Improved Outcomes in Gallbladder Cancer with Early Diagnosis and Negative Nodal Status


Background: Gallbladder cancer (GBC) is a rare disease of the hepatobiliary tract characterized by silent presentation, poor prognosis, and limited therapy. Current imaging modalities, clinical symptoms and laboratory values are of limited value in diagnosis and tumour markers are used as a clinical adjunct. Five year survival is 5% - 12% and a majority of patients survive less than 1 year. Early identification, negative nodal status, and extended cholecystectomy improve survival; adjuvant therapy does not appear to play a role. Objective: To evaluate the effects of stage and nodal status of GBC on survival by analyzing clinical and radiological factors leading to preoperative diagnosis and appropriate subsequent management. Results: Forty-three patients (31 female, 12 male) had primary GBC. Average age was 69 years. The most common presenting symptom was pain (65%). Fifteen (35%) patients presented with acute cholecystitis; 9 were suspicious for a mass. Ultrasound and computed tomography were the imaging modalities most often used. Preoperative diagnoses were made in only 7 (16%) patients, whereas 16 (37%) patients were diagnosed intra-operatively and 20 (47%) post-operatively. Adjuvant chemotherapy was offered in 16 (37%) patients. Average survival was 28 months (range 0.5 - 238 months), with a 5-year survival of 13% across all stages. Early GBC (stages 1 - 2) had a 5-year survival of 43%, and late GBC (stages 3 - 4) had no survival at 5 years, with an average survival of 9 months. Positive nodes decreased survival. Conclusion: Our results mirror what has been reported in the literature. Most patients presented with acute cholecystitis, with confounding clinical data, but few were preoperatively diagnosed with GBC. Imaging was rarely diagnostic. Late stage GBC, as well as node-positive status, had dismal outcomes with low 1-year and 5-year survival rates. Improved preoperative suspicion of early GBC would allow for more intentional curative resections, before nodes become positive.

Share and Cite:

L. Smithson, C. Keto, L. Ferguson, S. Silapaswan, M. J. Jacobs, R. Kolachalam, J. C. Flynn and V. K. Mittal, "Improved Outcomes in Gallbladder Cancer with Early Diagnosis and Negative Nodal Status," Journal of Cancer Therapy, Vol. 3 No. 2, 2012, pp. 137-145. doi: 10.4236/jct.2012.32019.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] D. F. Ransohoff and W. A. Gracie, “Treatment of Gallstones,” Annals of Internal Medicine, Vol. 119, No. 7, 1993, pp. 606-619.
[2] C. D. Anderson, M. H. Rice, C. W. Pinson, et al., “Fluorodeoxyglucose PET Imaging in the Evaluation of Gallbladder Carcinoma and Cholangiocarcinoma,” Journal of Gastrointestinal Surgery, Vol. 8, No. 1, 2004, pp. 90-97. doi:10.1016/j.gassur.2003.10.003
[3] K. M. Reid, M.A. de la Ramos and J. H. Donohue, “Diagnosis and Surgical Management of Gallbladder Cancer: A Review,” Journal of Gastrointestinal Surgery, Vol. 11, No. 5, 2007, pp. 671-681. doi:10.1007/s11605-006-0075-x
