B5-100 Pancreatic Cancer Flashcards
exocrine cells of the pancreas
acinar cells
endocrine cells of the pancreas
islet of langerhans
endocrine secretions of the pancreas
4
- insulin
- glucagon
- somatostatin
- pancreatic polypeptide
exocrine secretion of the pancreas
3
- pancreatic amylase
- proteases
- lipase
risk factors for pancreatic cancer
3
- smoking
- high body mass, lack of physical activity
- diabetes mellitus
most pancreatic cancer begins in the […] of the pancreas
head
tumors in the head of pancreas more commonly present with
3
- jaundice
- steatorrhea
- weight loss
descibe pain characteristic of pancreatic cancer
- insidious onset
- gnawing, visceral epigastric pain
- radiates to both sides of back
- worse when lying down, after meal, at night
- improves with sitting forward
25% of pancreatic cancer is heralded by new onset
diabetes mellitus
pruritis
dark urine
and pale stool are signs of
jaundice
thromboembolic events occur more commonly with tumors in the […] of the pancreas
body/tail
typical sites of metastasis of pancreatic cancer
3
liver
peritoneum
lungs
jaundice from pancreatic cancer is caused by […] hyperbilirubinemia
conjugated
- most frequently mutated gene
- presenting in >90% of cases
activating KRAS
D>V>C
[…] inactivation occurs in 95% of pancreatic cancer
loss of checkpoint
p16/CDKN2A
tumor suppressors
- inactivation in 75-80% of pancreatic cancer
- inactivation through LOH
- loss of regulation of proliferation/apoptosis
p53
- inactivation in 50% of pancreatic cancer
- inactivation through LOH
- inhibition of TGFb and BMP signaling pathways
SMAD4
used diagnostically to suggest pancreas as possible primary with mets of unknown site
gene
SMAD4
most common cause of familial pancreatic cancer
BRCA2/1
PALB2 less frequent
BRCA and PALB2 mutations are sensitive to what therapies?
PRAP inhibitor
mitomycin
platinum chemo drugs
- germline mutation of tumor suppressor
- regulates cell polarity
- PJS
STK I
for a patient presenting with epigastric pain we should get […] to evaluate for pancreatitis
lab
serum lipase
- intital imaging for patients with jaundice
- high sensitivity for biliary obstruction and pancreatic mass > 3cm
transabdominal ultrasound
first test for patients with jaundice and a high suspicion of choledocholithiasis
ERCP or MRCP
- most widely used and most sensitive imaging modality for evaluation of pancreatic cancer
- can detect tumor <2cm
CT
preferred intital imaging in patients without jaundice
CT
used to guide biopsies when histological confirmation is needed
EUS
if the tumor involves the SMA, celiac axis, and/or common hepatic it is T[..] regardless of size
staging
T4
N category of staging assesses
regional lymph node involvement
- NX- cannot be assessed
- N0- none
- N1- 1 to 3 lymph nodes
- N2- 4+ lymph nodes
M category of staging assesses
distant metastasis
M0- none
M1- distant metastasis
if tumor is M1, it is stage […] regardless of T or N
4
treatment for metastatic disease
first and second line
first: folfirinox or gemcitabine
second: folfox
treatment for non-metastatic resectable disease
resect
gemcitabine
treatment for non-metastatic, non-resectable disease
folfirinox
what makes a patient a candidate for resection?
- limited to pancreas
- limited nodal involvement
- limited vascular involvement
only 15-20% are resectable
why do only 38% of patients with resectable disease receive surgery?
- low SES
- physician pessimism regarding prognosis
most commonly used procedure for resectable pancreatic cancer
Whipple
pancreaticoduodenectomy
postoperative complications of resecting pancretic cancer
3
- delayed gastric empyting
- pancreatic fistulas
- wound infections
is a standard or extended lymphadenectomy the preffered operation?
standard
extended shows no benefit and may have worse outcomes
if a pancreatic tumor in the body/tail is deemed resectable (rare), what procedure is performed?
distal subtotal pancreatectomy with combine splenectomy
mutations associated with pancreatic NETs
2
PTEN
MEN1
what functional PanNET causes hypoglycemia?
insulinoma
what functional PanNET causes Zollinger Ellison and steatorrhea?
ulcers in unsual places
gastrinoma
what functional PanNET causes watery diarrhea, hypokalemia, and achlohydria?
VIPoma
what functional PanNET causes diabetes mellitus and necrolytic migratory erythema?
glucagonoma
what functional PanNET causes DM, steatorrhea, and hypochlorhydria?
somatostatinoma
VIPoma is due to a tumor in what cell type?
