1. Gall bladder and Biliary Disease (3).ppt

1. Gall bladder and Biliary Disease (3).ppt

1. Diseases of the Gallbladder and
Biliary Tract
Shimelis zewdie (General surgeon ,AHMC)

2. A 95 year-old woman presented with upper abdominal pain and jaundice;
ultrasound demonstrated gallstones. Symptoms were short in duration, and
jaundice began to clear rapidly. In view of her age and improving condition, she
was treated conservatively for cholecystitis. However, she then developed
protracted vomiting; endoscopy demonstrated several stones in the duodenum.
What is the most likely cause this type of complication?
a. Malignancy extending into duodenum
b. Perforation of gallbladder
c. Caroli’s syndrome
d. Metastasis from another primary tumor

4. Normal Biliary Physiology
Liver produces 500-1500 mL of bile/day
Major physiologic role of biliary tract and GB
is to concentrate bile and conduct it in well-
timed aliquots to the intestine.
In the intestine:
bile acids participate in normal fat digestion
Cholesterol and other endogenous/exogenous
cmpds in bile excreted in feces.

5. Biliary Physiology
Complex fluid secreted by hepatocytes
Passes through hepatic bile ducts into common hepatic duct
Tonic contraction of sphincter of Oddi during fasting diverts ~1/2 of bile
through the cystic duct into the GB – stored and concentrated.
CCK – released after food ingestion 
GB contracts, sphincter of Oddi relaxes
Allows delivery of timed bolus of bile into intestine.
Bile acids – detergent molecules
Have both fat and water soluble moieties
Convey phospholipids and cholesterol from liver to intestine 
Cholesterol undergoes fecal excretion

6. Enterohepatic circulation
Bile acids
solubilize dietary
fat and promote
its digestion and
absorption
Enterohepatic
circulation:
Bile acids
efficiently
reabsorbed by SI
mucosa (terminal
ileum)  recycled
to liver for re-
excretion

7. Cholelithiasis

8. Normal Gallbladder
Velvety green mucosa
Thin wall
Tall columnar cells lining
mucosal folds (right)
Submucosa and muscularis
at the left.

9. Cholelithiasis
Gallstones:
common biliary tract
disease in US (20-35% by
age 75)
2 types:
Cholesterol (75%)
Pigment
Calcium bilirubinate
and other calcium salts

10. Cholesterol StonesCholesterol Stones
Cholesterol:Cholesterol:
Insoluble in waterInsoluble in water
Normally carried in bile solubilized by bile acids and phospholipidsNormally carried in bile solubilized by bile acids and phospholipids
In most individuals, bile contains > cholesterol than can be maintained In most individuals, bile contains > cholesterol than can be maintained
in stable solutionin stable solution
““supersaturated” with cholesterol supersaturated” with cholesterol  microscopic cholesterol crystals microscopic cholesterol crystals
formform
Interplay of Interplay of nucleation nucleation (mucus, stasis) and “anti-nucleating” (mucus, stasis) and “anti-nucleating”
(apolipoprotein A-I) factors determine whether cholesterol gall stones (apolipoprotein A-I) factors determine whether cholesterol gall stones
formform
Gradual deposition of cholesterol layers Gradual deposition of cholesterol layers 
macroscopic cholesterol stonesmacroscopic cholesterol stones

11. Cholesterol Stones
Gallbladder:
key to stone formation
Area of bile stasis  slow crystal growth
Provides mucus or other material to act as a nidus for initiating
cholesterol crystal.
Mexican Americans and several American Indian tribes, particularly
the Pima Indians in the Southwest
high prevalence rates of cholesterol gallstones
↓bile acid secretion is believed to be the common denominator in these
ethnic groups

13. Pigment stones
Pathophysiology less well understood
 production of bilirubin conjugates (hemolytic
states)
 biliary Ca
2+
and CO
3
2-
 Cirrhosis
Bacterial deconjugation of bilirubin to less soluble
form

14. Predisposing Factors
Factors that increase biliary cholesterol saturation:
Estrogens
Multiparity
OCP’s
Obesity
Rapid weight loss
Terminal ileal disease (decreases bile acid pool)
Factors that increase bile stasis:
Bile duct strictures
Parenteral hyperalimentation
Fasting
Choledochal cysts
Pregnancy – (GB hypomotility)

