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The previously unreported ultrasonographic (US) features of liver metastases of pancreatic glucagonoma and of pancreatic acinar cell carcinoma are described. They present as complex masses with hyperechoic solid component, containing echo-free cystic areas; these sonographic features markedly differ from the echo-poor US pattern of the much more common metastases of pancreatic ductal carcinoma. Survival from diagnosis of liver metastases was 45 months in the patient with pancreatic glucagonoma and 23 months in the patient with acinar cell carcinoma. These survivals were much longer than the expected survival of patients with pancreatic ductal carcinoma metastatic to the liver. The US finding of highly reflective lesions in the liver, containing echo-free cystic areas, should alert one that the primary pancreatic tumor has a histotype different from ductal carcinoma. Such US findings could affect the decision to resect the pancreatic tumor and its liver metastases, if histology confirms a malignancy less aggressive than ductal carcinoma.

In an open phase III study, octastatin was given as a continuous subcutaneous (s.c.) infusion to 35 patients (mean age 62 years) with malignant neuroendocrine gastro-intestinal tumours and the carcinoid syndrome. The wash-out was often incomplete because of the advanced stage of disease. The starting dose of 1.5 mg/24 h was increased up to 3.0 mg/24 h at 3 months in some patients. The carcinoid syndrome disappeared in 20% of patients at 3 months and in 23% at 6 months, with 43 and 45% of patients, respectively, experiencing an improvement. The mean Karnovsky index increased by > 10% in 40% of patients at 3 and 6 months. Urinary 5-hydroxyindoleacetic acid (U-5-HIAA) levels at 3 months normalised in 1 patient, fell in 20% (by > 50%; p = 0.0021) and stabilised in 66%. The respective values at 6 months were 1, 17% (p = 0.023) and 60%. There was also a significant decrease in plasma chromogranin levels at 3 months (p = 0.042), which did not persist at 6 months. Tumour size fell (by > 50%) in 1 patient by 6 months but this patient had undergone chemoembolisation one month prior to the start of the study. Most patients had tumour size stabilisation (76 and 68%) or progression (20 and 24%) at 3 and 6 months, respectively. Dose escalation from 1.5 to 3.0 mg did not significantly improve clinical, biochemical or tumour responses. The treatment was well tolerated with minor adverse events. In an open pilot phase II study of 19 patients (mean age 58 years), patients were given high dose somatuline with a maintenance dose of 12,000 mg/day in 4 divided s.c. injections. U-5-HIAA, which was elevated in 13 patients with a mean of 444 mumol/day before the start, was reduced to 58% of baseline at 3 months, 68% at 6 months (p = 0.04), 66% at 9 months and 75% at 12 months (p = 0.14). P-chromogranin was elevated in 18 patients, with a mean of 5,300 micrograms/l before the start, and was reduced to 52, 55, 63 and 64% of the baseline at 3, 6 (p = 0.039), 9 and 12 (p = 0.013) months, respectively. In the responding patients, apoptosis was induced.

Methods: We used PET to characterize the uptake and decarboxylation of 11C-L-DOPA in vivo in two patients with endocrine pancreatic tumors: one glucagonoma and one gastrinoma., Results: With L-DOPA labeled with 11C in the beta position, in which the radioactive label follows the molecule through decarboxylation to dopamine, significant uptake was observed in the tumors. With L-DOPA labeled in the carboxyl group, in which the label is rapidly eliminated from the tissue as 11CO2 if decarboxylation takes place, an almost complete lack of uptake is noted., Conclusion: This study shows that, using selective position labeling, an in vivo action of enzymatic activity can be observed with PET and that significant decarboxylation occurs in the tested endocrine pancreatic tumors. Also, marked retention of radioactivity occurs after treatment with somatostatin analogs. It is hypothesized that this is a reflection of a reduction of exocytosis which is induced by this treatment.

Glucagonoma is a rare islet cell tumor of pancreas. Only 122 proven cases have been reported in the English literature so far. Diagnosis of glucagonoma has usually been delayed. The average size of clinically detected glucagonomas was 5.8 cm, and 54.7% of them exhibited metastasis. We describe the case of a 0.7-cm asymptomatic pancreatic glucagonoma. A 45-yr-old female was demonstrated to have a demarcated, small, low echoic mass in the pancreatic head by routine ultrasonography. Table incremental dynamic computed tomography showed a small well-enhanced mass recognized only in an early phase. A 0.7 x 0.7 cm firm nodule on the pancreatic head was excised at operation. Immunohistochemical and ultrastructural studies revealed that this tumor was a glucagon-producing adenoma. This may be the smallest glucagonoma detected by image diagnostics that has been reported in the English literature. Possible early detection of glucagonoma was discussed in this report.

