gastrins and Liver-Neoplasms

Gastrin has been identified as the principal effector of gastric secretion, but several studies have demonstrated its role as a biomarker of cancer risk and as a growth factor for colorectal, stomach, liver, and pancreatic cancer. Hypergastrinemia characterizes autoimmune gastritis, with body and fundic gland atrophy and increased risk for both gastric adenocarcinoma and neuroendocrine tumors. Gastric type I carcinoids develop in the context of autoimmune gastritis because of the stimulus exerted by gastrin on enterochromaffin-like cells and remain gastrin-sensitive for long durations because the removal of hypergastrinemia leads to tumor regression. The treatment of gastric carcinoid is still open to debate, but when the disease frequently relapses, or is multicentric or infiltrating, surgery is advocated or, in the alternative, a costly and long-lasting treatment with long-acting somatostatin analogues is prescribed. A technology allowing the preparation of an immunogen eliciting an immune system response with generation of antibodies against G17 has been developed. This vaccine has been tested in patients with colorectal, pancreatic or advanced gastric cancer. The vaccine has also been used in the treatment of gastric type I carcinoids, and the administration of G17DT in patients harboring these lesions leads to carcinoid regression. Antigastrin vaccination in the treatment of gastrointestinal cancer obviously needs validation, but this immunotherapy may well represent a simple, inexpensive, and active 'adjuvant' treatment.

Topics: Adenocarcinoma; Autoimmune Diseases; Cancer Vaccines; Carcinoid Tumor; Colorectal Neoplasms; Gastrins; Gastritis; Humans; Liver Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms

Cross sectional imaging in the assessment of gastrinomas has three major applications: Tumor localization (sporadic gastrinoma, MEN I) in patients undergoing primary or secondary surgery. Staging of metastasized tumors, especially assessment of lymph nodes and liver metastases, possibly including a risk analysis prior to liver resection. Post-surgery follow-up and monitoring of bio- or chemotherapy. Detection of primary tumors is strongly correlated with their size. However, the sensitivity of surgical assessment of the mostly small tumors by experienced surgeons is much higher than that of any imaging modality. Of all imaging modalities, endoultrasonography (EUS) followed by Somatostatin receptor scintigraphy (SRS) is the most sensitive modality for the assessment of pancreatic tumors in asymptomatic patients suffering from a MEN-I syndrome. Scintigraphy has the highest sensitivity in tumors of symptomatic patients and in the assessment of metastases. CT and MRI are only second line diagnostic modalities. Their sensitivity is largely dependent on the selection of patients. As a potential application, 3D reconstruction of nearly isotropic CT data sets for the risk assessment prior to liver resection is currently developing. Due to the absent radiation exposure, MRI is increasingly utilized to monitor the response of metastases under systemic therapy, e.g. in clinical trials.

Topics: Angiography; Clinical Trials as Topic; Duodenal Neoplasms; Duodenum; Gastrinoma; Gastrins; Humans; Liver; Liver Neoplasms; Lymphatic Metastasis; Magnetic Resonance Imaging; Multiple Endocrine Neoplasia Type 1; Neoplasm Staging; Pancreas; Pancreatic Neoplasms; Tomography, X-Ray Computed; Ultrasonography; Zollinger-Ellison Syndrome

The physiologic sequelae of a gastrinoma can be well controlled with medical therapy. The role of surgery has shifted from managing acid hyper-secretion and ulcer complications to preventing metastatic disease and managing symptomatic metastases. With improved methods of imaging for the detection of occult gastrinomas, the prospective evaluation of the role for surgery in altering the natural history of these tumors is now possible.

Topics: Algorithms; Diagnosis, Differential; Disease-Free Survival; Gastrinoma; Gastrins; Humans; Liver Neoplasms; Multiple Endocrine Neoplasia Type 1; Pancreatic Neoplasms; Sensitivity and Specificity; Tomography, X-Ray Computed; Zollinger-Ellison Syndrome

The assessment of fasting serum gastrin (FSG) is essential for the diagnosis and management of patients with the Zollinger-Ellison syndrome (ZES). Although many studies have analyzed FSG levels in patients with gastrinoma, limited information has resulted from these studies because of their small size, different methodologies, and lack of correlations of FSG levels with clinical, laboratory, or tumor features in ZES patients. To address this issue, we report the results of a prospective National Institutes of Health (NIH) study of 309 patients with ZES and compare our results with those of 2229 ZES patients in 513 small series and case reports in the literature. In the NIH and literature ZES patients, normal FSG values were uncommon (0.3%-3%), as were very high FSG levels >100-fold normal (4.9%-9%). Two-thirds of gastrinoma patients had FSG values <10-fold normal that overlap with gastrin levels seen in more common conditions, like Helicobacter pylori infection or antral G-cell hyperplasia/hyperfunction. In these patients, FSG levels are not diagnostic of ZES, and gastrin provocative tests are needed to establish the diagnosis. Most clinical variables (multiple endocrine neoplasia type 1 status, presence or absence of the most common symptoms, prior medical treatment) are not correlated with FSG levels, while a good correlation of FSG values was found with other clinical features (prior gastric surgery, diarrhea, duration from onset to diagnosis). Increasing basal acid output, but not maximal acid output correlated closely with increasing FSG. Numerous tumoral features correlated with the magnitude of FSG in our study, including tumor location (pancreatic > duodenal), primary size (larger > smaller) and extent (liver metastases > local disease). In conclusion, this detailed analysis of FSG in a large number of patients with ZES allowed us to identify important clinical guidelines that should contribute to improved diagnosis and management of patients with ZES.

Topics: Adult; Diagnosis, Differential; Fasting; Female; Gastrinoma; Gastrins; Humans; Liver Neoplasms; Male; Middle Aged; Multiple Endocrine Neoplasia Type 1; Multivariate Analysis; Pancreatic Neoplasms; Prospective Studies; Zollinger-Ellison Syndrome

Duodenal and pancreatic endocrine tumors are uncommon and their surgical treatment is often difficult. The management of these tumors has changed with recent advancements in tumor localization, intraoperative hormone measurements, standardized surgical techniques, and a better understanding of the genetic basis of multiple endocrine neoplasia syndrome. We present our experience with 191 endocrine tumors and elaborate the contemporary management of functioning duodenopancreatic endocrine tumors.

Topics: Duodenal Neoplasms; Endosonography; Gastrinoma; Gastrins; Gastrointestinal Agents; Humans; Insulinoma; Liver Neoplasms; Magnetic Resonance Imaging; Multiple Endocrine Neoplasia Type 1; Octreotide; Pancreatectomy; Pancreatic Neoplasms

Gastrinomas secrete gastrin and cause symptoms related to gastric acid hypersecretion that can be controlled by antisecretory medications. Primary tumors are located within the pancreas or duodenum and 60% metastasize. Liver metastases are associated with decreased survival. Localization studies especially somatostatin receptor scintigraphy are indicated to image the extent of disease. Surgery is indicated to potentially cure the patient, or control the malignant tumoral process and prolong survival.

Topics: Diagnostic Imaging; Duodenal Neoplasms; Gastric Acid; Gastrinoma; Gastrins; Humans; Liver Neoplasms; Multiple Endocrine Neoplasia Type 1; Pancreatic Neoplasms; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Somatostatin; Survival Rate; Zollinger-Ellison Syndrome

The rationale for a multifaceted operative procedure in all MEN 1 patients with pancreaticoduodenal neuroendocrine disease who present without liver metastases is presented. The results in 36 patients with MEN 1 ZES are encouraging in that more than two-thirds are eugastrinemic and none have liver metastases after follow-up as long as 20 years.

Topics: Adult; Duodenal Neoplasms; Female; Follow-Up Studies; Gastrins; Hormones; Humans; Liver Neoplasms; Male; Mass Screening; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Octreotide; Pancreatectomy; Pancreatic Neoplasms; Radionuclide Imaging; Radiopharmaceuticals; Zollinger-Ellison Syndrome

Four cases of primary hepatic carcinoid were identified during a retrospective study of liver resections for primary tumor. The cases included two adult males, one adult female, and a 9-year-old boy in whom gastrin levels were documented. The estimation of gastrin levels was prompted by symptoms suggestive of acid-peptic disease. One patient died postoperatively. The other three are alive and well at 3 years, 2 years, and at 1 year, respectively, after surgery, outcomes distinctly different from hepatocellular carcinomas. Diagnostic difficulties may be experienced in histologic assessment, and this may require recourse to immunohistochemistry and electron microscopy. Long-term follow-up and careful exclusion of a possible primary elsewhere are necessary for establishing the primary nature of liver carcinoids.

Topics: Adult; Carcinoid Tumor; Child; Fatal Outcome; Female; Gastrins; Hepatectomy; Humans; Liver; Liver Neoplasms; Male; Middle Aged

The treatment with streptozotocin of a patient with metastatic gastrinoma is described. Two courses of intravenous streptozotocin were without effect. However, three months after two doses of 4 g streptozotocin were given into the coeliac axis, there was a marked reduction in hepatic size and a fall in fasting plasma gastrin levels from 1430 pmol/l to 240 pmol/l. Seven months after treatment fasting plasma gastrin levels were 125 pmol/l.

Topics: Adenoma, Islet Cell; Adult; Female; Gastrectomy; Gastrins; Hepatectomy; Humans; Liver Neoplasms; Neoplasm Metastasis; Pancreatic Neoplasms; Streptozocin; Zollinger-Ellison Syndrome

Functioning tumors of the pancreatic islets are now recognized as the source of clinical syndromes affecting the gastrointestinal tract which have a wide variety of catastrophic symptoms. Experiences with thirty-six cases suggest at least four separate diagnostic categories in the ulcerogenic tumor syndrome. These include: a typical history, gastric analysis, and roentgenographic findings with boderline fasting serum gastrin levels; ulcerogenic tumor with evidence of hyperparathyroidism; iatrogenic ulcerogenic syndrome associated with failure of a previous operation for duodenal ulcer; and the classic ulcerogenic syndrome associated with a fulminating ulcer diathesis or diarrhea and high serum gastrin levels. The problems presented at operation include: decisions to be make in the presence of a negative exploration; the finding of a solitary tumor in the wall of the duodenum; solitary pancreatic tumors particularly in the body and tail; ulcerogenic tumors in the very young; liver metastases in the elderly; and the wisdom of removing gross metastases in combination with total gastrectomy. The long-term survival in the ulcerogenic tumor syndrome approximated 50 per cent, with 40 per cent of those having proved malignancy living five years. Evidence of hyperparathyroidism is relatively common in association with both the ulcerogenic and the diarrheogenic tumor syndromes. The association may by a result of a congenital abnormality, metabolic alkalosis, or a direct effect of the islet cell tumor. Parathyroidectomy may be indicated when both the serum calcium and parathormone levels are elevated in the presence of borderline fasting gastrin levels. The latter may return to normal after parathyroidectomy. The evidence of hyperparathyroidism closely parallels the episodes of diarrhea in the diarrheogenic syndrome, and hyperparathyroidism may regress spontaneously after total removal of the pancreatic tumor. Just as routine calcium determinations made the diagnosis of hyperparathyroidism more commonplace, it is suggested that the gastrointestinal syndromes associated with islet cell tumor would receive wider recognition if radioimmunoassays for gastrin as well as secretin, and the other secretin-like polypeptides, were carried out routinely.

Topics: Adenoma, Islet Cell; Age Factors; Celiac Disease; Diagnosis, Differential; Diarrhea; Duodenal Neoplasms; Follow-Up Studies; Gastrins; Humans; Hyperparathyroidism; Liver Neoplasms; Neoplasm Metastasis; Pancreatic Hormones; Pancreatic Neoplasms; Preoperative Care; Secretin; Zollinger-Ellison Syndrome

Serum chromogranin A levels (CgA) are reported by some authors to be of clinical utility for assessing the presence or absence of a pancreatic endocrine tumor and tumor extent or growth. The aim of the current study was to assess this finding and compare the results with those from serum gastrin determinations (FSG) in a large cohort of patients with gastrinomas.. In 112 consecutive patients with the Zollinger-Ellison syndrome serum CgA and FSG levels were measured and correlated with disease activity, extent of disease, and the presence of multiple endocrine neoplasia type-1 (MEN-1) or gastric carcinoid tumors.. Serum CgA levels drawn on 2 consecutive days correlated closely (P < 0.00001) as did serum gastrin levels. Serum CgA levels correlated significantly with FSG levels (P < 0.00001). Serum CgA and FSG levels were significantly higher in patients with active disease than in disease free patients (P < 0.00001). The sensitivity for the presence of disease was higher for CgA compared with FSG (92% vs. 80%; P = 0.021). However, the specificity of CgA was 67%. Serum CgA levels were not significantly different in the four disease categories (stable extrahepatic disease, increasing extrahepatic disease, stable liver metastases, and increasing liver metastases). FSG levels were significantly lower in patients with stable extrahepatic disease compared with those with increasing extrahepatic disease. However, both tumor markers decreased significantly with a gastrinoma resection in five patients. The presence of MEN-1 or a gastric carcinoid tumor did not influence the results.. The results of the current study showed that serum CgA and FSG levels both are sensitive tumor markers for the detection of a gastrinoma; however, CgA levels have a relatively low specificity. Neither the magnitude of the serum CgA nor gastrin level correlated with tumor growth or tumor extent and therefore cannot be used to determine these variables. However, in contrast to some other studies, the results of the current study show that changes in serum CgA or gastrin in a given patient with time are related to the tumor extent and not to gastric mucosal changes due to hypergastrinemia.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoid Tumor; Chromogranin A; Chromogranins; Female; Gastrinoma; Gastrins; Humans; Liver Neoplasms; Male; Middle Aged; Multiple Endocrine Neoplasia Type 1; Prospective Studies; Sensitivity and Specificity; Stomach Neoplasms; Zollinger-Ellison Syndrome

