Treatment-induced pathologic necrosis: a predictor of local recurrence and survival in patients receiving neoadjuvant therapy for high-grade extremity soft tissue sarcomas.

PURPOSE: To determine whether treatment-induced pathologic necrosis correlates with local recurrence and overall survival in patients who receive neoadjuvant therapy for high-grade extremity soft tissue sarcomas. PATIENTS AND METHODS: Four hundred ninety-six patients with intermediate- to high-grade extremity soft tissue sarcomas received protocol neoadjuvant therapy. All patients underwent surgical resection after neoadjuvant therapy and had pathologic assessment of tumor necrosis in the resected specimens. RESULTS: The 5- and 10-year local recurrence rates for patients with > or = 95% pathologic necrosis were significantly lower (6% and 11%, respectively) than the local recurrence rates for patients with less than 95% pathologic necrosis (17% and 23%, respectively). The 5- and 10-year survival rates for the patients with > or = 95% pathologic necrosis were significantly higher (80% and 71%, respectively) than the survival rates for the patients with less than 95% pathologic necrosis (62% and 55%, respectively). Patients with less than 95% pathologic necrosis were 2.51 times more likely to develop a local recurrence and 1.86 times more likely to die of their disease as compared with patients with > or = 95% pathologic necrosis. The percentage of patients who achieved > or /= 95% pathologic necrosis increased to 48% with the addition of ifosfamide as compared with 13% of the patients in all the other protocols combined. CONCLUSION: Treatment-induced pathologic necrosis is an independent predictor of both local recurrence and overall survival in patients who receive neoadjuvant therapy for high-grade extremity soft tissue sarcomas. A complete pathologic response (> or = 95% pathologic necrosis) correlated with a significantly lower rate of local recurrence and improved overall survival.     

Experimental chemotherapy of xenotransplanted oral squamous epithelial carcinoma: effectiveness of docetaxel (taxotere) in the nude mouse model]

Originating from plants, the taxoids, in particular docetaxel (Taxotere), represent progress in antitumoral chemotherapy. In addition to their use as palliative treatment they have also proved to be increasingly important for adjuvant and neoadjuvant treatment of oral squamous cell carcinoma (SCC). In the present nude mouse model the efficacy of chemotherapeutic agents against exemplary oral SCC were examined using cell line HNSCC 001. Typical biological properties such as expression of serum tumor markers and treatment-related alteration were reviewed. Intraperitoneal administration of 30 mg docetaxel per kilogram body weight at a time resulted in significant growth inhibition (P < 0.001), however without complete remission. Mean values of relative tumor volume ranged from 95% to 131% in the treated groups as compared to 311% in animals without treatment. Application more frequently than weekly did not result in a significant increase in antitumor activity. From the present experimental study no final conclusion can be drawn regarding weekly docetaxel administration mostly used in clinical phase II trials. Except for SCC, for which values correlated well with tumor volume (r = 0.85 without treatment and r = 0.87 with treatment), on the one hand, and a distinct treatment-related decrease, on the other, the tested tumor markers TPA and TPS proved to be less valuable for screening of treatment and follow-up in this murine model.     

Magnetic resonance coronary angiography with vasovist™: in-vivo T 1 estimation to improve image quality of navigator and breath-hold techniques

The purpose of the study was to estimate T ₁ values of blood and myocardium after a single injection of Vasovist™ and to assess Vasovist™ for magnetic resonance coronary angiography (MRCA). For all exams 0.05 mmol/kg of Vasovist™ was injected. T ₁ values of blood and myocardium were estimated over 30 min after injection. Twelve volunteers were examined on a 1.5-T Siemens system using a SSFP sequence with incrementally increasing inversion times for T ₁-estimation and a breath-hold 3D IR-FLASH sequence for MRCA. Eleven examinations were performed on 1.5-T Philips system using the Look-Locker approach for T ₁ estimation and a whole-heart inversion-prepared, 3D SSFP sequence for MRCA. SNR, CNR and image quality were assessed. T ₁ values of blood (5 min: 230 ms vs. 30 min: 275 ms) and myocardium (5 min: 99 ms vs. 30 min: 130 ms) increased over time. Whereas the blood SNR (1 min: 23.6 vs. 30 min: 21.2) showed no significant differences, the blood-to-myocardium CNR (1 min: 18.1 vs. 30 min: 13.8) and the image quality (1 min: 2.9 vs. 30 min: 3.8) degraded over time. Due to long plasma half-time the T1-shortening effect of Vasovist™ remains effective over 30 min, which allows for multiple breath-hold or high-resolution MRCA.     

Polysomnographische Untersuchungen für Säuglinge und Kinder—Anleitung für die Laborarbeit

Zusammenfassung Die AG Pädiatrie der DGSM hat Standards für die Durchführung und Auswertung von Polysomnographien erarbeitet. Die Berücksichtigung der beschriebenen Standards ermöglicht die Vergleichbarkeit von polysomnographischen Untersuchungen aus unterschiedlichen Schlaflaboren. Sie beziehen sich auf Routine-Polysomnographien. Unter bestimmten Umständen sind Modifizierungen gerechtfertigt. Diese sollten jedoch im Polysomnographie­bericht beschrieben werden, da eine Vergleichbarkeit mit der Routineuntersuchung damit u. U. nicht mehr gegeben ist. Für wissenschaftliche Belange sind in Abhängigkeit von der Fragestellung detailliertere Untersuchungen erforderlich. Unter Zugrundelegung der hier vorgestellten Standards wird es eine der künftigen Aufgaben der AG Pädiatrie der DGSM sein, die den Schlafstörungen bei Säuglingen und Kindern zugrundeliegenden Krankheitsbilder näher zu definieren und therapeutische Strategien weiter zu entwickeln.     

