1. Cardiovascular and Gastroenterological Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University 890-8520, Kagoshima, Japan
2. Department of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan
3. Department of Surgery, Kirishima Medical Center, Kirishima 899-5112, Japan.
4. Department of Surgery, Kagoshima Medical Center, National Hospital Organization, Kagoshima 892-0853, Japan
5. Department of Epidemiology and Preventive Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan
* These authors share joint senior authorship
Purpose: Serotonin (5-hydroxytryptamine, 5-HT) is well known for its growth stimulatory effect on several types of carcinoma and tumor cells. Since a large portion of 5-HT is stored and transported by platelets, the aim of this study was to assess the influence of platelet-sequestered 5-HT on post-resection hepatocellular carcinoma (HCC) recurrence.
Methods: This pilot study was conducted in a cohort of forty patients diagnosed with HCC undergoing partial hepatectomy. 5-HT levels in serum, plasma and intra-platelet (IP) were monitored preoperatively and four weeks after liver resection. The patients were followed every three months after the surgery.
Results: Follow-up was standardized to a fixed length of time. Fifteen patients (37.5%) developed HCC recurrence during 18 months follow-up. Patients with recurrence had significantly reduced serum and IP 5-HT levels at four weeks of liver resection (P = 0.003 and P = 0.014 respectively). Accordingly, in the Cox regression hazard model, serum and IP 5-HT were able to independently predict the recurrence (hazard ratio = 0.1, 95% confidence interval = 0.01 - 0.75 and hazard ratio = 0.1, 95% confidence interval = 0.01 - 0.89 respectively). The optimal cut-off value of 42.77 ng/ml for serum [area under the curve (AUC): 0.78, P = 0.003] and 0.3117 ng per 106 platelets (AUC: 0.733, P = 0.015), on receiver operating characteristic (ROC) curve corresponded to maximum sensitivity and specificity of prediction. The disease free interval was significantly worse in patients with low serum and IP 5-HT (P = 0.001 and P = 0.029 respectively).
Conclusion: IP 5-HT monitored during early follow-up, after liver resection may represent a useful marker of early HCC recurrence.
Keywords: Hepatocellular Carcinoma, liver cirrhosis, liver resection, platelet, serotonin