| 181. |
- Wängberg, Bo, 1953, et al.
(författare)
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Embolisation therapy in the midgut carcinoid syndrome: just tumour ischaemia?
- 1993
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Ingår i: Acta oncologica (Stockholm, Sweden). - 0284-186X. ; 32:2, s. 251-6
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Tidskriftsartikel (refereegranskat)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.
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| 182. |
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| 183. |
- Wängberg, Bo, 1953, et al.
(författare)
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Intraoperative detection of somatostatin-receptor-positive neuroendocrine tumours using indium-111-labelled DTPA-D-Phe1-octreotide.
- 1996
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Ingår i: British journal of cancer. - 0007-0920. ; 73:6, s. 770-5
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Tidskriftsartikel (refereegranskat)abstract
- After injection of 111In-labelled DTPA-D-Phe1-octreotide, intraoperative tumour localisation was performed using a scintillation detector in 23 patients with neuroendocrine tumours. Count rates from suspect tumour lesions and adjacent normal tissue were expressed as a ratio before (Rin situ) and after (Rex vivo) excision. 111In activity concentration ratios of tumour tissue to blood (T/B) were determined in a gamma counter. In patients with midgut carcinoids, (all scintigraphy positive), false Rin situ recordings were found in 4/29 macroscopically identified tumours. T/B ratios were all high (27-650). In patients with medullary thyroid carcinomas (eight out of ten scintigraphy positive), misleading Rin situ results were found in 4/37 macroscopically identified tumours. T/B ratios were lower (3-39) than those seen in midgut carcinoids. Two out of four patients with endocrine pancreatic tumours had positive scintigraphy, reliable intraoperative measurements and very high T/B ratios (910-1500). One patient with a gastric carcinoid had correct measurements in situ and ex vivo with high T/B ratios (71-210). In situ measurements added little information to preoperative scintigraphy and surgical findings using the present detection system. Rex vivo measurements were more reliable. The very high T/B ratios seen in midgut carcinoids and some endocrine pancreatic tumours would be favourable for future radiation therapy via somatostatin receptors.
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| 184. |
- Wängberg, Bo, 1953, et al.
(författare)
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Malignant pheochromocytoma in a population-based study: survival and clinical results.
- 2006
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923. ; 1073, s. 512-6
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Tidskriftsartikel (refereegranskat)abstract
- One hundred fifty-four consecutive patients with pheochromocytoma (PC, n=137) or paraganglioma (PG, n=17) were treated at our unit. Twenty patients had MEN 2, 15 VRD, and 1 VHL tumors. Twelve had malignant tumors and were classified according to mode of presentation: (1) Distant metastases (n=4); three underwent surgical debulking (with chemotherapy in one); and three had 131I-MIBG therapy. Within 4 years two patients died of tumor progression. (2) Locally advanced disease (n=4), all resected for cure. (3) Malignancy disclosed during follow-up after adrenalectomy with "benign" histopathology (n=4). All patients in groups 2 and 3 developed recurrence 9 (1-17) years after primary surgery; four underwent resection, one remains tumor-free. The others were treated chronically with phenoxybenzamine, combined with 131I-MIBG in one. These eight patients were observed 20 (5-35) years after primary surgery and 11 (1-19) years after recurrence. This series is population-based and may better reflect the natural history of malignant PC/PG than the series from national referral centers. Active surgical treatment and phenoxybenzamine resulted in low tumor-related mortality in groups 2 and 3; five patients died 8-30 years after diagnosis, four of PC/PG (three from group 2 and one from group 3) and one of other causes. We propose tumor uptake studies (MIBG- and octreotide scintigraphy) in patients with nonresectable metastases; to select individual radionuclide therapy data on the expression of CA-transporters/somatostatin receptors may be helpful. To diagnose PC/PG early, screening of adrenal incidentalomas has been suggested. In a regional population-based prospective study, 503 incidentalomas were reported during 18 months, but only one patient with PG was identified.
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| 185. |
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| 186. |
- Wängberg, Bo, 1953, et al.
(författare)
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Somatostatin Receptors in the Diagnosis and Therapy of Neuroendocrine Tumor.
