surgical treatment of pancreatic cancer - dimitris p. korkolis
TRANSCRIPT
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