Biliary tract

Question 1

List 5 complications of cholecystitis

Answer 1

• Bacterial superinfection, cholangitis or sepsis - Perforation and abcess formation - Gallbladder rupture with diffuse peritonitis - Porcelain gallbladder with increased risk of CA

Question 2

List 5 risk factors for gallbladder CA

Answer 2

• gallstones - porcelain gallbladder - choledochal cyst - pancreatic duct abnormalities - polyps

Question 3

List 3 causes of acalculous cholecystitis

Answer 3

• gallbladder ischemia due to severe volume depletion (sepsis, multiorgan failure, major trauma/burns) - infections in immunosuppressed (CMV, HIV) - DM

Question 4

List 4 types of non-neoplastic and 3 neoplastic gallbladder polyps

Answer 4

• non-neoplastic: cholesterol, hyperplastic, adenomyoma, lymphoid - neoplastic: pyloric gland type, intestinal type, biliary type

Question 5

What are Klatskin tumors?

Answer 5

• Hilar carcinomas at confluence of right and left hepatic ducts

Question 6

List histologic features to distinguish bile duct adenocarcinoma from reactive changes

Answer 6

• Perineural invasion - Haphazard arrangement of irregular glands - Loss of nuclear polarity and increased N/C ratio - cytoplasmic CEA staining, MUC1 and nuclear p53 - ***CEA, MUC1, MUC5AC usually limited to apical membrane in benign cells

Question 7

How can frozen sections be used in surgical management of congenital extrahepatic biliary atresia?

Answer 7

• Determine the caliber of residual bile ducts in portal hepatic scar - If >100 um, 80-90% success with Kasai procedure to restore bile flow

Question 8

What is the most important complication of choledochal cyst?

Answer 8

• Cholangiocarcinoma, 20x greater risk than normal population - CA in cyst wall, gallbladder or other parts of biliary tree

Question 9

What is the difference between Caroli disease and Caroli syndrome?

Answer 9

• Caroli disease: saccular dilatation of intrahepatic bile ducts alternating with segments of normal caliber (ductal plate malformation, associated with polycystic kidneys, increased risk cholangiocarcinoma) - Caroli syndrome: caroli disease + congenital hepatic fibrosis

Question 10

Classify gallstones and give 4 risk factors in each category

Answer 10

Cholesterol stones: advanced age, obesity, hyperlipidemia, female sex hormones pigment stones: chronic hemolytic syndromes, biliary infection, ileal resection, ileal crohns

Question 11

What 2 molecules are involved in dissolving cholesterol into bile

Answer 11

• Water soluble bile salts - Water insoluble lecithins

Question 12

Cholelithiasis-list 5 pertinent facts (random question)

Answer 12

• Cholesterolosis not correlated with atherosclerosis - Acute cholecystitis doesn’t need acute inflammatory cells (edema, hemorrahge, ischemia) - Intestinal metaplasia portends increased risk of carcinoma - Gallbladder mucosa nodularity is not adenoma, unless greater than 0.5cm - echinococcus multilocularis is a hydatid cyst with infiltrative growth pattern

Question 13

Describe conditions that facilitate formation of cholesterol stones, and conditions that facilitate pigment stones

Answer 13

• Cholesterol gallstone formation: requires cholesterol supersaturation, hypomotility of gallbladder, accelerated cholesterol nucleation in bile, hypersecretion of mucous in gallbladder - Pigment stones, “black”: chronic extravascular hemolytic anemia (eg. sickle cell) increased secretion of conjugated bilirubin, excess bilirubin precipitates to calcium bilirubinate “brown” stones required bacterial contamination releasing b-glucuronidases; result in unconjugated bilirubin in biliary tree exceeding solubility

Question 14

List 5 common complications of gallstones

Answer 14

• Depends on whether it is in gallbladder, CBD, or intrahepatic - calculous cholecystitis acute/chronic, hydrops/mucocele, empyema, perforation, fistula - Obstructive cholestasis or pancreatitis - Cholangitis/hepatic abecss - secondary biliary cirrhosis - carcinoma

Question 15

What are Bouveret and Mirizzi syndromes

Answer 15

• Bouveret: large stone erodes into adjacent loop of bowel=obstruction - Mirizzi: stones in gallbaldder neck compress CBD extrinsically

Question 16

What are gross and histologic features of acute and chronic cholecystitis?

Answer 16

Acute: enlarged, tense, red/blotchy, fibrin on surface, +/- stones in lumen. If filled with pus, empyema. If green-black and necrotic, gangrenous.Micro: edema, hemorrhage, may have inflammatory cells chronic: smooth serosa +/- adhesions, thickened wall, preserved mucosa. Micro shows variable inflammation, subepithelial fibrosis, buried crypts in gallbladder wall (Rokitansky-Aschoff sinuses).

Question 17

What is porcelain gallbladder?

Answer 17

• Extensive dystrophic calcification within gallbladder wall, usually superimposed on chronic cholecystitis - Increased incidence of carcinoma

Question 18

What are some features of carcinoma of the gallbladder?

