| 1. |
- Ahlman, Håkan, 1947, et al.
(author)
-
Aspects on diagnosis and treatment of the foregut carcinoid syndrome.
- 1992
-
In: Scandinavian journal of gastroenterology. - 0036-5521. ; 27:6, s. 459-71
-
Journal article (peer-reviewed)abstract
- Eight patients with the foregut carcinoid syndrome (two gastric and six bronchial primary tumors) are reported. The patients presented with complex clinical symptoms including ectopic production of adrenocorticotrophic hormone and growth hormone-releasing factors. The most alarming symptoms were facial flush and edema, accompanied by severe bronchoconstriction, which easily was misinterpreted as asthmatic attacks. Conventional bronchodilatory drugs may be potentially dangerous in these patients, in whom combined blockade of histamine receptors and treatment with cortisone and octreotide are recommended. Owing to the patients' age and general condition individualized long-term therapy was instituted. Surgical therapy under optimal protection by drugs can be of substantial value also in patients with advanced disease. One patient with life-threatening hormonal symptoms underwent hyperthermic perfusion of the liver with cytotoxic drugs, resulting in good palliation.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Ahlman, Håkan, 1947, et al.
(author)
-
Clinical efficacy of octreotide scintigraphy in patients with midgut carcinoid tumours and evaluation of intraoperative scintillation detection.
- 1994
-
In: The British journal of surgery. - 0007-1323. ; 81:8, s. 1144-9
-
Journal article (peer-reviewed)abstract
- 111In-diethylenetriamine penta-acetate-D-Phe1-octreotide scintigraphy was evaluated in a group of 27 patients with disseminated midgut carcinoid tumour. Additional information gained by the intraoperative use of a scintillation detector was studied in five patients with midgut carcinoid tumours and in two with endocrine pancreatic tumours. In 19 patients tumours not recognized by non-invasive radiological methods were visualized in 27 locations, most commonly in liver and para-aortic lymph nodes. Three false-negative tumour locations were noted (ovarian and peritoneal). With guidance from scintigraphic findings, nine patients underwent surgical tumour reduction, leading to complete remission in three. Clinically suspect tumour lesions were measured by the detector in situ, and ex vivo after excision. After excision the tissue:blood activity concentration ratios were calculated. In situ measurements were helpful in the localization of tumours and in the control of adequate clearance of tumour tissue. High tissue:blood activity concentration ratios at 1, 2 and 5 days in the five patients with midgut carcinoid tumour indicate a potential role for radiation therapy with radiolabelled octreotide in patients with somatostatin receptor-positive tumours.
|
|
| 5. |
- Ahlman, Håkan, 1947, et al.
(author)
-
Clinical management of gastric carcinoid tumors.
- 1994
-
In: Digestion. - 0012-2823. ; 55 Suppl 3, s. 77-85
-
Journal article (peer-reviewed)abstract
- Four types of gastric carcinoids have been identified: (1) multiple small body-fundus carcinoids associated with chronic atrophic gastritis type A (A-CAG); (2) sporadic solitary lesions without specific pathogenetic background (non-A-CAG); (3) carcinoidosis associated with Zollinger-Ellison/MEN 1 syndrome, and (4) rare tumors, e.g. gastrin cell tumors, neuroendocrine carcinomas and mixed endocrine-exocrine tumors. In a retrospective study of 15 patients with gastric carcinoids (11 A-CAG, 3 non-A-CAG and 1 gastrin cell tumor) over a 10-year period, the histopathological and clinical features were assessed. The A-CAG-type carcinoids were clinically silent with lymph node metastases in 2/11 cases but no hepatic metastases. The non-A-CAG-type carcinoids were malignant with disseminated disease, hormonal symptoms and increased urinary excretion of the main histamine metabolite, MeImAA. Five patients with A-CAG tumors were subjected to antrectomy to remove hypergastrinemia, which is thought to be of pathogenetic importance for these tumors. During the observation period (1.5-8 years) 1 patient developed recurrent tumors, while the other 4 showed persistent argyrophil cell hyperplasia. A prospective treatment protocol of these tumors is suggested with endoscopic removal of less numerous, small lesions as first-step therapy, followed by antrectomy at recurrence. Larger lesions should be excised in combination with antrectomy. Gastrectomy is reserved for the rare cases of invasive tumors with lymph node metastases. As evident from the outcome of patients with non-A-CAG tumors radical surgery should be performed whenever practicable.
|
|
| 6. |
- Ahlman, Håkan, 1947, et al.
(author)
-
Growth regulation in carcinoid tumors.
