Advertisement

Diagnosis and Surgical Management of Gallbladder Cancer: A Review

  • Kaye M. Reid
  • Antonio Ramos-De la Medina
  • John H. DonohueEmail author
Article

Abstract

Gallbladder cancer is one of the most lethal carcinomas and continues to pose many challenges for surgeons. Identifiable risk factors for carcinoma of the gallbladder include cholelithiasis, an anomalous pancreaticobiliary junction, and focal mucosal microcalcifications. Adenocarcinoma is the primary histologic type in most patients and the tumor is frequently associated with Kras and p53 mutations. Radiologic and endoscopic advances in endoscopic ultrasonography and magnetic resonance cholangiopancreatogram, plus helical computed tomography, have enhanced preoperative staging. Surgical options include cholecystectomy for disease limited to the mucosa (Tis/T1) or a radical cholecystectomy (subsegmental resection of segments IVB and V plus a hepatoduodenal ligament lymphadenectomy) for advanced disease without signs of distant metastasis (T2-4/N0-N2). Some surgeons have advocated more radical hepatic resection including extended right hepatectomy or central bisegmentectomy plus caudate lobectomy. Japanese surgeons have reported studies that included patients having a pancreaticoduodenectomy to improve distal ductal margins and lymphadenectomy for T3 and T4 cancers. These patients have a lower rate of local recurrence but no survival advantage. Options for adjuvant therapy remain limited. Radiation therapy with fluorouracil radiosensitization is the most commonly used postoperative treatments. Current trials are investigating the role of capecitabine, oxaliplatin, and bevacizumab in the management of gallbladder carcinoma.

