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