脊柱转移瘤治疗的Meta分析研究进展

随着癌症患者生存率的提高,肿瘤的脊柱转移日益严重。若不治疗可引起疼痛、椎体稳定性减弱、神经功能障碍等,严重影响患者生存能力和生活质量。脊柱转移瘤的治疗是十分复杂的,随着研究的不断深入,外科技术的不断进步和放射外科的实现彻底改变了脊柱转移瘤的治疗模式。脊柱转移瘤的手术和非手术治疗有望在未来得到不断的改进。目前治疗方法包括传统肿瘤全切术、椎板切除减压术、椎体成形术、椎体后凸成形术、射频消融技术和微创手术等外科手段;常规放射治疗、立体定向放射治疗和调强放射治疗等疗法。笔者对已发表的文献中脊柱转移瘤患者的治疗方法的选择和疗效的Meta分析研究进行了总结分析。     

椎体后凸成形骨水泥注入治疗脊柱转移瘤:脊柱稳定性与疼痛的变化

背景:脊柱转移瘤患者会出现不同程度的疼痛及脊柱稳定性异常等现象,临床可以利用经皮球囊扩张椎体后凸成形骨水泥注入方式进行治疗。目的:观察经皮球囊扩张椎体后凸成形骨水泥注入对脊柱转移瘤患者脊柱稳定性和疼痛的影响。方法:纳入脊柱转移瘤患者23例,其中女10例,男13例,年龄23-71岁,均实施经皮球囊扩张椎体后凸成形聚甲基丙烯酸甲酯骨水泥注入治疗。观察患者治疗前后的目测类比评分、椎体前缘与椎体后缘高度、生活质量评分及运动能力评分。结果与结论:与治疗前比较,23例患者治疗后24 h的目测类比评分和运动能力评分显著下降,椎体前、后缘平均高度显著上升(P均0.05)。随访12个月,无脊髓神经根损伤、不良反应及骨水泥渗漏等现象,患者生活质量评分较治疗前显著提高(P0.05)。表明经皮球囊扩张椎体后凸成形聚甲基丙烯酸甲酯骨水泥注入治疗脊柱转移瘤,可以显著改善脊柱稳定性,减轻疼痛程度,效果确切。     

经皮椎体成形术治疗脊柱转移瘤病人的护理

脊柱转移瘤占脊柱恶性肿瘤的一半以上,以腰椎多见,其次为胸椎、骶椎、颈椎。脊柱转移瘤的根治较为困难。临床症状主要是剧烈疼痛,因而缓解疼痛,提高病人生活质量成为治疗护理的主要内容。经皮椎体成形术是在影像学技术(如CT、X线等)引导下,应用骨穿针经皮肤穿刺到病变椎体,然后     

微创治疗中脊柱转移瘤椎体成形骨水泥注入及射频消融和放射疗法

背景：微创技术的发展明显降低了脊柱转移瘤手术并发症,目前微创治疗方法主要有椎体骨水泥增强、射频消融联合椎体成形、术中放疗联合椎体成形3大类。 目的：总结上述3大类微创治疗脊柱转移瘤的研究进展。 方法：以“脊柱转移瘤,椎体成形,射频消融,放射治疗;spinal metastases,vertebroplasty,radiofrequency ablation,radiotheray”为关键词,检索PubMed、万方数据库文献。 结果与结论：骨水泥增强技术应用广泛、止痛效果很好,有效率达80%-90%,但骨水泥产热杀灭肿瘤的效果非常有限,不能控制肿瘤生长;射频消融及放疗能够杀灭肿瘤,但不能重建稳定性,将不同技术结合可以提高脊柱肿瘤的治疗效果。术中应用放射线、植入放射性粒子或放射性骨水泥是近年发展起来的新技术,因报道较少,缺乏长期随访,目前还不能得出优于单纯骨水泥增强技术的结论。尤其是针对椎体后壁破坏及部分侵入椎管的转移瘤患者,虽然做了很多尝试,但骨水泥渗漏导致神经功能加重的风险依旧很高,所以目前还没有一种完善的微创治疗方法。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

43例脊柱转移瘤CT影像及临床分析

目的 探讨脊柱转移瘸的CT影像特点.方法 回顾性分析43例脊柱转移瘤的CT影像表现.结果 累及63节椎体、18处椎弓根、15处棘突及横突、1例胸骨、1例肱骨.40例均表现为溶骨性破坏;2例为成骨性破坏;1例为混合性骨破坏.结论 脊柱转移瘤好发脊柱椎体,主要表现为溶骨性破坏,CT检查是诊断脊柱转移瘤的主要方法.     