Since December 1993, in the 1st Nuclear Medicine Service of the University of Padua, eleven somatostatin-receptor scintigraphic studies with 111In-labelled pentetreotide have been performed. The patients (6 men and 5 women, age 28-68, mean 45 years) were affected by a variety of tumors which supposedly express somatostatin receptors: 2 meningotheliomatous meningiomas post-surgery; 2 glucagonomas with liver metastases observed on CT; 2 patients with suspicion of insulinoma; 2 carcinoids, one after surgery; 1 ectopic-ACTH Cushing's syndrome; 1 intracranial germinoma, post-surgery, in whom the study was requested to evaluate a doubtful finding of pulmonary metastatic lesion on CT; and 1 acromegaly showing, on MRI, and empty sella turcica occupied by and extraflexion of the lower portion of the chiasmatic cisterna without signs of adenoma and the sphenoidal sinus occupied by tissue wit inflammmatory characteristics. Somatostatin-receptor whole body scintigraphy was performed 4 and 24 hours after intravenous injection of 110 MBq 111In-pentetreotide (Octreoscan 111); spot images were acquired when judged necessary. In one case of glucagonoma, a tomographic scan (SPECT) was also performed to better evaluate the spatial relationship between the primitive pancreatic tumor and surrounding tissues. Focal accumulation of 111In-pentetreotide was scintigraphically detected in 5 of the 11 cases. Intense uptake of the radiopharmaceutical was observed in the meningiomas, in the glucagonomas with liver metastases, and in the case of acromegaly, corresponding to a GH-secreting adenoma. The negative scans seem to be true negative scans with the possible exception of one patient with a still unconfirmed suspicion of insulinoma, still not confirmed.

A phase 3 multicenter clinical study was performed to investigate the efficacy, safety and usefulness of MP-1727, a novel tumor imaging agent which binds to somatostatin receptors, in 23 patients with gastrointestinal hormone producing tumor. The efficacy was graded effective or very effective in 16 cases (76.2%) out of 21 cases who could be evaluated. Positive predictive accuracy was 77.8% (7/9) for carcinoids, 100% (5/5) for gastrinomas and 40.0% (2/5) for insulinomas. In three cases, tumor lesions which had been unknown were detected by MP-1727 scintigraphy. The consistent ratio between scintigraphically positive sites and preinjection localizations was 82.0% (41/50 sites) in total. Although adverse drug reactions were observed in two cases, the safety was graded 'not problematic at all' in all of 23 cases. These results show that MP-1727 is a very useful radiopharmaceutical for detection and localization of gastrointestinal hormone producing tumors.

It was the aim of the present study to examine whether 111In-pentetreotide, a somatostatin analogue with predominantly renal excretion, is a suitable receptor agonist for scintigraphic imaging of endocrine gastro-entero-pancreatic (GEP) tumors, and to evaluate the contribution of the usual imaging times 4 and 24 h p.i. In 36 patients, planar scintigrams obtained 4 h, and 24 h after i.v. injection of 111 or 222 MBq 111In-pentetreotide were compared to the results of other imaging procedures and of surgery. Single photon emission computed tomography (SPECT) was also performed 24 h p.i. Positive scintigraphies were obtained in 32 out of 36 patients (18/19 patients with carcinoid syndrome, 8/9 with non hormone-producing endocrine GEP tumors, 2/4 with gastrinomas, 1/1 with glucagonoma, 1/1 with a VIPoma, 2/2 with paragangliomas). In 9 patients tumor manifestations previously not detected by conventional imaging procedures were disclosed by 111In-pentetreotide scintigraphy. 24-h images yielded significantly more true positive findings than 4-h images. In 4 patients liver metastases missed on planar scans were detected by SPECT. A discrepancy between patient-based and organ-based analysis of the results was encountered thus indicating a possible intraindividual heterogeneity in somatostatin receptor expression. In conclusion, 111In-pentetreotide is a suitable somatostatin analogue for scintigraphic in vivo demonstration of somatostatin receptors and for imaging of most tumor manifestations in patients with endocrine GEP tumors. Further studies will have to evaluate whether or not a positive receptor scintigraphy predicts response to treatment with long-acting somatostatin analogues.

Unlabelled: Uptake of 123I-Tyr-3-octreotide (TOCT) by hormone-secreting abdominal tumors was studied to compare scintigraphic observations with the reduction in hormone levels brought about by a brief therapeutic test., Methods: A prospective study was conducted on 17 patients, totalizing 46 proven lesions, with endocrine tumors of the pancreas (10 patients, 20 lesions) and/or carcinoid metastases (8 patients, 26 lesions). Tumor hormonal hypersecretion was inhibited by octreotide., Results: There was good agreement between the results of these examinations., Conclusions: The detection of abdominal tumors using this radiotracer is strongly related to its functional characteristics. Variations in the scintigraphic and test results according to different tumor types were in agreement with published data on the density of somatostatin receptors measured by in vitro studies or scintigraphy and by the therapeutic effects of octreotide.

