Minimal-invasive hepatectomy (MIH) has been increasingly performed for benign and malignant liver lesions with most promising short-term results. However, the oncological role of MIH in the treatment of patients with colorectal liver metastases (CRLM) needs further investigation. Clinicopathological data of patients who underwent liver resection for CRLM between 2012 and 2017 at the Department of Surgery, Charité-Universitätsmedizin Berlin, and the Inselspital Bern were assessed. Postoperative outcomes und long-term survivals of patients following MIH were compared with those after conventional open hepatectomy (OH) after 1:1 propensity score matching. During the study period, 229 and 91 patients underwent liver resection for CRLM at the Charité Berlin and the Inselspital Bern, respectively. Patients who underwent MIH in one of the two centers (n = 69) were compared with a matched cohort of patients who underwent OH. MIH was associated with lower complication rates (23% vs. 44%, p = 0.011), shorter length of intensive care unit stay (ICU, 1 vs. 2 days, p = 0.043), shorter length of hospital stay (7 vs. 11 days, p < 0.0001), and a reduced need for intraoperative transfusions (12% vs. 25%, p = 0.047) compared to OH. R0 status was achieved in 93% and 75% of patients after MIH and OH, respectively (p = 0.005). After a median follow-up of 31 months, MIH resulted in similar five-year overall survival (OS) rate (56% vs. 48%, p = 0.116) in comparison to OH. MIH for CRLM is associated with lower postoperative morbidity, shorter length of ICU and hospital stay, reduced need for transfusions, and comparable oncologic outcomes compared to the established OH. Our findings suggest that MIH should be considered as the preferred method for the treatment of curatively resectable CRLM.

(1) Background: Liver transplantation (LT) is an established treatment for selected patients with end-stage liver disease resulting in a subsequent need for long-term immunosuppressive therapy. With cumulative exposure to immunosuppression (IS), the risk for the development of de novo lung carcinoma increases. Due to limited therapy options and prognosis after diagnosis of lung cancer, the question of the mode and extent of IS in this particular situation is raised. (2) Methods: All patients diagnosed with de novo lung cancer in the follow-up after LT were identified from the institution’s register of liver allograft recipients (Charité—Universitätsmedizin Berlin, Germany) transplanted between 1988 and 2021. Survival analysis was performed based on the IS therapy following diagnosis of lung cancer and the oncological treatment approach. (3) Results: Among 3207 adult LTs performed in 2644 patients at our institution, 62 patients (2.3%) developed de novo lung carcinoma following LT. Lung cancer was diagnosed at a median interval of 9.7 years after LT (range 0.7–27.0 years). Median survival after diagnosis of lung carcinoma was 13.2 months (range 0–196 months). Surgical approach with curative intent significantly prolonged survival rates compared to palliative treatment (median 67.4 months vs. 6.4 months). Reduction of IS facilitated a significant improvement in survival (median 38.6 months vs. 6.7 months). In six patients (9.7%) complete IS weaning was achieved with unimpaired liver allograft function. (4) Conclusion: Reduction of IS therapy after the diagnosis of de novo lung cancer in LT patients is associated with prolonged survival. The risk of acute rejection does not appear to be increased with restrictive IS management. Therefore, strict reduction of IS should be an early intervention following diagnosis. In addition, surgical resection should be attempted, if technically feasible and oncologically meaningful.

(1) Background: Sinusoidal obstruction syndrome (SOS) after oxaliplatin-based chemotherapy is associated with unfavorable outcomes after partial hepatectomy for colorectal liver metastases (CLM). Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), may prevent SOS development. We investigated the impact of VEGF-inhibition on the development of SOS in a murine model. (2) Methods: Male wild-type and CD39-null mice received oxaliplatin, additional anti-VEGF (OxAV), or controls, and were sacrificed or subjected to major partial hepatectomy (MH). Specimen were used for histological analysis of SOS. Liver damage was assessed by plasma transaminases. The VEGF pathway was elucidated by quantitative PCR of liver tissue and protein analysis of plasma. (3) Results: Mice treated with oxaliplatin developed SOS. Concomitant anti-VEGF facilitated a reduced incidence of SOS, but not in CD39-null mice. SOS was associated with increased plasma VEGF-A and decreased hepatocyte growth factor (HGF). After OxAV treatment, VEGF-R2 was upregulated in wild-type but downregulated in CD39-null mice. Oxaliplatin alone was associated with higher liver damage after MH than in mice with concomitant VEGF-inhibition. (4) Conclusions: We established a murine model of oxaliplatin-induced SOS and provided novel evidence on the protective effect of VEGF-inhibition against the development of SOS that may be associated with changes in the pathway of VEGF and its receptor VEGF-R2.

Article Abstracts DGAV was published on April 1, 2021 in the journal Innovative Surgical Sciences (volume 6, issue s1).

Sex-specific differences in pharmacokinetics are increasingly recognized as clinically relevant, yet most population pharmacokinetic models for antibiotics have been developed in predominantly male populations with limited transferability to female patients. This study aimed to develop and externally evaluate a population pharmacokinetic model of piperacillin specifically for critically ill women to support model-informed precision dosing (MIPD). A total of 923 samples from 165 critically ill women (from four previously published studies) receiving piperacillin/tazobactam were analyzed. The data set was randomly split into a training set (80%) and an independent external evaluation set (20%). Non-linear mixed-effects modeling was employed based on the training data using NONMEM, and covariates were identified using stepwise covariate modeling with cross-validation. Prediction accuracy and bias were quantified using the median prediction error (MDPE) and the median absolute prediction error (MDAPE) in an MIPD scenario. Model predictions for future concentrations were generated both a priori and through Bayesian forecasting based on one prior sample. A two-compartment model provided the best fit for the data. Clearance was significantly affected by renal function estimated by the Cockcroft–Gault equation, along with procalcitonin and serum albumin. The external evaluation demonstrated strong predictive performance with very low systematic bias. In the MIPD scenario, a priori predictions exhibited good predictive performance (MDPE < |5.2|%, MDAPE < 33.4%), which substantially improved with Bayesian forecasting (MDPE < |3.2|%, MDAPE < 19.1%). A female-specific population pharmacokinetic model of piperacillin was developed and externally validated, demonstrating robust predictive performance and clear benefits for Bayesian forecasting.