Reports on Lenvatinib-based therapies show promising treatment outcomes for patients with unresectable hepatocellular carcinoma (uHCC). However, the effect and safety of Lenvatinib-based therapies ...still need to be further studies.
This was a retrospective, single-center study on the safety and treatment efficacy of Lenvatinib-based combination therapies for uHCC Patients. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were progressive disease (PD), stable disease (SD), partial response (PR), and complete response (CR).
Of 91 patients, there were 16 females and 75 males with uHCC who received systemic therapies based on Lenvatinib in our center. Forty-six patients (50.5%) received Lenvatinib combined with PD-1 antibody treatment. All these patients also received local therapy with the exception of 2 patients. The remaining 36 patinets received Lenvatinib combined with transcatheter arterial chemoembolization (TACE), 1 patient treated Lenvatinib combined with radiotherapy, 8 patients received Lenvatinib alone. At a median treatment time of 8 months, the objective response rate (ORR) of the entire cohort was 58.2% (53 patients), including 7 patients with CR and 46 patients with PR. 21 patients (23.1%) had SD. The disease control rate (DCR) of all patients was 81.3% (74 patients). However, 17 patients (18.7%) developed PD. The 1- and 2-year cumulative OS rates for the entire cohort were 66.8% and 39.3%, while the corresponding PFS rates were 38.0% and 17.1%, respectively. Univariate and multivariate Cox regression analysis revealed multiple tumor sites to be an independent OS risk factor for uHCC patients (HR=2.204, 95% CI=1.104-4.399,
=0.025). The most frequently reported adverse events in all patients were AST elevation (51.6%), followed by hypertension (33.0%), ALT elevation (26.4%), and decreased appetite (25.3%). After a combination treatment of Lenvatinib-based therapies, 15 patients met the criteria for salvage liver resection and underwent down-staging hepatectomy with a curative intent. The combination of PD-1 treatment was not very effective in improving the prognosis of uHCC patients treated with Lenvatinib combined with TACE.
Our study demonstrated that a proportive of patients benefited from Lenvatinib-based combination therapies with manageable safety profiles, allowing these patients to undergo downstaging surgery with curative intent.
This randomized controlled study investigated the feasibility of early ambulation after liver resection and the effect of the amount of activity on postoperative recovery.
A total of 120 patients who ...underwent liver resection were randomly divided into two groups for the comparative analysis of the following factors: amount of activity, pain control, sleeping state, perioperative gastrointestinal function recovery, incidence of complications and postoperative hospital stay.
Compared with the control group, patients undergoing liver resection performing early postoperative ambulation had faster gastrointestinal function recovery (First exhaust time 2.2 ± 1.4 vs. 3.3 ± 2.3 p < 0.01; First flatus time 2.3 ± 1.7 vs. 3.1 ± 2.5 p = 0.04) and shorter postoperative hospital stays (6.6 ± 2.3 vs. 7.7 ± 2.1 p = 0.01), with statistically significant differences. There was no significant difference in the incidence of postoperative complications between the two groups (p > 0.05).
Early ambulation after liver resection is safe and feasible. It can reduce the patient's pain and economic burden, increase the patient's comfort, reduce the nursing workload, achieve rapid recovery, and improve patient satisfaction.
•Quantitative study on early enforced mobilization for ERAS of liver resection.•Early enforced mobilization after liver resection is safe and feasible.•Wireless smart wristband available for clinical observation.
•hMOF is down-regulated in human hepatocellular carcinoma.•hMOF level predicts overall and disease-free survival.•hMOF regulates liver cancer cell growth and transformation.•hMOF regulates SIRT6 in ...human hepatocellular carcinoma.
