Management of Primary Neuroendocrine Tumors

Surgical Management of Primary Neuroendocrine Tumors

Carl R. Schmidt, MD, FACS

Management of Primary Neuroendocrine Tumors

Objectives

• Discuss goals of surgical resection

• Management of GI primary tumors

• Management of pancreatic primary tumors (PNET)

Management of Primary Neuroendocrine Tumors

Goals of Surgical Resection

• Cure

• Survival

• Palliation

Management of Primary Neuroendocrine Tumors

Cure

• Carcinoid = cancer

• Five-year survival 67%

• Death often due to metastatic disease– Extent of disease workup– Multi-phase CT or MRI (liver mets)– Octreoscan

Management of Primary Neuroendocrine Tumors

Survival

• Typically indolent

• Long-term survival common

• Management of symptoms is important

Management of Primary Neuroendocrine Tumors

Palliation

• Hormone syndromes– Carcinoid syndrome usually liver metastases

• Jaundice

• Bowel obstruction

• Pain

Management of Primary Neuroendocrine Tumors

GI Carcinoid Locations

• Distal small bowel (25-30%)

• Colon/appendix

• Rectum

• Stomach

Management of Primary Neuroendocrine Tumors

GI Carcinoid Symptoms

• Diagnosis difficult– 2-3 years from symptom

onset to diagnosis– Normal exam, labs,

endoscopy

• Abdominal pain (mesenteric ischemia)

• Partial small bowel obstruction

Management of Primary Neuroendocrine Tumors

Gastric Carcinoids

Type Etiology Gastrin Manifestations Treatment options

I70-80%

Autoimmune first, atrophic gastritis, achlorhydria

High Low grade, multiple small <5% mets

Surveillance EGD; EMR or antrectomy *

II5-10%

ZES (neoplasia first)MEN1

High Ulcers multicentric 10% metastasize

Call Dr. Ellison

III15-20%

Sporadic malignancy Normal Solitary mass 50% metastasize

Radical operation

Gladdy Annals Surg Onc 2009

*rarely associated with gastric adenocarcinoma

Management of Primary Neuroendocrine Tumors

Type III

• Gastric NEC• 4 cm well-diff• One + LN• No adjuvant

therapy• Cancer

surveillance

Management of Primary Neuroendocrine Tumors

Small Bowel Primary

• Curative intent:– Bowel resection with regional LND– Multicentric (20-40%)– Consider prophylactic cholecystectomy

(gallstones associated with Octreotide)

• Palliation– Small bowel bypass

Management of Primary Neuroendocrine Tumors

Small Bowel Primary• >80% risk of recurrence after initial resection

– Moertel J Clin Oncol 1987

• Probability of developing metastases to new sites– Follow-up 1-11 years (mean 5.2)– Makridis World J Surg 1996

Initial mets Mesentery Liver Extra-abdominal

None (N=8) 0.25 0.13 0

Mesentery (N=37) 0.56 0.05

Liver (N=15) 0.27 0.60

Mesentery and Liver (N=59)

0.22

Management of Primary Neuroendocrine Tumors

Appendiceal Primary

• Incidence decreasing – ?less incidental

appendectomies

• Generally good prognosis– 5-30% localized– 86% 5-yr survival

Sandor Am J Gastro 1998

Management of Primary Neuroendocrine Tumors

NCCN - Appendix

• ≤ 2cm, confined to appendix– Appendectomy, no surveillance

• > 2cm, incomplete resection, nodal spread– Abdomen/pelvis CT or MRI– Right hemicolectomy

• Goblet cell or adenocarcinoid – manage as colon adenocarcinoma

Management of Primary Neuroendocrine Tumors

Rectal Primary

• Need colonoscopy and CT, consider EUS

• < 2 cm - transanal or EMR if possible

• > 2cm – LAR or APR

Management of Primary Neuroendocrine Tumors

Pancreatic Primary (PNET)

• Family history – MEN1 (gastrinoma and insulinoma)

• 60% functional• 90% of non-functional

are malignant– Chromogranin A

(pancreastatin)– CT, MRI– Octreoscan?

