Does surgical resection of hepatocellular carcinoma accelerate cancer dissemination?

Abstract

AIM:This study was to investigate whether surgery could increase cancer dissemination and postoperative recurrence in patients with hepatocellular carcinoma (HCC) by detection of human α-fetoprotein messenger RNA (hAFP mRNA). hAFP mRNA in the peripheral blood of patients with HCC has been considered as a surrogate marker for circulating tumor cells. METHODS:Eighty-one consecutive patients who underwent curative resection for HCC entered this prospective cohort study. We examined hAFP mRNA from the peripheral blood obtained preoperatively, perioperatively, and postoperatively to correlate the prognosis after curative resections from HCC patients and from the control subjects. Detection of hAFP mRNA by reverse transcriptase and polymerase chain reaction amplification (RT-PCR) was performed with primers specifically. The relations between the clinical variables (age, sex, associated liver cirrhosis, hepatitis B virus infection, hepatitis C virus infection, serum α-fetoprotein and ChildPugh class), the histological variables (size, capsule, vascular permeation, grade of differentiation, and daughter nodules), hAFP mRNA in peripheral blood of 3 different sessions, and postoperative course (recurrence, and recurrence related death) were analysed. RESULTS:No hAFP mRNA was detected in control group subjects. Twenty-two (27%), 24 (30%) and 19 (23%) of 81 HCC patients had hAFP mRNA positivity in the preoperative, perioperative and postoperative peripheral blood. The preoperative presence did not influence the risk of HCC recurrence (55% vs 41%, P=0.280). In contrast, patients with postoperative presence had a significantly higher recurrence (90% vs 31%, P<0.001; odds ratio 19.2; 95% confidence interval: 4.0-91.7). In the multivariate analysis by COX proportional hazards model, postoperative positivity had a significant influence on recurrence (P=0.067) and recurrence related mortality (P=0.017). Whereas, the perioperative positivity of hAFP mRNA did not increase HCC recurrence (58% vs.39%, P=0.093). The correlation between perioperative hAFP mRNA positivity and recurrence related mortality had no statistical significance (P=0.836).CONCLUSION: From our study, perioperative detection of hAFP mRNA in peripheral blood of patients has no clinical relevance and significant role in the prediction of HCC recurrence. Surgical resection itself may not accelerate cancer dissemination and does not increase postoperative recurrence significantly either.

Connexins as Precocious Markers and Molecular Targets for Chemical and Pharmacological Agents in Carcinogenesis

“…By applying high-resolution deconvolution microscopy, that allows the visualization of Cx signal within tumor testis, we proposed Cx43 delocalization as an early event associated with uncontrolled cell proliferation and a neoplastic marker of testis tumorisation since this aberrant Cx localization preceded down-regulation of Cx protein levels in a mouse testis cancer [169]. Other authors reported in patients who have undergone curative resection for hepatocellular carcinoma (HCC) that the reduced Cx32 mRNA expression in noncancerous liver tissues may play a significant role in the prediction of postoperative recurrence of this cancer [223].…”

Influence of surgical resection of hepatocellular carcinoma(HCC) for hematogenous dissemination of HCC cells and its effect on recurrence and metastasis: 3 years prospective study

“…We think surgical resection of HCC may caused HCC cells spreading into peripheral blood shortly, but it is not concerning with recurrence and metastasis of HCC, just as the report from Sheen's [23]. HCC tumor vaccines may also play important role in clearance of these circulating HCC cells which may concern with HCC recurrence or metastasis, the further study is on the way [24,25,26].…”

Detecting Carcinoma Cells in Peripheral Blood of Patients With Hepatocellular Carcinoma by Immunomagnetic Beads and RT-PCR

“…14 Most CTCs may die in the blood by various host immune and nonimmune defenses, and can be destroyed by mechanical forces including turbulence and the trauma associated with vascular adhesion and transcapillary passage, or lysed by lymphocytes, monocytes, natural killer cells. 3 Other tumor cells may escape these defense mechanisms, and migrate to a new site where they adhere to the walls of the capillary system of a new organ and form new metastatic foci. Early detection of CTCs may help to assess the stage of the patients' diseases and prognosis as well as recurrence.…”

“…Over half of those who undergo resection develop recurrence within 3 years. 2,3 Five-year survival rate of patients undergoing hepatic resection and orthotopic liver transplantation is 17% to 50% and 20% to 36%, respectively. 2,4 Patients detected early is up to 86.4% with the similar treatments.…”