BY JANGAM CHAKRAVRTHI 3RD YEAR MEDICAL STUDENT

1. BY
JANGAM CHAKRAVARTHI
Pancreatic
Cancer
9/27/2018
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2. OUTLINE
 Storyboard Of Steve Jobs
 Anatomy Of Pancreas
 Functions Of Pancreas
 Epidemiology
 TypesofPancreaticCancer
 Pathophysiology
 Risk Factors
 Clinical Presentation
 Essentials Of Diagnosis
 Imaging Studies
 Lab studies
 Treatment
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3. STORYBOARD OF STEVE
JOBS
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4. ANATOMY
 Thepancreasisprismoidin shapeandappearstriangular
withtwomajorregions i.e. headandtailportion.
 The headofthe pancreaslaysin theduodenalC loopin front
ofthe inferiorvena cava(IVC) andthe left renalvein.
 The bodyandtailofthe pancreasrun obliquelyupwardto
the leftin frontofthe aortaandleftkidney.
 The mainpancreaticduct(Duct ofWirsung) runsfromthe
tailthroughthebodytothe headofthe pancreaswhereit
descends intothe lower(inferior) partofthe head.
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5. CONTINUED
 There it joins the duct of the uncinate process coming from left and then
the lower part ofthe common bile duct toform a commonchannel
(hepatopancreatic ampulla).
 This duct runs through the medial duodenal wall and opens on the dome
of the major duodenal papilla.
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6. FUNCTIONS OF PANCREAS
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 Exocrine  Endocrine
 Inhibition
 Stimulation
Enzyme Substrat
e
Product
Amylase
(active)
Starch,
glycogen
Glucose,
maltose.
Trypsinogen,
Trypsin
(active)
Chymotrypsin
(active).
Cleave
peptide
bondsin
amino
acids
Free amino
acidsand
dipeptides.
Pancreatic
lipase (active)
Triglyceride Mono
glycerides
fattyacids.
Beta cells
(Insulin)
Alpha
Cells
(Glucago
n)
D-Cells
(Somat
o
statin)

7. PANCREATIC CANCER
 Pancreaticcanceris a malignant neoplasm
originating from transformed cells arising in
tissues forming the pancreas.The most
common type ofpancreatic cancer,
accounting for 95% of these tumors, is
adenocarcinoma.
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8. EPIDEMIOLOGY
 Pancreaticcanceris currentlythe fourth leadingcause
of cancerdeathin the united states and is associated
with a poor prognosis.
 The rateof incidence isincreasing which meansthat
the disease is becomingmorecommonand it isalso
extremelydifficultto treat.
 Signs and symptomsof the disease seldom
appear untilmore advanced stages ofcancer.
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9. CONTINUED
 By the timesymptomsappears, cancercellsarelikelyto havemetastasized
toother partsof thebody.
 While currently pancreaticcancercanberemovedby surgery
followed bychemotherapy.
 Theoverall 5-year survival ratefor this disease is less than 5%.
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10. TYPES OF PANCREATIC CANCER
 Pancreaticcancerhas beenclassifiedinto two classes viz. exocrineand
endocrine pancreatic cancer.Thesearefurther classified into various
subclasses
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11. SUBCLASSES OF ENDOCRINE PANCREATIC
CANCER
 Gastrinoma (Zollinger-Ellison Syndrome) :- Gastrinomas overproduce
gastrin. Most aremalignant orhavethe ability to becomemalignant.
 Glucagonoma :-Glucagonomas overproduce glucagon.They are usually
large,often metastasize and about 70% aremalignant.
 Insulinomas:-Insulinomasoverproduceinsulin.They arethe most
commonpancreatic neuroendocrinetumors.
 Nonfunctional isletcelltumors:-Nonfunctional isletcelltumorsare
usually malignant.Theyare hard todetect.
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12. CONTINUED
 Somatostatinoma :-Somatostatinomas overproduce somatostatin. They
can occuranywhere in the pancreas and in the duodenum.
 Vasoactive Intestinal Peptide-ReleasingTumor :-VIPomas overproduce
vasoactive intestinal peptide (VIP). These tumors are usually located in the
body and tail of the pancreas.
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13. VARIOUS SUBCLASSES OF EXOCRINE
PANCREATIC CANCER
 Acinar Cell Carcinoma :-Rareform of pancreatic cancerthat may cause
excessiveproduction ofpancreatic lipase, the enzymesecreted to digest
fats.
 Adenocarcinoma :-Adenocarcinoma accounts for about 90% of all
pancreatic cancersand it begins in cells lining the pancreatic duct.
 Adenosquamous Carcinoma :-Adenosquamous carcinoma is similar to
adenocarcinoma in that it forms glands butit flattens as it grows.
 Intraductal Papillary-Mucinous Neoplasm :-Nonfunctional isletcelltumors
areusually malignant.They are hard todetect.
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14. CONTINUED
 Mucinous Cystadenocarcinoma :-Mucinous cystadenocarcinoma is a rare,
malignant, spongy, cystic tumor. The cyst is filled with a thick fluid called
mucin.
