Virchows Archiv

, Volume 463, Issue 5, pp 651–661 | Cite as

Early gallbladder carcinoma has a favorable outcome but Rokitansky–Aschoff sinus involvement is an adverse prognostic factor

  • Juan C. Roa
  • Oscar Tapia
  • Carlos Manterola
  • Miguel Villaseca
  • Pablo Guzman
  • Juan Carlos Araya
  • Pelin Bagci
  • Burcu Saka
  • Volkan Adsay
Original Article


The general impression about gallbladder carcinomas is that they are uniformly fatal; however, for the early forms, an entirely different picture indicating a very good prognosis is evolving from the high-incidence regions. We subjected 190 early gallbladder carcinomas (EGBC), defined as carcinomas confined to and above the tunica muscularis (AJCC's Tis, T1a, and T1b), and identified in cholecystectomy specimens sampled entirely according to an established protocol, to detailed analysis. Average patient age was 57.9 years (29–95). In more than half of the cases (114/190; 60 %), the tumor was inapparent by gross examination. In 81 cases (42.6 %), carcinomatous epithelium abutted the muscularis, whereas 57.4 % (n = 109) were qualified as intramucosal with no overt contiguity with muscularis. Intraepithelial extension into Rokitansky–Aschoff sinuses (RAS) was found in 34 cases (17.8 %). At the time of data analysis, 171 patients (99 %) were alive. Overall actuarial survival was 92.3 % at 5 years and 90.4 % at 10 years. The 5- and 10-year actuarial survival rates of the intramucosal group (93.2 and 92.1 %, respectively) were not statistically different from that of the muscle-abutting group (89.7 % and 88.2 % ; p = 0.334). Patients with RAS involvement had a significantly shorter survival than those without (p < 0.001). Of the 33 patients with RAS involvement, 13 (39 %) died of disease, whereas only 6 of the 154 patients (4 %) without RAS involvement died of disease. Disease-related mortality in these cases occurred relatively late (median 48 months). EGBC has a very good prognosis with a 90 % 10-year survival rate. It is seen on average in patients almost a decade younger than those with advanced cancers. RAS involvement is an independent prognostic factor, and additional surgery may have to be considered for such cases. Occasional recurrences are encountered several years later, which suggests a field-effect phenomenon and warrants long-term follow-up.


Gallbladder Adenocarcinoma Early stage 



This study was financed in part by the Office of Research of the Universidad de la Frontera and Fondecyt Grant 1090171.

Conflict of interest

We declare that we have no conflict of interest.