This study was designed to determine whether or not chemo-endocrine therapy after the resection of liver metastasis from colorectal cancer would prevent re-recurrence in the liver. Postoperatively, seven patients received proglumide gastrin antagonist (1,200 mg/day) +5'-DFUR (800 mg/day) orally for 2 years. MMC 6-10 mg and ADR 20 mg were infused every two weeks alternately for 1 year via catheter in the common hepatic artery. After median follow-up of 39 months, re-recurrence rate in the remnant liver after hepatic resection was 14% (1/7) for patients with chemo-endocrine therapy and 52% (24/46) for the controls. These results suggest the possibility that chemo-endocrine therapy is effective to prevent re-recurrence of liver metastasis in patients with colorectal cancer.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colorectal Neoplasms; Doxorubicin; Female; Floxuridine; Gastrins; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Male; Middle Aged; Mitomycin; Neoplasm Recurrence, Local; Proglumide

Metastatic gastrinoma is becoming increasingly recognized in patients with Zollinger-Ellison Syndrome. The mean 5-year survival of these patients is < 20%. Chemotherapeutic regimens are of limited benefit. The aim of this study was to evaluate the use of interferon in these patients because a preliminary report suggested it might be effective.. The efficacy and toxicity of interferon was assessed in 13 consecutive Zollinger-Ellison syndrome patients with liver metastases. Patients were treated with human recombinant alpha interferon (5 million IU, subcutaneously [SC]) daily and followed up at 3-month intervals with multiple imaging studies. At each follow-up, toxicity of therapy was assessed and fasting serum gastrin concentrations were obtained.. No patient showed a reduction in tumor size at any follow-up. One patient died after 2 months. At 6 months, six patients (46%) had stable tumor size in the liver, although new bone metastases developed in one patient. Three patients showed stable disease for up to 21 months. Changes in serum gastrin correlated with tumor response at 6 months. All patients developed some side effects of therapy. Thirty-one percent required dose reduction, and one patient (8%) had to have interferon therapy interrupted briefly.. These results fail to define a therapeutic role for interferon in the treatment of metastatic gastrinoma.

Topics: Adult; Female; Follow-Up Studies; Gastrinoma; Gastrins; Humans; Interferon-alpha; Liver Neoplasms; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Zollinger-Ellison Syndrome

We have examined the effects of the somatostatin analogue (SMS 201-995) in 10 patients with gastrinoma syndrome. Four had hepatic metastases, one had a tumor in a peripancreatic lymph node, two had resectable intrahepatic and intraduodenal gastrinomas, and in three the primary tumor was not found. Acutely, SMS 201-995 decreased acid secretion and restored the BAO/MAO ratio to normal in eight of eight patients. Basal and secretin-stimulated gastrin responses were suppressed but not normalized in eight of eight patients. Suppression of endogenous gastrin restored responsiveness to exogenous gastrin. Treatment for up to 12 months with SMS 201-995 controlled symptoms in six of eight patients, suppressed serum gastrin in three of five, and suppressed acid secretion in three of three patients. Treatment with SMS 201-995 in three patients for 5 months decreased tumor secretion of gastrin and diminished basal acid secretion, an effect that persisted in two of three patients 48 hours after withdrawal of SMS. In patients with metastatic disease who had high levels of gastrin, SMS treatment for 5 to 12 months did not inhibit tumor growth or decrease gastrin levels. SMS treatment arrested progression of tumor growth only in patients who had a reduction in gastrin and gastric acid secretion. We conclude that SMS may be useful in the management of gastrinoma patients by decreasing hypersecretion of gastrin and gastric acid and, over a longer term, may even change tumor capacity to release gastrin and gastric acid secretion. SMS may thus be useful as a palliative agent and as an adjunct to conventional treatment of the gastrinoma syndrome. SMS does not appear to shrink tumor mass in patients with very high basal gastrin levels.

Topics: Adult; Clinical Trials as Topic; Drug Administration Schedule; Female; Follow-Up Studies; Gastric Acid; Gastrinoma; Gastrins; Humans; Liver Neoplasms; Male; Middle Aged; Octreotide; Somatostatin; Syndrome

Proton pump inhibitors (PPIs) are administered commonly to aged people; however, their effect on colorectal cancer (CRC) has still not been fully elucidated. Here, we examined the effect of PPIs and consequent alkalization on CRC cells. PPI administration alkalized the fecal pH and increased serum gastrin concentration. PPI and pH8 treatment (alkalization) of CMT93 mouse colon cancer cells inhibited cell growth and invasion, increased oxidative stress and apoptosis, and decreased mitochondrial volume and protein levels of cyclin D1 and phosphorylated extracellular signal-regulated kinase (pERK) 1/2. In contrast, gastrin treatment enhanced growth and invasion, decreased oxidative stress and apoptosis, and increased mitochondrial volume and cyclin D1 and pERK1/2 levels. Concurrent treatment with a PPI, pH8, and gastrin increased aldehyde dehydrogenase activity and also enhanced liver metastasis in the BALB/c strain of mice. PPI administration was associated with

Topics: Animals; Apoptosis; Cell Line, Tumor; Cell Proliferation; Clostridium perfringens; Colorectal Neoplasms; Cyclin D1; Enterotoxins; Extracellular Signal-Regulated MAP Kinases; Feces; Gastrins; Hydrogen-Ion Concentration; Liver Neoplasms; Male; Mice; Mice, Inbred BALB C; Mitochondria; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Transplantation; Oxidative Stress; Proton Pump Inhibitors

Topics: Adult; Bile Duct Neoplasms; Disease-Free Survival; Female; Gastrinoma; Gastrins; Hepatectomy; Humans; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Omeprazole; Prognosis; Prospective Studies; Proton Pump Inhibitors; Secretin; Survival Rate; Zollinger-Ellison Syndrome

Staging of colorectal cancer often fails to discriminate outcomes of patients with morphologically similar tumours that exhibit different clinical behaviours. Data from several studies suggest that the gastrin family of growth factors potentiates colorectal cancer tumourigenesis. The aim of this study was to investigate whether progastrin expression may predict clinical outcome in colorectal cancer.. Patients with colorectal adenocarcinoma of identical depth of invasion who had not received neoadjuvant therapy were included. The patients either had stage IIa disease with greater than 3-year disease-free survival without adjuvant therapy or stage IV disease with liver metastases on staging CT. Progastrin expression in tumour sections was scored with reference to the intensity and area of immunohistochemical staining.. Progastrin expression by stage IV tumours was significantly greater than stage IIa tumours with mean progastrin immunopositivity scores of 2.1 ± 0.2 versus 0.5 ± 0.2, respectively (P < 0.001).. This is the first study to show that progastrin expression may be predictive of aggressive tumour behaviour in patients with colorectal cancer and supports its clinical relevance and potential use as a biomarker.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Colorectal Neoplasms; Female; Gastrins; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Protein Precursors

Neuroendocrine tumors in the pancreas and the gastrointestinal tract may secrete hormones which cause specific syndromes. Well-known examples are gastrinomas, glucagonomas, and insulinomas. Cholecystokinin-producing tumors (CCKomas) have been induced experimentally in rats, but a CCKoma syndrome in man has remained unknown until now.. Using a panel of immunoassays for CCK peptides and proCCK as well as for chromogranin A, we have examined plasma samples from 284 fasting patients with gastroenteropancreatic neuroendocrine tumors. In hyperCCKemic samples, plasma CCK was further characterized by chromatography.. One of the patients displayed gross hyperCCKemia. She was a 58-year old woman with a pancreatic endocrine tumor, liver metastases, 500-1000-fold elevated basal CCK concentration in plasma, diarrhea, severe weight loss, recurrent peptic ulcer and bilestone attacks from a contracted gallbladder. The CCK concentrations in plasma were not affected by resection of the pancreatic tumor, but decreased to normal after hemihepatectomy with removal of the metastases.. A CCKoma syndrome with severe hypersecretion of CCK exists in man. The duodenal ulcer disease and diarrhea with permanently low gastrin in plasma suggest that CCKomas may mimic gastrinoma-like symptoms, because CCK peptides are full agonists of the gastrin/CCK-B receptor.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Child; Cholecystokinin; Denmark; Female; Gastrinoma; Gastrins; Humans; Intestinal Neoplasms; Liver Neoplasms; Male; Middle Aged; Neuroendocrine Tumors; Pancreas; Pancreatic Neoplasms; Rats; Stomach Neoplasms; Young Adult

A 5-year-old castrated Japanese domestic cat was presented with persistent vomiting. Ultrasound examinations revealed many masses only in the liver, and the fine needle aspiration was performed. Cytologically, polygonal or oval shaped tumor cells forming rosette and cord-like patterns were demonstrated, and then, the hepatic lesions were diagnosed as neuroendocrine carcinoma tentatively. The cat died one month after admission and was necropsied. Histopathologically, the tumor cells of the hepatic mass were arranged in typical rosette and cord-like structures. They were considerably uniform in size with hyperchromatic round nuclei and eosinophilic cytoplasm. Most of tumor cells were immunopositive for chromogranin A, and some were positive for gastrin. The findings indicate the possibility that the present case was a gastrin-producing neuroendocrine carcinoma.

Topics: Animals; Biopsy, Fine-Needle; Carcinoma, Neuroendocrine; Cat Diseases; Cats; Chromogranin A; Fatal Outcome; Gastrins; Immunohistochemistry; Japan; Liver Neoplasms; Male

Topics: Animals; Cholecystokinin; Chromogranin A; Diagnosis, Differential; Fatal Outcome; Female; Gastrins; Humans; Liver; Liver Neoplasms; Middle Aged; Neuroendocrine Tumors; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Progastrin (PG) is processed into a number of smaller peptides including amidated gastrin (Gamide), non-amidated glycine-extended gastrin (Ggly) and the C-terminal flanking peptide (CTFP). Several groups have reported that PG, Gamide and Ggly are biologically active in vitro and in vivo, and are involved in the development of gastrointestinal cancers. CTFP is bioactive in vitro but little is known of its effects in vivo. This study investigated the bioactivity of CTFP in vivo in normal tissues using gastrin deficient (GASKO) mice and in two mouse models of cancer (SCID mice bearing xenograft tumors expressing normal or knocked-down levels of gastrin and a mouse model of hepatic metastasis). As with Ggly, CTFP treatment stimulated colonic proliferation in GASKO mice compared to control. CTFP also significantly increased apoptosis in the gastric mucosa of male GASKO mice. CTFP did not appear to effect xenograft growth or the incidence of liver metastases. This is the first demonstration that CTFP has specific biological activity in vivo in the colon and stomach.

Topics: Animals; Apoptosis; Cell Division; Cell Line, Tumor; Cell Movement; Cell Proliferation; Female; Gastric Mucosa; Gastrins; Heterografts; Humans; Liver Neoplasms; Male; Mice; Mice, Inbred CBA; Mice, Knockout; Mice, SCID; Neoplasm Invasiveness; Neoplasm Transplantation; Peptide Fragments; Protein Precursors

To describe disease characteristics and treatment modalities in a group of rare patients with metastatic gastric carcinoid type 1 (GCA1).. Information on clinical, biochemical, radiological, histopathological findings, the extent of the disease, as well as the use of different therapeutic modalities and the long-term outcome were recorded. Patients' data were assessed at presentation, and thereafter at 6 to 12 monthly intervals both clinically and biochemically, but also endoscopically and histopathologically. Patients were evaluated for the presence of specific symptoms; the presence of autoimmune disorders and the presence of other gastrointestinal malignancies in other family members were also recorded. The evaluation of response to treatment was defined using established WHO criteria.. We studied twenty consecutive patients with a mean age of 55.1 years. The mean follow-up period was 83 mo. Twelve patients had regional lymph node metastases and 8 patients had liver metastases. The primary tumor mean diameter was 20.13 ± 10.83 mm (mean ± SD). The mean Ki-67 index was 6.8% ± 11.2%. All but one patient underwent endoscopic or surgical excision of the tumor. The disease was stable in all but 3 patients who had progressive liver disease. All patients remained alive during the follow-up period.. Metastatic GCA1 carries a good overall prognosis, being related to a tumor size of ≥ 1 cm, an elevated Ki-67 index and high serum gastrin levels.

