Surgical Approach & Techniques of Tumours Reduction

E A Antoniou MD PhD Ass Prof of Gen. Sutgery & Organ Transplantation 2nd Propaedeutic Surgical Department, University of Athens G.H.A. Laiko

NET MASTERCLASS EVGENIDES FOUNDATION ATHENS, 5 July 2014

GI- Neuroendocrine Tumours (GI-NETs)

Relatively rare – complex neoplams

Presenting many clinical challenges Sporadic, multiple, component of a familial syndrome Location assessment- GI-NETs extent : crucial for

management

Yao JC, et al. Clin Oncol 2008 Diez M, et al. Annals of Gastroenterology 2013

GI- Neuroendocrine Tumours (GI-NETs)

Appropriate diagnosis/treatment: Multiple disciplines specialists involvement Novel imaging modalities for micro-metastases detection under evaluation Management strategies: surgery, radiological intervention, cytotoxic chemotherapies, somatostatin analogs, novel biological agents (ERL, Sunitinib, etc)

Yao JC, et al. Clin Oncol 2008

Diez M, et al. Annals of Gastroenterology 2013

GI-NETs: Surgical Approach Background

NETs : family of Neuroendocrine Neoplasms Heterogenus group arising from dispersed

neuroendocrine cells – embryological gut 3 Groups of NETs:

Panceatic Neuroendocrine Tumours Arising from GI tract Arising from Bronchopulmonary system 25.3%

NETs secrete hormones + peptides Secretory products: different clinical syndromes

Modlin IM, et al. Cancer 2003 Vinik AI, et al, Pancreas 2010

67.5%

GI-NETs: Surgical Approach Background

GI-NETs: Surgical Approach

Surgery in localized disease

Surgery of metastatic disease

Liver transplantation (?)

GI-NETs: Surgical Approach

Surgery in localized disease

Only potentially curative therapeutic strategy Radical oncological surgery indicated, except:

<2cm carcinoids of stomach, appendix, rectum Small pancreatic insulinomas (90% benign) –enucleation

No Adjuvant therapy in well-differentiated – R0 Adjuvant in poorly differentiated – R0 resection Surgery: major role in advance disease

Modlin IM, et al. Lancet oOncol 2008.

GI-NETs: Surgical Approach

Surgery in localized disease

Appendical carcinoid

Pancreatic head insulinoma

GI-NETs: Surgical Approach Surgery of Metastatic disease: 39% Liver Mets (LM)

Primary tumour resection at early phase/ <complications LM surgery: if complete resection feasible Major cytoreductive therapy-palliative purposes

Even R0 not achievable, >70% resectable – extensive LM, hormonal syndrome refractory to medical therapy

Tumours reduction: hormone secretion reduction, symptoms improvement

Prophylactic cholecystectomy: GB stones prevention, somatostatin treatment

Regional control of LM: RF-A, MW-A, Laser-Ablation, TACE Öberg K, et al. Ann of Oncol 2012

MW-A

GI-NETs: Surgical Approach Surgery of Metastatic disease

GI-NETs: Surgical Approach

Functioning tumour diagnosed before Surgery Carcinoid crisis risk, during tumour’s operation Prevention: continuous/boluses i.v. Octreotide Avoid drugs releasing histamine or sympathetic

nervous system activation Insulinoma: glucose infusion Gastrinomas: PPI & Octreotide

Roy RC, et al. Anaesthesia 1987 Dougherty TB, et al. Int Anesth Clin 1998

GI-NETs: Surgical Approach Liver Transplantation (OLTx)

NET: slow growth tumours, unlike other tumours Small group of Pts with bilobar liver mets- no

extrahepatic disease concidered for OLTx: Intent to cure, but high rate of recurrence Palliation from life-threatening hormonal disturbances

High rate of recurrence Better survival in mets from SB NETs, than Pancreas Pts <50years, low Ki-67, E-cadherin: can benefit

Pfitzmann R, et al. Liver Transpl 2007 Ahlman H, et al. Ann N Y Acad Sci 2004

Chan G, et al. Curr Oncol, 2012

GI-NETs: Surgical Approach Liver Transplantation (OLTx) OLTx photo

Steeve Jobs

GI-NETs: Surgical Approach Conclusion

1. Surgery in localized disease: Curative resection of the primary tumor and locoregional

lymph node metastases improved patients’ outcomes. excellent 5- and 10-year survivals of 100% in stage 1-2 Pts still favorable outcomes in stage 3 disease with 5- and 10-

year survivals of more than 95% and 80%, respectively. Surgical procedures: small intestinal resection or right

hemicolectomy. Distal pancreatectomy, Whipple, enuclation. Clearance of mesenterial / retroperitoneal LNs metastases by dissection around the mesentery, preserving the intestinal vascular supply.

GI-NETs: Surgical Approach Conclusion

2. Surgery of Metastatic disease Primary intestinal NET/regional LN metastases Resection, in PTs with

LMs: prevention of mesenteric fibrosis, SB obstruction, painful vascular encasement. Survival is prolonged in most studies (retrospective)

Mortality <1%, morbidity <10% Pancreatic NETs: Curative surgery, whenever possible, including

localised LMs, if potentially resectable, Pt can tolerate surgery.

Surgical procedures: small intestinal resection (no large ones) or right hemicolectomy.

Whipple, Distal pancreatectomy, nucleation in combination with LMs. Mandatory LNs Clearance, as frequently malignancy of pancreatic NETs Cytoreductive surgery: when metastatic disease is localized or if >70% of

tumor load is thought resectable

GI-NETs: Surgical Approach Conclusion

3. Liver Transplantation (OLTx) OLTx role for LMs from NET: recognised, still yet undefined Literature review: studies of heterogenus population, wide-range tumour

burdens, variety of operative procedures 5-year survival (4 studies): 67-90%, (UNOS:44-49%), recurrence free:

20-48% Criteria: Unresectable LMs, absence of extrahepatic metastases,

symptomatic disease refractory to medical therapy, low grade tumour with Ki-67 <2%, previous resection of primary disease, previous therapy for metastatic NET, age <50-year.

Surgical procedures: Orthotopic Liver Transplantation: DBD, DCD, Split-graft, LRLD

Treatment Algorithm (ESMO)

Lets go for retrieval now…….

Thank you