Surgical Therapy of GEP-NET: An Overview

Transcription

1 Surgical Therapy of GEP-NET: An Overview Pierce K.H Chow MBBS, MMed, FRCSE, FAMS, PhD Professor, Duke-NUS Graduate School of Medicine Senior Consultant Surgeon, Singapore General Hospital Visiting Senior Consultant, National Cancer Center 3 rd Nov 2012

2 Overview of the Surgical management GEP-NET Surgical resection provides the only opportunity for cure in localized neuroendocrine tumours Different surgical strategies are required for tumours depending on presentation, location, biological characteristics and size Patients with gastrointestinal neuroendocrine tumors often present as acute surgical emergencies.

3 Surgery is the primary therapy in non-metastatic GEPNETs NCCN Recommendation: Definitive resection should be considered in both malignant and benign lesions Aim for R0 resection total removal of tumor with negative resection margins May require concomitant resection of adjacent organs Kidney, spleen, pancreas, stomach, colon, IVC

4 Outline Surgical Strategy in Gastro-intestinal NETs. Surgical Strategy in Pancreatic NETs. The role of surgery in Metastatic and Recurrent GEP-NETs Anesthetic Considerations in GEP NETs

5 Surgical Strategy in Gastro-Intestinal NETs Emergency surgeries are common

6 Gastro-intestinal Neuro-endocrine Tumors The presentation of GI NETS depends on site of origins, size, and the production of hormones From the point of surgical strategy, GI NETs may be divided into four main groups: Gastric - 7% Small bowel/colon - 45%/11% Appendix - 17% Rectum - 20%

7 Gastric NETs (7%) Type I - (75%) CAG, multiple small, incidental, indolent Type 2 - (5%) ZES, LN 30%, liver mets 10 20% Type 3 - (20%) sporadic, single larger, LN 20%, liver > 70% Type 4 - poorly differentiated Akerstrom 2010

8 Surgery for Gastric NETs Type I - (75%) CAG, multiple small, incidental, indolent - endoscopic resection, wedge resetion, antrectomy Type 2 - (5%) ZES, LN 30%, liver mets 10 20% - radical resection + resection of gastrinoma Type 3 - (20%) sporadic, single larger, LN 50%, liver > 70% - radical resection as for carcinoma Type 4 - poorly differentiated - radical resection but many unresectable

9 Small bowel NETs (45%) Typically from submucosa of distal ileum Tend to be small, can be multiple LN metatases in 80 90% Tend to be large Most mesenteric mass to the right of the SMA Liver metastases in 60 80%, small, miliary, sometimes difficult to detect Significant fibrosis leading to obstruction/ischemia Up to 40% diagnosed at emergency surgery Carcinoid syndrome in up to 20%

10 In the elective setting, radical resection of primary tumor with lymphadenectomy and resection of hepatic mets prolong survival. Pre-operative imaging to delineate vascular anatomy Mobilization and retroperitoneal dissection Surgical Strategy in Small bowel NETs

11 50% in the caecum Tend to be large Colonic NETs (11%) presentation similar to adenocarcinoma Tend to be aggressive LN and hepatic metastases common Radical resection as for adenocarcinoma when possible Small lesions < 1.0 cm rarely metastasize and may be resected endoscopically

12 Most often at tip (70%) and if < 1.0 cm (90%) is cured by appendectomy. For tumor > 2.0 cm or involving base, right hemicolectomy with ileocecal LN clearance For tumor 1 2 cm Limited right hemicolectomy with LN clearance in if Resection margin + Invasion of mesoappendix LN metastases Appendiceal NETs (appendiceal carcinoids) 17%

13 Usually small (60% < 1cm) and found at anterior and lateral walls above dentate line < 1 cm : rarely mets 1-2 cm : 10-15% metastasize > 2cm : 60 80% metastasize Surgical strategy depends on size and depth of invasion Rectal NETs (20%)

14 < 1 cm : rarely mets Endoscopic resection 1-2 cm : 10-15% mets Transanal US or MRI If no muscularis invasion, transanal local resection Otherwise radical resection > 2cm Radical resection : 60 80% mets Surgical Strategy for Rectal NETs

