Minimal invasive surgery for pancreatic insulinoma: Current evidence

Dr. HO Man-fung

Prince of Wales Hospital

CURRENT TREATMENT

Medical therapy

Dietary modification Diazoxide Somatostatin analogue

Minimal effect on disease progression (especially for non-responder)

Pre-operative symptoms control

Surgery

Surgery is the Mainstay of treatment for insulinoma Curative (local disease / limited liver metastasis) Symptomatic control in metastastic disease

Enucleation Distal pancreatectomy +/- splenectomy Pancreaticoduodenectomy Central / total pancreatectomy Resection of liver metastasis

Special concerns of insulinoma

Small size < 2cm in ~ 80% Difficulty in localization

90% benign and solitary Resection strategy Room for minimal invasive surgery

Overt symptoms, poorly controlled by drugs Pre-operative control of symptoms Even palliative resection in metastatic disease wound be

beneficial

Surgical approach

Pre-operative localization IOUS Enucleation or Pancreatectomy ? Blind distal pancreatectomy

Lo et al. Surgical Endoscopy (2004) 18: 297-302 60% with CT, 80% with EUS, 100% with THPVS

K. Ravi et al. Ann R Coll Surg Engl 2007; 89: 212-217. 67% (incl. USG, CT, MRI, THPVS)

Mehrdad Nikfarjam et al. Annals of Surgery • Volume 247, Number 1, January 2008 29-80% with non invasive investigation, 85-100% with invasive

investigations

Surgical approach

Pre-operative localization IOUS Enucleation or Pancreatectomy ? Blind distal pancreatectomy

Ref: A Fuller Understanding of Pancreatic Neuroendocrine Tumours Combined with Aggressive Management Improves Outcome. S.L.Ong et al. Pancreatology 2009;9:583–600

Amelia C. Grover et al. A prospective evaluation of laparoscopic exploration with intraoperative ultrasound as a technique for localizing sporadic insulinomas. Surgery 2005; 138:1003-8

See the difficulties?

Ref: The American association of endocrine surgeons.Pancreatic neuroendocrine tumors: insulinoma

Surgical approach

Pre-operative localization IOUS Enucleation or Pancreatectomy ? Blind distal pancreatectomy

Enucleation Solitary lesion Size < 2cm Away from major vessels / pancreatic ducts

Pancreatectomy Multifocal lesions Size > 2cm Close to major vessels / pancreatic ducts MEN 1

Ref: L.Fernandez-Cruz et al. Is laparoscopic ressection adequate in patients with neuroendocrine pancreatic tumour. World Journal of Surgery (2008) 32: 904-917.

Surgical approach

Pre-operative localization IOUS Enucleation or Pancreatectomy ? Blind distal pancreatectomy

? Blind resection•4/61 persistent symptoms despite resection

•Further resection jeopadized parachymal preservation (90% benign)

•Importance of pre-operative localization

•Portal venous sampling (~100% localization)

Ref: Improved Contemporary Surgical Management of Insulinomas. A 25-year Experience at the Massachusetts General Hospital. Mehrdad Nikfarjam et al. Annals of Surgery • Volume 247, Number 1, January 2008

K. Ravi et al. Ann R Coll Surg Engl 2007; 89: 212-217.

Management of liver metastasis

Resection Transarterial chemoembolization Ablation Systemic chemotherapy Targeted therapy(e.g. Sunitinib,

everolimus) Liver transplantation

MINIMAL INVASIVE SURGERY

Lapasroscpic pancreatic resection 1st laparoscopic pancreatic resection -1992

Gagner M et al (1996). J Gastrointest Surg 1: 20-26 Cushieri A. et al (1996). Ann Surg 223:280-285

1st laparoscopic resection of insulinoma – 1992

Low incidence and difficult anatomical location, laparoscopic experience published relatively late compared to other laparoscopic surgery

2 enucleations and 2 distal pancreatectomies done laparoscopically

100% pre-operative localization Only for lesions over body and tail 1 patient with post operative pancreatic leakage

1st comparative study of laparoscopic vs open approach (12 vs 9)

Comparison with historical cohort No significant difference in morbidty, mortality,

intraoperative variables Only 1 patient used intra-operative USG Denied use of intra-operative USG to be

necessary

Laparoscopic USG Only way to replace palpation in laparoscopic

surgery

Localization of lesion(s) Sensitivity 83-98%a

Comparable to THPVS b

Define anatomical relationship with major vessels, main pancreatic duct

a) Mehrdad Nikfarjam et al . Improved Contemporary Surgical Management of Insulinomas. A 25-year Experience at the Massachusetts General Hospital.. Annals of Surgery • Volume 247, Number 1, January 2008

b) Amelia C. Grover et al. A prospective evaluation of laparoscopic exploration with intraoperative ultrasound as a technique for localizing sporadic insulinomas. Surgery 2005; 138:1003-8

pNETs with pancreatic resection, 20 patients with insulinoma

Pre-op localization 100% 1/20 conversion to open Mean follow up of 36 months, no recurrence Significant less blood loss and operative time for

laparoscopic enucleation

21 patients Pre-operative localization - unknown 1/21 converted open IOUS: localization, intraoperative decision, marking

of transection line 3 patients with pancreatic fistula All except 1 discharged in 1 week No recurrence