[4] G. Randi, S. Franceschi and V. C. La, “Gallbladder Cancer Worldwide: Geographical Distribution and Risk Factors,” International Journal of Cancer, Vol. 118, No. 7, 2006, pp. 1591-1602. doi:10.1002/ijc.21683
[5] X. de Aretxabala, I Roa, L. Burgos, et al., “Gallbladder Cancer: An Analysis of a Series of 139 Patients with Invasion Restricted to the Subserosal Layer,” Journal of Gastrointestinal Surgery, Vol. 10, No. 2, 2006, pp. 186-192. doi:10.1016/j.gassur.2005.11.003
[6] K. L. Mekeel and A. W. Hemming, “Surgical Management of Gallbladder Carcinoma: A Review,” Journal of Gastrointestinal Surgery, Vol. 11, No. 9, 2007, pp. 1188-1193. doi:10.1007/s11605-007-0115-1
[7] H. Onoyama, M. Yamamoto, M. Takada, et al., “Diagnostic Imaging of Early Gallbladder Cancer: Retrospective Study of 53 Cases,” World Journal of Surgery, Vol. 23, No. 7, 1999, pp. 708-712. doi:10.1007/PL00012373
[8] S. Kondo, Y. Nimura, N. Hayakawa, et al., “Regional and Para-Aortic Lymphadenectomy in Radical Surgery for Advanced Gallbladder Carcinoma,” British Journal of Surgery, Vol. 87, No. 4, 2000, pp. 418-422. doi:10.1046/j.1365-2168.2000.01384.x
[9] M. C. Misra and S. Guleri, “Management of Cancer Gallbladder Found as a Surprise on a Resected Gallbladder Specimen,” Journal of Surgical Oncology, Vol. 93, No. 8, 2006, pp. 690-698. doi:10.1002/jso.20537
[10] E. C. Lazcano-Ponce, J. F. Miquel, N. Munoz, et al., “Epidemiology and Molecular Pathology of Gallbladder Cancer,” CA: A Cancer Journal for Clinicians, Vol. 51, No. 6, 2001, pp. 349-364. doi:10.3322/canjclin.51.6.349
[11] F. Levi, F. Lucchini, E. Negri and V. C. La, “The Recent Decline in Gallbladder Cancer Mortality in Europe,” European Journal of Cancer Prevention, Vol. 12, No. 4, 2003, pp. 265-267. doi:10.1097/00008469-200308000-00004
[12] W. H. Chow, C. Johansen, G. Gridley, et al., “Gallstones, Cholecystectomy and Risk of Cancers of the Liver, Biliary Tract and Pancreas,” British Journal of Cancer, Vol. 79, 1999, pp. 640-644. doi:10.1038/sj.bjc.6690101
[13] D. L. Bartlett, Y. Fong, J. G. Fortner, et al., “Long-Term Results after Resection for Gallbladder Cancer. Implications for Staging and Management,” Annals of Surgery, Vol. 224, No. 5, 1996, pp. 639-646. doi:10.1097/00000658-199611000-00008
[14] A. K. Diehl, “Gallstone Size and the Risk of Gallbladder Cancer,” Journal of the American Medical Association, Vol. 250, No. 17, 1983, pp. 2323-2326. doi:10.1001/jama.1983.03340170049027
[15] C. J. Moerman, M. P. Berns, H. B. Bueno de Mesquita and S. Runia, “Reproductive History and Cancer of the Biliary Tract in Women,” International Journal of Cancer, Vol. 57, No. 2, 1994, pp. 146-153. doi:10.1002/ijc.2910570203
[16] M. Pandey and V. K. Shukla, “Lifestyle, Parity, Menstrual and Reproductive Factors and Risk of Gallbladder Cancer,” European Journal of Cancer Prevention, Vol. 12, No. 4, 2003, pp. 269-272. doi:10.1097/00008469-200308000-00005
[17] E. E. Calle, C. Rodriguez, K. Walker-Thurmond and M. J. Thun, “Overweight, Obesity, and Mortality from Cancer in a Prospectively Studied Cohort of U.S. Adults,” The New England Journal of Medicine, Vol. 348, 2003, pp. 1625-1638. doi:10.1056/NEJMoa021423