 Pancreatoblastoma :-Pancreatoblastoma is a rareform of pancreatic cancer
found in children underthe age of 10. It is often called “pancreatic cancer
ofinfancy.”
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15. PATHOPHYSIOLOGY:
 Pancreatic cancerscan arise from both the exocrineand endocrine portions
ofthe pancreas.
 Of pancreatic tumors, 95% develop from the exocrine portion of the
pancreas.
 Approximately 75% of all pancreatic carcinomas occurwithin the head or
neck of the pancreas.
 15-20% occurin the body of the pancreas.
 and 5-10% occur in the tail.
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16. PATHOPHYSIOLOGY:
 Typically, pancreatic cancerfirst metastasizes to regional lymph nodes,
then to the liver
 It canalso directly invade surrounding visceral organs such as the:
 ► duodenum
 ► stomach, and colon.

 ► and less commonly, to the lungs.
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17. PATHOPHYSIOLOGY:
 Themolecular genetics of pancreatic adenocarcinoma have beenwell
studied.
 Of these tumors, 60-75% have mutations in the KRAS gene.
 and 95% have mutations, ordeletions, in the CDKN2/ p16 gene.
 50 –70 % havemutations in TP53.
 and about 55% have deletions ormutations of SMAD4.
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18. PATHOPHYSIOLOGY:
 As in other organs, chronicinflammation is a predisposing factorin the
development ofpancreatic cancer.
 Patients with chronic pancreatitis from alcohol, especially those with
familial forms, have much higher incidence and an earlier age of onset of
pancreatic carcinoma.
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19. FREQUENCY:
 Worldwide, pancreatic cancerranks thirteenth in incidence but It remains
the eighth mostcommon cause of cancerdeath in men and the ninth most
common inwomen.
 Sex:
 Themale-to-female ratio for pancreatic canceris 2:1.
 Age:
 Themedian age at diagnosis is 65 –84 years of both sexes.
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20. MORTALITY/MORBIDITY:
 Pancreatic carcinoma is unfortunately usually a fatal disease.
 Patients eventually succumb to the consequence of :
 ► Local lymph node metastasis
 ►Distant metastasis
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21. RISK FACTORS
 Smoking
 Smokingis themostcommonenvironmental riskfactorforpancreaticcarcinoma.
 The incidenceof pancreaticcancerappearstobehigher in people with increased energy
(obesity)
.
 Diabetes mellitus
►Patientswithdiabetesmellitus ofatleast5-years'durationhavea2-foldincreasedriskof
developing pancreaticcarcinoma.
 Dietary factors
Alcoholconsumptiondoesnotappeartobeanindependentriskfactorforpancreaticcancer
unless itis associatedwith chronicpancreatitis.
ABO blood group status.
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22. RISK FACTORS (CONTINUED )
 Chronic pancreatitis.
 Genetic factors
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23. SIGNS AND SYMPTOMS
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24. CLINICAL PRESENTATION
 History
 Theearly clinical diagnosis of pancreatic cancer
is fraught with difficulty.
 Unfortunately, the initial symptoms are often
quite nonspecific and subtle in onset.
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25. CLINICAL PRESENTATION
 History
 These initial symptoms can be easily attributed to
other processes unless a physician has a high index
of suspicion for the possibility of underlying
pancreatic carcinoma.
 Delayed diagnosis is a common problem in patients
with pancreatic cancer.
 With fewer than a third of patients being diagnosed
within 2 months of the onset of their symptoms.
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26. CLINICAL PRESENTATION
 History
 Patients typically report the gradual onset of
nonspecific symptoms such as:
 Anorexia
 Malaise
 Nausea
 Fatigue
 and midepigastric orback pain.
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27. CLINICAL PRESENTATION
 History
 Significant weight loss is a characteristic
feature ofpancreatic cancer.
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28. CLINICAL PRESENTATION
 History
 Pain is the most common presenting symptom in
patients with pancreatic cancer.
 Typically, it is midepigastric in location, with radiation
ofthe pain sometimes occurring to the mid - or lower-
back region.
 Back radiation of the pain is a worrisome sign indicating
retroperitoneal invasion of the splanchnic nerveplexus
by the tumor.
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29. CLINICAL PRESENTATION
 History
 Weight loss may be related to:
 anorexia
 malabsorption from pancreatic exocrine insufficiency caused by
pancreatic ductobstruction by the cancer.
 Theonset of diabetes mellitus within the previous year is sometimes
associated with pancreatic carcinoma
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30. CLINICAL PRESENTATION
 History
 The most characteristic sign of pancreatic carcinoma of the head
of the pancreas is painless obstructive jaundice.
 a) Patients with this sign may come to medical attention before
their tumor grows large enough to cause abdominal pain.
 b) These patients usually notice a darkening of their urine and
lightening of their stools before they or their families notice the
change in skin pigmentation.
 c) Pruritus mayaccompany obstructive jaundice.
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31. CLINICAL PRESENTATION
 History
 Migratory thrombophlebitis (i.e.Trousseausign) and
venous thrombosis also occurwith higher frequency in
patients with pancreatic cancer.
