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)

A diagnostic and therapeutic strategy for the management of patients with Zollinger-Ellison syndrome has been developed, based on the review of a large personal experience and the most recent literature. The mainstay of a modern ZES management is the eradication of tumoral processes whenever feasible. Diagnosis is centred upon gastric acid and gastrin secretion measurements both in basal conditions and on secretin stimulation. Recognition of other endocrine involvement and familial inheritance is of the utmost importance in distinguishing sporadic ZES patients from those who have the condition known as multiple endocrine neoplasia type I. Blood calcium and phosphorus levels, parathyroid hormone concentration, combined if necessary with urinary cyclic AMP excretion measurement, should be performed routinely once ZES diagnosis is established or highly suspected. Localization of the tumour is the next essential step, and this has been considerably facilitated by the recent development in imaging techniques: it involves computerized axial tomography and selective abdominal angiography, a combination of which allows tumour detection in 60-70% of sporadic gastrinoma patients, with a maximal sensitivity for well-developed hepatic metastases. In sporadic ZES exploratory laparotomy is legitimate when preoperative localization of the tumour has failed; this laparotomy will allow further detection and then eradication of gastrinomas in a significant number of patients. Control of gastric acid secretion is mandatory throughout the work-up period; modern antisecretory agents are efficacious in most cases; total gastrectomy, when control of acid hypersecretion has failed, is now exceptional. Eradication of the tumour should be attempted in cases of sporadic ZES in the absence of recognizable liver involvement. The chance of a definite cure provided by surgery when performed by an experienced surgeon varies from 20% to 60% in pancreatic and ectopic gastrinomas respectively. In ZES patients with MEN I, exploratory laparotomy is seldom indicated (other than for symptomatic associated endocrine secretion), as the chance of a definite cure by surgery is very rare. Parathyroid surgery is often indicated and should take place before any form of abdominal surgery. In cases of hepatic metastases, chemotherapy with streptozocin and fluorouracil is indicated and soon, perhaps, chemo-embolization.
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PMID:Diagnosis and treatment of Zollinger-Ellison syndrome. 304 57

Five patients with the Zollinger-Ellison syndrome who had extra-pancreatic (duodenal or paraduodenal) gastrinoma with lymph node metastases responded favourably to simple excision or mere shelling out of macroscopic tumour. Acid studies, serum gastrin and the secretin test became normal in all cases in the immediate postoperative period and remained so in three of the five patients when tested at 57, 33 and 8 months. The tests became abnormal in two patients when tested 8 and 53 months after surgery, but both patients are currently well-controlled on ranitidine 150 mg b.d. 22 and 65 months respectively after surgery. These results suggest that in patients with extra-pancreatic gastrinoma who have lymph node metastases simple excision of all macroscopic tumours may offer the prospect of long-term control. The place of total gastrectomy in such patients is questioned.
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PMID:Favourable response to conservative surgery for extra-pancreatic gastrinoma with lymph node metastases. 356 10

Eight cases of the Zollinger-Ellison syndrome were diagnosed at St Vincent's Hospital in the period 1966-84. Although a rare tumour, its true incidence is almost certainly greater than the number of cases represented in this series. The Zollinger-Ellison syndrome should be suspected in all cases of recurrent peptic ulceration, in cases of peptic oesophagitis not responding to medical treatment, in some cases of diarrhoea and in those cases of peptic ulceration associated with hypercalcaemia. Rarely the gastrinoma may first present as a mass in the head of the pancreas causing obstructive jaundice. Diagnosis has been made easier by estimation of fasting serum gastrins and the use of the secretin test. Localization is difficult. The treatment of the condition remains contentious. In those cases shown to be harbouring a so-called solitary gastrinoma, laparotomy should be performed with a view to resection. If the gastrinoma cannot be localized then it is reasonable to use H2 blocking agents to control hypersecretion. The presence of hypercalcaemia due to hyperparathyroidism must be controlled by parathyroidectomy. Total gastrectomy is reserved for those few cases who for one reason or another are not controlled by adequate H2 blocking therapy. In the presence of malignant gastrinoma with metastatic disease, hypersecretion is controlled by the use of H2 blocking agents. In this group cytotoxic chemotherapy may be used in an attempt to control the mass effects of the tumour.
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PMID:The Zollinger-Ellison syndrome: a review of the St Vincent's Hospital, Melbourne experience. 386 9

