Prognostic Factors for Death in Small Intestinal Neuroendocrine Tumours

  • Datum:
  • Plats: Rosénsalen, Akademiska Sjukhuset, Uppsala
  • Doktorand: Eriksson, John
  • Om avhandlingen
  • Arrangör: Endokrinkirurgi
  • Kontaktperson: Eriksson, John
  • Disputation

The principal aim of this thesis was to establish prognostic factors over the entire life span of patients with SI-NETs.

Tumours in the small intestine are rare compared to those in other gastrointestinal organs. Small intestinal neuroendocrine tumours (SI-NETs) are the most common small bowel tumours with an annual incidence of 0.3-1.7 per 100 000 persons. They are characterised by their usually indolent nature and, even though many patients present with metastatic disease, survival is favourable compared to most other gastrointestinal malignancies. The principal aim of this thesis was to establish prognostic factors over the entire life span of patients with SI-NETs. Paper I confirmed the known prognostic factors of metastatic and symptomatic disease as preoperative prognostic factors. In this paper, we also showed that patients with symptomatic Stage IV disease are the most likely patients to die from their SI-NET. Patients who undergo surgery in an emergency setting fared better than patients who had elective surgery and this can possibly be explained by patients having less advanced disease in emergency procedures.  Paper II focused on the perioperative period, during which liver metastases and peritoneal carcinomatosis stood out as the most important prognostic factors. A macroscopically radical surgery had a positive prognostic impact, as did radical locoregional surgery (LRS). In univariable analysis, LRS was a positive prognostic factor regardless of TNM stage. In Paper III, the specific findings that had prognostic impacts in the postoperative period were the negative impacts of carcinoid heart disease and non-radical secondary surgery.  The occurrence of a second malignancy seemed to have positive prognostic value but was most likely a result of study design. Paper IV studied expression patterns seen on immunohistochemistry of primary and metastatic tissue sections from the primary operation in 40 patients.  In this study, low TFF3 expression in primary tumours was correlated to decreased survival. We also proposed a dual mechanism for TFF3 in the dedifferentiation of SI-NETs based on the finding of high TFF3 expressions in metastatic tissue. The expression of mindin and ACTG2 was higher in G2 tumours and we suggested that mindin played a role as an indirect promoter of proliferation and cell migration. Finally, in Paper V, we calculated the mean annual incidence of clinical and subclinical SI-NETs from autopsy material comprised of the very high number of autopsies from the Malmö region between the years 1970 and 1982. The total mean annual incidence of SI-NETs was 5.7 per 100 000 and males were more likely to harbour a SI-NET than females. In this material, 40% of those with a SI-NET had at least one other malignancy, which constitutes a more than three-fold increased rate of synchronous malignancies in SI-NET cases.