Independent factors and predictive score for extrahepatic metastasis of hepatocellular carcinoma following curative hepatectomy.

BACKGROUND: Postoperative extrahepatic metastasis (EHM) contributes to a poor prognosis in patients with hepatocellular carcinoma (HCC) after hepatectomy. This study was aimed to develop a practical method that can be used to predict postoperative EHM. METHODS: In total, 578 patients were enrolled. We analyzed the clinicopathological features of the tumors and did a long-term follow-up to observe HCC recurrence. Postoperative EHM was detected in 136 patients, and multivariate analysis was used to confirm independent risk factors for postoperative EHM. After the factors were identified, a predictive scoring system was constructed as a weighted sum of these factors. The cutoff value that determines a high risk for EHM was defined by maximizing the Youden's index of the receiver operating characteristic curve. RESULTS: Microvascular invasion, incomplete capsule, and larger tumor diameter were the three independent factors predictive for a high risk for EHM. The scoring system was derived with an area under the curve (AUC) of 0.81 for postoperative 10-year EHM prediction. A cutoff value of 43 was derived and validated with a sensitivity >90% and specificity >60% to predict the development of EHM. This system was further verified in a subgroup of Barcelona Clinic Liver Cancer stage 0-A patients with an AUC of 0.82. When the cutoff value was set at 43, the sensitivity and specificity were 90.38% and 64.88%, respectively. CONCLUSIONS: Our predictive scoring system may be used to identify HCC patients who have a high risk for EHM following curative hepatectomy.

Apotransferrin is internalized and distributed in the same way as holotransferrin in K562 cells.

Transferrin (Tf), a naturally existing protein, has received considerable attention in the area of drug targeting since it is biodegradable, non-toxic, and non-immunogenic. The efficient cellular uptake of Tf shows it has potential in the delivery of anti-cancer drugs, proteins, and therapeutic genes into proliferating malignant cells that overexpress transferrin receptor (TfR). In human serum, about 30% of Tf exists in the iron-saturated form (Fe(2)-Tf) and the remainder exists as apotransferrin (apo-Tf). Understanding the uptake of apo-Tf by cells will provide key insights into studies on Tf-mediated drug delivery. In the present study, we investigated visually the transport of apo-Tf into K562 cells and its intracellular localization by laser-scanning confocal microscopy (LSCM) and flow cytometry analysis (FCA). It was found that, like Fe(2)-Tf, apo-Tf can be taken up into the cells. The process is time- and temperature-dependent, competitively inhibited by Fe(2)-Tf, and significantly abolished by pronase pretreatment. Visual evidence showed that the transport of apo-Tf into K562 cells is a TfR-mediated process. Furthermore, the investigations using optical-slicing technique demonstrated that the distribution of apo-Tf is similar to that of Fe(2)-Tf, both appearing in the perinuclear region in ball-in-bowl shape.