Pancreatic and Gallbladder Disorders Flashcards

Question

Gallstone Ileus

Answer 1

* Inflammation from cholecystitis causes a **fistula from gallbladder directly to small intestine** * Stone travels through fistula * Causes **small bowel obstruction** at ileocecal valve * Plain x-ray shows air in biliary tree and SBO

Answer 2

Stone **impacted in cystic duct** _mimics choledocholithiasis_ in presentation and labs

Answer 3

* **Multiple attacks of acute cholecystitis** * May appear as if it is an acute attack * ± Prior dx/sx of acute cholecystitis * **90% of pts have stones** * _Morphology:_ * **Fibrosis** w/ **↑ wall thickness**, mucosa usually preserved * **Mononuclear cells**: lymphocytes, plasma cells and MΦ * ± **D****ystrophic calcification** in GB wall ⇒ ‘porcelain gallbladder’ * **↑ Incidence of GB cancer** * **Hydrops**: resorption of bile solids and mucin secretion

Answer 4

* Labs * Ultrasound * CT scan * HIDA (hepatobiliary scintigraphy) * MRI/MRCP * EUS (endoscopic ultrasound) * ERCP (endoscopic retrograde cholangiopancreatography)

Answer 5

* **Liver Associated Enzymes (LAE’s)** ⇒ Alk phos, GGT, ALT, AST * **Liver function tests** ⇒ Bilirubin, INR, albumin * _Stages of biliary obstruction:_ * **ALT elevation** ⇒ within hrs * **Bilirubin elevation** ⇒ within one to several days (CA 19-9) * **Duct dilation** ⇒ within several days * **Liver labs (LAE and bilirubin) often lag behind** * Reflect clinical status of pt _6-24 hours before drawn_ * ALT and LAE first to improve, then bili then duct dil, then CA 19-9

Answer 6

* **Stones** appear as mobile, dependent **echogenic foci** in gallbladder lumen w/ **shadowing** * **Sludge** appears as **layering echogenic material w/o shadows** * Sensitivity \> 95% for stones \> 2 mm * Stones seen in CBD in 50%

Answer 7

Not great for detecting uncomplicated stones Excellent test for detecting **complications** such as: Abscess, gallbladder perforation, CBD stone, and pancreatitis

Answer 8

* Assessment of **cystic duct patency** * Normal scan: radioactivity in gallbladder, CBD, and small bowel in 30–60 min * Positive scan (abnormal): non-visualization of gallbladder w/ preserved excretion into CBD or small bowel * Sensitivity 95%, specificity 90% for **acute cholecystitis** * Do not use if bilirubin very high

Answer 9

* Does not require contrast for stones but does for masses * Can’t give contrast w/ GFR \< 30 due to Derm condition * Best at **high stones/common hepatic duct** * Very sensitive and specific but institution dependent * **Still lots of false pos and neg’s** ⇒ only use if changes management * Takes time (1-1.5hr) * Does not see stents, calcifications well * Can be hard to get/read at night and on weekends * Pt cooperation a problem * Movement obscures * Claustrophobia

Answer 10

* Sometimes used pre-ERCP * Not available at all centers * **Invasive (sedation)** but low risk, much lower than ERCP * **May be better than MRCP at distal stones** * Allows for **fine needle aspiration** if tumor suspected * Much better at **ampullary visualization** than MRCP * Can rule out ampullary tumors

Answer 11

* Gold standard test for **choledocholithiasis** * Sensitivity and specificity rates 95% * **Ability to extract stones** (or drain infected bile) * Lifesaving in severe cholangitis * **Complication rate as high or higher than cholecystectomy**

Answer 12

* **Accumulation of cholesterol esters and TAGs in MΦ within lamina propria** * Common, and usually **asymptomatic** * _Pathogenesis theories:_ * Supersaturation of bile w/ cholesterol * Abnormal lipid transport * **No association w/ elevated blood cholesterol** * _Gross appearance:_ * **Strawberry Gallbladder** * Yellow color on mucosa * _Microscopic:_ * Cholesterol esters and triglycerides accumulate in subepithelial “**foamy MΦ**” and gallbladder epithelium