聚甲基丙烯酸甲酯骨水泥对原代培养脊柱转移瘤细胞的影响和意义

背景：目前经皮椎体成形技术已广泛应用于治疗老年骨质疏松椎体压缩性骨折以及椎体肿瘤并取得良好疗效,但仍有一些问题需关注和探讨。 目的：观察聚甲基丙烯酸甲酯骨水泥对脊柱转移瘤细胞周期变化和细胞凋亡的影响,分析其对脊柱转移瘤的体外抗肿瘤效应。 方法：原代培养脊柱转移瘤细胞,将其分为对照组、拉丝期聚甲基丙烯酸甲酯骨水泥组、冷却后聚甲基丙烯酸甲酯骨水泥组,药物处理24 h后利用流式细胞术观察凋亡率以及细胞周期,通过SYBR GreenⅠ荧光实时定量-聚合酶链反应法检测肿瘤细胞Bax和Caspase-3 mRNA表达的变化。 结果与结论：聚甲基丙烯酸甲酯骨水泥有促进脊柱转移瘤细胞凋亡的作用,对照组、拉丝期聚甲基丙烯酸甲酯骨水泥组、冷却后聚甲基丙烯酸甲酯骨水泥组的凋亡率分别为(3.80±1.09)%,(43.46±8.55)%,(28.77±9.39)%,两骨水泥组均能明显提高细胞凋亡率,拉丝期聚甲基丙烯酸甲酯骨水泥组作用更明显(P < 0.05)。两骨水泥组均能明显减少G0/G1期细胞,增加S期细胞(P < 0.05)。拉丝期聚甲基丙烯酸甲酯骨水泥组作用于脊柱转移瘤细胞后Bax、Caspase-3 mRNA的表达显著高于对照组(P < 0.05)。提示聚甲基丙烯酸甲酯骨水泥可在体外细胞水平诱导肿瘤细胞凋亡,拉丝期聚甲基丙烯酸甲酯骨水泥作用更加显著。      

射频消融联合人工骨椎体成形治疗脊柱转移瘤的疗效分析

目的探讨射频消融(RFA)联合注射用人工骨椎体成形术(PVP)治疗脊柱转移瘤的疗效。方法 58例脊柱转移瘤患者随机分为骨水泥1组(n=12)、人工骨1组(n=16)、骨水泥2组(n=16)、人工骨2组(n=14),骨水泥组行RFA注射用Ⅲ型丙烯酸树脂骨水泥PVP,人工骨组行RFA联合自固化磷酸钙人工骨PVP。对比分析各组术前及术后1周、1个月、3个月、6个月、9个月、12个月椎体形态及骨折发生率,以及视觉模拟评分(VAS),脊柱ODI评分。结果术后随访12个月内骨水泥组12例(42.9%)出现手术椎体或周围椎体变形,显著高于人工骨组(6.7%)(χ2=8.476 8,P=0.003 6)。各组术后VAS及ODI评分均较术前显著降低(P0.01),骨水泥组术后6、9、12个月高于人工骨组(P0.05)。结论 RFA联合骨水泥或人工骨PVP治疗脊柱转移瘤均效果显著,人工骨PVP疗效维持时间更持久。     

骨转移瘤的溶骨与成骨机制研究进展

骨骼是一种动态重塑的组织,终身以骨质溶解和骨质形成的方式进行骨骼动态重塑循环。骨微环境适宜实体肿瘤定植与生长。实体肿瘤骨转移发生率高,骨转移瘤可以导致明显溶骨性和(或)成骨性骨病灶,如乳腺癌主要以溶骨性病灶为典型,前列腺癌主要以成骨性病灶为主。骨转移瘤的骨骼生理以过度溶骨和(或)成骨为中心。溶骨和成骨的主要机制相互区别独立,本质上均为溶骨与成骨的相关因子打破机体正常骨骼重塑动态循环：RANK-RANKL-OPG系统、甲状旁腺激素相关肽和转移生长因子β参与溶骨,Wnts、内皮素1、甲状旁腺激素相关肽和骨形态发生蛋白参与成骨。骨转移瘤的溶骨与成骨效应都属于正反馈性"恶性循环"。本综述在理解正常骨骼生理与骨骼重塑动态循环的基础上重点阐述骨转移瘤的溶骨和成骨生理机制。探索骨转移瘤的溶骨和成骨生理机制可以为研究者研发靶向药物提供契机。     

恶性肿瘤骨转移早期＆quot;niche＆quot;微环境内相关分子的研究进展北大核心CSCD

骨组织是恶性肿瘤远处转移的第三好发器官,仅次于肺和肝.上皮来源的肿瘤更倾向于骨转移,常见于乳腺癌和前列腺癌患者.骨转移导致骨质破坏,可引起一系列骨相关事件,如高钙血症、脊髓压迫、剧烈疼痛、病理性骨折、瘫痪等,严重影响患者的生活质量.目前治疗骨转移瘤的药物比较单一,主要是晚期骨质破坏后的补救治疗,效果往往不理想,且不能从根本上预防骨相关事件的发生.     

