vascular resection during … resection during pancreaticoduodenectomy. ... smv and portal venous...

Vascular resection during pancreaticoduodenectomy.

Ryan Turley, MDResearch Fellow, Duke University

Vascular Resection during PD

Outline

Review of pancreatic adenocarcinoma

Role of PD in treatment of pancreatic adenocarcinoma

Theory for vascular resection for locally invasive disease

Summary of current literature

Types of reconstruction

Duke experience

Conclusions

Pancreatic Adenocarcinoma


Classic Presentation

Jaundice, sometimes painless

Dark urine

Light colored stool

Labs

Bilirubin ↑

Ca 19-9 (Normal < 37)

37-100 less specific

> 100 suggest malignancy


Imaging Head mass with PV invasion

Fine-cut CT scan

High quality MRI scan

Other

EUS

ERCP

Role

of Pancreaticoduodenectomy (PD)

PD is the only chance for cure.

Mortality rates ranges from 0-8%.

5 year survival after resection ranges from 7-

25%.2

Survival after surgery is worse for patients with positive margins.3

2. Bachellier, et al. Is pancreaticoduodenectomy with mesentericoportal venous resection safe and worthwhile . Am J Surgery 2001;182: 120-9.

3. Zervos EE et al. Surgical management of early-stage pancreatic cancer. Cancer Control. 2004; 11:23-31.


SMV and Portal Venous Resection -

Theory

Grossly positive margins after resection associated with early recurrence.

Close relationship between pancreatic head and superior mesenteric vein.

Barriers to margin free resection include tumor involvement of SMV.

Invasion of SMV can occur without retroperitoneal invasion.

SMV not always accurately defined on pre-operative imaging.


SMV/PV invasion

Loss of the fat plane on CT

Absence of normal pancreatic parenchyma between the low-density tumor and the vein wall

NCCN Practice Guidelines v.1.2009

Resectable

No distant metastases

Clear fat plane around celiac and superior mesenteric artery.

Patent SMV/PV

Borderline Resectable

Severe unilateral or bilateral SMV/portal impingement

Less than 180 degree tumor abutment of SMA

Abutment or enasement

of hepatic artery, if reconstructible.

SMV occlusion, if of a short segment, and reconstructible.

SMA or celiac encasement < 180 degrees.

Unresectable

Distant Metastases

Greater than 180 degree SMA encasement, any celiac abutment.

Unreconstructible

SMV/Portal Vein

Aortic invasion or encasement.

Metastases to lymph nodes beyond the field of resection.

Flow Diagram-

NCCN GuidelinesPancreatic Protocol

CT scan

Resectable

Resection Clinical Trial Neoadjuvant Therapy

Borderline Unresectable

Resection Neoadjuvant Therapy

Chemotherapy/

Radiation

Restage

ResectionSystemic Therapy

History

First PD with SMV reconstruction by Moore et al. at the University of Minnesota in 1951.

Symbas

et al. concluded autologous grafts vein grafts remained patent while synthetic prosthesis had high rates of occlusion in 1961.

Asada

et al. in Japan reported radical pancreatectomy with PVR in 1963.

First attempts in the 1970s by Fortner

produced poor results with high morbidity and mortality.

Reemergence in the 1990s by the MD Anderson group.

Current literature

Modern debate is charged in comparing vascular resection for isolated invasion of SMV, PV, or SMV-PV confluence.

Reported Morbidity

25-55%

PD with Vascular Resection has not yet been universally accepted due to failure to prove:

(1) the procedure can be performed with acceptable morbidity and mortality even if margin free resections are increased.

(2) PD with SM-PVR has survival similar characteristics as standard PD.

Reconstruction options

V1 –

Tangential resection with saphenous vein patch

V2 –

Segmental resection with splenic vein ligation and primary anastomosis

V3 –

Segmental resection with splenic vein ligation and interposition graft.

V4 –

Segmental resection without splenic vein ligation and primary anastomosis.

V5 –

Segmental resection without splenic vein ligation and interposition graft.

Available SMV-PVR techniques

Vein Patch

Greater Saphenous Vein

Continuous 6-0 prolene

Choice for less extensive tumor involvement

< 1/3 vessel circumference

Interposition Grafting

More extensive tumor involvement

(> 1/3 vessel circumference)

Interrupted 6-0 prolene

Splenic vein can be ligated or reimplanted in side of interposition graft.