  1. 1.
    Adsay NV, Klimstra DS (2007) Tumors of the bile ducts and pathologic aspects. In: Blumgart LH (ed) Surgery of the liver, biliary tract and pancreas, 4th edn. Elsevier, PhiladelphiaGoogle Scholar
  2. 2.
    Albores-Saavedra J, Henson DE, Klimstra DS (2000) Tumors of the gallbladder, extrahepatic bile ducts, and ampulla of vater. Atlas of tumor pathology, 3rd edn. Armed Forces Institute of Pathology, Washington, DC, pp 21–35Google Scholar
  3. 3.
    Albores-Saavedra J, Shukla D, Carrick K, Henson DE (2004) In situ and invasive adenocarcinomas of the gallbladder extending into or arising from Rokitansky–Aschoff sinuses: a clinicopathologic study of 49 cases. Am J Surg Pathol 28:621–628PubMedCrossRefGoogle Scholar
  4. 4.
    Barreto SG, Shukla PJ (2008) Defining the completeness of surgery for early gallbladder cancer. Ann Surg 248:896. doi: 10.1097/SLA.0b013e31818b7723, author reply 896–897PubMedCrossRefGoogle Scholar
  5. 5.
    Bertran E, Heise K, Andia ME, Ferreccio C (2010) Gallbladder cancer: incidence and survival in a high-risk area of Chile. Int J Cancer 127:2446–2454. doi: 10.1002/ijc.25421 PubMedCrossRefGoogle Scholar
  6. 6.
    Cangemi V, Fiori E, Picchi C, De Cesare A, Cangemi R, Galati G, Volpino P (2006) Early gallbladder carcinoma: a single-center experience. Tumori 92:487–490PubMedGoogle Scholar
  7. 7.
    Chan KM, Yeh TS, Jan YY, Chen MF (2006) Laparoscopic cholecystectomy for early gallbladder carcinoma: long-term outcome in comparison with conventional open cholecystectomy. Surg Endosc 20:1867–1871. doi: 10.1007/s00464-005-0195-5 PubMedCrossRefGoogle Scholar
  8. 8.
    Coburn NG, Cleary SP, Tan JCC, Law CHL (2008) Surgery for gallbladder cancer: a population-based analysis. J Am Coll Surg 207:371–382. doi: 10.1016/j.jamcollsurg.2008.02.031 PubMedCrossRefGoogle Scholar
  9. 9.
    de Aretxabala X, Roa I, Araya JC, Burgos L, Flores P, Huenchullan I, Miyazaki I (1990) Operative findings in patients with early forms of gallbladder cancer. Br J Surg 77:291–293PubMedCrossRefGoogle Scholar
  10. 10.
    de Aretxabala X, Roa I, Burgos L (1999) Gallbladder cancer, management of early tumors. Hepatogastroenterology 46:1547–1551PubMedGoogle Scholar
  11. 11.
    de Aretxabala X, Roa I, Burgos L, Araya JC, Wistuba I, Villaseca MA, Fonseca L, Flores P, Sotomayor F (1991) Inapparent cancer of the gallbladder. Rev Med Chil 119:881–886PubMedGoogle Scholar
  12. 12.
    de Aretxabala X, Roa I, Burgos L, Losada H, Roa JC, Mora J, Hepp J, Leon J, Maluenda F (2006) Gallbladder cancer: an analysis of a series of 139 patients with invasion restricted to the subserosal layer. J Gastrointest Surg 10:186–192. doi: 10.1016/j.gassur.2005.11.003 PubMedCrossRefGoogle Scholar
  13. 13.
    Downing CKOG Sr et al (2011) Early-stage gallbladder cancer in the surveillance, epidemiology, and end results database: effect of extended surgical resection. Arch Surg 146:734–738. doi: 10.1001/archsurg.2011.128 PubMedCrossRefGoogle Scholar
  14. 14.
    Duffy A, Capanu M, Abou-Alfa GK, Huitzil D, Jarnagin W, Fong Y, D'Angelica M, DeMatteo RP, Blumgart LH, O'Reilly EM (2008) Gallbladder cancer (GBC): 10-year experience at Memorial Sloan-Kettering Cancer Centre (MSKCC). J Surg Oncol 98:485–489. doi: 10.1002/jso.21141 PubMedCrossRefGoogle Scholar
  15. 15.
    Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A (eds) (2010) Gallbladder cancer. Springer, New YorkGoogle Scholar
  16. 16.
