Gas Chromatography-Mass Spectrometry Detection of Thymoquinone in Oil and Serum for Clinical Pharmacokinetic Studies.

Thymoquinone (TQ) is the primary component of Nigella sativa L. (NS) oil, which is renowned for its potent hepatoprotective effects attributed to its antioxidant, anti-fibrotic, anti-inflammatory, anti-carcinogenic, and both anti- and pro-apoptotic properties. The aim of this work was to establish a method of measuring TQ in serum in order to investigate the pharmacokinetics of TQ prior to a targeted therapeutic application. In the first step, a gas chromatography-mass spectrometry method for the detection and quantification of TQ in an oily matrix was established and validated according to European Medicines Agency (EMA) criteria. For the assessment of the clinical application, TQ concentrations in 19 oil preparations were determined. Second, two serum samples were spiked with TQ to determine the TQ concentration after deproteinization using toluene. Third, one healthy volunteer ingested 1 g and another one 3 g of a highly concentrated NS oil 30 and 60 min prior to blood sampling for the determination of serum TQ level. After the successful establishment and validation of the measurement method, the highest concentration of TQ (36.56 g/L) was found for a bottled NS oil product (No. 1). Since a capsule is more suitable for oral administration, the product with the third highest TQ concentration (No. 3: 24.39 g/L) was used for all further tests. In the serum samples spiked with TQ, the TQ concentration was reliably detectable in a range between 5 and 10 µg/mL. After oral intake of NS oil (No. 3), however, TQ and/or its derivatives were not detectable in human serum. This discrepancy in detecting TQ after spiking serum or following oral ingestion may be attributed to the instability of TQ in biomatrices as well as its strong protein binding properties. A pharmacokinetics study was therefore not viable. Studies on isotopically labeled TQ in an animal model are necessary to study the pharmacokinetics of TQ using alternative modalities.

Solitary colorectal liver metastasis: overview of treatment strategies and role of prognostic factors.

The following is an overview of the treatment strategies and the prognostic factors to consider in the therapeutic choice of patients characterized by solitary colorectal liver metastasis. Liver resection is the only potential curative option; nevertheless, only 25% of the patients are considered to be eligible for surgery. To expand the potentially resectable pool of patients, surgeons developed multidisciplinary techniques like portal vein embolization, two-stage hepatectomy or associating liver partition and portal vein ligation for staged hepatectomy. Moreover, mini-invasive surgery is gaining support, since it offers lower post-operative complication rates and shorter hospital stay with no differences in long-term outcomes. In case of unresectable disease, various techniques of local ablation have been developed. Radiofrequency ablation is the most commonly used form of thermal ablation: it is widely used for unresectable patients and is trying to find its role in patients with small resectable metastasis. The identification of prognostic factors is crucial in the choice of the treatment strategy. Previous works that focused on patients with solitary colorectal liver metastasis obtained trustable negative predictive factors such as presence of lymph-node metastasis in the primary tumour, synchronous metastasis, R status, right-sided primary colon tumor, and additional presence of extrahepatic tumour lesion. Even the time factor could turn into a predictor of tumour biology as well as further clinical course, and could be helpful to discern patients with worse prognosis.

Ligation of the middle hepatic vein to increase hypertrophy induction during the ALPPS procedure.

PURPOSE: Here, we analyse the technical modification of the ALPPS procedure, ligating the middle hepatic vein during the first step of the operation to enhance remnant liver hypertrophy. METHODS: In 20 of 37 ALPPS procedures, the middle hepatic vein was ligated during the first step. Hypertrophy of the functional remnant liver volume was assessed in addition to postoperative courses. RESULTS: Volumetric analysis showed a significant volume increase, especially for patients with colorectal metastases. Pre-existing liver parenchyma damage (odds ratio = 0.717, p = 0.017) and preoperative chemotherapy were found to be significant predictors (odds ratio = 0.803, p = 0.045) of higher morbidity and mortality. In addition, a survival benefit for maintenance of middle hepatic vein was shown. CONCLUSION: This technical modification of the ALPPS procedure can accentuate future liver remnant volume hypertrophy. The higher morbidity and mortality observed are most likely associated with pre-existing parenchymal damage within this group.

[A glimpse into the future: smart technologies and enhanced recovery after surgery (ERAS)]. / Blick in die Zukunft: smarte Technologien und ERAS ("enhanced recovery after surgery").

Smart technologies facilitate our daily life in many respects, e.g. by rendering travel safer. In medicine, however, they have so far hardly been used, even though the demographic changes with an aging population in small or single households warrant an urgent change of our traditional care structures. Furthermore, patients are more demanding and better informed than they were a few decades ago. Enhanced recovery after surgery (ERAS) focusses on good prehabilitation as well as fast rehabilitation and therefore represents, even almost 20 years after the first publication, a modern and evidence-based treatment concept. Nevertheless, it is still not comprehensively implemented nationwide. The reasons for this may be concerns regarding an early discharge. In addition, there is often a gap in care care between discharge from hospital and start of the follow-up rehabilitation. In order to improve acceptance of the ERAS concept, to fulfil the patients' needs for better information while decreasing the workload of the medical staff and to close the gap in care after discharge from hospital, integrating ERAS into the concept of a smart hospital with subsequent transition into a temporary smart home is an appealing idea. With the use of an individually configurated online learning platform, a large part of the information flow can be transferred from the outpatient clinic to the pre-outpatient area (i.e. the patient's home). Consequently, patients will be better prepared for their first contact with the hospital. After a short stay in hospital the patient is then discharged into the serviced apartments of the smart quarter, where a stress-free recovery in a home-like environment is possible. The further rehabilitation is undertaken there under virtual guidance, following individualized schedules on demand.

[Living related liver transplantation]. / Lebertransplantation durch Lebendspende.

Liver transplantation has become established as a standard procedure in the treatment of end-stage liver diseases. Despite intense efforts by all parties involved up to the amendment of the German Transplantation Act, the lack of suitable donor organs was still one of the limiting factors of this therapeutic procedure. One way out of this problem is to make so-called marginal organs usable, e.g. with the help of machine perfusion or by utilizing living liver donation, which are used in some countries for more than 90% of organ donations. In general, there is no difference in the indications for liver transplantation between a (partial) organ obtained by post-mortem or living donation. Before any living donation, a thorough evaluation of the donor is carried out in order to minimize postoperative morbidity as far as possible. Technically the partial liver donation is based on the oncological liver resection, while the partial liver transplantation is a further development of split liver transplantation after post-mortem liver donation. In specialized centers comparable or even better results can nowadays be achieved using living liver donation instead of post-mortem donation.