Article first published online: 27 JUN 2003
Copyright © 2003 American Cancer Society
Volume 98, Issue 5, pages 1101–1102, 1 September 2003
How to Cite
Dhar, D. K., Ono, T., Yamanoi, A. and Nagasue, N. (2003), Author reply. Cancer, 98: 1101–1102. doi: 10.1002/cncr.11590
- Issue published online: 20 AUG 2003
- Article first published online: 27 JUN 2003
We thank Dr. Tez for their interest in the our study.1 We appreciate them seeking this vital point regarding modulation of the serum endostatin level by the extent of hepatic resection. This is indeed a vital issue for those clinicians who perform hepatic resections for hepatocellular carcinoma (HCC) or metastatic liver tumors. In our series the data regarding the postoperative endostatin level were available for 28 patients. Of these 28 patients, 11 underwent limited hepatic resection (LHR) (segmentectomy and subsegmentectomy) and 17 patients underwent major hepatic resections (MHR) (left or right hepatectomy). There was a marginally significant difference found with regard to the postoperative serum endostatin level between patients who underwent LHR and those who underwent MHR (P = 0.0455 according to the Mann–Whitney U test and P = 0.1766 according to the F-test;, 13.56 ± 5.10 ng/mL vs. 6.78 ± 2.75 ng/mL, respectively). This trend toward a lower postoperative serum endostatin level after an MHR may indicate that the liver tissue itself was a source of serum endostatin.
However, several factors should be taken into consideration before interpreting these data. Because the tumor size also was larger in all cases in which an MHR was performed, the tumor size may have affected the posthepatectomy serum endostatin level. In addition, to our knowledge the effect of the regenerative drive on the serum endostatin level after hepatectomy is not known. Hepatic regeneration status after differing extents of liver resection may have modulated the serum endostatin level but this could not be addressed in our study. The precise mechanism of endostatin release from Type XVIII collagen has yet to be understood clearly. It has been postulated that several proteolytic enzymes such as cathepsin L and elastase are involved in the cleavage of endostatin from Type XVIII collagen.2, 3 However, in an in vitro study, it was shown that several Type XVIII collagen-producing cells could not generate endostatin, even when large amounts of proteolytic enzymes were supplemented into the cultures,3 indicating that the release of endostatin is a strictly controlled process. Therefore, the exact mechanism of release of endostatin from hepatocytes after hepatic resection and during the regenerative process remains to be elucidated. Further animal studies are needed to address these vital and interesting issues regarding whether the liver actually is the major source of serum endostatin and how this is changed by the extent of liver resection and the regenerative process.