Determining resectability in pancreatic cancer
Transcript of Determining resectability in pancreatic cancer
DETERMINING RESECTABILITYIN PANCREATIC CANCER
Moderator :
Dr. B. Srihari rao M.SDr. C. Srikanth Reddy M.SDr. K. Keerthinmayee M.S
Presenter: Dr. Harish Y S
Discussed by
INTRODUCTION CLASSIFICATION OF TUMORS STAGING OF TUMORS ANATOMY OF PANCREAS National Comprehensive Cancer Network (NCCN)
GUIDELINES INCREASING RESECTABILITY RATES VENOUS RESECTION ARTERIAL RESECTION. MANAGEMENT
INTRODUCTION It is the 13th most common cancer worldwide. 5th MC cause of cancer-related mortality.
Incidence rate is 9.7 per 100,000. Its peak incidence between the 7 & 8 decades
and It is rare < 40yrs. Male to female ratio is 1:1
Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The globalpicture. Eur J Cancer. 2001;37 Suppl 8:S4-66
INTRODUCTION It has an overall survival of 0.4% to 4%. These patients presents late,
At the time of diagnosis < 20% of patients are surgically resectable disease
Of the inoperable ones, 1/3 rd. with distant metastases and Remaining 1/3 rd. with locally advanced disease.
Defining resectability is therefore one of the most important and crucial aspects in the management of pancreatic cancer.
WHO Classification of pancreatic exocrine tumors
Benign tumors:
Serous cystadenoma
Mucinous cystadenoma Intraductal papillary-mucinous adenoma Mature teratoma Borderline (uncertain malignant potential) Solid-pseudopapillary neoplasm
Most common
WHO Classification of pancreatic exocrine tumorsMalignant tumors: Ductal adenocarcinoma
Mucinous noncystic carcinoma Signet ring cell carcinoma Adenosquamous carcinoma Undifferentiated (anaplastic) carcinoma
Serous cystadenocarcinoma Mucinous cystadenocarcinoma intraductal papillary-mucinous carcinoma Acinar cell carcinoma Pancreatoblastoma Solid-pseudopapillary carcinoma
TNM STAGING:
The American joint committee on cancer stage
Arterial supply of pancreas
Venous drainage of pancreas
Lymphatic drainage of pancreas
Historically pancreatic tumours have been classified as either resectable or unresectable.
It is primarily the relationship of the pancreatic cancer to the vessels that defines resectability.
Over the last two decades the terms “locally advanced” and “borderline resectable” pancreatic cancer have come in to use.
LOCALLY ADVANCED PANCREATIC CANCER Locally advanced pancreatic cancer is described as
Tumor invaded locally adjacent structures such as major blood vessels, lymph nodes, bowel or the bile duct, without evidence of distant metastatic disease.
Involvement of para-aortic LN considered as metastasis and sugically contrindicated.
Locally advanced pancreatic cancer may or may not be resectable and would include T3 and T4, whereas T1 and T2 are considered resectable tumours.
BORDERLINE RESECTABLE PANCREATIC CANCER It is defined by two groups
MD Anderson Cancer Center (MDACC) American HepatoPancreatoBiliary Association (AHPBA)/
Society of Surgical Oncology (SSO)/Society for Surgery of the Alimentary Tract (SSAT)
MDACC group describes any venous involvement as resectable disease and only occlusion of the SMV or PV (with the possibility of reconstruction) as borderline.
Cooper AB, Tzeng CW, Katz MH. Treatment of borderline resectable pancreaticcancer. Current treatment options in oncology. 2013;14(3):293-310.
National Comprehensive Cancer Network (NCCN) Guidelines for pancreatic cancer treatment. Pancreatic cancers classified in to
Resectable Borderline resectable and Unresectable.
Resectable Arterial: Clear fat planes around the coeliac axis (CA), SMA
and HA. Venous: The SMV or PV abutment but no distortion of the
vessels.