    Foster J, Hoshi H, Gibbs J, Iyer R, Javle M, Chu Q, Kuvshinoff B (2007) Gallbladder cancer: defining the indications for primary radical resection and radical re-resection. Ann Surg Oncol 14:833–840. doi: 10.1245/s10434-006-9097-6 PubMedCrossRefGoogle Scholar
  17. 17.
    Glazer ES, Liu P, Abdalla EK, Vauthey JN, Curley SA (2012) Neither neoadjuvant nor adjuvant therapy increases survival after biliary tract cancer resection with wide negative margins. J Gastrointest Surg 16:1666–1671PubMedCrossRefGoogle Scholar
  18. 18.
    Goetze T, Paolucci V (2012) The prognostic impact of positive lymph nodes in stages T1 to T3 incidental gallbladder carcinoma: results of the German Registry. Surg Endosc 26:1382–1389. doi: 10.1007/s00464-011-2044-z PubMedCrossRefGoogle Scholar
  19. 19.
    Goetze TO, Paolucci V (2008) Immediate re-resection of T1 incidental gallbladder carcinomas: a survival analysis of the German Registry. Surg Endosc 22:2462–2465. doi: 10.1007/s00464-008-9747-9 PubMedCrossRefGoogle Scholar
  20. 20.
    Goetze TO, Paolucci V (2011) Immediate radical re-resection of incidental T1b gallbladder cancer and the problem of an adequate extent of resection (Results of the German Registry “Incidental Gallbladder Cancer”). Zentralbl Chir Mar 1Google Scholar
  21. 21.
    Gold DG, Miller RC, Haddock MG, Gunderson LL, Quevedo F, Donohue JH, Bhatia S, Nagorney DM (2009) Adjuvant therapy for gallbladder carcinoma: the Mayo Clinic Experience. Int J Radiat Oncol Biol Phys 75:150–155. doi: 10.1016/j.ijrobp.2008.10.052 PubMedCrossRefGoogle Scholar
  22. 22.
    Jensen EH, Abraham A, Habermann EB, Al-Refaie WB, Vickers SM, Virnig BA, Tuttle TM (2009) A critical analysis of the surgical management of early-stage gallbladder cancer in the United States. J Gastrointest Surg 13:722–727. doi: 10.1007/s11605-008-0772-8 PubMedCrossRefGoogle Scholar
  23. 23.
    Kapoor VK (2007) Advanced gallbladder cancer: Indian “middle path”. J Hepatobiliary Pancreat Surg 14:366–373. doi: 10.1007/s00534-006-1189-y PubMedCrossRefGoogle Scholar
  24. 24.
    Kawarada Y, Sanda M, Mizumoto R, Yatani R (1986) Early carcinoma of the gallbladder, noninvasive carcinoma originating in the Rokitansky–Aschoff sinus: a case report. Am J Gastroenterol 81:61–66PubMedGoogle Scholar
  25. 25.
    Kijima H, Ishihara N, Iwafuchi M, Watanabe H (1986) Characteristics of early carcinoma of the gallbladder—clinico-pathological study. Gan No Rinsho 32:1240–1245PubMedGoogle Scholar
  26. 26.
    Klimstra DS, Adsay NV (2008) Pathology of biliary tract cancer. In: Kelsen DP (ed) Gastrointestinal oncology: principles and practice, 2nd edn. Lippincott, Williams and Wilkins, PhiladelphiaGoogle Scholar
  27. 27.
    Konstantinidis It DVGM et al (2009) Trends in presentation and survival for gallbladder cancer during a period of more than 4 decades: a single-institution experience. Arch Surg 144:441–447. doi: 10.1001/archsurg.2009.46 PubMedCrossRefGoogle Scholar
  28. 28.
    Mizumoto R, Ogura Y, Kusuda T (1993) Definition and diagnosis of early cancer of the biliary tract. Hepatogastroenterology 40:69–77PubMedGoogle Scholar
  29. 29.
    Ohta T, Nagakawa T, Miyazaki I (1989) Definition, diagnosis and treatment of early carcinoma of the biliary tract. Nippon Rinsho 47:1130–1134PubMedGoogle Scholar
  30. 30.
    Reid KM, Ramos-De la Medina A, Donohue JH (2007) Diagnosis and surgical management of gallbladder cancer: a review. J Gastrointest Surg 11:671–681. doi: 10.1007/s11605-006-0075-x PubMedCrossRefGoogle Scholar
  31. 31.
