Significance of Zinc Replacement Therapy After Pancreaticoduodenectomy.

BACKGROUND/AIM: Recently, a decrease in serum zinc levels and the need for zinc preparations have been reported in the perioperative period of gastrointestinal surgery. In this study, we examined treatment outcomes among patients supplemented with zinc after pancreaticoduodenectomy (PD) and evaluated the significance of zinc replacement therapy. PATIENTS AND METHODS: From June 2020 to April 2021, 56 patients who received zinc acetate hydrate (50 mg/day) from postoperative day 3 after PD in our department were retrospectively reviewed. Patients' characteristics and preoperative as well as postoperative data, including serum zinc levels and surgical results at 1 month were reviewed. RESULTS: Preoperative zinc deficiency was present in 86.1% (46/56) of the patients. Moreover, despite zinc supplementation, 17.8% (10/56) of patients had postoperative zinc deficiency. A comparison between the low zinc level group (Zn <80 µg/dl) and the normal zinc level group (Zn ≥80 µg/dl) after surgery showed siginificant differences among patients with malignant diseases (vs. benign diseases, p=0.044), those undergoing open surgery (vs. minimally invasive surgery, p=0.036), and those with intraoperative blood loss ≥346 ml (vs. <346 ml: p=0.041) in the univariate analysis. Multivariate analysis revealed that zinc deficiency was significantly associated with open surgery [odds ratio (OR)=15.885, 95% confidence interval (CI)=1.77-142.01, p=0.013] and intraoperative blood loss (OR=9.329, 95% CI=1.50-57.74, p=0.016). CONCLUSION: In patients undergoing open PD for pancreatic cancer, zinc preparations of 50 mg may not be sufficient and further supplementation may be necessary.

The Eltrombopag antitumor effect on hepatocellular carcinoma.

Currently, sorafenib is the only available chemotherapeutic agent for advanced hepatocellular carcinoma (HCC), but it cannot be used in patients with liver cirrhosis (LC) or thrombocytopenia. In these cases, sorafenib is likely effective if given in combination with treatments that increase the number of platelets, such as thrombopoietin (TPO) receptor agonists. Increasing the platelet count via TPO treatment resulted in reduction of LC. Eltrombopag (EP), a TPO receptor agonist, has been reported to have antitumor effects against certain cancers, despite their lack of TPO receptor expression. We hypothesized that EP may possess antitumor activity against HCC in addition to its ability to suppress hepatic fibrosis by increasing the platelet count. In the present study, the antitumor activity of EP was examined by assessing the inhibition of cell proliferation and then ascertaining the ability of iron supplementation to reverse these effects in HepG2, Hep3B and Huh7 cells. In addition, a cell cycle assay was performed using flow cytometry, and signal transduction was evaluated by analyzing cell cycle-related protein expression. The results of EP were compared with those of the most common iron chelator, deferoxamine (DFO). The combined effect of EP and sorafenib was also assessed. The results revealed that EP exerts antitumor activity in HCC that is mediated by the modulation of intracellular iron content. EP suppressed the expression of the cell cycle-related protein cyclin D1 and elicited cell cycle arrest in the G0/G1 phase. The activity of EP was comparable to that of DFO in HCC, and EP did not compete with sorafenib at low concentrations. In conclusion, our findings suggest that EP is a good candidate chemotherapeutic agent for the treatment of HCC in patients with LC and thrombocytopenia.