Presentation of a PTHrP-secreting pancreatic neuroendocrine tumour, with hypercalcaemic crisis, pre-eclampsia, and renal failure. (49/805)

Severe hypercalcaemia during pregnancy is rare and most cases are secondary to hyperparathyroidism. This is the first report of a parathyroid hormone related protein (PTHrP) secreting neuroendocrine tumour of the pancreas manifesting with severe hypercalcaemia during pregnancy. Measurement of PTHrP was useful in both the diagnosis and follow up of our patient and should be considered in the diagnostic workup of patients with unexplained hypercalcaemia. A raised PTHrP concentration is a strong indicator of malignancy.  (+info)

Minimal effects of dietary restriction on neuroendocrine carcinogenesis in Rb+/- mice. (50/805)

The efficacy of dietary restriction in retarding tumor growth is well established in rodents. However, gene and cell lineage specificity of dietary restriction effects is far less defined. Mice with a single copy of the retinoblastoma susceptibility gene (Rb) develop a well-established syndrome of mouse neuroendocrine neoplasia associated with Rb deficiency. Thus, if DR represses tumor growth in this model, it should be unambiguously attributed to the Rb defect in neuroendocrine cell lineages. To address this possibility, Rb(+/-) mice were entered into a diet restriction study. Surprisingly, 40-50% reductions in dietary intake, relative to an ad libitum group, started on either postnatal day 28 or 42 had little to no effect on either the frequency or growth of pituitary tumors either during the latency period (postnatal day 224) or at the time of their natural death. Consistent with cross-section data, survival of 65 diet restricted Rb(+/-) mice was almost identical to that of 67 Rb(+/-) mice fed ad libitum (AL); median life span was 414 and 436 days for AL and DR groups, respectively. These findings indicate that diet restriction provides no significant benefit in delaying growth and progression of neuroendocrine tumors exhibiting loss of RB function. They also introduce the possibility that RB is required for the tumor-repressive effects of DR.  (+info)

Somatostatin receptor scintigraphy in liver metastasis detection from gastroenteropancreatic neuroendocrine tumors. (51/805)

In patients with gastroenteropancreatic (GEP) neuroendocrine tumors, we investigated the usefulness of somatostatin receptor scintigraphy (SRS) in the detection of liver metastasis, which represents the most important prognostic factor in these tumors, and in the management of affected patients. METHODS: We enrolled 149 patients with GEP tumors, 69 during initial staging and 80 in follow-up. All patients underwent whole-body scanning at 4 and 24 h, followed by abdominal planar and SPECT imaging after intravenous injection of 250 MBq (111)In-pentetreotide. The patients had previously been submitted to 2 of 3 conventional imaging procedures (CIP), such as CT, MRI, and ultrasound of the abdomen within 1 mo before SRS; on the basis of liver CIP data, the patients had been classified into 3 groups as follows: no evidence of liver metastases, the presence of resectable metastases, or the presence of nonresectable metastases. RESULTS: Liver metastases were histologically proven in 65 cases. SPECT identified malignant lesions in 60 of 65 patients with metastases (sensitivity, 92.3%), planar imaging identified malignant lesions in 38 of 65 patients (sensitivity, 58.5%), and CIP identified malignant lesions in 52 of 65 patients (sensitivity, 80%). Only SPECT demonstrated liver involvement in 13 patients, whereas CIP showed liver involvement in 5 other cases. Moreover, SPECT was significantly more sensitive than planar imaging and CIP in identifying patients with single lesions. Neither SPECT nor planar imaging showed false-positive results in patients with no evidence of liver metastases, including 21 patients with hemangiomas (specificity, 100%), 12 of which were false-positive on CIP (specificity, 85.7%). SPECT per-lesion sensitivity (92.4%) was significantly higher than that of planar imaging (52.4%) and CIP (79.4%). Moreover, SPECT correctly changed patient classification and, thus, management in 28 of 149 patients (18.8%), whereas planar imaging changed classification in 13 patients (8.7%), identifying new or additional metastases not evident on CIP or excluding metastases on CIP of patients with false-positive findings, thus avoiding unnecessary surgery; however, SPECT classification was incorrect in 3.3% of patients, and planar imaging was incorrect in 17.4%. CONCLUSION: (111)In-Pentetreotide SRS is a useful diagnostic tool in the detection of liver metastases in GEP tumor patients. In particular, SPECT proved to be significantly more sensitive and accurate than both planar imaging and CIP. Moreover, SPECT was also the most reliable procedure to obtain correct patient classification, thus guiding the most appropriate therapeutic strategy.  (+info)