Answer 13

* _Demographics:_ * **F:M ratio is 2:1** * Affects **older population** * ↑ incidence in Southwest US * _Associations:_ * **Gallstones**: present in 95% of cases, BUT only 1-2% of pts w/ gallstones develop GB cancer

Answer 14

* _Clinical:_ * Sx similar to **cholelithiasis** * _Pathogenic factors:_ * **Chronic inflammation** * Stones and infections * _Growth patterns:_ * **Infiltrating** * More common * Poorly defined area of **diffuse wall thickening and firmness** * **Deep ulcers** can result in **penetration** through wall to liver or loops of bowel * **Exophytic (Fungating)** * Grows into lumen as a **cauliflower-like mass** * _Outcome_: Dismal * Usually unresectable at dx * 5 yr survival rate is less than 10%

Answer 15

* **Adenocarcinoma** (95%) * Microscopically Indistinguishable from adenocarcinoma of the bile ducts (cholangiocarcinoma) or pancreatic duct * **Adenosquamous/squamous** (5%) * Can see areas of dysplasia in epithelium adjacent to invasive cancer

Answer 16

* Arises from **fusion of dorsal and ventral buds** of the _developing duodenum_ * **Pancreatic duct** = fusion of ventral duct w/ distal portal of dorsal duct * **Accessory duct of Santorini** = persistence of proximal portion of dorsal duct * PD forms confluence w/ CBD and empties via **Ampulla of Vater** into duodenum in ⅔ of people * Empties via **separate orifice** into duodenum in remainder

Answer 17

* 80-85% of organ * **Acini**: small glandular units * **Ducts**: drainage system * Exocrine cells are filled w/ enzymes * **Pancreatic injury** ⇒ failure of protective mechanisms ⇒ **autodigestion** of pancreatic tissue * _Protective Mechanisms:_ * Digestive enzymes packaged in secretory granules as inactive proenzymes (**zymogens**) * Proenzymes activated by **trypsin** * Activated in the duodenum * _Acinar and ductal cells_ secrete **trypsin inhibitors**

Answer 18

**Islets of Langerhans** Represents only 1-2% of organ * **Beta cells** ⇒ insulin * **Alpha cells** ⇒ glucagon * **D cells** ⇒ somatostatin * **D1** ⇒ vasoactive polypeptide * **PP** ⇒ pancreatic polypeptide * **EC** ⇒ serotonin and motilin

Answer 19

* Responsible for the vast majority of **chemical digestion** in the body * Pancreas produces **Zymogens** (precursors to enzymes) * Zymogens become **activated to trypsin** by **enterokinase** or **trypsin itself** * Creates a feedback loop and more and more trypsin become activated

Answer 20

* **Pancreas divisum** * Most common (3-10%) * **Failure of fusion of dorsal and ventral pancreatic primordia in the fetus** * Most pancreatic tissue drains into duodenum through small-caliber **minor papilla** * ? inadequate drainage ⇒ ↑ susceptibility to pancreatitis * **Annular pancreas** * **Encircles duodenum** * Can cause **obstruction** * **Ectopic pancreas** * Stomach, duodenum, other sites * Can cause **inflammation** or **bleeding** * **Agenesis** * Unusual

Answer 21

**Acute Inflammation of the pancreas and associated adjacent organs** w/o evidence of chronic pancreatitis “Intraabdominal burn” * _Defined clinically as 2 of 3 of the following:_ * **Typical pancreatic type pain** * **Radiographic findings of acute pancreatitis** * **Elevations in blood chemistries** * Typically amylase and/or lipase \> 3x ULN * Amylase and lipase can be elevated due to other reasons in addition to pancreatitis * _Amylase alone_: paroditis; tumors; ectopic pregnancy; macroamylasemia * _Amylase and lipase_: biliary disease; renal failure; **intestinal obstruction, ulceration, or ischemia**; and **perforated viscus**

Answer 22

* 5-35/100k * ↑ incidence (detection? meds? iatrogenic?) * ↑ with ↑ age * Onset before 14-15 yrs unusual * Unless hereditary, traumatic, anatomic anomaly * 250k admissions per year in US (2^nd GI) * $2 billion in direct costs per year * 6^th costliest GI disease behind ESLD, cancers, IBD

