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Pancreatic Cancer: TheSurgical Oncologist’sPerspectiveMark Bloomston, MDAssistant Professor of SurgeryThe Ohio State UniversityPresentation Symptoms9 Unexplained weight loss9 Vague abdominal/back pain9 Early satiety, nausea, vomiting9 Steatorrhea9 JaundicePancreatic Cancer Surgical resection is only hope for cure9 Very few present with resectablediseasePresentation Signs9 Elevated LFT’s9 Elevated blood glucose Novel approaches needed9 Unexplained pancreatitis Early detection is a must9 Palpable mass9 High index of suspicion1

Diagnostic Work-up Spiral CT scanSurgical ConsultationCA19-9ERCPEUSBiopsy2

Resectability Resectable:9 No metastatic disease9 Clear fat plane around celiac axis andSMA9 Patent SMV and portal vein3

Resectability Resectable:9 No metastatic disease9 Clear fat plane around celiac axis and SMA9 Patent SMV and portal vein Unresectable9 Celiac/SMA encasement9 Portal vein/SMV occlusion9 Aorta/IVC invasion4

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Resectability Borderline resectable9 Portal vein impingement9 Tumor abutting SMA9 Gastroduodenal artery encasement atorigin9 Limited IVC invasion9 Short segment SMV occlusion7

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Treatment Multidisciplinary discussion Surgical consultation Preoperative biliary decompression9 If planning neoadjuvant therapy onprotocol9 If severe symptoms or cholangitis9 Logistics9

Surgical“Controversies”BiliaryDecompression Not mandatory Causes inflammation in porta hepatis Can be endoscopic (preferred) ortranshepatic May increase postoperative complicationsSurgical Resection Pancreaticoduodenectomy (Whipple)9 Head/uncinate lesions Subtotal pancreatectomy9 Neck/body lesions Distal pancreatectomy9 Tail lesions Pylorus preservationSpleen preservationPortal vein resectionLaparoscopyProphylactic gastrojejunostomyExtended lymph node dissectionPancreas reconstructionTotal pancreatectomyPylorus PreservingWhipple Pros9 Less ulcergenic9 Less dumping syndrome Cons9 Increased delayed gastric emptying No difference in outcomes Æ surgeonchoice10

Spleen Preservation Pros Pros9 Fewer complications9 No pancreatic anastamosis9 Complete extirpation of neck tumors Cons9 Time consuming9 less oncologic operation No real difference Æ surgeon preferenceLaparoscopy For Staging9999Total PancreatectomyDetection of occult metastasesAvoid laparotomy in up to 1/3 of patientsAdds time, cost, and frustrationNot good for determination of local tumorextent For Resection9 Less morbid for distal/subtotalpancreatectomies9 Unproven for Whipple/total pancreatectomy Cons9 Guaranteed exocrine insufficiency9 Difficult glucose controlProphylacticDuodenal Bypass Pros9 Safe operation9 Avoids future gastric outlet obstructionin unresectable patients Cons9 Often doesn’t work well9 Ulcergenic9 More recuperation11

Portal Vein Resection Pros9 Can be done safely9 Extends resectability Cons9 Risk of postoperative thrombosis9 Survival benefit unclear Should be done in high volume centers inmultidisciplinary setting12

SurgicalComplications Occur in 30 – 40% Rarely life-threatening9 Mortality 5% Delayed gastric emptying (most common) Pancreatic fistula (most dangerous)Long-Term Sequelae Diabetes9 rare Pancreatic exocrine insufficiency9 Common and easily treatable Marginal ulcers9 Lifelong acid suppression13

Long-Term Sequelae Post-gastrectomy syndromes9 Dumping syndrome9 Diarrhea Vitamin B12 deficiency Biliary stenosis (rare)Palliation Jaundice9 Biliary stenting9 Biliary bypass Gastric outlet obstruction9 Duodenal bypass9 Duodenal stenting Pain9 Neurolysis14

ManagementAlgorithmKatz et al. J Am Coll Surg 2008; 207(1):106‐20Pancreatic CancerTreatment Resectable Æ resection and CLINICALTRIAL Borderline resectable Æ neoadjuvant onCLINICAL TRIAL and resection Locally advanced Æ CLINICAL TRIAL Metastatic Æ CLINICAL TRIAL When in doubt Æ CLINICAL TRIALPancreatic CancerLuis Pompa, MDAssistant ProfessorDivision of GastroenterologyThe Ohio State University15