Borderline ResectableArterial :Pancreatic head /uncinate process: Solid tumor contact with CHA without extension to
celiac axis or hepatic artery bifurcation. Solid tumor contact with the SMA of ≤180° Presence of variant arterial anatomy (ex:
accessory right hepatic artery, replaced right hepatic artery, replaced CHA) and the presence and degree of tumor contact should be noted if present as it may affect surgical planning.
Borderline ResectablePancreatic body/tail: Solid tumor contact with the CA of ≤180° Solid tumor contact with the CA of ˃180°
without involvement of the aorta and with intact and uninvolved gastroduodenal artery.
Venous: Venous involvement of the SMV or PV with distortion or narrowing of the vein or occlusion of the vein with suitable vessel proximal and distal, allowing for safe resection and replacement.
Unresectable:
Arterial (Head of Pancreas): Greater than 180° encasement of the circumference of the SMA or any CA abutment.
Arterial (Body/Tail of Pancreas): SMA or CA encasement >180°.
Arterial (Any Part of the Pancreas): Aortic invasion or encasement.
Venous: Unreconstructable SMV and/or PV.
Nodal Status: Metastases to lymph nodes beyond the field of resection should be considered unresectable.
Grading system proposed by Lu et al. for predicting vascular invasion by tumor based on the degree of tumor contiguity with a vessel
GRADE DESCRIPTION COMMENTGrade 0 No contiguity of tumor with a
vesselVascular invasion in 0% of cases
Grade 1 Tumor is encasing <25% of the circumference of a vessel
0%
Grade 2 25–50% of the circumference of a vessel
57%
Grade 3 50–75% of the circumference of a vessel
88%
Grade 4 >75% of the circumference of a vessel or any vessel constriction
All cases
A fat plane is seen between thetumor and the superior mesenteric artery (SMA) and superior mesentericvein. No evidence of vascular invasion is seen.
The tumor is contiguous with < 90° of the superior mesenteric vein (Lu grade 1). There is no narrowing or wall irregularity of the SMV
MDCT OF PANCREATIC CARCINOMA
The tumor is contiguous with 90°- 180 of the superior mesenteric vein (Lu grade 2). There is no narrowing or wall irregularity of the SMV.
The tumor (T) in the head ofthe pancreas eroding the wall of the superior mesenteric vein (SMV) and penetrating it to form a tumor thrombus
Grading system proposed by Loyer et al. for predicting vascular invasion by tumorGRADE DESCRIPTION COMMENTType A Fat plane separates the tumor
and the normal pancreatic parenchyma from adjacent vessels
Overall resection rate: 100%.
Type B Normal parenchyma separates the tumorfrom adjacent vessels
Overall resection rate: 100%.
Type C Tumor is inseparable from adjacent vessels, and the points of contact form a convexity against the vessels
Overall resection rate: 89%.
Type D The points of contact form a concavityagainst the vessels or partially encircle the vessels
Overall resection rate: 47%.
Type E Tumor encircles adjacent vessels, and nofat plane is identified between the tumor and the vessels
Overall resection rate: 0%.
Type F Tumor occludes the vessels Overall resection rate: 0%.
APPROCH TO A PATIENT
Clinical suspicion of pancreatic cancer or evidence of dilated pancreatic duct.
