Updated March 17, 2013

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1 Updated March 17, 2013 Cntents If patient has clinical suspicin f pancreas cancer, we suggest the fllwing:...2 Tests we recmmend in the evaluatin f pancreas cancer prir t surgery:...2 Hw we classify cases f pancreatic cancer, using 3 levels f tumr extent:...2 Treatment f resectable tumrs...3 Treatment f brderline resectable tumrs...3 Treatment lcally advanced tumrs...4 Preperative care...4 Day f surgery, preparatin...4 Day f surgery, perative care...4 Pst-perative care...5 Pathlgic analysis f specimens...5 Fllw-up...6 References...6 **Click the Cntent tpic abve t jump t that sectin**

2 If patient has clinical suspicin f pancreas cancer, we suggest the fllwing: CT abdmen with cntrast Referral t gastrenterlgy with MD experienced in EUS EUS encuraged unless results nt thught t change management Mandatry in patients wh are brderline, unresectable, r nn-visualized n preperative CT (NCCN 12.2) May nt be necessary in patients with tissue diagnsis and clearly resectable n imaging Tissue cnfirmatin shuld be attempted n all right sided lesins (2009 AHPBA cnsensus guidelines) EUS bipsy preferred ver percutaneus (NCCN 12.2) ERCP & placement f durable stent is discuraged except in the fllwing scenaris: if neadjuvant r nn-surgical therapy planned if surgery will be delayed > 2 weeks if fevers, chills, severe pruritis r ther clinical evidence f chlangitis Shrt metal stents at the discretin f gastrenterlgists, nn-cnsensus recmmendatin Serum CA 19-9 (bld test that is elevated in many patients with pancreas cancer) D nt measure in patients with elevated bilirubin. In these cases, measure nly after biliary cmpressin reduces bilirubin t nrmal; r if n preperative stenting is perfrmed, then measure CA 19-9 pstperatively t fllw fr recurrence (NCCN 12.2) as the preperative measurement will be inaccurate. Tests we recmmend in the evaluatin f pancreas cancer prir t surgery: Pancreatic prtcl CT Triphasic study with visualizatin SMA and SMV, 3 mm cuts* New study if triphasic nt dne r inadequate r > 8 weeks ld Acceptable alternative: MRI Chest CT PET/CT nt necessary except if suspicin f therwise ccult metastases: if nn reginal lymphadenpathy if CA 19-9 > 180 in setting f nrmal bilirubin Preperative separate staging laparscpy with peritneal washings nly in rare circumstances: Equivcal PET/CT (SUV 1-3, enlarged ndes) and suspicin fr peritneal spread Presentatin at ur liver and pancreas cancer cnference Hw we classify cases f pancreatic cancer, using 3 levels f tumr extent: Resectable N distant metastases Mesenteric veins and arteries free f tumr, withut abutment, narrwing, encasement, thrmbsis N adenpathy in celiac, SMA regins r left f the arta Updated March 17, 2013 Page 2

3 Clear fat planes arund celiac axis, hepatic artery, SMA Brderline resectable N distant metastases Venus invlvement f the SMV/prtal vein demnstrating tumr abutment with impingement and narrwing f the lumen, encasement f the SMV/prtal vein but withut encasement f the nearby arteries, r shrt-segment venus cclusin resulting frm either tumr thrmbus r encasement but with suitable vessel prximal and distal t the area f vessel invlvement, allwing fr safe resectin and recnstructin. Islated jejunal r ileal vein suitable fr distal venus recnstructin Gastrdudenal artery encasement up t the hepatic artery with either shrt segment encasement r direct abutment f the hepatic artery, withut extensin t the celiac axis Tumr abutment f the SMA nt t exceed greater than 180 degrees f the circumference f the vessel wall Lcally advanced Distant metastases, greater than 180 degrees SMA encasement, any celiac abutment, nnrecnstructible SMV/prtal cclusin, artic invasin r encasement Psitive peritneal cytlgy n staging laparscpy with n visualized metastases Nt suitable fr resectable r brderline classificatin as published management guidelines nt cnsistent with NCCN Guidelines , cnsider systemic therapy initially, delayed lcal therapy may be apprpriate[1] Treatment f resectable tumrs (tumrs that dn t require treatment befre surgery, unless und er prtcl) 1. Enter int clinical trial if eligible, discuss with patient Gugh study (all pancreatic mass cases) Neadjuvant (nne pen ; prtcl under discussin but nt yet written) Pst-perative (ACOSOG/A5041; RTOG 0848) 2. Biliary decmpressin ptinal, see previus discussin 3. Tissue cnfirmatin nt available, repeat EUS and/r laparscpy with u/s guided cre bipsy, unless suspicius mass r resectin therwise indicated 4. Surgical resectin 5. Pst-perative adjuvant therapy, Gemcitabine based Treatment f brderline resectable tumrs (tumrs that have limited grwth int surrunding bld vessels f the intestine specific definitin discussed later) Offer therapy under prtcl if available Gugh trial Chemradiimmuntherapy prtcl Crcenzi (IRB pending) ACOSOG/Alliance trial when pen Matt Katz PI Updated March 17, 2013 Page 3