Topics: Adult; Aged; Carcinoid Tumor; Chemotherapy, Adjuvant; Disease Progression; Europe; Female; Gastrectomy; Gastric Bypass; Gastrins; Gastroscopy; Humans; Israel; Ki-67 Antigen; Liver Neoplasms; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Multimodal Imaging; Positron-Emission Tomography; Retrospective Studies; Stomach Neoplasms; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Tumor Burden

Recent advances in localization techniques, such as the selective arterial secretagogue injection test (SASI test) and somatostatin receptor scintigraphy have promoted curative resection surgery for patients with pancreatic neuroendocrine tumors (PNET). For patients with sporadic functioning PNET, curative resection surgery has been established by localization with the SASI test using secretin or calcium. For curative resection of functioning PNET associated with multiple endocrine neoplasia type 1 (MEN 1) which are usually multiple and sometimes numerous, resection surgery of the pancreas and/or the duodenum has to be performed based on localization by the SASI test. As resection surgery of PNET has increased, several important pathological features of PNET have been revealed. For example, in patients with Zollinger-Ellison syndrome (ZES), duodenal gastrinoma has been detected more frequently than pancreatic gastrinoma, and in patients with MEN 1 and ZES, gastrinomas have been located mostly in the duodenum, and pancreatic gastrinoma has been found to co-exist in 13% of patients. Nonfunctioning PNET in patients with MEN 1 becomes metastatic to the liver when it is more than 1 cm in diameter and should be resected after careful observation. The most important prognostic factor in patients with PNET is the development of hepatic metastases. The treatment strategy for hepatic metastases of PNET has not been established and aggressive resection with chemotherapy and trans-arterial chemoembolization have been performed with significant benefit. The usefulness of octreotide treatment and other molecular targeting agents are currently being assessed.

Topics: Animals; Diagnosis, Differential; Gastrins; Humans; Liver Neoplasms; Male; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Pancreatic Neoplasms; Secretin; Zollinger-Ellison Syndrome

This report presents a case of pancreatic neuroendocrine cell carcinoma with multiple liver metastases secreting gastrin and parathyroid hormone-related protein (PTHrP) related to lumbar bone fracture and hypercalcemia. A 58-year-old woman visited an affiliated hospital with a chief complaint of lumbago without any evidence of trauma. She was diagnosed with hepatic dysfunction and hypercalcemia as well as multiple lumbar compression fractures without osteolytic lesions. Abdominal computed tomography (CT) showed a hypervascular mass in the pancreatic tail and multiple liver tumors. Duodenal ulcers were found with gastrointestinal endoscopy. There was a marked increase in the serum gastrin level. She was diagnosed as gastrinoma with multiple liver metastases and was admitted to the hospital. She had an increase in serum PTHrP level without the elevation of intact parathyroid hormone at the time of admission. She underwent an extended right hepatectomy in addition to a distal pancreatectomy with a regional lymphadenectomy and splenectomy. The postoperative course was uneventful, and serum gastrin and PTHrP activities reduced to normal levels. She remained symptom-free, and serum calcium, gastrin, and PTHrP levels remain within the normal ranges 19 months after surgery without adjuvant therapy.

Topics: Endoscopy, Gastrointestinal; Female; Gastrins; Hepatectomy; Humans; Hypercalcemia; Liver Neoplasms; Middle Aged; Pancreatectomy; Pancreatic Neoplasms; Parathyroid Hormone-Related Protein; Spinal Fractures; Tomography, X-Ray Computed

Carcinoid is a rare gastrointestinal tumor, with an incidence varying from 1 to 2.5 per 100,000 in the general population. In this article, we report an elevated incidence of carcinoid tumor in an obese population, showing the importance of performing an endoscopic procedure before bariatric surgery.

Topics: Adult; Bariatric Surgery; Carcinoid Tumor; Duodenal Neoplasms; Endoscopy, Digestive System; Female; Gastrectomy; Gastrins; Hepatectomy; Humans; Hysterectomy; Incidental Findings; Liver Neoplasms; Male; Middle Aged; Obesity, Morbid; Preoperative Care; Stomach Neoplasms; Uterine Neoplasms; White People

Vipoma is a rare neuroendocrine tumor most frequently localized in the pancreas. When it is extrapancreatic, it is most often neurogenic. We report a case of primary extrapancreatic vipoma that is non neurogenic localized in the right liver in a patient with severe diarrhea and hypokaliema. Computed tomography, magnetic resonance imaging, intraoperative tomography and surgical exploration did not show any other extrahepatic primary lesion. The diagnosis was performed by immunochemistry, tumorous cells were positives with anti-VIP antibody. Forty two months after right hepatectomy, the patient was asymptomatic.

Topics: Adult; Antibodies, Neoplasm; Chromogranin A; Chromogranins; Diarrhea; Female; Gastrins; Hepatectomy; Humans; Hypokalemia; Immunohistochemistry; Liver Neoplasms; Magnetic Resonance Imaging; Serotonin; Tomography, X-Ray Computed; Treatment Outcome; Vipoma

Topics: Adolescent; Biopsy; Diagnosis, Differential; Duodenal Ulcer; Endoscopy, Gastrointestinal; Gastrinoma; Gastrins; Hepatectomy; Humans; Liver; Liver Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Pancreatectomy; Peptic Ulcer Hemorrhage; Peptic Ulcer Perforation; Reoperation; Splenectomy

Malignant pancreatic endocrine tumors (PETs) have a poor prognosis and existing antitumor treatments are unsatisfactory. Recent studies have shown somatostatin analogues to have antitumor growth effects in patients with malignant PETs; however, to the authors' knowledge, little information exists regarding their efficacy or effect on survival in patients with progressive malignant gastrinoma, the most common symptomatic malignant PET. The purpose of the current study was to study prospectively the efficacy, safety, and effect on survival of long-term treatment with octreotide in consecutive patients with progressive malignant gastrinoma.. Fifteen consecutive patients with malignant gastrinoma with progressive hepatic metastases were studied. All patients underwent conventional imaging studies (computed tomography scan, magnetic resonance imaging, ultrasound, and, if needed, selective angiography) and somatostatin receptor scintigraphy prior to treatment and at 3-6-month intervals while receiving treatment. The patients all were treated initially with octreotide, 200 microg every 12 hours, and at last follow-up were being maintained on long-acting release octreotide, 20-30 mg every month. Tumor size and/or number were used to classify patient responses as either no tumor response or tumor response (stabilization or decrease in size). Treatment response was correlated with tumor and clinical characteristics.. Tumors in 8 of the 15 patients studied (53%) responded at 3 months, with 47% (7 of 15 patients) demonstrating tumor stabilization and 6% (1 of 15 patients) demonstrating a decrease in tumor size. The mean duration of response was 25.0+/-6.1 months (range, 5.5-54.1 months). Six of the eight responders were continuing to respond at the time of last follow-up. Tumor response did not correlate with any clinical parameter (e.g., tumor extent, fasting gastrin, or acid secretory rates). However, slow-growing tumors were more likely to respond prior to treatment (86% vs. 0%) (P < 0.0014). During follow-up (range, 4-8 years), 25% of the responders died compared with 71% of the nonresponders, a difference that approached statistical significance (P = 0.10). Two patients (13%) developed serious side effects that required the withdrawal of octreotide.. Octreotide is an effective antitumor treatment in patients with progressive malignant gastrinoma. In approximately 50% of these patients octreotide has an antigrowth effect; treatment is associated with a low incidence of serious side effects compared with other antitumor treatments commonly used and, in contrast to many studies, the growth response is long-lasting. The results of the current study suggest that octreotide treatment should replace chemotherapy as the standard treatment for these patients, especially those patients with slow-growing tumors. Additional studies involving larger numbers of patients will be needed to determine a convincing effect on survival.

Topics: Adult; Aged; Antineoplastic Agents, Hormonal; Disease Progression; Female; Follow-Up Studies; Gastrinoma; Gastrins; Humans; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Octreotide; Pancreatic Neoplasms; Predictive Value of Tests; Prospective Studies; Receptors, Somatostatin; Time Factors; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

Topics: Adult; Biopsy, Needle; Calcinosis; Carrier State; Female; Gastrinoma; Gastrins; Hepatitis B; Humans; Immunohistochemistry; Liver Neoplasms; Tomography, X-Ray Computed

To assess the value of the initial fasting serum gastrin (FSG) at presentation in patients with Zollinger-Ellison Syndrome (ZES) in predicting primary tumor characteristics and survival.. A total of 239 patients were treated for ZES between December 1981 and September 1998, with a mean follow-up of 9.1 +/- 0.6 years. At initial evaluation, 86 patients (36%) had mild (0 to 499 pg/mL), 61 (25.5%) had moderate (500 to 1,000 pg/mL), and 92 (38.5%) had severe (> 1,000 pg/mL) elevations in FSG. Primary tumor location and size, presence of lymph node or hepatic metastases, and survival were analyzed based on the level of initial FSG.. In patients with sporadic ZES, but not in those with multiple endocrine neoplasia type 1 (MEN-1) and ZES, there was a significant relationship between the level of initial FSG and tumor size and location of primary tumor, frequency of lymph node and liver metastases, and survival. The median 5- and 10-year survival decreased with increasing initial FSG (P <.001) in patients with sporadic ZES; MEN-1 patients lived longer than sporadic ZES patients (P =.012), and survival in this group was not associated with the level of initial FSG. Multivariate analysis showed that factors independently associated with death from disease in patients with sporadic ZES were liver metastases (P =.0001), a pancreatic site (P =.0027), and primary tumor size (P =.011) but not initial FSG (P >.30).. The severity of FSG at presentation is associated with size and site of tumor and the presence of hepatic metastases, factors that are significant independent predictors of outcome. The level of FSG at presentation may be useful in planning the nature and extent of the initial evaluation and management in patients with sporadic ZES.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Child; Female; Gastrins; Humans; Incidence; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Predictive Value of Tests; Prognosis; Prospective Studies; Survival Analysis; Survival Rate; United States; Zollinger-Ellison Syndrome

Gastrinoma is a rare endocrine tumor that is frequently associated with liver metastasis. The liver metastasis is usually seen simultaneously or soon after a primary operation. A 47-year-old woman who had had a total gastrectomy 20 years earlier developed liver metastasis. An interval of this length between surgery and metastasis is extremely rare. The total gastrectomy prevented the patient from developing the usual symptoms of hypergastrinemia that would have enabled early diagnosis of the metastasis. Laboratory examinations on admission revealed a high serum gastrin concentration (1500 pg/ml). Computed tomography showed an irregularly enhanced mass lesion with an uneven, low-density central area in the right anterior inferior segment of the liver. An extended right hepatectomy was performed. Intraoperative ultrasonography showed no abnormalities in the remnant pancreas. Examination of the cut surface of the specimen revealed a yellow, firm, elastic tumor, 55 mm in diameter. The interior of the tumor appeared necrotic. Histopathologically, the tumor was composed of cells with hyperchromatic, dysplastic nuclei arranged in a trabecular pattern with nest formation. Gastrin staining was positive. A histologic diagnosis of metastatic gastrinoma was made. The patient's gastrin concentration returned to normal and she was well at 2-year follow-up.

Topics: Female; Gastrectomy; Gastrinoma; Gastrins; Humans; Liver; Liver Neoplasms; Middle Aged; Stomach Neoplasms; Time Factors; Tomography, X-Ray Computed

Gastrin is a trophic factor within the normal gastrointestinal tract and is also a mitogen for a number of gastrointestinal and non-gastrointestinal tumours. Precursor forms of gastrin including progastrin (proG) and glycine-extended gastrin (G-gly) as well as the fully processed amidated gastrin (G-NH2) are expressed by tumours. There has been little study of the role of gastrin in either normal liver or liver tumours. The aim of this study was to identify the expression of CCK-B/gastrin receptor (CCK-BR), proG, G-gly and G-NH2 in normal liver and liver tumours.. Tissue sections from patients with hepatocellular carcinoma, fibrolamellar carcinoma, cholangiocarcinoma as well as normal liver biopsies were assessed for expression of CCK-BR and gastrin isoforms.. Most liver tumours express CCK-BR and are able to process gastrin as far as proG and G-gly, although not as far as the amidated form. There appears to be little expression of the receptor and no expression of precursor forms of gastrin in normal liver.. Liver tumours express the CCK-BR and precursor forms of gastrin. This expression may be associated with tumour proliferation.

Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Carcinoma, Hepatocellular; Cholangiocarcinoma; Gastrins; Humans; Immunohistochemistry; Liver; Liver Neoplasms; Protein Processing, Post-Translational

Medical treatment is the elective therapy for patients with gastrinoma when the tumor is not found at surgery or is unresectable or when there is a metastatic disease. H2-blockers and omeprazol are able to control gastric acid secretion and, in addition, somatostatin analogues decrease gastrin levels. A new long-acting and slow release formulation of a somatostatin analogue (lanreotide, SR-L) has been developed. We treated two patients suffering from gastrinoma, total gastrectomy and hepatic metastases with 30 mg intramuscular injections of SR-L every 15 and 10 days, respectively, for a seven-month period. After the treatment, gastrin levels decreased from 35,494 and 15,086 ng/l to 3,211 and 167 ng/l (92 and 98% below pre-treatment levels) in case 1 and 2 respectively, with a relief of symptoms and no side effects.

Topics: Adult; Antineoplastic Agents; Gastrectomy; Gastrinoma; Gastrins; Gastrointestinal Agents; Humans; Injections, Intramuscular; Liver Neoplasms; Male; Middle Aged; Octreotide; Peptides, Cyclic; Somatostatin

We present a 57-year-old man with Zollinger-Ellison syndrome who had undergone total gastrectomy 12 years previously. At that time, a cystic mass in the left lobe of the liver was palpated but was not removed. The patient currently had high serum gastrin levels. Abdominal ultrasound, CT and MR images showed a well defined liver mass with solid and cystic components. The lesion was resected and a primary hepatic carcinoid tumour was diagnosed. Post-operatively, serum gastrin levels were normal. A primary liver carcinoid may appear as multicystic liver mass with solid components. Careful exclusion of a primary tumour elsewhere is required to establish the diagnosis of this rare entity.