MDCT angiography
Mass in pancreas
No mass in pancreas
No metastasis
Multidisciplanary review• LFT• EUS• Chest
imaging
Metastasis
Biopsy confirmation
No metastasis
• LFT• EUS/FNA• Chest
imaging• MRCP/ERCP
Metastasis
Biopsy confirmation
EUS
APPROCH TO A PATIENT
No metastatic disease on physical examination and imaging
No jaundice jaundice
Symptoms of cholangitis or fever
Short or self expanding metal stents and antibiotic coverage
No symptoms of cholangitis
Per operative CA-19-9
RESECTABLEBORDERLINE RESECTABLE
LOCALLY ADVANCED , UNRESECTABLE
RESECTABLE TUMORConsider staging laparoscopy in high risk patients
LAPAROTOMY
Surgical resection
Adjuvent treatment and surveillance
Unresectable tumor
Biopsy confirmation, if not performed previously
No jaundice
Gastrojujunostomy + celiac plexus
neurolysis (if pain)
Jaundice
Self expanding metal stents or biliary
bypass +Gastrojujunostomy
+ celiac plexus neurolysis (if pain)
The goals of surgical extirpation of pancreatic carcinoma focus on the achievement of an R0 resection
a margin positive specimen is associated with poor long-term survival
Achievement of a margin negative dissection must focus on meticulous perivascular dissection of the lesion in resectional procedures, recognition of the need for vascular resection and/or reconstruction
Surgical Procedures
Tumors of the Body and Tail Distal
Pancreatectomy
Removal of body & tail of pancreas
spleen
Surgical Procedures
Head of the pancreas: Whipple Procedure Removal of:
Distal stomach Duodenum and
proximal jejunem Head of pancreas Gallbladder and
common bile duct
Total pancreatectomy Indicated in tumor with multilocular or large
tumors.
It is combination of pancreaticoduodenectomy and distal pancreatectomy with local lymphadenectomy.
Complications are post operative exocrine and endocrine insufficiency and associated with high mortality rates.
If the tumor is found to be unresectable during surgery
biopsy confirmation of adenocarcinoma can be done.
If a patient with jaundice is found to be unresectable at surgery stenting or biliary bypass can be done
BORDERLINE RESECTABLE, NO METASTASISPlanned neoadjuvent therapy
Biopsy/ EUS+FNA / staging laparoscopy
Biopsy confirmed
Imaging: abdomen , chest and pelvis
Consider staging laparoscopy
Surgical resection Unresectable
Cancer not confirmed
Repeat biopsy
Biopsy confirmed
Biopsy not confirmed
Planned resection
INCREASING RESECTABILITY RATES Survival for pancreatic cancer has not changed in
the last 40 years. However, with advancement in surgical technique and improvement in perioperative care.
In Specialised centres, postoperative mortality rates of 2–3% have been reported.
The increased resectability and improve in long-term survival for patients with pancreatic cancer, extensive surgical procedures have been developed, mainly involving vascular reconstruction techniques.
INCREASING RESECTABILITY RATES Birkmeyer et al. first reported aggressive surgery
for borderline resectable pancreatic cancer with the first SMV resection and reconstruction in 1951.
In 1973, Fortner first described the regional pancreatectomy. This involved a total pancreatectomy, radical lymph node clearance, combined PV resection (type 1) and/or combined arterial resection and reconstruction (type 2).
Venous Resection Venous involvement is not considered a contraindication
to surgical resection.
Pancreatic resection requiring venous reconstruction is technically challenging and may be associated with a higher morbidity.
Ravikumar et al. published multicentre retrospective cohort study comparing, PD with venous resection (PDVR) and surgical bypass for T3 adenocarcinoma of the head of the pancreas.
1.Morbidity was similar between the PDVR and PD groups,
2.Patients requiring blood transfusion being greater in the PDVR group.Ravikumar R, Sabin C, Abu Hilal M, et al. Portal vein resection in borderline
resectable pancreatic cancer: a United Kingdom multicenter study. J Am Coll Surg. 2014;218(3):401-11.
Venous Resection
In 2006, Siriwardana reported a large systematic review of 1646 patientswho had undergone portal-SMV resection during pancreatectomy forcancer.
concluded that, with the high rate of nodal metastases and thelow five-year survival rates, once the PV is involved cure is unlikely evenwith radical surgery.