4 Treatment f lcally advanced tumrs (tumrs that cmpletely surrund bld vessels f the intestine) Clinical trial Gugh trial Chemradiimmuntherapy prtcl Crcenzi (IRB pending) FOLFIRINOX n ACOSOG trial if available FOLFIRINOX ff prtcl fr excellent functinal status patients if intent curative Gemcitbine based cmbinatin therapy with cncurrent gem/rt if ff prtcl Salvage surgery fr majr respnders if under prtcl r ambivalence regarding initial staging r M1 by cytlgy nly Preperative care Rutine preperative labs plus CA 19-9 Advise ral intake f Impact Advanced Recvery 8 fl z/237 ml per day fr 7 days prir t surgery. Review f imaging, including arterial, venus anatmy and staging studies with team at fellws cnference (Wednesday pm and Thursday am) Offer entry int tissue studies and ther relevant prtcls, discuss study plans and preperative studies and labs with Trinh Stephens--HPB clinic crdinatr Day f surgery, preparatin Re review imaging at time f surgery, with films displayed in OR, discuss vascular anatmy, and if secndary prcedures planned Discussin f plans fr specimen handling fr pathlgy and research as part f the time ut prcess just befre surgery begins. Telephne cntact with apprpriate lab persnnel befre starting case Talicia/Ben Office: Talicia s cell: Ben s cell: Pippa s cell: Avidance f epidural catheter. Use f submuscular pain pumps r lcal blcks fr pain cntrl encuraged. Intrathecal narctic injectin ptinal in rutine case, nt difficult cases r pts treated with neadjuvant therapy. Psitining, tuck right arm and bed at 90 degrees if rbtic case. Day f surgery, perative care Laparscpic evaluatin f abdmen and liver u/s prir t pen surgery Culture bile if pancreatic stent placed pre p Cnsider external stenting f high risk anastmses (sft gland, small duct < 3 mm) Drain pancreas unless lw risk f leaking (firm gland, duct > 3 mm) Avid NG[2] Updated March 17, 2013 Page 4

