Soft tissue sarcomas with complex genomic profiles.

Soft tissue sarcomas (STS) with complex genomic profiles (50% of all STS) are predominantly composed of spindle cell/pleomorphic sarcomas, including leiomyosarcoma, myxofibrosarcoma, pleomorphic liposarcoma, pleomorphic rhabdomyosarcoma, malignant peripheral nerve sheath tumor, angiosarcoma, extraskeletal osteosarcoma, and spindle cell/pleomorphic unclassified sarcoma (previously called spindle cell/pleomorphic malignant fibrous histiocytoma). These neoplasms show, characteristically, gains and losses of numerous chromosomes or chromosome regions, as well as amplifications. Many of them share recurrent aberrations (e.g., gain of 5p13-p15) that seem to play a significant role in tumor progression and/or metastatic dissemination. In this paper, we review the cytogenetic, molecular genetic, and clinicopathologic characteristics of the most common STS displaying complex genomic profiles. Features of diagnostic or prognostic relevance will be discussed when needed.

Neurologie [2012: news in neurology].

In 2012, intramuscular midazolam appears as effective as intravenous lorezepam for the first line treatment of convulsive status epilepticus. Perampanel, a new anti-epileptic drug, will be soon available. Two oral treatments are now available for stroke prevention in atrial fibrillation setting. The methylphenidate and the Tai Chi could increase the walk capacity of patients suffering from Parkinson disease. A comprehensive cardiac work-up is essential for some congenital myopathy. A new drug against migraine seems free from vasoconstrictive effect. Antioxidants are harmful in Alzheimer disease. Some oral medication will be available for multiple sclerosis.

Treatment of advanced soft-tissue sarcomas using a combined strategy of high-dose ifosfamide, high-dose doxorubicin and salvage therapies.

Having determined in a phase I study the maximum tolerated dose of high-dose ifosfamide combined with high-dose doxorubicin, we now report the long-term results of a phase II trial in advanced soft-tissue sarcomas. Forty-six patients with locally advanced or metastatic soft-tissue sarcomas were included, with age <60 years and all except one in good performance status (0 or 1). The chemotherapy treatment consisted of ifosfamide 10 g m(-2) (continuous infusion for 5 days), doxorubicin 30 mg m(-2) day(-1) x 3 (total dose 90 mg m(-2)), mesna and granulocyte-colony stimulating factor. Cycles were repeated every 21 days. A median of 4 (1-6) cycles per patient was administered. Twenty-two patients responded to therapy, including three complete responders and 19 partial responders for an overall response rate of 48% (95% CI: 33-63%). The response rate was not different between localised and metastatic diseases or between histological types, but was higher in grade 3 tumours. Median overall survival was 19 months. Salvage therapies (surgery and/or radiotherapy) were performed in 43% of patients and found to be the most significant predictor for favourable survival (exploratory multivariate analysis). Haematological toxicity was severe, including grade > or =3 neutropenia in 59%, thrombopenia in 39% and anaemia in 27% of cycles. Three patients experienced grade 3 neurotoxicity and one patient died of septic shock. This high-dose regimen is toxic but nonetheless feasible in multicentre settings in non elderly patients with good performance status. A high response rate was obtained. Prolonged survival was mainly a function of salvage therapies.

Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: meta-analysis of individual data

BACKGROUND: Individually, randomised trials have not shown conclusively whether adjuvant chemotherapy benefits adult patients with localised resectable soft-tissue sarcoma.METHODS: A quantitative meta-analysis of updated data from individual patients from all available randomised trials was carried out to assess whether adjuvant chemotherapy improves overall survival, recurrence-free survival, and local and distant recurrence-free intervals (RFI) and whether chemotherapy is differentially effective in patients defined by age, sex, disease status at randomisation, disease site, histology, grade, tumour size, extent of resection, and use of radiotherapy.FINDINGS: 1568 patients from 14 trials of doxorubicin-based adjuvant chemotherapy were included (median follow-up 9.4 years). Hazard ratios of 0.73 (95% CI 0.56-0.94, p = 0.016) for local RFI, 0.70 (0.57-0.85, p = 0.0003) for distant RFI, and 0.75 (0.64-0.87, p = 0.0001) for overall recurrence-free survival, correspond to absolute benefits from adjuvant chemotherapy of 6% (95% CI 1-10), 10% (5-15), and 10% (5-15), respectively, at 10 years. For overall survival the hazard ratio of 0.89 (0.76-1.03) was not significant (p = 0.12), but represents an absolute benefit of 4% (1-9) at 10 years. These results were not affected by prespecified changes in the groups of patients analysed. There was no consistent evidence that the relative effect of adjuvant chemotherapy differed for any subgroup of patients for any endpoint. However, the best evidence of an effect of adjuvant chemotherapy for survival was seen in patients with sarcomas of the extremities.INTERPRETATION: The meta-analysis provides evidence that adjuvant doxorubicin-based chemotherapy significantly improves the time to local and distant recurrence and overall recurrence-free survival. There is a trend towards improved overall survival.