Keywords

Gallbladder cancer Biliary tract Gastrointestinal cancer 

References

  1. 1.
    DeStoll M. Rationis mendendi, in nosocomio practico vendobonensi. part 1 lugduni batavarum, Haak et Socios et A et J Honkoop 1788.Google Scholar
  2. 2.
    Donohue JH, Stewart AK, Menck HR. The national cancer data base report on carcinoma of the gallbladder, 1989–1995. Cancer 1998;83:2618–2628.PubMedCrossRefGoogle Scholar
  3. 3.
    Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, et al. Cancer statistics, 2005. CA: A Cancer Journal for Clinicians 2005;55:10–30.Google Scholar
  4. 4.
    Lazcano-Ponce EC, Miquel JF, Munoz N, Herrero R, Ferrecio C, Wistuba II, et al. Epidemiology and molecular pathology of GBC. CA: A Cancer Journal for Clinicians 2001;51:349–364.Google Scholar
  5. 5.
    Taner CB, Nagorney DM, Donohue JH. Surgical treatment of gallbladder cancer. Journal of Gastrointestinal Surgery 2004;8(1):83–89.PubMedCrossRefGoogle Scholar
  6. 6.
    Pandey M. Risk factors for gall bladder cancer: a reappraisal. European Journal of Cancer Prevention 2003;12:15–24.PubMedCrossRefGoogle Scholar
  7. 7.
    Pandey M, Shukla VK. Lifestyle, parity, menstrual and reproductive factors and risk of gallbladder cancer. European Journal of Cancer Prevention 2003;12:269–272.PubMedCrossRefGoogle Scholar
  8. 8.
    Strom BL, Soloway RD, Rios-Dalenz JL, Rodriguez-Martinez HA, West SL, Kinman JL, et al. Risk factors for gall bladder cancer: an international collaborative case-control study. Cancer 1995;76:1747–1756.PubMedCrossRefGoogle Scholar
  9. 9.
    Szot J. Epidemiological analysis of mortality caused by solid tumors in the Metropolitan Region, Chile, 1999. Revista Medica de Chile 2003;131:641–649.PubMedGoogle Scholar
  10. 10.
    Csendes A, Becerra M, Smok G, Medina E, Maluenda F, Morales E. Prevalence of gallbladder neoplasms in cholecystectomies. Revista Medica de Chile 1991;119:887–890.PubMedGoogle Scholar
  11. 11.
    Lowenfels AB, Maisonneuve P, Boyle P, Zatonski WA. Epidemiology of gallbladder cancer. Hepatogastroenterology 1999;46:1529–1532.PubMedGoogle Scholar
  12. 12.
    Maringhini A, Moreau JA, Melton LJ III, Hench VS, Zinmeister AR, DiMagno EP. Gallstones, gall bladder cancer, and other gastrointestinal malignancies. An epidemiologic study in Rochester, Minnesota. Annals of Internal Medicine 1987;107:30–35.PubMedGoogle Scholar
  13. 13.
    Diehl AK. Gallstone size and the risk of gall bladder cancer. JAMA 1983;250(17):2323–2326.PubMedCrossRefGoogle Scholar
  14. 14.
    Csendes A, Becerra M, Rojas J, Medina E. Number and size of stones in patients with asymptomatic and symptomatic gallstones and gall bladder cancer: a prospective study of 592 cases. Journal of Gastrointestinal Surgery 2000;4:481–485.PubMedCrossRefGoogle Scholar
  15. 15.
    Albores-Saavedra J, Alcantra-Vazquez A, Cruz Ortiz H, Herrera-Goepfert R. The precursor lesions of invasive gall bladder cancer: hyperplasia, atypical hyperplasia and carcinoma in situ. Cancer 1980;45:919–927.PubMedCrossRefGoogle Scholar
  16. 16.
    Wee A, Teh M, Raju GC. Clinical importance of p53 protein in gall bladder cancer and its precursor lesions. Journal of Clinical Pathology 1994;47:453–456.PubMedGoogle Scholar
  17. 17.
    Misra S, Chaturvedi A, Misra NC, Sharma ID. Carcinoma of the gallbladder. Lancet Oncology 2003;4:167–176.PubMedCrossRefGoogle Scholar
  18. 18.
    Ransohoff DF, Gracie WA. Treatment of gallstones. Annals of Internal Medicine 1993;119:606–619.PubMedGoogle Scholar
  19. 19.
    Etala E. Cancer de la vesicula biliar. Prensa MeÂdica Argentina 1962;49:2283–2299.Google Scholar
  20. 20.
    Stephen AE, Berger DL. Carcinoma in the porcelain gallbladder: a relationship revisited. Surgery 2001;129:699–703.PubMedCrossRefGoogle Scholar
  21. 21.
    Tazuma S, Kajiyama G. Carcinogenesis of malignant lesions of the gall bladder. The impact of chronic inflammation and gallstones. Langenbecks Archives of Surgery 2001;386:224–229.CrossRefGoogle Scholar
  22. 22.
    Hu B, Gong B, Zhou DY. Association of anomalous pancreaticobiliary ductal junction with GBC in Chinese patients: an ERCP study. Gastrointestinal Endoscopy 2003;57:541–545.PubMedCrossRefGoogle Scholar
  23. 23.
