SGH – Surgery

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
SGH – Surgery
3rd Nov 2012
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.
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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
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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
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Surgical Strategy in
Gastro-Intestinal NETs
Emergency surgeries are common
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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
Small bowel/colon
Appendix
Rectum
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- 7%
- 45%/11%
- 17%
- 20%
Gastric NETs (7%)
Type I
Type 2
Type 3
Type 4
- (75%) CAG, multiple small, incidental, indolent
- (5%) ZES, LN 30%, liver mets 10 – 20%
- (20%) sporadic, single larger, LN 20%, liver > 70%
- poorly differentiated
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Akerstrom 2010
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
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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%
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• 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
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Surgical Strategy in
Small bowel NETs
Colonic NETs (11%)
• 50% in the caecum
– Tend to be large
– 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
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• 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
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Appendiceal NETs
(appendiceal
carcinoids) 17%
• 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
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Rectal NETs (20%)
• < 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
: 60 – 80% mets
– Radical resection
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Surgical
Strategy for
Rectal NETs
Surgical Strategy for
Pancreatic NETs
functioning and non-functioning
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Pancreatic
NETS
• Most occur
sporadically but some
can be in association
with familial
syndromes
– MEN1
– Von Hipple-Lindau
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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,
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• 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
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Insulinoma
• Large tumor (> 4 cm) high
chance of malignancy
• Small pancreatic body/tail
tumor should be resected by
distal pancreatectomy
Surgical Strategy
for Insulinoma
– 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
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Familial insulinoma may
be multiple
Gastrinoma
• 2nd 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
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Surgical resection
for Pancreatic NETs: the Singapore
General Hospital experience
• 61 patients resected between 1991 – 2008
• 20 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
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Pierce Chow FRCSE PhD
PNETs resection at SGH
61patients
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2 with MEN1
1 with Von Hipple Lindau
Goh, 2010
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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%
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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
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The Role of Surgery in metastatic
and recurrent GEPMETs:
Resection for improved survival
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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
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Pierce Chow FRCSE PhD
Hepatic resection for NET metastasis
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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
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Pierce Chow FRCSE PhD
Resection for hepatic metastases from NET
Median overall survival 9.6 years
5-year overall survival 77.4%
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Glazier 2010
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Pierce Chow FRCSE PhD
Resection for
recurrent
Pancreatic NET
Annals of Surgery 2006
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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%
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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 0.0007)
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Actuarial survival after re-operation:
5-yr
10-yr
25-yr
Overall
84%
76%
38%
Malignant 81%
72%
36%
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Pierce Chow FRCSE PhD
Should resection of hepatic metastases
be now preceded or superseded by
Lu-77 PRRT?
• 5th April 2012
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• 3rd October 2012
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Anesthetic Considerations in
Surgery for GEPMET
Beware of Storms!
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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
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Pierce Chow FRCSE PhD
Thank
You!
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