Liver transplantation for hepatolithiasis: Is terminal hepatolithiasis suitable for liver transplantation?

Hepatolithiasis, originally as oriental cholangiohepatitis, especially prevails in Asia, but globalization and intercontinental migration have also converted the endemic disease dynamics around the world. Characterized by its high incidence of ineffective treatment and recurrence, hepatolithiasis, always, poses a therapeutic challenge to global doctors. Although the improved surgical and non-surgical techniques have evolved over the past decade, incomplete clearance and recurrence of calculi are always so common and disease-related mortality from liver failure and concurrent cholangiocarcinoma still exists in the treatment of hepatolithiasis. In the late stage of hepatolithiasis, is it suitable for liver transplantation (LT)? Herein, we propose a comprehensive review and analysis of the LTx currently in potential use to treat hepatolithiasis. In our subjective opinion, and as is objective from the literatures so far, also given the strict indications, LT remains one of the definitive treatments for terminal hepatolithiasis.

Questioning the staging of tumor deposits of colorectal cancer in the eighth edition of the TNM classification: validation by prognosis.

Tumor deposits (TD) of colorectal cancer (CRC) in the 8th edition of TNM classification (TNM 8th) were staged as N1c, but the number of TDs was ignored. The aim of this study was to analyze the association of TD with CRC and verify the rationale for TD staging in the TNM 8th. A total of 517 patients with CRC, surgically treated from Aug. 2013 to Dec. 2017, were retrospectively reviewed. Univariate and multivariate analyses were used to observe the correlations between clinicopathologic features and TD. The reasonability of TD staging in TNM 8th was validated by prognostic analysis. The occurrence of TD in CRC was 11.2% (154/1375). Multivariate analysis indicated that T stage (P<0.001, OR = 2.026 and 5.380, 95% CI: 0.917-4.474 and 2.229-12.981 for T3 and T4 respectively) and TNM stage (P<0.001, OR = 9.051 and 16.305, 95% CI: 2.055-39.857 and 3.780-70.323 for TNM II and TNM III respectively) were independent risk factors for TD status. Only degree of differentiation (P = 0.020, OR = 0.197, 95% CI: 0.050-0.774 for poorly differentiated) was an independent risk factor for number of TDs. Survival analysis showed that patients with TD exhibited a significantly worse prognosis compared to patients without TD (P<0.001), and a significant prognostic difference was found among groups TD = 1, TD = 2/3 and TD≥4 (all P<0.05). Patients in T3-4aN1a/1b had a worse prognosis than patients in T3-4aN1c did, although both groups were classified as TNM IIIB (P = 0.022). TD was an adverse indicator in CRC, and the varying number of TDs represented a classified prognostic factor in CRC. TD staging in the TNM 8th might not be reasonable as it ignores the status and the number of TDs.

Microencapsulation of recombinant adenovirus within poly-DL-lactide-poly(ethylene glycol) microspheres for enhanced gene transfection efficiency and inhibitory effects on hepatocellular carcinoma cells in vitro.

When gene therapy is performed for the treatment of malignant tumors, gene transfer efficiency and selectivity are highly important. Polymer vehicle microspheres are a novel type of therapy, which have been developed rapidly in recent years and are able to control drug release, prolong the biological half-life of drugs, decrease side effects and achieve targeted delivery. The present study was designed to construct a polymer microsphere-encapsulated recombinant adenovirus with human tissue inhibitors of the matrix metalloproteinase-1 (TIMP-1) gene, and to discuss its characterization for the purpose of liver cancer gene therapy. The microsphere was prepared from biodegradable poly-DL-lactide-poly(ethylene glycol) (PELA) encapsulating rAdTIMP-1, the recombinant adenovirus carrying TIMP-1, by a modified double-emulsion method. The particle morphology, diameter, virus encapsulation, loading rate and release kinetics of the rAd-microspheres were determined in vitro. Hepatocellular carcinoma (HCC) HepG2 cells were transfected with the rAd-microsphere and the efficiency of transfection was assessed by fluorescent microscopy. The production and expression of TIMP-1 was identified by gelatin zymography and western blot analysis, and the invasiveness was detected by a matrigel matrix invasion assay. The microsphere encapsulating rAdTIMP-1 was successfully constructed with a diameter of 1.965 µm, encapsulation efficiency of 60.0%, a viral load of 10.5 x 10(8)/mg, a virus release of ~60% within 120 h and a total release time of >240 h. The resultant rAd-microspheres were able to efficiently transfect HepG2 cells with the transfection efficiency enhanced by ~90%. As a result, the transfected HepG2 cells had significantly increased TIMP-1 enzyme activity and the expression of TIMP-1 was detected by western blot analysis. In addition, the proliferation and invasion ability of the HCC cells was markedly inhibited by the rAd-microspheres. The resultant rAd-microspheres, PELA-encapsulated recombinant TIMP-1 adenovirus, had enhanced transfection efficiency and were able to markedly inhibit the in vitro biological behavior of HepG2 cells. This provides an experimental basis for this polymer application and may pave the way for prospective in vivo clinical trials and further comprehensive therapy for liver cancer.