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Indication for Liver Transplantation in Young Patients with Small Intestinal NETs Is Rare?
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
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2014 (English)In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 38, no 3, 742-747 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

A majority of patients with small intestinal neuroendocrine tumors (SI-NETs) present with or develop liver metastases (LM). A number of treatments for LM are used clinically, including liver transplantation (LTx). Indications for LTx are under debate; young age (<65 years), absence of extrahepatic disease, resected primary tumor and limited extent of LM have been suggested as inclusion criteria for LTx with the aim to optimize outcome.

MATERIALS AND METHODS:

From our series of 672 patients with SI-NET treated at the University Hospital in Uppsala between 1985 and 2012, we identified 78 patients according to the following criteria: <65 years of age, locoregional surgery (LRS) of the primary tumor and mesenteric metastases successfully performed, LM present but no extrahepatic disease. Baseline was chosen as the first date the following points were met: First visit to our center, LRS performed, LM present. The patients underwent treatment according to the standard clinical protocols at our center, and during this time period we did not perform or refer any SI-NET patients for LTx. Kaplan-Meier survival analyses were performed in three different groups based on hypothetical criteria for LTx.

RESULTS:

Five-year overall survival rates for patients <65 years (n = 78) and <55 years (n = 36) of age were 84 ± 8 and 92 ± 9 %, respectively. For patients fulfilling the Milan criteria (n = 33) the 5-year survival was 97 ± 6 %.

CONCLUSIONS:

Most young patients (<65 years) with SI-NET and LM have a favorable survival with standardized multimodality treatment. Indeed, most survival figures reported after LTx of NET do not surpass these figures.

Place, publisher, year, edition, pages
2014. Vol. 38, no 3, 742-747 p.
National Category
Surgery
Identifiers
URN: urn:nbn:se:uu:diva-212143DOI: 10.1007/s00268-013-2331-zISI: 000333151700032PubMedID: 24233660OAI: oai:DiVA.org:uu-212143DiVA: diva2:676601
Available from: 2013-12-06 Created: 2013-12-06 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Small Intestinal Neuroendocrine Tumors: Clinical Studies, Novel Serum Biomarkers and Sensitivity to Cytotoxic and Targeted Agents
Open this publication in new window or tab >>Small Intestinal Neuroendocrine Tumors: Clinical Studies, Novel Serum Biomarkers and Sensitivity to Cytotoxic and Targeted Agents
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Small Intestinal Neuroendocrine Tumors (SI-NETs) are indolent neoplasms with an increasing annual incidence of approximately 1/100 000 people. They are often diagnosed at a late stage, restricting treatment efficacy. The aim of this thesis was to investigate clinical aspects of patients with advanced and/or disseminated disease with regard to clinical signs and management of abdominal fibrosis, the role of locoregional surgery and liver transplantation, as well as the ex vivo sensitivity of tumor samples to cytotoxic and targeted agents. Additionally, novel serum biomarkers for the diagnosis and prognosis of SI-NETs were investigated. In Paper I, abdominal fibrosis induced by serotonin and other cytokines from tumor cells, was associated with clinically significant symptoms of intestinal ischemia and/or obstructive uropathy, and was linked to advanced disease. Prompt recognition and minimally invasive intervention with superior mesenteric vein stenting and/or percutaneous nephrostomy and J stent treatment were effective in disease palliation. Paper II challenged the role of prophylactic, upfront locoregional surgery in Stage IV, which conferred no survival advantage in asymptomatic SI-NET patients. The option of delayed surgery as needed seemed to be comparable in all the outcomes examined, whilst also offering the advantage of fewer re-operations for intestinal obstruction in patients with already disseminated disease. Paper III confirmed that most young patients (<65 years) with SI-NET and liver metastases had a favorable survival with standardized multimodality treatment and that survival figures reported after liver transplantation for NETs do not surpass these figures. In Paper IV, 145 biomarkers were analyzed in blood serum using two different multiplex proximity assays. Subsequent ELISA and immunohistochemical analyses identified DcR3, TFF3 and midkine as novel serum biomarkers for SI-NETs. In Paper V, SI-NET samples were profiled with respect to sensitivity ex vivo to a panel of standard chemotherapeutics and targeted agents using a short-term total cell kill assay. SI-NETs exhibited variable but generally intermediate sensitivity ex vivo compared with other cancer diagnoses, calling for individualized selection of therapy.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. 84 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1386
Keyword
SI-NET, fibrosis, locoregional surgery, liver transplantation, biomarkers, ex vivo sensitivity.
National Category
Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-330554 (URN)978-91-513-0113-6 (ISBN)
Public defence
2017-12-08, Rosénsalen, Akademiska sjukhuset, ing 95-96, Uppsala, 09:00 (Swedish)
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Supervisors
Available from: 2017-11-16 Created: 2017-10-02 Last updated: 2017-11-16
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Norlén, OlovDaskalakis, KosmasÖberg, KjellÅkerström, GöranStålberg, PeterHellman, Per

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