Answer 23

* **Reversible pancreatic parenchymal injury** due to **inappropriate release and activation of pancreatic enzymes (including trypsin)** * Tissue destruction (pancreatic parenchyma, fat and blood vessels) * Acute inflammatory reaction * Duct obstruction ⇒ **acinar cell injury** * Causes deranged intra-cellular transport and the release of activated enzymes * **Premature/intracellular activation of trypsin** * _Trypsin is the major catalyst for pancreatitis_ * Not amylase or lipase (but later lipase gets to abd fat) * Leads to activation of chymotrypsinogen, more trypsinogen, elastase, phospholipase A2, complement ⇒ **autodigestion** * Activates **prekallikrein** and sets off kinin system * Activates **coagulation factor XII** ⇒ inflammation and small vessel thromboses * _Enzyme release causes:_ * Proteolysis * Lipolysis * Hemorrhage

Answer 24

* **Alcohol** * Excess alcohol intake causes 65% of US pancreatitis * Biliary disease + Alcoholism = 80% of acute pancreatitis * M:F 6:1 for alcoholism * **Biliary** * Gallstones: present in 35-50% of cases * M:F 1:3 for biliary tract disease * **Circulatory issues**: shock, vascular thrombosis/embolus, vasculitis * Infection: e.g. mumps * Can directly injury acinar cells * **Mechanical trauma** * Blunt trauma, surgery, ERCP * **Drugs** * **Metabolic** * Hypertriglyceridemia, hypercalcemia * **Idiopathic** * Other includes: neoplastic; structural; inherited; autoimmune; scorpion bites

Answer 25

**Gallstones or sludge** * Most common etiology in world * Still 35% in US * **More in women** * Usually small ones that don’t obstruct cystic duct or most of CBD (common bile duct) until at major papilla * **ALT \> 150**: 50% sensitivity and 90% specificity * _Treatment:_ * Usually pass on it’s own, but don’t be complacent! * If Cholangitis: call GI for ERCP; remove gallbladder * If not cholangitis: call surgery just remove gallbladder

Answer 26

* _Alcohol has been shown to cause:_ * Transient ↑ contraction of Sphincter of Oddi * Secretion of protein-rich pancreatic fluid * Deposit inspissated protein plugs that obstruct small pancreatic ducts * Direct toxic effects on acinar cells * Take a careful history * **More in men** * **Lipase 2x amylase**? * 1^st or 2^nd most common in US (31-40%) * Usually fairly high doses for at least few years * Any dose, though, can cause AP * Often after cessation (24 hrs after a binge, etc) * Why only 10% of alcoholics get pancreatitis? * Often have chronic pancreatitis

Answer 27

* Usually \> 1,000: an endocrine emergency! * Alcohol raises TAG usually to 400-500 range, can be higher * **Can have normal amylase and lipase** * Uncontrolled **hyperglycemia** can lead to high trigs * Often have **chronic pancreatitis**

Answer 28

* Adenocarcinoma * Ampullary tumors and intraductal papillary mucinous neoplasm (IPMN) * Post-acute pancreatitis with pancreatic duct stricture * Pancreas divisum? Controversial * Annular pancreas _All unexplained pancreatitis pts \> 50 y/o should have a CT 6 wks after episode_

Answer 29

* HIV: didanosine, pentamidine * Diuretics: thiazides (sulfa?), ACE Inhibitor * Immunosuppressive/antimetabolite: L-asparaginase, azathioprine/6-Mercaptopurine * Neuropsychiatric: valproic acid * Others: estrogen, Byetta (Exanetide), vitamin A (Accutane), etc.

Answer 30

* **Severe, steady band like upper abdominal pain** * **Radiate/bore to back** in 50% * Starts over 10-20 min, not as fast as a perforation * Lasts days (longer than biliary colic) * **90% vomit** * Fever * Can recur * **Painless in 5-10%** * Sometimes dx at autopsy * Typically causes ER visit and an admission * Unless recurrent/chronic * Wide spectrum of severity * **30% of choledocholithiasis pts** * **Treat by withholding oral intake, hydration, pain meds**

Answer 31

**Early (48-72hrs)** * SIRS / Hypotension * Ileus * Renal failure * Third spacing/ascites * Hypoxia * Acidosis * Cholangitis * Hypocalcemia/electrolytes abnormalities * Multisystem organ failure * Intraabdominal hemorrhage * Death