Topics: Carcinoid Tumor; Gastrins; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Zollinger-Ellison Syndrome

Topics: Diagnosis, Differential; Echinococcosis, Hepatic; Follow-Up Studies; Gastrinoma; Gastrins; Hepatectomy; Humans; Liver Neoplasms; Male; Middle Aged; Phosphopyruvate Hydratase; Tomography, X-Ray Computed; Zollinger-Ellison Syndrome

Topics: Adult; Aged; Aged, 80 and over; Diagnosis, Differential; Female; Gastrins; Humans; Liver Neoplasms; Male; Middle Aged; Prognosis; Zollinger-Ellison Syndrome

To evaluate localization of hepatic metastases with the intraarterial secretin injection test in Zollinger-Ellison syndrome (ZES).. Results in 74 patients with ZES (aged 15-70 years) were retrospectively studied. All patients had undergone computed tomography (CT), magnetic resonance (MR) imaging, ultrasound, abdominal angiography, and an intraarterial secretin test, in which venous blood is sampled periodically after injection of secretin.. Twenty-two patients had liver metastases. An increase in venous gastrin concentration of at least 25% at 20 seconds or 50% at 30 seconds after injection indicated a positive result. Results were positive in 41% of patients with and 2% without liver metastases (P < .0001). Sensitivity of the intraarterial secretin test was 41%; of CT and ultrasound, 64%; and of MR imaging and angiography, 77%. Intraarterial secretin test results assisted in clinical management in 22% of patients.. With the criteria developed, the intraarterial secretin test had high specificity but low sensitivity. It should be used when imaging results are unclear.

Topics: Adolescent; Adult; Aged; Angiography; Female; Gastrinoma; Gastrins; Hepatic Artery; Hepatic Veins; Humans; Injections, Intra-Arterial; Liver Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Pancreatic Neoplasms; Retrospective Studies; Secretin; Sensitivity and Specificity; Tomography, X-Ray Computed; Zollinger-Ellison Syndrome

Topics: Carcinoid Tumor; Diagnostic Errors; Diarrhea; Female; Gastrins; Gastritis; Humans; Liver Neoplasms; Middle Aged; Pain; Stress, Psychological

To determine whether human liver cells respond to gastrin peptides by reducing their secretion of triacylglycerols, as recently observed in rat hepatocytes.. Cells of the human hepatoblastoma cell line Hep G2 were incubated with pentagastrin and heptadeca gastrin, followed by lipid analysis of media and cells.. Cultivation of cells; analyses of triacylglycerols, cholesterol and protein; statistical analysis.. As the secretion of triacylglycerols in Hep G2 cells incubated with basal medium (Eagle's minimum essential medium with non-essential amino acids, penicillin, streptomycin and glutamine) is only about 20% of the triacylglycerol secretion reported for human liver cells, the possibility of detecting statistically significant effects of gastrin peptides on lipid secretion is reduced compared to the situation in normal hepatocytes. However, by a combined addition of 0.1 mmol/l albumin-bound oleate, 10 mmol/l sodium butyrate and 0.1 mg/ml dextran sulphate to the basal medium, the triacylglycerol secretion in Hep G2 cells was found to be more than twice as high as in cells incubated with basal medium alone. With this supplemented medium a biphasic concentration-dependent statistically significant inhibitory effect of both pentagastrin and heptadeca gastrin on triacylglycerol secretion in Hep G2 cells was demonstrated.. These results indicate that gastrin peptides may play a role in the regulation of lipoprotein secretion in human liver cells.

Topics: Culture Media; Gastrins; Hormones; Humans; Liver; Liver Neoplasms; Pentagastrin; Triglycerides; Tumor Cells, Cultured

Malignant transformation in bile duct hamartomas has been previously reported in very rare instances. Here, we describe a unique case of a neuroendocrine tumor of the liver arising within an area of unusually large hamartoma with predominant bile duct component, hitherto unreported and distinct from the conventional von Meyenburg complex. The tumor was apparently secreting gastrin and chromogranin, with associated gastrinoma syndrome over several years. The histologic picture was reminiscent of a moderately differentiated adenocarcinoid, with positive mucin staining in a signet ring pattern. Tumor cells showed positive staining for neuron-specific enolase, chromogranin A, gastrin, and serotonin. Staining for pancreatic hormone peptides was negative. Resection of the tumor was apparently curative, with complete resolution of the patient's symptoms.

Topics: Bile Duct Diseases; Carcinoid Tumor; Chromogranin A; Chromogranins; Female; Gastrins; Hamartoma; Humans; Immunohistochemistry; Liver Diseases; Liver Neoplasms; Magnetic Resonance Imaging; Middle Aged; Radionuclide Imaging; Tomography, X-Ray Computed

Ultrasound-guided, laser-induced thermocoagulation with Nd:YAG laser (1064 nm) was performed in a child with metastatic gastrinoma disease. The emitted laser energy to coagulate a radius of 15-20 mm of metastatic liver tissue was 4 W with a duration time of 300 s. Marked reduction of gastrin was observed after interstitial laser hyperthermia.

Topics: Biomarkers, Tumor; Child; Chromogranin A; Chromogranins; Combined Modality Therapy; Duodenal Neoplasms; Gastrinoma; Gastrins; Humans; Hyperthermia, Induced; Liver Neoplasms; Lymphatic Metastasis; Patient Care Team

The effect of endogenous hypergastrinemia on growth of human colon carcinoma is not known. Our aim was to study the growth of human colon carcinoma in an animal model with endogenous hypergastrinemia.. Human colon carcinoma was transplanted to the colon of 40 athymic rats. Of these, 25 underwent gastric fundectomy to accomplish endogenous hypergastrinemia, and 15 were sham operated to serve as controls. The duration of the study was 8 weeks. During the last week, 12 fundectomized animals received a gastrin (cholecystokinin B) receptor antagonist. Metaphase arrest index, local invasion, and distant spread of the tumor were investigated. Expression of gastrin and cholecystokinin B receptor messenger RNA was examined by reverse-transcription polymerase chain reaction.. Tumor spread by direct extension outside the colon was observed in all animals, and liver metastases were observed in 10 of the 25 fundectomized animals. Sham-operated animals showed none of these features. The metaphase arrest index of the tumor did not differ between fundectomized animals given the cholecystokinin B receptor antagonist and sham-operated animals, whereas it was significantly increased in fundectomized animals not given the antagonist. The tumor expressed both gastrin and cholecystokinin B receptor messenger RNA.. The results indicate that endogenous hypergastrinemia may promote proliferation and spread of human colon carcinoma expressing cholecystokinin B receptor.

Topics: Aged; Animals; Carcinoma; Colonic Neoplasms; Female; Gastric Fundus; Gastrins; Humans; Liver Neoplasms; Male; Neoplasm Transplantation; Rats; Rats, Inbred Lew; Rats, Nude; Receptors, Cholecystokinin

To investigate further the presence of an autocrine proliferative loop involving gastrin in colorectal carcinomas and to clarify the receptor responsible, 102 human colorectal carcinomas and 10 hepatic metastases were investigated for the expression of the genes encoding gastrin, the gastrin/CCK-B receptor and the gastrin/CCK-C receptor. Levels of RNA expression were assayed by RNase protection assay. In addition, gastrin/CCK receptors on crude membranes of tumour tissue were assayed by radioligand binding. High-affinity gastrin/CCK-B receptors were not detected in any of the carcinomas investigated, whereas in 36% low-affinity binding was observed, consistent with the expression of the gastrin/CCK-C receptor. RNase protection assay detected the RNA for the gastrin/CCK-B receptor in 11% of the carcinomas investigated, whereas the RNA for the gastrin/CCK-C receptor was demonstrated in 75% and the RNA for gastrin in 86% of the carcinomas investigated. These results confirm the recent demonstration of progastrin fragments in colorectal carcinomas. One possible explanation for progastrin expression is that such progastrin fragments may participate in an autocrine proliferative loop. The receptor involved in this loop is more likely to be the low-affinity gastrin/CCK-C receptor rather than the gastrin/CCK-B receptor, which is rarely expressed in colorectal carcinomas.

Topics: Binding, Competitive; Colorectal Neoplasms; Female; Gastrins; Gene Expression Regulation, Neoplastic; Humans; Liver Neoplasms; Male; Protein Binding; Protein Precursors; Radioligand Assay; Receptors, Cholecystokinin; Ribonucleases; RNA Probes; RNA, Messenger

Topics: Colorectal Neoplasms; Gastrins; Humans; Indoles; Liver Neoplasms; Predictive Value of Tests; Proglumide; Prognosis

14 patients with metastatic endocrine gastro-entero-pancreatic carcinoma (6 patients with Carcinoid-syndrome, 3 with gastrinoma and 5 with non-functioning tumor) have been treated with Octreotide 3 x 200 micrograms/die plus Interferon-Alpha 3 x 5 Mio U/week after documented tumor progression during preceding Octreotide-monotherapy. 6 out of 14 patients responded favourable to the treatment: one patient with partial regression and 5 patients with stillstand of tumor growth. In only one patient initial tumor stillstand for 6 months was followed by tumor progression whereas in five patients a beneficial effect on tumor growth could be documented up to 34 months. Inhibition of tumor growth and tumor progression was not necessarily paralleled by respective changes in peripheral hormone levels. These results should initiate a controlled prospective study to prove the hypothesis that in patients with metastasized endocrine gastro-entero-pancreatic tumors the combination of Octreotide and Interferon-Alpha is superior to monotherapy with Octreotide or Interferon-Alpha and to identify those patients who respond to this combined therapy.

Topics: Biomarkers, Tumor; Combined Modality Therapy; Female; Gastrinoma; Gastrins; Gastrointestinal Neoplasms; Humans; Hydroxyindoleacetic Acid; Interferon alpha-2; Interferon-alpha; Liver Neoplasms; Male; Malignant Carcinoid Syndrome; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Pancreatic Neoplasms; Recombinant Proteins

Topics: Carcinoma, Islet Cell; Fatal Outcome; Female; Gastrins; Gastrointestinal Hemorrhage; Humans; Liver Neoplasms; Middle Aged; Pancreatic Neoplasms

Nude mice bearing xenografts of HT-29 human colon cancer cell line were treated for 4 weeks with somatostatin analog (RC-160), bombesin/gastrin releasing peptide (GRP) antagonists (RC-3095 and RC-3440). In three separate experiments somatostatin analog RC-160 (50 micrograms/day) released from microgranules significantly reduced tumor growth. Bombesin/GRP antagonists, RC-3095 and RC-3440 injected subcutaneously (s.c.) twice daily at a dose of 10 micrograms had the greatest and consistently significant inhibitory effect on tumor growth. RC-3095 given once daily s.c. at a dose of 20 micrograms was less effective. RC-3095 also inhibited metastatic tumor growth after intrasplenic injection of HT-29 cells in nude mice. Specific binding sites of somatostatin, bombesin and epidermal growth factor (EGF) were detected on intact HT-29 cells or on the membranes from HT-29 tumor xenografts. The inhibitory effects of bombesin antagonists on tumor growth were consistently linked with a significant down-regulation of EGF receptors. Bombesin/GRP antagonists and somatostatin analogs could be considered for the development of new hormonal therapies for colon cancer.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Bombesin; Colonic Neoplasms; Drug Screening Assays, Antitumor; ErbB Receptors; Gastrin-Releasing Peptide; Gastrins; Growth Hormone; Humans; Insulin-Like Growth Factor I; Liver Neoplasms; Male; Mice; Mice, Nude; Neoplasm Transplantation; Peptide Fragments; Peptides; Radioligand Assay; Somatostatin

To investigate the hypothesis that gastrin might be synthesized by tumour tissues in cancer of the colon, samples from six human colon tumours, one hepatic metastasis, four normal colonic mucosal samples and two antral and one fundic gastric mucosal samples from nine patients were analysed to determine whether gastrin mRNA was present. RNA was extracted from surgical specimens by ultracentrifugation on a CsCl cushion, purified using the guanidinium thiocyanate method, reverse-transcribed and amplified by polymerase chain reaction. Gastrin mRNA was detected in each colonic carcinoma sample (including the hepatic metastasis), while no such signal was observed in normal colon biopsies. Positive and negative controls (gastric antrum and fundus respectively) gave the expected results. In each of the positive samples, the chemiluminescent revelation of amplified products after Southern blotting corresponded to gastrin mRNA without the intron. These findings demonstrate the ability of primary and metastatic human colonic tumours to produce gastrin mRNA. Since malignant cell lines have been reported to produce gastrin peptide, and since gastrin receptors were present in some cases, our results support the idea that gastrin may be involved in an autocrine mechanism.