Effect of adrenalectomy on ethanol-associated immunosuppression

The alterations in lymphoid cell numbers and lymphocyte function due to administration of ethanol was found to be associated with high levels of circulating corticosteroids. The role of corticosteroids in the ethanol-induced alterations in the immune system was studied by administering ethanol to adrenalectomized rats. The results of these experiments showed that the ethanol-induced loss of cells from the thymus was not completely prevented by adrenalectomy and the ethanol-induced loss of cells from the spleen was not affected by adrenalectomy. Likewise the ethanol-induced decrease in antibody production to the T-cell-dependent antigen sheep erythrocytes were not affected by adrenalectomy. The ability of animals to produce antibodies of the T-cell-independent antigen, TNP-Ficoll, was not affected by ethanol regardless of whether the animals had adrenal glands or not. These data indicate that adrenal corticosteroids are responsible for some but not all of the thymic involution due to ethanol intoxication. Also, adrenalectomized rats did not show as much impairment in lymphocyte proliferation as sham adrenalectomized animals after ethanol administration. However, this loss of cells from peripheral lymphoid organs such as the spleen and the decreased ability to respond to T-cell-dependent antigens is not influenced by adrenalectomy indicating mechanisms other than corticosteroids mediate these effects of ethanol.     

Validation analysis of the novel imaging-based prognostic radiomic signature in patients undergoing primary surgery for advanced high-grade serous ovarian cancer (HGSOC)

Background Predictive models based on radiomics features are novel, highly promising approaches for gynaecological oncology. Here, we wish to assess the prognostic value of the newly discovered Radiomic Prognostic Vector (RPV) in an independent cohort of high-grade serous ovarian cancer (HGSOC) patients, treated within a Centre of Excellence, thus avoiding any bias in treatment quality.Methods RPV was calculated using standardised algorithms following segmentation of routine preoperative imaging of patients (n = 323) who underwent upfront debulking surgery (01/2011-07/2018). RPV was correlated with operability, survival and adjusted for well-established prognostic factors (age, postoperative residual disease, stage), and compared to previous validation models.Results The distribution of low, medium and high RPV scores was 54.2% (n = 175), 33.4% (n = 108) and 12.4% (n = 40) across the cohort, respectively. High RPV scores independently associated with significantly worse progression-free survival (PFS) (HR = 1.69; 95% CI:1.06–2.71; P = 0.038), even after adjusting for stage, age, performance status and residual disease. Moreover, lower RPV was significantly associated with total macroscopic tumour clearance (OR = 2.02; 95% CI:1.56–2.62; P = 0.00647).Conclusions RPV was validated to independently identify those HGSOC patients who will not be operated tumour-free in an optimal setting, and those who will relapse early despite complete tumour clearance upfront. Further prospective, multicentre trials with a translational aspect are warranted for the incorporation of this radiomics approach into clinical routine.Subject terms: Prognostic markers, Cancer imaging     

Dose-related effects of ethanol on visual sustained attention and event-related potentials

The effects of acute ethanol intoxication on visual sustained attention were investigated in male social drinkers. Four doses ranging from 0 (placebo) to 1.05 g/kg lean body weight, with periodic maintenance dosing of 0.12 g/kg, were given in separate sessions. The task required subjects to monitor a series of blurred digits presented singly at a rate of one per sec and to respond to occasional (p = 0.25) target digits with a speeded button press. Detection performance deteriorated as a function of both dose and time on task. In addition, the factors of dose and time on task interacted to produce a more rapid performance decrement under the higher doses. Early event-related potential (ERP) components (N1 and P2) were not greatly affected, suggesting that the performance decrement reflects central rather than peripheral factors. Later components related to cognitive appraisal processes (N2, P3), in contrast, varied in both amplitude and latency. Ethanol yielded dose-related delays in N2 and P3 latencies, which paralleled reaction time increases. The amplitude of N2 also decreased over time on task, and P3 amplitude decreased both as a function of dose and time on task. ERP and performance data were interpreted as demonstrating an adverse effect of ethanol on central processing capacity.     

Resolution of left atrial appendage thrombi: No difference between phenprocoumon and non‐vitamin K‐dependent oral antagonists

BackgroundAtrial fibrillation is the most important risk factor for left atrial appendage (LAA) thrombi, a potentially life‐threatening condition. Thrombus resolution may prevent embolic events and allow rhythm‐control strategies, which have been shown to reduce cardiovascular complications.HypothesisThere is no significant difference between phenprocoumon and non‐Vitamin K‐dependent oral anticoagulants (NOACs) in the resolution of LAA‐thrombi in a real‐world setting.MethodsConsecutive patients with LAA‐thrombi from June 2013 to June 2017 were included in an observational single‐center analysis. The primary endpoint was defined as the resolution of the thrombus. The observational period was 1 year. Resolutions rates in patients on phenprocoumon or NOACs were compared and the time to resolution was analyzed.ResultsWe identified 114 patients with LAA‐thrombi. There was no significant difference in the efficacy of resolution between phenprocoumon and NOACs (p = .499) at the time of first control which took place after a mean of 58 ± 42.2 (median 48) days. At first control most thrombi were dissolved (74.6%). The analysis after set‐time intervals revealed a resolution rate of 2/3 of LAA‐thrombi after 8–10 weeks in the phenprocoumon and NOAC groups. After 12 weeks a higher number of thrombi had resolved in the presence of NOAC (89.3%) whereas in the presence of phenprocoumon 68.3% had resolved (p = .046).ConclusionIn this large observational study NOACs were found to be potent drugs for the resolution of LAA‐thrombi. In addition, the resolution of LAA‐thrombi was found to be faster in the presence of NOAC as compared to phenprocoumon.