1. St. John Providence Health System
2013 GI Cancer Symposium
Advanced Surgical Techniques
For Pancreatic Cancer
Dr. Janak Parikh, MD, MSHS
November 2, 2013
St. John Providence Health System

2. Overview Background Basic Whipple Operation History Resection criteria
2013 GI Surgery Symposium
Overview
Background
Basic Whipple Operation
History
Resection criteria
Technique (Pylorus-Preservation vs. Classic)
Advanced Whipple Operation
Vascular resection/reconstruction
Laparoscopic Whipple
Robotic Whipple
Distal Pancreatectomy
Technique (w/ or w/o splenectomy, Appleby)
Minimally invasive (Laparoscopic, Robotic)

3. Incidence and Mortality
2013 GI Surgery Symposium
Incidence and Mortality
45,000 new cases in US in 2013
3% of malignancies in the United States
Fourth leading cause of cancer death in the United States

4. Most patients are treated with palliative therapies
2013 GI Surgery Symposium
Pancreatic Cancer
High incidence of regionally advanced and metastatic disease
Only 10-15% pts have resectable disease
Head 60% Body/Tail 40%
 
20% resectable <5% resectable
 
20% 5-yr survival <15% 5-yr survival
 
<3% alive at 5 years
Most patients are treated with palliative therapies

5. Historical Context (1985-2008)
2013 GI Surgery Symposium
Historical Context ( )
By way of introduction, while pancreatic cancer accounts for only 2% of all new cancers diagnosed in the United States, it remains the fourth leading cause of cancer-related death in both men and women.
Because it is usually diagnosed at an advanced stage, survival rates remain poor compared to that in other types of cancer. The overall incidence and mortality rates in pancreatic cancer have changed little over the past three decades although evidence suggests that both the incidence and death rate have increased slightly since 2003.
In 2007, an estimated 37,130 individuals will be diagnosed with pancreatic cancer and an estimated 33,370 deaths will occur as a result of this disease.
It is estimated that approximately $1.5 billion is spent in the United States each year on the treatment of pancreatic cancer.
Here’s data form the National Cancer Institutes SEER Program showing essentially parallel incidence and morality rates for pancreas cancer over a twenty-three year period of time.
Incidence and Mortality Rates
NCI’s SEER Program 5

6. Fewer Than 1/3 Of Resectable Patients Receive Surgery
2013 GI Surgery Symposium
Fewer Than 1/3 Of Resectable Patients Receive Surgery

7. Pancreatoduodenectomy—Whipple Operation
2013 GI Surgery Symposium
Pancreatoduodenectomy—Whipple Operation
History and Evolution

8. History of Pancreatoduodenectomy
2013 GI Surgery Symposium
History of Pancreatoduodenectomy
George Hirschel (1914)
OttorinoTenani (1922)
Friedrich Trendelenburg (1882)
Allan O. Whipple (1935)
Walter Kausch (1909)
Allesandro Codivilla (1898)

9. 2013 GI Surgery Symposium
“Whipple Operation”
Allen Oldfather Whipple

10. 1960’s – 1970’s High perioperative morbidity Hospital mortality – 25%
2013 GI Surgery Symposium
1960’s – 1970’s
High perioperative morbidity
Hospital mortality – 25%
Long term survival for pancreatic cancer – 5%
Calls to abandon PD for pancreatic cancer
Crile, Surgery Gyn Obstet 1970;130:

11. Improving the Whipple Operation
2013 GI Surgery Symposium
Improving the Whipple Operation
The real key to the paper from Hopkins is that Dr Cameron followed up on this initial report by assembling a talented
group of GI surgeons and began to assimilate an experience that was unrivaled and audacious. 145, 201, 650, the numbers
Began rolling out and with them lower and lower morbidity and mortality rates, and higher survival rates. This Japanese also
got caught up in this numeric proliferation. The end result of this technological frenzy was set of standards proposed for
surgeons doing pancreatic resections which harkens back to the pleas made by Howard and Crile. 11

12. Pancreatic Surgery Is Safe At High-Volume Hospitals
2013 GI Surgery Symposium
Pancreatic Surgery Is Safe At High-Volume Hospitals
This seminal paper reviewed over 2.5 million medicare patients undergoing cv and cancer operations between 1994 and Notably, pancreatic resection (with esophagectomy) were the two cancer operations in which dramatic differences in mortality were seen between low and high-volume hospitals
NEJM 2002;346(15):

13. Long-Term Survival Better At High-Volume Hospitals
2013 GI Surgery Symposium
Long-Term Survival Better At High-Volume Hospitals
P=0.001
High Volume Hospital
Low Volume Hospital
A number of studies have demonstrated that surgical resection at high-volume centers is associated with improved short term survival. Whether long-term survival after resection for cancer are superior at high-volume centers is unknown.
Fong, Ann Surg 2005; 242:540-7

