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Peritoneal carcinomatosis from small intestinal neuroendocrine tumors: Clinical course and genetic profiling
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. (Endokrinkirurgi, Endocrine Surgery)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. (Endokrinkirurgi, Endocrine Surgery)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. (Endokrinkirurgi, Endocrine Surgery)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. (Endokrinkirurgi, Endocrine Surgery)
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2014 (English)In: Surgery, ISSN 0039-6060, E-ISSN 1532-7361, Vol. 156, no 6, 1512-1522 p.Article in journal (Refereed) Published
Abstract [en]

Background. One-fifth of all patients with small-intestinal neuroendocrine tumors (SI-NETs) present with or develop peritoneal carcinomatosis (PC). Our aim was to determine the prognosis and genetic profiles of tumors in patients with PC compared with tumors in patients without PC. Methods. We included SI-NET patients (cases with PC, n = 73, and controls without PC, n = 468) who underwent operation between 1985 and 2012. The Lyon prognostic index was used to correlate the amount of PC to survival. DNA samples from patients with (n = 8) and without (n = 7) PC were analyzed with a single-nucleotide polymorphism array (HumanOmni2.5 BeadChip, Illumina) to investigate genetic disparities between groups. Results. Patients with PC had poorer survival (median 5.1 years) than controls (11.1 years). An advanced postoperative Lyon prognostic index was a negative prognostic marker for survival by multivariable analysis (P = .042). Patients with and without PC clustered differently based on loss of heterozygosity and copy number variation data from single-nucleotide polymorphism array of the primary tumors (P = .042). Conclusion. SI-NET patients with PC have poor survival, which diminishes with increasing PC load after surgery. Clustering based on copy number variation and loss of heterozygosity data suggests different genotypes in primary tumors comparing patients with and without PC.

Place, publisher, year, edition, pages
2014. Vol. 156, no 6, 1512-1522 p.
National Category
Surgery
Identifiers
URN: urn:nbn:se:uu:diva-185070DOI: 10.1016/j.surg.2014.08.090ISI: 000345255700031PubMedID: 25456945OAI: oai:DiVA.org:uu-185070DiVA: diva2:570576
Available from: 2012-11-19 Created: 2012-11-19 Last updated: 2017-12-07
In thesis
1. Small Intestinal Neuroendocrine Tumor: A Rare Malignancy with Favorable Outcome
Open this publication in new window or tab >>Small Intestinal Neuroendocrine Tumor: A Rare Malignancy with Favorable Outcome
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Small intestinal neuroendocrine tumor (SI-NET) is the most common small bowel tumor in Europe and USA, with an annual incidence of around 0.3-1.3/100000 persons. SI-NETs are the most common type of gastroenteropancreatic NETs (GEP-NETs), and they are known for their ability to produce hormones such as tachykinins and serotonin, as well as for their favorable long-term prognosis in comparison to gastrointestinal adenocarcinoma. The overall aim of the thesis was to investigate unknown or unclear aspects of SI-NET disease, in connection with prognosis, treatment and follow-up. Paper I confirmed several known negative prognostic factors and also showed, for the first time, that para-aortal lymph node metastases and peritoneal carcinomatosis were associated with worse survival by multivariable analyses. Locoregional surgery was associated with a low post-operative mortality, and a prolonged long-term survival by multivariable analysis. In Paper II we continued to investigate peritoneal carcinomatosis and found it be a risk factor not only for death, but also for emergency re-surgery. Furthermore, genetic analyses of samples from primary tumors in patients with and without peritoneal carcinomatosis showed a difference in the DNA between these two groups. In Paper III the outcome after liver surgery and/or radiofrequency ablation of liver metastases was investigated. To summarize, no difference in survival was seen in patients treated with surgery/radiofrequency ablation in comparison with matched controls. However, a superior radiological response of liver metasases and lower U-5-HIAA values were seen in patients subjected to liver surgery and/or radiofrequency ablation compared to matched controls. Paper IV compared ultrasonography, computed tomography and 11C-5HTP-PET in the follow-up after radiofrequency ablation of NET liver metastases. The study concluded that 11C-5HTP-PET depicted all residual tumors after RFA and that it, if used, should be combined with computed tomography for easier interpretation, as RFA areas are not clearly distinguishable with 11C-5HTP-PET alone. Paper V studied gallstone complications after somatostatin analog treatment in SI-NET patients, and concluded that there was a rather high risk to be subjected to a cholecystectomy due to biliary colic, cholecystitis, cholangitis or pancreatitis after primary surgery in somatostatin analog treated patients.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 78 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 844
Keyword
Neuroendocrine tumor, peritoneal carcinomatosis, single nucleotide polymorphism array, liver metastases, radiofrequency ablation, liver surgery, positron emission tomography, somatostatin analogs, cholecystectomy
National Category
Surgery
Research subject
Surgery
Identifiers
urn:nbn:se:uu:diva-185071 (URN)978-91-554-8548-1 (ISBN)
Public defence
2013-01-25, Rosensalen, Entrance 95/96, Uppsala University Hospital, Uppsala, 09:15 (Swedish)
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Available from: 2012-12-21 Created: 2012-11-19 Last updated: 2013-02-11Bibliographically approved

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Norlén, OlovEdfeldt, KatarinaÅkerström, GöranWestin, GunnarHellman, PerBjörklund, PeymanStålberg, Peter

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