ΚΑΡΚΙΝΟΣ ΤΟΥ ΠΑΓΚΡΕΑΤΟΣΧΕΙΡΟΥΡΓΙΚΗ ΑΝΤΙΜΕΤΩΠΙΣΗ

ΔΗΜΗΤΡΗΣ Π. ΚΟΡΚΟΛΗΣ

ΧΕΙΡΟΥΡΓΟΣ

ΔΙΔΑΚΤΩΡ ΠΑΝΕΠΙΣΤΗΜΙΟΥ ΑΘΗΝΩΝ

Α.Ο.Ν.Α. «Ο ΑΓΙΟΣ ΣΑΒΒΑΣ»

No disclosures

Stage-specific survivalMonths From Dx

All patients 9.3

Stage I, II 15.4 resected 24.1 not resected 10.3 Stage III 9.9 borderline 17.6

Stage IV 6.1

MDACC: Pancreatic Cancer Program Database 1991-2007, N = 4,395Katz MHG, Hwang RF, et al. TNM staging of pancreatic adenocarcinoma. CA Cancer J Clin. 2008;58(2):111-25.

Imaging Template for Pancreatic Cancer

• Tumor size and location• Tumor and veins relationship – SMV, portal vein

and splenic vein• Tumor and arteries relationship – SMA, celiac

axis, common hepatic artery• Presence or absence of distant metastases – liver,

lung, peritoneum• CT scan: “Pancreatic Protocol”

Portal vein & SMV anatomy

PVSplenic Vein

SMV

Ileal branch of SMV Jejunal branch of SMV

IMV may enter spl vein or SMV

SMA

Vena cava

Resectable defined

• Resectable: No extension into the celiac, CHA, SMA stage I or II (cT1-3 +/- possible lymphadenopathy)

• Borderline: The stuff in the middle

• Locally advanced means unresectable: Involvement of the celiac, SMA encasement of >180°, stage III (cT4), aortic or caval involvement.

Kitts 527268

Resectable tumor, RRHA

SMV

SMA

T

Resectable adenocarcinoma of the pancreatic head

Resectable : Likely to require venous resection

SMV

SMA

T

Cava

SMA

Borderline Resectable

Varadhachary GR, et al. Ann Surg Oncol. 2006;13(8):1035-46

Katz MHG, et al. J Am Coll Surg. 2008;206(5):833-46

SMV

Locally Advanced (Stage III)

SMV

SMA

? Complete ResectionR Status

R Designation Gross Resection Microscopic Margin

R0 complete negative

R1 complete positive

R2 incomplete positive

Exocrine Pancreas. In Greene FL, Page DL, Fleming ID, et al., eds. AJCC Cancer Staging Manual. Chicago, IL: Springer, 2002. pp. 157-164.

Intraoperative Assessment of Resectability

Not clinically informative.

Intraoperative Assessment of Resectability• Inaccurate• Incomplete gross resection provides no survival benefit compared to chemoradiation without surgery

SMA (Retroperitoneal/uncinate)

Margin

Retroperitoneal Margin

RP margin

SMV

SMA

SMA (Retroperitoneal) Margin AJCC Cancer Staging Manual 7th Edition

Survival Curves

Resection Margins Lymph Nodes

Tumor Size Grade

Pancreatic Cancer

• 2,216 patients with panc adenocarcinoma1990-2002

• 337 (15%) surgical resection (panc head/whipple)

4 periop deaths (1%); 5 additional pts lost to F/U

• 91 (28%) of 328 actual 5-year survivors (4% of 2,216)

Matthew Katz, Jason Fleming, Rosa Hwang, SSO 2008

Critical view

• Retroperitoneal margin– Majority of surgery is done here– Majority of the blood loss

673729

SMV

SMA

PV

SMASMV

IVC

LRV

Portal system resection

• Important to obtain a negative margin

• Data supports resection

• Several reconstruction options

• Often is the SMV that requires resection– Not portal vein

Variable No. patients Median survival (mo)

95% CI P value

Overall 291 24.9 21.40-28.46 --

Male

Female

175

116

23.1

27.0

19.05-27.15

22.43-31.50

.47

Standard PD

PD with VR

181

110

26.5

23.4

21.1-31.89

19.50-27.37

.18

T1

T2

T3

25

56

206

30.8

25.9

23.7

16.61-44.92

20.2-31.46

19.94-27.46

.22

N0

N1

146

145

31.9

21.1

24.57-39.30

17.40-24.73

.005

R0

R1

246

45

26.5

21.4

22.29-30.71

17.05-25.68

.14

Adjuvant therapy

No adjuvant therapy

209

29

25.1

18.5

21.42-28.85

9.48-27.52

.92

Pancreatic AdenocarcinomaPD with Vein resection vs. standard PD (univariate analysis)

Pancreatic AdenocarcinomaPD with Vein resection vs. standard PD (univariate analysis)

Tseng, J Gastroint Surg 2004;8:935.

Pancreatic AdenocarcinomaVR vs. standard PD (multivariate analysis)

Pancreatic AdenocarcinomaVR vs. standard PD (multivariate analysis)

Covariate HR 95% CI P value

Female Gender .925 .665-1.286 .642

Age (per year) 1.008 .991-1.026 .351

Reoperative PD 1.094 .722-1.66 .671

Vascular resection 1.132 .789-1.625 .499

Operative blood loss 1.0 1.0-1.0 .445

Tumor size .953 .818-1.11 .537

RP margin positive 1.164 .772-1.755 .469

T stage (AJCC) .730

Nodal metastasis 1.502 1.10-2.05 .01

Any adjuvant treatment .962 .412-2.244 .929

Neoadjuvant treatment 1.176 .615-2.248 .623

Postop treatment .946 .538-1.663 .846

Tseng, J Gastroint Surg 2004;8:935.

