Einfluss der „in-situ Split“-Leberresektion vs. Standard-Leberresektion auf Proliferation, Apoptose und Angiogenese

Die „in-situ Split“-Leberrresektion (ISS-LR), ebenso als ALPPS bekannt, ist eine neue, zweizeitige Strategie, die in nur wenigen Tagen zu ausgeprägtem Wachstum des FLR („future liver remnant“) führt. Damit kann der drohenden Gefahr eines postoperativen Leberversagens aufgrund eines zu geringen FLR begegnet werden. Gleichzeitig können Patienten mit primär irresektablen Lebermalignomen in einen resektablen Zustand überführt werden. Jedoch sind die Auswirkungen dieses Verfahrens auf eine mögliche Tumorprogression bisher nicht klar. Wir untersuchten in dieser retrospektiven Studie, inwieweit die ISS-LR Einfluss auf Tumorproliferation, Apoptose und Angiogenese nimmt. Für 6 Patienten mit kolorektalen Lebermetastasen und 2 Patienten mit cholangiozellulären Karzinomen nach ISS-LR wurden anhand eines 1:2- bzw. 1:3-„Matchings“ passende Patienten nach Standard-Leberresektion (SLR) ausgewählt. Die jeweils größte resezierte Metastase bzw. der primäre Lebertumor wurde immunhistochemisch auf Vaskularisation (CD31), Proliferation (MIB-1), Apoptose (Caspase-3, TUNEL), Nekrose (TUNEL) und αSMA-Expression untersucht. Hinsichtlich Vaskularisation (CD31 p=0,149), Proliferation (MIB-1 p=0,244) und αSMA-Expression (p=0,205) zeigte sich für die kolorektalen Lebermetastasen kein statistisch signifikanter Unterschied zwischen den Gruppen nach ISS-LR und SLR. In der Caspase-3-Färbung waren in der Gruppe nach ISS-LR signifikant weniger (p<0,0001) apoptotische Zellen nachweisbar als in der Vergleichsgruppe nach SLR. Dieser Unterschied konnte anhand der TUNEL-Methode jedoch nicht bestätigt werden (p=0,734). Ebenso konnte die TUNEL-Färbung bezüglich nekrotischer Areale keinen statistisch signifikanten Unterschied zwischen den Gruppen zeigen (p=0,373). Für die cholangiozellulären Karzinome war hinsichtlich Vaskularisation (CD31 p=0,401), Proliferation (MIB-1 p=0,613), Apoptose (Caspase-3 p=0,131, TUNEL p=0,562) und Nekrose (TUNEL p=0,524) kein statistisch signifikanter Unterschied zwischen den beiden Gruppen nachweisbar. Im Vergleich von ISS-LR und SLR war die αSMA-positive Fläche in der Gruppe nach ISS-LR signifikant vermindert (p=0,015). Aufgrund dieser Ergebnisse muss im Rahmen der ISS-LR nicht von einer relevanten lokalen Tumorprogression im Vergleich zur SLR ausgegangen werden. Obwohl die geringe Patientenanzahl und die mögliche Heterogenität zwischen den Vergleichsgruppen beachtet werden müssen, deutet diese Studie nicht auf eine Stimulation des Tumorwachstums durch die ISS-LR hin

Monographs on drugs which are frequently analyzed in therapeutic drug monitoring

In addition to the monographs which have been published in the past 4 years by the working group "Drug Monitoring” of the Swiss Society of Clinical Chemistry (SSCC) [1-4], new monographs have been written. The data presented in these monographs provide an overview of important information for the request and interpretation of results. Therefore, laboratory health professionals and the receivers of the reports are the targeted readers. In this series, several antiepileptic drugs are presented. Monographs on carbamazepine [1], lamotrigine [2], phenobarbital [2], and valproic acid [2] have been published previously. First, information about pharmacology and pharmacokinetics of these drugs (protein binding, metabolic pathways and enzymes involved, elimination half-life time and elimination route(s) of the parent drug and therapeutic as well as toxic concentrations) is given. Second, the indications for therapeutic drug monitoring are listed. Last but not least, important pre-analytical information is provided, including time points of blood sampling and time interval after which steady-state concentrations are reached after changing the dose. Furthermore, the stability of the drug and its metabolite(s) after blood sampling is described. For readers with a specific interest, references to important publications are given. The number of the monographs will be further enlarged. The updated files are presented on the homepage of the SSCC (www.sscc.ch). We hope that these monographs are helpful for the better handling of therapeutic drug monitoring and we are looking forward to comments from the reader