15. Clinical Manifestations
Most are asymptomatic
Duct obstruction - underlying cause of all manifestations
Cystic duct obstruction
distends GB  biliary pain
Superimposed inflamm/ifx  acute cholecystitis
Common duct obstruction
pain, jaundice, ifx(cholangitis), pancreatitis, and/or
hepatic damage 2° to biliary cirrhosis

16. Asymptomatic Gallstones
60-80% patients with gallstones in US
Over 20-year period:
18% of these develop biliary pain
3% require cholecystectomy
Prophylactic cholecystectomy considered in 3 high-
risk groups:
1. Diabetics – 10-15% greater mortality
2. Calcified (porcelain) GB – Associated w/CA of GB
3. Sickle cell anemia –
hepatic crisis difficult to differentiate vs. acute cholecystitis

17. Porcelain Gallbladder

18. Treatment of Asx Gallstones
Chenodeoxycholic acid or Ursodeoxycholic acid
Dissolution of cholesterol stones
Expectant management  then cholecystectomy if
symptomatic disease develops = more cost effective
Alternatives:
Dissove cholesterol stones:
Instill Methyl-tert-butyl-ether or ethyl propionate into GB
Fragment stones:
extracorporeal shock wave lithotripsy

19. Extracorporeal Shockwave Lithotripsy

20. Chronic Cholecystitis and Biliary Pain
Nonacute sx. caused by presence of gallstones
Biliary Pain (misnamed biliary colic)
GB from symptomatic patients may be grossly normal
Mild histologic inflammation with fibrosis and thickening often from
previous attacks of acute cholecystitis.
Symptoms:
From contraction of GB during transient obstruction of cystic duct by
gallstones.
Steady ache in epigastrium or RUQ 
comes on quickly  plateau over a few minutes  subsides gradually over 30 min-
several hours
Referred pain at tip of scapula or right shoulder
N/V can accompany. (no fever, leukocytosis, or palpable mass)
Attacks occur at variable intervals (days – years)
Nonspecific symptoms:
Dyspepsia, fatty food intolerance, bloating and flatulence, heartburn, belching

21. Diagnosis
Ultrasonography
Sensitivity and specificity >95%
Oral cholecystograpy
90% sensitivity, 75% specificity
Reserved for ensuring cystic duct patency in pts whom
dissolution therapy or extracorporeal shock wave
lithotripsy is planned

22. Tokyo Guideline
•Diagnosis was made with
 One local sign (Murphy sign, RUQ pain or mass)
One systemic sign (fever, leukocytosis, or elevated C-
protein level)
 Confirmatory imaging test
•Sensitivity=91.2% ,specificty=96.9%
22

23. Treatment
Laparoscopic cholecystectomy
Treatment of choice for recurrent biliary pain
May need preoperative endoscopic or radiologic examination of CBD
for concomitant choledocholithiasis
Open cholecystectomy
Mortality rate <0.5%
Might be required if difficulties during procedure i.e. adhesions,
obesity
NSAIDS
Several reorts and trials suggest that use during biliary pain provides
adequate pain relief and ↓ progression to acute cholecystitis

24. Acute Cholecystitis

25. Acute Cholecystitis
Acute right subcostal pain and tenderness
from obstruction of cystic duct 
Distension, inflammation, and 2° ifx of GB
Acalculous cholecystitis (5%)
Triad - Prolonged fasting, immobility,
hemodynamic instability
Critically ill patients (burns, trauma, sepsis)
Parenteral hyperalimentation

26. Acute Cholecystitis
Epigastric or RUQ pain
Gradually  in severity and localizes to GB area
Unlike biliary pain, does not spontaneously resolve
Low grade fever, anorexia, n/v, right subcostal tenderness
(+)Murphy’s sign
subhepatic tenderness and inspiratory arrest during
deep breath
Tender enlarged gallbladder (1/3)
Mild jaundice (20%) – concomitant CBD stones or BD
edema

27. Murphy’s Sign

28. Complications
Onset of fever, shaking chills, leukocytosis, abdominal pain or
tenderness, or persistent severe symptoms =
progression of disease and development of complications
Emphysematous cholecystitis
Diabetics with bacterial gas present in GB lumen and wall
Empyema of gallbladder
Gangrene
Perforation
Mirizzi’s syndrome
Profound jaundice in which extrinsic CBD compression occurs from impacted stone
in GB neck

