Carcinoma Gall bladder

Objectives:
• Epidemiology
• Etiology
• Pathology and pathogenesis
• Clinical presentation
• diagnosis
• Treatment
• Prognosis
 Epidemiology

• 6500 cases annually (USA)

• 5th most common cause of GI malignancy (USA)
• Incidence increases with age
• 2-6 times more common in female
Ca GB - distribution
 Risk factors
• Cholelithiasis
– 75-98% of all patient with Ca GB
– Cholesterols type stones

• Old age

• Female

• Anomalous pancreaticobiliary duct junction

• Typhoid carriers- chronic inflammation

• Others- IBD
• The risk of developing gallbladder carcinoma increases
directly with increasing gallstone size

• Relative Risk =2.4 with stone size 2- 2.9cm diameter

• Relative risk 10.1 with >3cm diameter stones

 Lahmar A, Abid SB, Arfa MN, Bayar R, Khalfallah MT, Mzabi-Regaya S. Metachronous cancer of
gallbladder and pancreas with pancreatobiliary maljunction. World Journal of Gastrointestinal
Surgery. 2010;2(4):143-146. doi:10.4240/wjgs.v2.i4.143.

• Anomalous pancreaticobiliary duct junction

• with an incidence of 3.2%

in patients undergoing
ERCP or operative
Cholangiopancreatography
• Refluxed proteolytic pancreatic enzymes are activated in the
biliary tract and may induce biliary tract carcinoma

• The reflux of bile may activate pancreatic enzymes which may

cause chronic inflammation and metaplastic epithelial change
in the pancreatic duct and pancreatic cancer may eventually
develop
 Etiology
• Gall stones and chronic inflammation

• 3.3 to 3% among patients with GSD

• Porcelain GB (10-25%)

• Helicobacter bilis and Helicobacter pylori (about six fold

higher risk)

• Chemicals methyldopa,oral contraceptives, isoniazid, and

occupational exposure in the rubber
 Anatomic consideration
• The location of the primary tumor within the gallbladder and
the proximity of the portal vein, hepatic artery, and bile duct
are all important factors in the surgical management of this
tumor
• The gallbladder is attached to segments IVb and V of the liver and these
segments are involved early in tumors of the fundus and body of the
gallbladder- limited segmental resection often possible
• Tumors of the infundibulum or cystic duct readily obstruct the common
bile duct and may involve the portal vein.

• As with cholangiocarcinoma the tumor may be unresectable early in its

course-- tumor of this region require extended liver resections due to
proximity to portal pedicles
 Pathology

• GB epithelium progresses from dysplasia to carcinoma in situ

to invasive carcinoma

• Area of dysplasia and carcinoma in situ is often missed in

routine cholecystectomy specimens as there are no
associated gross characteristics that would target an area for
histological sections

• Carcinoma in situ may appear within the Rokitansky aschoff

sinuses and often mistaken for invasive carcinoma
• Rate of progression of precursor lesions to invasive carcinoma
has estimated around 15 years
Gross
 Gross morphology
• Difficult to diffrentiate grossly from chronic cholecystitis at
early stages and are often found incidentally on pathologic
sections

• 60% - fundus
• 30% body
• 10% neck
• Tumor arising from neck and hartmanns pouch may infiltrate
the cystic duct and common bile duct make it clinically
indistinguishable form hilar bile ducts tumor
1. Infiltrative- m/c
2. Nodular
3. Combined nodular- infiltrative- m/c
4. Papillary
5. Combined papillary- infiltrative
• Infiltrative tumors cause thickening and indurations of GB wall
and extending to entire GB

• Spreads in the subserosal plane which is the same as the

surgical plane used for routine cholecystectomy if tumor
unrecognized during surgery leads to regional dissemination

• Becomes more advanced if infiltrates liver

• Nodular type
– Early invasion through GB wall into liver or neighboring
structures
– Easier to control surgically than infiltrative whose margins
are less defined
• Papillary ca
– exhibit a polypoid or cauliflower like appearance
– Better prognosis
– May be larger filling the lumen but with minimal
invasion
• Histopathological grading
– G1- well differentiated
– G3- undifferentiated
– Majority of patient present with G3 poorly
differentiated tumors
 Tumor bilogy

• Multiple genetic changes

• P53 and k-ras gene mutation
 Pattern of spread
• Along peritoneal cavity

• Along needle biopsy sites

• Laparoscopic port sites

• direct extension to liver and other adjacent organs
– Gall bladder has thin wall, narrow lamina propia, and single muscle
layer

– Once penetrates to thin muscle layer has access to major lymphatic

and vascular channels
• tumor penetration into or through the muscularis has prognostic
implications because the lymphatic drainage of the gallbladder lies in the
layer between the muscle and the serosa.

• Also, most simple cholecystectomies for gallstone leave the serosa on the
liver side because the subserosal plane is the easiest for dissection.

