Spontaneous and iatrogenic spreading of liver-derived cells into peripheral blood of patients with primary liver cancer

Abstract

The prognosis for patients with primary liver cancer (PLC)Despite advances in the appraisal of the impact and role often depends on tumor recurrence and the development of of etiologic factors, improvement in diagnostic tools and surextrahepatic metastases, particularly after liver transplanta-gical and nonsurgical treatments, primary liver cancer (PLC), tion. We have developed a sensitive test to detect both sponta-the eighth commonest tumor worldwide, still represents a neous circulation of tumor cells and the spread of liver cells therapeutic challenge. [1][2][3][4][5][6] In Western countries, PLC generally due to chemoembolization and alcoholization. Reverse-tran-develops on a background of cirrhosis; this hampers surgical scription polymerase chain reaction was used to search for and nonsurgical efforts to eradicate the disease because circells expressing a-fetoprotein (AFP) messenger RNA in the rhosis is a permanent source of tumorous nodules, and it peripheral blood of 84 patients with PLC and 102 controls complicates treatment with severe liver failure. 7-11(55 patients with chronic hepatitis and/or cirrhosis, 10 paPartial hepatic resection is limited by tumor characteristics tients with benign liver tumors or liver metastases from intes-such as size, multifocality, topography, and severity of associtinal cancers, and 37 healthy individuals). By spiking the ated cirrhosis. Only 10% of patients with PLC are considered blood of healthy volunteers with HepG2 cells, we assessed acceptable for resection and, of these, the 3-year recurrence the sensitivity limit: one HepG2 cell mixed with 10 7 leuko-rate ranges from 60% to 80%, and the survival rate ranges cytes. All 102 controls tested negative. In contrast, 28 patients from 40% to 70%. 4,[11][12][13][14][15][16] An alternative treatment for small (33.3%) with PLC tested positive. Positivity for the test was tumors is alcoholization, 17 but the advantages of this apsignificantly associated with portal thrombosis, tumor size, proach are currently being debated. 18 The treatment of adintravascular tumor emboli, serum AFP level, and extrahe-vanced liver cancers by transarterial chemoembolization patic metastases. Patients were followed up for a mean period (TACE), chemotherapy, and hormonal treatment with taof 39 { 51 weeks: the probability of developing extrahepatic moxifen has provided discouraging results in previous pubmetastases was significantly higher in positive than in nega-lished trials. 2, 19 tive patients. Eighteen negative patients with PLC were testedDespite this overall poor prognosis, a main feature of PLC before, 1 hour after, and 24 hours after locoregional therapy: is the rarity of extrahepatic metastases, which generally only 9 tested positive either 1 or 24 hours after alcoholization or become evident at a late tumor stage.20 Liver transplantation chemoembolization. In conclusion, we have developed a has, therefore, been proposed to cure both liver cancer and highly specific and sensitive test to detect circulating tumor cirrhosis.1,21-24 S...

Liver transplantation for small hepatocellular carcinoma: The tumor-node-metastasis classification does not have prognostic power

“…However, it has been suggested that these invasive treatments may indeed induce tumor cell dissemination. 40,41 Probably, in immunocompetent individuals, the iatrogenic dissemination of cells is not relevant, but in subjects receiving immunosuppression with several agents this cell spread may increase the risk of presenting clinically apparent metastatic sites both inside and outside the liver. We do not ascribe the recurrences of other series to the application of coadjuvant treatment, but we have to stress that we did not perform any kind of adjuvant treatment and this has not prompted a significant recurrence rate or relevant tumor growth while waiting for OLT.…”

Does surgical resection of hepatocellular carcinoma accelerate cancer dissemination?

“…Both kinds of cells may contribute to the positivity of hAFP mRNA. According to Louha M, not only liver surgery but also nonsurgical invasive managements such as needle liver biopsy or intervention therapies such as TACE, chemotherapy and ethanol ablation therapy, the increased shedding of either HCC cells or normal hepatocytes into circulation might contribute to the increase of detection rate of hAFP mRNA [38] . This was also the reason why we excluded those who had received these intervention therapies from the current study.…”

“…Witzigmarn obtained blood samples before and during the operation (after mobilization of the liver), and on the second postoperative day [39] . Louha obtained peripheral blood samples before treatment, 1 hour and 24 hours after percutaneous ethanol injection or TACE treatment [38] . Witzigmann obtained blood samples on the second day after TACE [39] .…”

Present and Future Developments in Hepatic Tissue Engineering for Liver Support Systems

“…However, a concern with the use of hepatic tumor cell lines, e.g. HepG2, is the possible risk in the transmission of potentially tumorigenic cells to patients (Louha et al 1997). Instead, primary human and xenogeneic hepatocytes are used in bioartificial systems which have been or are currently in various stages of clinical evaluation.…”