This document provides an outline and overview of gallbladder carcinoma. It discusses the epidemiology, risk factors, presentation, workup, treatment and follow up of gallbladder cancer. Key points include: gallbladder cancer is the most common biliary tract malignancy and 20th most common cancer worldwide. The highest incidence is found in Chilean and Indian women. Risk factors include gallstones, salmonella infection, obesity and genetic predisposition. Presentation is often asymptomatic but can include jaundice, weight loss and palpable mass. Workup involves imaging like ultrasound, CT and MRI to determine extent of disease. Surgical resection along with lymph node dissection is the main treatment but prognosis remains poor with 5-year survival of only

1. ANUP SHRESTHA
DEPT OF SURGERY
CMC
Gallbladder Carcinoma

2. OUTLINE
 Introduction
 Epidemiology
 Risk Factors
 Etiology/Pathophysiology
 Relevent anatomy
 Presentation
 Workup
 Treatment
 Follow Up

3. INTRODUCTION
 Gallbladder cancer, although rare, is the most
common of biliary tract malignancy and the 20th
most common cancer worldwide.
 Gallbladder carcinoma was first described by
Maximilian Stoll in 1778.
 For resectable disease ,overall 5-year survival of 20%
with median survival of just 16 months. (Mayo et al,
2010)and for advanced, untreated gallbladder cancer
it’s generally 2 to 5 months

4. Epidemiology of Gallbaldder Carcinoma
 The highest incidence of gallbladder cancer is found in
Chilean Mapuche Indian women, followed by women
living in India, and natives of North America
 There were nearly 2,20,000 new cases in 2018
 6th most common cancer in Nepal .
 Nepal ranks 5th in the global overall incidence with
age-standardised rate(AGR) 6.7 per 100,000.
 Female to male ratio is 3:1
 Peak incidence is in 7th decade of life.
(World Cancer Research Fund International and American Institute of Cancer
Research)

5. RISK FACTORS
 Cholelithiasis (gallstones)
 Salmonella tiphy o parathypi (chronic
carrier)
 Genetic predisposition
 Obesity
 Chronic cholecystitis, (chronic mucosal
damage)
 Polypoid lesions in the bladder,
adenomiomatosis
 Autoimmune disease ( primary biliary
cirrhosis, primary sclerosing colangisits ,
inflammatory bowel disease)
 anomalous pancreatobiliary duct junction
 Biliary-enteric fistulae
 Porcelain gallbladder

6. RELEVENT ANATOMY
 Defn : Saccular partially
intraperitoneal structure located
at the inferior surface of the liver,
at the division of the right and
left lobes, just below segments
IVb and V
 Composed of 4 areas: fundus,
body, infundibulum, and neck
 Approx. 7-10 cm long and about
2.5-3.5 cm wide
 Normally contains approx. 30-50
mL of fluid(max up to 300 mL)

7. THE CYSTIC PLATE
 gallbladder that is attached to the liver, there is no
peritoneal covering, but there is a fibrous lining
known as the cystic plate

8. THE LYMPHATIC DRAINAGE

9. PATHOLOGY
Premalignant Lesions
Adenomatous polyps
 Papillary adenomas grow as pedunculated, complex,
branching tumors projecting into the gallbladder lumen.
 Tubular adenomas arise as a flat, sessile neoplasm.
Adenomyomatosis
 extensions of Rokitansky-Aschoff sinuses through the
muscular wall of the gallbladder
 USG reveals a thickened gallbladder wall with intramural
diverticula
 serial evaluation with USG is indicated to rule out enlarging
adenomatous polyps and gallbladder cancer

10. Gross pathology
 60% of tumors originate from the Fundus
 30% from the body
 10% from the neck
 Gross descriptions of gallbladder cancer have been
grouped into infiltrative, nodular, combined
nodular-infiltrative, papillary, and combined
papillary-infiltrative forms
 starting with chronic inflammation leading to
dysplasia, followed by carcinoma in situ, and finally
invasive carcinoma