Acute pancreatitis secondary to pancreatic neuroendocrine tumours. (52/805)

CONTEXT: Pancreatic neoplasms are an uncommon aetiology of acute pancreatitis. Pancreatic neuroendocrine tumours are a rare subgroup of pancreatic neoplasms. CASE REPORT: We report on three patients having acute pancreatitis secondary to pancreatic neuroendocrine tumours, one of them with severe pancreatitis, and review the published cases up to now. Only 22 patients with acute pancreatitis secondary to pancreatic neuroendocrine tumours have been reported (including the present cases). Most of these cases were of non-functioning neoplasms and the course of the pancreatitis tended to be mild. In the most recent reports and in the present cases, the initial diagnostic method was CT scan. Less than half had metastases when the tumour was diagnosed and mortality from these neoplasms reached approximately 50%. CONCLUSIONS: Pancreatic neuroendocrine tumours can cause acute pancreatitis even in patients under 50 years of age. On many occasions, the tumours are non-functioning; therefore, acute pancreatitis may be the first clinical symptom. Consequently, faced with acute pancreatitis of unknown origin, a non-functioning neuroendocrine tumour should be ruled out.  (+info)

Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA(0),Tyr3]octreotate. (53/805)

Medical treatment and chemotherapy are seldom successful in achieving objective tumour reduction in patients with metastatic neuroendocrine tumours. Treatment with the radiolabelled somatostatin analogue [(90)Y-DOTA(0),Tyr(3)]octreotide may result in partial remissions in 10-25% of patients. The newer analogue [DOTA(0),Tyr(3)]octreotate (octreotate) has a ninefold higher affinity for the somatostatin receptor subtype 2 as compared with [DOTA(0),Tyr(3)]octreotide. Also, labelled with the beta- and gamma-emitting radionuclide (177)Lu, it has proved very successful in achieving tumour regression in animal models. The effects of (177)Lu-octreotate therapy were studied in 35 patients with neuroendocrine gastro-entero-pancreatic (GEP) tumours who underwent follow-up for 3-6 months after receiving their final dose. Patients were treated with doses of 100, 150 or 200 mCi (177)Lu-octreotate, to a final cumulative dose of 600-800 mCi, with treatment intervals of 6-9 weeks. Nausea and vomiting within the first 24 h after administration were present in 30% and 14% of the administrations, respectively. WHO toxicity grade 3 anaemia, leucocytopenia and thrombocytopenia occurred after 0%, 1% and 1% of the administrations, respectively. Serum creatinine and creatinine clearance did not change significantly. The effects of the therapy on tumour size were evaluable in 34 patients. Three months after the final administration, complete remission was found in one patient (3%), partial remission in 12 (35%), stable disease in 14 (41%) and progressive disease in seven (21%), including three patients who died during the treatment period. Tumour response was positively correlated with a high uptake on the octreoscan, limited hepatic tumour mass and a high Karnofsky Performance Score. Because of the limited efficacy of alternative therapies, many physicians currently adopt an expectant attitude when dealing with patients with metastatic GEP tumours. However, in view of the high success rate of therapy with (177)Lu-octreotate and the absence of serious side-effects, we advocate its use in patients with GEP tumours without waiting for tumour progression.  (+info)

Effects of interferon alpha on vascular endothelial growth factor gene transcription and tumor angiogenesis. (54/805)

