10/20- Pathology of Endocrine/Exocrine Pancreas Flashcards

1
Q

She’s going for concepts not tiny facts; histo pictures from this lecture not tested (?)

A

woot

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2
Q

Describe relationship of anatomy to other abdominal organs

A
  • Head within C loop of the duodenum
  • Tail going out toward the spleen
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3
Q

What provides major blood supply to pancreas?

A
  • Hepatic a of celiac trunk
  • Superior mesenteric a
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4
Q

Is the pancreas (grossly) more endocrine or exocrine?

A

More exocrine cells (acinar)

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5
Q

Describe basic embryology of pancreas

A

Ventral and dorsal bud fuse to form the pancreas

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6
Q

Describe ductal system of pancreas

A
  • Major pancreatic duct enters at major duodenal papilla (typically with common bile duct)
  • Accessory pancreatic duct
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7
Q

What is pancreas divisum?

A
  • Developmental anomaly with failure of fusion of ducts of Wirsung and Santorini
  • Main part of pancreas drained by duct of Santorini -> minor papilla
  • Posterior-inferior head and uncinate drained by duct of Wirsung->major papilla after joining CBD
  • Small size of minor papilla predisposes to pancreatitis
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8
Q

What is acute pancreatitis?

  • Symptoms
  • Prognosis
A

Symptoms

  • Sudden severe mid-epigastric pain radiating to the back, sometimes to chest, flanks, lower abdomen
  • May present as acute abdomen

Most recover

Prognosis/Progression:

  • 25% severe with complications which may include:
  • Infection
  • Shock
  • Acute respiratory distress syndrome (ARDS)
  • Acute renal failure (ATN)
  • Death
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9
Q

What are the most common causes of acute pancreatitis?

A
  • GET SMASHED (other lecture)*
    • Gallstones, Ethanol, Trauma, Steroids, Mumps/Infxns, Autoimmune (IgG4), Scorpion sting, ERCP post op, Drugs (esp sulfas)*

This lecture: mostly obstruction and alcohol.

Obstruction

  • Gallstones (choledocholithiasis): mostly the small ones
  • Periampullary or pancreatic mass
  • Pancreas divisum with relative stenosis of minor papilla
  • Hypertrophic sphincter of Oddi
  • Parasites

Alcohol

Metabolic

  • Hyperlipidemia
  • Hypercalcemia

Drugs

  • Azathioprine
  • 6MP
  • Estrogens

Mechanical

  • Trauma
  • Iatrogenic: ERCP, sphincterotomy, surgery

Vascular/ischemia

  • Shock
  • Thromboemboli: atherosclerotic or vasculitis

Infection

  • Mumps
  • Coxsackievirus
  • Mycoplasma

AIDS

  • Infxn: HIV, CMV, Crypto, Toxo, Mycobacterium
  • Drugs: HAART, pentamidine, Bactrim

Penetrating peptic ulcer

Idiopathic

Hereditary

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10
Q

What are some causes of hereditary pancreatitis?

A
  • Germline mutations, most resulting in increased or sustained activity of trypsin
  • PRSS1
  • SPINK
  • CFTR (cystic fibrosis transmembrane conductance regulator); not associated with clinical CF
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11
Q

What is the pathogenesis of acute pancreatitis?

A
  • Duct obstruction
  • Acinar cell injury
  • Deranged IC transport of pancreatic proenzymes to lysosomes

All 3 mechanisms -> enzyme activation and acinar injury.

Activated enzymes result in:

  • Interstitial inflammation and edema
  • Proteolysis (proteases)
  • Fat necrosis (lipases, phospolipases)
  • Vascular damage (elastases)
  • Activation of prekallikrein -> coagulation cascade
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12
Q

What are some of the pancreatic enzymes? (recognize)

A
  • Trypsin
  • Chymotrypsin
  • Elastase
  • Amylase
  • Lipase
  • Phospholipase
  • Carboxypeptidase
  • Nuclease
  • Kallikrein
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13
Q

How to diagnose acute pancreatitis?

A
  • History/physical
  • Serum amylase (best early)
  • Serum lipase (high by 72 hrs)
  • US for exam of biliary tract
  • CT scan, MRI
  • ERCP, MRCP
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14
Q

What are complications of acute pancreatitis?

A
  • Necrosis: sterile or infected tissue
  • Abscess
  • Peritonitis
  • Pseudocysts
  • Systemic
  • Multisystem organ failure
  • Shock
  • Respiratory failure
  • Renal failure
  • Death
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15
Q

What is the typical presentation of chronic pancreatitis?

