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SURGERY COMBINED WITH MULTIMODAL THERAPY - A NOVEL CONCEPT IN THE TREATMENT OF ADVANCED SMALL BOWEL NEUROENDOCRINE NEOPLASMS
Panagiotis Drymousis1, Ashley K. Clift*2,3, Sydney Leaman2, Claudia von Arx2, Alexander von Roon2, Andrea Frilling2
1Frimley Park Hospital, Camberley, United Kingdom; 2Imperial College London, London, United Kingdom; 3Northwick Park & St Mark's Hospitals, London, United Kingdom

Introduction: Small bowel neuroendocrine neoplasms (SBNEN) are increasing in incidence according to multiple national cancer registries. The majority present at a metastasised stage and therefore challenge conventional surgical treatment approaches.
Methods: Retrospective review of a prospectively maintained single institutional registry for NEN (an ENETS Centre of Excellence) established in 2010. Individual patient files for histologically confirmed SBNEN were accessed, with demographic and clinicopathological data extracted. Details of treatment and therapy response throughout follow-up were recorded. Kaplan-Meier methodology was used to assess overall survival (% with 95% confidence intervals).
Results: We identified 132 patients (68 females). Median age at diagnosis was 64.5years (range 33-85). Thirty-eight patients had carcinoid syndrome (29%) and 8 had evidence of carcinoid heart disease (6.1%). Tumour grade assessed either on biopsy or surgical specimen was G1 in 102 (77.3%), G2 in 29 (22%), and G3 in 1 (0.8%). Initial imaging (CT, MRI, 68 Ga-DOTATATE PET/CT) data was available for 106 patients: 59 (55.7%) had distant metastases.
One hundred patients (75.8%) underwent surgery in terms of right hemicolectomy or segmental small bowel resection and mesenteric lymphadenectomy. We followed a "lymph nodes first"? approach. Liver metastases were resected in 10 (7.6%) patients. Multifocal primary tumours were seen in 28 patients (21.2%). In one patient with extensive level IV mesenteric lymph node metastases and a multifocal primary tumour we performed multivisceral intestinal transplantation. 30-days morbidity was 2.9% (grade 1 or 2 according to Clavien-Dindo classification in all patients) and 30-days mortality was 0%. Following intestinal resection no patients developed short bowel syndrome. None of the patients had exploratory laparotomy only. In addition to surgery, 50 patients (37.9%) had various non-surgical therapies including somatostatin analogues, peptide receptor radionuclide therapy, selective internal radiotherapy and mTOR inhibitors either as a single measure or consecutively during the course of the disease.
Median follow-up was 45months, during which there were 22 disease-related deaths. Kaplan-Meier estimated overall survival at 1-, 3-, and 5-years was 98.4% (96.3-100), 93.7% (89.3 to 98.4), and 88% (81.4-95.2), respectively.
Discussion: The majority of patients with SBNEN have low-grade disease but have lymph node and/or distant metastases at diagnosis. Multimodal treatment strategies including radical surgery are associated with favourable survival despite advanced tumour stage.


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