ICL 12.4: Pancreatic Cancer and Pre-Malignant Conditions of Pancreas Flashcards
how common is pancreas cancer?
9th in women
10th in men
however, it’s the 4th most lethal cancer in both genders which isn’t good…and it’s projected to be 2nd in the next decade
why does pancreatic cancer have a high mortality?
the incidence matches the mortality so not a lot of people survive…
what is the race association with pancreatic cancer?
predominance in african americans
multifactorial: health care access, PCP, earlier diagnosis, genetics
what is the mean cancer diagnosis age?
70
but it can happen in younger people too
what are the risk factors for pancreas cancer?
- tobacco*
- alcohol
- obesity
- DM and type I*
- non-O blood type
- H. pylori
- chronic pancreatitis*
- IPMN*
which genes are associated with pancreatic cancer?
- KRAS (80-95%)
- SMAD4 (55%)
- TP53 (50%)
- TP16
- BRACA2
pancreatic adenocarcinoma type has an average of sixty-three genetic aberrations at time of diagnosis…
how long does it take pancreatic cancer to develop?
~17 year latency from initial somatic mutation to acquisition of metastatic potential
what is the location of pancreatic cancer lesions?
75% occur in the head or neck region
15-20% occur in the body
5-10% in the tail
what’s the clinical presentation of a pancreatic cancer in the head of the pancreas?
the tumor is more likely to be near the bile duct so it can cause:
1. painless jaundice –> you’re obstructing the bile duct and it’ll back up into the liver and it’ll deposit all over your body and you get jaundice
- dark urine and light stool
- nausea
- unintended weight loss
what’s the clinical presentation of a pancreatic cancer in the body of the pancreas?
the tumor is more likely to be near the celiac nerve so tumors in this location can cause:
- back pain (pancreas is a retroperitoneal organ so pain will be referred to the back)
- upper abdomen pain
what’s the clinical presentation of a pancreatic cancer in the tail of the pancreas?
the tumor presses on the stomach and small intestines
if the tumor is toward the middle of the pancreas it can also be near the celiac nerve
it can cause:
1. lower abdomen pain
- back pain
- nausea
- loss of appetite
- unintended weight loss
- pain after eating
- indigestion
what clinical considerations should you keep in mind with pancreatic cancer?
- always be suspicious of painless jaundice, especially when accompanied by weight loss or risk factors (tobacco, diabetes, pancreatitis, etc.)
- nausea and vomiting may be the result of duodenal obstruction
what is the detection challenge with pancreatic cancer?
pancreatic adenocarcinomas remain small for most of their development
symptoms often do not result until the tumor becomes large (causing mass effect) or spreads to adjacent organs
conventional imaging (CT and MRI) has poor sensitivity for small (< 1 cm) lesions…you can’t even see them on imagining before they hit 1 cm
biomarker CA 19-9 correlates with tumor size but is neither sensitive nor specific for small tumors
how do you workup a suspected pancreatic cancer?
pancreatic cancer is a tissue diagnosis –suspicious masses should be biopsied, typically by endoscopic ultrasound
histology helps guide therapy
dvaluate locoregional lymphadenopathy
all patients with locoregional or metastatic disease will receive (neoadjuvant) chemotherapy; surgery isn’t really an option at that point
how do you image the pancreas?
- ultrasonography: transabdominal vs endoscopic
- triphasic CT scan with IV contrast (for spread and invasion and to see which blood vessels are associated with it)
- endoscopic retrograde cholangiopancreatography (ERCP)
- MRI / MRCP for high-resolution anatomical details
- PET/CT to detect distant metastases
- diagnostic laparoscopy
based on the location of the pancreatic tumor, what surgery do you do?
uncinate/head/neck lesion = pancreaticoduodenectomy = Whipple –> way harder; involves the liver, bile duct, duodenum, pancreas and stomach
body/tail = distal pancreatectomy and splenectomy
what is the pathology of pancreatic cancer?
cancers arise from both the exocrine and endocrine portions of glands
- exocrine cancers are way more common (95%) = acinar and duct tissue
ex. pancreatic ductal adenocarcinoma or acinar cell carcinoma - endocrine = involves islets of Langerhans and causes hormone secretion
ex. neuroendocrine tumors
what is the prognosis for pancreatic adenocarcinoma?
5 year survival is <10%
5 year survival is 20% after pancreatic resection –> to maximize survival make sure you do node resection, small tumors less than 3 cm, negative resection margins, well differentiated tumors
how do you treat pancreatic adenocarincoma?