A

No typical presentation; varies

  • Pain: repeated or persistent
  • May be silent until develop pancreatic insufficiency
  • May have mild jaundice
  • Late:
  • Weight loss
  • Steatorrhea
  • DM
  • Pseudocysts
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16
Q

What are causes of chronic pancreatitis?

A
  • Other lecture- I ACT SAD*
  • Idiopathic, Alcoholism, CF/Genetic factors, Tropical Pancreatitis, Smoking, Autoimmune, Duct obstruction*

Here:

  • Alcoholism (#1 cause)
  • Duct obstruction by stones, neoplasms
  • Hyperlipidemia, hyperCa
  • Pancreas divisum
  • Hereditary: germline mutations in PRSS1, SPINK 1 and CFTR genes
  • Autoimmune
  • Idiopathic
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17
Q

Chronic pancreatitis is associated with what?

A

40% lifetime risk of pancreatic cancer

18
Q

Describe autoimmune cause of chronic pancreatitis

  • Treatment
A
  • Increased IgG4 plasma cells
  • Increased serum IgG4
  • May mimic pancreatic cancer clinically and radiographically
  • Responsive to steroids
19
Q

What conditions may lead to pancreatic pseudocyts?

A
  • Acute pancreatitis
  • Chronic pancreatitis
  • Trauma
  • Cancer (rare)
20
Q

Pancreatic neoplasms may affect what parts of the pancreas?

A
  • Exocrine parts
  • Endocrine parts
  • Ampulla of Vater and distal common bile duct
21
Q

What are cystic pancreatic neoplasms?

A
  • Serous cystadenoma, most microcystic
  • Mucinous cystic neoplasm
  • Intraductal papillary mucinous neoplasm
  • Solid pseudopapillary tumor
  • Cystic pancreatic neuroendocrine neoplasm
22
Q

Describe serous cystadenoma

  • Composition
  • Malignant vs. benign
  • Treatment
A
  • Most microcystic (microcystic adenoma)
  • Occasionally oligocystic
  • Glycogen-rich
  • Almost all serous cystic neoplasms of pancreas are benign
  • Do not need to resect unless causing obstruction, bleeding or other problem
23
Q

Describe mucinous cystic neoplasms (MCN)

  • Treatment
A

Subclassified as MCN with

  • low or intermediate grade dysplasia
  • high grade dysplasia
  • associated invasive carcinoma

Should be completely resected because may harbor malignancy or may undergo malignant transformation

24
Q

Describe Intraductal papillary mucinous neoplasm (IPMN)

  • Location
  • Epidemiology
A
  • Occurs in men and women
  • May involve main pancreatic duct or branch of pancreatic duct
  • Most occur in head of pancreas
  • May involve entire pancreas
  • Visible duct distended by mucin
25
Q

Prognosis/treatment of Intraductal Papillary Mucinous Neoplasm (IPMN)

A
  • Invasive carcinoma develops in up to 30% of IPMNs
  • Significantly greater risk of associated carcinoma in main duct IPMN than in branch duct IPMN
  • Excellent prognosis for those without associated invasive carcinoma
26
Q

Describe solid pseudopapillary neoplasm

  • Epidemiology
  • Characteristics
  • Prognosis
  • Treatment
A
  • Usually occur in adolescent girls and young women
  • Often large, variably solid and cystic
  • Most behave indolently
  • 5-15% metastasize
  • Treatment of choice: complete surgical resection
27
Q

Describe carcinoma of the pancreas: epidemiology

A
  • 4th most common cancer death (1. lung, 2. colon, 3. breast)
  • Equal genders
  • Uncommon < 40 yo
  • Most 60-80 yo, but see many in 50s and some in 40s
28
Q

Progression/prognosis of pancreatic carcinomas?

A

BAD

  • Usually diagnosed late; rarely curable when diagnosed
  • Only 9% localized at diagnosis; without extension beyond pancreas or spread to regional LNs
  • Over 50% of pts have distant metastases at diagnosis
  • 5 yr survival 7%
  • Even with surgical resection, avg 5 yr survival 26%
  • May be better with neoadjuvant/adjuvant chemo w/ surgery
  • Hope for future targeted therapy
29
Q

What are the molecular genetics of pancreatic carcinoma?

