Minimally invasive mesohepatectomy for centrally located liver lesions-a case series.

BACKGROUND: Resection of centrally located liver lesions remains a technically demanding procedure. To date, there are limited data on the effectiveness and safety of minimally invasive mesohepatectomy for benign and malignant lesions. It was therefore the objective of this study to evaluate the perioperative outcomes of minimally invasive mesohepatectomy for liver tumors at a tertiary care hospital. METHODS: Consecutive patients who underwent a minimally invasive anatomic mesohepatectomy using a Glissonean pedicle approach from April 2018 to November 2021 were identified from a prospective database. Demographics, operative details, and postoperative outcomes were analyzed using descriptive statistics for continuous and categorical variables. RESULTS: A total of ten patients were included, of whom five patients had hepatocellular carcinoma, one patient had cholangiocarcinoma, three patients had colorectal liver metastases, and one patient had a hydatid cyst. Two and eight patients underwent robotic-assisted and laparoscopic resections, respectively. The median operative time was 393 min (interquartile range (IQR) 298-573 min). Conversion to laparotomy was required in one case. The median lesion size was 60 mm and all cases had negative resection margins on final histopathological analysis. The median total blood loss was 550 ml (IQR 413-850 ml). One patient had a grade III complication. The median length of stay was 7 days (IQR 5-12 days). Time-to-functional recovery was achieved after a median of 2 days (IQR 1-4 days). There were no readmissions within 90 days after surgery. CONCLUSION: Minimally invasive mesohepatectomy is a feasible and safe approach in selected patients with benign and malignant liver lesions.

TGF-ß2 silencing to target biliary-derived liver diseases.

OBJECTIVE: TGF-ß2 (TGF-ß, transforming growth factor beta), the less-investigated sibling of TGF-ß1, is deregulated in rodent and human liver diseases. Former data from bile duct ligated and MDR2 knockout (KO) mouse models for human cholestatic liver disease suggested an involvement of TGF-ß2 in biliary-derived liver diseases. DESIGN: As we also found upregulated TGFB2 in liver tissue of patients with primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), we now fathomed the positive prospects of targeting TGF-ß2 in early stage biliary liver disease using the MDR2-KO mice. Specifically, the influence of TgfB2 silencing on the fibrotic and inflammatory niche was analysed on molecular, cellular and tissue levels. RESULTS: TgfB2-induced expression of fibrotic genes in cholangiocytes and hepatic stellate cellswas detected. TgfB2 expression in MDR2-KO mice was blunted using TgfB2-directed antisense oligonucleotides (AON). Upon AON treatment, reduced collagen deposition, hydroxyproline content and αSMA expression as well as induced PparG expression reflected a significant reduction of fibrogenesis without adverse effects on healthy livers. Expression analyses of fibrotic and inflammatory genes revealed AON-specific regulatory effects on Ccl3, Ccl4, Ccl5, Mki67 and Notch3 expression. Further, AON treatment of MDR2-KO mice increased tissue infiltration by F4/80-positive cells including eosinophils, whereas the number of CD45-positive inflammatory cells decreased. In line, TGFB2 and CD45 expression correlated positively in PSC/PBC patients and localised in similar areas of the diseased liver tissue. CONCLUSIONS: Taken together, our data suggest a new mechanistic explanation for amelioration of fibrogenesis by TGF-ß2 silencing and provide a direct rationale for TGF-ß2-directed drug development.

Correction to: Human skin-derived ABCB5+ stem cell injection improves liver disease parameters in Mdr2KO mice.

We wish to submit a corrigendum to the above-mentioned article. Thank you very much for consideration and publication.

Human skin-derived ABCB5+ stem cell injection improves liver disease parameters in Mdr2KO mice.

Although liver transplantation is a potential effective cure for patients with end-stage liver diseases, this strategy has several drawbacks including high cost, long waiting list, and limited availability of liver organs. Therefore, stem cell-based therapy is presented as an alternative option, which showed promising results in animal models of acute and chronic liver injuries. ABCB5+ cells isolated from skin dermis represent an easy accessible and expandable source of homogenous stem cell populations. In addition, ABCB5+ cells showed already promising results in the treatment of corneal and skin injury. To date, the effect of these cells on liver injury is still unknown. In the current study, sixteen weeks old Mdr2KO mice were i.v. injected with 500,000 ABCB5+ cells using different experimental setups. The effects of cellular therapy on inflammation, fibrosis, apoptosis, and proliferation were analyzed in the collected liver tissues. Toxicity of ABCB5+ cells was additionally investigated in mice with partial liver resection. In vitro, the fibrosis- and inflammatory-modulating effects of supernatant from ABCB5+ cells were examined in the human hepatic stellate cell line (LX-2). Cell injections into fibrotic Mdr2KO mice as well as into mice upon partial liver resection have no signs of toxicity with regard to cell transformation, cellular damage, fibrosis or inflammation as compared to controls. We next investigated the effects of ABCB5+ cells on established biliary liver fibrosis in the Mdr2KO mice. ABCB5+ cells to some extent influenced the shape of the liver inflammatory response and significantly reduced the amount of collagen deposition, as estimated from quantification of sirius red staining. Furthermore, reduced apoptosis and enhanced death compensatory proliferation resulted from ABCB5+ cell transformation. The stem cells secreted several trophic factors that activated TGF-ß family signaling in cultured LX-2 hepatic stellate cells (HSCs), therewith shaping cell fate to an αSMAhigh, Vimentinlow phenotype. Taken together, ABCB5+ cells can represent a safe and feasible strategy to support liver regeneration and to reduce liver fibrosis in chronic liver diseases.