Lecture 74_75 - Diseases and pathology of Pancreas, GB

Question 1

Describe the anatomy of the biliary tree?

Answer 1

Right Hepatic duct and left hepatic duct converge to form the common hepatic duct (RHD branches more quickly than the left)

Cystic Duct (from GB) converges with the CHD to form the Common bile duct

Pancreatic duct and CBD converge at the Major Papilla (of Vater) (of the second part of the Duodenum), which is controlled by the Sphicter of Oddi

Question 2

what is ERCP?

Answer 2

Endoscopic Retrograde Cholangeo-pancrea-tography

Imaging technique designed to specifically look at biliary architecture

Question 3

what is a HIDA scan?

Answer 3

§ HIDA Scan – aka Liver/Spleen Scan
□ Radio tracer injected into the vein which follows the course of bile (taken up in liver and excreted into biliary tree)
® Liver should be dark; excreted to bile duct
® If stone in the Cystic Duct – no tracer will enter the gall bladder

Question 4

what are the different types of gall stones?

etiologies

Answer 4

1) Cholesterol stones – Comes from endogenous cholesterol when there is an imbalance between cholesterol, bile salts, and phospholipids, the cholesterol comes out of solution
2) Pigment Stones –

black – increased unconjugated bile (such as hemolysis of sickle cell disease)
brown – usually due to infection; common in asian populations (liver flukes)

Question 5

Treatment of Gall stones;
Symptomatic
asymptomatic

Answer 5

Asymptomatic – observation; unless the patient needs prophylaxis (eg sickle cell patients or porcelien GB patients)

Symptomatic – Threapuetic intervention is necessary due to increase complication rate

Question 6

Symptoms of Gall STones / impaction of a gall stones
(where can the pain radiate to?)

what symptoms should you not attribute to gall stones?

Answer 6

Symptoms: Biliary Cholic (episodic and crampy pain due to a stones transient impaction in the cystic duct)
pain is usually in the RUQ/Epigastrium but can radiate to the chest or R scapula

Never attribute Chronic pain, belching, bloating, fatty food intolerance or chronic pain to gall stones

Question 7

Pirmary method for dx of gall stones?

Answer 7

Ultrasound

Question 8

Complications of cholelithiasis?

what pattern of LFTs is observed

Answer 8

• Acute cholecystitis –
  
  • Choledocholithiasis – (Choledocholithiasis Cholangitis vs Choledocholithiasis Pancreatitis)

LFTs- – elevated BR / elevated ALP

Question 9

• Acute cholecystitis –
where is the stone?
typical presentation
eponymous physical exam finding

diagnostic techniques

Treatment

Answer 9

gall stone stuck in the cystic duct, leading to inflammation of the GB wall, due to bacteria in the now static media

resentation – RUQ pain with N/V, Fever, Luekocytosis, Jaundice,

Murphy’s Sign (palpate the gall bladder and have inspiratory arrests)

dx: RUQ pain, US, HIDA

Tx: Abx + surgical management

Question 10

Choledocholithiasis Cholangitis — where is the stone
what is charcot’s triad?

Choledocholithiasis Pancreatitis

Answer 10

Cholangitis – § Common bile Duct Obstruction leading to bacterial infection and inflammation

§ Charcot's Tirad -- pain, jaundice, fever 

Pancreatitis – Inflammation of the pancreas due to gallstone obstruction in the pacnreatic duct/ampulla of vater

Question 11

Treatments for choliolithiasis

Answer 11

○ Surgery – laproscopic cholecystectomy
Oral dissolution – bile salts over many month

Contact Dissolution — infuse ether , and solubilizes stones instantly, but lots of side effects

	○ Extracorporial lithotripsy 

ERCP – § Preferred method for removal of common bile duct stones

Question 12

• Primary Sclerosisng Cholangitis

what is it?
histo pattner?
commonly associated with?
how does it present on imaging?

Answer 12

Idiopathic fibrosing d/o of the intra and extra hepatic biliary ducts

○ Associated with IBD (Crohns, Ulcerative Colitis)

onion skinning of bile ducts

imaging: “chain of links”

Question 13

what is acute pancreatitis?

what is the a necessary symptom to make the dx?

Answer 13

Acute inflammation of the pancreases manifested by abdominal pain and increased amylase and lipase (atuodigestion of the pancreas by pancreatic enzymes)

PAIN is an absolutely necessary symptom to make the dx

Question 14

what kind of pain can manifest in acute pancreatitis?

what levels of amylase and lipase are seen on labs?