29. Emphysematous
Cholecystitis

30. Diagnosis Acute Cholecystitis
Radionuclide scanning after administration of
99m
Tc-DISIDA or HIDA
Most accurate test to confirm cystic duct
obstruction
If GB fills with isotope 
acute cholecystitis unlikely
If bile duct visualized but gallbladder not 
Clinical diagnosis strongly supported

32. Images taken shortly after injection
of the radiolabeled tracer.
Gallbladder (black spot) fills as
radioactive material is secreted
into bile and floods in.
Images after gallbladder filled.
Emptying stimulated by an injection of
CCK
Enlarging black streak representing the
CBD appears below the gallbladder.
As streak becomes visible, black spot
representing the GB ↓ in size and
almost disappears as bile is squeezed
into the small intestine.

33. Diagnosis Acute Cholecystitis
Ultrasonagraphy:
Gallstones (or sludge in acalculous) along with
localized tenderness over the GB, pericholecystic
fluid, and GB wall thickening
strong supportive evidence for acute cholecystitis
Oral cholecystograms = no clinical use
Unreliable in acutely ill patient

34. Tokyo Guideline cont…
34

35. Management of Acute Cholecystitis
Patients may improve over 1-7 days with expectant
management
NG suction for profound vomiting, and/or abdominal distension
IV fluids, ABX, and analgesics
Cholecystectomy
Because of high risk of recurrent acute cholecystitis
Within first 24-48 hours after acute episode
Emergency surgery if advanced disease and complications, usually associated
with infection and sepsis.
Cholecystostomy (operative or percutaneous)
Alternative to cholecystectomy in patients with high operative risk

36. Tokyo Guideline …..
•The current recommendations are
Mild and Moderate
Early cholecystectomy.
Severe
 Conservative management with antibiotics and
cholecystostomy tube as needed.
 Surgical treatment when conservative treatments
fail.
36

37. Prognosis
Mortality of acute cholecystitis = 5-10%
Almost entirely confined to patients >60 with
serious associated diseases and those with
supparative complications
Complications
Infection
Cholecystoenteric fistula  results in gallstone
ileus.

38. Choledocholithiasis
and Cholangitis

39. Choledocholithiasis & Acute Cholangitis
~15% of pts with gallstones have CBD stones
(choledocholithiasis)
CD stones usually originate from GB
Less commonly 
stones form de novo in the biliary tree
International incidence rate higher b/c
primary CBD stones caused by parasites

Asians  Ascaris lumbricoides and Clonorchis sinensis

40. Biliary tract lithiasis most often
begins with a calculus (stone) in the
gallbladder.
A small enough calculus (or part of a
calculus) may become impacted in
the neck of the gallbladder or cystic
duct  acute cholecystitis.
The stone may travel further down
into the common bile duct, and
impaction in this duct
(choledocholithiasis) may produce
obstruction with jaundice.
The stone may travel further down
and, near the ampulla, obstruct the
pancreatic duct, leading to acute
pancreatitis.
The stone may pass through the
ampulla and out into the duodenum.

41. Symptoms and Signs
Biliary colic
From rapid  in CBD pressure due to obstructed bile flow
Charcot’s Triad = classic cholangitis
1. RUQ pain – frequently recurring, severe, persists for several hours
2. Chills and Fever - associated with severe colic
3. Jaundice - associated with abdominal pain
Hepatomegaly – in calculous biliary obstruction
Tenderness – RUQ and epigastrium

42. Presentation of Choledocholithiasis
Pain = MC presenting symptom
colicky in nature, moderate in severity, and located in the RUQ
intermittent, transient, and recurrent and may be associated with nausea and vomiting.
Jaundice
CBD becomes obstructed and conjugated bilirubin enters the bloodstream.
History of clay-colored stools and tea-colored urine is obtained from such patients in approximately
50%
The jaundice can be episodic.
Fever
Indication of cholangitis
Charcot triad: fever, jaundice, and RUQ pain strongly favors the diagnosis.
Pancreatitis
Gallstones are responsible for 50% of all cases
Conversely, 4-8% of patients with gallstones develop pancreatitis.
Pancreatitis can be precipitated if CBD obstruction occurs at the level of the ampulla of Vater.