14. High-Volume Surgeons Have Better Outcomes
2013 GI Surgery Symposium
High-Volume Surgeons Have Better Outcomes

15. Pancreatoduodenectomy—Whipple Operation
2013 GI Surgery Symposium
Pancreatoduodenectomy—Whipple Operation
Evolution of Operative Techniques

16. Is Diagnostic Laparoscopy Necessary?
2013 GI Surgery Symposium
Is Diagnostic Laparoscopy Necessary?
Used less often with the evolution of imaging quality.
Considered when:
Marked weight loss
Very high CA19-9
Pain
Frail patient

17. Steps of the Whipple Abdominal exploration to r/o occult metastases.
2013 GI Surgery Symposium
Steps of the Whipple
Abdominal exploration to r/o occult metastases.
Mobilization of duodenum and head of pancreas.
Check for aberrant anatomy.
Isolation of bile duct, GDA, pylorus.
Tunnel under neck of pancreas.

18. 2013 GI Surgery Symposium
The Resection

19. 2013 GI Surgery Symposium
The Reconstruction

20. Pylorus Preserving vs. Classic Whipple?
2013 GI Surgery Symposium
Pylorus Preserving
vs.
Classic Whipple?

21. Theoretical Advantages
2013 GI Surgery Symposium
Theoretical Advantages
Pylous –preservation
More physiologic
Less dumping
Classic
Better tumor clearance

22. Reality You can do it however you want. No difference in DGE
2013 GI Surgery Symposium
Reality
You can do it however you want.
No difference in DGE
No difference in wt loss/wt gain
Everything evens out at around 6-8 weeks

23. Methods of Reconstruction
2013 GI Surgery Symposium
Methods of Reconstruction
Pancreatojejunostomy
Most common reconstruction
More physiologic
Pancreatogatrostomy
Lower leak rate
Access to PD
Techniques
Duct-to-mucosa
Invagination
Externalization

24. Externalizing the Pancreatic-Enteric Anastomosis
2013 GI Surgery Symposium
Externalizing the Pancreatic-Enteric Anastomosis
Used by some for high-risk patients:
Soft gland
Small duct
Frail patient

25. Palliation of Pain with Alcohol Splanchnicectomy
2013 GI Surgery Symposium
Palliation of Pain with Alcohol Splanchnicectomy
Lillemoe, et al. Ann Surg 217: , 1993

26. 2013 GI Surgery Symposium
Vascular Resection
Venous resection is acceptable to achieve an R0 resection.
Arterial resections not recommended.
Associated with increased blood loss, increased transfusions, increased OR time, and increased morbidity.
No difference in mortality

27. 2013 GI Surgery Symposium
Vascular Resection
Most require partial vein resection with primary repair.
Reconstruction options include:
Oversew or patch
end-to-end vs. interposition graft (internal jugular vein, left renal vein, PTFE)
Postop anticoagulation varies by surgeon: none, ASA/plavix, coumadin

28. Methods of Reconstruction
2013 GI Surgery Symposium
Methods of Reconstruction
Tseng, JF, et. al. Pancreaticoduodenectomy With Vascular Resection:
Margin Status and Survival Duration, J GASTROINTEST SURG 2004;8:935–950
Harrison, LE, et. al. Isolated Portal Vein Involvement in
Pancreatic Adenocarcinoma
A Contraindication for Resection? ANNALS OF SURGERY 1996 Vol. 224, No. 3,

29. Methods of Reconstruction
2013 GI Surgery Symposium
Methods of Reconstruction

30. Venous Resection in Pancreas Cancer
2013 GI Surgery Symposium
Venous Resection in Pancreas Cancer
Author N
Op Mort.
Vessel
Invasion
1 yr. survival
Median
Survival
Ishikawa 35 6%
86%
n.r. 9
Takahashi* 79
17%
61%
38% 14
Roder 31 0%
77%
20% 8
Tseng
141 2%
72% 23
Harrison 58 5%
59% 13
Yekebas
136 4%
73%
58% 15
I.U. 73 3%
65%
71%
These are some of the representative series reported in the literature utilizing portal vein resection for pancreatic adenocarcinoma. There patient numbers are low, but reasonable, and except for the series by Takahashi which included both venous and arterial reconstructions in their data, the mortality rate is no different than patients who do not undergo portal vein reconstruction. Of note, is the high incidence of transmural venous invasion in both the Japanese and European experience. Harrison’s report from Memorial Sloan Kettering and our own Series did not assess the histologic venous invasion. The one year survivals are respectable, and the median survivals, except for the experience
Of Ishikawa and Roder are similar to the standard Whipple. Portal venous resection and reconstruction can be done with acceptable morbidity and mortality. These patients must be carefully selected to maximize the opportunity to achieve a margin negative resection. Although this type of operation has not been shown to improve survival, it has similar survival to patients who undergo the standard operation