D1
treatment for most functional PanNETs
somatostatin analogs (octreotide)
which type of pancreatic adenocarcinoma precusor lesion is able to be radiographically detected?
cystic lesions
PanIN-1A mutations
ERBB2
KRAS
PanIN-2 mutation
CDKN2A
PanIN-3 mutations
tp53
SMAD4
BRCA2
tumer diameter <2cm
T_
T1
maximum tumor diameter greater than 2 cm less than 4 cm
T_
T2
maximum tumor diameter >4 cm
T_
T3
- fatigue
- shakiness
- hunger
- irritability
symptoms of
insulinoma
- gastric ulcers
- abdominal pain
- nausea
- vomiting
- elevated serum gastrin
gastrinoma
- thirst
- frequent urination
- abdominal pain
symptoms of
glucagonoma
hyperglycemia
imaging modality used to monitor functional NETs
dotatate PET/CT
- amylase: low
- CEA: low
- CA72-4: low
- CA 19-9: variable
- CA 125: low
serous cystadenoma
- amylase: low
- CEA: high
- CA72-4: high
- CA 19-9: variable
- CA 125: variable
mucinous cystic neoplasm
- amylase: high
- CEA: high
- CA72-4: high
- CA 19-9: variable
- CA 125: low
IPMN
- amylase: high
- CEA: low
- CA72-4: low
- CA 19-9: high
- CA 125: low
pseudocyst
most common type of pancreatic cancer?
ductal adenocarcinoma
most common symptoms in pancreatic cancer
3
jaundice
weight loss
epigastric pain
what gene mutation may have a better response to checkpoint inhibitor treatment?
MLH1/MSH2/6
defects in DNA mistmatch repair respond better
what organs are involved in a whipple?
5
- distal stomach
- duodenum
- head of pancreas
- common bile duct
- gallbladder
an immune checkpoint inhibitor can be used in what mutations?
DNA mistmatch repair
MLH/MSH
biomarker for pancreatic cancer
CA 19-9
new onset diabetes is an independent risk factor for
pancreatic cancer
hemolysis causes elevation of […] bilirubin
unconjugated
- ducts lined by a single layer of epithelial cells
- significant collagen within the walls of some ducts
- well organized ductal structure
normal pancreas
cells with large nuclear/cytoplasm ratio and marked nuclear polymorphism
pancreatic ductal adenocarcinoma
“drunken honeycomb”
pancreatic ductal adenocarcinoma
pancreatic ductal adenocarcinoma
left: normal honeycomb, right: drunken honeycomb
recommendation for treatment with low ECOG and favorable cormobidities
chemotherapy
metastasis is a […] to surgery
contraindication
when there is mismatch repair deficiency or microsatellite instability, what treatment can be used?
checkpoint inhibitors (PD1)
treatment for known HRR deficiency
PARP inhibitors
more than 180 involvement of SMV or portal vein but lacks contact with other vasculatures
borderline resectable
what is removed during a Whipple?
- distal stomach
- duodenum
- head of pancreas
- gallbladder
- part of common bile duct
tumor is in contact with aorta
unresectable
what is the advantages of PPPD?
- reduced blood loss during surgery
- shorter operating time
are most PNNs functional or nonfunctional?
nonfunctional
70%
a tumor in the head of the pancreas is in close proximity to what parts of the duodenum?
3
superior
descending
horizontal
what part of the duodenum is near the body and tail of the pancreas?
ascending
why is the stomach less likely to be invaded by pancreatic cancer?
it is intraperitoneal and can move
two arteries that supply the head of the pancreas
gastroduodenal
superior mesenteric
supplies body and tail of pancreas
splenic artery
normally expressed in fetal tissues and typically low in adults but some pancreatic neoplasms express
CEA
whipple triad
symptoms of hypoglycemia
low plasma glucose
relief of symptoms with glucose administration
insulinoma
- peptic/duodenal ulcers
- gastroesophageal reflux
- diarrhea
gastrinoma
4 Ds of glucagonoma
- diabetes
- dermatitis (necrolytic migratory erythema)
- deep vein thrombosis
- depression
verner-morrison syndrome
- watery diarrhea
- hypokalemia
- achlorhydria/hypochlorhydria
glucagonoma
- DM
- diarrhea
- steatorrhea
- anemia
- malabsorption
- cholelithiasis
somatostatinoma
what 2 NETs are closely associated with MEN1 mutations?
gastrinoma
insulinomas