Topics: Base Sequence; Colon; Colonic Neoplasms; Gastric Fundus; Gastric Mucosa; Gastrins; Humans; Intestinal Mucosa; Liver Neoplasms; Luminescent Measurements; Molecular Sequence Data; Neoplasm Proteins; Organ Specificity; Polymerase Chain Reaction; Pyloric Antrum; RNA-Directed DNA Polymerase; RNA, Messenger

We reviewed the age of presentation, malignant potential, and outcome of gastrinomas and pancreatic tumors in patients with multiple endocrine neoplasm, type 1.. Screening of one very large and one smaller, possibly related family on an island, including serum gastrin estimations and, when indicated, pancreatic ultrasound.. Over 2000 family members and their family physicians were advised on screening procedures.. Data were collected and reviewed retrospectively and prospectively for all medical records, investigations, surgical procedures, and available tissue samples.. Criteria for diagnosis were established for radiological, biochemical, and histological studies.. Sixty-two patients had evidence of gastrinoma or pancreatic neoplasm. In 19 patients the diagnosis was based on demonstration of a tumor. In 21 patients the diagnosis was based on elevated serum gastrin concentration in the absence of demonstrable tumor. None of these patients required gastric surgery if they first underwent parathyroidectomy. In 18 patients the diagnosis was based on the combination of demonstrated pancreatic tumor plus elevated glucagon (two patients), gastrin (11 patients), or insulin (five patients) concentration. Peptic ulcer was difficult to control in seven of the 11 patients with elevated gastrin concentrations plus demonstrated tumor. Four patients had liver metastases that appeared to be secondary to the pancreatic gastrinoma. In patients with insulinomas, the first symptoms occurred before age 20 years. Elevated serum gastrin concentrations were not seen before age 24 years and were observed to occur for the first time in two patients after age 50 years.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Female; Follow-Up Studies; Gastrinoma; Gastrins; Glucagon; Humans; Insulin; Insulinoma; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Prospective Studies; Retrospective Studies; Zollinger-Ellison Syndrome

There have been no reports on the relationship between serum gastrin level and liver metastasis in human colorectal cancer. One hundred forty patients who underwent surgery for colorectal cancer (T2 or more) were enrolled in this study. Fasting serum gastrin level was determined prior to the surgery. Incidence of liver metastasis was significantly (P < 0.01) higher in patients with a serum gastrin level of > or = 150 pg/ml (37 percent; 14/38) than in those with a serum gastrin level of < 150 pg/ml (12 percent; 12/102). As for the tumors with venous invasion, liver metastasis was detected in 11 of 55 patients (20 percent) with a serum gastrin level of < 150 pg/ml; however, it was detected in 11 of 19 patients (58 percent) with a serum gastrin level of > or = 150 pg/ml (P < 0.01). These results suggest that serum gastrin serves as a useful predictor of liver metastasis from colorectal cancer and that the predictability of liver metastasis can be improved when both serum gastrin level and venous invasion are considered.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Colorectal Neoplasms; Female; Gastrins; Humans; Incidence; Liver Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis; Prognosis; Veins

Topics: Adenocarcinoma; Animals; Antigens, Viral, Tumor; Carcinoma; Gastrinoma; Gastrins; Genetic Engineering; Hyperplasia; Liver Neoplasms; Mice; Mice, Transgenic; Pancreatic Neoplasms; Pyloric Antrum; Stomach Neoplasms

The authors report the case of a 48 years old man presenting a pancreatic islet cell carcinoma (gastrinoma) with liver, nodes and peritoneal metastases, associated with an elevated alpha-fetoprotein (AFP) concentration. Incomplete remission was first obtained with a chemotherapy using Streptozotocin combined with 5-Fluorouracil, in association with a Somatostatin analogue (SMS 201-995). But when relapses occur, another chemotherapy was not so effective. Serum gastrin and AFP levels had the same evolution and appear to have the same interest to follow the course of the disease.

Topics: alpha-Fetoproteins; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Fatal Outcome; Fluorouracil; Gastrinoma; Gastrins; Humans; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Octreotide; Pancreatic Neoplasms; Peritoneal Neoplasms; Remission Induction; Streptozocin

Although gastrinoma resection is generally advocated for patients with the sporadic form of nonmetastatic Zollinger-Ellison syndrome, there is controversy regarding the surgical management of the gastrinoma among patients with multiple endocrine neoplasia type I (MEN-I). Using strict criteria, to date no biochemical cures of the Zollinger-Ellison syndrome lasting greater than 5 months have been achieved by gastrinoma resection among patients with MEN-I. Whereas resections of hepatic metastases have been performed in patients with sporadic gastrinoma, none have been reported among patients with MEN-I. The current report describes a patient with MEN-I, closely followed up for 30 years, in whom enlargement of pancreatic gastrinoma and development of hepatic gastrinoma was observed to occur over 3 years. After preoperative localization, an 80% pancreatectomy and a left lateral segmentectomy of the liver were performed. Sixteen months after the operation, secretin and calcium provocative testing showed that the patient's fasting gastrin and stimulated plasma gastrin concentrations were normal; also, results of computerized tomographic angiography, selective abdominal angiography, and hepatic venous sampling for gastrin after intra-arterial secretin injection were negative for gastrinoma. By achieving a 16-month cure of gastrinoma, this case shows that an aggressive surgical approach can benefit certain patients with gastrinoma who have MEN-I even in the presence of hepatic metastases.

Topics: Angiography; Follow-Up Studies; Gastrinoma; Gastrins; Humans; Liver Neoplasms; Male; Middle Aged; Multiple Endocrine Neoplasia; Neoplasms, Second Primary; Pancreatic Neoplasms; Secretin; Zollinger-Ellison Syndrome

In a 30-year-old man with Zollinger-Ellison syndrome, the only detectable gastrinoma was in the right liver lobe. Removal of the lobe, without additional gastric surgery, was followed by normalization of the gastrin level. Long-term follow-up confirmed the good result. The usefulness of quick intraoperative gastrin assay is stressed.

Topics: Adult; Follow-Up Studies; Gastrinoma; Gastrins; Humans; Liver Neoplasms; Male; Time Factors; Zollinger-Ellison Syndrome

Colonic mucosa and adenocarcinoma are known to possess gastrin receptors. Recent studies have suggested that some patients with large intestinal cancers and polyps have elevated serum gastrin levels and that gastrin may stimulate growth of colonic neoplasms. The aim of the present investigation was to determine whether endogenous hypergastrinemia--induced by the proton pump inhibitor omeprazole--would influence growth in a subcutaneously implanted murine colonic cancer. The results show that despite a fivefold increase in serum gastrin levels (193 pg/ml median value, range 186-252, in the omeprazole-treated group vs 36 pg/ml median value, range 28-37 in controls), there were no differences in tumor size or survival of tumor-bearing animals. Additionally, there were no differences in serum gastrin values between tumor- (29 pg/ml, range 25-38) and non-tumor- (34 pg/ml, range 25-30) bearing, untreated animals. Endogenous elevation of the serum gastrin hormone to five times the normal level does not demonstrate trophic effects on the murine colon tumor MC-26.

Topics: Adenocarcinoma; Animals; Cell Division; Colonic Neoplasms; Gastrins; Liver Neoplasms; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Omeprazole

Specimens from the pancreas and duodenum of 26 patients with sporadic Zollinger-Ellison syndrome (ZES) and 18 patients with multiple endocrine neoplasia type 1 (MEN-1) and hypergastrinemia (17 with ZES) were screened immunocytochemically for gastrinomas. Location, size, multicentricity, and malignancy of the gastrinomas were evaluated. The MEN-1 patients had gastrinomas in the duodenum (nine of 18), pancreas (one of 18), and periduodenal lymph nodes (two of 18). No gastrinoma was identified in six patients. Most duodenal gastrinomas were multiple (five of nine) and smaller than 0.6 cm (six of nine). Lymph node metastases were present in eight of 12 patients. All 26 patients with sporadic ZES had a solitary gastrinoma; 14 were found in the pancreas and had a diameter greater than 2 cm. Ten patients had a duodenal gastrinoma, two with a diameter less than 0.6 cm. In two patients, only periduodenal "lymph node gastrinomas" were detected. Eighteen of the sporadic gastrinomas were malignant. These results suggest that duodenal location and multicentricity of gastrinomas are associated with the MEN-1 syndrome, and solitary gastrinomas, either in the pancreas or the duodenum, are predominantly seen in sporadic ZES.

Topics: Duodenal Neoplasms; Gastrinoma; Gastrins; Humans; Immunohistochemistry; Liver Neoplasms; Lymphatic Metastasis; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

We have evaluated the peripheral blood natural killer (NK) cell activity and the in vitro effect of recombinant gamma-interferon (r gamma-IFN) on NK cell activity in 23 patients with a neuroendocrine tumour of the pancreas, small intestine or liver, and 23 healthy controls. Patients with a gastrinoma showed a NK cell activity which was not different from that of the control group, whereas patients with another type of neuroendocrine tumour had a decreased NK cell activity compared to the controls (p less than 0.05) and the gastrinoma patients (p less than 0.02). The impaired NK cell activity in these patients was as such not related to the presence of liver metastasis or performance status of the patients. r gamma-IFN significantly stimulated the NK cell activity in patients and controls. However, the cytotoxic response of the patients with a hormone production other than gastrin remained lower than in the two other groups. Follow-up studies in 8 patients showed NK cell activities not to vary with stable disease, to decrease with progressive disease, and to increase with regression of disease. In conclusion, NK cell activity is suppressed in patients with neuroendocrine tumours that produce hormones other than gastrin. This impairment is not related to the presence of metastasis but seems to be related to the course of the disease.

Topics: Adult; Aged; Carcinoid Tumor; Cell Line; Female; Gastrinoma; Gastrins; Gastrointestinal Hormones; Humans; Interferon-gamma; Intestinal Neoplasms; Killer Cells, Natural; Lipoma; Liver Neoplasms; Male; Middle Aged; Pancreatic Neoplasms; Recombinant Proteins; Somatostatinoma; Tumor Cells, Cultured

Three Zollinger-Ellison syndrome patients were treated during the period January 1977 to June 1978. The first patient is in good health 11 years 3 months after a total gastrectomy as is the second patient, 11 year after the enucleation of a cephalo-pancreatic gastrinoma. However the third patient died from malignancy 5 years after a total gastrectomy and enucleation of a cephalo-pancreatic gastrinoma followed by therapeutic cycles with streptozotocin and 5-fluorouracil. The decline in the Zollinger-Ellison syndrome over the last ten years is examined and the type of surgical treatment is discussed. Total gastrectomy once advocated as the preferred treatment, is now reappraised because of the effectiveness of medical therapy in controlling ulcers and because of the frequent malignancy of pancreatic gastrinomas.

Topics: Adult; Carcinoma, Hepatocellular; Female; Follow-Up Studies; Gastrins; Humans; Italy; Liver Neoplasms; Male; Middle Aged; Zollinger-Ellison Syndrome

Topics: Bombesin; Gastrinoma; Gastrins; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Pancreatic Neoplasms; Secretin; Zollinger-Ellison Syndrome

A case of malignant gastrinoma of the jejunum and jejunal mesentery, with findings of metastasis in the liver was studied. Tumor resection and remnant gastrectomy, as well as liver biopsy, were performed. Of all the tumors removed, the metastatic tumor had the lowest gastrin content, which was 1.5 times that found in normal human antral mucosa. The gastrin distribution was of four peaks and one peak for the main tumor, versus two peaks for the metastatic tumor in which G17 was the main component. Seven years after the operation, computed tomography (CT) scan indicated there was stabilization of the liver metastasis, and now, ten years after the total gastrectomy, the patient is well and working full-time. Such an analysis can be of value in determining the prognosis in cases of malignant gastrinoma with liver metastasis.

Topics: Adult; Follow-Up Studies; Gastrectomy; Gastrins; Humans; Jejunal Neoplasms; Liver Neoplasms; Male; Time Factors; Zollinger-Ellison Syndrome

We have used the gastrinoma syndrome to examine the effects of SMS. Acutely, SMS decreased acid secretion and restored the BAO/MAO to normal in eight of eight patients. Basal and secretin-stimulated gastrin responses were suppressed but not normalized. Treatment for up to 2 years with SMS controlled symptoms, suppressed serum gastrin, and suppressed acid secretion. Treatment for 1 year or longer decreased tumor secretion of gastrin and diminished basal acid secretion, an effect that persisted for 48 hours after withdrawal of SMS. SMS treatment arrested progression of tumor growth only in patients in whom there was a reduction in gastrin and gastric acid secretion. In patients with metastatic disease who had high levels of gastrin, SMS treatment for 5 to 24 months did not inhibit tumor growth or decrease gastrin levels. In those patients in whom a reduction in the blood flow to liver tumors was shown angiographically, there was a progressive improvement in hormone secretion and in tumor size in the ensuing year of treatment, suggesting that a major target of SMS is that vascular supply of the tumors. Tumors shown to produce peptides other than gastrin, for example ACTH, were found to be markedly resistant to the action of SMS and continued to grow in an unbridled manner.

Topics: Adult; Bone Neoplasms; Combined Modality Therapy; Female; Gastric Acid; Gastrinoma; Gastrins; Gastrointestinal Neoplasms; Humans; Liver Neoplasms; Male; Octreotide; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes

Ten patients with metastatic pancreatic endocrine tumours were treated with the long-acting somatostatin analogue octreotide (SMS 201-995). Three patients showed no response, clinically or biochemically, and treatment was therefore withdrawn. The seven remaining patients continued treatment for a median period of 28 months (range 13-54 months). Treatment was initially effective, symptoms improved and the concentrations of tumour-related hormones were reduced. Worsening of symptoms and rising levels of tumour-related hormone concentrations occurred a median of 5 months (range 1-6 months) after the start of therapy and were initially reversed by increasing the dose of octreotide over a median of 10 months (range 6-16 months). However, after a median of 13 months (range 5-34 months) at the maximum dosage, symptoms recurred and were no longer responsive to a further increase in dosage of octreotide or other therapeutic measures. All patients died within a period of 5 months once this resistant phase of their illness had been reached.