31. Minimally Invasive Pancreatoduodenectomy
2013 GI Surgery Symposium
Minimally Invasive Pancreatoduodenectomy

32. Benefits of Laparoscopic Surgery
2013 GI Surgery Symposium
Benefits of Laparoscopic Surgery
Less post-operative pain
Less post operative ileus
Preserved immune function
Decreased stress response
Shorter hospital stay
Improved cosmesis
Decreased complications ?
Faster time to receipt of chemo?

33. Drawbacks Learning curve Increased operative time Laparoscopic U/S
2013 GI Surgery Symposium
Drawbacks
Learning curve
Increased operative time
Laparoscopic U/S
? Cost
? Risk
? Malignancy
Extent of resection
Adequate surgical margins
Lymph node basin dissection
Port site recurrence

34. Laparoscopic Whipple First performed in 1994 by Gagner and Pomp.
2013 GI Surgery Symposium
Laparoscopic Whipple
First performed in 1994 by Gagner and Pomp.
Coversion rate 40%
OR time 8.5h
Authors concluded no advantage

35. Laparoscopic Whipple 7 centers report more than 30 lap Whipples.
2013 GI Surgery Symposium
Laparoscopic Whipple
7 centers report more than 30 lap Whipples.
Feasibility established
Lower EBL, fewer wound complications, shorter LOS
Increased OR time (541 min vs 401min)
No difference pancreatic fistula rates, overall complications, DGE, or mortality.

36. 2013 GI Surgery Symposium
Laparoscopic Whipple

37. Outcomes for Laparoscopic Whipple
2013 GI Surgery Symposium
Outcomes for Laparoscopic Whipple
Conv
Lap
Op Time
Comp
LOS
Panc
Author
Year N
(%)
Recon (%)
(Min)
(days)
Can (%)
Gagner
1997 10 40 60
510 30
22.3
Dulucq
2006 25 12 50
287 32
16.2 44
Palanivelu
2007 42
100
370 31
10.1 21
Pugliese
2008 19
461 37 18 58
Kendrick
2010 65 4 95
368 7 47
40 of 42 for Palanivelu for malignancy

38. Robotic Whipple Advantages vs. Laparoscopic Whipple:
2013 GI Surgery Symposium
Robotic Whipple
Advantages vs. Laparoscopic Whipple:
Better visualization (3-D)
More precise suturing
Disadvantages
Steep learning curve
Longer operative time
Need for 2 experienced surgeons

39. Robotic Whipple Largest experience from U of Pitt (n=132).
2013 GI Surgery Symposium
Robotic Whipple
Largest experience from U of Pitt (n=132).
30-day mortality 1.5%
90-day mortality 3.8%
Minor complications: 41%
Major complications: 21%

40. Robotic Whipple HJ leak: 2% DJ leak: 6% Bleeding: 3.7%
2013 GI Surgery Symposium
Robotic Whipple
HJ leak: 2%
DJ leak: 6%
Bleeding: 3.7%
Pseudoaneurysm: 14.8%
Grade B fistula: 3.7%
Grade C fistula: 3.7%

41. Robotic Whipple Mean OR time 527 min (360min last 50) Conversion: 8%
2013 GI Surgery Symposium
Robotic Whipple
Mean OR time 527 min (360min last 50)
Conversion: 8%
Reoperation: 3%
LOS: 10 days
Readmission: 28%

42. Distal Pancreatectomy
2013 GI Surgery Symposium
Distal Pancreatectomy

43. Body/Tail Cancers Tend to present later and with larger tumors.
2013 GI Surgery Symposium
Body/Tail Cancers
Tend to present later and with larger tumors.
Most will be metastatic at time of presentation (10-15% surgical candidates).
Diagnostic laparoscopy performed for most (esp. w/ large tumors, high CA 19-9, debilitated patients)

44. Is Splenectomy Necessary?
2013 GI Surgery Symposium
Is Splenectomy Necessary?
Splenectomy is required during resection for malignancy to obtain adequate lymph node harvest.
For premalignant or benign lesions, spleen-preservation attempted when possible.
Warshaw technique: splenic artery and vein ligation without removal of spleen

45. Laparoscopic Approach Is Standard of Care
2013 GI Surgery Symposium
Laparoscopic Approach Is Standard of Care
Associated with:
Decreased complication rate
Decreased blood loss
Shorter LOS
Higher splenic preservation rate

