Hepatocellular carcinoma (HCC) is the sixth-most common cancer and the third leading cause of cancer-related death in the world. However, 40–70% patients eventually suffer from postoperative recurrence within 5 years. HCC recurrence after surgery severely affects prognosis of the patients. Nevertheless, there is an opportunity to improve patients’ prognosis if doctors and researchers can recognize the importance of a standardized perioperative management and study it in clinical and pre-clinical settings. Hence, based on our own experience and published studies from other researchers, we develop this consensus regarding multidisciplinary management of locally recurrent and metastatic hepatocellular carcinoma after resection. This consensus consists of the entire course of recurrent hepatocellular carcinoma (RHCC) management, including prediction of recurrence, prevention, diagnosis, treatment and surveillance of RHCC. Consensus recommendations are presented with grades of evidences (Ia, Ib, IIa, IIb, III and IV), and strength of recommendations (A, B, C, D and E). We also develop a decision-making path for RHCC treatment, which can intuitively demonstrate the management for RHCC. It is hoped that we may make some effort to standardize the management of RHCC and ultimately understand how to improve outcomes.

Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with high mortality and metastasis, which is difficult to diagnose and treat. MicroRNA-143-3p (miR-143-3p) acts as a tumor suppressor in various cancers. However, its role in pancreatic ductal adenocarcinoma has not been explored. Here we examined the potential role and mechanism of miR-143-3p in PDAC. The levels of miR-143-3p and KRAS mRNA in matched PDAC and normal tissues as well as PDAC cell lines were determined by quantitative RT-PCR. The effect of miR-143-3p on cell proliferation was evaluated by Cell Counting Kit-8 assay, colony-forming assay and a mouse subcutaneous transplantation model. Transwell assay, wound healing assay and a mouse orthotopic implantation model were conducted to examine the role of miR-143-3p on cell migratory and invasive capacities. The target gene and mechanisms of miR-143-3p were explored by qRT-PCR, western blot and luciferase assays. The expression of miR-143-3p was down-regulated in PDAC tissues compared with the paired adjacent normal tissues. Cell proliferative, migratory and invasive capacities in PDAC cells were significantly decreased by miR-143-3p up-regulation. Moreover, we identified KRAS as a direct target of miR-143-3p, revealed its expression to be inversely correlated with miR-143-3p in PDAC samples. Up-regulated expression of KRAS partially reversed the phenotypes induced by miR-143-3p overexpression. What's more, KRAS could activate the ERK signaling pathway, which is associated with tumorigenesis. MiR-143-3p may suppress tumorigenesis in PDAC by targeting KRAS. This might provide a theoretical basis for miR-143-3p in treatment of pancreatic cancer.

Background: Post-treatment alpha-fetoprotein (AFP) response has been reported to be associated with prognosis of hepatocellular carcinoma (HCC) patients, but the results were not consistent. This meta-analysis aimed to explore the relationship between AFP response and clinical outcomes of HCC. Methods: PubMed, Embase, Medline and Cochrane library were searched for relevant articles published before March 20, 2019. The data were analyzed using RevMan5.3 software. Results: Twenty-nine articles with 4726 HCC patients were finally included for analysis. The pooled results showed that post-treatment AFP response was significantly associated with overall survival (OS) (hazard ratio (HR) = 0.41, 95% confidence interval (CI): 0.35–0.47, P <.001), progression free survival (PFS) (HR = 0.46, 95% CI: 0.39–0.54, P <.001) and recurrence free survival (RFS) (HR = 0.41, 95% CI: 0.29–0.56, P <.001) of HCC patients. Conclusion: post-treatment AFP response might be a useful prognostic marker for HCC patients.