Males absent on the first (MOF) is a histone acetyltransferase belongs to the MYST (MOZ, Ybf2/Sas3, Sas2 and TIP60) family. In mammals, MOF plays critical roles in transcription activation by acetylating histone H4K16, a prevalent mark associated with chromatin decondensation. MOF can also acetylate transcription factor p53 on K120, which is important for activation of pro-apoptotic genes; and TIP5, the largest subunit of NoRC, on K633. However, the role of hMOF in hepatocellular carcinoma remains unknown. Here we find that the expression of hMOF is significantly down-regulated in human hepatocellular carcinoma and cell lines. Furthermore, our survival analysis indicates that low hMOF expression predicts poor overall and disease-free survival. We demonstrate that hMOF knockdown promotes hepatocellular carcinoma growth in vitro and in vivo, while hMOF overexpression reduces hepatocellular carcinoma growth in vitro and in vivo. Mechanically, we show that hMOF regulates the expression of SIRT6 and its downstream genes. In summary, our findings demonstrate that hMOF participates in human hepatocellular carcinoma by targeting SIRT6, and hMOF activators may serve as potential drug candidates for hepatocellular carcinoma therapy.
Background & Aims To investigate diagnostic and prognostic values of sulfite oxidase (SUOX) in patients with hepatocellular carcinoma (HCC) who underwent curative resection. Methods We investigated ...immunohistochemically the expression dynamics of SUOX, aldo-ketoreductase family 1 member B10 (AKR1B10) and CD34 at different stages of HCC. The differential diagnostic performance of three markers or their combinations in high-grade dysplastic nodules (HGDNs) and well-differentiated small HCC (WD-sHCC) were investigated by logistic regression models and validated in an independent testing set. Overall survival (OS) and time to recurrence (TTR) were evaluated in 300 patients with HCC as the testing cohort, and validated in 198 patients with HCC. Results SUOX was decreased and AKR1B10 and CD34 were increased with the stepwise progression of hepatocarcinogenesis. For differential diagnosis of WD-sHCC from HGDNs, the sensitivity and specificity of the SUOX + AKR1B10 + CD34 combination for WD-sHCC detection were 93.8% and 95.2%, respectively, and overall accuracy was much higher than any of the three individual markers and two marker combinations. In addition, SUOX, but not AKR1B10 and CD34, was an independent prognostic factor for OS and TTR, and showed better correlation with OS and TTR if combined with serum α-fetoprotein (AFP) for both the testing and validation cohorts. Conclusions SUOX + AKR1B10 + CD34 combination could make a substantial contribution to hepatic immunopathological diagnosis to distinguish WD-sHCC from HGDNs. Meanwhile, SUOX combined with serum AFP may predict postoperative outcome and tumor recurrence risk.
Background
The impact of hepatic resection type on long-term oncological prognosis of patients with early-stage hepatocellular carcinoma (HCC) has not been systematically investigated. We sought to ...determine risk factors, recurrence patterns, and survival outcomes after anatomical resection (AR) versus non-anatomical resection (NAR) for early-stage HCC.
Methods
From a prospectively collected multicenter database, consecutive patients undergoing curative hepatectomy for early-stage HCC were identified. Recurrence patterns, overall survival (OS), recurrence-free survival (RFS), and risk factors were investigated in patients undergoing AR versus NAR using propensity score matching (PSM), subgroup analysis, and COX regression analysis.
Results
A total of 3585 patients with early-stage HCC were enrolled, including 1287 and 2298 in the AR and NAR groups, respectively. After PSM, the OS and RFS of patients in the AR group were 58.8% and 42.7%, which were higher than those in the NAR group (52.2% and 30.6%, both
p
< 0.01). The benefits of AR were consistent across most subgroup analyses of OS and RFS. Multivariable COX regression analysis showed that AR was independently associated with better OS and RFS. Notably, although recurrence patterns were comparable, the risk factors for recurrence were not identical for AR versus NAR. Microvascular invasion and narrow resection margin were only associated with a higher recurrence rate after NAR.
Conclusions
This study demonstrated that AR decreases the risk of tumor recurrence and improves OS and RFS in patients with early-stage HCC. AR should be adopted as long as such a surgical maneuver is feasible for initial treatment of early-stage HCC.