- 1993
-
In: Endocrinology and metabolism clinics of North America. - 0889-8529. ; 22:4, s. 889-915
-
Research review (peer-reviewed)abstract
- In hormone-producing tumors such as the carcinoids, overproduction of certain hormones may activate proto-oncogenes. Hormones, or growth factors, thus can be of importance for growth regulation. Information is presented on some growth factors and their receptors in this respect and on the involvement of gastrin and its receptor on tumor development in the experimental Mastomys model. The relevance of differential expression of cell adhesion molecules in endocrine tumors is discussed also.
|
|
| 7. |
|
|
| 8. |
- Ahlman, Håkan, 1947, et al.
(author)
-
Somatostatin receptors on neuroendocrine tumors--a way to intraoperative diagnosis and localization.
- 1994
-
In: The Yale journal of biology and medicine. - 0044-0086. ; 67:3-4, s. 215-21
-
Journal article (peer-reviewed)abstract
- Intraoperative radionuclide detection using 111In-DTPA-D-Phe1-octreotide was evaluated in five patients with midgut carcinoids and in three patients with recurrent medullary thyroid carcinoma. Three different time intervals (24, 48 and 120 hr) from injection of the radiopharmaceutical to surgery were used. At surgery, suspect tumors were measured by probe in situ and ex vivo after excision. All tissue specimens and blood samples withdrawn during surgery were measured for 111In activity, and tissue/blood activity concentration ratios were calculated. In situ measurements were valuable especially in neck surgery, where the probe was helpful not only in localization of tumors but also in the control of tumor clearance. Ex vivo measurements were helpful in diagnosing tumor tissue. All five patients with midgut carcinoids were somatostatin receptor-positive, while only three out of seven patients with medullary thyroid carcinoma were receptor-positive. The tissue/blood activity concentration ratios and probe measurement ratios were in general higher in patients with midgut carcinoid than in patients with medullary thyroid carcinoma. Of particular interest were the high tissue/blood concentration ratios in all receptor-positive patients at all time intervals studied. This fact suggests a potential role for radiolabelled octreotide in radiotherapy of these tumor types.
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
- Nilsson, Ola, 1957, et al.
(author)
-
Growth factors and carcinoid tumours.
- 1993
-
In: Acta oncologica (Stockholm, Sweden). - 0284-186X. ; 32:2, s. 115-24
-
Journal article (peer-reviewed)abstract
- The presence of growth factors and their receptors in human midgut carcinoids and in gastric carcinoids of Mastomys have been investigated. Human midgut carcinoid tumours produce IGF-I as demonstrated by immunocytochemistry and radioimmunoassay. IGF-I receptors were detectable in half of the tumours and stimulation of cultured tumour cells with IGF-I enhanced DNA synthesis. IGF-I may therefore act as an autocrine stimulator of carcinoid tumour growth. Expression of TGF-alpha and EGF-receptors could also be demonstrated in midgut carcinoids by immunocytochemistry and Northern analysis, suggesting that TGF-alpha participates in the autocrine modulation of carcinoid growth. Co-culture of human midgut carcinoid tumours and rat fetal cholinergic neurons demonstrated secretion of a potent neuronotrophic factor by cultured tumour cells. IGF-I and TGF-alpha may account for these neuronotrophic effects, but carcinoid tumours may also secrete an as yet unidentified growth factor. Gastric (ECL cell) carcinoids developed rapidly in Mastomys during hypergastrinemia due to histamine2-receptor blockade, suggesting that gastrin is an essential growth factor for these carcinoids.
|
|
| 12. |
- Nilsson, Ola, 1957, et al.
(author)
-
Human pheochromocytoma cells studied in culture contain large amounts of DSIP-like material.
- 1991
-
In: Peptides. - 0196-9781. ; 12:5, s. 1077-83
-
Journal article (peer-reviewed)abstract
- Delta sleep-inducing peptide (DSIP)-like immunoreactive (LI) material has been detected in nine different human pheochromocytoma tumors by immunocytochemistry. In primary tumors subjected to indirect immunofluorescence a variable number of tumor cells (25-75%) showed positive cytoplasmic labeling after incubation with DSIP antiserum. Tumor cells grown in culture were strongly labeled by the DSIP antiserum with DSIP-LI concentrated to cell bodies. Electron microscopic immunocytochemistry (immunogold labeling) of pheochromocytoma cells demonstrated DSIP-LI over the dense core of secretory granules. The presence of DSIP-LI in several HPLC fractions from conditioned culture media indicates secretion of DSIP-LI from cultured pheochromocytoma cells. The observations suggest that DSIP-LI is synthesized and stored in secretory granules before release. The different HPLC profiles from each of the tumors may reflect differences in processing or turnover of DSIP-LI in pheochromocytoma cells.
|
|
| 13. |
|
|
| 14. |
- Nilsson, Ola, 1957, et al.