Topics: Adenoma, Islet Cell; Gastrins; Glucagon; Humans; Liver Neoplasms; Octreotide; Pancreatic Neoplasms; Time Factors; Vasoactive Intestinal Peptide

Topics: Carcinoma, Hepatocellular; Gastrins; Humans; Liver Neoplasms; Middle Aged

Gastrinoma cells from surgical specimens of a primary pancreatic tumor and an hepatic metastasis in two patients with a Zollinger-Ellison syndrome were grown and subcultured for 7 mo. Cultured cells displayed a strong reactivity to heptadecapeptide gastrin antibody and maintained an ultrastructural appearance resembling that of the original tumor cells with the presence of secretory granules of variable size and electron density. Cultured cells also showed the ability to secrete immunoreactive gastrin, and this secretion was further concentration-dependently stimulated by secretin (10(-10)-10(-6) M), carbachol (10(-6) M), and bombesin (10(-10)-10(-6) M). The latter peptide was the more potent stimulant with a maximal effect at 10(-9) M (460 +/- 20% of basal release; P less than 0.05). This stimulation occurred in the absence of extracellular Ca2+ and was potentiated by the addition of dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP; 10(-3) M) into the culture medium. The somatostatin analogue, somatostatin-(201-995), did not alter basal gastrin release but inhibited secretin, carbachol, and bombesin stimulation. Moreover, DBcAMP (10(-3) M) and Ca2+ (1-3 mM) stimulated gastrin release; Ca2+ ionophore A23187 (6 micrograms/ml) enhanced gastrin response to Ca2+ in the early time intervals of incubation. Furthermore the phorbol ester derivative, 12-O-tetradecanoyl phorbol-13-acetate, dramatically stimulated gastrin release (10 times the basal value). We conclude that gastrinoma cells can be cultured over an extended period with maintenance of their capacity to secrete gastrin in response to various hormones and mediators.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Bombesin; Bucladesine; Calcimycin; Calcium; Carbachol; Culture Media; Gastrinoma; Gastrins; Humans; In Vitro Techniques; Liver Neoplasms; Pancreatic Neoplasms; Secretin; Stimulation, Chemical; Tumor Cells, Cultured

Functional gastrin-containing tumor cells (GT cells) have been maintained in short-term culture on microporous membranes, and their response to selected agents has been determined. After dispersion of gastrinoma by collagenase-DNAase digestion coupled with mechanical disruption, dispersed cells were depleted in stromal material by selective attachment to a plastic substrate, then cultured for 72 hours on porous cellulose membranes. Cultures contained 68 +/- 5% GT cells with a viability of 92 +/- 2%. Secretin stimulated the rate of gastrin release from cultured GT cells in both a time- and a dose-dependent fashion. To examine the possible involvement of adenylate cyclase- and protein kinase C-mediated mechanisms in regulating gastrin release from the neoplastic GT cells, we evaluated the effects of 8-bromoadenosine 3':5'-cyclic monophosphate (8-BrcAMP; 10(-4) - 10(-2) mol/L), the diterpene forskolin (10(-5) mol/L), 12-0-tetradencanoylphorobol 13-acetate (TPA; 10(-8) - 10(-6) mol/L), and 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD; 10(-8) - 10(-6) mol/L) on gastrin release. Among all compounds tested, 8-BrcAMP (10(-2) mol/L) was the most potent, stimulating the rate of gastrin release 263% above basal. Both 8-BrcAMP and TPA stimulated gastrin release in a dose-dependent fashion. The biologically inactive phorbol ester, 4 alpha PDD, was without effect at all concentrations. Somatostatin (10(-8) - 10(-6) mol/L) inhibited 8-BrcAMP-stimulated gastrin release in a dose-dependent fashion to a maximum of 75%.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Adult; Cells, Cultured; Chromaffin System; Colforsin; Enterochromaffin Cells; Female; Gastrins; Humans; Immunohistochemistry; Liver Neoplasms; Phorbol Esters; Radioimmunoassay; Secretin; Somatostatin; Tetradecanoylphorbol Acetate; Zollinger-Ellison Syndrome

There is a potential phosphorylation site in the C-terminal region of the precursor for the acid-stimulating hormone gastrin, which is immediately adjacent to an important cleavage point. In the present study we have sought to identify, separate, quantify and characterize phosphorylated and unphosphorylated forms of human progastrin and its fragments. Identification was made by two radioimmunoassays: (a) a novel assay employing an antibody raised to intact human progastrin; and (b) an assay using antibody reacting with the C-terminal tryptic fragment of human progastrin, as well as progastrin itself. Two forms of human progastrin isolated from a gastrinoma were separated by ion-exchange h.p.l.c., and had similar elution positions on reverse-phase h.p.l.c. and on gel filtration. The more acidic peptide contained close to equimolar amounts of phosphate. On trypsinization, peptides were released that co-eluted on ion-exchange h.p.l.c. with, and had the immunochemical properties of, naturally occurring C-terminal fragments of progastrin. One of the latter was isolated and shown by Edman degradation after derivatization with ethanethiol to have the sequence Ser (P)-Ala-Glu-Asp-Glu-Asn. Similar peptides occur in antral mucosa resected from ulcer patients. The unphosphorylated forms of progastrin predominated, whereas the phosphorylated forms of the C-terminal fragments were predominant. This distribution could be explained by preferential cleavage of phosphorylated progastrin. We conclude that in human progastrin, Ser-96 can occur in the phosphorylated form; this residue immediately follows a pair of basic residues (Arg-Arg) that are cleaved during synthesis of the biologically active product.

Topics: Amino Acid Sequence; Chromatography, High Pressure Liquid; Gastric Mucosa; Gastrinoma; Gastrins; Humans; Liver Neoplasms; Molecular Sequence Data; Peptide Fragments; Phosphorylation; Protein Precursors; Trypsin

Topics: Gastrins; Humans; Liver Neoplasms; Male; Middle Aged; Octreotide; Pancreatic Neoplasms; Radionuclide Imaging; Somatostatin; Zollinger-Ellison Syndrome

A patient with metastatic islet cell carcinoma demonstrated multiple clinical syndromes simultaneously with secretion of ACTH, gastrin, glucagon, and serotonin. Hepatic arterial embolization resulted in an initial decrease in all secretory products, which was sustained for glucagon and serotonin. Recrudescence of the Cushings and Zollinger-Ellison syndrome was managed by surgical extirpation of the primary tumor and regional metastases as well as bilateral adrenalectomy. Electron microscopy and immunocytochemistry of the primary tumor and the metastatic lesions revealed the presence of multiple types of granules within single cells and, different patterns of secretory profiles in different tumor sites.

Topics: Adenoma, Islet Cell; Adrenocorticotropic Hormone; Adult; Cushing Syndrome; Female; Gastrins; Glucagon; Humans; Liver Neoplasms; Microscopy, Electron; Neoplasm Metastasis; Pancreatic Neoplasms; Tomography, X-Ray Computed

Topics: Adult; Gastrins; Hormones, Ectopic; Humans; Insulin; Liver Neoplasms; Male; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Secretin was injected into a feeding or nonfeeding artery of a gastrinoma and blood samples were taken from the hepatic vein (HV) or a peripheral artery (PA) to measure the changes of serum immunoreactive gastrin concentration (IRG). The IRG in the HV rose within 40 seconds and in the PA rose within 60 seconds after the injection of secretin into a feeding artery, but not after secretin was injected into a nonfeeder. These results indicated that secretin directly stimulates a gastrinoma to release gastrin in vivo. The selective arterial secretin injection test (SASI test) was applied in three patients in whom gastrinomas could not be located by computed tomography, ultrasonography, or arteriography, and functioning gastrinomas were located in all three patients. In one patient, malignant gastrinomas in the head of the pancreas and in the duodenum could be resected radically with the help of this test.

Topics: Adult; Aged; Angiography; Duodenal Neoplasms; Female; Gastrins; Histocytochemistry; Humans; Insulin; Laparotomy; Liver Neoplasms; Male; Microscopy, Electron; Middle Aged; Pancreatic Neoplasms; Secretin; Zollinger-Ellison Syndrome

The molecular species of gastrin in the circulation and in tumor extracts were studied in two groups of patients: (1) with benign gastrinoma and (2) with gastrinoma with liver metastases. Radioimmunoassays (RIAs) and immunoaffinity chromatography for the amino (NH2)- and amidated COOH-terminus of gastrin-17 (antiserum G17) and the NH2-terminus of gastrin-34 (antiserum G34) were employed. In both benign and metastatic tumors the molecular forms of gastrin in boiling water extracts measured by the gastrin-17 NH2- and COOH-terminal assays were similar. In addition to a molecular component resembling the amidated gastrin-17, there were also significant amounts of larger molecular weight (mol. wt.) forms. The larger mol. wt. forms absorbed by the NH2-terminus of G17 antiserum corresponded to the COOH-terminus-extended forms of gastrin-17. Furthermore, larger mol. wt. gastrins immunopurified by antiserum to the NH2-terminus of gastrin-34 corresponded to gastrin-34 extended molecules. Sera of patients with liver metastases had higher concentrations of the NH2-terminal of gastrin-17 whereas sera of patients with benign gastrinoma contained predominantly gastrins detected by the COOH-terminal assay. These results suggest that: (a) there are differences in the molecular pattern of gastrin in the circulation of patients with benign and metastatic gastrinomas; (b) gastrins which are fully processed with carboxy-terminal amidation predominate in the circulation of patients with benign gastrinoma; and (c) gastrins containing the gastrin-17 and COOH-terminally extended gastrin-17 and gastrin-34 precursor molecules occur in high concentration in the circulation of gastrinoma patients with metastases to the liver.

Topics: Chromatography, Gel; Gastrins; Humans; Immune Sera; Immunosorbent Techniques; Liver Neoplasms; Molecular Weight; Radioimmunoassay; Zollinger-Ellison Syndrome

Antibodies to the extreme C-terminal region of human progastrin have been used to monitor the isolation of high-Mr immunoreactive material in a gastrinoma extract. Microsequence analysis of the product revealed amino acid residues in the first 18 positions corresponding to those predicted from the cDNA sequence for preprogastrin starting at position 22; the sequence and immunochemical data together allow the identification of this material as intact progastrin. Implications for gastrin biosynthesis are discussed.

Topics: Amino Acid Sequence; Gastrins; Humans; Liver Neoplasms; Protein Precursors; Zollinger-Ellison Syndrome

Forty-six patients with the gastrinoma syndrome were divided into 2 categories: 1) benign sporadic gastrinoma (n = 30), and 2) gastrinoma with metastases to liver (n = 16). Thirteen of the 46 patients had multiple endocrine neoplasia type I syndrome. Serum gastrin levels in patients fasted overnight were determined by RIA using antisera directed toward the NH2- and COOH-terminals of heptadecapeptide gastrin (G17) and the NH2-terminus of the triacontatetrapeptide (G34). These results were compared with findings in 50 normal subjects. In the normal subjects, the mean COOH-terminal gastrin-17 level was higher [65 +/- 8 (+/- SEM) pg/ml] than the NH2-terminal gastrin-17 level (11 +/- 0.2 pg/ml) and lower than the NH2-terminal gastrin-34 level (134 +/- 20 pg/ml). The levels of NH2-terminal gastrin-17 were higher in patients with metastatic disease than in those with benign gastrinoma, whereas the COOH-terminal gastrin-17 and the NH2-terminal gastrin-34 levels were similarly high in both groups. The mean ratio of NH2-terminal gastrin-17 to COOH-terminal gastrin-17 was less than 1 in normal subjects (0.22 +/- 0.02) and benign gastrinoma patients (0.2 +/- 0.04), and it was 2.2 +/- 0.41 in the patients with metastatic gastrinoma. An NH2 to COOH gastrin-17 ratio greater than 1 was found in 13 of 16 patients with metastatic gastrinoma, but in none of the patients with benign gastrinoma or normal subjects. Similar results were found in multiple endocrine neoplasia type I patients with benign and metastatic disease. A high NH2 to COOH gastrin-17 ratio is suggestive of metastatic gastrinoma. In 4 patients with metastatic gastrinoma, the NH2 to COOH gastrin-17 ratio fell in parallel with the response to chemotherapy.

Topics: Chromatography, Gel; Gastrins; Humans; Liver Neoplasms; Multiple Endocrine Neoplasia; Protein Precursors; Radioimmunoassay; Zollinger-Ellison Syndrome

Fifteen patients with Zollinger-Ellison syndrome followed at the National Institutes of Health with extensive metastatic disease had an actuarial 5-year survival of 20%. Therefore, in 1982 a prospective study to examine the effect and feasibility of removing all gross tumor in selected patients with extensive metastatic disease was instituted. Five patients with extensive metastatic gastrinoma confined to the abdomen in whom imaging studies suggested the possibility of complete surgical resection were entered into this study and underwent attempted complete surgical resection and chemotherapy with streptozotocin, doxorubicin, and 5-fluorouracil. Median follow-up was 24 months. Surgical resection of all gastrinoma was possible in 4/5 patients attempted. In one patient in whom all gross disease could not be resected, the residual tumor progressed and the patient died 19 months after operation. All four patients with all disease resected appeared to benefit since all of them had a significant reduction in antisecretory medications and are enjoying normal activity and work. Three patients have had no detectable tumor on follow-up, and two of these patients are clinically and biochemically "cured" with normal fasting gastrin levels and negative provocative gastrin tests at 14 and 32 months. Therefore, aggressive resection of metastatic disease in selected patients with malignant gastrinoma is recommended.