Graphical abstract
Pterygium is a common ophthalmic disease affecting humans only. Extensive epidemiological data have demonstrated a causative effect of chronic ultraviolet (UV) radiation on pterygia. Progress has ...been made in determining the origin of pterygia, their nasal predilection and wing-shaped appearance, and the roles of UV radiation in the initiation and the development of pterygia. In the present review, the current understanding of the involvement of UV radiation in the pathogenesis of pterygia is summarized. This involvement includes the alteration of limbal stem cells and fibroblasts that contribute to the initiation of pterygia and the induction of various pro-inflammatory cytokines, growth factors and matrix metalloproteinases that promote the progression of pterygia. Further elucidation of the roles of UV radiation in the pathogenesis of pterygia may help to encourage individuals at risk of developing pterygia to take preventive measures and aid researchers in the development of novel targeted therapeutic agents to treat pterygia.
Objective:
To evaluate the importance of preoperative blood platelet to lymphocyte ratio (PLR) in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after liver surgery and ...to examine the connection with CD8
+
lymph cell infiltration.
Methods:
Between 2009 and 2014, consecutive HCC patients who received curative liver surgery were included into this retrospective study. Baseline clinicopathological characteristics were analyzed to identify predictors of recurrence-free and overall patient survival rate after liver resection. The samples of all patients were under Tissue Microarray (TMA) construction and immunohistochemical staining for CD8+.The association of the number of CD8+T-cells in the cancer nests and peritumoral stroma with PLR level was analyzed.
Results:
A total of 1,174 HBV-related HCC patients who received a liver resection without any peri-operative adjuvant therapy were enrolled into this retrospective study. Univariate and Multivariate analysis using Cox regression model showed that PLR was an independent factor affecting recurrence and overall survivals. The optimal cutoff of PLR using the receiver operating characteristic curve was 150. There were 236 patients (20.1%) who had a PLR of 150 or more. The 5-year survival rate after liver resection was 71.8% in patients with a PLR of < 150 and it was 57.2% in those with a PLR of 150 or more (
P
< 0.001). Both 5-year recurrence-free and overall survival rates in liver cancer stage A patients at Barcelona Clinic with different PLR group were also significantly different (
P
= 0.007 for recurrence and
P
= 0.001 for overall survival). Similar results were also observed in stage B patients (
P
< 0.001 for recurrence and
P
= 0.033 for overall survival). To determine the association between PLR and the severity of liver inflammation, an immuno-histological examination using CD8
+
staining was performed on the liver specimens of 1,174 patients. Compared with low PLR (<150) group, more CD8
+
T-cells were found in the peritumoral tissue in high PLR (≥ 150) group.
Conclusions:
PLR played as an independent factor for predicting the survival after hepatectomy for HCC patients. A high PLR was associated with an accumulation of CD8
+
T-cells in the peritumoral stroma.
The surface structure, stability, and electrocatalytic activity of the Pt3Co alloy toward oxygen reduction reaction (ORR) (with reference to Pt black) in both alkaline and acidic media were studied ...by X-ray photoelectron spectroscopy (XPS), cyclic voltammetry, and by the rotating disk electrode method. The XPS data show that two species of cobalt, metallic cobalt and cobalt oxides, coexist in the as-received Pt3Co sample. In combination with the voltammetric results, the XPS data demonstrate that there is dissolution of cobalt upon exposure of the sample to acidic media, whereas the cobalt forms in the catalyst are stable in alkaline media. In addition, the Pt 4f binding energy was found by XPS to be upshifted by 0.2 eV vs that of the pure Pt black reference. In acids, Pt3Co alloy has a slightly but demonstratively higher activity than Pt black toward the oxygen reduction reaction as shown by the positive half-wave potential shift of ca. 10 ± 2 mV, while in alkaline media a decrease in the ORR activity was found. The latter was indicated by the half-wave potential negative shift of about 30 ± 4 mV vs the half-wave potential of the Pt reference. However, the activity of the Pt3Co alloy catalyst (vs the Pt black reference) was restored by holding the alloy catalyst at 0.85 V in acid. The observed catalytic enhancement is overall due to Pt skin formation as concluded from the literature study and from the data of this work.
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