RESUMO
Objective:To compare the safety and short-term prognosis of laparoscopic hepatectomy after conversion therapy versus pure laparoscopic hepatectomy for patients with hepatocellular carcinoma (HCC).Methods:A total of 740 patients with HCC undergoing laparoscopic hepatectomy at Sun Yat-sen Memorial Hospital of Sun Yat-sen University between January 2019 and December 2022 were screened for study eligibility, among which 433 patients were eligible, including 364 males and 69 females, aged (57.2±11.1) years. Patients who underwent laparoscopic hepatectomy after conversion therapy (including interventional therapy combined with targeted therapy or targeted therapy combined with immunotherapy, etc.) were marked as conversion resection group ( n=36), and those who underwent laparoscopic hepatectomy alone were marked as pure resection group ( n=397). After propensity score matching (PSM), 29 cases in the conversion resection group and pure resection group were finally enrolled. Preoperative (tumor number, maximum tumor diameter, etc.), intraoperative (operation time, intraoperative blood loss, etc.) and postoperative (hospital stay, drainage volume, complications, etc.) data and short-term prognosis were compared between the two groups. Survival curves and rates were analyzed using Kaplan-Meier and log-rank test. Results:The baseline characteristics including the occurrence of liver cirrhosis, the tumor number and maximum diameter showed no significant differences between the two groups after PSM (all P>0.05), indicating comparability. There were no statistical differences between the two groups in terms of operation time, intraoperative blood loss, postoperative hospital stay, postoperative drainage volume etc. (all P>0.05). The incidences of postoperative complications and severe complications (Clavien-Dindo grade ≥Ⅲ) were 34.5% (10/29) and 6.9% (2/29) in pure resection group, and 41.4% (12/29) and 10.3% (3/29) in conversion resection group, respectively, with no significant difference between the two groups (χ 2=0.29, 0, P=0.588, 1.000). The recurrence-free survival rates at 6, 12 and 18 months after surgery were 79.2%, 70.7% and 70.7% in conversion resection group and 86.2%, 82.8% and 79.3% in pure resection group, the overall survival rates at 6, 12, and 18 months after surgery were 96.4%, 89.5%, 74.6% in conversion resection group, and 100.0%, 96.6% and 93.1% in pure resection group, with no significant difference (χ 2=1.90, 1.91, P=0.168, 0.167). Conclusion:Laparoscopic hepatectomy after conversion therapy for initially unresectable HCC has comparable safety and short-term prognosis with the pure laparoscopic hepatectomy.
RESUMO
Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.