Pancreatic CancerPancreatic CancerRisk Factors 4th leading cause of cancer death in US Smoking (aromatic amines)- 2-fold increase 33,000-34,000 cases annually Hereditary pancreatitis- risk by age 70 is 40% 32,000 deaths annually Chronic pancreatitis- 4% at 20 years ofdisease Highest incidence-death ratio Family history- 5 year survival 5%9 1 family member: 13-fold risk Peak incidence in 7th decade of life9 2 family members: 18-fold risk9 3 family members: 57-fold riskPancreatic CancerPancreatic CancerSigns & Symptoms 90% are ductal adenocarcinomas Abdominal pain- up to 80% Remaining cases include cysticneoplasms, neuroendocrine tumors Painless jaundice- 50% 10-15% of patients are candidates forsurgical resection at time of diagnosis(stage I and II) Weight loss 50% of patients are unresectable atdiagnosis (stage III and IV) Fatigue Back pain- may represent nerveinvolvement (celiac plexus) and precludesurgical resection Steatorrhea uncommon presentation16

Pancreatic CancerTumor Markers All markers lack sensitivity and specificity CA19-9: most sensitive 70%, specificity87% CA19-9 less sensitive in setting of biliaryobstruction Other markers not as useful as they lacksensitivity and specificity or are too costlyfor clinical practicePancreatic CancerDiagnosis & StagingPancreatic Cancer - EUS Obtain tissue with fine needle aspiration (FNA) Determine resectability for borderline tumorson CT Most accurate for local extent (T stage) Most accurate for lymph node involvement (Nstage) Palliation of cancer pain with celiac plexusneurolysisPancreatic Cancer Staging T1- tumor confined to pancreas 2cm size CT imaging prompted by symptoms T2- tumor confined to pancreas 2cm size ERCP: “double duct” sign representingobstruction of pancreatic and bile ducts T3- tumor extends to surrounding structuressuch as PV, SMV, CBD, duodenum ERCP bile duct brushings are notoriouslyinsensitive for malignancy T4- tumor extends into stomach, spleen, colonor vascular structures SMA and celiac trunk MRCP: highly sensitive for pancreaticcancer, but is expensive M0/M1- absence/presence of metastasis N0/N1- absence/presence of LN involvement17

Pancreatic CancerChemotherapy Fluorouracil and gemcitabine basedregimens Limited survival benefitT1 Lesion Radiation:9 Adjuvant after resection for cure9 Treatment of unresctable disease incombination with chemotherapyPancreatic CancerSurgical Approach Dr. BloomstonT3 Lesion18

Pancreatic CancerT4 LesionEndoscopic Management ofComplicationsComplications Common bile duct obstruction Duodenal obstruction Intractable pain Pancreatic duct obstruction(uncommon)19

Bile Duct Obstruction CBD obstruction can lead to vitamin K def Cholangitis rare in malignant biliaryobstruction Cholangitis can complicate endoscopicbiliary drainage procedures Goals of therapy:9 Relieve jaundice and pruritis9 Biliary drainage in preparation for chemotherapy9 Biliary drainage for surgery prep and palliationBile Duct Obstruction-StentsBile Duct Obstruction-Stents Self Expanding Metal Stents (SEMS):Longer patency: 6 to 9 monthsTechnically more difficult deploymentPermanent and not removableInterferes with radiation treatment & surgicalfield9 Palliation for patients: life expectancy 6months9 No effect on patient survival9 Less tumor in-growth/obstruction withcovered vs. uncovered SEMS9999Complications- Bowel Obstruction Different stents, different indications Direct compression of duodenum by mass Plastic Stents: Surrounding inflammatory reaction withedema contributes to luminal narrowing9 Technically easy deployment9 Patency: 2 to 3 months, needs changing Reduced duodenal motility9 No interference with external beam radiation Symptoms of gastric outlet obstruction orsmall bowel obstruction9 Removable but can migrate proximal ordistal Goal of therapy:9 Will not interfere with surgical field9 Reduce symptoms9 Bridge to definitive therapy (surgery)9 Improve oral intake and nutrition9 No effect on survival9 Pleasure of eating20

Obstructed Bowel SegmentDuodenal StentStomach ÆÅObstructionSEMSComplications-Bowel Obstruction Complications of stent placement areessentially that of EGD Diet limitations after placement- lowresidual liquid to soft mechanical diet Increase in bowel perforation whenballoon dilation is required to placeSEMS21

Complications-Bowel Obstruction Symptom relief in 80-90% in 2-3 days Re-intervention required in 20-25%:9 Stent occlusion, migration and bowelperforationIntractable Pain Due to involvement of celiac neural plexus,located on either side of celiac arterial trunk Initial symptom of pain at diagnosis conferspoor prognosis Pain leads to poor PO intake, weight lossand poor quality of life Goals of therapy:9 Decrease pain, improve PO intake andweight, improve quality of life andfunctional statusCystic Lesions ofthe PancreasCystic Lesions ofPancreas Widespread use of imaging (CT) has ledto increased detection of cystic lesionsof the pancreas Incidentally discovered mostly, somediscovered due to jaundice, pain, orpancreatitis Often confused or misdiagnosed aspseudocysts based on clinical history22