Answer 14

○ PAIN – epigastric, central and radiates to the back (bc the pancreas is retroperionteal)

§ Some of the worst pain a patient can have

○ Enzymes Amlyase and Lipase – 3x upper limits of normal

Question 15

what are some etiologies of acute pancreatitis (GET SMASHED)

Answer 15

Gall-stones
Alcohol
Trauma 
Steroids/sulfonamides, other durgs such as 6MP 
Mumps 
Auto-immune disease 
Scorpion sting 
Hypercalcemia/Hypertriglyceridemia
ERCP
Drugs (sulfa drugs)

Question 16

what are some effcts (local and systemic) of increased trypsin and lipase ?

Answer 16

○ Activation of multiple cascades
§ Capillary leak
§ Peripheral white cell response

§ DIC

§ Local Fat Necrosis - -autodigestion of the pancrease

§ Coagulopathy

Renal failure

can lead to pancreatic psuedocyst which can rupture and hemorrhage

Question 17

Complications of acute pancreatitis?

how may it present

Answer 17

Psuedocysts – Extrapancreatic Fluid in the retroperitoneal space; a rind can form around it

§ Pseudocysts – form 3-6 weeks after sever acute pancreatitis

Severe pain, obstruction duodenum, dissection, bleeding of the cyst (hemosucus pancreaticus), infection, erosion into other structures, pleural effusion with high amylase and lipase

Question 18

Treatment goals of Chronic pancreatitis

Answer 18

Supportive care – clinical surveillance, NPO, aggressive IV fluid replacement (helps perfuse the pancreas and mitigates renal dysfunction), pain relief , nutritional support , (+/- IV abx of necrosis)

	○ Reduce inflammation 
	○ Assess and treatment complications

Question 19

• Chronic Pancreatitis –

What is it ?

• Presentation ?

Answer 19

Long standing inflammation in abnormal gland, usually after repeat bouts of acute pancreatis which has caused gland scarring

	○ Chronic pain 
	○ Calcificaitons of the pancrease 

	○ Pancreating endo and exocrine insufficiency

Question 20

Major etiologies of chronic pancreatitis?

Answer 20

Alcohol's 
CF,
 herediatary pancreatitis,
hypertriglyceridemia
autoimmune
Idiopathic 

Pancreas Divisum

Question 21

Presentation and symptoms of chronic pancreatitis?

Answer 21

Pain (which may die down as the disease progresses)

exocrine insufficienies
Steatorrhea (if alcohol related) (lipase < 10%)

endocrine insufficiencies:
DMT1 – loss of insulin and glucagon
Risk of DKA

Question 22

what dx test can be made for chronic pancreatitis?

Answer 22

ERCP, CT, US – look for stones, ductal dilation
□ Calcifications in the gland —

		§ Function -- Secretin tests (enzymes, bicarb), fecal chymotrypsin, or fat

Question 23

• acute cholecystitis vs chronic

Gross path
symptoms

Answer 23

acute: GB appears red or hemorrhagic
RUQ pain, N, Fever, anorexia

Chronic:
The GB wall is thick and fibrotic
RUQ Pain, N, Fever, anorexia — but usually a more indolent course
May be asymptomatic

Question 24

Biliary Atresia:

what is it?
etiology?
pathology?
prognosis?

Answer 24

Hypoplasia or narrowing of biliary tract in infancy;

Pathology — Cholestasis; bile tries to found other routes of the liver; biliary cirrhosis; bile duct obliterated by inflammation

* Etiology unknown
* Most important cause of liver disease in early childhood -- frequent and severe 

Prognosis – ○ Cirrhosis develops by 3-6 months (8 weeks) of age without treatment

Question 25

biliary atresia – treatment

complications of the treatment

Answer 25

Kasai Procedure – transection of the small bowel such that the bile ducts can drain directly into the bowel

		§ Complications: Increased Incidence of Cholangitis 
		§ Many patients go on to develop cirrhosis later in life anyway

Question 26

Choledochal Cyst

• what is it ?
  how does it present?
  treatmnet

Answer 26

• Congenital, tpyically present with obstructive jaundice

- - Treatment: Resection

Question 27

three Congenital Abnormalities of the Pancreas

Answer 27

Pancreas Divisum — small Duct of Wirsung; most of the pancreas is left to the drain through minor papillum.

Pancreatinc Heteropia ( normal pancreatic tissue elsewhere in the GI tract)

Annular Pancreas – a pancreas that encircles the duodenum;
Predispose: to Pancreatitis

Question 28

Acute vs chronic pancreatitis

pathologies
histology –

(what happens to the ducts in chronic pancreatitis)

Answer 28

Acute:
Pathology: Inflammation, fat necrosis, Hemorrhage
Release of Digestive Enzymes (lipases, phospholipase, elastase)
Local and Distant Injury

Histology — viable pancreas, necrosis (no nuceli, red is dead), fat necrosis (white lobules)

Chronic:
loss of excorine and then endocrine function
patients present with steatorrhea, then DM symptoms
first – loss of the acini
second – loss of the islets
replacement by fibrosis
dilation of the ducts

Question 29

Pancreatic Cysts:

what are the different kinds
which are benign vs have malignant potential vs malignant

Answer 29

Non neoplastic/Benign: Congeital, Psuedocysts

Neoplastic/Benign: Serous Cysts

Neoplastic/Malignant Potential: Mucinous cysts (MCNs, IPMNs)

neoplastic/malignant: Solid pseudopapillary + cystic changes in actual tumors

Question 30

treatment options for cysts?

