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Published in: Digestive Diseases and Sciences 9/2013

01-09-2013 | Review

Key Factors Influencing Prognosis in Relation to Gallbladder Cancer

Authors: Charles Henry Caldow Pilgrim, Ryan T. Groeschl, Kiran K. Turaga, T. Clark Gamblin

Published in: Digestive Diseases and Sciences | Issue 9/2013

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Abstract

Introduction

The 5-year survival of patients with gallbladder cancer remains low. However, patients can be stratified into prognostic categories based on established factors such as T, N, and R status. New concepts regarding prognostic significance of lymph node disease, the importance of residual gallbladder fossa disease, and the gravity of presentation with jaundice are reviewed. In addition, a number of new prognostic factors proposed in recent years are considered.

Methods

PubMed was searched for “gallbladder cancer” with builder “date-completion” 2008 to present. A total of 1,490 articles were screened from which 168 were retrieved. From this, 40 articles specifically related to prognosis form the basis for this review.

Discussion

Key factors of prognostic significance remain T and N stage and R0 resection. Residual disease either in the gallbladder fossa, lymph nodes, or cystic duct margin dictates hepatectomy, lymphadenectomy and bile duct resection, respectively. Adequate lymphadenectomy requires removal of six nodes, and hepatectomy must be sufficient to achieve R0. Subtleties regarding lymph node ratio, significance of pathological features such as dedifferentiation, and budding may hold value for stratifying patients with early stage disease, but require further investigation.
Literature
1.
go back to reference Butte JM, Matsuo K, Gonen M, et al. Gallbladder cancer: differences in presentation, surgical treatment, and survival in patients treated at centers in three countries. J Am Coll Surg. 2011;212:50–61.PubMedCrossRef Butte JM, Matsuo K, Gonen M, et al. Gallbladder cancer: differences in presentation, surgical treatment, and survival in patients treated at centers in three countries. J Am Coll Surg. 2011;212:50–61.PubMedCrossRef
2.
go back to reference Edge SB, American Joint Committee on Cancer, American Cancer Society. AJCC Cancer Staging Handbook: From the AJCC Cancer Staging Manual. New York: Springer; 2010. Edge SB, American Joint Committee on Cancer, American Cancer Society. AJCC Cancer Staging Handbook: From the AJCC Cancer Staging Manual. New York: Springer; 2010.
4.
go back to reference Greene FL, American Joint Committee on Cancer, American Cancer Society. AJCC Cancer Staging Handbook: From the AJCC Cancer Staging Manual. New York: Springer; 2002. Greene FL, American Joint Committee on Cancer, American Cancer Society. AJCC Cancer Staging Handbook: From the AJCC Cancer Staging Manual. New York: Springer; 2002.
5.
go back to reference House MG, Gonen M, Jarnagin WR, et al. Prognostic significance of pathologic nodal status in patients with resected pancreatic cancer. J Gastrointest Surg. 2007;11:1549–1555.PubMedCrossRef House MG, Gonen M, Jarnagin WR, et al. Prognostic significance of pathologic nodal status in patients with resected pancreatic cancer. J Gastrointest Surg. 2007;11:1549–1555.PubMedCrossRef
6.
go back to reference Pawlik TM, Gleisner AL, Cameron JL, et al. Prognostic relevance of lymph node ratio following pancreaticoduodenectomy for pancreatic cancer. Surgery. 2007;141:610–618.PubMedCrossRef Pawlik TM, Gleisner AL, Cameron JL, et al. Prognostic relevance of lymph node ratio following pancreaticoduodenectomy for pancreatic cancer. Surgery. 2007;141:610–618.PubMedCrossRef
7.