15 Surgical Strategy for Pancreatic NETs functioning and non-functioning

16 Pancreatic NETS Most occur sporadically but some can be in association with familial syndromes MEN1 Von Hipple-Lindau

17 Pancreatic NETS 1% of incidence but 10% of prevalence of pancreatic cancers Up to 50% are non-functional Most (90%) are malignant Of functional tumours Up to 50% are insulinomas 90% of insulinomas are benign Other functional tumours Gastrinoma, Glucagonoma, VIPoma,

18 Most common functioning PNET 5 10% assoc with MEN1 Generally small, 90% benign EUS 90%. In our experience pre-operative MRI has sensitivity of 63% Goh 2009 If not located preoperatively Kocherisation to expose head and uncinate Exploration of body and tail Palpation and IOUS Insulinoma

19 Large tumor (> 4 cm) high chance of malignancy Small pancreatic body/tail tumor should be resected by distal pancreatectomy may be resected laparoscopically Head or uncinate tumour that are small may be enucleated (IOUS) If close to duct pre-operative insertion of pancreatic stent by ERCP Surgical Strategy for Insulinoma Familial insulinoma may be multiple

20 Gastrinoma 2 nd most common functioning PNET Mostly in the duodenum Majority (60-90%) are malignant Up to 1/3 are metastatic at time of diagnosis Sporadic in 80%, most common functioning PNET in MEN1 Pre-operative radionuclide scan IOUS limited in duodenal gastrinoma

21 Surgical resection for Pancreatic NETs: the Singapore General Hospital experience 61 patients resected between functional 41 non-functional Functional tumours Insulinoma (17), Gastrinomas (2) VIPoma (1) 53 had resection with curative intent i.e. nonmetastatic at time of resection

22 PNETs resection at SGH Pierce Chow FRCSE PhD 61patients 2 with MEN1 1 with Von Hipple Lindau Goh,

23 Pierce Chow FRCS, PhD Prognostic factors for disease-specific survival (DSS) after surgery and for recurrence-free survival (RFS) after curative resection 53 R0/R1 resections operative mortality 3% 23

24 Outcomes of Surgical resection for pancreatic NETs: the SGH/NCC experience Overall outcome in 61 patients: 5-year actuarial DSS was 85% median actuarial DSS was 179 months For the 53 curative resections: 5-year actuarial RFS was 90% median actuarial RFS was 187 months

25 The Role of Surgery in metastatic and recurrent GEPMETs: Resection for improved survival

26 Surgery for metastatic and recurrent GEPNETs NCCN Recommendations: In fit patients with loco-regional recurrence or distal metastases, resection should be considered if complete ablation can be achieved In selected symptomatic patients who are fit, palliative resection to reduce tumour load should be considered

27 Pierce Chow FRCSE PhD Hepatic resection for NET metastasis 27

28 Liver metastases from GEPNETs Surgical resection is an established treatment modality for metastatic GEPNETs and confers significantly improved survival (NCCN 2012) No randomized controlled trials Significant long term survival with resection for hepatic metastases (Soreide 1992) Median survival without resection 48 months Median survival with hepatic resection 216 mths

29 Resection for hepatic metastases from NET Pierce Chow FRCSE PhD Median overall survival 9.6 years 5-year overall survival 77.4% Glazier

30 Pierce Chow FRCSE PhD Resection for recurrent Pancreatic NET Annals of Surgery

31 Pierce Chow FRCS, PhD Of 125 cases from Marburg resected for PEN between 1987 and 2004, 33 had repeat surgical resection for recurrent tumour Operative mortality of 4.8% 31

32 Pierce Chow FRCSE PhD 10 of 33 had more than 1 re-operation median follow-up of 124 months 82% (27 of 33) were malignant 36% remained disease-free at end of study better survival in age < 50 (p ) Actuarial survival after re-operation: 5-yr 10-yr 25-yr Overall 84% 76% 38% Malignant 81% 72% 36% 32

33 Pierce Chow FRCSE PhD Should resection of hepatic metastases be now preceded or superseded by Lu-77 PRRT? 5 th April rd October

34 Anesthetic Considerations in Surgery for GEPMET Beware of Storms!

35 Pierce Chow FRCS, PhD a major concern with resection of metastatic carcinoids is the risk of carcinoid crisis (storm) peri-operative octreotide reduced intra-operative complications from 11% (73 patients) to 0% (45 patients) NCCN: routine peri-operative octreotide recommended 35

36 Pierce Chow FRCSE PhD Thank You! 36