(author)
-
Praomys (Mastomys) natalensis: a model for gastric carcinoid formation.
- 1992
-
In: The Yale journal of biology and medicine. - 0044-0086. ; 65:6
-
Journal article (peer-reviewed)abstract
- The gastric carcinoid tumors of Praomys (Mastomys) natalensis have been reviewed with respect to histogenesis, development, biochemistry, and morphological properties. Multicentric gastric carcinoids frequently develop in the oxyntic mucosa of aging Mastomys. The development of these tumors can be significantly enhanced by drug-induced hypergastrinemia, e.g., histamine2-receptor blockade. Spontaneous and drug-induced gastric carcinoids are endocrine in nature, as evidenced by their argyrophilic staining properties and chromogranin A content. They are also rich in histidine decarboxylase activity and produce large amounts of histamine, although other hormones, such as peptide YY and enteroglucagon, have also been demonstrated in these tumors. Ultrastructurally, gastric carcinoids are composed of tumor cells with typical secretory granules resembling those of enterochromaffin-like (ECL) cells. A close examination of the gastric carcinoids in Mastomys reveals striking similarities with gastric carcinoids developing in humans suffering from chronic atrophic gastritis type A or from the Zollinger-Ellison syndrome in combination with multiple endocrine neoplasia type 1 (MEN-1). Both these conditions are associated with hypergastrinemia and a higher risk for developing multi-centric gastric carcinoids of ECL-cell origin. The Mastomys tumor model therefore appears to be a significant experimental model in which induction and formation of gastric carcinoid tumors can be studied.
|
|
| 15. |
- Nilsson, Ola, 1957, et al.
(author)
-
Presence of IGF-I in human midgut carcinoid tumours--an autocrine regulator of carcinoid tumour growth?
- 1992
-
In: International journal of cancer. Journal international du cancer. - 0020-7136. ; 51:2, s. 195-203
-
Journal article (peer-reviewed)abstract
- The presence of IGF-I and IGF-I receptors in human midgut carcinoid tumours has been investigated. Using immunocytochemistry, IGF-I-positive tumour cells were demonstrated in 11/11 tumour cases studied. Labelling of consecutive sections with antibodies against IGF-I and proliferating cell nuclear antigen (PCNA)/cyclin demonstrated a co-distribution of the 2 antigens in carcinoid tumours. Extracts of tumour tissues were subjected to radioimmunoassay and shown to contain significant amounts of IGF-I. Reverse-phase HPLC of tumour extracts demonstrated a major IGF-I-immunoreactive component eluting in the position of rhIGF-I, but also 2 other more hydrophobic forms. Conditioned serum-free media from primary cultures of carcinoid tumors contained detectable amounts of IGF-I, indicating a spontaneous release of IGF-I from tumour cells into the culture medium. Levels of IGF-I in media were reduced (19%) after incubation of cultures with a somatostatin analogue for 4 days. IGF-I receptors were observed on tumour cells in 4/10 tumours by immunocytochemistry. Tumour cells with immunoreactive IGF-I receptors could be stimulated to enhanced growth, measured as an increase in DNA contents, by exogenous administration of IGF-I every 3-4 days for 2 weeks. The results show that cultured human midgut carcinoid tumours secrete IGF-I and that some of the tumours also have IGF-I receptors. We therefore suggest that IGF-I may act as an autocrine or paracrine regulator of carcinoid tumour-cell growth.
|
|
| 16. |
- Wängberg, Bo, 1953, et al.
(author)
-
Amine handling properties of human carcinoid tumour cells in tissue culture.