go back to reference Ito H, Ito K, D’Angelica M, et al. Accurate staging for gallbladder cancer: implications for surgical therapy and pathological assessment. Ann Surg. 2011;254:320–325.PubMedCrossRef Ito H, Ito K, D’Angelica M, et al. Accurate staging for gallbladder cancer: implications for surgical therapy and pathological assessment. Ann Surg. 2011;254:320–325.PubMedCrossRef
8.
go back to reference Negi SS, Singh A, Chaudhary A. Lymph nodal involvement as prognostic factor in gallbladder cancer: location, count or ratio? J Gastrointest Surg. 2011;15:1017–1025.PubMedCrossRef Negi SS, Singh A, Chaudhary A. Lymph nodal involvement as prognostic factor in gallbladder cancer: location, count or ratio? J Gastrointest Surg. 2011;15:1017–1025.PubMedCrossRef
9.
go back to reference Shirai Y, Sakata J, Wakai T, et al. Assessment of lymph node status in gallbladder cancer: location, number, or ratio of positive nodes. World J Surg Oncol. 2012;10:87.PubMedCrossRef Shirai Y, Sakata J, Wakai T, et al. Assessment of lymph node status in gallbladder cancer: location, number, or ratio of positive nodes. World J Surg Oncol. 2012;10:87.PubMedCrossRef
10.
go back to reference Mayo SC, Shore AD, Nathan H, et al. National trends in the management and survival of surgically managed gallbladder adenocarcinoma over 15 years: a population-based analysis. J Gastrointest Surg. 2010;14:1578–1591.PubMedCrossRef Mayo SC, Shore AD, Nathan H, et al. National trends in the management and survival of surgically managed gallbladder adenocarcinoma over 15 years: a population-based analysis. J Gastrointest Surg. 2010;14:1578–1591.PubMedCrossRef
11.
go back to reference Downing SR, Cadogan KA, Ortega G, et al. Early-stage gallbladder cancer in the surveillance, epidemiology, and end results database: effect of extended surgical resection. Arch Surg. 2011;146:734–738.PubMedCrossRef Downing SR, Cadogan KA, Ortega G, et al. Early-stage gallbladder cancer in the surveillance, epidemiology, and end results database: effect of extended surgical resection. Arch Surg. 2011;146:734–738.PubMedCrossRef
12.
go back to reference Sakata J, Shirai Y, Wakai T, et al. Number of positive lymph nodes independently determines the prognosis after resection in patients with gallbladder carcinoma. Ann Surg Oncol. 2010;17:1831–1840.PubMedCrossRef Sakata J, Shirai Y, Wakai T, et al. Number of positive lymph nodes independently determines the prognosis after resection in patients with gallbladder carcinoma. Ann Surg Oncol. 2010;17:1831–1840.PubMedCrossRef
13.
go back to reference Sasaki E, Nagino M, Ebata T, et al. Immunohistochemically demonstrated lymph node micrometastasis and prognosis in patients with gallbladder carcinoma. Ann Surg. 2006;244:99–105.PubMedCrossRef Sasaki E, Nagino M, Ebata T, et al. Immunohistochemically demonstrated lymph node micrometastasis and prognosis in patients with gallbladder carcinoma. Ann Surg. 2006;244:99–105.PubMedCrossRef
14.
go back to reference Tanabe M, Endo I, Masunari H, et al. Is lymph-node micrometastasis in gallbladder cancer a significant prognostic factor? Hepatogastroenterology. 2012;59:31–35.PubMed Tanabe M, Endo I, Masunari H, et al. Is lymph-node micrometastasis in gallbladder cancer a significant prognostic factor? Hepatogastroenterology. 2012;59:31–35.PubMed
15.
go back to reference Bartlett DL, Fong Y, Fortner JG, et al. Long-term results after resection for gallbladder cancer. Implications for staging and management. Ann Surg. 1996;224:639–646.PubMedCrossRef Bartlett DL, Fong Y, Fortner JG, et al. Long-term results after resection for gallbladder cancer. Implications for staging and management. Ann Surg. 1996;224:639–646.PubMedCrossRef
16.
go back to reference Lowe K, Khithani A, Mejia A, et al. All lymph node positive patients are not equal: a new paradigm in gallbladder cancer. Am Surg. 2012;78:147–148.PubMed Lowe K, Khithani A, Mejia A, et al. All lymph node positive patients are not equal: a new paradigm in gallbladder cancer. Am Surg. 2012;78:147–148.PubMed
17.