Types of Pancreatic Cysts Benign, pre-malignant and malignantSerous CysticNeoplasm- SCN Most are pseudocysts- 90% Nearly universally benign lesion Cystic neoplasms- 10% Approximately 25% of cystic lesions9 Serous cystic neoplasms9 Mucinous cystic neoplasms9 Mucinous cystadenocarcinomas9 Intraductal Papillary Mucinous Neoplasmsmain duct and side-branch varietiesCystic Lesions Prevalence Some autopsy studies- 73/300 (24%) In U.S.- nearly 20% Often patients have surgicalresection for benign entity Advancements in pancreatic imagingaim to reduce this occurrenceSCN Image Characteristics CT: Microcystic, often with central stellatescar Increases with age Difficult to determine communication withpancreatic duct (differentiate with IPMN) Located throughout the pancreas EUS: Microcystic with central stellate scar Cyst epithelium: benign epithelium,atypical hyperplasia and carcinoma in situ Much easier to document pancreatic ductcommunication23

Mucinous CysticNeoplasm- MCNIntraductal PapillaryMucinous Neoplasm- IPMN Pre-malignant or malignant lesions Main duct and side-branch varieties Discrete individual cysts/compartments Strong tendency for malignanttransformation Difficult to distinguish between MCN andIPMN lesions radiographically Difficult to distinguish between MCN andmacrocystic SCN Demographic overlap with SCN and IPMNMCN ImageCharacteristics CT:9 Macrocystic, unilocular with occasionalseptations9 Difficult to image mural nodularity andcommunication with main pancreatic duct EUS:9 Macrocystic unilocular with occasionalseptations9 Better assessment of mural nodularity andcommunication with main pancreatic duct Difficult to distinguish between MCN andside-branch IPMN Side-Branch type can be single focus ormultifocalIPMN ImageCharacteristics Side-Branch type:9 CT/MRI/MRCP: Unilocular without septations, /- communication with main pancreatic duct9 EUS: Unilocular /- septations andcommunication with main pancreatic duct Main duct type:9 CT/MRI/MRCP: Main pancreatic duct dilation,difficult to image mural nodularity or solidcomponent9 EUS: Main pancreatic duct dilation, muralnodularity and solid component more readilyvisualized24

Clinical Presentation Most cysts are asymptomaticDifferential Diagnosis Most important: distinguish mucinouscystic neoplasms and IPMN from serouscystic lesions (benign from potentiallymalignant) Incidentally discovered with imagingperformed for other reasons Symptoms usually due to pancreatitis butcan uncommonly present as jaundice Ramifications for further managementsuch as surgery vs. surveillance Can be confusing as cystic lesions can bemistaken for pseudocystsPancreatic Cyst k ofMalignancySerous CysticNeoplasmFMiddle ageMicrocysticCentroacinarLowMucinous CysticNeoplasmFMiddle ageMacrocystic/unilocularmucinousMucinous,columnar epith,ovarian stromaModerateMucinous CystadenocarcinomaFMiddle AgeAssociated mass, yUnilocularPapillary,mucinousModerate-HighCystic EndocrineTumorM:FMiddle AgeAssociated ed massMixed solid andcystic- endocrineLowDiagnostic Methods RUQ ultrasound not helpful- poorpancreatic visualization MRCP can demonstrate ductal dilation andcommunication with cyst CT:9 Mode most often responsible for finding lesion9 Unilocular or macrocystic features9 Main pancreatic duct dilation in IPMN9 Communication with main PD in side-branch type25

Diagnostic Methods CT/MRI in general not sufficient todetermine lesion type or presence ofmalignancy EUS:9 Very sensitive for cyst type9 FNA further differentiates lesion type9 FNA safety profile very good?Serous Cystic Neoplasm?26

Mucinous CysticNeoplasmSide-BranchIntraductal PapillaryMucinous NeoplasmMCN with Mural NoduleMain Duct IntraductalPapillary MucinousNeoplasm27

Diagnositc EvaluationCyst FNA Mucin in aspirated fluid is moderatelypredictive of mucinous neoplasm CEA, CA 72-4, CA 19-9, amylase, lipaseand fluid viscosity can be used CEA, amylase and “string test” for mucinare most commonly used and mostaccuratePrediction of pancreatic cystic neoplasm by usingresults of cyst fluid analysis formula (SCN vs MCN)PredictivevaluesCystCyst fluid analysis formulaSensitivity Specificity PCVIS 1.6 or lipase UL 6000 andCEA ng/mL 48091.3SCNVIS 1.6 and lipase UL VIS 1.6 and CEA ng/mL 600085.710010096.297.2VIS 1.6 and CEA ng/mL 60001009284.010094.3Gastrointestinal Endoscopy, Vol 64 (5),Nov 2006; p 697‐702Results of cyst fluid analysis SCN vs MCN: rametersPC (n 23)SCN (n 13)MCN (n 21)MCN-CA (n 14)VIS1.3 (1.1-1.6)1.3 (1.1-1