Management of Primary Neuroendocrine Tumors

Functional PNETTumor Sx Hormone Maligna

ntOther

Gastrinoma PUD Gastrin Very Diarrhea

Insulinoma (70%)

Hypo-glycemia

Insulin Low CatecholamineExcess

Glucagonoma DM, rash Glucagon Very DVT/PEWeight loss

VIPoma Watery diarrhea, hypoKachlorhydria

VIP High Met. AcidosisHyperglycemiaHyperCaFlushing

Somatostatinoma

DMDiarrhea

Somatostatin

Very Weight loss

PPoma HepatomegPain

Pancreatic polypeptide

Very Watery diarrhea

Management of Primary Neuroendocrine Tumors

Glucagonoma

Management of Primary Neuroendocrine Tumors

Surgical Approach - PNET

• Locoregional disease– Radical resection– Enucleation (small,

localized lesions)

• Advanced disease– Cytoreduction– Optimal management

unclear

Management of Primary Neuroendocrine Tumors

Bloomston J GI Surg 2006

Management of Primary Neuroendocrine Tumors

Advanced PNET

Mortality: R2 > R0/1 (21% vs. 2%, p=0.009)

Bloomston J GI Surg 2006

Management of Primary Neuroendocrine Tumors

Advanced PNET

• Long-term survival possible with complete resection of PNET– 5 year survival 74% with R0 resection

• Noncurative pancreatectomy requires extensive resection resulting in substantial morbidity and mortality– Approach cautiously

Management of Primary Neuroendocrine Tumors

Insulinoma

• Basic stats– ~10% “malignant”– ~10% >2 cm– ~10% multiple*– <10% associated with MEN1*

• Multicentric– 6 of 207 (3%) non-MEN1– 10 of 17 (59%) MEN1

Service Mayo Clinic Proceedings 1991

Management of Primary Neuroendocrine Tumors

Insulinoma Surgical Approach

• Non-MEN1– enucleation if small >2-3 mm from PD– partial pancreatectomy for large/deep tumors

• MEN1– subtotal pancreatectomy + enucleation of

head lesions

O’Riordain World J Surg 1994

Management of Primary Neuroendocrine Tumors

Pancreas Bottom Line

• PNET require complex management like any pancreas mass or malignancy

• Multidisciplinary approach – HPB, Surg Onc, GI, Med Onc, Rad Onc, Radiology, Pathology

• PancreaticTumorClinic@OSUMC.edu

Management of Primary Neuroendocrine Tumors

Leave Primary Alone?

197 Patients Undergoing

TACE

100 Primary Tumors Intact at

TACE

97 Primary Tumors Not

Intact at TACE

7 Primaries Symptomatic at

TACE

93 Primaries Asymptomatic at

TACE

67 Primaries Symptomatic at

Resection

30 Primaries Asymptomatic at

Resection

4 PrimariesDeveloped Symptoms

89 PrimariesRemained

Asymptomatic

Courtesy M. Bloomston, unpublished

Management of Primary Neuroendocrine Tumors

Surveillance

• NCCN guidelines exist• Data does not

• Generally– Exams, labs and imaging within 3-12 months– Endoscopy (gastric or rectal) – Exams and labs every 6 months or annual

after first year – imaging when indicated

Management of Primary Neuroendocrine Tumors

The Horizon is Here

• Minimally-invasive operations• Focal radiation• Ablation

Management of Primary Neuroendocrine Tumors

Intraoperative detectionSPECT/CT

Management of Primary Neuroendocrine Tumors

Robotic Distal Pancreatectomy/Splenectomy

Management of Primary Neuroendocrine Tumors

Video

Management of Primary Neuroendocrine Tumors

Robotic Distal Pancreatectomy/Splenectomy