• Thus, simple cholecystectomies performed for unsuspected gallbladder

cancer is likely to leave a positive margin for any tumor that penetrates
the muscle layer
• Autospy

• 94.4% lymphatic mets

• 64.% hematogenous dissemination

• Hematogenous form small veins extensding directly from gall

bladder to portal venous system of GB fossa leading to
segment IV and V of liver or via larger veins to portal venous
branch of segment V and VIII
1-pericholedochal, nodes along
the common bile duct

2- cystic duct, node(s) along the

cystic duct

3-retroportal, nodes posterior

to the portal vein and cephalad to
the uncinate process

4-posterior superior
pancreaticoduodenal, nodes on
the posterosuperior aspect of the
head of the
pancreas
5-hepatic artery, nodes
along the common or
proper hepatic artery

6-right celiac, nodes

located right of the
celiac axis and
posterior to the
common
hepatic artery

7-hilar, nodes within

the porta hepatis
 Radiologic investigation
Discontinious GB mucosa
Echogenic mucosa
Submucosal echolucency
Inhomogenous mass replacing all or part of GB
Diffuse thickening of GB wall

Lypmh nodes- a soft tissue mass with AP diameter of

atleast 10mm showing ring like heterogenous
enhancement ( 89% accuracy)
Positive LN may alter surgeons decisions to operate or
change operative approach
 MRCP
• More detail information than CT sccan and Usg

• Angiography
– Portal vein and hepatic artery encasement avoids
unneccesay laparotomy

• EUS
– Peripancreatic and periportal adenotpathy
– Needle bipdy can be performed
• Endoscopic and percutaneous cholangiographs
– GB cancer with obstructive jaundice- direct invasion or
compression of CHD or by pericholedochal LN
– Intraheptic bile ducts obstruction. High ALP

– Planning of palliative managemt of Gall bladder carcinoma

– Also indicated in atypical cases with vague sypmtoms and
abnormal lft where other imaging modalities have not
yeilded diagnosis
– Stricturing, distortion or nonfiling of bile ducts draining
segment IV and V with no effects on other segmental ducts
• Biliary colic or chronic cholecystitis, elderly
patients with atypical symptoms, suspicious lab
findings ( anemia, hypoalbunemnia or abnormal
LFT)
• USG- mnass, abnormal mucosal finnding, or
segmental duct dilatation
• CT scan
• Lab or radiologic investigation shows evidence for
ductal obstructionMRCP, ERCP or PTC
• Advanced mass encroaching on the porta
hepatis duplex USG or arteriography
 Preop pathologic diagnosis

• Suscpicious mass- pre op biopsy contoversial

• Cholec( ystectomy as diagnositic biopsy
unaccesptale
• ERCP and bile cytology (73% sensitivity)
• Percutaneous FNAC- mass not considered for
surgical resection ( 88% accuracy)
• Percutaneous core needle biospy if FNAC fails
as high chance of needle tract seeding
 staging

1. Modified Nevin system ( Donohue et.a l 1990, Nevin et. al

1976)

2. Japanese Biliary Surgical Society system (Onoyama et al

1995)

3. AJCC/UICC TNM staging system ( Beahrs and Myers 1983)

 management
• Stage O and Stage I ( Tis, T1a – Ca invades
lamina propia but don’t extend to muscularis)
• frequently detected on pathological
examination
• Imaging based staging
• Watch cholecystectomy specimen to ensure
negative margin
 Margin negative,negative
Margin postive imaging
• No evidence of residual or
metastatic GB ca
• But cystic duct margin • No further surgery
positive

• Rexploration with CBD

excision , regional
lymphadenectomy and HJ
• Stage T1b ( cancer that invases the muscularis
but don’t extend to perimusccular connective
tissue

• T1 b cancer treat same as T2 Ca GB

 Stage II ( T2NOMO)
• T2- cancer invasion into perimuscular
connectivetissue of GB
• regional LN mets- 28-63%

• Rexploration with liver resection and regional

lymphadenectomy of hepatoduodenal
ligament
• Preoperative T2 suscpicious
• staging
• In no contraindication
• Proceed for exploration with en bloc resection
of GB and adjacent liver to depth of at least 2 cm
with regional lymphadenectomy of
hepatoduodenal ligament
• Non anatomic
• Anatomic segment 4b, 5 resection – less bleeding
 Stage III
• T3 lesions ( locally advanced cancers that
perforate the GB serosa or directly invade the
liver and/ or one adjacent organ and
• T1-T3 lesions associated with regional LN mets
 Stage III
• Careful planning,individualized

• Liver invasion- hepatic resection seg 4b and 5

– Trisegmentectomy if GB foss bridges both right
and left hepatic lobes
– Enbloc resection of hepatic flexure of colon

– Long term survival- 15-63%

 Stage IV
• IV A-Invasion to main portal vein, common
hepatic artery, multiple extrahepatic organs

• Stage IVB
– N2 and or distance mets

– Uresectable
– Main portal vein, CHA if reseccted – confers
morbidity and mortality ares
 Adjuvant therapies
• Adjuvant chemoradiotherapy after resection
• External beam or intraoperative radiation
therapy alone or in combination with 5FU-
decreasse local recurrence

• Data inadequate
 palliation
• Goal- relief pain, manifestation of biliary
obstruction ( pruritis and cholangitis) and
bowel obstruction
• Endscopic stenting than surgical bypass in
weeks to month survival
• Palliative radiotherapy
• Regional intra- arterial chemotherapy
andchemoradiotherapy
• Gemcitabine plus cisplantin
 outcome
Five year survival %
T1N0 39
T2N0 15
T3N0 12
• T1- 85-100%

• with radical resection-

– T2 80-90%
– T3 15-63%
– T4 2-25%
• Radical resection of node positive- 60% 5 year
survival
– Morbidity and mortality

– Morbidity--5-54%
– Mortality- 0-21%

– More the extensive dissection more morbidity and

mortalitiy rates
 CT
• GB cancer protocol
• Dual phase contrast – arterial and venous