Resectable : Likely to require venous resection

SMV

SMA

T

Cava

553869

SMV

SMA

PV

Division of the jejunal branch of the SMV which was accessed by developing the plane of dissection between the SMA and SMV

PV

SMV

IJSMA

SMA

553869

SMV

Jejunal branch of the SMV has been divided and the involved segment of the ileal branch is resected and an IJ interposition graft used to reconstruct the SMV

PV

Spl V

492495

SMV

Spl A

CHA

Spl V

saph veinpatch

dividedbile duct PV

Rev saph vein graft

Final path:R0Lymph nodes: 0/24

Tumor

Tumor

SMV

SMA

Jejunal branch

Branch of SMVTo ileum

Final path:R1: microscopic focus of adenocarcinoma at SMA marginLymph nodes: 0/22

SMA

SMV

Resection of the ileal branch without reconstruction as the jejunal branch is not involved

PV

Ileal branch of SMV

Branch of SMVto jejunum

SMV

SMV

SplV

SMA

606785

Final path:R0Lymph nodes: 0/20

IJgraft

SMV

SMA

PV CHAReplacement of the SMV-PV confluence with an IJ interposition graft (splenic vein divided)Spl V

A closer look at Borderline resectable

Borderline Resectable

1. Arterial abutment (< 180o): SMA, celiac2. Short segment abutment/encasement of the

CHA/PHA (typically at GDA origin)3. Segmental venous occlusion with option for

reconstruction

(Many consider any aspect of venous invasion as Borderline Resectable)

Varadhachary GR, et al. Ann Surg Oncol. 2006;13(8):1035-46Katz MHG, et al. J Am Coll Surg. 2008;206(5):833-46

MDACC Classification System for Borderline Resectable Disease

• Type A: Anatomically borderline resectable tumor

• Type B: Indeterminant extrapancreatic metastasis

• Type C: Patient of marginal performance status

Katz MHG, et al. J Am Coll Surg. 2008;206(5):833-46

Rates of Resection, Path Response, Survival160 Patients with Borderline Resectable PC

No. of Patients (%) Median Survival (Mos) p*MDACC Type Total Resected

Path Resp. IIb, III, IV

All Pts Resected Unresected

A 84 (53) 32 (38) 19 (59) 21 40 15 0.001

B 44 (28) 22 (50) 13 (59) 16 29 12 0.001

C 32 (20) 12 (38) 5 (42) 15 39 13 0.009

Total 160 66 (41) 37 (56) 18 40 13 0.001

*p: comparison of median survival between resected and unresected patients of each type

Katz MHG, et al. J Am Coll Surg. 2008;206(5):833-46

Treatment of Borderline Resectable Pancreatic CancerUnderlying hypothesis / assumption

1. Neoadjuvant treatment sequencing used to: • select those with favorable biology• treat radiographically occult M1 disease• enhance the chance of a complete (R0,

R1) resection

2. Outcome for R1 different than R2 (ie, better)

Accurate Pathology and Multimodality TherapyPancreaticoduodenectomy: Ductal Adenocarcinoma

M D Anderson (N = 360)

Variable No. Pts Med Sur p value

Overall 360 25

N0 174 32 .002

N1 186 22

R0 300 28 .03

R1 60 22Maj Comp

No 263 27 .01

Yes 93 22

R0 17 moR1 11 mo

ESPAC-1Ann Surg 2001

Raut, Ann Surg 2007;246:52-60 Local Failure (All pts) 8%

Preoperative Therapy

R1 Resection

YES 13%

NO 19%

The Importance of Neoadjuvant TherapyPancreaticoduodenectomy: Ductal Adenocarcinoma

M D Anderson (N = 360)

Raut, Ann Surg 2007;246:52-60 Local Failure (All pts) 8%

Treatment phase Break ~ 6 wks

CTXgem combo

Staging CT

Restaging

Dropout

Borderline Resectable PC MDACC Treatment Approach

Restaging

Dropout

Chemo-XRT

OR

Classification as Borderline

Katz MHG, et al. J Am Coll Surg. 2008;206(5):833-46

Body and tail lesions

• R.A.M.P.– Radical anti-grade modular pancreatectomy– Lateral to Medial approach– 40% of lesions require resection of another

organ in addition to the spleen• GU: Adrenal, kidney

• GI: Transverse colon, stomach or duodenum

Distal Pancreatectomy - Splenectomy

Definitions: SSO/AHPBA CCResectable:

no extension to celiac, CHA, SMA, SMV-PV confluencestage I, II (T1-3, Nx, M0)

Borderline:a) venous abutment or encasement (with option for reconstruction)b) arterial abutment (< 1800)

Locally Advanced: celiac, SMA encasement (> 1800)stage III (T4, Nx, M0)

Resectable

Borderline Resectable

Locally AdvancedCourtesy of R Wolff, MD

SMV SMA

Surrounding perineural plexus

NO YES

Resection operative risk

Low High

If resect, is the resection complete (R0)

Usually Usually not

Kitts 527268

Resectable tumor, RRHA

SMV

SMA

T

Resectable adenocarcinoma of the pancreatic head

Resectable : likely to require venous resection

SMV

SMA

Resectable : likely to require venous resection

SMA

Borderline Resectable

Varadhachary GR, et al. Ann Surg Oncol. 2006;13(8):1035-46

Katz MHG, et al. J Am Coll Surg. 2008;206(5):833-46

Locally Advanced (Stage III)

SMV

SMA

Locally Advanced (Stage III)

Celiac encasement SMA encasement

- Aggressive Approach