Answer 32

* Gut failure /malnutrition * Hypoalbuminemia * Infected necrosis/abscess * Biliary obstruction * Hospital acquired infections * Chronic ventilator dependence * Pseudocysts/walled off necrosis * Splenic vein thrombosis * Death

Answer 33

Overall 2-5% and ↓ slightly * **Interstitial/mild pancreatitis** (80% of all cases) * ≤ 1% mortality * **Necrotizing/severe pancreatitis** (20% of all cases) * 20% mortality, long ICU stays (1-3 months) * **Infected necrotizing pancreatitis** (occurs late) * 50% mortality

Answer 34

* _Gross:_ * Edematous * Firm * Yellow and white * Red/black clot * _Microscopic:_ * Parenchymal destruction * Acute Inflammation * Fat necrosis * Destruction of vessels w/ interstitial hemorrhage

Answer 35

* _Serum markers:_ * **Serum Amylase** * Marked elevation in first 24 hours * **Serum Lipase** * Rises 72-96 hours after attack begins * May also see **glycosuria, hypocalcemia** * **LDH** * **Imaging by CT is useful** * Can be very serious * Necrotizing pancreatitis w/ sequelae including pancreatic abscess and/or pseudocyst

Answer 36

* **Cullen’s sign** * Superficial edema and bruising in the subcutaneous fat around the umbilicus * **Grey Turner’s sign** * Bruising of the flanks due to retroperitoneal hemorrhage Note: Neither of these are very common in pancreatitis (less than 3% of cases)

Answer 37

* **Interstitial pancreatitis** * Inflamed fat or fluid around the pancreas * Swollen, enlarged pancreas * **Necrotizing pancreatitis** * _Takes a couple of days_ to develop on imaging * Abdomen is distended * Pancreas and peri-pancreatic fat dies * Weeks later pancreas is replaced by a **cystic, necrotic cavity**

Answer 38

* **NPO** (bowel rest)/ **Lots of IV Fluids** (lactate ringers)/ **Pain control** * Close clinical monitoring * Triage to floor or ICU (intensive care) * Imaging: * US if gallbladder in situ * Wait on CT for a few days unless diagnosis not clear or pt very ill * **GI consult for cholangitis/biliary obstruction** * **Surgery consult** for gallstone/severe/infected necrosis * **Abx** for cholangitis/infected necrosis * Enteral feeding beyond lig of Treitz if severe ill (within 48 hrs) * _Prediction of mortality/danger:_ * Scientific studies (APACHE-O APACHE 2, APACHE 3, Ranson, BISAP, Glasgow, Balthazaar) * Prediction of mortality/danger - bedside * Repeat labs 6 hrs after presentation, BID labs, esp. electrolytes, Mg²⁺, Ca²⁺ * Have intern look at urine output, abdominal exam, vitals, orthostatics at night * EKG, CXR, serial glucoses even non-diabetics

Answer 39

* **Permanent damage to the pancreas** * **Prolonged inflammation** → irreversible destruction of exocrine parenchyma → fibrosis → destruction of the endocrine pancreas * Most common cause is **long-term alcohol abuse** * Most pts are **adult males** * Exocrine/endocrine dysfunction or destruction of such tissue on biopsy * Fibrosis seen on biopsy/Endoscopic US * _Practical_: **calcifications, pancreatic duct stones, dilated irregular pancreatic duct without mass, “beads on a string”, “chain of lakes” dilated side branches, atrophy without mass** * What is dilated? (\> 2-3mm in the body/tail) * Spectrum of presentations * _NOT necessarily any of the following:_ * Chronic elevations in amylase/ lipase * Chronic abdominal pain with elevations in amylase/lipase * Acute relapsing pancreatitis – though this distinction is murky * Post-surgical exocrine dysfunction * Anyone with isolated steatorrhea * Swelling of the pancreatic head

Answer 40

* Mainly due to **alcohol and tobacco** * Metabolic (hypertriglyceridemia) * Long-standing obstruction of pancreatic duct by stones or neoplasms * Autoimmune pancreatitis * Hereditary pancreatitis (up to 25% of chronic pancreatitis) * Idiopathic causes

