The incidence of Cholangiocellular Carcinoma (CCA) is increasing in the western world. The tumour has a high proportion of desmoplastic stroma and is correlated with a worse prognosis when cancer associated myofibroblasts (CAFs) are present. Recent studies showed promising results after liver transplantation (LTx) in non-resectable early stage CCA. Mycophenolic acid (MPA) and the mTor inhibitor Everolimus are used to prevent organ rejection but recently were shown to exhibit an antiproliferative effect on CCA-cells. Little is known about the influence of immunosuppressive drugs on tumour cell proliferation and migration after paracrine stimulation by CAFs. Moreover, it is still unknown, which signaling pathways are activated following these specific cell-cell interactions. CCA cell lines HuCCT1 and TFK1 were utilized for the study. CAFs were derived from resected CCA cancer tissue. Cell viability was measured by the crystal violet assay and tumour cell invasion was quantified using a modified co-culture transmigration assay. Semiquantitative cytokine-expression was measured using a cytokine-array. Protein expression and phosphorylation of ERK, STAT3 and AKT was determined by Western-blot analysis. CCA cells treated with MPA exhibited a dose related decrease in cell viability in contrast to Cyclosporine A (CSA) treatment which had no effect on cell viability. Everolimus significantly inhibited proliferation at very low concentrations. The pro-invasive effect of CAFs in co-culture transmigration assay was significantly reduced by Everolimus at a concentration of 1nM (p = 0.047). In contrast, MPA and CSA showed no effect on tumour cell invasion. Treatment of CAFs with 1nM Everolimus showed a significant reduction in the expression of IL 8, IL 13, MCP1, MIF and Serpin E1. CCA-cells showed significant increases in phosphorylation of ERK, STAT3 and AKT under the influence of conditioned CAF-media. This effect was suppressed by Everolimus. The secretion of proinflammatory cytokines by CAFs may lead to increased activation of JAK/STAT3-, ERK- and AKT-signaling and increased migration of CCA-cells. Everolimus abrogates this effect and inhibits proliferation of CCA-cells even at low concentrations. LTx for non-resectable early stage CCA is currently performed in several clinical studies. Consistent with a role for common immunosuppressants in inhibiting tumour cell-proliferation and -invasion, our study indicates that a combination of standard therapies with Everolimus and MPA is a promising therapy option to treat CCA following LTx.

Recent developments in robotic surgery have led to an increasing number of robot-assisted hepatobiliary procedures. However, a limitation of robotic surgery is the missing haptic feedback. The fluorescent dye indocyanine green (ICG) may help in this context, which accumulates in hepatocellular cancers and around hepatic metastasis. ICG accumulation may be visualized by a near-infrared camera integrated into some robotic systems, helping to perform surgery more accurately. We aimed to test the feasibility of preoperative ICG application and its intraoperative use in patients suffering from hepatocellular carcinoma and metastasis of colorectal cancer, but also of other origins. In a single-arm, single-center feasibility study, we tested preoperative ICG application and its intraoperative use in patients undergoing robot-assisted hepatic resections. Twenty patients were included in the final analysis. ICG staining helped in most cases by detecting a clear lesion or additional metastases or when performing an R0 resection. However, it has limitations if applied too late before surgery and in patients suffering from severe liver cirrhosis. ICG staining may serve as a beneficial intraoperative aid in patients undergoing robot-assisted hepatic surgery. Dose and time of application and standardized fluorescence intensity need to be further determined.

Human cytomegalovirus (CMV) remains a major cause of mortality and morbidity in human liver transplant recipients. Anti-CMV therapeutics can be used to prevent or treat CMV in liver transplant recipients, but their toxicity needs to be balanced against the benefits. The choice of prevention strategy (prophylaxis or preemptive treatment) depends on the donor/recipient sero-status but may vary between institutions. We conducted a series of consultations and roundtable discussions with German liver transplant center representatives. Based on 20 out of 22 centers, we herein summarize the current approaches to CMV prevention and treatment in the context of liver transplantation in Germany. In 90% of centers, transient prophylaxis with ganciclovir or valganciclovir was standard of care in high-risk (donor CMV positive, recipient CMV naive) settings, while preemptive therapy (based on CMV viremia detected during (bi) weekly PCR testing for circulating CMV-DNA) was preferred in moderate- and low-risk settings. Duration of prophylaxis or intense surveillance was 3–6 months. In the case of CMV infection, immunosuppression was adapted. In most centers, antiviral treatment was initiated based on PCR results (median threshold value of 1000 copies/mL) with or without symptoms. Therefore, German transplant centers report similar approaches to the prevention and management of CMV infection in liver transplantation.

Improving long-term patient and graft survival after liver transplantation (LT) remains a major challenge. Compared to the early phase after LT, long-term morbidity and mortality of the recipients not only depends on complications immediately related to the graft function, infections, or rejection, but also on medical factors such as de novo malignancies, metabolic disorders (e.g., new-onset diabetes, osteoporosis), psychiatric conditions (e.g., anxiety, depression), renal failure, and cardiovascular diseases. While a comprehensive post-transplant care at the LT center and the connected regional networks may improve outcome, there is currently no generally accepted standard to the post-transplant management of LT recipients in Germany. We therefore described the structure and standards of post-LT care by conducting a survey at 12 German LT centers including transplant hepatologists and surgeons. Aftercare structures and form of cost reimbursement considerably varied between LT centers across Germany. Further discussions and studies are required to define optimal structure and content of post-LT care systems, aiming at improving the long-term outcomes of LT recipients.

Introduction: Robotic-assisted liver surgery (RALS) with its known limitations is gaining more importance. The fluorescent dye, indocyanine green (ICG), is a way to overcome some of these limitations. It accumulates in or around hepatic masses. The integrated near-infrared cameras help to visualize this accumulation. We aimed to compare the influence of ICG staining on the surgical and oncological outcomes in patients undergoing RALS. Material and Methods: Patients who underwent RALS between 2014 and 2021 at the Department of General Surgery at the University Hospital Schleswig-Holstein, Campus Kiel, were included. In 2019, ICG-supported RALS was introduced. Results: Fifty-four patients were included, with twenty-eight patients (50.9%) receiving preoperative ICG. Hepatocellular carcinoma (32.1%) was the main entity resected, followed by the metastasis of colorectal cancers (17%) and focal nodular hyperplasia (15.1%). ICG staining worked for different tumor entities, but diffuse staining was noted in patients with liver cirrhosis. However, ICG-supported RALS lasted shorter (142.7 ± 61.8 min vs. 246.4 ± 98.6 min, p < 0.001), tumors resected in the ICG cohort were significantly smaller (27.1 ± 25.0 mm vs. 47.6 ± 35.2 mm, p = 0.021) and more R0 resections were achieved by ICG-supported RALS (96.3% vs. 80.8%, p = 0.075). Conclusions: ICG-supported RALS achieve surgically and oncologically safe results, while overcoming the limitations of RALS.