A

Common somatic mutations and epigenetic silencing

  • k-ras (90-95%), codon 12, most frequently altered oncogene
  • p16 (95%), most frequently inactivated tumor suppressor gene
  • SMAD4 (>50% inact) inactivated tumor suppressor; codes for protein with role in signal transduction
  • p53 (50-75% inact): tumor suppressor gene
30
Q

What are risk factors for pancreatic carcinoma?

A
  • Cause unknown
  • Smoking: strongest evidence, 2x risk
  • Diet of high saturated fats, obesity
  • S/P partial gastrectomy
  • N-nitroso products of bacteria
  • Exposure to chemical carcinogens
  • Chronic alcoholism
  • Chronic pancreatitis - ? cause or effect
  • Diabetes – ? cause or effect
31
Q

What are genetic syndromes with increased risk of pancreatic carcinoma?

A
  • Lynch syndrome: mutations in DNA mismatch repair genes
  • Hereditary breast and ovarian carcinoma
  • BRCA2 mutations
  • Peutz-Jeghers’s syndrome
  • Familial multiple mole melanoma syndrome (FAMMM); p16 mutation
  • Hereditary pancreatitis: PRSS1, SPINK1, CFTR
  • Familial pancreatic ca: unknown mutation
32
Q

Most common locations for carcinoma of the pancreas?

A
  • Head (60%)
  • Body (15%)
  • Tail (5%)
  • Diffuse (20%
33
Q

Describe carcinoma of the head of the pancreas

  • Symptoms
A
  • Obstructive jaundice, often painless
  • May have abdominal pain
  • May have back pain
  • Weight loss, anorexia, malaise, weakness; usually in advanced disease
  • May present with new onset DM
34
Q

Describe carcinoma of the tail of the pancreas

  • Symptoms
A
  • Insidious onset, weight loss, pain
  • Trousseau sign (migratory thrombophlebitis) which is due to procoagulants and platelet - aggregating factors from tumor
  • May have severe depression
  • Often distant metastases at diagnosis
35
Q

Most carcinomas of the pancreas are ______

Characteristics

A

Most carcinomas of the pancreas are ductal adenocarcinomas

  • Perineural, lymphatic and vascular invasion
  • Direct invasion around and into adjacent major vessels and organs
  • Metastases to lymph nodes, liver, peritoneum, lung
36
Q

How is carcinoma of the pancreas diagnosed?

A
  • History and physical
  • Bilirubin, alkaline phosphatase
  • CA 19.9, CEA
  • CT scan, MRI, endoscopic ultrasound
  • ERCP - Biliary cytology
  • FNA: percutaneous, endoscopic ultrasound-guided (EUS)
  • Surgery
37
Q

Describe carcinoma of the ampulla of Vater and distal common bile duct

  • Most are ___
  • Presentation
  • Prognosis
A
  • Most are adenocarcinomas
  • Present earlier with jaundice

Prognosis: much better than pancreatic carcinoma

  • 40-80% 5 yr survival after surgery with negative nodes
  • 30-40% 5 yr survival after surgery with positive nodes
38
Q

What are some neoplasms of the endocrine pancreas?

A
  • Pancreatic NE tumors
  • Insulinoma
  • Gastrinoma
39
Q

Describe pancreatic NE tumors

  • Aka
  • Epidemiology
  • Prognosis
A

Aka “islet cell tumors”

  • Mainly in adults
  • Hormonally functional or nonfunctional
  • Even with hepatic metastases, behavior less aggressive than pancreatic adenocarcinoma and can live for several yrs with mets
40
Q

Describe insulinoma

  • Malignant vs. benign
  • Presentation
A
  • 90% benign

Whipple’s triad:

  • Attacks of hypoglycemia with blood glucose < 50mg/dl
  • Anxiety, cold sweat, confusion, loss of consciousness, stupor
  • Precipitated by fasting or exercise, relieved by eating or IV glucose
41
Q

Describe gastrinoma

  • Location
  • Prognosis
  • Association
A

Most arise in:

  • Pancreas
  • Duodenum
  • Peripancreatic tissue

Prognosis:

  • At diagnosis, over half are locally invasive or have metastasized
  • Most metastasize if left untreated

Associations:

  • In 25%, associated with multiple endocrine neoplasia 1 (MEN 1)
  • May -> Zollinger-Ellison syndrome
  • Gastric acid hypersecretion
  • Intractable peptic ulcers, stomach and small bowel, often multiple
  • Ulcers may occur in unusual sites, e.g., jejunum