Answer 41

* **Ductal obstruction hypothesis** * Protein precipitates/calcifications in ducts ⇒ ⊕ trypsin ⇒ upstream inflammation/destruction * Apoptosis/fibrosis of upstream acini * **Toxic/Metabolic hypothesis** * Oxidative stress/free radicals from ETOH/CCK stimulation/smoking ⇒ stellate cell activation/fibrosis * **Necrosis/Fibrosis hypothesis** * Acute inflammatory attacks ⇒ necrosis/apoptosis * Cytokines from MΦ ⇒ chronic damage by converting to an anti-inflammatory fibrotic/”healing” state * Fibrosis ⇒ local ischemia ⇒ more necrosis/apoptosis

Answer 42

* _Follows repeated episodes of acute pancreatitis_ * Initiates sequence of **perilobular fibrosis, duct distortion, altered pancreatic secretions** * Fibrogenic factors predominate * Including **TGF-****β****and PDGF** * Induce activation and proliferation of **periacinar fibroblasts (pancreatic stellate cells)** * Results in **loss of pancreatic parenchyma and fibrosis** * Special case: **Autoimmune pancreatitis** * Associated w/ presence of **IgG4-secreting plasma cells** in the pancreas * May respond to steroid therapy

Answer 43

* _Gross appearance_ * Firm gland, may see **visibly dilated ducts**, can contain **calcified material** * _Microscopic_ * **Loss of acini w/ relative sparing of islets** (until late) * Variable **duct obstruction** * **Duct dilation** * **Inspissated secretion** in ducts ± calcification * **Fibrosis** * Variable **chronic inflammation around lobules and ducts**

Answer 44

_May be difficult to diagnose_ * Elevation of amylase may be compromised by loss of acinar cells * Look for jaundice and elevated alk phos w/ gallstones * Imaging may show calcifications * KUB (plain X-ray) * CT / MRCP (MRI) * Ultrasound * EUS (Endoscopic Ultrasound) * ERCP (Endoscopic RetroCholangioPancreatography) * Stool studies * Function tests (S-MRCP, secretin stimulation) * Ex lap with direct palpation

Answer 45

* Chronic pain * Pancreatic exocrine insufficiency * Steatorrhea * Chronic malabsorption * B12 deficiency * Diabetes * Biliary obstruction * Cancer * Pseudocysts (10%) * 20-25 year mortality rate of 50%

Answer 46

* **Disabling** * Often requires narcotics * Since pts often former ETOH, maybe neglected * Hard to detect, CT often negative for acute inflammation * Amylase and lipase can be low or normal * _Causes_: (plumbing and wiring) * **Neural** * **Obstructed pancreatic duct** with pancreatic stones * **Malabsorption** (cramps) * _Management of chronic pancreatic pain:_ * **High dose uncoated pancreatic enzymes** * **Quit ETOH and tobacco**, lower Triglycerides, etc. * **Neural modulators** * **Narcotics** (use sparingly) * **ERCP** to remove pancreatic stones/dilate strictures * **Surgery**

Answer 47

* Happens at **90% destruction of pancreas** – Nonlinear, cliff * Definition: **\> 7g fat/24hrs** * Broad (extra-pancreatic) differential diagnosis * Sx have terrible sensitivity/specificity * Loose, oily stool, hard to flush, foul, ring in bowl, undigested pieces * Jejunum adapts (watch post-surgery closely) * Usually pts do not get dehydrated * **Spot (qualitative) fecal fat**, insensitive * Treatment: **40,000 IU coated lipase/meal** * Complications: osteoporosis, vit A low, rarely low in vit K/E, magnesium

Answer 48

“Thin, adult-onset insulin requiring” “Type 3” * Development **can indicate cancer** even if no chronic pancreatitis * No glucagon or somatostatin, so **hypoglycemia** * Usually **no ketoacidosis** * Very insulin sensitive peripherally * Still, use **metformin with insulin**

Answer 49

* Sneaky in chronic pancreatitis (CP) * Most already have pain, worsening * Yet it is common * **4% lifetime risk** (**30-x** **↑****risk**) * CP pts can get jaundiced from benign biliary obstruction of bile duct (intrapancreatic portion)

