Abstract. Lesions of natural Helichrysum argyrosphaerum poisoning were studied in eight sheep and one goat. Light microscopic examination revealed widespread, bilaterally symmetrical status spongiosis of the white matter of the brain consistently present in the subependymal area adjacent to the lateral ventricles, cerebellar peduncles, and brain stem in all animals. In three animals, the ultrastructural finding of intramyelinic vacuolation due to splitting of the myelin lamellae at the intraperiod lines indicated myelin edema. There was also mild distension of perivascular and extracellular spaces in the severely affected areas. Significant changes were absent in neurons, glial cells, axons, or blood vessel walls. Myelin edema associated with degeneration and loss of axons and myelin and astrocytic gliosis was present in the intraorbital and intracranial portions of the optic nerves. In the intracanalicular portions of the nerves in three animals that were studied, more chronic lesions consisting of fibrosis and atrophy of the nerve suggested that the optic neuropathy follows compression of the nerve in the optic canal as a result of myelin edema. The toxic principle of the plant also caused a degenerative retinopathy in five animals. The essential histopathologic change was degeneration and loss of the photoreceptor outer segments predominantly in the nontapetal retina. These retinal lesions were associated with hyperplasia and hypertrophy and with migration of the pigmented epithelium, focal retinal separation, and depletion and loss of the nuclear layers.

BackgroundThe purpose of the study was to investigate a novel BRAF and CDK 4/6 inhibitor combination therapy in a murine model of BRAF-V600-mutant human melanoma monitored by 18F–FDG-PET/CT and diffusion-weighted MRI (DW-MRI).MethodsHuman BRAF-V600-mutant melanoma (A375) xenograft-bearing balb/c nude mice (n = 21) were imaged by 18F–FDG-PET/CT and DW-MRI before (day 0) and after (day 7) a 1-week BRAF and CDK 4/6 inhibitor combination therapy (n = 12; dabrafenib, 20 mg/kg/d; ribociclib, 100 mg/kg/d) or placebo (n = 9). Animals were scanned on a small animal PET after intravenous administration of 20 MBq 18F–FDG. Tumor glucose uptake was calculated as the tumor-to-liver-ratio (TTL). Unenhanced CT data sets were subsequently acquired for anatomic coregistration. Tumor diffusivity was assessed by DW-MRI using the apparent diffusion coefficient (ADC). Anti-tumor therapy effects were assessed by ex vivo immunohistochemistry for validation purposes (microvascular density – CD31; tumor cell proliferation – Ki-67).ResultsTumor glucose uptake was significantly suppressed under therapy (∆TTLTherapy − 1.00 ± 0.53 vs. ∆TTLControl 0.85 ± 1.21; p < 0.001). In addition, tumor diffusivity was significantly elevated following the BRAF and CDK 4/6 inhibitor combination therapy (∆ADCTherapy 0.12 ± 0.14 × 10−3 mm2/s; ∆ADCControl − 0.12 ± 0.06 × 10−3 mm2/s; p < 0.001). Immunohistochemistry revealed a significant suppression of microvascular density (CD31, 147 ± 48 vs. 287 ± 92; p = 0.001) and proliferation (Ki-67, 3718 ± 998 vs. 5389 ± 1332; p = 0.007) in the therapy compared to the control group.ConclusionA novel BRAF and CDK 4/6 inhibitor combination therapy exhibited significant anti-angiogenic and anti-proliferative effects in experimental human melanomas, monitored by 18F–FDG-PET/CT and DW-MRI.

ZusammenfassungDieses Fallbeispiel zeigt ein bisher selten beschriebenes Myxosarkom in der ventrolateralen Halsregion eines 1-jährigen Teddy-Hamsters. Die zytologische Beurteilung eines Feinnadelaspirats aus der Umfangsvermehrung zeigte zahlreiche pleomorphe Spindelzellen, die in hohen Mengen in einer muzinösen Matrix gelegen waren. Zytologisch wurde aufgrund der ausgeprägten Malignitätskriterien der Spindelzellpopulation der Verdacht auf eine maligne mesenchymale Neoplasie geäußert. Die Matrix war dabei hinweisend auf ein zugrundeliegendes Myxosarkom. Der Hamster verstarb im Rahmen der operativen Entfernung der Zubildung. Die Histopathologie zeigte eine vollständige Übereinstimmung mit den zytologischen Befunden. In der Immunhistochemie stellte sich der Tumor Vimentin-positiv mit Alzianblau-positiver Matrix dar und bestätigte die zytologische Verdachtsdiagnose. Der Fall zeigt, dass die Zytologie als minimalinvasives Diagnostikum auch beim Kleinsäuger angewendet werden kann und Rückschlüsse auf die zugrundeliegende Pathologie von Zubildungen ermöglicht. Zum biologischen Verhalten des Myxosarkoms beim Hamster ist aufgrund der seltenen Fallbeschreibungen jedoch bislang wenig bekannt.

Introduction Laparoscopic cholecystectomy is the gold standard definitive treatment option for benign biliary disease. There has been increasing interest in novel robotic surgical techniques; robotic cholecystectomy (RC) represents the most recent innovation in the management of gallstones. The IDEAL Collaboration has provided guidance for the rigorous and comprehensive reporting of surgical innovations, despite this, transparency in patient selection has been limited. We aimed to assess the reporting of patient selection in studies reporting RC. Method A collaborative, systematic review was conducted in accordance with the PRISMA guidance to identify all published studies reporting RC. Study specific inclusion and exclusion criteria were detailed in a protocol. Results Searches identified 1425 abstracts; 90 papers were included for data extraction. Inclusion criteria were reported in 38 (42%) studies. The most frequently cited were age (20%), aetiology (20%), presence of symptoms (16%) and comorbidities (10%). Forty-nine (54%) studies reported exclusion criteria. Numerous and variably reported exclusion criteria were reported; acute cholecystitis (26%), previous abdominal surgery (25%), comorbidity (17%), pregnancy (13%), common bile duct stones (13%) and pancreatitis (10%) among others. Seven reported no exclusion criteria. Three reported numbers of patients who declined RC. Conclusions Patient selection criteria were inconsistently reported and when present lacked standardisation. Concern persists around patients being “cherry picked” for inclusion in studies reporting innovative robotic surgical procedures, making interpretation and applicability of results impossible. Standardised inclusion criteria are needed to enable greater transparency and reproducibility to ensure the safe adoption of new technologies into clinical practice.

No abstract