Several studies have shown that PV resection in patients with pancreatic cancer has comparable survival compared to standard pancreatectomy and
It is a safe procedure when performed in specialist HPB Units
Siriwardana HP, Siriwardena AK. Systematic review of outcome of synchronous portal-superior mesenteric vein resection during pancreatectomy for cancer. Br J Surg. 2006;93(6):662-73
Venous Resection
Lygidakis et al. compared en bloc splenopancreatic and venous resection versus palliative gastrobiliary bypass and reported two-year survival rates of 81.8% and 0%, respectively.Randomised controlled trial by Doi et al. in 2008 was closed early when interim analysis showed a clear survival benefit for PDVR with chemoradiotherapy compared with chemoradiotherapy with or without a surgical bypass
Lygidakis NJ, Singh G, Bardaxoglou E, et al. Mono-bloc total spleno-pancreaticoduodenectomyfor pancreatic head carcinoma with portal-mesenteric venous invasion. A prospective randomized study. Hepatogastroenterology. 2004;51(56):427-33. Doi R, Imamura M, Hosotani R, et al. Surgery versus radiochemotherapy for resectable locally invasive pancreatic cancer: final results of a randomized multi-institutional trial. Surg Today. 2008;38(11):1021-8.
Arterial Resection In 2007, Hirano et al. reported their long-term
follow-up for patients undergoing distal pancreatectomy with en bloc CA resection (DP-CAR)
They reported 1yr and 5yr survival rates of 71% and 42%, respectively, and
concluded that DP-CAR offers a high resectability rate and may potentially achieve complete local control in selected patients.
Hirano S, Kondo S, Hara T, et al. Distal pancreatectomy with en bloc celiac axis resection for locally advanced pancreatic body cancer: long-term results. Ann Surg. 2007;246(1):46-51.
Arterial Resection Bachellier et al., in 2011, matched a group of patients
undergoing pancreatectomy with arterial resection to conventional pancreatectomy and demonstrated similar three-year survival rates.
Bockhorn et al. reported one of the largest series on pancreatectomy with simultaneous arterial resection (n = 29) and
concluded that there was no overall difference in disease-specific survival for patients who underwent arterial reconstruction versus those patients who underwent pancreatectomy alone
Bachellier P, Rosso E, Lucescu I, et al. Is the need for an arterial resection a contraindication to pancreatic resection for locally advanced pancreatic adenocarcinoma? A case-matched controlled study. J Surg Oncol. 2011;103(1):75-84.
Bockhorn M, Burdelski C, Bogoevski D, et al. Arterial en bloc resection for pancreatic carcinoma. Br J Surg. 2011;98(1):86-92.
Arterial Resection Mollberg et al. in 2011, systematic review and meta-
analysis. This report included 26 studies, a total of 2609 patients,
366, out of the 2609 patients underwent an arterial resection and reconstruction in conjunction with a pancreatectomy.
Results: Significantly increased perioperative morbidity and a mortality
rate compared with standard pancreatectomy . Significantly poorer survival outcomes at
one year (49.1%), three years (8.3%) and five years (0%) were demonstrated in this study
LOCALLY ADVANCED UNRESECTABLE TUMOR
Biopsy ,if not previously performed
Adenocarcinoma confirmed
If jaundice, placement of
self expanding
metal stents.
CHEMOTHERAPY
Cancer not confirmed
Repeat biopsy
Others cancers
Treat as appropriate
LOCALLY ADVANCED UNRESECTABLE TUMOR
FOLFIRINOX or
Gemcitabine or
Gemcitabine + albumine bound paclitaxel. or
Capecitabine + continuous IV
5-FU or
Fluropyrimidine + oxaliplatine or
Clinical trial preferred.
Fluropyrimidine based therapy if previously treated with Gemcitabine based therapy
Gemcitabine based therapy if previously treated with Fluropyrimidine based therapy
PALLIATIVE AND BEST SUPPORTIVE CARE
METASTATIC DISEASE
If jaundice, placement of self expanding metal stents.
Good performance
CHEMOTHERAPY
Poor performance
Palliative and supportive care.
SURVIVAL 5-year survival rate of
R0 resection - 24.2% R1 and R2 resection - 4.3%
Median survival in R0 resected patients, the was 28 months with pancreaticoduodenectomy and 26 months with PPPD.
R1 resected patients - 15 months R2 resected patients - 9.8 months Wagner M, Redaelli C, Lietz M, Seiler CA, Friess H, Buchler MW. Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. Br J Surg 2004;91:58694
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