Abstract
The objective of this study was to analyze the predictive significance of different prognostic factors associated with recurrence and metastasis after the radical resection in patients with hepatolithiasis complicated by intrahepatic cholangiocarcinoma (HLA/IHCC). A total of 138 patients with HLA/IHCC admitted during April 2006–April 2009 were selected for this study and they were divided into two groups, with and without recurrence/metastasis. After a radical resection surgery, the patients were followed up for 5 years to monitor the recurrence and/or metastasis. The general and clinical data of the two groups were analyzed to evaluate the relevant risk factors. The study showed that recurrence/metastasis occurred in 48 patients with a rate of 34.8 %. Recurrence in liver accounted for 85.4 % (41 cases), whereas in lung and bone metastases occurred at rates of 8.3 % (4 cases) and 6.3 % (3 cases), respectively. Univariate analysis revealed that CA19-9, tumor diameter, tumor amount, lymphatic metastasis, and AJCC stage of the recurrence/metastasis group were significantly different from those of the non-recurrence/metastasis patients (p < 0.05). The multivariate analysis showed that CA19-9 > 200 U/mL, tumor diameter >5 cm, presence of multiple tumors, lymphatic metastasis, and III–IV AJCC stages were independent risk factors of tumor recurrence and metastasis after the radical surgery (p < 0.05). During the 5 years of follow-up, 65 patients (47.1 %) died, including 31 in the recurrence/metastasis and 34 in the non-recurrence/metastasis groups, accounting for 64.5 % (31/48) and 37.8 % (34/90) of mortality in the two groups, respectively. Thus, the 5-year mortality in the recurrence/metastasis group was significantly higher than that in the non-recurrence/metastasis group (p < 0.05). The CA19-9 antigen, tumor diameter, tumor amount, lymphatic metastasis, and AJCC stage were significantly associated with increased risk of post-resection recurrence and metastasis of HLA/IHCC. The massive lymphadenectomy during the surgery and perioperative control of inflammation decreased the risk of recurrence/metastasis and further improved the disease prognosis.
Similar content being viewed by others
References
Uenishi, T., Kubo, S., Yamazaki, O., Yamada, T., Sasaki, Y., Nagano, H., & Monden, M. (2008). Indications for surgical treatment of intrahepatic cholangiocarcinoma with lymph node metastases. Journal of Hepatobiliary Pancreatic Surgery, 15(4), 417–422.
Tan, J., Tan, Y., Chen, F., Zhu, Y., Leng, J., & Dong, J. (2015). Endoscopic or laparoscopic approach for hepatolithiasis in the era of endoscopy in China. Surgical Endoscopy, 29(1), 154–162. doi:10.1007/s00464-014-3669-5.
Kasai, K., Kooka, Y., Suzuki, Y., Suzuki, A., Oikawa, T., Ushio, A., et al. (2014). Efficacy of hepatic arterial infusion chemotherapy using 5-fluorouracil and systemic pegylated interferon alpha-2b for advanced intrahepatic cholangiocarcinoma. Annals of Surgical Oncology, 21(11), 3638–3645.
Yang, X. Q., Xu, Y. F., Guo, S., Liu, Y., Ning, S. L., Lu, X. F., et al. (2014). Clinical significance of nerve growth factor and tropomyosin-receptor-kinase signaling pathway in intrahepatic cholangiocarcinoma. World Journal of Gastroenterology : WJG, 20(14), 4076–4084.
Mavros, M. N., Economopoulos, K. P., Alexiou, V. G., & Pawlik, T. M. (2014). Treatment and prognosis for patients with intrahepatic cholangiocarcinoma: Systematic review and meta-analysis. JAMA Surgery. doi:10.1001/jamasurg.2013.5137.
Chen, M. F., Jan, Y. Y., Hwang, T. L., Jeng, L. B., & Yeh, T. S. (2000). Impact of concomitant hepatolithiasis on patients with peripheral cholangiocarcinoma. Digestive Disease Science, 45, 312–316.
Zhou, Y. M., Yin, Z. F., Yang, J. M., et al. (2008). Risk factors for intrahepatic cholangiocarcinoma: A case-control study in China. World Journal of Gastroenterology, 14, 632–635.