43. Primary CBD Stones
Caused by conditions leading to bile stasis and chronic bactibilia.
Up to 90% of patients with brown pigment CBD stones have (+) bile culture results
Usually brown pigment stones. Brown stones differ from black pigment stones by
having a higher content of cholesterol. Brown stones are soft and earthy in
consistency and take the shape of the duct.
In Western populations, biliary stasis is secondary to factors such as:
sphincter of Oddi dysfunction, benign biliary strictures, sclerosing cholangitis, and cystic
dilatation of the bile ducts.
In Asian populations, A lumbricoides and C sinensis promote stasis:
Either blocking the biliary ducts or by damaging the duct walls
Results in stricture formation.
Bactibilia is also common in these instances, probably secondary to episodic portal
bacteremia.

44. Secondary CBD Stones
Arise from the gallbladder  migrate to the
CBD
Have a typical spectrum of cholesterol stones
and black pigment stones.
Bacteria can be cultured from the surface of
cholesterol and pigment stones but not from
the core, suggesting that bacteria do not play a
role in their formation.

45. Laboratory Diagnosis
 WBC  nonspecific.
 Serum and urine bilirubin - indicate obstruction of the CBD
the higher the bilirubin level, the greater the predictive value.
CBD stones are present in approximately 60% of patients with serum bilirubin levels
greater than 3 mg/dL.
 Serum amylase and lipase
acute pancreatitis complicating choledocholithiasis.
 Alkaline phosphatase and gamma-glutamyl transpeptidase
obstructive choledocholithiasis
good predictive value for the presence of CBD stones.
 Prothrombin time
In prolonged CBD obstruction, secondary to depletion of vitamin K (the absorption of
which is bile-dependent).
 Liver transaminases
choledocholithiasis complicated by cholangitis, pancreatitis, or both.
Blood culture
positive in 30-60% of patients with cholangitis.

46. Preoperative Diagnosis
Transabdominal ultrasonography
It is usually the first modality used in the diagnosis of patients with biliary-related symptoms.
Ultrasonography findings are accurate in the diagnosis of gallbladder stones, but CBD stones are missed
frequently (sensitivity 15-40%).
On the other hand, CBD dilatation is identified accurately, with up to 90% accuracy.
Endoscopic ultrasonography
Introduction of a high-frequency (7.5-12 MHz) ultrasonic probe advanced into the duodenum
under endoscopic guidance. A water-filled balloon is used to provide an acoustic window.
Sensitivity and specificity of CBD stone detection are reported in range of 85-100%.
Invasive, $$$, need experienced enoscopist/ultrasonographer
Computed tomography scan
very accurate in the detection of biliary tree obstruction and ductal dilatation
sensitivity of 75-90% in the detection of CBD stones = essential in evaluation of jaundice.
Capable of defining the level of the obstruction and provides information about the
surrounding structures, especially the pancreas.
MRCP
noninvasive tool with 97% accuracy, 92% sensitivity, and 100% specificity.
$$$, inconvenience, and limitations (eg, obesity, presence of metal objects, eg, pacemakers)

47. Endoscopic Ultrasound (EUS)

48. MRCP

49. Cholangiography
Criterion standard for the detection of CBD stones
Endoscopic Retrograde Cholangiopancreatography (ERCP)
The CBD is cannulated through the ampulla, contrast injected, and films
are obtained.
Experience of the endoscopist is best predictor of success, (90-95% in
expert hands)
Complications = hyperamylasemia and cholangitis.
Percutaneous Transhepatic Cholangiography (PTC)
may be the modality of choice in patients in whom ERCP is difficult
(eg, previous gastric surgery)
percutaneously and transhepatically into an intrahepatic duct, and
cholangiography is performed.

50. Complications
Biliary Cirrhosis:
CBD obstruction >30 days  liver damage 
cirrhosis
Hypoprothrombinemia:
Pts may bleed excessively d/t PT
Responds to 10mg parenteral vitamin K or water
soluble oral vitamin K within 24-36h.

