2. INTRODUCTION
• Rare – Most common biliary tract malignancy
• F > M (3-4 : 1)
• Higher rate of cholelithiasis and inflammation
• Generally, disease of older age (6th-7th decade)
3. • Aggressive malignant disease
• Poor prognosis
• Late presentation
• Higher incidence in India and Pakistan
4. Etiology
Chronic inflammation
• Cholelithiasis
• 75-90% of Ca GB associated with GB
stones
• Incidence of Ca GB – 0.3-3%
• ABPJ
• PSC
• Biliary-enteric fistulae
• Typhoid infection
• Porcelain GB
• Calcification due to chronic
inflammation
• GB polyp
• > 10 mm
5. Anatomic considerations
• GB – partially intraperitoneal – attached to undersurface
of liver on segments IVb andV
• On liver side – no peritoneal covering, but fibrous lining known as
cystic plate
• During cholecystectomy – plane between muscularis of GB and cystic
plate dissected – inadequate for malignancy
6.
7. • Segment IVb andV resection – adequate for tumors of fundus and
body
• Tumors of infundibulum and cystic duct – may require bile duct
resections or major hepatic resections
9. Pattern of spread
• Lymphatics
• Hematogenously
• Into peritoneal cavity
• Along biopsy or surgical wound tracts
10. • Ca GB seems to invade and metastasize early – due to anatomy
• Thin wall
• Narrow lamina propria
• Single muscular layer
• No serosal covering between GB and liver
11. • Thin wall – early hematogenous and lymphatic spread
• Once through muscular layer – access to major lymphatics and
vascular channels – early dissemination
12. Clinical presentation
• Varies depending on geographic location
• Study (Duffy et al, 2008) of 435 patients with Ca GB treated at MSKCC
during 10-year period
• 47% discovered incidentally at routine laparoscopic cholecystectomy
• 53% presented with locally advanced (16%) or disseminated (37%) disease
13. • Asymptomatic in early stages
• Symptomatic – similar presentation to biliary colic or chronic
cholecystitis
• Constant RUQ pain
• Jaundice – usually representative of locally advanced disease
• Weight loss
• Anemia
14. Presentation
• Three common clinical scenarios
1. Identified by final pathology after routine cholecystectomy
2. Discovered intraoperatively
3. Suspected before surgery
15. Laboratory investigation
• Generally not helpful except for typical signs of advanced disease
• Anemia
• Hypoalbuminemia
• Leukocytosis
• Elevated ALP or bilirubin
16. Tumor markers
• Only tumor markers studied
• Carcinoembryonic antigen (CEA)
• CarbonicAnhydrase 19-9 (CA 19-9)
• Elevated CEA
• Specificity 90%
• Sensitivity 50%
• Elevated CA 19-9 – more consistent marker
• Sensitivity and specificity ~75% if >20 U/mL
17. Tumor markers
Helpful in following patient for recurrence if elevated before treatment
and normalize after treatment
18. Radiologic investigation
• Ultrasonography
• Excellent imaging modality for GB
• Direct extension of Ca GB
• Limitation in identifying LN metastases
• Most common finding – Heterogeneous mass replacing all or part of GB
19. Cross-sectional imaging
CT or MRI
• Important for preoperative assessment
• Local extent and metastases
• Most common finding – mass involving all or part of GB
• Assessment of lymph node
• Size >1 cm
• Ring-like heterogeneous enhancement 80% accuracy
20. • CT
• 71-84% accurate inT-staging
• T1 vsT2 : 79%
• T2 vsT3 : 93%
• T3 vsT4 : 100%
• MRI
• Utility improved in recent years
• Sensitivity 70-100% for hepatic invasion & 60-75% for LN metastases
• No added information than CT
21. • First test – USG
• Suspicion or proven malignancy – CT or MRI
• Role of PET
• In searching metastatic disease when CT or MRI provides equivocal information
Blumgart's Surgery of the Liver, Biliary Tract, and Pancreas, 6th edition
26. Polyps
• Polyp with malignant potential – Adenomatous polyps
• Most common polyp – Cholesterol polyp – no malignant potential
• USG
• Diagnostic modality of choice to measure and characterize polyps
• Any suspicion of malignancy – Cross-sectional imaging
27. • Polyps found in context of abdominal symptoms
• Another cause of pain is sought
• No other cause found – Cholecystectomy
• Polyps <1cm
• USG follow up at 12-month intervals for 2-3 years
• No additional imaging if polyp stable and no new or suspicious symptoms
28. • Polyps >1cm
• Cholecystectomy
• Laparoscopic method if no suspicion of malignancy and availability of frozen
section biopsy
• Low threshold for open conversion
30. 1. Incidental finding at surgery
• If expertise available – definitive resection
• Radical cholecystectomy with segments IV b andV with lymphadenectomy
• If diagnosis not clear – frozen section biopsies
31.
32. 2. Incidental finding on pathology
• Pathologic re-review by hepatobiliary pathology expert
• Diagnostic laparoscopy – but low yield unless advanced disease
• Cross-sectional imaging of chest, abdomen and pelvis
33. 2. Incidental finding on pathology contd..
• Initial exploration
• To rule out distant LN metastases in celiac axis or aortocaval groove
• If present – defer surgery
• Hepatic resectin of IV b andV or extended resections
• Lymphadenectomy
• Port site resection – not effective – surrogate marker of underlying
disseminated disease
34.