Kuroki, T., Tajima, Y., & Kanematsu, T. (2005). Hepatolithiasis and intrahepatic cholangiocarcinoma: Carcinogenesis based on molecular mechanisms. Journal of Hepatobiliary and Pancreatic Surgery, 12, 463–466.
Lazaridis, K. N., & Gores, G. J. (2005). Cholangiocarcinoma. Gastroenterology, 128, 1655–1667.
Tischoff, I., & Tannapfel, A. (2007). Hepatocellular carcinoma and cholangiocarcinoma-different prognosis, pathogenesis and therapy. Zentralblatt für Chirurgie, 2007(132), 300–305.
Nakayama, T., Tsuchikawa, T., Shichinohe, T., Nakamura, T., Ebihara, Y., & Hirano, S. (2014). Pathological confirmation of para-aortic lymph node status as a potential criterion for the selection of intrahepatic cholangiocarcinoma patients for radical resection with regional lymph node dissection. World Journal of Surgery, 38(7), 1763–1768.
Peycru, T., Hardwigsen, J., Gregoire, E., Barbier, L., Richa, H., Campan, P., & Le Treut, Y. P. (2009). Radical surgery in intrahepatic cholangiocarcinoma. Gastroenterologie Clinique et Biologique, 33(3), 187–193.
Zhang, G. W., Lin, J. H., Qian, J. P., & Zhou, J. (2014). Identification of prognostic factors and the impact of palliative resection on survival of patients with stage IV hepatolithiasis-associated intrahepatic cholangiocarcinoma. Journal of Surgical Oncology, 109(5), 494–499.
Jiang, K., Su, M., Zhang, W., Zhao, X., Wang, J., Dong, J., & Huang, Z. (2014). Complete radiofrequency ablation of hepatolithiasis-associated cholangiocarcinoma and successful management of post-ablation bronchobiliary fistula. Cell Biochemistry and Biophysics, 68(3), 555–559.
Zhu, Q. D., Zhou, M. T., Zhou, Q. Q., Shi, H. Q., Zhang, Q. Y., & Yu, Z. P. (2014). Diagnosis and surgical treatment of intrahepatic hepatolithiasis combined with cholangiocarcinoma. World Journal of Surgery, 38(8), 2097–2104.
Jiang, Z. J., Chen, Y., Wang, W. L., Shen, Y., Zhang, M., Xie, H. Y., et al. (2013). Management hepatolithiasis with operative choledochoscopic FREDDY laser lithotripsy combined with or without hepatectomy. Hepatobiliary & Pancreatic Diseases International, 12(2), 160–164.
Han, S. L., Zhou, H. Z., Cheng, J., et al. (2009). Diagnosis and surgical treatment of intrahepatic hepatolithiasis associated cholangiocarcinoma. Asian Journal of Surgery, 32(1), 1–6.
Edge, S. B., & Compton, C. C. (2010). The American Joint Committee on Cancer: The 7th edition of the AJCC cancer staging manual and the future of TNM. Annals of Surgical Oncology, 17, 1471–1474.
Lin, C. C., Lin, P. Y., & Chen, Y. L. (2013). Comparison of concomitant and subsequent cholangiocarcinomas associated with hepatolithiasis: Clinical implications. World Journal of Gastroenterology, 19(3), 375–380.
Yang, T., Lau, W. Y., Lai, E. C., Yang, L. Q., Zhang, J., Yang, G. S., et al. (2010). Hepatectomy for bilateral primary hepatolithiasis: A cohort study. Annals of Surgery, 251(1), 84–90.
Takaoka, M., Shimatani, M., Ikeura, T., Koyabu, M., Kusuda, T., Fukata, N., et al. (2009). Diagnostic and therapeutic procedure with a short double-balloon enteroscope and cholangioscopy in a patient with acute cholangitis due to hepatolithiasis. Gastrointestinal Endoscopy, 70(6), 1277–1279.
Bellocq, J. P., Michiels, J. F., Egele, C., & Chenard, M. P. (2012). ICC and IHC: Techniques and quality assurance. Lessons from the French external quality assessment trials in IHC. Annales de Pathologie, 32(5 Suppl), S94–S95.