From 1978 to 1984, six patients (four men and two women) with functioning extrapancreatic gastrinomas were treated at the University of Michigan Medical Center. In all but one patient, who was known to have a liver metastasis, selective portal and peripheral venous sampling was performed to localize the site(s) of increased gastrin levels. Serum levels of carboxy (C) and amino (N) terminal gastrin moieties were measured before surgery with region-specific antisera and N/C ratios were calculated. All patients underwent operative exploration and successful resection of all gastrinomas present including a single large liver metastasis in one case. The C-terminal gastrin level was elevated in all cases and the N/C ratios were well below 1.0 (greater than 1 is consistent with malignancy and metastases) in all but the one patient with a liver metastasis. All patients have remained clinically free of tumor and have had normal basal and secretin-stimulated gastrin levels for as long as 5 years after operation. Three of the patients had undergone previous total gastrectomies and had done well apart from persistent hypergastrinemia before resection of the tumor. Two patients have not undergone any type of gastric operation. Appropriately selected patients with Zollinger-Ellison syndrome, particularly those with extrapancreatic primary lesions, may be candidates for a curative resection.
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PMID:Extrapancreatic gastrinomas. 407 87

Review of a 5 year clinical experience with the histamine H2-receptor antagonists metiamide, cimetidine, and ranitidine in 20 patients with Zollinger-Ellison syndrome disclosed a treatment failure rate of 50 percent. The criterion for failure was hemorrhage in four patients, obstruction followed by hemorrhage in one patient, perforation in one, and intractable pain in four. Nine of the 10 patients in whom treatment failed required total gastrectomy for control of complications; the 10th patient refused operation. Retrospective analysis identified hepatic metastases, the multiple endocrine adenomatosis-type I syndrome, refractory diarrhea, and breaks in the medication schedule as being more common in the treatment failure group, but these trends were not statistically significant in our small series of patients. Nonhealing or recurrent ulcers were found in 90 percent of the patients in whom drug therapy failed and in only 10 percent of those patients in whom therapy was successful (p less than 0.01). There were no differences related to age, sex, duration of symptoms, previous gastric operation, ulcer location, presence of diarrhea, or amount of drug prescribed. Basal and peak acid outputs, basal serum gastrin levels, and response to secretin challenge were also nondiscriminatory. The degree of acid inhibition in response to cimetidine was highly variable from one patient to another and on repeat testing in individual patients, and there was no correlation between acid secretory inhibition and clinical course. When severe complications occurred, reinstituting H2-receptor antagonist therapy or increasing the dose did not avert the need for total gastrectomy. Patients refractory to drug treatment who have persistent or recurrent ulcers should be managed with prompt total gastrectomy to prevent life-threatening complications.
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PMID:Failure of histamine H2-receptor antagonist therapy in Zollinger-Ellison syndrome. 612 12

Nine patients with the Zollinger-Ellison syndrome seen at a single referral centre between 1976 and 1981 are presented to highlight changes in the recognition, diagnosis and management of the condition. Less well recognized manifestations such as diarrhoea and features of the multiple endocrine neoplasia (MEN) type I syndrome are described, and the simplification of the pre-operative diagnosis by the use of both the serum gastrin estimation and the secretin provocation test considered. The problem of tumour localization is discussed with special reference to the newer techniques such as ultrasound, endoscopic retrograde cholangiopancreatography (ERCP) and CAT scanning, and the value of arteriography confirmed. The striking advances in management during the past few years are stressed with special reference to the role of the H2-receptor blocking drugs. Despite their profound inhibitory effect on both acid secretion and symptoms, all patients with the exception of those with proven metastases or the MEN type I syndrome underwent laparotomy to exclude a resectable lesion. If no resectable lesion was found truncal vagotomy was performed to facilitate acid secretory control post-operatively and H2-receptor blocking drugs continued in a dose necessary to maintain basal acid secretion under 5 mmol/hr.
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PMID:Changing concepts in the presentation, diagnosis and management of the Zollinger-Ellison syndrome. 613 24

Four patients with Zollinger-Ellison Syndrome (ZES) are presented to highlight the difficulties in the recognition, diagnosis and management of this rare disease. The presentation of ZES is usually indistinguishable from ordinary peptic ulcer disease and in those patients with symptoms not related to peptic ulcer, i.e., diarrhoea, as their main complaint, the diagnosis is often not even considered. A high index of suspicion is required, however, in patients with recurrent ulcers, multiple ulcers and in those with resistant or rapidly relapsing ulcers after conventional therapy. A presumptive diagnosis can be made by the demonstration of grossly elevated fasting serum gastrin levels combined with a secretin stimulation test in doubtful cases. The main problem is the location of the gastrin-secreting tumour which is usually pancreatic but often too small to be detected by currently available techniques. Histamine H2-receptor antagonists in high doses are effective in controlling the gastric acid hypersecretion which is chiefly responsible for the morbidity and mortality in ZES. They provide the treatment of choice in patients where the tumour cannot be located, though every attempt should be made to do this as surgery is the treatment of choice for this invariably malignant tumour. Total gastrectomy is now reserved for those patients in whom medical therapy has failed. The role of chemotherapy in metastatic disease has yet to be established.
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PMID:Zollinger-Ellison syndrome--report of four cases and review of literature. 614 89

