Surgical resection of the primary lesion for osteosarcoma patients with metastasis at initial diagnosis.
- 作者列表："Zhang L","Akiyama T","Fukushima T","Iwata S","Takeshita K","Kawai A","Tanaka S","Kobayashi H
BACKGROUND:Approximately 10-20% of osteosarcoma patients present with metastasis on diagnosis. Completely resecting the lesion is associated with better prognosis. However, evidence regarding optimal surgical strategies for patients with unresectable metastasis is limited. METHODS:This retrospective analysis was based on the Japanese Nationwide Bone and Soft Tissue Tumor registry. In total, 335 patients diagnosed with osteosarcoma with metastasis were included. Factors affecting overall survival were identified using multivariate analysis. Kaplan-Meier method was used to compare the overall survival by the status of surgical intervention. Two hundred and four patients who did not undergo surgery for metastasis were divided into two groups, depending on whether they underwent surgery for the primary lesion. The background differences between these two groups were adjusted with propensity score matching, with 43 patients per group. The overall survival was calculated using the Kaplan-Meier method and compared with a log-rank test. RESULTS:Factors positively impacting overall survival were age <40, female sex, extremity origin, surgery for the primary lesions, surgery for metastasis and radiotherapy without surgery. For patients with unresectable metastasis, after propensity score matching, the survival rate was higher in the group that underwent primary lesion surgery than the group without surgery. Their median survival was 19 (95% confidence interval: 11.7-26.3) and 11 months (95% confidence interval: 4.5-17.5) (P = 0.02), respectively. CONCLUSIONS:Surgical resection of the primary osteosarcoma lesion did not worsen prognosis, even in patients with unresectable metastasis. Further study is needed to identify which patient group will benefit from primary lesion resection.
背景: 大约10-20% 的骨肉瘤患者在诊断时出现转移。彻底切除病灶预后较好。然而，关于不可切除转移患者的最佳手术策略的证据有限。 方法: 这项回顾性分析基于日本全国骨和软组织肿瘤登记。共纳入335例诊断为骨肉瘤伴转移的患者。使用多变量分析确定影响总生存期的因素。采用Kaplan-Meier方法比较手术干预状态下的总生存期。二百零四名未接受转移手术的病人，根据是否接受原发病灶手术，分为两组。这两组之间的背景差异通过倾向评分匹配进行调整，每组43例患者.使用Kaplan-Meier方法计算总生存期，并与时序检验进行比较。 结果: 年龄 <40岁、女性、肢体来源、原发灶手术、转移灶手术和放疗不手术是影响总生存期的因素。对于无法切除转移的患者，在倾向评分匹配后，接受原发病灶手术的组的生存率高于未接受手术的组。他们的中位生存期分别为19个月 (95% 置信区间: 11.7-26.3) 和11个月 (95% 置信区间: 4.5-17.5) (P = 0.02)。 结论: 手术切除原发性骨肉瘤病灶并没有恶化预后，即使在不能切除的转移患者中。需要进一步研究以确定哪一组患者将从原发病灶切除中获益。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.