10/20- Pathology of Endocrine/Exocrine Pancreas Flashcards
She’s going for concepts not tiny facts; histo pictures from this lecture not tested (?)
woot
Describe relationship of anatomy to other abdominal organs
- Head within C loop of the duodenum
- Tail going out toward the spleen
What provides major blood supply to pancreas?
- Hepatic a of celiac trunk
- Superior mesenteric a
Is the pancreas (grossly) more endocrine or exocrine?
More exocrine cells (acinar)
Describe basic embryology of pancreas
Ventral and dorsal bud fuse to form the pancreas
Describe ductal system of pancreas
- Major pancreatic duct enters at major duodenal papilla (typically with common bile duct)
- Accessory pancreatic duct
What is pancreas divisum?
- 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
What is acute pancreatitis?
- Symptoms
- Prognosis
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
What are the most common causes of acute pancreatitis?
- 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
What are some causes of hereditary pancreatitis?
- Germline mutations, most resulting in increased or sustained activity of trypsin
- PRSS1
- SPINK
- CFTR (cystic fibrosis transmembrane conductance regulator); not associated with clinical CF
What is the pathogenesis of acute pancreatitis?
- 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
What are some of the pancreatic enzymes? (recognize)
- Trypsin
- Chymotrypsin
- Elastase
- Amylase
- Lipase
- Phospholipase
- Carboxypeptidase
- Nuclease
- Kallikrein
How to diagnose acute pancreatitis?
- History/physical
- Serum amylase (best early)
- Serum lipase (high by 72 hrs)
- US for exam of biliary tract
- CT scan, MRI
- ERCP, MRCP
What are complications of acute pancreatitis?
- Necrosis: sterile or infected tissue
- Abscess
- Peritonitis
- Pseudocysts
- Systemic
- Multisystem organ failure
- Shock
- Respiratory failure
- Renal failure
- Death
What is the typical presentation of chronic pancreatitis?
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
What are causes of chronic pancreatitis?
- 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
Chronic pancreatitis is associated with what?
40% lifetime risk of pancreatic cancer
Describe autoimmune cause of chronic pancreatitis
- Treatment
- Increased IgG4 plasma cells
- Increased serum IgG4
- May mimic pancreatic cancer clinically and radiographically
- Responsive to steroids
What conditions may lead to pancreatic pseudocyts?
- Acute pancreatitis
- Chronic pancreatitis
- Trauma
- Cancer (rare)
Pancreatic neoplasms may affect what parts of the pancreas?
- Exocrine parts
- Endocrine parts
- Ampulla of Vater and distal common bile duct
What are cystic pancreatic neoplasms?
- Serous cystadenoma, most microcystic
- Mucinous cystic neoplasm
- Intraductal papillary mucinous neoplasm
- Solid pseudopapillary tumor
- Cystic pancreatic neuroendocrine neoplasm
Describe serous cystadenoma
- Composition
- Malignant vs. benign
- Treatment
- 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
Describe mucinous cystic neoplasms (MCN)
- Treatment
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
Describe Intraductal papillary mucinous neoplasm (IPMN)
- Location
- Epidemiology
- 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
Prognosis/treatment of Intraductal Papillary Mucinous Neoplasm (IPMN)
- 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
Describe solid pseudopapillary neoplasm
- Epidemiology
- Characteristics
- Prognosis
- Treatment
- 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
Describe carcinoma of the pancreas: epidemiology
- 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
Progression/prognosis of pancreatic carcinomas?
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
What are the molecular genetics of pancreatic carcinoma?
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
What are risk factors for pancreatic carcinoma?
- 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
What are genetic syndromes with increased risk of pancreatic carcinoma?
- 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
Most common locations for carcinoma of the pancreas?
- Head (60%)
- Body (15%)
- Tail (5%)
- Diffuse (20%
Describe carcinoma of the head of the pancreas
- Symptoms
- 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
Describe carcinoma of the tail of the pancreas
- Symptoms
- 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
Most carcinomas of the pancreas are ______
Characteristics
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
How is carcinoma of the pancreas diagnosed?
- 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
Describe carcinoma of the ampulla of Vater and distal common bile duct
- Most are ___
- Presentation
- Prognosis
- 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
What are some neoplasms of the endocrine pancreas?
- Pancreatic NE tumors
- Insulinoma
- Gastrinoma
Describe pancreatic NE tumors
- Aka
- Epidemiology
- Prognosis
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
Describe insulinoma
- Malignant vs. benign
- Presentation
- 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
Describe gastrinoma
- Location
- Prognosis
- Association
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