51. Treatment of Choledocholithiasis
CBD stone in pt with cholelithiasis and cholecystitis:
endoscopic papillotomy and stone extraction followed by laparoscopic
cholecystectomy.
ERCP before cholecystectomy in patients with:
Gallstones and jaundice (serum bili >2 mg/dL)
Dilated CBD (>7mm)
Stones in bile duct seen on ultrasound or CT

52. Treatment in summary
For symptomatic pts do either preoperative ERCP or IOC .
 If an ERC reveals stones,
sphincterotomy and ductal clearance of the stones followed by
a lap cholecystectomy.
If an IOC at the time of cholecystectomy reveals stone .
Lap CBDE via the cystic duct or with formal choledochotomy.
 If Lap CBDE is not feasible go for open choledochotomy.
If a choledochotomy is performed, a T tube is left in place.
If Stones are impacted in the ampulla
Choledochoduodenostomy
Roux-en-y choledochojejunostomy
52

53. If a CBE was performed and a T tube left in place,
a T-tube cholangiogram is obtained before its removal.
Retained stones can be retrieved either endoscopically
or via the T-tube tract once it has matured (2–4 weeks).
Retained or recurrent stones following
cholecystectomy are best treated endoscopically
Recurrent stones - may be multiple and large.
 A generous endoscopic sphincterotomy will allow stone
retrieval and as spontaneous passage of stone.
53

54. Neoplasms in the
Biliary Tract

55. Carcinomas of Biliary Tract
Manifestations
weight loss (77%)
nausea (60%)
anorexia (56%)
abdominal pain (56%)
fatigue (63%)
pruritus (51%)
fever (21%)
malaise (19%)
diarrhea (19%)
constipation (16%)
abdominal fullness (16%)
Symptomatic patients
usually have advanced
disease, with spread to hilar
lymph nodes before
obstructive jaundice occurs.
It is associated with a poor
prognosis.

56. Carcinoma of the Gallbladder
Uncommon malignancy – 2.5/100,000
Most common of biliary tract cancers (54%)
>90% are adenocarcinomas
In Native Americans, GB carcinoma is the most commonly seen GI
malignancy
Male:Female = 1:3
Overall mean survival rate = 6 months, 5-year survival rate is 5%
At diagnosis, most of the GB is replaced or destroyed by the cancer

57. Risk Factors for GB Cancer
Cholelithiasis
often large and symptomatic stones present
Chronic infection of gallbladder
Salmonella Typhi
Genetic Factors
GB polyps >1cm in diameter
Mucosal calcification of GB (Porcelain GB)
carcinoma in 25%
Anomalous pancreaticobiliary ductal junction
Congenital biliary cysts
Environmental carcinogens

58. Symptoms and Signs
Jaundice
skin or icteric sclerae
Early  Pain in RUQ with radiation into back
Anorexia, weight loss, fever and chills (cholangitis), supraclavicular LN
Courvoisier’s Law
 Palpable GB with obstructive jaundice signifies malignant disease
This generalization accurate only 50% of time
Hepatomegaly
Usually present and associated with liver tenderness
Ascites
Can occur with peritoneal implants
Hematemesis or melena
From erosion of tumor into blood vessel (hemobilia)

59. Carcinoma of Gallbladder
Location:
 fundus (60%), body (30%), neck (10%)
Notoriously insidious
Diagnosis made incidently at surgery
Spread
Early lymphatic spread  retroperitoneal, right celiac, and
pancreaticoduodenal nodes.
Direct invasion of the liver, extrahepatic biliary ducts, and
duodenum and colon (less common) occurs.
Intraperitoneal seeding may occur.

60. TNM Staging
Tis = Carcinoma in situ
T1a = GB wall: invades lamina propria
T1b = GB wall: invades muscle layer
T2 = Perimuscular connective tissue
T3 = Perforates serosa or directly invades
liver or adjacent organ
T4 = Invades main portal vein or hepatic artery
or multiple organs
N1a = Hepatoduodenal ligament nodes
N1b = Other regional lymph nodes
M0 = No distant metastases
M1= Distant metastases
Stage 0: Tis N0 M0
Stage I: T1 N0 M0
Stage II: T2 N0 M0
Stage III: T1-2 N1 M0
T3 N0-1 M0
Stage IVA: T4 N0-1 M0
Stage IVB: T1-4 N2 M0
T1-4 N0-2 M1

61. Carcinoma of Bile Ducts
(Cholangiocarcinoma)
Tumor that arises from the intrahepatic or extrahepatic biliary epithelium
3% of all cancer deaths in the US
> 90% are adenocarcinomas, remainder are squamous cell CA
3 Geographic Locations:
Intrahepatic
Least common
Extrahepatic (ie, perihilar)
Perihilar (Klatskin tumors) = Most common
At bifurcation of R and L hepatic ducts
Distal extrahepatic
Upper border of pancreas  ampulla
The etiology of most bile duct cancers remains undetermined.

