer disease, severe diarrhoea and gastric acid hypersecretion associated with an islet-cell tumor of the pancreas (gastrinoma). ZES is sporadic in 62-80% of cases and in 20-38% of cases is associated with multiple endocrine neoplasia type 1 (MEN 1). The diagnosis of ZES is certain when the plasma gastrin is >1000 pg/mL and the basal acid output is >15 mEq/h in patients with an intact stomach, >5 mEq/h in gastrectomised patients, or when the hypergastrinemia is associated with a pH <2. Treatment is based on the control of gastric acid hypersecretion and of the malignant tumor and its possible metastases. Proton pump inhibitors are the most effective antisecretory drugs and can be administered at high dosages without drug-related adverse effects. All sporadic, localised gastrinomas should be excised if possible. When liver metastases are also present, their debulking may improve symptoms and survival, and facilitate medical treatment. There is some controversy as to the surgical approach for gastrinomas associated with MEN 1. Somatostatin analogues can be useful in reducing gastric acid hypersecretion, serum gastrin and gastric enterochromaffin-like cells, and can thus contribute to treating the disease more effectively. Their antiproliferative effect can be used in treating liver metastases. Chemotherapy and/or interferon are indicated only in patients with malignant progressive disease. Embolisation and chemoembolisation are effective in controlling clinical symptoms; however, they do not seem to improve survival.
 ...
PMID:Zollinger-Ellison syndrome. Diagnosis and therapy. 1617 61

Zollinger-Ellison syndrome is characterised by refractory peptic ulcer disease, diarrhoea and gastric acid hypersecretion associated with a gastrin-secreting tumour. The incidence is unknown, but, in the US, the frequency is 0.1-3.0 million people. Zollinger-Ellison syndrome is associated with multiple endocrine neoplasia type 1 in 25-35% of the cases. The diagnosis of Zollinger-Ellison syndrome is suggested when plasma gastrin is > 1000 pg/ml and the basal acid output is > 15 mEq/h or when associated with a pH < 2. The treatment is focused on controlling gastric acid hypersecretion and localisation of the tumour and its metastases. Proton pump inhibitors are the most effective antisecretory drugs and can be administered at high dosages. This review focuses on the role of the proton pump inhibitors in the management of gastric acid hypersecretion in Zollinger-Ellison syndrome.
 ...
PMID:The role of proton pump inhibitors in the treatment of Zollinger-Ellison syndrome. 1643 82

The surgical management of pancreatic endocrine tumors in patients with multiple endocrine neoplasia type 1 remains controversial. Gastrinoma and insulinoma are the 2 most common functional pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1. Gastrinomas cause gastric acid hypersecretion and peptic ulcer disease that are best managed using proton pump inhibitors. Surgery to remove the gastrinoma in patients with multiple endocrine neoplasia type 1 is seldom curative unless a more extensive Whipple pancreaticoduodenectomy is performed. Because the prognosis is excellent, aggressive resections such as a Whipple procedure are only indicated for large, locally metastatic, advanced tumors. Furthermore, surgery to remove imageable tumors that are 2 cm in diameter is associated with excellent outcomes and decreased probability of liver metastases. Because gastrinomas are commonly multiple and most originate in the duodenum and develop lymph node metastases, the duodenum should be opened and all tumors and lymph nodes excised. Insulinomas cause hypoglycemia that results in neuroglycopenic symptoms. Medical management of the hypoglycemia is less effective than that of the gastric acid hypersecretion. Fortunately, the insulinoma is usually clearly identified using routine pancreatic imaging studies. There is a high likelihood of cure when the insulinoma is excised surgically. However, recurrent hypoglycemia may occur, and careful follow-up is indicated.
 ...
PMID:Surgery for gastrinoma and insulinoma in multiple endocrine neoplasia type 1. 1645 71

The Zollinger-Ellison syndrome is characterized pathophysiologically by a significant hypergastrinemia derived from a gastrin-secreting neuroendocrine tumor with a primary location in the pancreas or duodenum. Chronic hypergastrinemia in turn triggers gastric acid hypersecretion yielding in chronic or recurrent or refractory peptic ulcer disease and/or chronic diarrhea. One half of patients with ZES will have distant metastases in the liver by the time the diagnosis is established and one half of all patients with ZES will experience chronic diarrhea as chief complaint rather than peptic ulcer-related symptoms and signs. Gastrinomas have been reported to either manifest sporadically or to occur in conjunction with the genetic background of the MEN-I syndrome. Diagnosis is based on the patients history which is typically characterized by recurrent episodes of peptic ulcer disease or by severe reflux esophagitis and/or diarrhea or by acid-related symptoms which fail to respond to standard treatment regimens. Upper gastrointestinal tract endoscopy will provide evidence for peptic ulcer disease in anatomical regions located aborally the duodenal bulb within the descending part of the duodenum or even farther distally within the jejunum. Peptic ulcers frequently occur in groups indicating some substantial acid hypersecretion. A gastric pH > 2 is mutually exclusive for ZES. Increased serum gastrin levels confirm the diagnosis biochemically. Gastrin secretion can be determined in the basal state or following stimulation with secretin or calcium. High sensitivity and specificity for the diagnosis of ZES is provided by determining the ratio of basal versus pentagastrin-stimulated gastric acid secretion: The ratio of BAO / MAO > 0.6 is highly specific for gastrinoma. To localize the gastrin-secreting tumor computer-assisted tomography, endoscopic ultrasound, and somatostatin receptor scintigraphy provide useful help but most recently, endoscopic ultrasound with high resolution transducers appear to improve preoperative site localization. If modern imaging techniques fail to elucidate the site of the tumor, intraoperative diaphany may help to detect gastrinomas within the duodenal wall. Definitive treatment will only be achieved by total surgical resection of the gastrin-producing tumor in the pancreas or duodenum including dissection of the regional lymph nodes. Control of symptoms will have to be achieved by administration of highly potent proton pump inhibitors in up to 2-3-fold increased standard doses to inhibit gastric acid hypersecretion. Elevation of gastric pH > 4 will be the therapeutic target to protect the mucosa of the upper gastrointestinal tract. Basal acid output should be reduced to less than 10 mEq H(+) per hour which requires administration of highly potent proton pump inhibitors with a recommended starting dose of 60 mg omeprazole equivalents per day.
 ...
PMID:Diagnosis and treatment of gastrinoma in the era of proton pump inhibitors. 1798 90


1 2 3 Next >>