35. Neoadjuvant therapy
• Outside the setting of clinical trial, neoadjuvant therapy – not
recommended for surgically resectable ca GB
Gallbladder Cancer in the 21st Century, Rani Kanthan, 2015
36. 3. Mass on imaging
• Staging with cross-sectional imaging of chest, abdomen and pelvis
• Biopsy not necessary – definitive resection
• Diagnostic laparoscopy – recommended
• Diagnosis not clear – cholecystectomy – frozen section biopsy –
followed by definitive resection if pathology report confirms
malignancy
37.
38. Terms
• Wedge resection – Liver resection around GB taking 2 cm margin
• Extended/Radical cholecystectomy – Resection of segments IV b andV
with dissection of LN within hepatoduodenal ligament
• Extended radical cholecystectomy – Resection of lymphatics within
hepatoduodenal ligament, posterosuperior head of pancreas with
dissection around portal vein, and common hepatic artery with GB, rim of
liver and extrahepatic bile duct
• Extended right hepatectomy – Resection of segments 4,5,6,7,8
39. Extent of resection
• T1a – Simple cholecystectomy
• T1b – liver resection and lymph node dissection
• T2,T3 – complete resection of tumor en bloc with segments IVb andV
• If tumor invasion of hepatic inflow vascular structures – extended right
hepatectomy
• LN dissection of hepatoduodenal ligament
42. Liver resection
• Goal:To ensure a margin of resection ~1-2 cm
• Standard resection – anatomic resection of segments IV b andV
• But smaller wedge resection for early-stage cancers with no radiographic
disease in liver
• Inflow pedicles to segments IV b andV
• Generally taken within liver substance
• But segment IV b pedicles can be dissected in umbilical fissure –
divided before parenchymal dissection
43. • Extended right hepatectomy
• Large tumors invading right portal pedicle
• Tumors of lower end of GB encroaching porta hepatis – may require bile duct
resection
• Isolated invasion of local organs (stomach, duodenum, and colon)
• Local resection
44. Lymph node dissection
• First maneuver – mobilization of duodenum to assess aortocaval and
retropancreatic LNs – assessment of celiac node
• Suspicious – Frozen section analysis
• If positive –Termination of procedure
• Regional lymphadenectomy
• All N1 LNs
• American Joint Committee on Cancer (AJCC) recommendation
• Resection of a minimum of three regional lymph nodes
45.
46. Adjuvant therapy
• Meta-analysis favors adjuvant therapy –
• High risk patients – node-positive gallbladder cancer
• Question remains unsolved in low risk patients
• ChemoradiotherapyVS chemotherapy alone – unsolved
Gallbladder Cancer in the 21st Century, Rani Kanthan, 2015
47. • NCCN
• Adjuvant fluoropyrimidine chemoradiation or
• Fluoropyrimidine or gemcitabine chemotherapy
For >T1N0 following curative surgery
• European Society of Medical Oncology (ESMO) guidelines
• Also suggest postoperative chemoradiotherapy in patients with high risk
gallbladder cancer
• Optimal adjuvant therapy – unknown
• Though six months duration of adjuvant therapy can be considered
Gallbladder Cancer in the 21st Century, Rani Kanthan, 2015
50. Targeted therapies
• Common mutations
• KRAS 10-67%
• EGFR 63%
• BRAF 0-33%
• erbB2/HER2 16-64%
• Phase III Korean trial evaluated gemcitabine and oxaliplatin with/out
erlotinib (oral tyrosine kinase inhibitor)
• Improvement in median progression-free survival (PFS)
51. • VEGF – overexpressed in biliary tract cancers
• Proposed as therapeutic target
• Efficacy of bevacizumab in combination of erlotinib – assessed in a
phase II trial
52. Radiation
• Poorly described in literature
• Conflicting and largely disappointing results
• Combination of EBRT with fluorouracil – encouraging results
• But further investigation required
• External radiation – may be considered in palliative patients
53. Conclusion
• Ca GB – high case fatality rate
• Most ca GB – discovered incidentally or present as advanced stage
disease
• Adenocarcinomas – majority of ca GB
• Surgery – only curative therapy, however, at diagnosis, ~20% are
candidates for curative surgery
• Extent of surgical resection depends onTNM stage
54. • Regional nodal status andT status – two most important prognostic
factors
• Role of adjuvant therapy – not well defined
• T2 or higher or node positive disease – 6 months of gemcitabine or
fluoropyrimidine-based chemotherapy considered
• Due to high risk of recurrence
• Targeted therapy – limited role
• “Orphan disease”
Anatomy of the plate system. A, Cystic plate, above the gallbladder. B, Hilar plate, above the biliary confluence and at the base of segment IV. C, Umbilical plate, above the umbilical portion of the portal vein. Large, curving arrows indicate the plane of dissection of the cystic plate during cholecystectomy and of the hilar plate during approaches to the left hepatic duct.
Lymphatic channels from the gallbladder lead first to the cystic and pericholedochal nodes.
From these nodes, the primary drainage areas are the retroportal and posterosuperior pancreaticoduodenal nodes.
From these lower portal areas, the lymphatics course to the celiac, superior mesenteric, and interaortocaval nodes.
Tumors invade the liver at a thickness where in many organs a second muscular layer would be encountered.
Neoadjuvant therapy – If evidence of locoregionally advanced disease (big mass invading liver and/or nodal disease, including cystic duct node positive) – to rule out rapid progression and avoid futile surgery
Goal – because no serosal surface on liver side of GB
Though targeted therapies appear promising in the management of Ca GB, their definitive recommendation is not provided till date