Small Intestinal Neuroendocrine Tumor : A Rare Malignancy with Favorable Outcome

Sammanfattning: 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.