89 patients (Lap vs open : 43 vs 46) 100% pre-operative localization

Whipple’s operation

Distal pancreatectomy

Enucleation

Number of patients 85 496 101

Mortality (%) 3.5 0.4 0

Mobidity (%) 30.7 34.1 47

Mean blood lost (ml) 126 311 -

Conversion rate (%) 8.75 12.1 23.3

Mean operation time (min)

371 229 132

Mean hospital stay 13.6 7.5 7.8

Represent early experience Highly selected cases Indicating minimal invasive surgery is feasible Pancreatic fistula is still the most prevalent

complication Lacking of long term results, e.g. survival,

recurrence Heterogeneous disease

Total n= 1814 (18 studies)

Laparoscopic arm (LDP): 773 (43%) Open arm : 1041 (57%)

Conversion rate : 0 – 30% (not reported in 4 studies)

Operative parameters: Blood loss

Post operative recovery: Length of stay

Post operative complications: pancreatic fistula

Laparoscopic distal pancreatectomy has the advantage of:Lower blood lossFaster recoveryComparable complication profile with open approach

This technique is a reasonable approach in selected cancer patients

What about robots?

1st 30 cases in University of Pittsburgh Compared with 94 patient with laparoscopic

distal pancreatectomy 0% conversion rate 100% R0 resection Median LN harvest (Lap vs Robot = 9 vs 19)

v

Better visualization, freedom of movement, stability Preservation of spleen and splenic vessels 21/22 patient with successful splenic preservation 17 patient with splenic vessels preserved 1 patient developed post op splenic infarct

Further expand the advantage minimal invasive surgery by improving rate of spleen preservation

Open vs Laparoscopic / robotic Whipple’s operation

Open vs Laparoscopic / robotic distal pancreatectomy

Longer operative time Decreased blood lost Shorter hospital stay Similar complication profile Improved rate of R0 resection

Robotic pancreatic surgery

Literature in its infancy Small cohort available

even for high volume centres

Case selection bias Learning curve Long term results

Local ablative therapy

Percutaneous RFA ablation Stephan Limer et al. European Journal of

Gastroenterology and Hepatology 2009, 21:1097-1101

EUS Guided ablation of insulinoma: a new treatment option Michael J. Levy et al. gastrointestinal Endoscopy, Vol

75, No.1;200-206

Conclusion

Insulinoma is benign most of the time, but causing significant biochemical disturbance that require surgical treatment

Localization is of utmost importance in surgical success

Laparoscopic surgery offers treatment with less trauma and similar safety profile

Novel treatment for surgically unfit individuals

Conclusion

Insulinoma is an ideal entity for minimal invasive pancreatic surgery

Lesion are small and benign most of the time no concern for involved margin, lymphatic dissection

Laparoscopic and robotic pancreatic surgery is feasible for management of pancreatic insulinoma

INSULINOMA

Insulinoma

Subgroup of pancreatic neuroendocrine tumours (pNETs)

Commonest functional pNETs (25%) Incidence : 4 in 1,000,000 Unsuppressed production of endogenous

insulin As part of genetic syndromes (5-8%)

MEN I, VHL, NF I, TS

Presentation

Whipple’s triad: Fasting hypoglycaemia (< 2.2 mmol/L)Symptomatic hypoglycaemia (autonomic and

neuroglycaemic symptoms)Relieve of symptoms after administration of

glucose Weight gain Other related syndromes

Biochemical diagnosis

Ref: A Fuller Understanding of Pancreatic Neuroendocrine Tumours Combined with Aggressive Management Improves Outcome. S.L.Ong et al. Pancreatology 2009;9:583–600

Localization Non-invasive

UltrasounographyComputed tomographyMagnetic resonance imagingSomatostatin receptor scintigraphy

Localization Invasive

Selective arteriographyTranshepatic portal venous

sampling +/- calcium stimulationSurgical exploration + intra-

operative US (IOUS)

Endoscopic ultrasound +/- FNAC

Ref: A Fuller Understanding of Pancreatic Neuroendocrine Tumours Combined with Aggressive Management Improves Outcome. S.L.Ong et al. Pancreatology 2009;9:583–600

WHO classification

Ref: A Fuller Understanding of Pancreatic Neuroendocrine Tumours Combined with Aggressive Management Improves Outcome. S.L.Ong et al. Pancreatology 2009;9:583–600

Ref: L.Fernandez-Cruz et al. Is laparoscopic resection adequate in patients with neuroendocrine pancreatic tumour. World Journal of Surgery (2008) 32: 904-917.