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Prognostic Factors for Death in Small Intestinal Neuroendocrine Tumours
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. , p. 107
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1450
Keywords [en]
Surgery, SI-NET, Prognostication, Immunohistochemistry
National Category
Surgery
Research subject
Surgery
Identifiers
URN: urn:nbn:se:uu:diva-347235ISBN: 978-91-513-0297-3 (print)OAI: oai:DiVA.org:uu-347235DiVA, id: diva2:1193854
Public defence
2018-05-18, Rosénsalen, Akademiska Sjukhuset, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2018-04-25 Created: 2018-03-28 Last updated: 2018-10-08
List of papers
1. The Influence of Preoperative Symptoms on the Death of Patients with Small Intestinal Neuroendocrine Tumors
Open this publication in new window or tab >>The Influence of Preoperative Symptoms on the Death of Patients with Small Intestinal Neuroendocrine Tumors
2017 (English)In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 24, no 5, p. 1214-1220Article in journal (Refereed) Published
Abstract [en]

Small intestinal neuroendocrine tumors (SI-NETs) are uncommon tumors with an annual incidence of about 1 per 100,000. Usually, SI-NETs have a slow progression, and patients often present with generalized disease. Many patients do well, and the disease has a relatively favorable 5-year survival rate. Some SI-NETs, however, have a more negative prognosis. This study aimed to establish prognostic factors for death identifiable at primary surgery. A nested case-control study investigated 1150 patients from the cohort of all patients with a diagnosis of SI-NETs in Sweden between 1961 and 2001. The study cases consisted of all patients who died of SI-NETs during the study period. Each case was assigned a control subject matched by age at diagnosis and calendar period. Possible prognostic factors [gender, degree of symptoms, indication for surgery, World Health Organization (WHO) stage] were evaluated in uni- and multivariable analyses. The patients with symptomatic disease had an increased risk of dying. The indication for primary surgery influenced survival, showing a more negative prognosis for elective surgery. The WHO stage influenced survival, and stage 4 patients had an almost threefold risk of dying compared with stages 1 to 3b patients. This study showed that preoperative symptoms are important in prognostication for SI-NETs. Hormonal symptoms generally signify a patient with a more advanced disease stage and a worse prognosis. Including symptomatic disease together with the WHO stage and grade could possibly increase the accuracy of prognostication.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-322084 (URN)10.1245/s10434-016-5703-4 (DOI)000399013200012 ()27904972 (PubMedID)
Available from: 2017-05-16 Created: 2017-05-16 Last updated: 2018-03-28Bibliographically approved
2. Symptomatic disease at the time of surgery have prognostic impact in small intestinal neuroendocrine tumours
Open this publication in new window or tab >>Symptomatic disease at the time of surgery have prognostic impact in small intestinal neuroendocrine tumours
(English)In: British Journal of Surgery OpenArticle in journal (Refereed) Accepted
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-347231 (URN)
Available from: 2018-03-28 Created: 2018-03-28 Last updated: 2018-04-08
3. Prognostic factors for death after surgery for small intestinal neuroendocrine tumours
Open this publication in new window or tab >>Prognostic factors for death after surgery for small intestinal neuroendocrine tumours
(English)In: Article in journal (Refereed) Submitted
National Category
Surgery
Research subject
Surgery
Identifiers
urn:nbn:se:uu:diva-347232 (URN)
Available from: 2018-03-28 Created: 2018-03-28 Last updated: 2018-04-08
4. TFF3 in primary tumours has a negative impact on survival in small intestinal neuroendocrine tumours
Open this publication in new window or tab >>TFF3 in primary tumours has a negative impact on survival in small intestinal neuroendocrine tumours
Show others...
(English)In: Article in journal (Refereed) Submitted
National Category
Surgery
Research subject
Surgery
Identifiers
urn:nbn:se:uu:diva-347233 (URN)
Available from: 2018-03-28 Created: 2018-03-28 Last updated: 2018-03-28
5. Primary small intestinal tumours are highly prevalent and often multiple before metastatic disease develops
Open this publication in new window or tab >>Primary small intestinal tumours are highly prevalent and often multiple before metastatic disease develops
Show others...
(English)In: Article in journal (Refereed) Submitted
National Category
Surgery
Research subject
Surgery
Identifiers
urn:nbn:se:uu:diva-347234 (URN)
Available from: 2018-03-28 Created: 2018-03-28 Last updated: 2018-03-28

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