Zusammenfassung
Für Patienten mit fortgeschrittenen Weichteilsarkomen UICC-Stadium III (d. h. Größe >5cm, tiefe Lokalisation, Grading ≥II nach FNCLCC) sollten grundsätzlich präoperative/neoadjuvante ...Therapieverfahren erwogen werden. Dies gilt also für alle High-Grade-Sarkome, bei denen nicht zuverlässig ein ausreichender Sicherheitsabstand (1 cm, Faszie) erreicht werden kann. Ein geringerer Abstand gilt nach neueren Daten als negativer prädiktiver Faktor für das Erleiden von Lokalrezidiven
1
. Zu den präoperativen/neoadjuvanten Therapieverfahren zählen, neben einer alleinigen Strahlentherapie, v. a. multimodale Therapieansätze wie die kombinierte Chemostrahlentherapie, ggf. auch der Einsatz der isolierten Extremitätenperfusion mit TNF-α. Idealerweise sollte diese Therapie unter kontrollierten Bedingungen erfolgen. Eine alleinige neoadjuvante Chemotherapie hat bislang keinen klar definierten Stellenwert, auch wenn sie bei ca. 30% der Patienten zu einer objektiven Remission führen kann. Die Entscheidung hinsichtlich der im Einzelfall geeigneten Therapie lokal fortgeschrittener und grenzwertig resektabler Sarkome sollte auf jeden Fall interdisziplinär mit/in einem Sarkomzentrum abgestimmt werden. Im neoadjuvanten Therapiekonzept ist eine hohe Dosisintensität erforderlich und ist hier eher erreichbar als postoperativ. Die adjuvante Chemotherapie nach Resektion eines Sarkoms ist mit einer Verbesserung des erkrankungsfreien Überlebens verbunden. Diese Therapie ist jedoch toxisch. Daher sollte sie auf Hochrisikopatienten begrenzt werden, nach detaillierter Aufklärung über die Risiken und unter Beachtung von Allgemeinzustand, Alter, Lokalisation, histologischem Subtyp, Organfunktion, Komorbidität und Erfahrung der Institution.
The optimal sizing design of truss structures is studied using the recently proposed particle swarm optimization algorithm (PSOA). The algorithm mimics the social behavior of birds. Individual birds ...in the flock exchange information about their position, velocity and fitness, and the behavior of the flock is then influenced to increase the probability of migration to regions of high fitness. A simple approach is presented to accommodate the stress and displacement constraints in the initial stages of the swarm searches. Increased social pressure, at the cost of cognitive learning, is exerted on infeasible birds to increase their rate of migration to feasible regions. Numerical results are presented for a number of well-known test functions, with dimensionality of up to 21.
Gene transfer of the cytidine deaminase (CDD) cDNA has recently been shown to induce cellular resistance to cytarabine (AraC) in vitro. To investigate the role for CDD in acute myeloid leukaemia ...(AML) we analysed the CDD activity and CDD gene structure in blast material from well‐defined patients with untreated and AraC refractory (RF) AML. Median CDD activity in previously untreated AML was significantly lower than in RF‐AML blasts (P = 0.015) and was significantly lower in patients with complete remission than with blast persistence following induction chemotherapy (P = 0.043). Structural investigation of the CDD gene by Southern analyses and RT‐PCR showed no detectable aberrations. Sequence analysis of the CDD cDNA from nine RF‐AML patients showed inconsistent aberrations in three patients. Semiquantitative assessment of CDD mRNA expression revealed a significant correlation with CDD activity. In conclusion, concordant with another recent study our data suggest a correlation of pretherapeutic CDD activity with induction treatment response. Besides the previously described prognostic impact of mdr1 expression, this result could be useful for the development of risk‐adapted AML treatment strategies and warrants further studies of CDD activity in well‐defined cohorts of AML patients and of the mechanisms involved in the regulation of CDD activity.
Please cite this paper as: la Chapelle C, Schutte J, Schuitemaker N, Steegers E, van Roosmalen J on behalf of the Dutch Maternal Mortality Commitee. Maternal mortality attributable to vascular ...dissection and rupture in the Netherlands: a nationwide confidential enquiry. BJOG 2012;119:86–93.
Objective To determine the incidence of maternal deaths attributable to vascular dissection and rupture in the Netherlands, and to assess clinical features, risk factors and the frequency of substandard care in the cases identified.
Design Confidential enquiry into the causes of maternal deaths.
Setting Nationwide in the Netherlands.
Population A total of 3,108,235 live births.
Methods Data analysis of all cases of maternal death from vascular dissection and rupture in the period 1993–2008. A literature review was also performed.
Main outcome measures Incidence, clinical features, risk factors and frequency of substandard care.
Results A total of 23 maternal deaths attributable to vascular dissection and rupture were reported. In most cases the location was aortic (n = 13), followed by coronary (n = 4) and splenic (n = 3) arteries. Clinical features were various, but most women presented with sudden unexplainable pain. Risk factors were present in 14 cases (61%), with hypertension being most frequently reported in ten cases (43%). Substandard care was determined to have been received in 13 cases (56%), inadequate assessment of complaints and a delay in diagnosis being the most frequent problems identified.
