Copyright ©The Author(s) 2021.
World J Gastrointest Oncol. Oct 15, 2021; 13(10): 1317-1335
Published online Oct 15, 2021. doi: 10.4251/wjgo.v13.i10.1317
Table 1 Risk factors for gallbladder cancer[35]
Patient predispositionEnvironmental factorsPatient factors/conditions
Female sexChronic bacterial infectionsDiabetes
AgeAflatoxinsHigh body mass index
Race/ethnicityOchratoxinPrimary sclerosing cholangitis
Genetics (variants)ArsenicPorcelain gallbladder
Liver flukeGallbladder polyps
GeographyCrohn’s disease
Anomalous biliary ductal insertion
Sjogren’s syndrome
Table 2 Staging of gallbladder cancer
T stage
Primary tumor
TxPrimary tumor cannot be assessed
T0No evidence of primary tumor
TisCarcinoma in situ
T1Tumor invades the lamina propria or muscular layer
T1aTumor invades lamina propria
T1bTumor invades muscle layer
T2Tumor invades the perimuscular connective tissue on the peritoneal side, without involvement of the serosa (visceral peritoneum) or tumor invades the perimuscular connective tissue on the hepatic side, with no extension into the liver
T2aTumor invades the perimuscular connective tissue on the peritoneal side, without involvement of the serosa (visceral peritoneum)
T2bTumor invades the perimuscular connective tissue on the hepatic side, with no extension into the liver
T3Tumor perforates the serosa (visceral peritoneum) and/or directly invades the liver and/or other adjacent organ or structure, such as the stomach, duodenum, colon, pancreas, omentum, or extrahepatic bile ducts
T4Tumor invades main portal vein or hepatic artery or invades two or more extrahepatic organs or structures
N stageRegional lymph nodes
NXRegional lymph nodes cannot be assessed
N0No regional lymph node metastasis
N1Metastasis to one to three regional lymph nodes
N2Metastasis to four or more regional lymph nodes
M stageDistant metastasis
M0No distant metastasis
M1Distant metastasis
Table 3 Cancer stage grouping
0TisN0M0Cancer in situ
IT1N0M0Tumor is only in the gallbladder and has not spread
IIT2N0M0Tumor has extended to the perimuscular connective tissue but has not spread elsewhere
IIIAT3N0M0Tumor has spread beyond the gallbladder but not to nearby arteries or veins. It has not spread to any lymph nodes or other parts of the body
IIIBT1-3N1M0Tumor of any size has spread to nearby lymph nodes but not to nearby arteries and/or veins or to other parts of the body
IVAT4N0 or N1M0Tumor has spread to nearby arteries, veins, and/or nearby lymph nodes, but it has not spread to other parts of the body
IVBAny TAny NM1Any tumor that has spread to other parts of the body
Any TN2M0Any tumor that has distant lymph node spread, even if it has not spread to distant organs
Table 4 Surgical procedures performed for gallbladder cancer
Curative procedures
Simple cholecystectomyDissection, ligation, and transection of cystic duct and artery at the level of Calot triangle and dissection of the cystic plateBenign gallbladder conditions, gallbladder polyps, porcelain gallbladder, GBC (T0, Tis, and T1a)
Extended cholecystectomySimple cholecystectomy + hepatic wedge resection at the level of gallbladder fossa (2-3 cm in depth)T1b and higher GBC
IVb/V hepatic bisegmentectomyResection of liver segments IVb and V en bloc with the gallbladder with intra-parenchymal transection of the middle hepatic veinGBC invading liver parenchyma
Extended liver resectionsMost commonly right hepatectomy, rarely left hepatectomyGBC invading structures of porta hepatis
Bile duct resectionResection of the extrahepatic bile duct + Roux-en-Y hepaticojejunostomyGBC invading extrahepatic bile ducts or positive cystic duct margin at frozen section pathology
LymphadenectomyRemoval of lymph nodes from N1 and N2 zonesT1b and higher GBC, N+ GBC
Multivisceral resectionMay involve right colectomy, pancreaticoduodenectomy, resection of abdominal wall, etc.Locally advanced GBC
Palliative procedures
Biliodigestive anastomosesRoux-en-Y hepaticojejunostomyLocally advanced unresectable GBC presenting with jaundice
Digestive anastomosesGastro-enteric anastomosis, ileo-transverse colon anastomosisLocally advanced unresectable GBC presenting with intestinal obstruction
Table 5 Historical prognosis of gallbladder cancer
Survival time (mo)
Gall et al[96], 19911131970-1989Curative resection42
Non-curative resection (metastasis +)12.5
Cubertafond et al[97], 19947241980-1989Curative resection 25%Overall 3
Non-curative resection 75%
Jarnagin et al[98], 2003971990-2001Curative resection31.3
Hawkins et al[29], 20042401995-2002Curative resection34
Non-curative resection8
Nishio et al[99], 20071661977-2004Curative resection12
Non-curative resection6
Duffy et al[28], 20082061995-2005Overall10.3
Incidental GBC15.7
Curative surgery30.3
Curative surgery + adjuvant therapy23.4
D’Hondt et al[25], 20131021998-2008Overall7.2
Incidental GBC25.8
Non-Incidental GBC4.4
Butte et al[100], 20112611999-2007OverallDSS 16.97
Ito et al[55], 20111221992-2007R0 resectionDSS 41
Butte et al[101], 20141351998-2009OverallDFS 25.9
Residual disease11.2
Non-residual disease93.4
Ethun et al[18], 20174492000-2014Incidental GBC27.6
Zhang et al[102], 201814222010-2014Resection13
Yu et al[86], 2019812006-2015T3 Anatomical resection54
T3 Wedge resection49
Ref.nYearStatusSurvival rate (%)
Ogura et al[103], 199116861979-1988Radical resection66.2 (3 yr) 50.7 (5 yr)
Non-radical resection14.1 (3 yr) 6.2 (5 yr)
Cubertafond et al[97], 19947241980-1989Curative resection 25%Overall 14 (1 yr) 5 (5 yr)
Non-curative resection 75%
Carriaga and Henson[104], 199544121973-1987Overall12.3 (5 yr)
Bartlett et al[105], 19961491985-1993Resection51 (5 yr)
Fong et al[17], 20004101986-2000Resection38 (5 yr)
Non-resection4 (5 yr)
Nakeeb et al[106], 20021401990-2001Resection31 (5 yr)
Pawlik et al[107], 20071151984-2006Resection12 (5 yr)
Kayahara and Nagakawa[57], 200747701988-1997Overall39 (5 yr)
Shih et al[108], 20071071995-2004Overall15 (5 yr)
Incidental GBC33 (5 yr)
D’Angelica et al[59], 20091091988-2002Overall42 (5 yr)
Fuks et al[15], 20112181998-2008Incidental GBC41 (5 yr)
Hari et al[109], 201311151988-2008Cholecystectomy50 (5 yr)
Cholecystectomy + LN dissection70 (5 yr)
Radical cholecystectomy79 (5 yr)
Barreto et al[110], 20141632003-2010OverallDFS 79.6 (2 yr)
Shindoh et al[42], 20152521981-2011T242.6 (5 yr)