    Elnemr A, Ohta T, Kayahara M, Kitagawa H, Yoshimoto K, Tani T, et al. Anomalous pancreaticobiliary ductal junction without bile duct dilatation in GBC. Hepatogastroenterology 2001;48:382–386.PubMedGoogle Scholar
  24. 24.
    Lee KF, Wong J, Li JC, Lai PB. Polypoid lesions of the gallbladder. The American Journal of Surgery 2004;188:186–190.CrossRefGoogle Scholar
  25. 25.
    Dixit VK, Prakash A, Gupta A, Pandey M, Gautam A, Kumar M, et al. Xanthogranulomatous cholecystitis. Digestive Diseases and Sciences 1998;43(5):940–942.PubMedCrossRefGoogle Scholar
  26. 26.
    Shukla VK, Singh H, Pandey M, Upadhyay SK, Nath G. Carcinoma of the gallbladder—is it a sequel of typhoid? Digestive Diseases and Sciences 2000;45(5):900–903.PubMedCrossRefGoogle Scholar
  27. 27.
    Yamamoto T, Uki K, Takeuchi K, Nagashima N, Honjo H, Sakurai N, et al. Early gall bladder cancer associated with primary sclerosing cholangitis and ulcerative colitis. Journal of Gastroenterology 2003;38(7):704–706.PubMedCrossRefGoogle Scholar
  28. 28.
    Buckles DC, Lindor KD, Larusso NF, Petrovic LM, Gores GJ. In primary sclerosing cholangitis, gallbladder polyps are frequently malignant. American Journal of Gastroenterology 2002;97(5):1138–1142.PubMedCrossRefGoogle Scholar
  29. 29.
    Black WC. The morphogenesis of gall bladder carcinoma. In Fenoglio CM, Wolff M, eds. Progress in Surgical Pathology. New York: Masson, 1984, pp 207–223.Google Scholar
  30. 30.
    Roa I, Araya JC, Villaseca M, De Aretxabala X, Riedemann P, Endoh K, et al. Preneoplastic lesions and gall bladder cancer: an estimate of the period required for progression. Gastroenterology 1996;111:232–236.PubMedCrossRefGoogle Scholar
  31. 31.
    Nassenstein K, Kissler M. Gallbladder metastasis of non-small cell lung cancer. Onkologie 2004;27(4):398–400.PubMedCrossRefGoogle Scholar
  32. 32.
    Crippa S, Bovo G, Romano F, Mussi C, Uggeri F. Melanoma metastatic to the gallbladder and small bowel: report of a case and review of the literature. Melanoma Research 2004;14(5):427–430.PubMedCrossRefGoogle Scholar
  33. 33.
    Fujii K, Yokozaki H, Yasui W, Kuniyasu H, Hirata M, Kajiyama G, et al. High frequency of p53 gene mutation in adenocarcinomas of the gallbladder. Cancer Epidemiology, Biomarkers & Prevention 1996;5:461–466.Google Scholar
  34. 34.
    Washington K, Gottfried MR. Expression of p53 in adenocarcinoma of the gallbladder and bile ducts. Liver 1996;16:99–104.PubMedGoogle Scholar
  35. 35.
    Itoi T, Watanabe H, Yoshida M, Ajioka Y, Nishikura K, Saito T. Correlation of p53 protein expression with gene mutation in gall-bladder carcinomas. Pathology International 1997;47:525–530.PubMedCrossRefGoogle Scholar
  36. 36.
    Hanada K, Itoh M, Fujii K, Tsuchida A, Ooishi H, Kajiyama G. K-ras and p53 mutations in Stage I gallbladder cancer with an anomalous junction of the pancreaticobiliary duct. Cancer 1996;77:452–458.PubMedCrossRefGoogle Scholar
  37. 37.
    Donohue JH. Present status of the diagnosis and treatment of gallbladder cancer. Journal of Hepato-biliary-pancreatic Surgery 2001;8:530–534.PubMedCrossRefGoogle Scholar
  38. 38.
    Ramos-De la Medina A, Medina-Franco H. Biliary-colonic fistulas. Analysis of 2 cases and literature review. Revista de GastroenterologiÂa de MeÂxico 2002;67:207–209.Google Scholar
  39. 39.
    Kubota H, Kageoka M, Iwasaki H, Sugimoto K, Higuchi R, Honda S, et al. A patient with undifferentiated carcinoma of gallbladder presenting with hemobilia. Journal of Gastroenterology 2000;35(1):63–68.PubMedCrossRefGoogle Scholar
  40. 40.
    Henson DE, Albores-Saavedra J, Corle D. Carcinoma of the gallbladder. Histologic types, stage of disease, grade, and survival rates. Cancer 1992;70:1493–1497.PubMedCrossRefGoogle Scholar
  41. 41.
    Nevin JE, Moran TJ, Kay S, King R. Carcinoma of the gallbladder: staging, treatment, and prognosis. Cancer 1976;37:141–148.PubMedCrossRefGoogle Scholar
  42. 42.
    Donohue JH, Nagorney DM, Grant CS, Tsushima K, Ilstrup DM, Adson MA. Carcinoma of the gallbladder. Does radical resection improve outcome? Archives of Surgery 1990;125(2):237–241.PubMedGoogle Scholar
  43. 43.
    Fleming ID, Cooper JS, Henson DE, Hutter RVP, Kennedy BJ, Murphy GP, O’Sullivan B, Sobin LH, Yarbro JW eds. AJCC cancer staging manual (5th ed.). Philadelphia: Lippincott-Raven, 1997.Google Scholar
  44. 44.