Medical students' skills and needs for training in breaking bad news.

This study assessed medical students' perception of individual vs. group training in breaking bad news (BBN) and explored training needs in BBN. Master-level students (N = 124) were randomised to group training (GT)-where only one or two students per group conducted a simulated patient (SP) interview, which was discussed collectively with the faculty-or individual training (IT)-where each student conducted an SP interview, which was discussed during individual supervision. Training evaluation was based on questionnaires, and the videotaped interviews were rated using the Roter Interaction Analysis System. Students were globally satisfied with the training. Still, there were noticeable differences between students performing an interview (GT/IT) and students observing interviews (GT). The analysis of the interviews showed significant differences according to scenarios and to gender. Active involvement through SP interviews seems required for students to feel able to reach training objectives. The evaluation of communication skills, revealing a baseline heterogeneity, supports individualised training.

Telomerase activity and human telomerase reverse transcriptase mRNA expression in soft tissue tumors: correlation with grade, histology, and proliferative activity.

Telomerase activity (TA) is detected in most human cancers but, with few exceptions, not in normal somatic cells. Little is known about TA in soft tissue tumors. We have examined a series of benign and malignant soft tissue tumors for TA using the telomerase repeat amplification protocol assay. Analysis of the expression of the human telomerase reverse transcriptase was also carried out using RT-PCR. TA was undetectable in benign lesions (15 of 15) and low-grade sarcomas (6 of 6) and was detectable in 50% (19 of 38) of intermediate-/high-grade sarcomas. Although the presence of TA in soft tissue tumors is synonymous with malignancy, it is neither a reliable method in making the distinction between reactive/benign and malignant (especially low-grade) lesions nor a reliable marker of tumor aggressiveness. Leiomyosarcomas and storiform/pleomorphic malignant fibrous histiocytomas rarely showed TA, irrespective of their grade. A strong correlation between human telomerase reverse transcriptase mRNA expression and TA was observed, supporting the close relationship between both parameters. No significant relationship was observed between proliferative activity (as assessed by MIB-1 immunolabeling) and TA. We verified that the absence of telomerase expression was not due to the presence of telomerase inhibitors and therefore alternative mechanism(s) for cell immortalization, yet to be determined, seem to be involved in the development and/or maintenance of some soft tissue sarcomas.

Neurologie [News in neuroloey 2014].

In 2014, breastfeeding during maternal antiepileptic therapy seems to be safe for the children and can be recommended. Intravenous thrombolysis by Alteplase improves the outcome after a stroke if administered within 4.5 hours and it is also recommended in elderly population over 80 years. ProSavin genic therapy for Parkinson disease is under investigation. The Transcranial Magnetic Stimulation (TMS) has an analgesic effect in neuropathic pain as well as an antidepressant effect. Antagonists of calcitonin gene-related peptide can have a beneficial role in migraine prevention. Diagnostic biomarker panels for Alzheimer disease are under investigation. Oral teriflunomide and dimethyl fumarate (BG-12) for relapsing multiple sclerosis treatment are now available in Switzerland.

Psychological challenges for the oncology clinician who has to break bad news

Work-related stress of the oncology clinician is not only due to heavy clinical and administrative duties, but also arises when breaking bad news. However, there is important interindividual variation in stress levels during patient encounters, mainly due to the significance the situation represents for the oncologist. A reflection on his own development, his professional identity, and ways of dealing with the patient's suffering can reduce his levels of stress and distress and prevent burnout and other psychiatric disturbances. This chapter summarizes the psychological challenges the oncology clinician is facing when he announces the diagnosis of cancer, deals with the deception of relapse, discusses the transition to palliative care, copes with progression of the disease and uncertainty, and cares for the dying who is facing the unknown. Ways of refiecting on and dealing with these situations from a psychological and communicational perspective are described and illustrated by case vignettes.

Neurologie [News in neurology 2013].

In 2013, perampanel is approved as an add-on treatment for generalised and focal seizures in pharmaco-resistant epilepsy. New anticoagulants are superior to antivitamin K in stroke secondary prevention in case of atrial fibrillation. DBS remains a valid therapeutic option for advanced Parkinson's disease. Intranasal ketamine seems to reduce the intensity of severe migraine aura. High concentrations of topic capsaicin improve post-herpetic neuralgia. In Alzheimer's disease, statins might deteriorate cognitive functions. Oral immuno-modifing treatments for relapsing remitting multiple sclerosis have shown to slow cerebral atrophy progression at two years.