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Prognostic factors and survival in 324 patients with pancreatic endocrine tumor treated at a single institution
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Endokrin tumörbiologi)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Endokrin tumörbiologi)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Onkologisk endokrinologi)
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2008 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 14, no 23, 7798-7803 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE:

Unequivocal pathologic markers for the prognosis of pancreatic endocrine tumors are often lacking. Suggestions for prognostic guidance include the WHO classification. Recently, a tumor-node-metastasis (TNM) staging system was proposed. We evaluate this system, as well as assess other potential prognostic factors such as tumor Ki67, size, endocrine syndrome, heredity, body mass index (BMI), and plasma chromogranin A, in a large patient material treated at a single institution.

EXPERIMENTAL DESIGN:

A total of 324 patients with pancreatic endocrine tumor, consecutively diagnosed and treated at a tertiary referral center, were retrospectively evaluated. Median follow-up was 54 months (range, 1-423 months). Patient and tumor data were extracted from medical records. Univariate and multivariate analyses were done to recognize factors of prognostic value.

RESULTS:

The median overall survival was 99 months (95% confidence interval, 81-117). Five- and 10-year survival rates were 64% and 44%, respectively. In univariate analysis, TNM stage, radical surgery, WHO classification, nonfunctioning tumor, Ki67 ≥2%, chromogranin A ≥3 times the upper normal limit, BMI <20 kg/m2, sporadic tumor, tumor size, and referral from our primary uptake area had a significant prognostic effect. In multivariate analysis, TNM stage, WHO classification, radical surgery, and Ki67 ≥2% retained their significance. Having a nonfunctioning tumor was not an independent marker of poor prognosis and neither was heredity.

CONCLUSIONS:

The recently suggested TNM staging system emerged as a useful clinical tool.

Place, publisher, year, edition, pages
2008. Vol. 14, no 23, 7798-7803 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-87132DOI: 10.1158/1078-0432.CCR-08-0734ISI: 000261392300027PubMedID: 19047107OAI: oai:DiVA.org:uu-87132DiVA: diva2:133446
Available from: 2009-01-12 Created: 2008-12-17 Last updated: 2017-01-25Bibliographically approved
In thesis
1. Pancreatic Endocrine Tumors and GIST - Clinical Markers, Epidemiology and Treatment
Open this publication in new window or tab >>Pancreatic Endocrine Tumors and GIST - Clinical Markers, Epidemiology and Treatment
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Pancreatic endocrine tumors and gastrointestinal stromal tumors are rare. Evidence regarding prognostic factors, and in the former also treatment, is scarce.

We evaluated the survival and prognostic factors in a consecutive series of 324 patients with pancreatic endocrine tumors treated at a single institution. Radical surgery, WHO classification, TNM stage, age and Ki67 ≥2% emerged as independent prognostic factors. Having a non-functioning tumor was not an independent prognostic marker, and neither was hereditary tumor disease. We present the first evaluation of the newly proposed TNM staging system for these patients. A separate analysis of well-differentiated neuroendocrine carcinomas is reported, suggesting tumor size ≥5cm and Ki67 ≥2% as negative prognostic markers in this group.

The first 36 patients with advanced neuroendocrine tumors treated with temozolomide at our clinic were evaluated. The median time to progression was seven months. Fourteen percent showed partial regression and 53% stabilization of disease. Side effects were generally mild. Investigation of O6-methylguanine DNA methyltransferase revealed a low expression in a subset of tumors. Four out of five patients responding to treatment had tumors with low expression.

Concomitant expression of the orexigen ghrelin and its receptor in pancreatic endocrine tumors is demonstrated. No significant difference in mean plasma ghrelin between patients and controls were found, but elevated plasma ghrelin was seen in five patients.

We provide the first report of expression of ghrelin and its receptor in gastrointestinal stromal tumors. Concomitant expression was frequent, indicating the presence of an autocrine loop. The tumors also expressed the neuroendocrine marker synaptic vesicle protein 2. Together, these findings are suggestive of neuroendocrine features.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 64 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 267
Keyword
Medicine, Pancreatic endocrine tumor, Gastrointestinal stromal tumor, Neuroendocrine, Multiple endocrine neoplasia type 1, Prognostic factors, Temozolomide, TNM staging, O6-methylguanine DNA methyltransferase, Growth hormone secretagogue receptor, Ghrelin, Medicin
Identifiers
urn:nbn:se:uu:diva-7937 (URN)978-91-554-6921-4 (ISBN)
Public defence
2007-09-07, Enghoffsalen, ing. 50, b.v., Akademiska Sjukhuset, Uppsala, 09:15 (English)
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Available from: 2007-05-24 Created: 2007-05-24 Last updated: 2009-08-13Bibliographically approved

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