11.  an infiltrative pattern as at least part
of their presentation
 causing diffuse thickening and
induration of the gallbladder wall
.These types of tumors seem to spread
in a subserosal plane and can invade
the whole gallbladder wall and even
invade into the porta hepatis, causing
jaundice from diffuse biliary
involvement. These types of tumor can
also diffusely invade the liver

12.  Nodular types of tumors
tend to grow as a more
circumscribed mass.
Despite invasion into the
liver, these lesions are
more easily resected
because they are less
diffuse in their invasive
pattern.
 Papillary tumors of the
gallbladder are polypoid
lesions with frondlike
extensions giving a
cauliflower-like appearance
tumors can grow quite
large, they tend to have a
better prognosis than the
other gross types
 Even at large sizes,
papillary gallbladder
tumors may have minimal
invasion into the
gallbladder wall

13. Histology
 Most carcinomas of the
gallbladder are
adenocarcinomas.
 Some are papillary in
architecture and are well to
moderately differentiated;
others are infiltrative and
poorly differentiated to
undifferentiated
 About 5% are squamous
cell carcinomas or have
adenosquamous
differentiation

14. Spread Pattern
 spreads via lymphatics, hematogenously, and notoriously into
the peritoneal cavity or along biopsy or surgical wound tracts
 Gallbladder Ca seems to invade and metastasize relatively
early;.The thin wall of the gallbladder may be responsible for
early hematogenous and lymphatic spread.
 Hematogenous metastases originate from small veins
extending directly from the gallbladder into the portal venous
system of the gallbladder fossa.
 Autopsy studies have shown widely disseminated disease,
including liver metastases in greater than 90%, abdominal
lymph node metastases in more than 80%, and peritoneal
metastases in 60% of patients

15. Clinical Presentation
 Three clinical scenarios :
(1) identified by final pathology after routine cholecystectomy;
(2) discovered intraoperatively
(3) suspected before surgery
 Usually asymptomatic at the time of diagnosis
 Symptoms if present are similar to benign diseases such as
cholecystitis or biliary colic
 Jaundice , weight loss and anorexia are late features
 Palpable mass is a late sign
 . An elevated CEA tends to be specific (90%) but lacks
sensitivity (50%) CA19-9 is more consistent with sensitivities
and specificities of approximately 75%

16. Radiological investigation
Ultrasonography
 : early malignancy: discontinuous mucosa, echogenic
mucosa, and submucosal echolucency
 Indications of maligancy : a thick gallbladder wall,
– vascular polyp
– a mass projecting into the lumen or invading the
wall, multiple masses or a fixed mass in the
gallbladder,
– a porcelain gallbladder, and an extracholecystic
mass.
-- Invasion of the liver can also be seen on USG

17. Cross-sectional imaging with CT or MRI
 The MC finding on CT is a
mass involving all or part
of the gallbladder
 71% to 84% accurate in
T-staging gallbladder
cancer
 MRI have shown
sensitivities of 70% to
100% for hepatic invasion
and 60% to 75% for
lymph node metastases

18. PET Scan
 help differentiate between benign and malignant
tumors and diagnose extrahepatic spread
 PET was significantly more valuable in patients with
suspicious nodal disease
 Con -Difficult to differentiate between inflammation
and malignancy

19. DIAGNOSTIC PROCEDURES
 Percutaneous CT scan – guided biopsy avoided (risk
of peritoneal seeding)
 Percutaneous CT scan – guided biopsy is a useful
diagnostic tool in patients who appear to have a non-
resectable tumor.
 Tissue diagnosis is necessary for palliative treatment.
 Endoscopic ultrasonography with fine-needle
aspiration
 Biopsy can be used to evaluate for peripancreatic and
periportal lymphadenopathy.