    Onoyama H, Yamamoto M, Tseng A, Ajiki T, Saitoh Y. Extended cholecystectomy for carcinoma of the gallbladder. World Journal of Surgery 1995;19:758–763.PubMedCrossRefGoogle Scholar
  45. 45.
    Fong Y, Jarnagin W, Blumgart LH. Gall bladder cancer: comparison of patients presenting initially for definitive operation with those presenting after prior noncurative intervention. Annals of Surgery 2000;232:557–569.PubMedCrossRefGoogle Scholar
  46. 46.
    Tsukada K, Hatakeyama K, Kurosaki I, Uchida K, Shirai Y, Muto T, et al. Outcome of radical surgery for carcinoma of the gallbladder according to the TNM stage. Surgery 1996;120:816–821.PubMedCrossRefGoogle Scholar
  47. 47.
    Bartlett DL, Fong Y, Fortner JG, Brennan MF, Blumgart LH. Long-term results after resection for gallbladder cancer. Implications for staging and management. Annals of Surgery 1996;224:639–645.PubMedCrossRefGoogle Scholar
  48. 48.
    Yamaguchi K, Chijiiwa K, Saiki S, Nishihara K, Takashima M, Kawakami K, et al. Retrospective analysis of 70 operations for gallbladder cancer. British Journal of Surgery 1997;84:200–204.PubMedCrossRefGoogle Scholar
  49. 49.
    Chijiiwa K, Nakano K, Ueda J, Noshiro H, Nagai E, Yamaguchi K, et al. Surgical treatment of patients with T2 gallbladder cancer invading the subserosal layer. Journal of the American College of Surgeons 2001:192:600–607.PubMedCrossRefGoogle Scholar
  50. 50.
    Hederstrom E, Forsberg L. Ultrasonography in carcinoma of the gallbladder. Diagnostic difficulties and pitfalls. Acta Radiologica 1987;28(6):715–718.PubMedCrossRefGoogle Scholar
  51. 51.
    Haribhakti SP, Kapoor VK, GujralRB, Kaushik SP. Staging of carcinoma of the gallbladder—an ultrasonographic evaluation. Hepatogastroenterology 1997;44(17):1240–1245.PubMedGoogle Scholar
  52. 52.
    Jacobson BC, Pitman MB, Brugge WR. EUS-guided FNA for the diagnosis of gallbladder masses. Gastrointestinal Endoscopy 2003;57(2):251–254.PubMedCrossRefGoogle Scholar
  53. 53.
    Pandey M, Sood BP, Shukla RC, Aryya NC, Singh S, Shukla VK. Carcinoma of the gallbladder: role of sonography in diagnosis and staging. Journal of Clinical Ultrasound 2000;28(5):227–232.PubMedCrossRefGoogle Scholar
  54. 54.
    Kim BS, Ha HK, Lee IJ, Kim JH, Eun HW, Bae IY, et al. Accuracy of CT in local staging of GBC. Acta Radiologica 2002;43(1):71–76.PubMedCrossRefGoogle Scholar
  55. 55.
    Yun EJ, Cho SG, Park S, Park SW, Kim WH, Kim HJ, et al. Gallbladder cancer and chronic cholecystitis: differentiation with two-phase spiral CT. Abdominal Imaging 2004;29(1):102–108.PubMedCrossRefGoogle Scholar
  56. 56.
    Kim JH, Kim TK, Eun HW, Kim BS, Lee MG, Kim PN, et al. Preoperative evaluation of GBC: efficacy of combined use of MR imaging, MR cholangiography, and contrast-enhanced dual-phase three-dimensional MR angiography. Journal of Magnetic Resonance Imaging 2002;16(6):676–684.PubMedCrossRefGoogle Scholar
  57. 57.
    Oberoi R, Jena A, Kumar R, Pandey P, Pandey K. MRI in preoperative evaluation of GBC. Asian Oceanian Journal of Radiology 2004; 9(2–3):57–63.Google Scholar
  58. 58.
    Weber SM, DeMatteo RP, Fong Y, Blumgart LH, Jarnagin WR. Staging laparoscopy in patients with extrahepatic biliary carcinoma. Analysis of 100 patients. Annals of Surgery 2002;235(3):392–399.PubMedCrossRefGoogle Scholar
  59. 59.
    Ito H, Matros D, Brooks C, Osteen T, Zinner MJ, Swanson RS, et al. Treatment outcomes associated with surgery for gallbladder cancer: a 20 year experience. Journal of Gastrointestinal Surgery 2004;8(2):183–190.PubMedCrossRefGoogle Scholar
  60. 60.
    Fong Y, Brennan MF, Turnbull A, Colt DG, Blumgart LH. Gallbladder cancer discovered during laparoscopic surgery. Potential for iatrogenic tumor dissemination. Archives of Surgery 1993;128(9):1054–1056.PubMedGoogle Scholar
  61. 61.
    Shirai Y, Yoshida K, Tsukada K, Muto T, Watanabe H. Early carcinoma of the gallbladder. European Journal of Surgery 1992;158:545–548.PubMedGoogle Scholar
  62. 62.
    De Aretxabala XA, Roa IS, Burgos LA, Araya JC, Villaseca MA, Silva JA. Curative resection in potentially resectable tumours of the gallbladder. European Journal of Surgery 1997;163:419–426.PubMedGoogle Scholar
  63. 63.