[18] K. Yagyu, Y. Lin, Y Obata, et al., “Bowel Movement Frequency, Medical History and the Risk of Gallbladder Cancer Death: A Cohort Study in Japan,” Cancer Science, Vol. 95, No. 8, 2004, pp. 674-678. doi:10.1111/j.1349-7006.2004.tb03328.x
[19] A. Muratore, R. Polastri and L. Capussotti, “Radical Surgery for Gallbladder Cancer: Current Options,” European Journal of Surgical Oncology, Vol. 26, No. 5, 2000, pp. 438-443. doi:10.1053/ejso.1999.0918
[20] J. H. Donohue, A. K. Stewart and H. R. Menck, “The National Cancer Data Base Report on Carcinoma of the Gallbladder, 1989-1995,” Cancer, Vol. 83, No. 12, 1998, pp. 2618-2628. doi:10.1002/(SICI)1097-0142(19981215)83:12<2618::AID-CNCR29>3.0.CO;2-H
[21] Y. Fong, W. Jarnagin and L. H. Blumgart, “Gallbladder Cancer: Comparison of Patients Presenting Initially for Definitive Operation with Those Presenting after Prior Noncurative Intervention,” Annals of Surgery, Vol. 232, No. 4, 2000, pp. 557-569. doi:10.1097/00000658-200010000-00011
[22] M. Pandey, B. P. Sood, R. C. Shukla, et al., “Carcinoma of the Gallbladder: Role of Sonography in Diagnosis and Staging,” Journal of Clinical Ultrasound, Vol. 28, No. 5, 2000, pp. 227-232. doi:10.1002/(SICI)1097-0096(200006)28:5<227::AID-JCU4>3.0.CO;2-4
[23] J. C. Box and S. B. Edge, “Laparoscopic Cholecystectomy and Unsuspected Gallbladder Carcinoma,” Seminars in Surgical Oncology, Vol. 16, 1999, pp. 327-331. doi:10.1002/(SICI)1098-2388(199906)16:4<327::AID-SSU8>3.0.CO;2-V
[24] W. G. Hawkins, R. P. DeMatteo, W. R. Jarnagin WR, et al., “Jaundice Predicts Advanced Disease and Early Mortality in Patients with Gallbladder Cancer,” Annals of Surgical Oncology, Vol. 11, 2004, pp. 310-315. doi:10.1245/ASO.2004.03.011
[25] M. Artico, E. Bronzetti, V. Alicino, et al., “Human Gallbladder Carcinoma: Role of Neurotrophins, MIB-1, CD34 and CA15-3,” European Journal of Histochemistry, Vol. 54, 2010, p. e10. doi:10.4081/ejh.2010.e10
[26] K. Fujii, H. Yokozaki, W. Yasui W, et al., “High Frequency of p53 Gene Mutation in Adenocarcinomas of the Gallbladder,” Cancer Epidemiology, Biomarkers & Prevention, Vol. 5, 1996, pp. 461-466.
[27] I. Hatzaras, C. Schmidt, P. Muscarella, et al., “Elevated CA 19-9 Portends Poor Prognosis in Patients Undergoing Resection of Biliary Malignancies,” HPB (Oxford), Vol. 12, No. 2, 2010, pp. 134-138. doi:10.1111/j.1477-2574.2009.00149.x
[28] W. Kwon, J. Y. Jang, S. E. Lee, et al., “Clinicopathologic Features of Polypoid Lesions of the Gallbladder and Risk Factors of Gallbladder Cancer,” Journal of Korean Medical Science, Vol. 24, No. 3, 2009, pp. 481-487. doi:10.3346/jkms.2009.24.3.481
[29] A. H. Patel, D. M. Harnois, G. G. Klee, et al., “The Utility of CA 19-9 in the Diagnoses of Cholangiocarcinoma in Patients without Primary Sclerosing Cholangitis,” American Journal of Gastroenterology, Vol. 95, No. 1, 2000, pp. 204-207. doi:10.1111/j.1572-0241.2000.01685.x