Cancer associated fibroblasts (CAFs) support tumors via multiple mechanisms, including maintaining the immunosuppressive tumor microenvironment and limiting infiltration of immune cells. The prolyl isomerase Pin1, whose overexpression in CAFs has not been fully profiled yet, plays critical roles in tumor initiation and progression. To decipher effects of selective Pin1 inhibition in CAFs on pancreatic cancer, here we formulate a DNA-barcoded micellular system (DMS) encapsulating the Pin1 inhibitor AG17724. DMS functionalized with CAF-targeting anti-FAP-α antibodies (antiCAFs-DMS) can selectively inhibit Pin1 in CAFs, leading to efficacious but transient tumor growth inhibition. We further integrate DNA aptamers (AptT), which can engage CD8+ T lymphocytes, to obtain a bispecific antiCAFs-DMS-AptT system. AntiCAFs-DMS-AptT inhibits tumor growth in subcutaneous and orthotopic pancreatic cancer models.

Intrahepatic cholangiocarcinoma (iCCA) is closely correlated with hepatic progenitor cell (HPC) expansion and liver fibrosis. Brahma‐related gene 1 (Brg1), an enzymatic subunit of the SWltch/Sucrose Non‐Fermentable (SWI/SNF) complex that is critical in stem cell maintenance and tumor promotion, is prominently up‐regulated in both HPCs and iCCA; however, its role in this correlation remains undefined. A retrospective cohort study indicated that high Brg1 expression suggests poor prognosis in iCCA patients. In chronically injured livers induced by a 0.1% 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine (DDC) diet or bile duct ligation (BDL) surgery, HPCs were dramatically activated, as indicated by their enhanced expression of Brg1 and a subset of stem cell markers; however, Brg1 ablation in HPCs strongly suppressed HPC expansion and liver fibrosis. Furthermore, in a chemically induced iCCA model, inhibition of Brg1 by a specific inhibitor or inducible gene ablation markedly improved histology and suppressed iCCA growth. Mechanistically, in addition to transcriptionally promoting both Wnt receptor genes and target genes, Brg1 was found to bind to the β‐catenin/transcription factor 4 (TCF4) transcription complex, suggesting a possible novel approach for regulation of Wnt/β‐catenin signaling. Conclusion: We have demonstrated the function of Brg1 in promoting HPC expansion, liver cirrhosis, and ultimately iCCA development in chronically injured livers, which is largely dependent on Wnt/β‐catenin signaling. Our data suggest that therapies targeting Brg1‐expressing HPCs are promising for the treatment of liver cirrhosis and iCCA.

Microvascular invasion (MVI) is well established as a negative prognostic factor for hepatocelluar carcinoma (HCC). However, its prognostic value in different subgroups of Barcelona Clinical Liver Cancer (BCLC) stages remains to be elucidated. Four hundred fifty-eight MVI-negative and 204 MVI-positive patients who underwent hepatectomy were retrospectively analyzed. After propensity score matching (PSM) analysis, 187 pairs of matched patients were generated. Long-term survival was compared by the Kaplan–Meier method. Patients with MVI commonly had more advanced tumors. All the patients with MVI had significantly worse survival rate compared to the patients without MVI before and after PSM(p < 0.001). In the subgroup analysis, BCLC stage A HCC patients without MVI had better prognosis than those with MVI before and after PSM (p < 0.001 and p = 0.024). For BCLC stage B HCCs, long-term survival was significantly better for patients without MVI before PSM(p = 0.001). However, the overall survival (OS) rate was comparable between both groups after PSM (p = 0.682), although MVI-positive group had a higher rate of recurrence (p = 0.011).. Surgery type, satellite lesions, tumor size, and serum ALT level were statistically significant factors associated with survival in MVI-positive group. Tumor number, tumor size and neutrophil to lymphocyte ratio (NLR) were predictors of survival in MVI-negative group. Its prognostic value in different subgroups of BCLC stages differed. MVI is an independent predictor of prognosis in patients with BCLC stage A. For BCLC stage B HCCs, MVI-positive group had poor prognosis through more advanced HCCs.