Everolimus Plus Ku0063794 Regimen Promotes Anticancer Effects against Hepatocellular Carcinoma Cells through the Paradoxical Inhibition of Autophagy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Everolimus only inhibits mammalian target of rapamycin complex 1 (mTORC1), whereas Ku0063794 inhibits both mTORC1 and mTORC2. Although they have similar anticancer effects, their combination has a synergistic effect against hepatocellular carcinoma (HCC) cells. We aimed to determine the mechanism underlying the synergistic effects of everolimus and Ku0063794 associated with autophagy in HCC cells. MATERIALS AND METHODS: We compared the effects of everolimus and Ku0063794, individually or in combination, on both the in vitro and in vivo models of HCCs. RESULTS: HepG2 cells treated with both agents had significantly lower rates of cell proliferation and higher apoptosis than the individual monotherapies (p < 0.05). Autophagic studies consistently indicated that, unlike the monotherapies, the combination therapy significantly reduced autophagy (p < 0.05). Autophagic blockage directly promoted the pro-apoptotic effects of combination therapy, suggesting autophagy as the survival mechanism of HCC cells. Unlike the monotherapies, combination therapy showed the potential to inhibit sirtuin 1 (SIRT1), the positive regulator of autophagy. SIRT1 overexpression abrogated the autophagy-inhibiting and pro-apoptotic effects of combination therapy. In a nude mouse xenograft model, the shrinkage of tumors was more prominent in mice treated with combination therapy than in mice treated with the respective monotherapies (p < 0.05). The immunohistochemical and immunofluorescence stains of the tumor obtained from the xenograft model showed that combination therapy had the potential of reducing autophagy and promoting apoptosis. CONCLUSION: The combination of everolimus and Ku0063794 potentiates anticancer effects on HCCs through a decrease in autophagy, which is prompted by SIRT1 downregulation.

The feasibility of single-port laparoscopic appendectomy using a solo approach: a comparative study

PURPOSE: To investigate the feasibility and safety of solo surgery with single-port laparoscopic appendectomy, which is termed herein solo-SPLA (solo-single-port laparoscopic appendectomy). METHODS: This study prospectively collected and retrospectively analyzed data from patients who had undergone either non-solo-SPLA (n = 150) or solo-SPLA (n = 150). Several devices were utilized for complete, skin-to-skin solo-SPSA, including a Lone Star Retractor System and an adjustable mechanical camera holder. RESULTS: Operating times were not significantly different between solo- and non-solo-SPLA (45.0 +/- 21.0 minutes vs. 46.7 +/- 26.1 minutes, P = 0.646). Most postoperative variables were also comparable between groups, including the necessity for intravenous analgesics (0.7 +/- 1.2 ampules [solo-SPLA] vs. 0.9 +/- 1.5 ampules [non-solo-SPLA], P = 0.092), time interval to gas passing (1.3 +/- 1.0 days vs. 1.4 +/- 1.0 days, P = 0.182), and the incidence of postoperative complications (4.0% vs. 8.7%, P = 0.153). Moreover, solo-SPLA effectively lowered the operating cost by reducing surgical personnel expenses. CONCLUSION: Solo-SPLA economized staff numbers and thus lowered hospital costs without lengthening of operating time. Therefore, solo-SPLA could be considered a safe and feasible alternative to non-solo-SPLA.

Does Korea's current diagnosis-related group-based reimbursement system appropriately classify appendectomy patients?

PURPOSE: As several years have passed since the implementation of the Korean diagnosis-related group (DRG) payment system for appendicitis, its early outcomes should be assessed to determine if further improvements are warranted. METHODS: We retrospectively analyzed clinical data from Korean patients who underwent appendectomy, dividing the sample into 2 groups of those who received services before and after implementation of the DRG system. Based on the DRG code classification, patient data were collected including the amount of DRG reimbursement and the total in-patient costs. We subsequently performed univariate and multivariate analyses to identify independent factors contributing to higher total in-patient cost. RESULTS: Although implementation of the DRG system for appendicitis significantly reduced postoperative length of stay (2.8 ± 1.0 days vs. 3.4 ± 1.9 days, P 70 years) have greater comorbidities, which contribute to higher inpatient costs. Thus, our study suggests that patient age be considered as a DRG classification variable.