Answer 30

Watch
Cytology (FNA) to risk stratification
Excision

Question 31

Pseudocysts

benign vs malignant?
associated with?
why is it called psudocyst?
Prognosis?

Answer 31

non neoplastic; Benign
Usually in the setting of chronic pancreatits (alcohol)
but can result from inflammation or trauma

lack true lining

prognosis: May resolve, become infected (in the pool of protein), or impinge on other structures

Question 32

Serous Cysts -

benign vs malignant?
Gross path appearance?
males vs females predominance?

Prognosis?

Answer 32

Neoplastic; Benign
○ ‘Sponge-like’ gross appearance
○ Female predominance (2:1), older adults (7th decade)
○ May become very large, present as mass

Question 33

Mucinous Cysts

benign vs malingnant?
what are the two kinds?

Answer 33

Potential for Malignancy

	○ Mucinous Cystic Neoplasm: MCM 

	○ Intraductal Papillary Mucinous Neoplasms -- IPMN

Question 34

Mucinous Cysts: Intraductal Papillary Mucinous Neoplasms – IPMN

• • male or female predominance?
• • where in the pancreas does it occur?

Answer 34

§ Older patients, male predominance, more in the pancreatic head

Question 35

Mucinous Cyst: Mucinous Cystic Neoplasm: MCN

• • male or female predominance?
• • where in the pancreas does it occur?
• • histology appears like what other organ?

Answer 35

§ Young women, in body or tail of pancreas

§ ‘ovarian type’ stroma

Question 36

Pancreatic Cysts: Solid Pseudopapillary Tumor

benign vs malingnant?
- male or female predominance?

what mutations/proteins are good for diagnosis ?

treatment and prognosis of treatment?

Answer 36

Malignant but very low-grade

Strong female predominance (9:1), young patients

Mutations in the Beta-catenin/APC

	○ Treatment: Resection is curative

Question 37

Pancreatic Cancers:

vast majority are….?

precursors include …?

genetic pathogenesis…(name a few genes which become mutated?)

Answer 37

Vast Majority: Ductal Adenocarcinoma

	Development of Pancreatic cancer: 
		Cystic Lesions (mucinous -- MCMs, IPMNs) --- may progress to cancer (benign --> low grade --> high grade --> invasion) 

	Mutations In K ras 
	Inactivation of P16 
	Inactivation of P53
	SMAD4 = DPC4 = ("deleted in pancreatic cancer")

Question 38

Ductal Adenocarcinoma –

mortality?
reason for this mortality?

where in the pancreas are the typically found?
histology?

Answer 38

High mortality — 7% survival at 5 year
Presents at high stage bc you have to wait for symptoms. No effective screening methods
Majority (60%) are in the Head

	Histology -- 
			Invasive gland like structures 
			Perineural invasion 
			Invasion outside of pancreas 
			Lymphatic and vascular invasion

Question 39

Treatment options for pancreatic malignancies:
what are the different types of surgical procedures

what can be done beside surgery

Answer 39

Surgical - the only real treatment
Head of Pancreas: Whipple Procedure (pancreatic duodenectomy)

			Body/Tail of Pancreas: Distal pancreatectomy & Splenectomy 

			Neoadjuvant therapy may be given in unresectable cases to possible shrink the tumor enough to make it resectable 

		Adjuvant Radiation and Chemotherapy

Question 40

Pancreatic Endocrine (Islets) Neoplasms

what stains can be done on histology?

what are they histological classification? — which can be treated with chemo?

what are the functional classifications? — which are benign / malignant?

Answer 40

stain positive for chromogranin and synaptophysin

Histo class:
§ Well differentiated tumor (type 1) – not treated with chemo
§ Well differentiated carcinoma (type 2) — treatment with chemo
Poorly-differentiated carcinoma (type 3; rare)

	○ Functional classification § Insulinomas: Majority are benign (symptomatic at early stage) § Gastrinomas: Majority are malignant Glucagonomas: Majority are malignant

Question 41

Acinar Cell Carcinoma of the pancreas

• characteristic feature?

Answer 41

Arises from acinar cells rather than ducts

§ Increased levels of amylase and lipase

Question 42

Pancreoblastoma

• who is mostly affected by this?
  how common is it?
  histology?
  treatment

Answer 42

Rare – mainly in children

	Histology: Undifferentiated cells with squamoid nests 

	Treatment: Chemotherapy