This document summarizes the surgical aspects of treating gallbladder cancer. It discusses the epidemiology, risk factors, staging, diagnosis, and management of gallbladder cancer. For early stage I tumors, surgery including cholecystectomy is usually sufficient. For more advanced stages II-III, aggressive surgery involving liver resection and lymphadenectomy may improve survival rates. Stage IV cancer with metastases has a very poor prognosis with chemotherapy and palliation the only options. An aggressive surgical approach can benefit carefully selected patients without metastatic disease.

1. Surgical Aspects of the
Multidisciplinary Treatment
of Gallbladder Cancer
Eduardo A Guzman MD

2. “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

3. Introduction
•Aggressive malignancy
•Elderly patients
•Poor prognosis
•Many tumors are unresectable
•Distant metastasis
•Selected patients will benefit from an aggressive surgical
approach

4. 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

5. Epidemiology

6. 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

7. Gallbladder polyp
• > 1 cm increased
incidence of cancer
• Treatment is
laparoscopic
cholecystectomy
• If mass do open
choelcystectomy

8. 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

9. Location
• Neck 10 %
• Body 30 %
• Fundus 60 %

10. Lymphatic drainage of the gallbladder
• Cystic
• Pericholedocal
• Posterior pancreaticoduodenal
• Periportal
• Common hepatic artery nodes
• Celiac, interaortocaval, SMA

11. Staging
• Multiple classifications
– Nevin
– Japanese
– AJCC / TNM
• Recent modification of AJCC / TNM

12. 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

13. T1a
T1b
T2
T3
T4
T stage

14. 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

15. Other points
• Stage I includes 2
different surgical
therapies
• T4 tumors can be
resectable
• N2 nodes are
considered metastatic
disease

16. Extent of disease on initial presentation
Stage
I 25 %
II - III 35 %
IV 40 %

17. Laparoscopic cholecystectomy and positive margins
Mucosa
Submucosa
Muscularis
Serosa
Liver
During a laparoscopic cholecystectomy the plane
of dissection is subserosal

18. 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

19. Clinical syndromes
Chronic
cholecystitis
32%
Acute
Cholecystitis
16%
Malignant biliary
obstruction
24%
Malignant non
biliary tumors
24%
Other
4%

20. 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

21. Incidental diagnosis
• It is the most common
presentation
• Intraoperative
• Postoperative
– Pathology
• 1 % of all elective
cholecystectomies for
cholelithiasis harbor an occult
GB cancer

22. 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

23. 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

24. Staging Laparoscopy
• Important consideration
• Staging modality
• Patients with incurable
disease can avoid a
laparotomy
• Yield 50 %

25. 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

26. 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

27. Couinaud Segments
Liver Anatomy

28. 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

29. Liver resection of segment IVb and V and
lymphadenectomy

30. 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

31. 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

32. 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

33. Adjuvant Chemotherapy
• 85 % of the recurrences occur in distant disease sites
• Minimal data
• Regimens
– 5 flouroracil
– Mitomycin C
– Gemcitabine

34. LNLN++
PatientsPatients
SEER National Database 1992 - 2002SEER National Database 1992 - 2002
YEARSYEARS
100
20
40
60
80
1 2 3 4 5
SURVIVAL%SURVIVAL%
RadiationRadiation
No RadiationNo Radiation
p <0.0001p <0.0001
11% 5yr11% 5yr
04% 5yr04% 5yr
survival
Mojica, Smith and Ellenhorn 2006
Adjuvant Radiation

35. Stage IV
• M1
– N2 lymph nodes
– Extrahepatic metastasis
– Chemotherapy
– Palliation
• Obstructive jaundice
• Pain

36. • 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

37. Survival
• Overall 5 yr survival 15 %
• T1a 95 %
• T1b 85 %
• T2
– Cholecystectomy 18 %
– Liver resection 60 %
• Stage IV
– Median survival 2 months

38. 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

39. “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