Answer 50

* Recurrent attacks of severe acute pancreatitis can **begin in childhood** and result in chronic pancreatitis * Pts have **40% lifetime risk of pancreatic cancer** * Shared feature: **Defect that ↑ or sustains the activity of trypsin** * Many genes, many mutations * **PRSS1** * Trypsinogen gene * See GOF mutations * Autosomal dominant * **SPINK1** * Encodes a trypsin inhibitor * See LOF mutations * Autosomal recessive * **CFTR mutations** seen in cystic fibrosis

Answer 51

* **Viscous secretions** * Due to _abnormal electrolyte balance_ * Plug the ductal system (**inspissation**) ⇒ **obstruction** * Obstruction leads to inflammation (**pancreatitis**) * Most common autosomal recessive disorder in US Caucasians * In the US: major cause of pancreatic disease

Answer 52

* **Congenital cyst** * _Anomalous development of pancreatic ducts_ results in **unilocular thin-walled cysts** * Up to 5cm in diameter * **Sporadic** or associated w/ **AD Polycystic Kidney Disease** or **von Hippel-Lindau** * **Pseudocyst** (75% of all pancreatic cysts) * Localized collection of **necrotic and hemorrhagic debris** _lacking an epithelial lining_ * 2-30 cm diameter * Often **follow acute pancreatitis**, particularly if superimposed on chronic alcoholic pancreatitis * Can also follow **trauma**

Answer 53

* _Exocrine_ * Ductal adenocarcinoma (\> 90 % of exocrine tumors) * Acinar cell carcinoma * Intraductal papillary mucinous tumor * Mucinous cystic neoplasm * Serous cystadenoma * Solid and Cystic Papillary Epithelial Neoplasm * Pancreatoblastoma * _Pancreatic Endocrine Neoplasms_ * Neuroendocrine Tumors (Islet Cell Neoplasms)

Answer 54

* Diverse group of tumors ranging from **harmless benign cysts** to **precursors of cancer** * Comprise **5-15% of cysts** since most are pseudocysts * Comprise **\< 5% of all pancreatic neoplasms** * Types: * **Serous cystic neoplasms (serous cystadenomas)** * Benign * 25% of all pancreatic cystic neoplasms * **Mucinous Cystic Neoplasms**

Answer 55

* **95% in women** * Usually **slow growing mass in pancreatic tail** * Filled w/ **thick, tenacious mucin** * Lined by **columnar mucin-producing epithelium** associated w/ **dense ovarian-like stroma** * Up to ⅓ of these masses show **invasive adenocarcinoma upon resection**; 50% of pts in this situation will die * Important to detect and treat _before invasive cancer develops_

Answer 56

* **Mucin-producing** neoplasm involving _larger ducts_ * **Seen more in men** * Usually in **head of pancreas** * 10-20% are **multifocal** * **No “ovarian” stroma** * _Can progress to invasive cancer_ so early detection is important

Answer 57

* Seen mainly in **young women** * **Large, well circumscribed, malignant** * Can grow very large * Associated w/ **hyperactivation of Wnt signaling pathway** * D/t acquired activating mutations of the **CTNNB (Beta-catenin) oncogene** * Surgery is often curative

Answer 58

* **Lesion in small ducts** * Believed to be the **precursor to invasive pancreatic ductal carcinoma** * Progression from **non-neoplastic epithelium** to PanIN to invasive carcinoma * Similar **genetic and epigenetic alterations** in PanIN and invasive CA * See PanIN adjacent to invasive CA * Epithelial cells in PanIN show **dramatic telomere shortening**

Answer 59

* **Comprises the vast majority of pancreatic carcinomas (\>90%)** * #4 cause of cancer death in US * **Very high mortality rate** * 5-year survival \< 5% * Approximately 44,000 new cases in US in 2013

Answer 60

* **K-ras** * Most frequently altered **oncogene** * _Activating_ point mutations in 90-95% of cases * **CDKN2A** * _Inactivated_ in 95% of cases * **Tumor suppressor gene** * **SMAD4** * _Inactivated_ in 55% of cases * **Tumor suppressor gene** * **TP53** * _Inactivated_ in 70-75% of cases * Encodes p53 * **Tumor suppressor gene** * Other chromosome alterations * **DNA methylation abnormalities** * **Abnormal gene expression pathways**