20. American Joint Committee on Cancer (AJCC)System
for Gallbladder Cancer (7th edition)

21. Other Systems

22. SURGICAL MANAGEMENT
Benign Polyps
 adenomatous polyps have malignant potential and are
associated with a significant rate of harboring
malignancy .
 Other benign lesions, such as fibromas, lipomas,
hemangiomata, cholesterol polyps, inflammatory polyps,
and adenomyomas
 factors associated with malignancy single polyp, size
greater than 1 cm, age >50 yrs and primary sclerosing
cholangitis.
 Recommendation for ultrasound follow-up at 12-month
intervals for 2 to 3 years, then consideration of no
additional imaging if the polyp is stable and there are no
new or suspicious clinical symptoms.

23. Gallbladder Ca Incidentally Discovered During
Routine Cholecystectomy
 Gallbladder cancer is found in 0.2% to 2.0% of all
laparoscopic cholecystectomies
 If expertise unavailable-document all findings , refer to
higher centres
 If suspicious mass seen – Biopsy not advised (peritoneal
dissemination)
 If expertise available
1)if clinical evidence is adequate –definitive resection
2)if clinically not clear – frozen section biopsies before
resection

24. Incidental Finding On Pathologic Review
 Consider pathologic re-review by hepatobiliary
pathology expert.
 Staging laparoscopy can be done.
 Repeat CT of chest, abdomen & pelvis
 Initial exploration to rule out metastasis in coeliac
axis, aortocaval groove ( contraindication )
 Hepatic resection/extended resections/bile duct
resection with lymphadenectomy.
 Port site resection not effective(indicates
disseminated disease)

25. Staging Laparoscopy
 In order to exclude the presence of undetected intra-
abdominal metastases prior to curative laparotomy.
 Surgery is contraindicated in the presence of distant
metastases (occult metastases)
 Advantages
# less pain, less morbidity,
# quicker hospital discharge
# more rapid resumption of normal activity
# earlier start of other therapies

26. Extent of Resection by Stage
 T1a lesions (limited to the mucosa) Simple
cholecystectomy
 T1b or greater lesions  Radical cholecystectomy and
lymphadenectomy with or without bile duct excision;
hepatic resection is performed to obtain clear margins,
which usually consists of segments IV B and V.
 T2 and T3 tumors a complete resection of the tumor
en bloc with segments IVb and V of the liver should be
carried out to ensure complete clearance
 Suspected invasion of hepatic inflow vascular structures,
an extended right hepatectomy may be necessary to clear
all tumor

27. Extent of Resection (continue ..)
 A negative margin at the cystic duct should be
assessed  if necessary bile duct resection .
 lymph node dissection of the hepatoduodenal
ligament also should be done.
 It is important to stage the patient at operation
major resection should be abandoned if distant
nodal (retropancreatic or celiac) or other metastases
are found
 If gallbladder was not removed by bag during lap
chole  Port site resection.

28. Liver Resection
 Recommendations from limited 2-cm wedge
resection of the gallbladder bed to a routine
extended right hepatectomy.
 standard resection is an anatomic resection of
segments IVb and V
 If a segment IVb/V resection would result in an
inadequate margin, an extended right hepatectomy
may be required.

29. Lymph Node Dissection Steps
Kocherization of the duodenum and dissection of the
lymph nodes behind the pancreatic head and the
duodenum

30.  Exposure of the common hepatic artery
 Dissection along the hepatic artery branches

31.  Skeletonization of the common bile duct

32. PORT SITE RECURRENCES
 exacerbated by spillage of bile or stones inside the
peritoneal cavity
 At a median of 180 days, 17% of patients were
diagnosed with laparoscopic port site recurrences.
(Paolucci et al, 1999).
 surgeons recommend port site excision during
reoperation for gallbladder cancer
 If port site recurrence  not to include empiric
resection of port sites during reexploration for
gallbladder cancer

33. ADJUVANT THERAPY
 Studies of adjuvant radiation therapy over the last
few decades have suggested modest benefits for
patients with gallbladder cancer
 No difference in 5-year survival, compared to those
who did not receive adjuvant radiotherapy
 contemporary drug gemcitabine was compared to
best supportive care and 5-FU in a three-arm trial for
patients with unresectable gallbladder cancer

34. The END