1. Minimal invasive surgery for pancreatic insulinoma: Current evidence
Dr. HO Man-fung
Prince of Wales Hospital

2. CURRENT TREATMENT

3. Medical therapy Dietary modification Diazoxide Somatostatin analogue
Minimal effect on disease progression (especially for non-responder)
Pre-operative symptoms control
60% response rate only…

4. 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

5. 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

6. Surgical approach Pre-operative localization IOUS
Enucleation or Pancreatectomy
? Blind distal pancreatectomy

7. 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:
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, % with invasive investigations

8. Surgical approach Pre-operative localization IOUS
Enucleation or Pancreatectomy
? Blind distal pancreatectomy

9. IOUS being the most sensitive test among all investigations of choice
Ref: A Fuller Understanding of Pancreatic Neuroendocrine Tumours Combined with Aggressive Management Improves Outcome. S.L.Ong et al. Pancreatology 2009;9:583–600

10. 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

11. See the difficulties?
Ref: The American association of endocrine surgeons.Pancreatic neuroendocrine tumors: insulinoma

12. Surgical approach Pre-operative localization IOUS
Enucleation or Pancreatectomy
? Blind distal pancreatectomy

13. Enucleation Pancreatectomy Solitary lesion Size < 2cm
Away from major vessels / pancreatic ducts
Pancreatectomy
Multifocal lesions
Size > 2cm
Close to major vessels / pancreatic ducts
MEN 1

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

15. Surgical approach Pre-operative localization IOUS
Enucleation or Pancreatectomy
? Blind distal pancreatectomy

16. ? 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

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

18. Management of liver metastasis
Resection
Transarterial chemoembolization
Ablation
Systemic chemotherapy
Targeted therapy(e.g. Sunitinib, everolimus)
Liver transplantation

19. MINIMAL INVASIVE SURGERY
Inapproapiate large wound for small benign tumours
Going through evidence of lapasroscopic treatment.
Lack of RCT due to scarcity of case
MINIMAL INVASIVE SURGERY

20. 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:
1st laparoscopic resection of insulinoma – 1992
Low incidence and difficult anatomical location, laparoscopic experience published relatively late compared to other laparoscopic surgery

21. 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
Pancreatic head tumour were traeted with open surgeries.
2004

22. 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
2007

23. 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
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

24. 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
Published in 2008: from
Concerning the result of insulinoma only
Converted to open due to failure to identify the lesion

25. Pre-operative localization - unknown 1/21 converted open
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
Convert due to previous pancreatitis resulted un dense adhesion
1 grade B fistula stayed 60 days

26. 89 patients (Lap vs open : 43 vs 46) 100% pre-operative localization

27. No recurrence in 6 months
Only the 4 patients with tumour cannot located intra-operatively remain symptomatic (tumour not resected)

28. Distal pancreatectomy Enucleation Number of patients 85 496 101
Whipple’s operation
Distal pancreatectomy
Enucleation
Number of patients 85
496
101
Mortality (%)
3.5
0.4
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
Pancreatic fistula / intra-abdominal collection and respiratory complications are most common cause of morbidity
Results for laparoscopic distal pancreatectomy is more favourable compared with open
Lack of survival analysis

29. 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

30. Laparoscopic arm (LDP): 773 (43%) Open arm : 1041 (57%)
Total n= 1814 (18 studies)
Laparoscopic arm (LDP): 773 (43%)
Open arm : 1041 (57%)
Conversion rate : 0 – 30% (not reported in 4 studies)
Among all pancreatic surgery, laparoscopic distal pancreatectomy seen getting more attention than others

31. Operative parameters: Blood loss

32. Post operative recovery: Length of stay

33. Post operative complications: pancreatic fistula

34. Laparoscopic distal pancreatectomy has the advantage of:
Lower blood loss
Faster recovery
Comparable complication profile with open approach
This technique is a reasonable approach in selected cancer patients
Also commented on oncological clearance with only positivity of resection margin (4 studies only) 4.5% vs 8.8%– Not adequate to draw conclusion
10 of 18 studies excluded cases of malignant lesion / invasive ductal carcinoma
Results maybe applicable to patients with insulinoma, that laparoscopic surgery could have benefits

35. Most extensive experience in published literature are from USA, Italy and South Korea
Focused on distal pancreatectomy
What about robots?

36. 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)
Similar tumour size

37. Notice a high rate of planned splenic resection on this initial cohort

38. 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
DP with splenic preservation has been documented to increase hospital stay – mainly due to splenic complications
Splenic infarct in 1 paitent with splenic vessles sacrifies. Managed conservatively
Robot confers additional advantage for splenic preservation

40. 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
Inlcuded few series up to 40 patients comparing… with results of …

41. Robotic pancreatic surgery
Literature in its infancy
Small cohort available even for high volume centres
Case selection bias
Learning curve
Long term results ?

42. Local ablative therapy
Percutaneous RFA ablation
Stephan Limer et al. European Journal of Gastroenterology and Hepatology 2009, 21:
EUS Guided ablation of insulinoma: a new treatment option
Michael J. Levy et al. gastrointestinal Endoscopy, Vol 75, No.1;

43. 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

44. 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

46. INSULINOMA

47. 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

48. Presentation Whipple’s triad: Weight gain Other related syndromes
Fasting hypoglycaemia (< 2.2 mmol/L)
Symptomatic hypoglycaemia (autonomic and neuroglycaemic symptoms)
Relieve of symptoms after administration of glucose
Weight gain
Other related syndromes

49. 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
To rule out other causes of hypoglycaemia

50. Localization Non-invasive Ultrasounography Computed tomography
Magnetic resonance imaging
Somatostatin receptor scintigraphy

51. Localization Invasive Endoscopic ultrasound +/- FNAC
Selective arteriography
Transhepatic portal venous sampling +/- calcium stimulation
Surgical exploration + intra-operative US (IOUS)
Endoscopic ultrasound +/- FNAC

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

53. 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

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