Interposition Graft

Graft types

Splenic vein

Left Renal Vein

Internal Jugular

Ovarian Vein

Femoral Vein*

Primary Reconstruction

A.

Pancreatic head tumor and involvement of the portal vein.

B.

En-bloc PD with Segmental portal venous resection.

C.

Reconstruction of the portal vein.

Previous StudiesAuthor Location N (%) Mortality

30 days (%)

Morbidity (%)

Median Survival

Neg

Margins (%)

Sindelar

1989

NCI 20 20 55 12

Trede

1990,97

Mannheim 60 (10.7) 6.7 12

Allema1994

Amsterdam 20 (11.4) 15 55 8 15

FortnerHarrison1996

MSK 58 (17.5) 5 12 (Re-X-Lap)

13 73

Roder1996

Munich 31 (10.4) 0 41.9 8 32

Previous StudiesAuthor Location N (%) Mort.

30 days (%)

Morbidity (%)

Median Survival

Neg

Margins (%)

LeachFurman1996, 98

MD Anderson

31 (41.7)

0 30 22 87

Tseng2004

MD Anderson

110 (38)

1 18 23.43 78

Imaizumi1998

Tokyo 172 (69)

5 23

Nakao1993, 95

Nagoya (Japan)

104 (78)

8 14% 5-year

49

Takahashi1994, 97

Keio 107 (55.7)

3.8 23.1 19 26.5

Klempnauer1996

Hannover 37 (19.6)

13.5 35.1 (Re-X-Lap)

9.0

Previous StudiesAuthor Location N (%) Mort.

30 days (%)

Morbidity (%)

Median Survival

Neg Margins (%)

LeachFurman1996, 98

MD Anderson

31 (41.7)

0 30 22 87

Tseng2004

MD Anderson

110 (38)

1 18 23.43 78

Imaizumi1998

Tokyo 172 (69)

5 23

Nakao1993, 95

Nagoya (Japan)

104 (78)

8 14% 5-year

49

Takahashi1994, 97

Keio 107 (55.7)

3.8 23.1 19 26.5

Klempnauer1996

Hannover 37 (19.6)

13.5 35.1 (Re-X-Lap)

9.0

Duke Experience Hypothesis

Superior mesenterico-portal venous tumor invasion is function of location and not a harbinger of metastatic disease or worse outcome after resection.

Combined pancreaticoduodenectomy with vascular resection offers previously unresectable patients a chance for cure without significant additional morbidity or mortality.

Duke Experience

204 patients who underwent PD for pancreatic adenocarcinoma from 1997-2008.

Patients who underwent PD with VR (N=42) were compared to patients who underwent standard PD (N=162).

Vascular reconstructions were performed by a vascular surgeon using primary repair (N=7), vein patch (N=26), or interposition grafting (N=8) with saphenous or femoral vein conduit.

Inclusion Criteria

All patients undergoing standard PD or PD with VR from 1997-2008 at Duke.

Pathology confirming Pancreatic Ductal Adenocarcinoma.

Exclusion criteria

Patients with significant missing clinicopathological data.

All tumors not described in surgical pathology as pancreatic adenocarcinoma.

Previous pancreas surgery.

Methods

All available post-operative CT scans reviewed for patency by Duke radiology fellow KP.

χ2 test was used to compare categorical variables.

Independent t tests were used to evaluate continuous variables.

Survival and follow-up were calculated from the time of surgery to date of death or last follow-up.

Overall survival was estimated using the method of Kaplan and Meier.

The log-rank test was used to evaluate differences between survival curves.

Multivariate analyses of the effects of potential prognostic factors on survival were done using a Cox proportional hazards regression.

