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 followup 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 z2%, chromogranin A z3 times the upper normal limit, BMI <20 kg/m 2 , 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 z2% 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.

Purpose: A retrospective analysis of the toxicity and efficacy of temozolomide in advanced neuroendocrine tumors. Experimental Design: Thirty-six patients with advanced stages of neuroendocrine tumor (1gastric, 7 thymic and 13 bronchial carcinoids, 12 pancreatic endocrine tumors, 1 paraganglioma, 1 neuroendocrine foregut, and 1 neuroendocrine cecal cancer) were treated with temozolomide (200 mg/m 2

We report the first immunohistochemical data on expression of the ghrelin receptor in pancreatic endocrine tumours: 70% of tumours in our material. Concomitant ghrelin and receptor expression was seen in 50% of tumours, indicating an autocrine loop. Ghrelin was expressed in 68% of tumours (8/9 MEN1). Despite frequent ghrelin expression, elevated circulating ghrelin is rare in these patients.

BackgroundBetter prognostic markers are needed for pancreatic endocrine tumors. Survivin is an apoptosis inhibitor that is suggested to have a negative prognostic impact in several tumor types. Contradictory data exist, especially regarding the significance of a nuclear versus cytoplasmic location of survivin. The prognostic relevance of nuclear and cytoplasmic survivin expression in pancreatic endocrine tumors—controlled for the tumor Ki-67 index, World Health Organization classification, and TNM stage—was investigated.MethodsA total of 111 patients treated at a tertiary referral center were retrospectively evaluated. Clinical data were gathered from medical records. Immunohistochemistry for survivin and Ki-67 was performed on paraffin-embedded tissue. Univariate and multivariate Cox analyses were performed.ResultsPatients with tumors that had <5% survivin-positive nuclei had a mean survival of 225 months [95% confidence interval (CI) 168–281]. The corresponding figure for patients with 5 to 50% survivin-positive tumor cell nuclei was 101 months [95% CI 61–140; hazard ratio (HR) 2.4; P < 0.01) and with >50% survivin-positive nuclei 47 months (95% CI 24–71; HR 4.9; P < 0.001). Nuclear survivin expression in >50% of the tumor cells was an independent marker of a poor prognosis (HR 5.7; P < 0.01). Cytoplasmic survivin was not a significant prognostic factor in the multivariate analysis (HR 0.94; P = 0.90).ConclusionsHigh expression of nuclear survivin is a significant marker of a poor prognosis in patients with a pancreatic endocrine tumor.

Pancreatic endocrine tumours can cause hormonal symptoms by over-secretion of hormones. They are less aggressive than exocrine pancreatic cancer, but carry a variable prognosis. The tumours are either sporadic or hereditary, as part of the multiple endocrine neoplasia type 1 syndrome. Despite the rarity of these tumours, they evoke significant interest in the research community and important advances have been made over the past years. This chapter provides an overview of the tumours and recent advances in the field. Hereditary forms of pancreatic endocrine tumours are caused by mutations in the MEN1 gene. Menin, the protein encoded by this gene, has been shown to interact with numerous transcription factors and proteins involved in cell-cycle control, shedding some light on the importance of the protein. Several genes have been shown to be up- or down-regulated, suggesting candidates to be further evaluated for a role in tumourigenesis. Several advances have been made in prognostication; a tumour-node-metastasis system has been evaluated and seems to have prognostic value, and several new molecular prognostic markers are under evaluation. It is hoped that the tumour-node-metastasis system and other prognostic markers will be adopted in clinical routine and improve prognostication and treatment choices. Surgery is still the only cure, but several new palliative drugs and interventions are in use or under investigation. Radiofrequency ablation is increasingly used for liver metastases, and a number of new chemotherapy drugs are being tested. Despite improvements in treatment, no clear improvement in survival has been demonstrated.