Topics: Abdominal Neoplasms; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cimetidine; Combined Modality Therapy; Doxorubicin; Female; Fluorouracil; Follow-Up Studies; Gastrins; Humans; Kidney Neoplasms; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Prognosis; Prospective Studies; Radiography; Ranitidine; Streptozocin; Zollinger-Ellison Syndrome

A 44-year-old woman with hepatocellular carcinoma presented with intractable watery diarrhea and her condition was evaluated angiographically. Surgical ablation of the tumor resulted in complete resolution of the diarrhea. The tumor cells of the hepatocellular carcinoma were found to contain vasoactive intestinal polypeptide, gastrin, and prostaglandinlike immunoactivity. To our knowledge, this is the first report of such an association.

Topics: Adult; Carcinoma, Hepatocellular; Diarrhea; Dinoprostone; Female; Gastrins; Histocytochemistry; Humans; Liver Neoplasms; Paraneoplastic Endocrine Syndromes; Prostaglandins E; Radiography; Vasoactive Intestinal Peptide

In 1982, a prospective study was initiated of 52 consecutive patients with proven Zollinger-Ellison syndrome (ZES), involving surgical exploration with the goal of removing the gastrinoma after an extensive protocol to localize the tumor. Each patient underwent ultrasound, computed tomography (CT) with oral/intravenous (IV) contrast, and selective arteriography. Eighteen patients had metastatic disease identified by imaging studies and confirmed by percutaneous biopsies, and two patients had multiple endocrine neoplasia type I (MEN-I) with negative imaging studies; therefore, these 20 patients did not undergo laparotomy. Each of the remaining 32 patients (3 with MEN-I and positive imaging studies) underwent laparotomy, and gastrinomas were removed in 20 patients. Preoperative ultrasound localized tumors in 20% of patients, CT in 40%, arteriography in 60%, and any of the modalities in 70% of patients. Infusion CT and arteriography were 100% specific. In 18 patients with either negative imaging (17) or false-positive imaging (1 ultrasound), gastrinomas were found and removed in six patients (33%). Twenty-four gastrinomas were found in 20 patients at laparotomy: eight in lymph nodes around the pancreatic head, four in the pancreatic head, one in the pancreatic body, three in the pancreatic tail, three in the pyloric channel, one in the duodenal wall, two in the jejunum at the ligament of Treitz, one in the ovary, and multiple liver metastases in one patient. If one excludes patients with MEN-I or liver metastatic disease, 12/28 (43%) of patients were biochemically "cured" immediately after operation. This result decreased to 7/23 (30%) with greater than 6 months follow-up. No patients with gastrinomas resected have developed recurrent gastrinoma on follow-up imaging studies (longest follow-up: 4 years). This study indicates that 95% of metastatic gastrinoma can be diagnosed before operation and that, by a combination of careful imaging studies and thorough exploration at surgery, 30% of patients with gastrinomas may be curable.

Topics: Adult; Aged; Female; Follow-Up Studies; Gastric Acid; Gastrins; Humans; Liver Neoplasms; Male; Middle Aged; Prospective Studies; Tomography, X-Ray Computed; Ultrasonography; Zollinger-Ellison Syndrome

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.

Topics: Adult; Angiography; Female; Gastrins; Humans; Jejunal Neoplasms; Liver Neoplasms; Lymph Nodes; Male; Middle Aged; Peptide Fragments; Pyloric Antrum; Secretin; Stomach Neoplasms; Tomography, X-Ray Computed; Zollinger-Ellison Syndrome

Four cases involving cystic endocrine neoplasms of the pancreas and liver are reported. Because of their rich collateral blood supply, islet cell tumors of the pancreas, even if large in size, rarely undergo central or cystic degeneration. However, failure to appreciate that a small percentage of these neoplasms may mimic benign pancreatic pseudocysts by their clinical and radiological appearance can lead to inappropriate surgical therapy. Ultrasound, computerized tomography, and/or angiography are rarely helpful in distinguishing between benign and neoplastic cysts. The definitive diagnosis can be made with assurance only by obtaining a generous biopsy of the cyst wall or any intracystic excrescences for histologic examination. Functional cystic tumors of the pancreas or liver should be excised totally whenever possible, and efforts should be made to remove as much of the tumor mass as possible even when a curative resection cannot be accomplished. Internal drainage may be acceptable as palliation for large, unresectable tumors.

Topics: Adenoma, Islet Cell; Adult; Cysts; Diagnosis, Differential; Female; Gastrins; Humans; Liver Neoplasms; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Cyst; Pancreatic Neoplasms; Tomography, X-Ray Computed

A clinicopathological and immunohistochemical study was carried out on 32 cases of neuroendocrine tumors of the rectum. Typical carcinoids consisted of 27 cases, histologically showing uniform round to columnar cells forming solid alveolar nests and ribbon-like or trabecular arrangement. Neuroendocrine carcinomas consisted of 5 cases in which tumor cells with prominent nuclear atypism were arranged in a ribbon-like or trabecular fashion and formed gland-like structures. There were also small round tumor cells resembling lymphocytes. The prognosis of neuroendocrine carcinomas is very poor with marked tumor invasion of lymphatics and veins resulting in liver metastases and death within one year after operation. Thirty cases out of the 32 showed a positive argyrophil reaction, while immunohistochemistry of 29 cases revealed more than one peptide hormone in 23 cases. The most common hormone was somatostatin being present in 18 of the 23 tumors and glucagon in 16 of the 23 tumors. Gastrin/CCK and calcitonin were proven in 6 of the 23 tumors and in 4 of the 23 tumors, respectively. On the other hand, more than two hormones was present in 15 of the 23 tumors examined. Histologically, neuroendocrine tumors have a very wide spectrum. Histogenetically, typical carcinoids and neuroendocrine carcinomas are considered to be of the same origin with the former showing morphological and functional differentiation to endocrine cells and the latter being more undifferentiated.

Topics: Adult; Aged; Calcitonin; Carcinoid Tumor; Cholecystokinin; Female; Gastrins; Glucagon; Humans; Liver Neoplasms; Male; Middle Aged; Prognosis; Rectal Neoplasms; Somatostatin

Histochemical, chemical and clinical features of two malignant endocrine pancreatic tumors were studied. Both tumors contained pancreatic polypeptide (PP)-immunoreactivity in the majority of tumor cells. In addition, one tumor contained a few scattered serotonin-fluorescent cells and the other scattered gastrin-immunoreactive cells. Pancreatic polypeptide hypersecretion was established from both tumors. Serotonin was produced by one tumor and gastrin was secreted by the other. No PP-associated endocrine symptoms were present, whereas the hypergastrinemia may have caused a bleeding duodenal ulcer in one patient. Although both tumors were highly malignant the clinical courses in the two patients were very different; one patient died within a few months whereas the other is alive 2 years after the diagnosis.

Topics: Adult; Female; Fluorescent Antibody Technique; Gastrins; Humans; Immunoenzyme Techniques; Liver Neoplasms; Male; Middle Aged; Pancreatic Neoplasms; Pancreatic Polypeptide; Serotonin

The authors report the case of a patient with a typical carcinoid syndrome and a severe hypoglycemia due to hyperinsulinism. He was found to have an ileal carcinoid tumor with hepatic metastasis and no evidence of pancreatic insulinoma at surgery and autopsy. By assaying serotonin and insulin in the tumor and in the supernatants of the culture derived from hepatic metastasis, the authors have been able to show that both hormones were produced by the carcinoid tissue. Cultured cells also synthesized minute amounts of gastrin and thyrocalcitonin.

Topics: Blood Glucose; Calcitonin; Carcinoid Tumor; Cells, Cultured; Cytoplasmic Granules; Gastrins; Humans; Ileal Neoplasms; Insulin; Insulin Secretion; Liver Neoplasms; Male; Malignant Carcinoid Syndrome; Microscopy, Electron; Middle Aged; Serotonin

An 8-year-old boy with persistent duodenal ulceration was found to have hypergastrinaemia due to a solitary hepatic gastrinoma. Surgical resection has been followed by total clinical remission for a period exceeding 2 years.

Topics: Child; Duodenal Ulcer; Gastrins; Humans; Liver Neoplasms; Male; Zollinger-Ellison Syndrome

Operative experience with 45 gastrinoma patients has led to the identification of an anatomic area where occult tumors can be discovered and where excision of these tumors had led to apparent cure. Of 36 patients with histologically confirmed gastrinomas, 27 patients (75 percent) had obvious and 9 patients (25 percent) had occult tumors. All nine occult lesions were found within an anatomic triangle defined by the junction of the cystic and common bile ducts superiorly, the junction of the second and third portions of the duodenum inferiorly, and the junction of the neck and body of the pancreas medially. Although occult tumors from three patients (in the lymph nodes in two patients and in the duodenum in one patient) were removed primarily for histologic diagnosis, postoperative serum gastrin levels have remained within the normal range (follow-up of 86 to 99 months). Two patients had excision of the tumor with intent to cure. One patient with a solitary duodenal tumor was apparently cured but committed suicide 3 months postoperatively. The other patient had both obvious primary and occult metastatic tumors within the triangle and was eugastrinemic 9 months after excision. In all patients in whom tumor was found, it was locally excised, and no patient was subjected to radical pancreatic resection. There were no postoperative complications related to tumor removal. An aggressive approach towards curative tumor excision is now advocated for all gastrinoma patients who are suitable operative risks and have no evidence preoperatively of liver metastases or the multiple endocrine neoplasm-type I syndrome.

Topics: Biopsy; Duodenal Neoplasms; Follow-Up Studies; Gastrins; Humans; Liver Neoplasms; Lymphatic Metastasis; Pancreatic Neoplasms; Zollinger-Ellison Syndrome

Topics: Adult; Female; Gastrins; Humans; Liver Neoplasms; Zollinger-Ellison Syndrome

Topics: Gastrins; Humans; Liver Neoplasms; Male; Middle Aged; Zollinger-Ellison Syndrome

In three families with the multiple endocrine adenomatosis type I (MEA I) trait, 51 members were investigated by measurement of circulating peptide hormones as tumor markers. Twenty-five of 51 members (49 percent) were considered to be affected by MEA I disorders. The incidence rose with age (75 percent in generation II). Both sexes were affected equally. Hyperparathyroidism was present in 20 of 25 affected members (80 percent), and pituitary tumors (prolactinomas) were found in four of 25 (16 percent). Endocrine pancreatic tumors were found in nine of 25 affected members (36 percent), but when "probable" tumors (seven) are included the frequency rises to 72 percent. Hyperparathyroidism was found in all except one member with proved lesions in other organs. Among patients with proved and possible endocrine pancreatic tumors, elevated serum levels of gastrin and pancreatic polypeptide were frequently found, 78 percent and 67 percent, respectively, and we suggest that serum gastrin and pancreatic polypeptide levels are the most useful screening markers at present for pancreatic lesions in MEA I.

Topics: Adenoma; Adolescent; Adult; Age Factors; Aged; Female; Gastrins; Humans; Hyperparathyroidism; Insulinoma; Liver Neoplasms; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Pancreatic Polypeptide; Parathyroid Neoplasms; Pedigree; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Aged; Coronary Disease; Gastrins; Glucagon; Humans; Liver Neoplasms; Male; Pancreatic Neoplasms; Pancreatic Polypeptide

Topics: Chromatography, Ion Exchange; Gastrins; Humans; Liver Neoplasms; Prognosis; Radioimmunoassay; Zollinger-Ellison Syndrome

Topics: Amino Acid Sequence; Animals; Cross Reactions; Gastric Mucosa; Gastrins; Humans; Liver Neoplasms; Pancreatic Neoplasms; Peptide Fragments; Radioimmunoassay; Swine

We determined the relative concentrations of gastrin molecular species in serum samples from 21 patients with Zollinger-Ellison syndrome with localized gastrinoma (n = 11) or gastrinoma with hepatic metastases (n = 10). Gastrin molecular species were separated by gel-filtration chromatography and quantitated by radioimmunoassay with a gastrin antiserum produced in our laboratory. The percentage gastrin-17 of the total gastrin in the two groups differed significantly (nonparametric Wilcoxon rank test; p less than 0.01). Patients with the Zollinger-Ellison syndrome with apparently localized gastrinoma had a lower percentage of G- 17 (7.6%, SEM 1.6%) than did patients with gastrinoma with hepatic metastases (31.1%, SEM 6.1%). This procedure may be useful in the early classification of tumors in patients with Zollinger-Ellison syndrome.

