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Diagnosis and Surgical Management of Gallbladder Cancer: A Review

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Journal of Gastrointestinal Surgery Aims and scope

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.

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References

  1. DeStoll M. Rationis mendendi, in nosocomio practico vendobonensi. part 1 lugduni batavarum, Haak et Socios et A et J Honkoop 1788.

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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.

    CAS  Google Scholar 

  5. Taner CB, Nagorney DM, Donohue JH. Surgical treatment of gallbladder cancer. Journal of Gastrointestinal Surgery 2004;8(1):83–89.

    Article  PubMed  Google Scholar 

  6. Pandey M. Risk factors for gall bladder cancer: a reappraisal. European Journal of Cancer Prevention 2003;12:15–24.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  11. Lowenfels AB, Maisonneuve P, Boyle P, Zatonski WA. Epidemiology of gallbladder cancer. Hepatogastroenterology 1999;46:1529–1532.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  13. Diehl AK. Gallstone size and the risk of gall bladder cancer. JAMA 1983;250(17):2323–2326.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  17. Misra S, Chaturvedi A, Misra NC, Sharma ID. Carcinoma of the gallbladder. Lancet Oncology 2003;4:167–176.

    Article  PubMed  Google Scholar 

  18. Ransohoff DF, Gracie WA. Treatment of gallstones. Annals of Internal Medicine 1993;119:606–619.

    PubMed  CAS  Google Scholar 

  19. Etala E. Cancer de la vesicula biliar. Prensa MeÂdica Argentina 1962;49:2283–2299.

    Google Scholar 

  20. Stephen AE, Berger DL. Carcinoma in the porcelain gallbladder: a relationship revisited. Surgery 2001;129:699–703.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  24. Lee KF, Wong J, Li JC, Lai PB. Polypoid lesions of the gallbladder. The American Journal of Surgery 2004;188:186–190.

    Article  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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. 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.

    Article  PubMed  CAS  Google Scholar 

  31. Nassenstein K, Kissler M. Gallbladder metastasis of non-small cell lung cancer. Onkologie 2004;27(4):398–400.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  Google Scholar 

  34. Washington K, Gottfried MR. Expression of p53 in adenocarcinoma of the gallbladder and bile ducts. Liver 1996;16:99–104.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  37. Donohue JH. Present status of the diagnosis and treatment of gallbladder cancer. Journal of Hepato-biliary-pancreatic Surgery 2001;8:530–534.

    Article  PubMed  CAS  Google Scholar 

  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. 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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  41. Nevin JE, Moran TJ, Kay S, King R. Carcinoma of the gallbladder: staging, treatment, and prognosis. Cancer 1976;37:141–148.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  50. Hederstrom E, Forsberg L. Ultrasonography in carcinoma of the gallbladder. Diagnostic difficulties and pitfalls. Acta Radiologica 1987;28(6):715–718.

    Article  PubMed  CAS  Google Scholar 

  51. Haribhakti SP, Kapoor VK, GujralRB, Kaushik SP. Staging of carcinoma of the gallbladder—an ultrasonographic evaluation. Hepatogastroenterology 1997;44(17):1240–1245.

    PubMed  CAS  Google Scholar 

  52. Jacobson BC, Pitman MB, Brugge WR. EUS-guided FNA for the diagnosis of gallbladder masses. Gastrointestinal Endoscopy 2003;57(2):251–254.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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. 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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  61. Shirai Y, Yoshida K, Tsukada K, Muto T, Watanabe H. Early carcinoma of the gallbladder. European Journal of Surgery 1992;158:545–548.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  67. Yildirim E, Celen O, Gulben K. Other surgical management of incidental GBC. European Journal of Surgical Oncology 2005;31(1):45–52.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  76. Finch MD, Butler JA. Palliation for non-pancreatic malignant obstruction of the biliary tract. Surgery, Gynecology & Obstetrics 1990;170(5):437–440.

    CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Surgery, Mayo Clinic, 200 First Street S.W., Rochester, MN, 55905, USA

    Kaye M. Reid, Antonio Ramos-De la Medina & John H. Donohue

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  1. Kaye M. Reid
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Reid, K.M., Ramos-De la Medina, A. & Donohue, J.H. Diagnosis and Surgical Management of Gallbladder Cancer: A Review. J Gastrointest Surg 11, 671–681 (2007). https://doi.org/10.1007/s11605-006-0075-x

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