    Memon MA, Anwar S, Shiwani MH, Memon B. GBC: a retrospective analysis of twenty-two years experience of a single teaching hospital. International Seminars in Surgical Oncology 2005;2(1):6.PubMedCrossRefGoogle Scholar
  64. 64.
    Ishikawa T, Horimi T, Shima Y, Okabayashi T, Nishioka Y, Hamada M, et al. Evaluation of aggressive surgical treatment for advanced carcinoma of the gallbladder. Journal of Hepato-biliary-pancreatic Surgery 2003;10(3):233–238.PubMedCrossRefGoogle Scholar
  65. 65.
    Wakabayashi H, Ishimura K, Hashimoto N, Otani T, Kondo A, Maeta H. Analysis of prognostic factors after surgery for stage III and IV gallbladder cancer. European Journal of Surgical Oncology 2004;30(8):842–846.PubMedGoogle Scholar
  66. 66.
    Behari A, Sikora SS, Wagholikar GD, Kumar A, Saxena R, Kapoor VK. Long term survival after extended resections in patients with gallbladder cancer. Journal of the American College of Surgeons 2003;196(1):82–88.PubMedCrossRefGoogle Scholar
  67. 67.
    Yildirim E, Celen O, Gulben K. Other surgical management of incidental GBC. European Journal of Surgical Oncology 2005;31(1):45–52.PubMedCrossRefGoogle Scholar
  68. 68.
    Kondo S, Nimura Y, Hayakawa N, Kamiya J, Nagino M, Uesaka K. Regional and para-aortic lymphadenectomy in radical surgery for advanced gallbladder cancer. British Journal of Surgery 2000;87(4):418–422.PubMedCrossRefGoogle Scholar
  69. 69.
    Shimizu Y, Ohtsuka M, Ito H, Kimura F, Shimizu H, Togawa A, et al. Should the extrahepatic bile duct be resected for locally advanced gallbladder cancer? Surgery 2004;136(5):1012–1017.PubMedCrossRefGoogle Scholar
  70. 70.
    Shinkai H, Kimura W, Sata N, Muto T, Nagai H. A case of gallbladder cancer with para-aortic lymph node metastasis who has survived more than seven years after the primary extended radical operation. Hepatogastroenterology 1996;43(11):1370–1376.PubMedGoogle Scholar
  71. 71.
    Terazawa T, Miyake H, Kurahashi M, Tashiro S. Direct lymphatic spreading route into the liver from the gallbladder: an animal experiment using pig. Journal of Medical Investigation 2004;51(3–4):210–217.PubMedCrossRefGoogle Scholar
  72. 72.
    Ogura Y, Matsuda S, Sakurai H, Kawarada Y, Mizumoto R. Central bisegmentectomy of the liver plus caudate lobectomy for carcinoma of the gallbladder. Digestive Surgery 1998;15(3):218–223.PubMedCrossRefGoogle Scholar
  73. 73.
    Shirai Y, Ohtani T, Tsukada K, Hatakeyama K. Combined pancreaticoduodenectomy and hepatectomy for patients with locally advanced gallbladder carcinoma: long term results. Cancer 1997;80(10):1904–1909.PubMedCrossRefGoogle Scholar
  74. 74.
    Sasaki R, Takahashi M, Funato O, Nitta H, Murakami M, Kawamura H, et al. Hepatopancreatoduodenectomy with wide lymph node dissection for locally advanced carcinoma of the gallbladder—long-term results. Hepatogastroenterology 2002;49(46):912–915.PubMedGoogle Scholar
  75. 75.
    Araida T, Yoshikawa T, Azuma T, Ota T, Takasaki KF. Indications for pancreatoduodenectomy in patients undergoing lymphadenectomy for advanced gallbladder carcinoma. Journal of Hepato-biliary-pancreatic Surgery 2004;11(1):45–49.PubMedCrossRefGoogle Scholar
  76. 76.
    Finch MD, Butler JA. Palliation for non-pancreatic malignant obstruction of the biliary tract. Surgery, Gynecology & Obstetrics 1990;170(5):437–440.Google Scholar
  77. 77.
    Kresl JJ, Schild SE, Henning GT, Gunderson LL, Donohue J, Pitot H, et al. Adjuvant external beam radiation therapy with concurrent chemotherapy in the management of GBC. International Journal of Radiation Oncology, Biology, Physics 2002;52(1):167–175.PubMedCrossRefGoogle Scholar
  78. 78.
    Takada T, Amano H, Yasuda H, Nimura Y, Matsushiro T, Kato H, et al. Is postoperative adjuvant chemotherapy useful for gallbladder cancer? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma. Cancer 2002;95(8):1685–1695.PubMedCrossRefGoogle Scholar
  79. 79.
    Alberts SR, Al-Khatib H, Mahoney MR, Burgart L, Cera PJ, Flynn PJ, et al. Gemcitabine, 5-fluorouracil, and leucovorin in advanced biliary tract and GBC: a North Central Cancer Treatment Group phase II trial. Cancer 2005;103(1):111–118.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Kaye M. Reid
    • 1
  • Antonio Ramos-De la Medina
    • 1
  • John H. Donohue
    • 1
    Email author
  1. 1.Department of SurgeryMayo ClinicRochesterUSA

Personalised recommendations