These authors contributed equally to this work.
Version of Record online: 25 JUN 2012
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 56, Issue 5, pages 1804–1816, November 2012
How to Cite
Cai, X., Zhai, J., Kaplan, D. E., Zhang, Y., Zhou, L., Chen, X., Qian, G., Zhao, Q., Li, Y., Gao, L., Cong, W., Zhu, M., Yan, Z., Shi, L., Wu, D., Wei, L., Shen, F. and Wu, M. (2012), Background progenitor activation is associated with recurrence after hepatectomy of combined hepatocellular-cholangiocarcinoma. Hepatology, 56: 1804–1816. doi: 10.1002/hep.25874
Potential conflict of interest: Nothing to report.
Supported by the Grant 2008ZX10002-025 from the State Key Project on Infectious Diseases of China. Additional support was provided by National Natural Science Foundation of China (No. 81030041), Key Basic Research Project of China (No. 2010CB945600, 2011CB966200), and China Scholarship Council (No. 2010658011).
- Issue online: 31 OCT 2012
- Version of Record online: 25 JUN 2012
- Accepted manuscript online: 9 JUN 2012 10:51AM EST
- Manuscript Accepted: 21 MAY 2012
- Manuscript Received: 5 DEC 2011
Additional Supporting Information may be found in the online version of this article.
|HEP_25874_sm_SuppFig1.tif||12954K||Supporting Figure 1. Histological diagnosis of combined epatocellular-cholangiocarcinoma. (A) Intermediate area showing combination of features of hepatocellular carcinoma (HCC, asterisk) and intrahepatic cholangiocellular carcinoma (ICC, arrow) embedding in stomal. For differential diagnosis, representative examples of the separated HCC and CC are shown: (B) Separated HCC and CC with synchronous but distinct HCC showing trabecular pattern (left, asterisk) and ICC showing malignant ductular structures (right, arrow) which are embedded in an inflamed fibrous stroma. (C) “collision tumor” showing nodules with distinct histological features separated by fibrosis. (D) Mucus lakes (Alcian blue-PAS staining, with nuclei staining with PCNA) in lumens of malignant ductular structures. (A-D bar=50µm) (E-F) HCC area is showing biliary differentiation confirmed by immunohistochemistry on sequential sections: (E), HepPar1 and (F) K7 stain (bar=100µm). (G-H) ICC area is also showing intermediate phenotype on sequential sections: (G), HepPar1 and (H) K7 stain (bar=50µm).|
|HEP_25874_sm_SuppFig2.tif||880K||Supporting Figure 2. Relative recurrence risk as a continuous function of HPCs related quantifications. The continuous function is represented by termplots for (A) PI-DR; (B) number of HPCs. The dashed curves indicate the risk scores ± standard errors.|
|HEP_25874_sm_SuppFig3.tif||1135K||Supporting Figure 3. Assessment of established Cox proportional hazards models for OS and DFS (Model A). (A) Plots of the deviance residuals for global models of OS (left) and DFS (right) show no wildly deviant observations. (B) Plots of the rescaled Schoenfeld residuals to assess the proportional hazards assumption for covariates in both OS and DFS models. Flat smooth curve confirmed by P>0.05 indicates a reasonable assumption.|
|HEP_25874_sm_SuppFig4.tif||1126K||Supporting Figure 4. Assessment of established Cox proportional hazards models for OS and DFS (Model B). (A) Plots of the deviance residuals for global models of OS (left) and DFS (right) show no wildly deviant observations. (B) Plots of the rescaled Schoenfeld residuals to assess the proportional hazards assumption for covariates in both OS and DFS models. Flat smooth curve confirmed by P>0.05 indicates a reasonable assumption.|
|HEP_25874_sm_SuppFig5.tif||1038K||Supporting Figure 5. PI-DR impacts recurrence of combined hepatocellular-cholangiocarcinoma, but in different pattern with K7-DR as well as inflammatory status. (A) Kaplan-Meier curves for cumulative recurrence hazard by severity of K7-DR (left), PI-DR (Right) in CHC patients with curative hepatectomy (n=70). Black curves showed overall recurrence, red curves showed late recurrence (K7 reactive DR, >20 months; PCNA index for DR, >10 months). (B) Kaplan-Meier curves for cumulative recurrence hazard by Ishak grade (left), NLR (Right) in CHC patients with curative hepatectomy (n=70). Black curves showed overall recurrence, red curves showed late recurrence (>10 months).|
|HEP_25874_sm_SuppFig6.tif||3296K||Supporting Figure 6. Univariate analysis of associations with “multicentric occurrence” (MO) of hepatocellular carcinoma component in combined hepatocellular-cholangiocarcinoma. (A) Representative photomicrograph of a patient with “MO” feature is shown in HCC-like area (bar=150µm). (B-C) Associations between present of MO and background liver related (B) or tumor related (C) factors are shown: PI-DRs, EpCAM expression in tumor (IOD) and OV-6 expressions (IOD) are represented by mean with SEM bar. Distribution of histological grading and staging of background liver diseases as well as presence of microvascular invasion (MVI) are shown by stacked column with percentage. Tumor sizes are shown by mean with SEM bar.|
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