[30] D. C. Buckles, K. D. Lindor, N. F. Larusso, et al., “In Primary Sclerosing Cholangitis, Gallbladder Polyps Are Frequently Malignant,” American Journal of Gastroenterology, Vol. 97, 2002, pp. 1138-1142. doi:10.1111/j.1572-0241.2002.05677.x
[31] T. Itoi, H. Watanabe, M. Yoshida, et al., “Correlation of p53 Protein Expression with Gene Mutation in GallBladder Carcinomas,” Pathology International, Vol. 47, 1997, pp. 525-530. doi:10.1111/j.1440-1827.1997.tb04535.x
[32] A. Wee, M. Teh and G. C. Raju, “Clinical Importance of p53 Protein in Gall Bladder Carcinoma and Its Precursor Lesions,” Journal of Clinical Pathology, Vol. 47, 1994, pp. 453-456. doi:10.1136/jcp.47.5.453
[33] S. Tazuma and G. Kajiyama, “Carcinogenesis of Malignant Lesions of the Gall Bladder. The Impact of Chronic Inflammation and Gallstones,” Langenbeck’s Archives of Surgery, Vol. 386, No. 3, 2001, pp. 224-229. doi:10.1007/s004230100220
[34] M. Tada, O. Yokosuka, M. Omata, et al., “Analysis of Ras Gene Mutations in Biliary and Pancreatic Tumors by Polymerase Chain Reaction and Direct Sequencing,” Cancer, Vol. 66, 1990, pp. 930-935. doi:10.1002/1097-0142(19900901)66:5<930::AID-CNCR2820660519>3.0.CO;2-W
[35] K. Hanada, M. Itoh, K. Fujii, et al., “K-ras and p53 Mutations in Stage I Gallbladder Carcinoma with an Anomalous Junction of the Pancreaticobiliary Duct,” Cancer, Vol. 77, 1996, pp. 452-458. doi:10.1002/(SICI)1097-0142(19960201)77:3<452::AID-CNCR5>3.0.CO;2-M
[36] K. Wu, M. Liao, B. Liu and Z. Deng, “ADAM-17 OverExpression in Gallbladder Carcinoma Correlates with Poor Prognosis of Patients,” Medical Oncology, Vol. 28, No. 2, 2011, pp. 475-480. doi:10.1007/s12032-010-9481-8
[37] T. Y. Lee, S. F. Ko, C. C. Huang, et al., “Intraluminal versus Infiltrating Gallbladder Carcinoma: Clinical Presentation, Ultrasound and Computed Tomography,” World Journal of Gastroenterology, Vol. 15, No. 45, 2009, pp. 5662-5668. doi:10.3748/wjg.15.5662
[38] T. Wakai, Y. Shirai, N. Yokoyama, et al., “Early Gallbladder Carcinoma Does Not Warrant Radical Resection,” British Journal of Surgery, Vol. 88, No. 5, 2001, pp. 675678. doi:10.1046/j.1365-2168.2001.01749.x
[39] Y. Fong, L. Wagman, M. Gonen, et al., “Evidence-Based Gallbladder Cancer Staging: Changing Cancer Staging by Analysis of Data from the National Cancer Database,” Annals of Surgery, Vol. 243, No. 6, 2006, pp. 767-771. doi:10.1097/01.sla.0000219737.81943.4e
[40] I. Endo, H. Shimada, M. Tanabe, et al., “Prognostic Significance of the Number of Positive Lymph Nodes in Gallbladder Cancer,” Journal of Gastrointestinal Surgery, Vol. 10, No. 7, 2006, pp. 999-1007. doi:10.1016/j.gassur.2006.03.006
[41] H. Onoyama, M. Yamamoto, A. Tseng, et al., “Extended Cholecystectomy for Carcinoma of the Gallbladder,” World Journal of Surgery, Vol. 19, No. 5, 1995, pp. 758-763. doi:10.1007/BF00295925
[42] Y. Ogura, R. Mizumoto, S. Isaji, et al., “Radical Operations for Carcinoma of the Gallbladder: Present Status in Japan,” World Journal of Surgery, Vol. 15, 1991, pp. 337-343. doi:10.1007/BF01658725
