Surgical Aspects of the Multidisciplinary Treatment of Gallbladder Cancer Eduardo A Guzman MD
Surgical Aspects of the Multidisciplinary Treatment of Gallbladder Cancer
Eduardo A Guzman MD
“In malignancy of the gallbladder, when a diagnosis
can be made without exploration, no operation
should be performed, inasmuch as it only shortens
the patient’s life”
Alfred Blalock, 1924
Introduction
•Aggressive malignancy
•Elderly patients
•Poor prognosis
•Many tumors are unresectable
•Distant metastasis
•Selected patients will benefit from an aggressive surgical
approach
Epidemiology
• Rare tumor
• Incidence 2.5 cases per 100,000 residents
• Most common malignancy of the biliary tract
• 5th most common gastrointestinal malignancy
• 2 times more common in women
• More than 75 % are older than 65
Epidemiology
Etiology
• Chronic gallgladder irritation and inflammation
• Gallstones– Gallstones in 80 % GB
cancer
– GB cancer is 7 times more common in people with gallstones
• Porcelain gallbladder
• Primary sclerosing cholangitis• Polyp
Gallbladder polyp
• > 1 cm increased incidence of cancer
• Treatment is laparoscopic cholecystectomy
• If mass do open choelcystectomy
Pathology
Tumor Type Percent of Total
Adenocarcinoma 75.8
Papillary 5.8
Mucinous 4.6
Adenosquamous 3.6
Oat cell 0.5
Nonspecific 7.6
Location
• Neck 10 %
• Body 30 %
• Fundus 60 %
Lymphatic drainage of the gallbladder
• Cystic
• Pericholedocal
• Posterior pancreaticoduodenal
• Periportal
• Common hepatic artery nodes
• Celiac, interaortocaval, SMA
Staging
• Multiple classifications
– Nevin– Japanese– AJCC / TNM
• Recent modification of AJCC / TNM
T1 = Mucosal or muscular invasion
T2 = Transmural invasion
T3 = < 2 cm hepatic invasion
T4 = > 2 cm hepatic invasion
N0 = No lymph node involvement
N1 = Lymph node involvement within hepatoduodenal ligament
N2 = Lymph node involvement beyond hepatoduodenal ligament
M0 = No distant metastasis
M1 = Distant metastasis
AJCC / TNM 6th edition
a b
T1a
T1b
T2
T3
T4
T stage
Stage
I T1 N0 M0
T2 N0 M0
II T3 N0 M0
T1-3 N1 M0
III T4 N0 M0
IV Tx Nx M1
AJCC / TNM 6th edition
Limited to gallbladder
Local invasion
Locally advanced
Metastasis
Other points
• Stage I includes 2
different surgical
therapies
• T4 tumors can be
resectable
• N2 nodes are
considered metastatic
disease
Extent of disease on initial presentation
Stage
I 25 %
II - III 35 %
IV 40 %
Laparoscopic cholecystectomy and positive margins
Mucosa
Submucosa
Muscularis
Serosa
Liver
During a laparoscopic cholecystectomy the plane of dissection is subserosal
Clinical presentation
• Undistinguishable from benign gallstone disease– Right upper quadrant pain – Weight loss
– Anorexia
– Abdominal mass
• Yet, one should suspect gallbladder cancer in an elderly person with weight loss and constant pain
Clinical syndromes
Chronic cholecystitis
32%
Acute Cholecystitis
16%
Malignant biliary obstruction
24%
Malignant non biliary tumors
24%
Other4%
Diagnosis
• Usually diagnosed late in the disease course
• Ultrasound– Heterogeneous mass
– Irregular GB wall
– Sensitivity 70 – 100 %
• CT scan– Mass replacing the gallbladder or with direct extension
• MRI– Identifies plane between gallbladder mass and adjacent liver
• Cholagiography– Stricture of the common hepatic duct
Incidental diagnosis
• It is the most common presentation
• Intraoperative
• Postoperative
– Pathology
• 1 % of all elective cholecystectomies for cholelithiasis harbor an occult GB cancer
Management
• Depends on stage
• Do open cholecystectomy if cancer suspected pre-operatively
• Convert to open procedure if cancer identified intra-operatively
• Avoid bile spillage or tumor implantation into port sites