DemographicsPD + VRPD + VR(n=42)(n=42)

Standard PDStandard PD(n=162)(n=162)

PP--valuevalue

Gender, n (%)Gender, n (%)MaleMaleFemaleFemale

22 (62)22 (62)16 (38)16 (38)

81 (50)81 (50)81 (50)81 (50)

0.97 (0.97 (ХХ22))

Med (mean) age (yr)Med (mean) age (yr)Range Range

63.5 (62.4)63.5 (62.4)4040--7878

66 (64.5)66 (64.5)3232--8787

0.30 (T0.30 (T--test)test)

Race, n (%)Race, n (%)CaucasianCaucasianAfricanAfrican--AmericanAmericanOtherOther

33 (79)33 (79)8 (19)8 (19)1 (1)1 (1)

126 (78)126 (78)32 (20)32 (20)

4 (2)4 (2)

0.93 (0.93 (ХХ22))

Med (mean) FUMed (mean) FURangeRange

10.7 (19.20)10.7 (19.20)(0.1(0.1--123.7)123.7)

13.1 (17.6)13.1 (17.6)(0.8(0.8--73.6)73.6)

0.67 (T0.67 (T--test)test)

ClinicopathologicalPD + VRPD + VR

(n=42)(n=42)Standard PDStandard PD

(n=162)(n=162)PP--valuevalue

Neoadjuvant CRT, Neoadjuvant CRT, n (%)n (%)

YesYesNoNo

23 (55)23 (55)19 (45)19 (45)

73 (45)73 (45)89 (55)89 (55)

0.26 (0.26 (ХХ22))

Path Tumor Size (cm)Path Tumor Size (cm)Median (Mean)Median (Mean)RangeRange

3 (3.4)3 (3.4)(1.5(1.5--7)7)

2.5 (2.6)2.5 (2.6)(0(0--7)*7)*

0.002 (T0.002 (T--test)test)

ComorbiditiesPD + VRPD + VR(n=42)(n=42)

Standard PDStandard PD(n=162)(n=162)

PP--valuevalue

Coronary Artery Coronary Artery DiseaseDisease

6 (14)6 (14) 23 (14)23 (14) 0.99 (0.99 (ХХ22))

DiabetesDiabetes 10 (24)10 (24) 41 (25)41 (25) 0.84 (0.84 (ХХ22))

COPDCOPD 7 (4)7 (4) 0 (0)0 (0) 0.17 (0.17 (ХХ22))

Chronic Renal Chronic Renal InsufficiencyInsufficiency

5 (3)5 (3) 1 (2)1 (2) 0.81 (0.81 (ХХ22))

HypertensionHypertension 20 (48)20 (48) 78 (48)78 (48) 0.95 (0.95 (ХХ22))

Congestive Heart Congestive Heart FailureFailure

1 (2)1 (2) 3 (2)3 (2) 0.83 (0.83 (ХХ22))




Neg Margins, n (%) Neg Margins, n (%) 31 (73)31 (73) 117 (72)117 (72) 0.84 (0.84 (ХХ22))

Positive LN, n (%)Positive LN, n (%) 21 (50)21 (50) 61 (38)61 (38) 0.14 (0.14 (ХХ22))

Histological Grade Histological Grade (n=181), n (%)(n=181), n (%)

1 1 ––

Well DiffWell Diff2 2 ––

Mod DiffMod Diff3 3 ––

Poor DiffPoor Diff

4 (10)4 (10)21 (52)21 (52)15 (38)15 (38)

22 (16)22 (16)75 (53)75 (53)44 (31)44 (31)

0.59 (0.59 (ХХ22))




Length of Stay Length of Stay Median (mean)Median (mean)

13 (15)13 (15) 12 (15)12 (15) 0.99 (T0.99 (T--test)test)

Estimated Blood Loss Estimated Blood Loss mL Median (mean)mL Median (mean)(n=162)(n=162)

875 (1040)875 (1040) 550 (700)550 (700) 0.001 (T0.001 (T--test)test)

Readmission in 30 Readmission in 30 days, n (%)days, n (%)

15 (36)15 (36) 49 (30)49 (30) 0.50 (0.50 (ХХ22))

Mortality, n (%)Mortality, n (%) 2 (5)2 (5) 6 (4)6 (4) 0.73 (0.73 (ХХ22))

MorbidityPD + VRPD + VR



(X(X22))