- 1997
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Ingår i: The oncologist. - 1549-490X. ; 2:1, s. 50-58
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Tidskriftsartikel (refereegranskat)abstract
- The expression of somatostatin receptors in neuroendocrine tumors has facilitated the diagnosis and surgical treatment of patients with these tumors. After injection of a radiolabeled long-acting somatostatin analog, (111)In-octreotide, scintigraphic tumor imaging can ben performed as well as intraoperative tumor localization. During localization studies very high (111)In concentration values were found in tumor tissues versus normal tissues, especially in carcinoid tumors and endocrine pancreatic tumors. Studies on such tumors in cell culture further indicated internalization of (111)In into tumor cells, which is a prerequisite for a radiobiological effect from short range Auger and conversion electrons. Attempts to systemic radionuclide therapy via somatostatin receptors in patients with neuroendocrine tumors have been initiated.
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| 187. |
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| 188. |
- Wängberg, Bo, 1953, et al.
(författare)
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Survival of patients with disseminated midgut carcinoid tumors after aggressive tumor reduction.
- 1996
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Ingår i: World journal of surgery. - 0364-2313. ; 20:7, s. 892-9; discussion 899
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Tidskriftsartikel (refereegranskat)abstract
- Sixty-four consecutive patients with disseminated midgut carcinoids were treated during an 8-year period according to a single clinical protocol aimed at aggressive tumor reduction by surgery alone or with subsequent hepatic artery embolization. All patients had markedly elevated urinary 5-hydroxyindoleacetic acid (5-HIAA) levels (581 +/- 79 micromol/24 h) and hormonal symptoms. Fourteen patients (22%) reached anatomic and biochemical cure by surgery alone. At follow-up, the mean 5-HIAA levels were still normal after 69.0 +/- 6. 2 months; two patients had died from unrelated causes. With the introduction of somatostatin receptor scintigraphy, subclinical disease was diagnosed in 7 of these 14 patients. Forty patients with bilobar hepatic disease underwent embolization in combination with octreotide. In this group, 5-HIAA levels were still reduced by 55% after 71 +/- 11 months of follow-up, and the 5-year survival was 56%, estimated from the total death hazard function. After embolization, two subgroups could be identified with marked differences in their long-term response to treatment. Ten patients were not embolized owing to complicating diseases. The 5-year survival for the entire series was 58%. A significantly increased risk of cardiovascular deaths was seen, which underlines the importance of total survival analysis in a disease with multiple hormonal effects. It is concluded that an active surgical approach must be recommended to patients with the midgut carcinoid syndrome. In patients with bilobar hepatic disease, embolization combined with octreotide treatment markedly reduced the 5-HIAA excretion and suggested a prolonged 5-year survival.
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| 189. |
- Wängberg, Bo, 1953, et al.
(författare)
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The effect of a somatostatin analogue on the release of hormones from human midgut carcinoid tumour cells.
- 1991
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Ingår i: British journal of cancer. - 0007-0920. ; 64:1, s. 23-8
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Tidskriftsartikel (refereegranskat)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.
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| 190. |
- Wängberg, Bo, 1953, et al.
(författare)
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The effect of vagotomy on enterochromaffin-like cells in Mastomys natalensis.
- 1996
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Ingår i: Journal of the autonomic nervous system. - 0165-1838. ; 59:3, s. 133-9
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Tidskriftsartikel (refereegranskat)abstract
- The effect of vagotomy on the development of ECL cell tumours was analyzed during drug-induced hypergastrinemia in Mastomys natalensis, a rodent prone to develop ECL cell tumours. Untreated animals were compared with animals receiving the histamine2-receptor blocker loxtidine (LOX) and with animals subjected to unilateral subdiaphragmatic vagotomy prior to loxtidine treatment (VAG+LOX). Loxtidine (2g/l) was administered in drinking water for 48 weeks to allow multiple ECL cell carcinoids to develop. Plasma gastrin levels were increased in LOX animals (94 +/- 31 pmol/l) and in VAG+LOX animals (181 +/- 59 pmol/l) compared to controls (45 +/- 4 pmol/l). Corpus weight and oxyntic mucosal thickness was almost doubled in all loxtidine-treated animals and the density of mucosal endocrine cells was increased by 65% in the LOX group and by 135% in VAG+LOX animals. No significant differences in mucosal thickness and endocrine cell density were seen when denervated and intact parts of the stomach were compared. In the VAG+LOX animals endocrine cell neoplasia was seen in 60% and dysplasia in 40% of animals compared to 40% neoplasia, 45% dysplasia and 15% hyperplasia in LOX animals. The frequency of neoplastic and dysplastic lesions did not differ between denervated and intact parts of the stomach. Untreated animals showed no neoplastic or dysplastic lesions. It is concluded that unilateral vagotomy has no protective effect on the development of ECL-cell tumours in Mastomys during hypergastrinemia, as opposed to previous studies in the rat.
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