go back to reference Jensen EH, Abraham A, Jarosek S, et al. Lymph node evaluation is associated with improved survival after surgery for early stage gallbladder cancer. Surgery. 2009;146:706–711; discussion 711–703. Jensen EH, Abraham A, Jarosek S, et al. Lymph node evaluation is associated with improved survival after surgery for early stage gallbladder cancer. Surgery. 2009;146:706–711; discussion 711–703.
18.
go back to reference Ito H, Matros E, Brooks DC, et al. Treatment outcomes associated with surgery for gallbladder cancer: a 20-year experience. J Gastrointest Surg. 2004;8:183–190.PubMedCrossRef Ito H, Matros E, Brooks DC, et al. Treatment outcomes associated with surgery for gallbladder cancer: a 20-year experience. J Gastrointest Surg. 2004;8:183–190.PubMedCrossRef
19.
go back to reference Aramaki M, Matsumoto T, Shibata K, et al. Factors influencing recurrence after surgical treatment for T2 gallbladder carcinoma. Hepatogastroenterology. 2004;51:1609–1611.PubMed Aramaki M, Matsumoto T, Shibata K, et al. Factors influencing recurrence after surgical treatment for T2 gallbladder carcinoma. Hepatogastroenterology. 2004;51:1609–1611.PubMed
20.
go back to reference de Aretxabala X, Roa I, Hepp J, et al. Early gallbladder cancer: is further treatment necessary? J Surg Oncol. 2009;100:589–593.PubMedCrossRef de Aretxabala X, Roa I, Hepp J, et al. Early gallbladder cancer: is further treatment necessary? J Surg Oncol. 2009;100:589–593.PubMedCrossRef
21.
go back to reference Lendoire JC, Gil L, Duek F, et al. Relevance of residual disease after liver resection for incidental gallbladder cancer. HPB (Oxford). 2012;14:548–553.CrossRef Lendoire JC, Gil L, Duek F, et al. Relevance of residual disease after liver resection for incidental gallbladder cancer. HPB (Oxford). 2012;14:548–553.CrossRef
22.
go back to reference Fetzner UK, Holscher AH, Stippel DL. Regional lymphadenectomy strongly recommended in T1b gallbladder cancer. World J Gastroenterol. 2011;17:4347–4348.PubMedCrossRef Fetzner UK, Holscher AH, Stippel DL. Regional lymphadenectomy strongly recommended in T1b gallbladder cancer. World J Gastroenterol. 2011;17:4347–4348.PubMedCrossRef
23.
go back to reference Pawlik TM, Gleisner AL, Vigano L, et al. Incidence of finding residual disease for incidental gallbladder carcinoma: implications for re-resection. J Gastrointest Surg. 2007;11:1478–1486; discussion 1486–1477. Pawlik TM, Gleisner AL, Vigano L, et al. Incidence of finding residual disease for incidental gallbladder carcinoma: implications for re-resection. J Gastrointest Surg. 2007;11:1478–1486; discussion 1486–1477.
24.
go back to reference Choi SB, Han HJ, Kim CY, et al. Surgical outcomes and prognostic factors for T2 gallbladder cancer following surgical resection. J Gastrointest Surg. 2010;14:668–678.PubMedCrossRef Choi SB, Han HJ, Kim CY, et al. Surgical outcomes and prognostic factors for T2 gallbladder cancer following surgical resection. J Gastrointest Surg. 2010;14:668–678.PubMedCrossRef
25.
go back to reference Chakravarty KD, Yeh CN, Jan YY, Chen MF. Factors influencing long-term survival in patients with T3 gallbladder adenocarcinoma. Digestion. 2009;79:151–157.PubMedCrossRef Chakravarty KD, Yeh CN, Jan YY, Chen MF. Factors influencing long-term survival in patients with T3 gallbladder adenocarcinoma. Digestion. 2009;79:151–157.PubMedCrossRef
26.
go back to reference Nakata T, Kobayashi A, Miwa S, et al. Impact of tumor spread to the cystic duct on the prognosis of patients with gallbladder carcinoma. World J Surg. 2007;31:155–161; discussion 162–153. Nakata T, Kobayashi A, Miwa S, et al. Impact of tumor spread to the cystic duct on the prognosis of patients with gallbladder carcinoma. World J Surg. 2007;31:155–161; discussion 162–153.
27.