Biopsy
• Risk of seeding cancer along the needle tract
• Worse with core biopsy
• Gallbladder cancer has a tendency to seed the peritoneum
• Percutaneous biopsy is indicated if disease has been determined to be unresectable and prior to initiation of chemotherapy
Staging Laparoscopy
• Important consideration
• Staging modality
• Patients with incurable
disease can avoid a
laparotomy
• Yield 50 %
Stage I
• T1a
– Disease limited to mucosa
– Almost always diagnosed following
cholecystectomy
– Negligible probability of lymph node metastasis
– Excellent survival 95 %
– No further intervention required
– Make sure cystic duct margin is negative for
tumor
Stage I
• T1b
– Disease limited to muscularis
– Higher locoregional recurrence
– 5 year survival = 85 %
– Treatment remains controversial
– Selected patients (young and healthy) may benefit
from liver resection of segment IVb and V along
with local lymphadenectomy
Couinaud Segments
Liver Anatomy
Stage I
• T2– Transmural invasion– Positive margin after cholecystectomy
– Good probability for lymph node positivity
– Optimal patient for aggressive surgical intervention. 5 yr survival 18 % Vs 61 %
– Liver resection of segment IVb and V and lymphadenectomy
• Cystic• Pericholedochal • Portal
• Right celiac• Hepatic• Posterior pancreaticoduodenal
Liver resection of segment IVb and V and lymphadenectomy
Stage II
• T3N0 / N1 disease– Cancer invades into contiguous liver for less than
2 cm and/or has positive hepatoduodenal lymph nodes
– Tumor is still resectable
– High increased incidence of lymph node metastasis
– Ideal patient for staging laparoscopy
– Liver resection of segment IVb and V and lymphadenectomy
Stage III
• T4N0MO
– Cancer invades into contiguous liver for more than
2 cm and negative lymph nodes
– Anecdotal evidence of resectability
– Extended liver resection
• Trisegmentectomy
Some other important surgical considerations
• Resect port sites
• Avoid spillage of bile
• En bloc resection
• Do not hesitate to do
CBD resection
• Do anatomic liver
resections
• Tumors in the infundibulum may require a trisegmentectomy
Adjuvant Chemotherapy
• 85 % of the recurrences occur in distant disease sites
• Minimal data
• Regimens
– 5 flouroracil
– Mitomycin C
– Gemcitabine
LNLN+ + PatientsPatients
SEER National Database 1992 - 2002SEER National Database 1992 - 2002
YEARSYEARS
100
20
40
60
80
1 2 3 4 5
SUR
VIV
AL
%SU
RV
IVA
L %
RadiationRadiationNo RadiationNo Radiation
p <0.0001p <0.0001
11% 5yr11% 5yr04% 5yr04% 5yr
survival
Mojica, Smith and Ellenhorn 2006
Adjuvant Radiation
Stage IV
• M1
– N2 lymph nodes
– Extrahepatic metastasis
– Chemotherapy
– Palliation
• Obstructive jaundice
• Pain
• S Kim et al – Korea• 29 pts inoperable GB cancer• Median age 52 yrs• No complete responses• 34 % partial response• Time to progression = 3 months• Overall survival = 11 mo• Toxicity (3 or 4) = 17 %
• Tolerable combination• Modest response rates
Survival
• Overall 5 yr survival 15 %
• T1a 95 %
• T1b 85 %
• T2
– Cholecystectomy 18 %
– Liver resection 60 %
• Stage IV
– Median survival 2 months
Summary
• Gallbladder cancer is a bad disease
• Accurate staging is critical
• Cholecystectomy is an inadequate operation in most
of the cases
• T1a tumors have excellent prognosis
• Selected patients would obtain significant benefit
from aggressive surgical interventions
• Nearly all patients without metastatic disease require
surgical evaluation to determine resectability
“In malignancy of the gallbladder, after careful
patient selection, an aggressive surgical approach
can have a significant impact in the patient’s life”
Eduardo Guzman, 2007