| 1. |
- Bümming, Per, 1965, et al.
(författare)
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Can the early reduction of tumour markers predict outcome in surgically treated sporadic medullary thyroid carcinoma?
- 2008
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Ingår i: Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie. - : Springer Science and Business Media LLC. - 1435-2443. ; 393:5, s. 699-703
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Patients with sporadic medullary thyroid carcinoma (MTC) have a variable clinical course. Our aim was to analyse the reduction of tumour markers after thyroidectomy with meticulous dissection and relate it to clinical outcome. MATERIALS AND METHODS: Twenty consecutive patients with palpable sporadic MTC underwent thyroidectomy with central and uni- or bilateral modified radical neck dissection; three were subjected to mediastinal dissection. Basal (b-) and stimulated (s-) calcitonin (CT) and carcinoembryonic antigen (CEA)-levels were measured before and 6-8 weeks after primary surgery, and the reduction of these tumour markers was determined. RESULTS: Median CT (b- and s-) were markedly reduced after surgery (98.5% and 99.1%, respectively), and CEA decreased 11 times. CT (b-) fell >99% in seven patients after surgery; in these and four additional patients, CT (s-) showed a similar reduction. During follow-up (median 52.5 months), two patients (stages IV B and C) died of MTC; they had <95% reduction of CT. Four patients (stage IV A) are alive with verified metastases. Eight patients (one stage III, seven stage IV A) are alive with hypercalcitoninemia. Five stages I-III patients and one stage IV A patient are disease-free. CONCLUSIONS: Thyroidectomy and meticulous dissection caused a pronounced reduction of tumour markers. A postoperative reduction of CT (s-) >/=97% seems to be associated with less aggressive clinical course, while CEA had lower predictive value.
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| 2. |
- Bümming, Per, 1965, et al.
(författare)
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Gastrointestinal stromal tumors regularly express synaptic vesicle proteins: evidence of a neuroendocrine phenotype.
- 2007
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Ingår i: Endocrine-related cancer. - 1351-0088. ; 14:3, s. 853-63
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Tidskriftsartikel (refereegranskat)abstract
- Gastrointestinal stromal tumors (GISTs) are thought to originate from the interstitial cells of Cajal, which share many properties with neurons of the gastrointestinal tract. Recently, we demonstrated expression of the hormone ghrelin in GIST. The aim of the present study was therefore to evaluate a possible neuroendocrine phenotype of GIST. Specimens from 41 GISTs were examined for the expression of 12 different synaptic vesicle proteins. Expression of synaptic-like microvesicle proteins, e.g., Synaptic vesicle protein 2 (SV2), synaptobrevin, synapsin 1, and amphiphysin was demonstrated in a majority of GISTs by immunohistochemistry, western blotting, and quantitative reversetranscriptase PCR. One-third of the tumors also expressed the large dense core vesicle protein vesicular monoamine transporter 1. Presence of microvesicles and dense core vesicles in GIST was confirmed by electron microscopy. The expression of synaptic-like microvesicle proteins in GIST was not related to risk profile or to KIT/platelet derived growth factor alpha (PDGFRA) mutational status. Thus, GISTs regularly express a subset of synaptic-like microvesicle proteins necessary for the regulated secretion of neurotransmitters and hormones. Expression of synaptic-like micro-vesicle proteins, ghrelin and peptide hormone receptors in GIST indicate a neuroendocrine phenotype and suggest novel possibilities to treat therapy-resistant GIST.
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| 3. |
- Bümming, Per, 1965, et al.
(författare)
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Neoadjuvant, adjuvant and palliative treatment of gastrointestinal stromal tumours (GIST) with imatinib: a centre-based study of 17 patients.
- 2003
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 89:3, s. 460-4
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Tidskriftsartikel (refereegranskat)abstract
- Malignant gastrointestinal stromal tumours (GIST) have a poor prognosis. Since these tumours are resistant to conventional radiation and chemotherapy, surgery has been the mainstay of treatment. However, surgery is usually inadequate for the treatment of malignant GIST. Imatinib, a KIT tyrosine kinase inhibitor, has recently been found to have a dramatic antitumour effect on GIST. In this centre-based study of 17 consecutive patients with high-risk or overtly malignant GIST, imatinib was used in three different settings - palliatively, adjuvantly, and neoadjuvantly. The treatment was found to be safe and particularly effective in tumours with activating mutations of exon 11 of the KIT gene. Clinical response to imatinib treatment correlated morphologically to tumour necrosis, hyalinisation, and reduced proliferative activity. The value of neoadjuvant imatinib treatment was illustrated in one case.