Answer 18

• most common malignancy of extrahepatic biliary tract - 7th decade - gallstones major risk factor - 2 growth patterns: infiltrating, exophytic - infiltrating more common, diffuse thickening of gallbladder wall. scirrhous. - exophytic shows irregular cauliflower mass, usualy fundus and neck - mostly all adenocarcinomas, 5% squamous or adenosquamous - papillary portend better prognosis

Question 19

Gallbladder-dx?

Answer 19

phrygian cap

Question 20

Gallbladder

Answer 20

pigment stones

Question 21

Gallbladder-dx?

Answer 21

adenocarcinoma of gallbladder

Question 22

Perihilar bile ducts: what items are required in the synoptic report?

Answer 22

Specimen: CBD, RHD, LHD, junction of RHD/LHD, common hepatic duct, cystic duct

procedure: hilar/hepatic resection, segmental resection, choledochal cyst resectin, hepatectomy

tumor site, size

histologic type, grade

tumor extension, margins, LVI, PNI

TNM staging

Question 23

What is the histologic grading for hilar bile duct carcinomas?

Answer 23

Note: Conventionally, cholangiocarcinoma means intrahepatic.

Adenocarcinoma
- Papillary adenocarcinoma (not graded)
- Adenocarcinoma, intestinal type
- Mucinous adenocarcinoma
-Clear cell adenocarcinoma (not graded)
- Signet-ring cell carcinoma (grade 3)
Adenosquamous carcinoma
Squamous cell carcinoma
High-grade neuroendocrine carcinoma
- Large cell neuroendocrine carcinoma
- Small cell neuroendocrine carcinoma (grade 4)
Undifferentiated carcinoma (grade 4)
Biliary cystadenocarcinoma

Question 24

How are hilar bile duct carcinomas graded?

Answer 24

Grade 1 Well differentiated (greater than 95% of tumor composed of glands)
Grade 2 Moderately differentiated (50% to 95% of tumor composed of glands)
Grade 3 Poorly differentiated (less than 50% of tumor composed of glands

Question 25

What is the importance of margins in hilar bile duct carcinomas?

Answer 25

Locoregional recurrence is usually the first site of disease recurrence, 59% of patients with perihilar bile duct carcinomas.

Tumor recurrence related to residual tumor located in the proximal or distal surgical margins of the bile duct or from tumor located along the dissected soft tissue margin in the portal area.

Complete surgical resection with microscopically negative surgical margins is an important predictor of
outcome with overall 5-year survival for perihilar tumor improved from 10% for all patients to 30% for those with negative margins

Malignant tumors of the extrahepatic bile ducts are often multifocal, and microscopic foci of
carcinoma or intraepithelial neoplasia may be found at the margin(s) even though the main tumor
mass has been resected. In some cases it may be difficult to evaluate margins on frozen section
preparations because of inflammation and reactive change of the surface epithelium or within the
intramural mucous glands. If surgical margins are free of carcinoma, the distance between the closest
margin and the tumor edge should be measured.

Because 5% of patients with bile duct carcinoma have synchronous carcinomas of the gallbladder,
examination of the entire surgical specimen, including the gallbladder, is advised

Question 26

Perineural invasion in hilar bile duct cancers: what is the signficance and in what other conditions can PNI be seen?

Answer 26

Perineural and lymphatic invasion are common in extrahepatic bile duct carcinomas, usually higher stage
Associated with adverse outcome on univariate analysis.

Ducts affected by primary sclerosing cholangitis and adenomatous hyperplasia may show PNI

Question 27

What are the T and N staging considerations for hilar bile duct carcinomas?

Answer 27

___ pTis: Carcinoma in situ
___ pT1: Tumor confined to the bile duct, with extension up to the muscle layer or fibrous tissue
___ pT2a: Tumor invades beyond the wall of the bile duct to surrounding adipose tissue
___ pT2b: Tumor invades adjacent hepatic parenchyma
___ pT3: Tumor invades unilateral branches of the portal vein or hepatic artery
___ pT4: Tumor invades main portal vein or its branches bilaterally; or the common hepatic artery; or
the second-order biliary radicals bilaterally; or unilateral second-order biliary radicals with
contralateral portal vein or hepatic artery involvement

Regional Lymph Nodes (pN)
___ pN0: No regional lymph node metastasis
___ pN1: Regional lymph node metastasis (including nodes along the cystic duct, common bile duct,
hepatic artery, and portal vein)
___ pN2: Metastasis to periaortic, pericaval, superior mesentery artery, and/or celiac artery lymph

Question 28

List some risk factors for hilar bile duct carcinomas

Answer 28

• Chronic inflammatory conditions affecting the bile ducts are associated with higher risk for biliary tract
  carcinomas.
• Most common in western countries: PSC, characterized by multifocal strictures and
  inflammation of the extrahepatic and intrahepatic biliary tree.
• In Japan and Southeast Asia, hepatolithiasis due to recurrent pyogenic cholangitis with biliary stones
• Biliary parasites such as Clonorchis sinensis and Opisthorchis viverrini, prevalent in parts of Asia

Question 29

Gallbladder carcinoma: what are the histologic types and grading system?