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32. CLINICAL PRESENTATION
 Physical
 Thephysical examination findings in a patient with pancreatic cancerare
usually limited to evidence of:
 jaundice
 cachexia, and
 Sitting up andleaning forward may afford some relief, and this usually
indicates that the lesion has spread beyond the pancreas and is inoperable
 scratch marks may bepresent.
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33. CLINICAL PRESENTATION
 Physical
 Patients with jaundice may havea palpable gallbladder (i.e.Courvoisier
sign).
 and may haveevidenceofskin excoriations from pruritus.
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34. CLINICAL PRESENTATION
 Physical
 Patients presenting with end-stage disease may have:
 ascites
 a palpable abdominal mass hepatomegaly from liver metastases
 orsplenomegaly from portal vein obstruction.
 left supraclavicular lymphadenopathy (Virchow’s node),and
 periumbilical nodules (Sister MaryJoseph’s nodes).
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35. ESSENTIALS OF DIAGNOSIS
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 Obstructive jaundice(may be painless).
 Enlarged gallbladder (may be painful).
 Upper abdominal pain with radiation to back,weight loss, and
thrombophlebitis are usually late manifestations.

36. IMAGING STUDIES
 Dual –phase ,constrant –enchancedspiral computed tomography (CT)
scanning :- modality of choice.
 Endoscopic ultrasound (EUS) :- is a more promising screening tool .
 Magnetic resonance imaging (MRI) :- noadvantage over CT
 Endoscopic retrograde cholangiopancreatography (ERCP) :-facilitating stent
placement ,identifying obstruction in pancreatic or common bile ducts.
 Magnetic resonance cholangiopancreatography :-depicting the level and
degreeof bile and pancreatic duct dilatation.
 And positron emission tomography (PET) :-Considered before surgeryor
chemoradiotherapy.
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37. LAB WORK UP
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38. LAB STUDIES
General laboratory studies
 The laboratory findings in patients with pancreatic cancerare usually
nonspecific.
 As with many chronic diseases, a mild anemia may be present.
 Thrombocytosis is also sometimes observedin patients with cancer.
 Tissue diagnosis and cytology :-EUS – Guided fine needle aspiration is the
technique ofchoice.
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39. LAB STUDIES
General laboratory studies
 Patients presenting with obstructive jaundice showsignificant elevations
in:
 Bilirubin (conjugated and total)
 Alkaline phosphatase (ALP)
 Gamma-glutamyl transpeptidase (GGT) and
 Aspartate aminotransferase (ASP) andalanine aminotransferase (ALT).
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40. LAB STUDIES
General laboratory studies
 Interestingly, amylase andlipase areinfrequentlyelevated in pancreatic
carcinoma.
 Tumormarkers
 Themajor useful tumor markerfor pancreatic carcinomais
carbohydrate antigen 19-9 (CA19-9).
 CEA (sensitivity of 56% and specificity of 75%).
 Patients may also have laboratory evidence of malnutrition
e.g.low serumalbumin orcholesterol levels.
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41. INTERPRETATION OF PANCREATIC CANCER
 Thereareseveralstagesinvolvedinpancreaticcancer,andtwo modelsfor accurately
describingthemareTNMandStagemodels
1. TNMModel
In the Tumor,Node, Metastasis (TNM) system,tumor size,lymph node health and
metastasisactivityaremeasuredseparately,eachwith itsown numberscale.
2. STAGEModel
Thesecondmodelforpancreaticcancerinvolves4numberedstages,asfollows:
 Stage1
 Stage2
 Stage3
 Stage4
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42. TNM MODEL
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43. STAGING OF PANCREATIC CANCER
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44. STAGE 1
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45. STAGE 2
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46. STAGE 3
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47. STAGE 4
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48. TREATMENT
 Medical Care:
 Chemotherapy
 Palliative therapy
 SurgicalCare:
 Pancreaticoduodenectomy (Whipple operation).
 Neoadjuvant chemoradiation.
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49. SURGICAL CARE:
 A Whipple procedure— also known as a pancreaticoduodenectomy —is a
complex operation to removethe head of the pancreas, the first part of the
small intestine (duodenum), the gallbladder and the bile duct. Theremaining
organs are reattached to allow you to digest food normally after surgery.
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50. MORTALITY/MORBIDITY:
 Remember
 Overall survival is less than 5%.
 Patients able to undergo surgery 20% of cases.
 ►After surgery:
 Survival time is 12-19 months
 5 years survival rate 15- 20%
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51. RADIATION THERAPY
 Radiationtherapy( radiotherapy,x-ray therapy,orirradiation)is theuse ofa beam of
energy(called ionizingradiation)to killcancer cellsand shrink tumors.
 Radiationtherapyinjures ordestroys cellsinthe areabeing treated(the “target
tissue”)by damagingtheirgenetic material(DNA), makingit impossibleforthese
cellstocontinueto growanddivide.
 Majorsideeffectis radiationdamagesbothcancercellsandnormalcells, most
normalcellscan recover fromtheeffectsofradiationandfunction properly.
 The goalof radiationtherapyis to damageasmanycancer cellsaspossible,while
limitingharmto nearbyhealthytissue.
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52. CHEMOTHERAPY
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