Findings at CT, MR imaging and angiography in 29 patients with pancreatic apudomas are presented. CT and angiography were performed in all the patients, MR imaging in 10. Twenty-five patients underwent laparotomy. The ability of the different imaging methods to localize the primary tumor and detect hepatic metastases was compared. CT and MR imaging depicted the primary tumor in 79% and 88% of the cases respectively, angiography in 72%. Enhancement patterns at CT and signal intensity variations at MR imaging were unspecific parameters regarding different types of tumors. CT and MR imaging were considerably more accurate than angiography in evaluating local tumor resectability. Angiography revealed more numerous small hepatic metastases (< 0.5 cm) than CT or MR imaging, but missed metastases in the left lobe in 5 patients. MR imaging seems promising in localizing and characterizing pancreatic apudomas, but further evaluation is needed before any conclusion can be drawn. At present dynamic incremental CT seems mandatory in the evaluation of pancreatic apudomas. Angiography is of value for preoperative and preembolization vascular mapping, and in localizing small pancreatic apudomas not shown at CT or MR imaging. Faster dynamic thin slice CT scanning and fast-sequence MR imaging may increase the sensitivity of detecting small primary pancreatic apudomas.

Mucosal thickening in the small bowel was seen on computed tomography (CT) in a patient with a pancreatic glucagonoma. A small bowel series demonstrated multiple fine filling defects throughout both jejunum and ileum associated with moderate fold thickening and prolonged transit time. Villous hypertrophy was indeed identified in a resected segment of jejunum. Elevated blood levels of enteroglucagon have previously been associated with small intestinal villous hypertrophy. Careful scrutiny of the bowel pattern on CT scans may suggest abnormalities which may then be confirmed by conventional barium studies. Such observations may change the evaluation of a clinical problem.

Four patients with metastatic glucagonoma are described. Angiography demonstrated a small avascular primary tumor of the tail of the pancreas in one patient and large hypervascular tumors of the pancreatic head in the other three. Liver metastases, were hypervascular in all four. Including our 4 with 21 cases from the literature, glucagonomas show a 92% incidence of increased tumor vascularity--thus increasing the likelihood of successful angiographic diagnosis. The awareness of clinically subtle or atypical glucagonomas and use of plasma glucagon determination are important factors leading to early diagnosis of these neoplasms. Since angiography can localize the tumor, assess its extent, and detect hepatic metastases, it is essential to the detailed evaluation of glucagonomas.

Seven patients with clinical features of the glucagonoma syndrome, including the characteristic rash, diabetes mellitus, and weight loss, were examined by CT. Computed tomography demonstrated a primary pancreatic tumor in all patients, and, in four, hepatic metastases were identified. The primary tumors, relatively large and solid in nature, varied in size from 2.5 to 6 cm in maximum diameter. The tumor was found in the tail of the pancreas in three patients and in the head of the pancreas in four. No obliteration of adjacent perivascular or peripancreatic fat planes was observed in any patient. Calcification was present in the primary tumor in three patients and in the hepatic metastases in one. All tumors that were studied angiographically were found to be hypervascular. In contrast to insulinomas, which are frequently quite small when clinically diagnosed, glucagonomas appear to attain considerable size prior to being clinically apparent. Thus, we conclude that CT ought to become the mainstay in the identification, localization, and staging of these tumors.

The authors report two cases of glucagonoma, a rare endocrine tumor of the pancreas, and describe the data currently found in literature. Glucagonoma is a single and usually large tumor, which develops in the alpha cells of the islets of Langerhans and evolves slowly. The combination of characteristic skin lesions, diabetes and weight loss should lead to searching for hyperglucagonemia and for the pancreatic tumor. The diagnosis is usually made rather late, average evolution is five years before diagnosis when it is detected. Imaging, in particular ultrasound and computed tomography (CT), proves to be necessary for the positive diagnosis of glucagonoma as it localizes the pancreatic mass and plays a role in local assessment, thus providing guidance for surgery. The role of imaging is also fundamental for the detection of metastases, which are the only sign of malignancy as no criterion of benignity is found for this tumor.

From the non-B-cell tumors of the pancreas the gastrinoma (Zollinger-Ellison-syndrome) is the best known. The glucagonoma and the vipoma are less known and less common. The diagnosis of these syndroms, produced by overproduction of hormones, is a clinical one. The radiodiagnost has to localize the primary tumor and to exclude metastases. The x-ray findings of the glucagonoma in 3 patients and of the vipoma in 1 patient are described.

A case of glucagonoma where repeated gastrointestinal examinations revealed excessive mucosal fold thickening of the duodenum and small bowel with a markedly delayed transit time is reported. These findings in the appropriate clinical setting led us to persevere with further investigations despite equivocal ultrasound and CT examinations. We wish to emphasize the importance of the classical gastrointestinal findings in the diagnosis of the glucagonoma syndrome.

Diffuse mucosal granularity was reported recently in small bowel Crohn's disease. The radiographic appearance corresponded on histopathologic examination to villous hypertrophy, fusion, or epithelial bridge formation. We have observed similar granularity in Crohn's disease but also in several other conditions, including radiation enteritis, pancreatic glucagonoma, protein-losing enteropathy, and small bowel ischemia. Histopathologic examination demonstrated various alterations in villous morphology, such as edema, hyperplasia, clubbing, or fusion. In Crohn's disease, this appearance was sometimes an indication of early inflammatory disease but was also seen following extensive small bowel resection, possibly due to villous enlargement resulting from intestinal adaptation. These findings suggest that granular mucosa in the small bowel is a nonspecific finding reflecting an alteration in villous structure.