BACKGROUND: Interferon alpha (IFN-alpha) has antiangiogenic activity, although the underlying mechanism of action is unclear. Because human neuroendocrine (NE) tumors are highly vascularized and sensitive to IFN-alpha, we investigated whether the therapeutic effects of IFN-alpha result from an inhibition of angiogenesis mediated by a decrease in vascular endothelial growth factor (VEGF) gene expression. METHODS: VEGF gene and protein expression was analyzed in NE tumors by immunohistochemistry and in NE tumor cell lines by quantitative competitive reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). VEGF promoter-reporter gene constructs containing various deletions or mutations and gel shift assays were used to identify minimal promoter requirements and potential transcription factors. A xenograft nude mouse model (five mice per group) was used to determine the effect of IFN-alpha on tumor growth (NE Bon cells and pancreatic Capan-1 cells) and microvessel density. Liver metastases from eight patients with NE tumors were analyzed for microvessel density, VEGF mRNA content, and VEGF plasma levels before and after initiation of IFN-alpha therapy. RESULTS: NE tumors and cell lines expressed VEGF mRNA and secreted VEGF protein. In vitro, IFN-alpha decreased transcription of VEGF gene expression through an Sp1- and/or Sp3-dependent inhibition of VEGF promoter activity. Compared with vehicle treatment in mice, IFN-alpha inhibited tumor growth by 36% and reduced microvessel density from 56 (95% confidence interval [CI] = 49 to 69) to 37 per x400 Field (95% CI = 32 to 41, P =.015). Patients with NE tumors had lower VEGF plasma levels and reduced VEGF mRNA levels and microvessel density in liver metastasis biopsy material after IFN-alpha treatment. CONCLUSION: IFN-alpha confers its antitumor activity, at least in part, by its antiangiogenic activity, which results from Sp1- and/or Sp3-mediated inhibition of VEGF gene transcription.  (+info)

A comparison between three commercial kits for chromogranin A measurements. (55/805)

Chromogranin (CgA) has been shown to be an excellent marker for neuroendocrine tumours. There are now three commercial assays on the market. We wanted to compare the usefulness of the different kits in a clinical situation. We have thus measured CgA in 77 patients and compared the results from the different methods. CgA was measured with three different commercial kits according to the recommendations from the manufacturers (CGA-RIA CT; CIS bio international, Gif-sur-Yvette cedex, France, DAKO Chromogranin A ELISA kit; DAKO A/S, Glostrup, Denmark and CgA; EuroDiagnostica, Malmo, Sweden). The sensitivity and specificity differed between the different kits. The CIS kit showed a sensitivity of 67% and a specificity of 96%. The sensitivity and specificity were both 85% for the DAKO kit and 93% and 88% respectively for the EuroDiagnostica assay. We have concluded that CgA is an important tumour marker for all neuroendocrine tumours. However, different analytical properties of the respective kits give different performances, a fact that must be taken into consideration when comparing results from different clinical studies. A recognised international standard for CgA would be a step on the way to harmonisation, but antibody selection and construction of the assays will probably still influence the results.  (+info)

NESP55, a novel chromogranin-like peptide, is expressed in endocrine tumours of the pancreas and adrenal medulla but not in ileal carcinoids. (56/805)

Neuroendocrine secretory protein 55, NESP55, is an acidic protein belonging to the chromogranin family. The distribution of NESP55 in human tumours is not known. The aim of the present study was to study the expression of NESP55 in human gastrointestinal, pancreatic and adrenal tumours. A total of 118 human endocrine and nonendocrine tumours were examined by immunocytochemistry, and compared to the expression of chromogranin A (CgA) in the same tumours. Pancreatic endocrine tumours (14 out of 25), pheochromocytomas (19 out of 19), and neuroblastomas (seven out of 14) expressed NESP55, with the same strong labelling pattern in both benign and malignant tumours. Expression of NESP55 in pancreatic endocrine tumours and pheochromocytomas was confirmed by Western and Northern blot analysis. Immunocytochemical analysis demonstrated no labelling in ileal carcinoids (zero out of 15), and adrenocortical adenomas (zero out of 15). The majority of gastrointestinal and pancreatic carcinomas were negative for NESP55, with focal staining observed in two out of 30 tumours. In contrast, CgA was present in all neuroendocrine tumours examined (25 out of 25 pancreatic endocrine tumours, 19 out of 19 pheochromocytomas, 14 out of 14 neuroblastomas and 15 out of 15 ileal carcinoids). Thus, the expression of NESP55 in endocrine tumours of the gastrointestinal tract, pancreas and adrenals differs from that of CgA. Neuroendocrine secretory protein 55 is found in a subset of neuroendocrine tumours showing differentiation towards adrenal chromaffin cells and pancreatic islets cells.  (+info)