Li, H. Y., Zhou, S. J., Li, M., Xiong, D., Singh, A., Guo, Q. X., et al. (2012). Diagnosis and cure experience of hepatolithiasis-associated intrahepatic cholangiocarcinoma in 66 patients. Asian Pacific Journal of Cancer Prevention, 13(2), 725–729.
Luo, H. L., Kang, C. H., Chen, Y. T., Chuang, Y. C., Lee, W. C., Cheng, Y. T., & Chiang, P. H. (2013). Severity of hydronephrosis correlates with tumour invasiveness and urinary bladder recurrence of ureteric cancer. BJU International, 112(4), 489–494.
Matsukawa, H., Fujiwara, Y., Satoh, D., Shiozaki, S., Ohno, S., Hamada, M., et al. (2013). Two cases of long-term survival after treatment of recurrent intrahepatic cholangiocarcinoma and intrahepatic metastasis in the remnant liver with repeated hepatectomy. Gan to Kagaku Ryoho Cancer & Chemotherapy, 40(12), 1828–1830.
Fukushima, K., Kido, M., Fukumoto, T., Hori, Y., Kusunoki, N., Tsuchida, S., et al. (2011). A case report of intrahepatic cholangiocarcinoma diagnosed as lung cancer with liver metastasis treated with radiofrequency ablation. Gan to Kagaku Ryoho Cancer & Chemotherapy, 38(12), 2030–2032.
Dechaphunkul, A., Kanngurn, S., Dechsukhum, C., Tanutit, P., Khow-Ean, U., & Sunpaweravong, P. (2010). The significance of galectin-3 immunohistochemistry, clinical characteristics and liver imaging in differentiating intrahepatic cholangiocarcinoma from adenocarcinoma liver metastasis. Journal of the Medical Association of Thailand = Chotmaihet Thangphaet, 93(5), 523–528.
Yu, Y., Liao, M., Liu, R., Chen, J., Feng, H., & Fu, Z. (2014). Overexpression of lactate dehydrogenase-A in human intrahepatic cholangiocarcinoma: Its implication for treatment. World Journal of Surgical Oncology, 12, 78.
Dhanasekaran, R., Hemming, A. W., Zendejas, I., George, T., Nelson, D. R., Soldevila-Pico, C., et al. (2013). Treatment outcomes and prognostic factors of intrahepatic cholangiocarcinoma. Oncology Reports, 29(4), 1259–1267.
Perkins, G., Slater, E., Sanders, G., & Prichard, J. (2003). Serum tumor markers. American Family Physician, 68(6), 1075–1082.
Goonetilleke, K. S., & Siriwardena, A. K. (2007). Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer. European Journal of Surgical Oncology, 33(3), 266–270.
Jan, Y. Y., Yeh, C. N., Yeh, T. S., et al. (2005). Prognostic analysis of surgical treatment of peripheral cholangiocarcinoma: Two decades of experience at Chang Gung Memorial Hospital. World Journal of Gastroenterology, 11, 1779–1784.
Li, Y. G., & Zhang, N. (2009). Clinical significance of serum tumour M2-pk and CA19-9 detection in the diagnosis of cholangiocarcinoma. Digestive Liver Disease, 44, 605–608.
Lazarov, N., Lazarov, L., & Lazarov, S. (2013). Tumor size and prognosis for patients with epithelial ovarian carcinoma at early stage. Akusherstvo i Ginekologiia, 52(4), 10–12.
Gupta, D., & Lis, G. (2010). CG: Pretreatment serum albumin as a predictor of cancer survival: A systematic review of the epidemiological literature. Nutrition Journal, 9, 69–84.
Yamamoto, M., Takasaki, K., & Yoshikawa, T. (1999). Lymph node metastasis in intrahepatic cholangiocarcinoma. Japanese Journal of Clinical OncoIogy, 29(3), 147–150.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zhu, Y., Zhu, Y., Cai, F. et al. Prognostic Risk Factors Associated with Recurrence and Metastasis After Radical Resection in Patients with Hepatolithiasis Complicated by Intrahepatic Cholangiocarcinoma. Cell Biochem Biophys 73, 455–460 (2015). https://doi.org/10.1007/s12013-015-0665-x
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12013-015-0665-x