Canine pseudopregnancy: an evaluation of prevalence and current treatment protocols in the UK

Background: There is a dearth of literature on pseudopregnancy in the bitch, with only a few treatment-based studies published since the 1990s. Pseudopregnancy may be under-recognised in bitches and may account for a proportion of behavioural cases seen in veterinary practices including aggression. Little is known about commonly used treatments for overtly pseudopregnant bitches and it is possible that current regimes may not be prescribed for a sufficient duration to control any clinical signs including, physical and behavioural changes. To investigate current trends in diagnosis and treatment of canine pseudopregnancy, a postal survey was sent to 2000 randomly selected veterinary surgeons in UK veterinary practices. The questionnaire queried how often vets recognise cases of pseudopregnancy in spayed and entire bitches, which physical or behavioural signs are commonly recognised for diagnosis, and which management or treatment protocols are used. Results: The response rate was 19.8% (397/2000). Ninety-six percent of veterinary surgeons reported seeing pseudopregnant bitches showing behavioural changes without any physical changes within the last 12 months. Of those behavioural changes, collecting and mothering objects was the most frequently reported behavioural sign (96%). Ninety-seven percent of vets had seen aggression in pseudopregnant bitches. Nevertheless, only 52% of vets routinely asked owners about behavioural changes during consultations. Forty-nine percent of respondents reported seeing pseudopregnancy in spayed bitches. The most commonly reported physical sign was enlarged mammary glands and/or milk production (89%). Treatment options varied (surgical, medical or none) and depended on duration and severity of physical and behavioural signs, owners’ preference, cost, concurrent disease, drug availability and previous history. Conclusions: This is the largest epidemiological study of canine pseudopregnancy in the UK. The prevalence and severity of clinical signs in dogs with pseudopregnancy are variable and possibly under-estimated. Dogs with overt pseudopregnancy experience diverse physical and behavioural changes and information on standard treatment protocols are lacking. Although, progress on our understanding of diagnosis and treatment of pseudopregnancy in spayed and entire bitches has been made, further studies are warranted

The "Ram Effect": A "Non-Classical" Mechanism for Inducing LH Surges in Sheep

During spring sheep do not normally ovulate but exposure to a ram can induce ovulation. In some ewes an LH surge is induced immediately after exposure to a ram thus raising questions about the control of this precocious LH surge. Our first aim was to determine the plasma concentrations of oestradiol (E2) E2 in anoestrous ewes before and after the "ram effect" in ewes that had a "precocious" LH surge (starting within 6 hours), a "normal" surge (between 6 and 28h) and "late» surge (not detected by 56h). In another experiment we tested if a small increase in circulating E2 could induce an LH surge in anoestrus ewes. The concentration of E2 significantly was not different at the time of ram introduction among ewes with the three types of LH surge. "Precocious" LH surges were not preceded by a large increase in E2 unlike "normal" surges and small elevations of circulating E2 alone were unable to induce LH surges. These results show that the "precocious" LH surge was not the result of E2 positive feedback. Our second aim was to test if noradrenaline (NA) is involved in the LH response to the "ram effect". Using double labelling for Fos and tyrosine hydroxylase (TH) we showed that exposure of anoestrous ewes to a ram induced a higher density of cells positive for both in the A1 nucleus and the Locus Coeruleus complex compared to unstimulated controls. Finally, the administration by retrodialysis into the preoptic area, of NA increased the proportion of ewes with an LH response to ram odor whereas treatment with the α1 antagonist Prazosin decreased the LH pulse frequency and amplitude induced by a sexually active ram. Collectively these results suggest that in anoestrous ewes NA is involved in ram-induced LH secretion as observed in other induced ovulators