    Roa I (2005) Proposición de procesamiento de biopsias de la vesícula biliar, clasificación y etapificación el cáncer de la vesícula biliar. Rev Chil Cirugia 57:436–442Google Scholar
  32. 32.
    Roa I, Araya JC, Villaseca M, Roa J, de Aretxabala X, Ibacache G (1999) Gallbladder cancer in a high risk area: morphological features and spread patterns. Hepatogastroenterology 46:1540–1546PubMedGoogle Scholar
  33. 33.
    Roa I, Araya JC, Wistuba I, de Aretxabala X (1990) Gallbladder cancer: anatomic and anatomo-pathologic considerations. Rev Med Chil 118:572–579PubMedGoogle Scholar
  34. 34.
    Roa I, Araya JC, Wistuba I, Villaseca M, de Aretxabala X, Burgos L (1994) Gallbladder cancer in the IX Region of Chile. Impact of the anatomopathological study of 474 cases. Rev Med Chil 122:1248–1256PubMedGoogle Scholar
  35. 35.
    Roa I, de Aretxabala X, Araya JC, Villaseca M, Roa J, Gilda IT, Burgos L, Munoz S (2002) Morphological prognostic elements in gallbladder cancer. Rev Med Chil 130:387–395PubMedGoogle Scholar
  36. 36.
    Roa I, de Aretxabala X, Araya JC, Villaseca M, Roa J, Guzman P (2001) Incipient gallbladder carcinoma. Clinical and pathological study and prognosis in 196 cases. Rev Med Chil 129:1113–1120PubMedGoogle Scholar
  37. 37.
    Shirai Y (1987) Histological differentiation of Rokitansky–Aschoff sinus involvement from stromal invasion of carcinoma of the gallbladder. Nippon Geka Gakkai Zasshi 88:970–981PubMedGoogle Scholar
  38. 38.
    Shirai Y, Yoshida K, Tsukada K, Muto T, Watanabe H (1992) Radical surgery for gallbladder carcinoma. Long-term results. Ann Surg 216:565–568PubMedCrossRefGoogle Scholar
  39. 39.
    Shiwani MH (2007) Surgical management of gall bladder carcinoma. J Pak Med Assoc 57:87–91PubMedGoogle Scholar
  40. 40.
    Sun CD, Zhang BY, Wu LQ, Lee WJ (2005) Laparoscopic cholecystectomy for treatment of unexpected early-stage gallbladder cancer. J Surg Oncol 91:253–257. doi: 10.1002/jso.20318 PubMedCrossRefGoogle Scholar
  41. 41.
    Terada T (2008) Gallbladder adenocarcinoma arising in Rokitansky–Aschoff sinus. Pathol Int 58:806–809. doi: 10.1111/j.1440-1827.2008.02316.x PubMedCrossRefGoogle Scholar
  42. 42.
    Vandenbroucke JP, von Elm E, Altman DG, Gotzsche PC, Mulrow CD, Pocock SJ, Poole C, Schlesselman JJ, Egger M (2007) Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. Epidemiology 18:805–835PubMedCrossRefGoogle Scholar
  43. 43.
    Wakai T, Ajioka Y, Nagino N, Yamaguchi N, Shirai Y, Hatakeyama K (2012) Morphological features of early gallbladder carcinoma. Hepatogastroenterology 59:1013–1017PubMedGoogle Scholar
  44. 44.
    Yildirim E, Celen O, Gulben K, Berberoglu U (2005) The surgical management of incidental gallbladder carcinoma. Eur J Surg Oncol 31:45–52. doi: 10.1016/j.ejso.2004.09.006 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Juan C. Roa
    • 1
    • 2
  • Oscar Tapia
    • 1
  • Carlos Manterola
    • 3
  • Miguel Villaseca
    • 1
  • Pablo Guzman
    • 1
  • Juan Carlos Araya
    • 1
  • Pelin Bagci
    • 4
  • Burcu Saka
    • 4
  • Volkan Adsay
    • 4
    • 5
  1. 1.Department of PathologyUniversidad de La FronteraTemucoChile
  2. 2.Department of PathologyPontificia Universidad Catolica de ChileSantiagoChile
  3. 3.Department of Surgery and TraumatologyUniversidad de La FronteraTemucoChile
  4. 4.Department of PathologyEmory UniversityAtlantaUSA
  5. 5.Department of Pathology and Laboratory MedicineEmory University HospitalAtlantaUSA

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