- inherently resistant to chemotherapeutic regimens
- 5-FU and gemcitabine have been the most active agents
- radiation therapy alone has little impact, often combined with radiosensitizing agents 5-FU or gemcitabine.
most high-volume centers advocate for neoadjuvant chemoradiation for all potentially operable disease or for patients with locally advanced disease – upon finishing this therapy patient is restaged and if disease still appears resectable, resection is undertaken
what is the 20-20 rule with pancreatic adenocarcinoma?
20% of patients present with resectable pancreas cancer
of those that get a resection, they have a 20% 5 year survival
what is a local advanced pancreatic tumor?
direction invasion of surrounding visceral organs and vessels
this would include things like mets to the liver, peritoneum or lung
treat with chemotherapy/chemoradiotherapy
when would you stage someone with pancreatic cancer?
staging laparoscopy for patients at high risk for occult metastatic disease
you would stage them if:
- tumors in the pancreatic body or tail
- large or anatomically extensive
- high CA 19-9 level
- equivocal CT findings of metastasis
- clinical findings suggestive of advanced disease (e.g., marked weight loss, ascites)
what are pancreatic neuroendocrine tumors?
tumors involving the islets of langerhans!
alpha cells = glucagon
beta cells = insulin
delta cells = somatostatin
G cells = gastrin
how do you image pancreatic neuroendocrine tumors?
gallium-68 DOTATATE scan
fancy PET scan where they give patients octreotide linked to radioactive isotope which binds to somatostatin receptors on neuroendocrine tumor
if you biopsy and find a NET you can assess for metastasis with this scan
what is the biomarker for a pancreatic neuroendocrine tumor?
chromogranin A
what are the symptoms of pancreatic neuroendocrine tumors?
- diarrhea
2. cramping
what is a glucagonoma?
rare tumor of alpha cells – malignant potential
treat with surgical resection
presents as weight loss and the D’s:
1. dermatitis (necrolytic migratory erythema)
- diabetes (hyperglycemia due to constantlyhigh glucagon levels)
- diarrhea
- DVT
- depression
what is an insulinoma?
most common pancreatic neuroendocrine tumor; 90% are benign –> treat with surgical resection
insulin-secreting tumor of B-cells
hypoglycemic symptoms = hunger, nervous, sweating, lethargy, confusion, coma
Whipple’s triad:
1. hypoglycemia (glucose < 55)
- symptoms of hypoglycemia
- correction of symptoms with glucose administration
what are the lab results in a patient with an insulinoma?
- hypoglycemia
- elevated insulin
- elevated C-peptide
what is a somatostatinoma?
rare tumor of delta cells, usually in the head of the pancreas –> malignant!!
treat with resection
symptoms are due to inhibition of secretion by somatostatin = gallstones, steatorrhea, weight loss
what is Zollinger-Ellison syndrome?
aka gastrinomas = tumors secreting gastrin that form in the pancreas or duodenum (“gastronome triangle”) –> this leads to excess acid production
elevated serum gastrin level (>1000) is the most sensitive and specific diagnostic factor
presents as:
1. peptic ulcer disease
- diarrhea
- steatorrhea
- B12 malabsorption
how do you treat Zollinger-ellison syndrome?
total gastrectomy is not necessary for managing patients with ZES because effective medical therapy (proton pump inhibitors) for the acid hypersecretion can prevent ulcer disease
surgical removal of the gastrinoma could eliminate the source of excessive gastrin release and present the chance for cure - this is frequently not accomplished
what is IPMN?
intraductal papillary mutinous neoplasm
they are cysts lined by columnar epithelium which secrete mucus
they have malignant potential!!!
suggestive indications: high cyst CEA, high serum CA 19-9, large size
what is a mutinous cystic neoplasm?
very female predominant 20:1
they are thick cyst wall (“eggshell calcification”) with thick viscous fluid (“ovarian-like stroma”) and septations
elevated cyst fluid CEA
malignant potential, resection recommended
associated with KRAS mutation in 20% of low-grade, 33% of intermediate-grade, and 90% of high-grade MCNs
what are serous cyst adenoma?
benign lesions; tend to be left alone unless they get too big
they are csyst lined with flat epithelium, contains serous fluid (glycogen rich cells*)
they typically occupy body and tail of pancreas
calcified central scar