PJ LeakPJ Leak 4 (9)4 (9) 30 (18)30 (18) 0.160.16

Delay Gastric Delay Gastric EmptyingEmptying

8 (19)8 (19) 22 (14)22 (14) 0.370.37

AbscessAbscess 10 (24)10 (24) 20 (12)20 (12) 0.060.06

DVT DVT 7 (17)7 (17) 8 (5)8 (5) 0.010.01

GI BleedGI Bleed 4 (9)4 (9) 7 (4)7 (4) 0.190.19

Wound DisruptionWound Disruption 16 (38)16 (38) 63 (38)63 (38) 0.930.93

Reoperation*Reoperation* 8 (19)8 (19) 28 (17)28 (17) 0.800.80

Fascial DehiscenceFascial Dehiscence 0 (0)0 (0) 2 (1)2 (1) 0.46 0.46

ECFECF 3 (7)3 (7) 4 (2)4 (2) 0.150.15

*Any*Any

operationoperation

relatedrelated

toto

initialinitial

WhippleWhipple

operationoperation




(X(X22))

PJ LeakPJ Leak 4 (9)4 (9) 30 (18)30 (18) 0.160.16

Delay Gastric Delay Gastric EmptyingEmptying

8 (19)8 (19) 22 (14)22 (14) 0.370.37

AbcessAbcess 10 (24)10 (24) 20 (12)20 (12) 0.060.06

DVT DVT 7 (17)7 (17) 8 (5)8 (5) 0.010.01

GI BleedGI Bleed 4 (9)4 (9) 7 (4)7 (4) 0.190.19

Wound DisruptionWound Disruption 16 (38)16 (38) 63 (38)63 (38) 0.930.93

Reoperation*Reoperation* 8 (19)8 (19) 28 (17)28 (17) 0.800.80

Fascial DehiscenceFascial Dehiscence 0 (0)0 (0) 2 (1)2 (1) 0.46 0.46

ECFECF 3 (7)3 (7) 4 (2)4 (2) 0.150.15

*Any*Any

operationoperation

relatedrelated

toto

initialinitial

WhippleWhipple

operationoperation




(X(X22))

C. Diff InfectionC. Diff Infection 3 (7)3 (7) 15(10)15(10) 0.670.67

MIMI 1 (2)1 (2) 4 (2)4 (2) 0.970.97

Biliary LeakBiliary Leak 1 (2)1 (2) 4 (2)4 (2) 0.960.96

Perc DrainPerc Drain 9 (22)9 (22) 25 (15)25 (15) 0.330.33

PneumoniaPneumonia 3 (7)3 (7) 10 (6)10 (6) 0.820.82

ArrhythmiaArrhythmia 6 (14)6 (14) 13 (8)13 (8) 0.210.21

Univariate Analysis of Survival Log Rank Test of Equality

VariableVariable PP--valuevalue

Vascular ResectionVascular Resection 0.890.89

Sex (F vs M)Sex (F vs M) 0.980.98

Tumor Size > 2 cmTumor Size > 2 cm 0.030.03

Neoadjuvant CRTNeoadjuvant CRT 0.0060.006

Perineural Invasion (n=192)Perineural Invasion (n=192) 0.0010.001

Vascular Invasion (n=183)Vascular Invasion (n=183) <0.001<0.001

Positive MarginsPositive Margins 0.010.01

Positive LNPositive LN 0.0010.001

Grade (High vs Moderate/Low) (n=181)Grade (High vs Moderate/Low) (n=181) 0.090.09

0.00

0.00

0.25

0.25

0.50

0.50

0.75

0.75

1.00

1.00

00 2020 4040 6060

MonthsMonths

afterafter

SurgerySurgery

ControlControl

(162) (162)

Overall

Survival

0.00

0.00

0.25

0.25

0.50

0.50

0.75

0.75

1.00

1.00

00 2020 4040 6060

MonthsMonths

afterafter

SurgerySurgery

ControlControl

(162) (162) PVRPVR

(42)(42)

LogLog--rankrank

testtest

forfor

equalityequality

of survivorof survivor

functionsfunctions

p=0.89p=0.89

Overall

Survival

Multivariate AnalysisPVR (n=40)PVR (n=40)

Standard PD (n=137)Standard PD (n=137)Hazard RatioHazard Ratio 95% CI95% CI PP--valuevalue