5 Feeding jejunstmy selectively (high risk f leak) Use LMH n frmulary sc every day, starting day after surgery, and scd s per high risk criteria until d/c r 30 days if vein recnstructin Famtadine 20 mg IV bid, transitin t meprazle when taking p If nt firm pancreas with duct < 3 mm: Octretide intrap at time f assessing anastmsis 100 mcg sc and 100 mcg every 8 hurs pst p fr 5 days r until fistula lw vlume < 50 ml/day. Operative nte includes the fllwing: pancreatic texture (sft, medium, firm) pancreatic duct size lcatin f drain placement. Clear liquid diet, d/c fley pd 2 Pst-perative care Full liquid diet pd 3 and drain amylase if applicable Remve drain (s) if amylase less than 3 times nrmal serum level and clinical pancreatic r lymphatic leak nt suspected, regardless f vlume Oral pain medicatin pd 3,4 Prbe any indurated/erythematus part f pen incisin early and pack withut starting antibitics unless infectin dcumented r strngly suspected Labratry tests as indicated clinically Pancreatic enzyme replacement when tlerating regular diet, cren 24,000 U with meals CT scan if any suspicin f leak (any day) r abscess (POD 5 r later), r elevated WBC r fever withut suspicin f leak, with percutaneus drainage as indicated, empiric antibitics (zsyn r directed antibitic if bile culture dne) fr significant pst p inflammatin, 5 days r lnger if indicated Expected median day f d/c is day 7 D/C medicatins include cren, meprazle Pathlgic analysis f specimens Specimens are generally kept sterile until research staff can dissect tissue fr Gugh study. Planning fr research staff presence at time f tissue availability shuld be discussed with the perative team befre the surgery starts. There shuld be either direct cmmunicatin between the surgen and pathlgist fr prper rientatin and margin identificatin, r the surgen shuld identify the imprtant margins with a clearly understd and dcumented methd, written n the pathlgy requisitin, fr example: stitch n SMA margin, safety pin n the retrperitneal/uncinate margin, frzen sectin n pancreatic duct margin and bile duct margin (see SOP: Liver and Pancreas Tumr Acquisitin) Psterir Margin: This margin is frm the psterir caudad aspect f the pancreatic head that merges with the uncinate margin and that appears t be cvered by lse cnnective tissue. Radial rather than en face sectins f this margin will mre clearly demnstrate whether it is invlved by tumr. In sme instances this margin can be included in the same sectin as the SMA margin sectin Updated March 17, 2013 Page 5

6 Prtal Vein Grve Margin: This is the smth-surfaced grve n the psterir-medial surface f the pancreatic head that rests ver the prtal vein. Radial rather than en face sectins f this margin will mre clearly demnstrate whether it is invlved by tumr and als will prvide the distance f the tumr frm the margin. As is true fr the psterir margin, in sme instances this margin can be included in the same sectin as the SMA margin sectin U Prtal Vein Margins: If an en blc partial r cmplete vein resectin is added t the surgical specimen it shuld be marked separately. En face prximal and distal end margins f the vein shuld be separately submitted as Prximal Prtal Vein Margin and Distal Prtal Vein Margin. A sectin dcumenting tumr invasin int the vein wall shuld als be submitted. If feasible, this sectin shuld be a full thickness f the vein wall demnstrating the depth f tumr invasin as this has been shwn t have prgnstic value Pancreatic Neck (transectin) Margin: This is the en face sectin f the transected pancreatic neck. The sectin shuld be placed int the cassette with true margin facing up s that the initial sectin int the blck represents the true surgical margin Bile Duct Margin: This is the en face sectin f the bile duct end. The sectin shuld be remved frm the unpened duct and placed int the cassette with true margin facing up s that the initial sectin int the blck represents the true surgical margin Other margins analyzed in Whipple specimens include the prximal and distal enteric margins (en face sectins) and anterir surface (clsest representative). The anterir surface is nt a true margin, but identificatin and reprting f this surface when psitive may prtend a risk f lcal recurrence, and s shuld be reprted in all cases. Cllectively, these pancreatic tissue surfaces cnstitute the circumferential transectin margin. Designating the varius specific margins with different clred inks will allw recgnitin n micrscpy Fllw-up Surgery clinic 1 2 weeks pst p, 3 mnths pst p x 2, every 6 mnths. Need pst-perative bld draw at first fllw up fr Gugh study. Medical nclgy referral and treatment per NCCN guidelines RTOG 0848, examines whether the additin f erltinib and/r delayed radiatin therapy t gemcitabine adjuvant chemtherapy imprves survival as cmpared t gemcitabine alne fllwing R0 r R1 resectin f head f pancreas adencarcinma (including adencarcinma f the head, neck, and uncinate prcess). Gemcitabine based chemtherapy +/- radiatin ff prtcl References 1. Yshika, R., et al., The Implicatins f Psitive Peritneal Lavage Cytlgy in Ptentially Resectable Pancreatic Cancer. Wrld J Surg, Rland, C., J. Mansur, and R. Schwarz, Rutine nasgastric decmpressin is unnecessary after pancreatic resectins. Arch Surg, (3): p Updated March 17, 2013 Page 6