Comparative study on prognosis of neoadjuvant chemotherapy followed by hepatic surgery versus upfront surgery in patients with synchronous colorectal liver metastasis / 中华胃肠外科杂志

Objective: To compare the survival outcome in patients with synchronous colorectal cancer liver metastasis receiving neoadjuvant chemotherapy followed by hepatic surgery versus upfront surgery strategies. Methods: A retrospective cohort study was carried out. Data of patients undergoing surgery at the Department of Hepatopancreatobiliary Surgery Unit I of Peking University Cancer Hospital from January 2008 to December 2018 for initially resectable synchronous colorectal liver metastasis were retrospectively collected. A total of 282 cases were enrolled, including 244 in the neoadjuvant chemotherapy group, 38 in the upfront surgery first group. The overall survival (OS) and progression-free survival (PFS) of the two groups were compared. A propensity score risk adjustment was used to eliminate potential bias between groups, and the covariates including sex, age, location of primary tumor, T stage, clinical risk score (CRS), RAS gene status, adjuvant chemotherapy, and resection margin status were included for adjustment. Results: In the neoadjuvant chemotherapy group, 244 cases received 4 (1-15) cycles of chemotherapy before hepatic resection, among whom 207 cases received oxaliplatin-based regimens, 37 cases received irinotecan-based regimens, and 90 cases received combined targeted agents in the first line treatment. The median follow-up time was 30 (5-134) months, and loss of follow-up was 1%. Before adjustment, Kaplan-Meier survival analysis showed that the 1-year and 3-year OS rates in the neoadjuvant chemotherapy group (95.1% and 66.4%) were better than those in the upfront surgery first group (94.7% and 51.5%, P=0.026); 1-year and 3-year PFS rates in neoadjuvant chemotherapy group (51.0% and 23.4%) were also better than those in surgery first group (39.5% and 11.5%, P=0.039). After propensity score risk adjustment, Cox multivariate analysis indicated that neoadjuvant chemotherapy was an independent protective factor of PFS (HR=0.664, 95% CI: 0.449-0.982, P=0.040), however, neoadjuvant chemotherapy was not an independent protective factor of OS (HR=0.651, 95% CI: 0.393-1.079, P=0.096). Subgroup analysis showed that the 1-year and 3-year OS rates in the patients with response to the first line treatment (194, including complete remission, partial remission and reduction but not partial remission) (96.9% and 67.1%) were better than those in the upfront surgery group (94.7% and 51.5%, P=0.026) after adjustment. However, the 1-year and 3-year OS rates in the patients without response to the first line treatment (50, including tumor progression or enlargement) were 90.0% and 63.3%, respectively, which were not significantly different with 94.7% and 51.5% in the upfront surgery group (P=0.310) after adjustment. Conclusions: For patients with resectable synchronous colorectal cancer liver metastasis, liver resection after neoadjuvant chemotherapy can provide longer PFS than upfront surgery. Although the whole OS benefit is not significant, patients with effective neoadjuvant first-line chemotherapy have better OS than those undergoing upfront surgery.

Expression of plasminogen activator inhibitor-2 is negatively associated with invasive potential in hepatocellular carcinoma cells / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the association between plasminogen activator inhibitor (PAI)-2 expression and invasive potential in hepatocellular carcinoma (HCC) cells.</p><p><b>METHODS</b>The HCC cell lines with high, low, and non-metastatic potentials, namely MHCC97-H, MHCC97-L, and SMMC-7721 respectively, were cultured in vitro. Matrigel invasion assay and Western blot of PAI-2 protein expression were conducted.</p><p><b>RESULTS</b>The number of invaded cells in MHCC97-L was significantly higher than that in SMMC-7721 (P=0.005), whereas that in MHCC97-H was higher than in MHCC97-L (P=0.017) and SMMC-7721 (P=0.001). Contrarily, PAI-2 protein expression was gradually reducing from SMMC-7721, MHCC97-L, to MHCC97-H (MHCC97-H vs. MHCC97-L, P<0.001; MHCC97-H vs. SMMC-7721, P=0.001; MHCC97-L vs. SMMC-7721, P=0.001). The Pearson's correlation analysis revealed a significant negative association between invaded cell number and PAI-2 expression (r=-0.892, P=0.001).</p><p><b>CONCLUSION</b>PAI-2 expression may be negatively associated with the invasive potential of HCC.</p>