go back to reference Pawlik TM, Choti MA. Biology dictates prognosis following resection of gallbladder carcinoma: sometimes less is more. Ann Surg Oncol. 2009;16:787–788.PubMedCrossRef Pawlik TM, Choti MA. Biology dictates prognosis following resection of gallbladder carcinoma: sometimes less is more. Ann Surg Oncol. 2009;16:787–788.PubMedCrossRef
28.
go back to reference Araida T, Higuchi R, Hamano M, et al. Should the extrahepatic bile duct be resected or preserved in R0 radical surgery for advanced gallbladder carcinoma? Results of a Japanese Society of Biliary Surgery Survey: a multicenter study. Surg Today. 2009;39:770–779.PubMedCrossRef Araida T, Higuchi R, Hamano M, et al. Should the extrahepatic bile duct be resected or preserved in R0 radical surgery for advanced gallbladder carcinoma? Results of a Japanese Society of Biliary Surgery Survey: a multicenter study. Surg Today. 2009;39:770–779.PubMedCrossRef
29.
go back to reference Bickenbach KA, Shia J, Klimstra DS, et al. High-grade dysplasia of the cystic duct margin in the absence of malignancy after cholecystectomy. HPB (Oxford). 2011;13:865–868.CrossRef Bickenbach KA, Shia J, Klimstra DS, et al. High-grade dysplasia of the cystic duct margin in the absence of malignancy after cholecystectomy. HPB (Oxford). 2011;13:865–868.CrossRef
30.
go back to reference Hawkins WG, DeMatteo RP, Jarnagin WR, et al. Jaundice predicts advanced disease and early mortality in patients with gallbladder cancer. Ann Surg Oncol. 2004;11:310–315.PubMedCrossRef Hawkins WG, DeMatteo RP, Jarnagin WR, et al. Jaundice predicts advanced disease and early mortality in patients with gallbladder cancer. Ann Surg Oncol. 2004;11:310–315.PubMedCrossRef
31.
go back to reference Regimbeau JM, Fuks D, Bachellier P, et al. Prognostic value of jaundice in patients with gallbladder cancer by the AFC-GBC-2009 study group. Eur J Surg Oncol. 2011;37:505–512.PubMedCrossRef Regimbeau JM, Fuks D, Bachellier P, et al. Prognostic value of jaundice in patients with gallbladder cancer by the AFC-GBC-2009 study group. Eur J Surg Oncol. 2011;37:505–512.PubMedCrossRef
32.
go back to reference Varma V, Gupta S, Soin AS, Nundy S. Does the presence of jaundice and/or a lump in a patient with gall bladder cancer mean that the lesion is not resectable? Dig Surg. 2009;26:306–311.PubMedCrossRef Varma V, Gupta S, Soin AS, Nundy S. Does the presence of jaundice and/or a lump in a patient with gall bladder cancer mean that the lesion is not resectable? Dig Surg. 2009;26:306–311.PubMedCrossRef
33.
go back to reference Kai K, Kohya N, Kitahara K, et al. Tumor budding and dedifferentiation in gallbladder carcinoma: potential for the prognostic factors in T2 lesions. Virchows Archiv. 2011;459:449–456.PubMedCrossRef Kai K, Kohya N, Kitahara K, et al. Tumor budding and dedifferentiation in gallbladder carcinoma: potential for the prognostic factors in T2 lesions. Virchows Archiv. 2011;459:449–456.PubMedCrossRef
34.
go back to reference Miura F, Asano T, Amano H, et al. New prognostic factor influencing long-term survival of patients with advanced gallbladder carcinoma. Surgery. 2010;148:271–277.PubMedCrossRef Miura F, Asano T, Amano H, et al. New prognostic factor influencing long-term survival of patients with advanced gallbladder carcinoma. Surgery. 2010;148:271–277.PubMedCrossRef
35.
go back to reference Murakami Y, Uemura K, Sudo T, et al. Prognostic factors of patients with advanced gallbladder carcinoma following aggressive surgical resection. J Gastrointest Surg. 2011;15:1007–1016.PubMedCrossRef Murakami Y, Uemura K, Sudo T, et al. Prognostic factors of patients with advanced gallbladder carcinoma following aggressive surgical resection. J Gastrointest Surg. 2011;15:1007–1016.PubMedCrossRef
36.
go back to reference Kobayashi A, Oda T, Fukunaga K, et al. Invasion of the hepatic artery is a crucial predictor of poor outcomes in gallbladder carcinoma. World J Surg. 2012;36:645–650.PubMedCrossRef Kobayashi A, Oda T, Fukunaga K, et al. Invasion of the hepatic artery is a crucial predictor of poor outcomes in gallbladder carcinoma. World J Surg. 2012;36:645–650.PubMedCrossRef