Topics: Gastrins; Humans; Liver Neoplasms; Neoplasm Metastasis; Stomach Neoplasms; Zollinger-Ellison Syndrome

Prior to total gastrectomy, serum levels of gastrin and human chorionic gonadotropin (HCG) and its alpha- and beta-subunits (alpha-HCG and beta-HCG) were determined by radioimmunoassays in 40 patients with the Zollinger-Ellison syndrome. Basal serum gastrin levels greater than 1,500 pg/mL were found only in patients with metastases to lymph nodes or liver, while levels greater than 8,000 indicated massive liver replacement by tumor. Gastrin levels less than 1,500 pg/mL had no correlation with malignant behavior. Neither the calcium-infusion nor secretin-injection test was useful in identifying tumors as benign or malignant. Basal serum levels of alpha-HCG were elevated (> 7 ng/mL) in four of 20 patients with metastatic gastrinoma and were normal in all 16 patients with benign disease. There was a significant correlation between basal gastrin and alpha-HCG levels in patients with malignant gastrinoma but not for those with benign tumors. The results suggest that serum gastrin and alpha-HCG levels can be useful in assessing the biologic behavior of gastrinomas and in planning appropriate surgical and nonsurgical treatment.

Topics: Adult; Chorionic Gonadotropin; Female; Gastrectomy; Gastrins; Humans; Liver Neoplasms; Lymphatic Metastasis; Male; Zollinger-Ellison Syndrome

A 57-year-old male patient with metastasizing non-beta islet cell carcinoma of the pancreas is described. Both gastrin and VIP levels were elevated and the patient suffered from a syndrome of pancreatic cholera and hyperacidity. The tumour contained gastrin and VIP as demonstrated by immunofluorescence. The patient also had a history of familial renal stone formation and parathyroid nodular hyperplasia. Resection of pancreatic tumour in 1973 resulted in four years without symptoms. In 1977 definite signs of multiple hepatic metastases appeared. These signs disappeared after streptozotocin given in a dosage of 2 g three times at weekly intervals. The patient had remained well for 20 months after this treatment. The causative agents for the clinical syndrome in this case are discussed in view of circulating hormone levels.

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Dehydration; Gastrins; Gastrointestinal Hormones; Humans; Liver Neoplasms; Male; Middle Aged; Pancreatic Neoplasms; Pancreatic Polypeptide; Streptozocin; Syndrome; Vasoactive Intestinal Peptide

Topics: Gastrins; Hormones, Ectopic; Humans; Insulin; Insulin Secretion; Liver Neoplasms; Male; Middle Aged; Somatostatin; Stomach Ulcer

A 61-year-old woman had watery diarrhea, hypochlorhydria, hypokalemia, and elevated serum gastrin levels. She had islet cell carcinoma of the body of the pancreas with multiple metastases to the liver. Radioimmunoassay and immunofluorescence demonstrated both vasoactive intestinal polypeptide (VIP) and gastrin in the surgically removed carcinoma and in a metastatic focus. Electron microscopical findings confirmed the presence of two cell types whose secretory granules had characteristics ascribed to these two hormones. Plasma prostaglandin E levels were also elevated above normal. Serum VIP levels became elevated to the Verner-Morrison range prior to her death of a bleeding duodenal ulcer two years after initial symptoms.

Topics: Adenoma, Islet Cell; Female; Gastrins; Gastrointestinal Hormones; Humans; Liver Neoplasms; Middle Aged; Neoplasm Metastasis; Pancreas; Pancreatic Neoplasms; Vasoactive Intestinal Peptide

Topics: Adult; Diagnosis, Differential; Diarrhea; Female; Gastrectomy; Gastric Mucosa; Gastrins; Humans; Hypercalcemia; Liver Neoplasms; Multiple Endocrine Neoplasia; Neoplasm Metastasis; Zollinger-Ellison Syndrome

Over a period of 21 years 39 patients with gastrinoma were surgically treated. Thirty-three patients had total gastrectomy with two postoperative deaths, and 6 patients had a lesser procedure. The postoperative fasting gastrin levels remained elevated and did not always indicate the extent of tumor involvement. Further mobilization of tumor gastrin by provocative infusion of calcium gluceptate, 15 mg/kg of body weight, should be carried out routinely. A hepatic angiogram should be considered when the gastrin levels exceed 1,000 picograms per ml. Chemotherapy consisting of Tubercidin, Streptozotocin and 5-Fluorouracil was given to 5 patients with extensive gastrinoma. All patients felt better and gained from three to 35 pounds in weight. Since 60% of the patients died or have definite evidence of tumor activity it is assumed that the tumor growth was not inhibited and that it is malignant. Approximately 40% of the patients seem to do well despite modest elevations in gastrin levels suggesting that the retained tumor could be considered benign.

Topics: Adenoma, Islet Cell; Fasting; Fluorouracil; Gastrins; Humans; Liver Neoplasms; Neoplasm Metastasis; Neoplasm Recurrence, Local; Postgastrectomy Syndromes; Prognosis; Stomach Neoplasms; Streptozocin; Tubercidin

Results of light and electron-microscopic studies of primary pancreatic tumor and of metastasis in a new case of Pancreatic Cholera (P.C.) are reported. The primary tumor but not the metastases, contained unusual, large cystic glandular formations, lined both by pancreatic-duct- and small-intestine-like epithelia and closely connected with the endocrine proliferation. A part from a few D-cells, the endocrine tumoral cells could not be identified by histochemical stainings. Their ultrastructural pattern, with small secretory granules (diameter less than 300 nm) and numerous cytoplasmic bunches of filaments, was very similar to that of gastric and duodenal D1-cells. Normal duodenal D1-cells have been said to produce gastric inhibitory peptide, a substance structurally and biologically similar to the vasoactive intestinal peptide actually secreted by the tumor. The normal histological appearance of gastric, gallbladder, jejunal, ileal, right and left colonic mucosae is consistent with the responsibility of the tumoral secretion in the impairment of gut functions in P.C.

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Adult; Cell Transformation, Neoplastic; Cytoplasmic Granules; Dehydration; Female; Gastric Mucosa; Gastrins; Histocytochemistry; Humans; Intestines; Liver Neoplasms; Neoplasm Metastasis; Pancreatic Neoplasms; Peptides; Syndrome

L-asparaginase (140,000 units) infused into the hepatic artery resulted in a remission from disabling hypoglycaemia for nine months in a man with islet cell carcinoma of the pancreas and hepatic metastases. The tumour produced insulin and gastrin with resulting hypoglycaemia and recurrent peptic ulceration which were unresponsive to other drugs. Following L-asparaginase there was a fall in both plasma and insulin and gastrin.

Topics: Adenoma, Islet Cell; Asparaginase; Gastrins; Humans; Hypoglycemia; Insulin; Liver Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms

Topics: Animals; Biliary Tract Diseases; Contraceptives, Oral; Duodenal Ulcer; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Gastrointestinal Diseases; Humans; Intestine, Small; Liver; Liver Neoplasms; Liver Regeneration; Pancreas Transplantation; Postoperative Complications; Rats; Stomach; Transplantation, Homologous; Vagotomy

Topics: Adolescent; Adult; Aged; Female; Gastrins; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Prognosis; Zollinger-Ellison Syndrome

Topics: Adult; Female; Gastrins; Humans; Liver Neoplasms; Neoplasm Metastasis; Zollinger-Ellison Syndrome

Topics: Adult; Aged; Carcinoid Tumor; Cholinesterases; Esterases; Female; Fluorescent Antibody Technique; Gastrins; Histocytochemistry; Hormones; Humans; Immunochemistry; Kidney Neoplasms; Liver Neoplasms; Male; Microscopy, Electron; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms; Peptide Biosynthesis; Staining and Labeling

Topics: Adult; Calcium; Follow-Up Studies; Gastrectomy; Gastrins; Hepatic Artery; Humans; Ligation; Liver Neoplasms; Lymph Node Excision; Lymphatic Metastasis; Male; Mesentery; Middle Aged; Neoplasm Metastasis; Peritoneal Neoplasms; Radiography; Radionuclide Imaging; Streptozocin; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Administration, Oral; Aged; Gastrectomy; Gastrins; Glucagon; Glucose; Glucose Tolerance Test; Humans; Injections, Intravenous; Insulin; Insulin Secretion; Liver; Liver Neoplasms; Male; Neoplasm Metastasis; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adult; Aged; Carcinoid Tumor; Diarrhea; Female; Gastrins; Humans; Liver Neoplasms; Male; Microscopy, Electron; Middle Aged; Neoplasm Metastasis; Pancreas; Pancreatic Neoplasms; Peptic Ulcer; Zollinger-Ellison Syndrome

The effect of total gastrectomy on the biologic behavior of malignant gastrinomas was studied from patient data collected in the ZE tumor registry. A total of 267 patients with documented metastatic tumor had definitive gastric operations. In the 137 patients who had total gastrectomy, survival was 75% at one year, 55% at five years and 42% at ten years. In the 130 patients who had lesser gastric operations, survival was 51% at one year, 27% at five years and 18% at ten years. Deaths from progressive tumor growth occurred in 17% of the patients at risk after total gastrectomy and 30% of the patients at risk after lesser gastric operations. A subgroup of 127 patients with documented liver metastasis had definitive gastric operations. Seventythree patients with liver metastasis had total gastrectomy with survival of 68% at one year, 42% at five years and 30% at ten years. Fifty-four patients with liver metastasis had lesser gastric operations with survival of 44% at one year, 7% at five years and none at ten years. Deaths from progressive tumor growth occurred in 25% of the patients at risk after total gastrectomy and 50% of the patients at risk after lesser gastric operations. Regression of metastatic ZE tumor was clearly documented in only four patients; all had total gastrectomy. Presumptive regression of primary tumor occurred in seven patients, five had total gastrectomy. The study clearly demonstrated that total gastrectomy was the procedure of choice for malignant ZE tumors, even in the presence of widespread metastasis. The results provided indirect evidence to support a gastric feedback effect which influences growth of gastrinomas; however, the results also show that total gastrectomy furnished neither predictable nor permanent protection from subsequent tumor growth and metastasis.

Topics: Adolescent; Adult; Female; Gastrectomy; Gastrins; Humans; Liver Neoplasms; Male; Neoplasm Metastasis; Neoplasm Regression, Spontaneous; Pancreatic Neoplasms; Prognosis; Zollinger-Ellison Syndrome

A pair of gastrin tridecapeptides (;minigastrins') have been isolated from Zollinger-Ellison tumour tissue; they correspond to the fragment 5-17 of the heptadecapeptides isolated from the same source. In one (type II) the tyrosine residue present is sulphated, in the other (type I) it is not. The proportion of types I and II is approximately 2:1 similar to that for the ;big' gastrins and the heptadecapeptides isolated from the same source and from human antral mucosa. Both minigastrins are potent stimulants of gastric acid secretion. Immunological evidence exists to indicate that both are present as circulating forms of the hormone gastrin in patients with the Zollinger-Ellison syndrome and in fed normal subjects.

Topics: Amino Acids; Chromatography; Chromatography, Gel; Gastrins; Humans; Liver Neoplasms; Molecular Weight; Neoplasm Metastasis; Neoplasm Proteins; Peptide Fragments; Peptides; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adolescent; Adult; Aged; Female; Gastrectomy; Gastric Juice; Gastrins; Humans; Hyperparathyroidism; Liver Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Radioimmunoassay; Secretory Rate; Zollinger-Ellison Syndrome

Topics: Adult; Autopsy; Bone Neoplasms; Calcinosis; Gastrins; Humans; Hypoglycemia; Liver; Liver Neoplasms; Male; Neoplasm Metastasis; Pancreatic Neoplasms; Radiography; Stomach; Zollinger-Ellison Syndrome

Topics: Acidosis; Adenoma, Islet Cell; Adult; Autopsy; Diarrhea; Female; Fluorescent Antibody Technique; Gastric Juice; Gastrins; Gastrointestinal Hormones; Humans; Hypokalemia; Liver Neoplasms; Male; Neoplasm Metastasis; Pancreatic Neoplasms; Peptides; Radioimmunoassay; Secretin; Syndrome

Topics: Adenoma, Islet Cell; Adult; Aged; Duodenal Ulcer; Female; Gastrins; Humans; Liver Neoplasms; Male; Neoplasm Metastasis; Zollinger-Ellison Syndrome

A patient with a multiple-hormone-producing islet cell carcinoma, who had previously been successfully treated with streptozotocin, was given three further infusions of this drug because of the redevelopment of gastric hypersecretion. Although some evidence of damage to the gastrinsecreting cells was obtained, the fasting plasma gastrin was not significantly altered and the patient died from a perforated duodenal ulcer. Serum insulin levels were considerably reduced and the patient became mildly diabetic but the main complication of treatment was a severe though reversible renal tubular defect. At necropsy considerable quantities of gastrin, but low levels of insulin and glucagon were extracted from a tumour metastasis.

Topics: Acetoacetates; Adenoma, Islet Cell; Antibiotics, Antineoplastic; Autopsy; Blood Glucose; Diabetes Insipidus; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Glucagon; Glucosamine; Humans; Insulin; Kidney Tubules; Lactates; Liver Neoplasms; Middle Aged; Mutagens; Neoplasm Metastasis; Nitroso Compounds; Nitrosourea Compounds; Peptic Ulcer Perforation; Pyruvates; Urea

Topics: Adolescent; Adult; Female; Follow-Up Studies; Gastrectomy; Gastrins; Humans; Hypophysectomy; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Prognosis; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Antibiotics, Antineoplastic; Blood Glucose; Female; Gastrins; Glucagon; Hormones, Ectopic; Humans; Hypoglycemia; Insulin; Insulin Secretion; Liver Neoplasms; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms; Radionuclide Imaging

Topics: Child; Gastrins; Humans; Liver Neoplasms; Neoplasms; Pancreatic Neoplasms; Pathology; Zollinger-Ellison Syndrome