Vascular ResectionVascular Resection 0.780.78 0.490.49--1.231.23 0.280.28

Tumor Size (cont)Tumor Size (cont) 1.201.20 1.041.04--1.391.39 0.010.01

Neoadjuvant CRTNeoadjuvant CRT 0.680.68 0.460.46--1.011.01 0.0530.053

Positive MarginsPositive Margins 1.301.30 0.870.87--1.941.94 0.200.20

Negative LN (Cont)Negative LN (Cont) 0.980.98 0.940.94--1.021.02 0.370.37

Positive LN (Cont)Positive LN (Cont) 1.111.11 1.001.00--1.221.22 <0.01<0.01

Grade (Cont)Grade (Cont) 1.351.35 1.011.01--1.811.81 0.010.01

Multivariate Analysis (No Grade)PVR (n=42)PVR (n=42)

Standard PD (n=156)Standard PD (n=156)Hazard RatioHazard Ratio 95% CI95% CI PP--valuevalue

Vascular ResectionVascular Resection 0.850.85 0.550.55--1.311.31 0.470.47

Tumor Size (cont)Tumor Size (cont) 1.121.12 0.990.99--1.281.28 0.080.08

Neoadjuvant CRTNeoadjuvant CRT 0.720.72 0.500.50--1.041.04 0.080.08

Positive MarginsPositive Margins 1.251.25 0.860.86--1.821.82 0.240.24

Negative LN (Cont)Negative LN (Cont) 0.980.98 0.950.95--1.011.01 0.290.29

Positive LN (Cont)Positive LN (Cont) 1.161.16 1.061.06--1.271.27 <0.01<0.01

SMV-PV Reconstruction OutcomesStatusStatus NN %%

PatentPatent 2727 7575

SMV/PV OcclusionSMV/PV Occlusion 33 88

Narrowing or Narrowing or Partial Vein Partial Vein OcclusionOcclusion

66 1717

SMV-PV

Reconstruction

Outcomes

*Only patients with Post*Only patients with Post--operative CT analyzed. Hepatic artery reconstruction excluded.operative CT analyzed. Hepatic artery reconstruction excluded.

0.00

0.00

0.25

0.25

0.50

0.50

0.75

0.75

1.00

1.00

00 2020 4040 6060

Months After ReconstructionMonths After Reconstruction

Duke KaplanDuke Kaplan--MeierMeier

EstimateEstimate

Arterial Reconstructions

6 patients underwent arterial reconstruction.

5 with post-operative imaging

4 Thrombosed

1 Indeterminant

Patent Reconstruction

78 year old woman.

Surgery 2/27/08

Technique Femoral Interposition Graft

Path T3N0, Margin Negative

Patent 5/12/09

Disease Free 5/18/10

Survival –

26.6 months

Complications: ED Visit for leg Edema and later a DVT.

Partial Occlusion

73 year old man.

Surgery 8/26/98

Technique Primary Venorraphy.


Non-occlusive thombus 9/16/02 on surveillance CT.

Recurrence 6/12/02.

Death 9/17/02

Survival –

48.2 months

Complications: None significant

Early Partial Occlusion, Late Failure

52 year old woman.

Surgery 3/19/08

Technique IMV Patch


Partial Occlusion -

12/1/08 – Surveillance CT scan

Total Occlusion -

7/13/09

Recurrence Confirmed - 5/15/09

Death –

1/31/10

Survival –

21.8 months

Complications –

Wound Infection, Failure to Thrive early in post-operative course.

Early Failure < 6 months

66 year old woman.

Surgery 10/21/08

Technique Femoral Interposition Graft


SMV Occluded 11/15/08 with collateralization. CT scan for fever workup.

Recurrence 3/10/09

Hospice Care

Survival –

15.3 months

Complications: None significant

Morbidity

Defined as major complications including 30 day mortality, reoperation, Pancreatic leak, GI bleed, Abscess, Fluid collection, Pneumonia, and MI as previously described by Tseng

et al. J Gastrointest Surg. 2004 Dec;8(8):935-49

Mortality

Median Survival

Negative Margins

Conclusions

Patients undergoing vascular resection had slightly larger tumors.

Vascular resection was associated with greater blood loss and likelihood being diagnosed with a lower extremity DVT.

Perioperative mortality, readmission rates, length of stay, and overall complication rates does significantly differ between standard PD and PD with VR.

Duke outcomes are equivalent or superior to other institutions.

Acknowledgments

Dr. White

Dr. Barbas

Dr. Tyler

Dr. Ceppa

Dr. Pappas

Dr. McCann

Dr. Clary

vascular resection during … resection during pancreaticoduodenectomy. ... smv and portal venous...

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