The intestinal carcinoid tumors of 26 patients were stained for the presence of serotonin, gastrin, somatostatin, motilin, secretin, glucagon, pancreatic polypeptide, ACTH, and neurotensin. Argentaffin and argyrophil stains were also performed in all cases. Thirty-five separate tumors (counting metastases and multiple primaries) from the 26 patients were studied. Serotonin was present in 30 of the 35 tumors. Nineteen tumors contained serotonin only. Fourteen tumors contained multiple neuroendocrine products. One tumor contained gastrin only. One tumor did not stain immunohistochemically, but was argyrophilic. Metastatic deposits were studied in nine patients. Some metastases produced the identical neuroendocrine products as the primary tumor, whereas others produced either additional or fewer hormones than the primary tumor. Moreover, different metastases from the same primary tumor were observed to produce different hormones. Argyrophilic cells were present in all cases and were much more numerous than cells staining by immunohistochemistry. Argyrophilic cells probably contain monoamines and polypeptide hormones in addition to those studied in this series. The argyrophil stain was the best general stain in this study for the demonstration of neuroendocrine cells. Argentaffin staining was negative in ten cases that were serotonin positive and two argentaffin positive cases were serotonin negative. The carcinoid syndrome, as clinically defined by the presence of flushing and diarrhea, was noted in five patients, all of whom had serotonin-containing small bowel carcinoids. Endocrine-related symptoms were not clinically appreciated in the remaining patients.
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PMID:The neuroendocrine products of intestinal carcinoids. An immunoperoxidase study of 35 carcinoid tumors stained for serotonin and eight polypeptide hormones. 618 28

Human pancreatic ductal adenocarcinoma line Capan-1 was studied in tissue culture and the nude mouse. In tissue culture, the neoplastic cells grew as large epithelial-like mucin-producing cells. Subcutaneous and intraperitoneal transplantation of neoplastic cells into nude mice resulted in tumor formation characterized by marked invasiveness and distant metastases. Histologically, the tumor appeared as a well-differentiated mucin-producing adenocarcinoma morphologically resembling the tumor of origin. Chromosomal analysis showed a human karyotype with a chromosome number between 51-61. Lactate dehydrogenase and beta 2-microglobulin used as tumor markers were present in both tissue culture and the serum of tumor-bearing mice. The neoplasm, which was characterized by an increased level of cAMP, had lost completely the ability to respond to secretin stimulation. The tumor grown in the nude mouse was resistant to treatment with 5-fluorouracil, behavior identical to that of the original tumor. Diphtheria toxin resulted in complete tumor destruction. Because Capan-1 tumor grown in the nude mouse shows morphologic, biologic, and biochemical characteristics similar to the tumor of origin, it may be an invaluable tool in furthering understanding of the biology of human pancreatic cancer.
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PMID:Human pancreatic adenocarcinoma line Capan-1 in tissue culture and the nude mouse: morphologic, biologic, and biochemical characteristics. 627 35

The diagnostic accuracies of measurement of carcinoembryonic antigen (CEA) and analysis of the cytologic characters of pure pancreatic juice were assessed in 16 control subjects, 20 patients with pancreatitis and 22 patients with pancreatic cancer. Pure pancreatic juice was collected from the pancreatic duct by endoscopic cannulation using a duodenofiberscope after intravenous administration of secretin. The pancreatic fluid was centrifuged and the supernatant was used for CEA assay, while the cell pellet was examined cytologically. Abnormally high CEA levels in the pure pancreatic juice were significantly more frequent in patients with pancreatic cancer; an increased CEA concentration in the pancreatic juice was found in 68.2% of the patients. The location of the cancer had no influence on the CEA level of the pancreatic juice, but the level tended to be high when the tumor had distant metastases. Positive cytologic findings were obtained in specimens of pure pancreatic juice of 68.2% of the patients with pancreatic cancer. Positive cytologic results were more frequent in patients with carcinoma of the head of the pancreas than in those with carcinoma of the body or tail, and those with localized tumors had the lowest yield of positive cytologic results. For sensitive tests, it was necessary to collect pure pancreatic juice containing no contrast medium. High CEA levels and positive cytological results were significantly more frequent in pancreatic juice obtained 10 to 20 minutes after secretin stimulation than in those collected immediately after stimulation. Correct diagnosis of malignancy was made by CEA assay alone or by cytological examination alone in 68.2% of the patients examined, while a combination of these methods raised the diagnostic rate to 86.4%.
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PMID:Significance of carcinoembryonic antigen levels and cytology of pure pancreatic juice in diagnosis of pancreatic cancer. 662 6


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