Answer 61

* 80% of cases occur at **ages 60-80** * **More blacks** than whites * Strongest environmental link: **cigarette smoking** * _Less certain_ * Consumption of **diet rich in fats** * **Chronic pancreatitis, DM** * Familial clustering is seen * **Germline BRCA2 mutation** in 10% of pancreatic CA cases in Ashkenazi Jews * Some families show germline mutations in **CDKN2A** * Pancreatic cancer and melanoma

Answer 62

* _Gross:_ * Location: * **Head** (60%) * Tumors **obstruct distal common bile duct** early * Causes **distention of biliary tree**, many pts develop **jaundice** * **Body** (15%) * Carcinomas here and in tail r**emain silent until large** and often **disseminated** * **Tail** 5% * **Diffuse** 20% * Morphology: * **Gray-white color** * Stands out from normal yellowish/tan pancreatic parenchyma * **Firm/hard** * Due to desmoplastic reaction * Proliferation of fibroblasts surrounding malignant cells and glands * Mass or diffuse replacement of pancreas * _Microscopic:_ * **Moderately to poorly differentiated adenocarcinoma** * Aggressive and **deeply infiltrative** * Elicits an **intense desmoplastic reaction** * Can make it difficult to distinguish from chronic pancreatitis at times * Both show **glands surrounded by fibrosis**

Answer 63

* Presentation: * **Often silent** until invades adjacent structures * **Pain** * **Jaundice** (sometimes before pain) * **Pruritis** * **Pancreatitis** * **Peripheral fat necrosis** * **Migratory thrombophlebitis** (_Trousseau sign_) * \< 20% of cases are resectable at dx * Have invaded vessels and other structures or metastasized widely * No effective screening technique

Answer 64

* Rare tumor * Peak: **5th-8th decade** * Usually **large** w/ foci of **necrosis** * Shows **acinar arrangement** of cells * Reminiscent of normal pancreatic acini * Contain **zymogen granules** * May be associated w/ **peripheral fat necrosis and polyarthralgias** (15% of pts)

Answer 65

* Rare neoplasm * Mainly seen in **children ages 1-15** * **Malignant**, but better survival than pancreatic ductal CA

Answer 66

* Comprise about 2% of pancreatic neoplasms * Tumors can be **sporadic** or **MEN I-associated** * May be **functional** (produces active hormone) or **non-functional** * May be **single or multiple**; **benign or malignant** * Difficult to predict behavior based on LM appearance * _Criteria for malignancy_ are **metastases, vascular invasion, infiltration of other tissues** * 90% of tumors **producing** **insulin** are _benign_ * 60-90% of **other neuroendocrine tumors** are _malignant_

Answer 67

* **MEN1 gene** * Causes MEN1 syndrome * Often altered in **sporadic neuroendocrine tumors** * _LOF mutations in tumor suppressor genes_ **PTEN and TSC2** * Results in **activation of mTOR** signaling pathway * _Inactivating mutations in two genes:_ * **ATRX** * Alpha-thalassemia/mental retardation syndrome (X-linked) * **DAXX** * Death-domain associated protein

Answer 68

* **Beta-cell tumor (insulinoma)** * Most common PanNET * **Hyperinsulinism** ⇒ may induce clinically significant hypoglycemia * See confusion, sweating, palpitations, stupor, LOC * Episodes precipitated by fasting or exercise * Relieved by feeding or giving glucose * _Gross_: Usually **benign**, **solitary**, often \< 2 cm, reddish-brown * _Micro_: look like **islet cells,** not much dysplasia * May contain **amyloid**

Answer 69

* **Gastrin producing islet cell tumor** * 2^nd most common pancreatic endocrine neoplasm (PanNET) * _Results in:_ * **Parietal cell hyperplasia** * **↑ HCl secretion** * **Peptic ulcers** * Tumor can also _arise in duodenum or peripancreatic soft tissue_ * Majority are **malignant** * May have metastasized at time of presentation * May be a component of **MEN1 syndrome** (often multifocal in this case)

Pancreatic and Gallbladder Disorders Flashcards

(94 cards)