Advanced Surgical Techniques For Pancreatic Cancer

Dr. Janak Parikh, MD, MSHSNovember 2, 2013

St. John Providence Health System

2013 GI Cancer 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)

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Incidence and Mortality

• 45,000 new cases in 45,000 new cases in

US in 2013US in 2013

• 3% of malignancies in

the United States

• Fourth leading cause

of cancer death in the

United States

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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 therapiesMost patients are treated with palliative therapies

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Historical Context (1985-2008)

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Incidence\100,000Mortality\100,000

Incidence and Mortality Rates 1985-2008NCI’s SEER Program http://www.seer.cancer.gov/

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Fewer Than 1/3 Of Resectable Patients Receive Surgery

Pancreatoduodenectomy—Whipple Operation

History and Evolution

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History of Pancreatoduodenectomy

Friedrich Trendelenburg (1882)

Allesandro Codivilla (1898)

Walter Kausch (1909)

George Hirschel (1914)OttorinoTenani (1922)

Allan O. Whipple (1935)

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“Whipple Operation”

Allen Oldfather Whipple

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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;130:1049-53

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Improving the Whipple Operation2013 GI Surgery Symposium

NEJM 2002;346(15):1128-37

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Pancreatic Surgery Is Safe At High-Volume Hospitals

Long-Term Survival Better At High-Volume Hospitals

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Low Volume Hospital

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Fong, Ann Surg 2005; 242:540-7

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High-Volume Surgeons Have Better Outcomes

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Pancreatoduodenectomy—Whipple Operation

Evolution of Operative Techniques

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• Used less often with the evolution

of imaging quality.

• Considered when:

– Marked weight loss

– Very high CA19-9

– Pain

– Frail patient

Is Diagnostic Laparoscopy Necessary?

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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.

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The Resection

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The Reconstruction

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Pylorus Preserving

vs.

Classic Whipple?

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Theoretical Advantages

• Pylous –preservation

– More physiologic

– Less dumping

• Classic

– Better tumor clearance

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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

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Methods of Reconstruction

• Pancreatojejunostomy– Most common

reconstruction– More physiologic

• Pancreatogatrostomy– Lower leak rate– Access to PD

• Techniques– Duct-to-mucosa– Invagination– Externalization

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Externalizing the Pancreatic-Enteric Anastomosis

• Used by some for high-risk patients:– Soft gland– Small duct– Frail patient

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Palliation of Pain with Alcohol Splanchnicectomy

N = 20 17 19 11 0 5 19 12

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8.0

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*

Lillemoe, et al. Ann Surg 217:447-457, 1993

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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

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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

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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 inPancreatic AdenocarcinomaA Contraindication for Resection? ANNALS OF SURGERY 1996 Vol. 224, No. 3, 342-349

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Methods of Reconstruction

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Venous Resection in Pancreas Cancer

Author NOp

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% n.r. 72% 23

Harrison 58 5% n.r. 59% 13

Yekebas 136 4% 73% 58% 15

I.U. 73 3% 65% 71% 14

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Minimally Invasive Pancreatoduodenectomy

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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?

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Drawbacks• Learning curve• Increased operative time• Laparoscopic U/S• ? Cost• ? Risk• ? Malignancy

Extent of resectionAdequate surgical marginsLymph node basin dissectionPort site recurrence

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Laparoscopic Whipple

• First performed in 1994 by Gagner and Pomp.

– Coversion rate 40%

– OR time 8.5h

– Authors concluded no advantage

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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.

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Laparoscopic Whipple

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Conv Lap Op Time Comp LOS Panc

Author Year N (%) Recon (%) (Min) (%) (days) Can (%)

Gagner 1997 10 40 60 510 30 22.3 40

Dulucq 2006 25 12 50 287 32 16.2 44

Palanivelu 2007 42 0 100 370 31 10.1 21

Pugliese 2008 19 31 31 461 37 18 58

Kendrick 2010 65 4 95 368 40 7 47

Outcomes for Laparoscopic Whipple

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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

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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%

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Robotic Whipple

• HJ leak: 2%

• DJ leak: 6%

• Bleeding: 3.7%

• Pseudoaneurysm: 14.8%

• Grade B fistula: 3.7%

• Grade C fistula: 3.7%

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Robotic Whipple

• Mean OR time 527 min (360min last 50)

• Conversion: 8%

• Reoperation: 3%

• LOS: 10 days

• Readmission: 28%

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Distal Pancreatectomy

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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)

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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

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Laparoscopic Approach Is Standard of Care

• Associated with:

– Decreased complication rate

– Decreased blood loss

– Shorter LOS

– Higher splenic preservation rate

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Laparoscopic Distal Pancreatectomy

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Robotic Distal

• 30-, 90-day mortality: 0%

• Minor complications: 59%

• Major complications: 13%

• Grade B fistula: 12%

• Grade C fistula: 4.8%

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Robotic Distal

•OR time: 256 min

•LOS: 6 days

•Readmission: 28%

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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.

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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

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Surgical Outcomes in 2013

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N Mortality Morbidity

Overall 1175 2% 38%

1970’s 2323 30%30% --

1980’s 65 5% 30%

1990’s 514 2% 31%

2000’s 573 1% 45%

1423 Pancreaticoduodenectomies for Pancreatic Cancer

Winter JM, et al. J Gastrointest Surg 2006, 10:1199-1210

Pancreatic Surgery Is Safe

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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 2006 123 15 mo 12% - Stage, margin

Ferrone 2008 618 - 12% 5% Stage, Margin

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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

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Paradigm Shift?

• Opposition:

– Resectable patients progress to unresectable

– Complications of chemo prevent/delay surgery, increase complications

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Pre-Operative Therapy Selects Patients Better than Upfront Surgery

● 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).

*Evans DB, et al. JCO, 2008

Protocol Regimen Number of pts

Resection Rate

Overall Survival

MDA

98-020*

Gem/XRT 86 74% 34 mo

MDA

01-341^

Gem/Cis

Gem/XRT

90 66% 31 mo

^Varadhachary GR, et al. JCO, 2008

●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.

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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.

2013 GI Surgery Symposium

Advanced Surgical Techniques For Pancreatic Cancer

Dr. Janak Parikh, MD, MSHSNovember 2, 2013

St. John Providence Health System

2013 GI Cancer Symposium