[43] H. A. Pitt, “Gallbladder Cancer: What Is an Aggressive Approach?” Annals of Surgery, Vol. 241, No. 3, 2005, pp. 395-396. doi:10.1097/01.sla.0000154119.55201.e9
[44] Y. Shirai, T. Wakai and K. Hatakeyama, “Radical Lymph Node Dissection for Gallbladder Cancer: Indications and Limitations,” Surgical Oncology Clinics of North Ameri ca, Vol. 16, 2007, pp. 221-232. doi:10.1016/j.soc.2006.10.011
[45] K. Yamaguchi, K. Chijiiwa, S. Saiki, et al., “Retrospective Analysis of 70 Operations for Gallbladder Carcinoma,” British Journal of Surgery, Vol. 84, No. 2, 1997, pp. 200-204. doi:10.1002/bjs.1800840217
[46] T. Todoroki, T. Kawamoto, H. Takahashi, et al., “Treatment of Gallbladder Cancer by Radical Resection,” British Journal of Surgery, Vol. 86, No. 5, 1999, pp. 622-627. doi:10.1046/j.1365-2168.1999.01085.x
[47] E. Dixon, C. M. Vollmer Jr., A. Sahajpal, et al., “An Aggressive Surgical Approach Leads to Improved Survival in Patients with Gallbladder Cancer: A 12-Year Study at a North American Center,” Annals of Surgery, Vol. 241, No. 3, 2005, pp. 385-394. doi:10.1097/01.sla.0000154118.07704.ef
[48] Y. Shirai, T. Ohtani, K. Tsukada and K. Hatakeyama, “Combined Pancreaticoduodenectomy and Hepatectomy for Patients with Locally Advanced Gallbladder Carcinoma: Long Term Results,” Cancer, Vol. 80, 1997, pp. 1904-1909. doi:10.1002/(SICI)1097-0142(19971115)80:10<1904::AID-CNCR5>3.3.CO;2-Z
[49] X. de Aretxabala, I. Roa, M. Berrios, et al., “Chemoradiotherapy in Gallbladder Cancer,” Journal of Surgical Oncology, Vol. 93, No. 8, 2006, pp. 699-704. doi:10.1002/jso.20538
[50] T. Andre, J. M. Reyes-Vidal, L. Fartoux, et al., “Gemcitabine and Oxaliplatin in Advanced Biliary Tract Carcinoma: A Phase II Study,” British Journal of Cancer, Vol. 99, 2008, pp. 862-867. doi:10.1038/sj.bjc.6604628
[51] S. R. Alberts, H. Al-Khatib, M. R. Mahoney, et al., “Gemcitabine, 5-Fluorouracil, and Leucovorin in Advanced Biliary Tract and Gallbladder Carcinoma: A North Central Cancer Treatment Group Phase II Trial,” Cancer, Vol. 103, No. 1, 2005, pp. 111-118. doi:10.1002/cncr.20753
[52] T. Takada, H. Amano, H. Yasuda, et al., “Is Postoperative adjuvant Chemotherapy Useful for Gallbladder Carcinoma? A Phase III Multicenter Prospective Randomized Controlled Trial in Patients with Resected Pancreaticobiliary Carcinoma,” Cancer, Vol. 95, No. 8, 2002, pp. 1685-1695. doi:10.1002/cncr.10831
[53] V. Gebbia, E. Majello, A. Testa, et al., “Treatment of Advanced Adenocarcinomas of the Exocrine Pancreas and the Gallbladder with 5-Fluorouracil, High Dose Levofolinic Acid and Oral Hydroxyurea on a Weekly Schedule. Results of a Multicenter Study of the Southern Italy Oncology Group (G.O.I.M.),” Cancer, Vol. 78, 1996, pp. 1300-1307. doi:10.1002/(SICI)1097-0142(19960915)78:6<1300::AID-CNCR19>3.3.CO;2-Y
[54] J. S. Park, D. S. Yoon, K. S. Kim, et al., “Actual Recurrence Patterns and Risk Factors Influencing Recurrence after Curative Resection with Stage II Gallbladder Carcinoma,” Journal of Gastrointestinal Surgery, Vol. 11, No. 5, 2007, pp. 631-637. doi:10.1007/s11605-007-0109-z

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.