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| 4. |
- Bümming, Per, 1965, et al.
(författare)
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Population-based study of the diagnosis and treatment of gastrointestinal stromal tumours
- 2006
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 93:7, s. 836-43
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this retrospective population-based study, which was conducted before the introduction of imatinib, was to evaluate the role of surgery in patients with gastrointestinal stromal tumours (GISTs) and clarify which subgroups might benefit from adjuvant treatment. METHODS: Two hundred and fifty-nine patients with clinically detected GISTs were studied. Univariate and multivariate analyses were performed to identify predictors for recurrent disease and survival. RESULTS: Thirty of 48 patients with high-risk GISTs and all of those with overtly malignant tumours developed recurrent tumour after complete (R0) resection. Thirty-four of 38 first recurrences occurred within 36 months of surgery. No recurrence was observed after 72 months. R0 resection, achieved in 48 (80 per cent) of 60 patients with high-risk tumours, was significantly associated with a decreased risk of death from tumour recurrence (P = 0.008). CONCLUSION: Completeness of surgical resection is an independent prognostic factor in patients with high-risk GISTs. A period of adjuvant treatment with imatinib is recommended in patients with high-risk or overtly malignant GISTs who have undergone R0 resection and have a tumour-free interval of less than 6 years.
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| 5. |
- Bümming, Per, 1965, et al.
(författare)
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Use of 2-tracer PET to diagnose gastrointestinal stromal tumour and pheochromocytoma in patients with Carney triad and neurofibromatosis type 1
- 2006
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Ingår i: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 41:5, s. 626-30
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Tidskriftsartikel (refereegranskat)abstract
- There is rapid evolution in the functional imaging of tumours. In two patients with concomitant pheochromocytoma and gastrointestinal stromal tumour (GIST), previously unrecognized tumours were visualized by combined 2-tracer positron emission tomography (PET), which also provided precise information about tumour type. PET imaging led to radical resection and the diagnoses were histopathologically confirmed. GISTs from the Carney patient and the patient with neurofibromatosis type 1 (NF1) both lacked KIT mutations.
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| 6. |
- Nilsson, Bengt E, 1949, et al.
(författare)
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Adjuvant imatinib treatment improves recurrence-free survival in patients with high-risk gastrointestinal stromal tumours (GIST)
- 2007
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 96:11, s. 1656-8
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Tidskriftsartikel (refereegranskat)abstract
- Palliative imatinib treatment has dramatically improved survival in patients with malignant gastrointestinal stromal tumours, particularly in patients with tumours harbouring activating KIT mutations. To evaluate the effectiveness of adjuvant imatinib after radical surgery, a consecutive series of patients with high-risk tumours (n=23) was compared with historic controls (n=48) who were treated with surgery alone. The mean follow-up period was over 3 years in both groups. Only 1 out of 23 patients (4%) in the adjuvant treatment group developed recurrent disease compared to 32 out of 48 patients (67%) in the control group. This preliminary study indicates that 1 year of adjuvant treatment with imatinib dramatically improves recurrence-free survival. Confirmation of these findings awaits the results of ongoing randomised studies.
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| 7. |
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| 8. |
- Simonsson, Tomas, 1965, et al.
(författare)
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Reducing uncertainty in health-care resource allocation
- 2007
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 96:12, s. 1834-8
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Tidskriftsartikel (refereegranskat)abstract
- A key task for health policymakers is to optimise the outcome of health care interventions. The pricing of a new generation of cancer drugs, in combination with limited health care resources, has highlighted the need for improved methodology to estimate outcomes of different treatment options. Here we introduce new general methodology, which for the first time employs continuous hazard functions for analysis of survival data. Access to continuous hazard functions allows more precise estimations of survival outcomes for different treatment options. We illustrate the methodology by calculating outcomes for adjuvant treatment of gastrointestinal stromal tumours with imatinib mesylate, which selectively inhibits the activity of a cancer-causing enzyme and is a hallmark representative for the new generation of cancer drugs. The calculations reveal that optimal drug pricing can generate all win situations that improve drug availability to patients, make the most of public expenditure on drugs and increase pharmaceutical company gross profits. The use of continuous hazard functions for analysis of survival data may reduce uncertainty in health care resource allocation, and the methodology can be used for drug price negotiations and to investigate health care intervention thresholds. Health policy makers, pharmaceutical industry, reimbursement authorities and insurance companies, as well as clinicians and patient organisations, should find the methodology useful.
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