62. Possible Etiologies
Infections
In SE Asia, chronic infx with liver flukes
Clonorchis sinensis, Opisthorchis viverrini and Fasciola Hepatica
Inflammatory bowel disease
CCC generally develops in patients with long-standing ulcerative colitis and
PSC.
Chemical exposures
primarily among workers in the aircraft, rubber, and wood finishing industries.
Thorotrast
Congenital diseases of the biliary tree
choledochal cysts and Caroli disease

63. Pathophysiology of CCC
Long-standing inflammation as with PSC, chronic
parasitic infection suggested to play a role by
inducing hyperplasia  cellular proliferation 
malignant transformation.
Grow slowly and infiltrate walls of the ducts,
dissecting along tissue planes
Local extension:
liver, porta hepatis, regional LN of the celiac and
pancreaticoduodenal chains.

64. Symptoms and Signs
Progressive jaundice
MC manifestation of bile duct cancer
The obstruction and subsequent cholestasis tends to occur early if the tumor is located
in the common bile duct or common hepatic duct.
Jaundice often occurs later in perihilar or intrahepatic tumors and is often a marker of
advanced disease.
The excess of conjugated bilirubin is associated with bilirubinuria and clay colored
stools.
Pruritus
usually is preceded by jaundice, but itching may be the initial symptom of CCC.
related to circulating bile acids.
Weight loss
Abdominal pain
common in advanced disease and often is described as a dull ache in the RUQ

65. Courvoisier’s Sign
If CCC located distal to
the cystic duct takeoff

the patient may have a
palpable gallbladder,
(Courvoisier sign)

66. Laboratory Examination
Biliary Neoplasms
 Conjugated Bilirubin
Total serum bilirubin from 5-30mg/dL
 Alkaline Phosphatase and GGT
 Serum Cholesterol
AST
normal or mildly elevated
CA 19-9
If elevated – may help distinguish CCC from benign biliary stricture

67. Imaging in Biliary Neoplasms
Ultrasonagraphy and CT:
Show GB mass in GB Carcinoma
Intrahepatic masses or biliary duct dilation
CT also shows involved regional LN
MRI with MRCP
Visualization of biliary tree
Detection of vascular invasion
Positron Emission Tomography (PET)
Can detect CCC as small as 1cm
The most helpful diagnostic studies before surgery are either
PTC or ERCP with biopsy and cytology

68. Treatment of Biliary Neoplasms
Curative Surgery (Gallbladder CA)
May be attempted in young and fit pts if tumor is well localized.
5 year survival for localized (stage 1, T1a, N0, M0) is as high as 80% with laparoscopic
cholecystectomy
Only 15% if muscular invasion (T1b)
If tumor unresectable at laparotomy
Cholecystoduodenostomy or T-tube drainage of CBD
Curative Surgery (CCC)
Curable in <10%
Palliation - place self-expandable metal stent via ERCP or PTC
Photodynamic therapy – palliative
Radiotherapy
Relieve pain and contributes to biliary decomression
Chemotherapy with gemcitabine – limited response
In general, prognosis is poor, with few patients surviving >12 months after surgery

69. A 95 year-old woman presented with upper abdominal pain and jaundice;
ultrasound demonstrated gallstones. Symptoms were short in duration, and
jaundice began to clear rapidly. In view of her age and improving condition, she
was treated conservatively for cholecystitis. However, she then developed
protracted vomiting; endoscopy demonstrated several stones in the duodenum.
What is the most likely cause this type of complication?
a. Malignancy extending into duodenum
b. Perforation of gallbladder
c. Caroli’s syndrome
d. Metastasis from another primary tumor

70. Answer
B. This stone could not be removed
endoscopically. Surgery confirmed the
suspicion that the gallbladder had perforated
into the duodenum, releasing the stones into
the duodenal lumen. Measurement of the
largest stone after surgical removal revealed it
to be over 5 cm in length (right).