- 1990
-
In: Neurochemistry international. - 0197-0186. ; 17:2, s. 331-41
-
Journal article (peer-reviewed)abstract
- Carcinoid tumour tissue from two patients was removed from lymph node metastases during surgery. Under sterile conditions the cells were prepared for tissue culture, and grew in clusters for a period of 3-4 weeks. Using immunofluorescence the neoplastic cells were investigated for the presence of various antigens characteristic for other amine handling cell types (adrenal medullary cells, adrenergic neurons, endocrine cells); thus, the presence of catecholamine synthesizing enzymes, 5-HT, MAOs, neuron specific enolase, synaptophysin, chromogranin A and neurofilaments was demonstrated in the carcinoid tumour cells. Also ?-adrenoceptor-like immunoreactivity was present, as was NGF-like immunoreactivity. The amine handling properties were investigated by measuring spontaneous and drug-induced release of 5-HT into the culture medium. Reserpine enhanced the 5-HT levels in the medium, and this was further potentiated by the MAO-inhibitor nialamide or the membrane pump blocker imipramine. The 5-HT synthetic capacity was pronounced, as indicated by measuring the cumulative 5-HT release into the medium after frequent changes of media (at 1 h intervals). If media were changed every 4 d 5-HT levels reached a saturation. In the fluorescence microscope the effect of reserpine in depleting the 5-HT stores was slow; at 24 h of reserpine presence in the media many cells still contained strong 5-HT fluorescence (partly with an agranular appearance) while some cells appeared depleted. Thus, there was a striking difference between individual cells in the reaction to reserpine. ?-Adrenoceptor activation with isoprenaline released 5-HT into the medium in a dose-dependent manner, not blocked by propranolol. This indicates unusual properties of the ?-adrenoceptor, also demonstrated to be present on these neoplastic cells by immunocytochemistry.
|
|
| 17. |
- Wängberg, Bo, 1953, et al.
(author)
-
Embolisation therapy in the midgut carcinoid syndrome: just tumour ischaemia?
- 1993
-
In: Acta oncologica (Stockholm, Sweden). - 0284-186X. ; 32:2, s. 251-6
-
Journal article (peer-reviewed)abstract
- Forty-eight patients with midgut carcinoid tumours and disseminated disease were treated at our unit 1986-1991. All patients underwent primary surgery with optimal tumour reduction. Twenty-seven patients with bilobar liver metastases had subsequent embolizations of the hepatic arteries to further reduce the functional tumour mass and were thereafter treated with a low dose of octreotide. The response to this treatment was evaluated by CT at 3 months postembolization. The patients could then be divided into 13 responders (no visible hepatic tumours or more than 50% reduction, group I) and 14 non-responders (less than 50 reduction or progression, group II). When these patients were studied biochemically and in terms of prognosis, the reduction of 5-HIAA levels postembolization was much more pronounced in group I (80 +/- 3%) then in group II (28 +/- 12%). The biochemical and radiological responses were long-lasting in group I, none of the patients needed further ischaemic treatment. Of specific interest were 3 patients with bilobar disease, who after selective unilobar embolisation normalised their 5-HIAA levels and had bilateral tumour regression. These findings indicate involvement of systemic effects in addition to tumour ischaemia alone. The initial biochemical response with marked decrease of 5-HIAA levels in combination with tumour regression may thus serve as an indicator of good prognosis.
|
|
| 18. |
- Wängberg, Bo, 1953, et al.
(author)
-
The effect of a somatostatin analogue on the release of hormones from human midgut carcinoid tumour cells.
- 1991
-
In: British journal of cancer. - 0007-0920. ; 64:1, s. 23-8
-
Journal article (peer-reviewed)abstract
- The use of a somatostatin analogue (SMS 201-995) has greatly facilitated the treatment of patients with the midgut carcinoid syndrome. Clinical studies have shown that SMS reduces the peripheral levels of tumour-produced serotonin (5-HT) and tachykinins, e.g. neuropeptide K (NPK), basally and after pentagastrin provocation. Some studies have indicated an inhibitory effect of SMS on tumour cell growth as well. In the present study we have investigated the effects of SMS on four different human midgut carcinoid tumours maintained in long term culture. Media levels of 5-HT and NPK-LI in tumour cell cultures decreased rapidly during incubation with SMS (10(-8)-10(-10) M) in all four tumours studied without evidence for tachyphylaxis (up to 6 weeks observation period). SMS treatment (10(-8) M) during 4 days reduced the media concentrations of 5-HT by 56%, while the intracellular contents of 5-HT were decreased by 27% indicating dual inhibitory effects on synthesis and secretion of 5-HT from tumour cells. The DNA contents of cultures were not affected by SMS (10(-8) M or 10(-10) M) treatment for 4 or 14 days. When tumour cell cultures were challenged with isoprenaline (IP) (10(-6) M) no reduction of the IP induced release of 5-HT could be detected after pretreatment of tumour cell cultures with SMS (10(-8) M) for 1 h, 4 h or 4 days. These studies provide evidence for a direct action of the somatostatin analogue on midgut carcinoid tumour cells, reducing both synthesis and secretion of hormones from tumour cells. This effect appears not to be related to inhibition of tumour cell growth. The inhibition of 5-HT secretion from tumour cells by SMS seems to operate via a second messenger system different from the one mediating the beta-adrenoceptor stimulated release of 5-HT.
|
|