37.
go back to reference Pilgrim C, Usatoff V, Evans PM. A review of the surgical strategies for the management of gallbladder carcinoma based on T stage and growth type of the tumour. Eur J Surg Oncol. 2009;35:903–907.PubMedCrossRef Pilgrim C, Usatoff V, Evans PM. A review of the surgical strategies for the management of gallbladder carcinoma based on T stage and growth type of the tumour. Eur J Surg Oncol. 2009;35:903–907.PubMedCrossRef
38.
go back to reference Steinert R, Nestler G, Sagynaliev E, et al. Laparoscopic cholecystectomy and gallbladder cancer. J Surg Oncol. 2006;93:682–689.PubMedCrossRef Steinert R, Nestler G, Sagynaliev E, et al. Laparoscopic cholecystectomy and gallbladder cancer. J Surg Oncol. 2006;93:682–689.PubMedCrossRef
39.
go back to reference Lee JM, Kim BW, Kim WH, et al. Clinical implication of bile spillage in patients undergoing laparoscopic cholecystectomy for gallbladder cancer. Am Surg. 2011;77:697–701.PubMed Lee JM, Kim BW, Kim WH, et al. Clinical implication of bile spillage in patients undergoing laparoscopic cholecystectomy for gallbladder cancer. Am Surg. 2011;77:697–701.PubMed
40.
go back to reference Maker AV, Butte JM, Oxenberg J, et al. Is port site resection necessary in the surgical management of gallbladder cancer? Ann Surg Oncol. 2012;19:409–417.PubMedCrossRef Maker AV, Butte JM, Oxenberg J, et al. Is port site resection necessary in the surgical management of gallbladder cancer? Ann Surg Oncol. 2012;19:409–417.PubMedCrossRef
41.
go back to reference Han HS, Cho JY, Yoon YS, et al. Preoperative inflammation is a prognostic factor for gallbladder carcinoma. Br J Surg. 2011;98:111–116.PubMedCrossRef Han HS, Cho JY, Yoon YS, et al. Preoperative inflammation is a prognostic factor for gallbladder carcinoma. Br J Surg. 2011;98:111–116.PubMedCrossRef
42.
go back to reference He XD, Liu W, Tao LY, et al. Gender-specific prognostic markers of patients with gallbladder cancer after surgical resection. Am Surg. 2010;76:1269–1274.PubMed He XD, Liu W, Tao LY, et al. Gender-specific prognostic markers of patients with gallbladder cancer after surgical resection. Am Surg. 2010;76:1269–1274.PubMed
43.
go back to reference Katz MH, Varadhachary GR, Fleming JB, et al. Serum CA 19–9 as a marker of resectability and survival in patients with potentially resectable pancreatic cancer treated with neoadjuvant chemoradiation. Ann Surg Oncol. 2010;17:1794–1801.PubMedCrossRef Katz MH, Varadhachary GR, Fleming JB, et al. Serum CA 19–9 as a marker of resectability and survival in patients with potentially resectable pancreatic cancer treated with neoadjuvant chemoradiation. Ann Surg Oncol. 2010;17:1794–1801.PubMedCrossRef
44.
go back to reference Shukla PJ, Neve R, Barreto SG, et al. A new scoring system for gallbladder cancer (aiding treatment algorithm): an analysis of 335 patients. Ann Surg Oncol. 2008;15:3132–3137. Shukla PJ, Neve R, Barreto SG, et al. A new scoring system for gallbladder cancer (aiding treatment algorithm): an analysis of 335 patients. Ann Surg Oncol. 2008;15:3132–3137.
45.
go back to reference Leon AR. A new scoring system for gallbladder cancer: the first step of a long walk. Ann Surg Oncol. 2008;15:2991–2992.PubMedCrossRef Leon AR. A new scoring system for gallbladder cancer: the first step of a long walk. Ann Surg Oncol. 2008;15:2991–2992.PubMedCrossRef
Metadata
Title
Key Factors Influencing Prognosis in Relation to Gallbladder Cancer
Authors
Charles Henry Caldow Pilgrim
Ryan T. Groeschl
Kiran K. Turaga
T. Clark Gamblin
Publication date
01-09-2013
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 9/2013
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-013-2713-y

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