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Gallbladder carcinoma

Section: Hepatobiliary Sub-section: Biliary Curriculum: Curriculum, page 88

Definition

Carcinoma arising from the gallbladder epithelium

Epidemiology

  • Most common bilary cancer
  • Incidence 1/100,000.
  • F : M – 3 : 1

Risk factors

  • Inflammatory
    • Chronic inflammation leading to high cell turnover
    • Infections
  • Calculus or calcification:
  • Anatomical
    • Cholecystoenteric fistula
    • Anomalous pancreatico-biliary junction
    • Choledochal cyst
  • Neoplastic
    • Gallbladder polyp (adenoma to carcinoma sequence)
    • Malignant potential - Risk: size >1cm, age >60, sessile, Asian, PSC
    • Cholesterol polpy – most common type of polyp.
      • Do not develop into cancer. Due to deposits of cholesterol.

Pathology

  • Majority adenocarcinoma
    • Papillary subtype more favourable
  • Other subtypes e.g. adenosquamous or squamous cell

Clinical

  • Mostly advanced stage (75% unresectable)
  • 2/3 abdo pain/biliary colic
  • 1/3 jaundice – usually advanced sign
  • 10% weight loss
  • For early stage
    • Pathological examination of cholecystectomy presumed biliary colic.
  • Imaging – suspicious for mass or irregularity of GB wall.

Investigations

  • Multiphase CT CAP – to evaluate extent of local disease and mets
  • MRCP C+ useful for hepatic invasion, vascular involvement and LNs
  • Duplex USS – may add info on extent of invasion into liver, biliary structures and vascular.
  • PET/CT – distant mets

Stage

8th Addition AJCC

  • Layers
    • Mucosa (surface epithelium and lamina propria)
      • The gallbladder does not have a muscularis mucosae or submucosa
    • A layer of loose smooth muscle bundles (tunica muscularis)
    • Perimuscular connective tissue (subserosa or adventitia)
    • (on the free surface) the serosa.
T1aLimited to lamina propria
T1bInvaded into tunica muscularis
T2Invaded into perimuscular connective tissue
T3Penetrated serosa and directly invade liver or another single extrahepatic organ
T4Locally advanced. Main portal vein, hepatic artery or multiple extrahepatic organs
N1Nodes along cystic duct, CBD, hepatic artery or portal vein
N2Nodes in periaortic, pericaval, SMA or coeliac
M1Distant mets

Management

Pre-operative considerations

  • Preop biopsy not required – false negative and risk of tumour seeding into peritoneum
  • Consider staging lap
  • Contraindications:
    • Distant spread
    • Involvement of vasculature or biliary tree that would preclude complete resection
    • Distant lymph nodes

Operative approach

  • Margin negative resection – R0 is better survival
    • ≥T1b, extended cholecystectomy including resection of segments IVb and V along with portal lymph node dissection.
    • If unable to obtain negative margin, may need to extend beyond this (major hepatectomy or bile duct resection)
  • Portal lymphadenectomy
    • Diagnostic information may help determine adjuvant therapy
    • Removal of nodes in porta hepatis, gastrohepatic ligament and retroduodenal space.
      • Prior to resection, need to check for metastatic disease in the LN that would preclude resection.
  • Cystic duct margin should be evaluated with frozen section to confirm R0 - bile duct only excised if involved

Operative approach by T stage

  • T1a
    • Cured by simple cholecystectomy
  • T1b
    • Cholecystectomy can be curative in up to 85% of case
    • Nodal metastases have been found in up to 12%
    • Extended resection recommend on a case by case basis
  • T2
    • Stage with CTCAP and liver MRI, consider staging laparoscopy
    • Eextended cholecystectomy within 2 months of index op
      • Dissection of pericholedochal, periportal, hepatoduodenal, right coeliac and posterior pancreaticoduodenal nodes
      • Send cystic duct margin for frozen section – if involved, do extrahepatic bile duct resection & Roux-en-Y hepaticojejunostomy if necessary to achieve R0
      • 2cm of Liver Parenchyma from cystic bed – variable recommendations – just need to achieve clear margins
  • Aim to achieve >6 nodes from lymphadenectomy
    • Total harvest associated with improved survival
      • Not as function of resected disease per se, more that it reduces chance of understaging (get more nodes, more likely to find a positive one) and thus direct pt to adjuvant therapies
    • Total node count >6 only has improved DFS in node negative disease – any positive node confers poor prognosis
  • T3/4
    • Locally advanced
    • As in cholangiocarcinoma, the extent of resection should be dictated by what is necessary to achieve a negative margin
    • Many cases will require division of left hepatic duct and excision of biliary confluence along with extended right hepatectomy.
    • In absence of right portal pedicle involvement, then amenable to resections of segment IVb and V.

Intra-operative findings of GB cancer

  • Frozen section
  • Oncological resection
  • HPB surgeon
  • Delayed radical and appropriate resection does not negatively influence the patient’s outcome
  • If not too late, leave GB in situ and refer to specialist centre (If experienced HPB surgeon ie not in the exam, do cholecystectomy with frozen section of GB. If positive, do extended resection

Extent of resection

  • The first RCT comparing segment IVb/V vs wedge resection (Annals of Surgery, 2025, n=163) found no difference in DFS, OS, morbidity or R0 rates — wedge had less blood loss and shorter operative time
  • https://pubmed.ncbi.nlm.nih.gov/40996213/
  • Singh et al

Adjuvant

  • Limited data
  • NCCN guidelines recommend adjuvant Capecitabine
    • BILCAP trial

Prognosis

T1a/b with complete resection = excellent

T2 with R0 = 60% 5 yr survival

T3 = 20% 5YS

T4 = months

Graph View

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