Conclusions Vascular dissection and rupture in pregnancy, although rare, carry a high risk of maternal and fetal morbidity and mortality. Because of the rarity of this condition and its variety in presentation, diagnosis is easily missed. A high index of suspicion when a woman presents with suggestive complaints, leading to an early diagnosis, may improve the prognosis for the woman and her child.
Objective: The natural history of non-functioning pituitary macroadenomas (NFMA) has not been completely elucidated. Therefore, we evaluated pituitary function, visual fields, and tumor size during ...long-term follow-up of non-operated patients with NFMA. Design: Follow-up study. Patients: Twenty-eight patients (age 55 ± 3 years) with NFMA, not operated after initial diagnosis, were included. Results: Initial presentation was pituitary insufficiency in 44%, visual field defects in 14%, apoplexy in 14%, and chronic headache in 7% of the patients. The duration of follow-up was 85 ± 13 months. Radiological evidence of tumor growth was observed in 14 out of 28 patients (50%) after duration of follow-up of 118 ± 24 months. Six patients (21%) were operated, because tumor growth was accompanied by visual field defects. Visual impairments improved in all the cases after transsphenoidal surgery. Spontaneous reduction in tumor volume was observed in eight patients (29%). No independent predictors for increase or decrease in tumor volume could be found by regression analysis. Conclusion: Observation alone is a safe alternative for transsphenoidal surgery in selected NFMA patients, without the risk of irreversibly compromising visual function.
BI 2536, a novel Polo-like kinase 1 inhibitor, was assessed in patients with unresectable advanced exocrine adenocarcinoma of the pancreas.
The study employed a two-stage design. Randomised ...first-line patients received BI 2536 200 mg on day 1 (n=43) or 60 mg on days 1-3 (n=43) every 21 days. Recruitment of second-line patients was planned for a second stage dependent on an interim analysis demonstrating ≥ 2 responses in the first 18 evaluable patients following 12 weeks of treatment and/or tumour control ≥ 12 weeks in 5 patients per schedule. Primary end point was objective response rate (ORR).
By independent review, ORR was 2.3% (all partial) and 24.4% had stable disease as confirmed best response. The second stage was not initiated. Median overall and progression-free survivals were 149 (95% confidence interval (CI), 91-307) and 46 days (95% CI, 44-56). Most common drug-related adverse events were neutropenia (37.2%), leukopenia (29.1%), fatigue (29.1%) and nausea (22.1%); most common grade 3/4-related events were neutropenia (36.0%), leukopenia (27.9%) and thrombocytopenia (8.1%).
Given the low ORR and poor survival, further development of BI 2536 monotherapy is not warranted in this population.
Objective of this prospective study was to evaluate the role of somatostatin receptor scintigraphy (SRS) in advanced renal cell carcinoma (RCC) with respect to potential therapy with somatostatin ...analogue (SST-A) and to assess the response rate under therapy with SST-A.
16 patients with documented progression of histologically confirmed advanced RCC were included. Planar whole-body SRS was performed 4, 24 and 48 h post i.v. injection of 175-200 MBq 111In-pentetreoide. 5 and 25 h p.i. SPECT of thorax and abdomen were performed. Documentation of somatostatin receptor expression via SRS in >50% of known tumour lesions was the criteria for treatment start with SST-A (Sandostatin LAR-Depot 30 mg i.m. every four weeks).
In 9/16 of the patients SRS showed at least one metastasis with moderate (n = 5) or intense (n = 4) tracer uptake. Lesion-based SRS evaluation showed only 12.1% (20/165) of all metastases. Most false-negative lesions were located in the lungs. In two patients, the majority of the known metastases was SRS positive and these patients received SST-A therapy. The first radiographic evaluation after a two-month interval showed progressive disease in both patients.
We conclude that SRS is of limited value in staging of advanced RCC. In our patients SST-A did not result in a growth control of RCC. Consequently, the use of SST-A in advanced RCC seems to be no relevant therapeutic option.
The axion emerges in extensions of the Standard Model that explain the absence of CP violation in the strong interactions. Simultaneously, it can provide naturally the cold dark matter in our ...universe. Several searches for axions and axion-like particles (ALPs) have constrained the corresponding parameter space over the last decades but no unambiguous hints of their existence have been found. The axion mass range below 1 meV remains highly attractive and a well motivated region for dark matter axions. In this White Paper we present a description of a new experiment based on the concept of a dielectric haloscope for the direct search of dark matter axions in the mass range of 40 to 400
μ
eV
. This MAgnetized Disk and Mirror Axion eXperiment (MADMAX) will consist of several parallel dielectric disks, which are placed in a strong magnetic field and with adjustable separations. This setting is expected to allow for an observable emission of axion induced electromagnetic waves at a frequency between 10 to 100 GHz corresponding to the axion mass.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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