46. Laparoscopic Distal Pancreatectomy
2013 GI Surgery Symposium
Laparoscopic Distal Pancreatectomy

47. Robotic Distal 30-, 90-day mortality: 0% Minor complications: 59%
2013 GI Surgery Symposium
Robotic Distal
30-, 90-day mortality: 0%
Minor complications: 59%
Major complications: 13%
Grade B fistula: 12%
Grade C fistula: 4.8%

48. Robotic Distal OR time: 256 min LOS: 6 days Readmission: 28%
2013 GI Surgery Symposium
Robotic Distal
OR time: 256 min
LOS: 6 days
Readmission: 28%

49. 2013 GI Surgery Symposium
Appleby Procedure
Originally described for locally advanced gastric cancer.
Involves en-bloc resection of celiac axis, body/tail of pancreas and spleen.
All should undergo neoadjuvant therapy before attempting an Appleby procedure.

50. Appleby: Plane of Resection
2013 GI Surgery Symposium
Appleby: Plane of Resection
Bonnet, S. et. al. Indications and surgical technique of Appleby's operation for tumor invasion of the celiac trunk and its branches. Journal de Chirurgie. Volume 146, Issue 1, February 2009, Pages 6–14

51. 2013 GI Surgery Symposium
Surgical Outcomes in 2013

52. Pancreatic Surgery Is Safe
2013 GI Surgery Symposium
Pancreatic Surgery Is Safe
1423 Pancreaticoduodenectomies for Pancreatic Cancer N
Mortality
Morbidity
Overall
1175 2%
38%
1970’s 23
30% -
1980’s 65 5%
1990’s
514
31%
2000’s
573 1%
45%
Winter JM, et al. J Gastrointest Surg 2006, 10:

53. Long-Term Survival Remains Poor
2013 GI Surgery Symposium
Long-Term Survival Remains Poor
Author
Year N
Median survival
5 year survival
10 year survival
Predictors
Ahmad
2001
116
16 mo
19% -
Adj tx
Cleary
2004
123
14 mo
15% 4%
Stage, grade
Winter
2006
1175
18 mo
18%
11%
Size, LN, margin, grade
Han
15 mo
12%
Stage, margin
Ferrone
2008
618 5%
Stage, Margin

54. 2013 GI Surgery Symposium
Paradigm Shift?
Neoadjuvant therapy for all patients with pancreatic adenocarcinoma.
Potential benefits:
Avoid surgery in patients with widely micrometastatic disease
Down-size tumor to avoid vein resection
Examination of tumor biology

55. Paradigm Shift? Opposition:
2013 GI Surgery Symposium
Paradigm Shift?
Opposition:
Resectable patients progress to unresectable
Complications of chemo prevent/delay surgery, increase complications

56. Pre-Operative Therapy Selects Patients Better than Upfront Surgery
2013 GI Surgery Symposium
Pre-Operative Therapy Selects Patients Better than Upfront Surgery
Surgery was avoided in 25-35% of the patients; their median survival was 7-10 mo.
Local failure occurred in 10-25% of patients undergoing resection; suggesting radiation may have a role in preoperative setting.
Avoids surgery in patients with rapidly progressive disease (unfavorable tumor biology).
Avoids surgery in patients unable to tolerate the stress of pre-operative therapy (those revealed to be unfit).
Protocol
Regimen
Number of pts
Resection Rate
Overall Survival
MDA
98-020*
Gem/XRT 86
74%
34 mo
01-341^
Gem/Cis 90
66%
31 mo
Thus, our group at the University of Texas, MD Anderson Cancer Center has been interested in evaluating the role of preoperative chemoradiation in those patients who appear to have potentially resectable disease. This strategy allows all patients to undergo preoperative therapy and provides for early treatment of microscopic metastatic disease. Morevover, it provides an interval of time to observe for the development of overt metastatic disease which may not have been apparent at the time of presentation. The morbidity of surgery is thereby avoided n those patients with rapidly progressive disease. Lastly, since pancreatic cancer often develops in elderly patients with medical comorbidities, it provides an opportunity to observe patient tolerance to preoperative therapy as a predictor of tolerance to surgery.
*Evans DB, et al. JCO, 2008
^Varadhachary GR, et al. JCO, 2008

57. Pancreatic Cancer in 2013 Surgery can be done safely
2013 GI Surgery Symposium
Pancreatic Cancer in 2013
Surgery can be done safely
Venous resection acceptable for R0 rxn.
Minimally invasive distal pancreatectomy should be standard of care.
Minimally invasive Whipple feasible, safe at selected centers.
Need better systemic therapy to impact long-term survival.

58. St. John Providence Health System
2013 GI Cancer Symposium
Advanced Surgical Techniques
For Pancreatic Cancer
Dr. Janak Parikh, MD, MSHS
November 2, 2013
St. John Providence Health System