环形减压结合骨水泥填充隔离治疗脊柱转移瘤

目的探讨脊柱360°环形减压结合骨水泥填充隔离、椎弓根钉棒系统内固定术治疗脊柱转移瘤的临床疗效。方法回顾性分析2012年4月至2016年10月于我院行脊柱360°环形减压结合骨水泥填充隔离、椎弓根钉棒系统内固定术的42例脊柱转移瘤患者的临床资料。术前、术后1周、术后3个月应用视觉模拟评分(VAS)评估疼痛程度,应用卡氏评分(KPS)评估功能状态,应用Frankel分级评估脊髓损伤。结果 42例患者术后随访3个月显示,未再次出现原节段神经症状,术后3个月VAS评分为(0.57±0.79)分,KPS评分为(72.61±19.12)分,两项评分相较于术前均有明显改善,差异具有统计学意义(P0.05),VAS改善率为(91.09±13.73)%,Frankel分级改善率为80%。结论环形减压结合骨水泥填充隔离治疗脊柱转移瘤可以有效改善脊柱转移瘤患者的疼痛及神经症状,提高患者生活质量,避免术后于原节段再次出现神经症状。     

Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients

The prognosis of prostate cancer is mainly determined by the presence or absence of metastases. Nevertheless, the metastatic pathways in prostate cancer are not entirely understood. Among 19,316 routine autopsies performed from 1967 to 1995 on men older than 40 years of age, the reports from those 1,589 (8.2%) with prostate cancer were analyzed. Hematogeneous metastases were present in 35% of 1,589 patients with prostate cancer, with most frequent involvement being bone (90%), lung (46%), liver (25%), pleura (21%), and adrenals (13%). Several lines of evidence suggested the existence of a backward metastatic pathway through veins from the prostate to the spine in addition to classical hematogeneous tumor spread via the vena cava. First, there was an inverse relationship between spine and lung metastases, suggesting that metastasis to the spine is independent of lung metastasis. Second, the maximum frequency of spine involvement occurred in smaller tumors (4 to 6 cm) as compared with the maximum spread to lung (6 to 8 cm) and liver (>8 cm), suggesting that spine metastases precede lung and liver metastases in many prostate cancers. Third, there was a gradual decrease in spine involvement from the lumbar to the cervical level (97% v 38%), which is consistent with a subsequent upward metastatic spread along spinal veins after initial lumbar metastasis. The results of this study show that bone, lung, and liver are the most frequent sites of distant prostate cancer metastases. Besides the cava-type of metastasis through lung passage, there are strong arguments for the existence and clinical significance of a backward venous spread to the spine, which is likely to occur early in the metastatic process.     

SPECT全身骨显像、血清tPSA及fPSA/tPSA比值及病理分级与前列腺癌骨转移的关系探讨

目的：探讨SPECT全身骨显像、血清tPSA水平、fPSA/tPSA比值及前列腺癌病理分级与前列腺癌骨转移的关系,并研究其发生骨转移的规律和特点。方法：以核医学SPECT全身骨显像为金标准,回顾性分析了体外放免法测定的107例前列腺癌患者的血清PSA（前列腺特异抗原）水平、血清fPSA/tPSA比值及全身骨显像和病理分级。结果：107例前列腺癌患者：49例发生骨转移,占45.8%（49/107）,其中不同病理分组之间骨转移发生率比较差异有统计学意义,分化程度越低,骨转移发生率越高;随着tPSA水平的升高,骨转移的发生率明显增加;血清tPSA（4～40）ng/ml时,采用fPSA/tPSA比值,可明显提高前列腺癌诊断特异性。结论：前列腺癌患者骨转移发生率与前列腺癌的分化程度、血清PSA水平及fPSA/tPSA比值有一定的关系。分化程度越低,骨转移发生率越高。     

前列腺癌骨转移的疼痛管理

在老年男性中前列腺癌发病率日益增高,晚期骨转移可产生顽固性骨痛,严重影响治疗效果和患者生活质量。对前列腺癌骨转移患者的疼痛管理需要从抗肿瘤治疗和镇痛治疗两方面入手,并防止长期治疗过程中的并发症,全程给予心理治疗。本文从前列腺癌骨转移的治疗入手,对疼痛管理现状作一综述。     

Fine needle aspiration of metastatic prostate carcinoma simulating a primary adrenal cortical neoplasm: A case report and review of the literature

Adrenal metastases usually occur in prostate cancer patients with widespread bone and visceral disease. Autopsy studies have shown that adrenal metastases may be found in up to 23% of these patients. However, the finding of an isolated adrenal metastasis without the involvement of other organs in a patient with prostate cancer is exceedingly rare. Thus, it may cause a diagnostic dilemma on FNA cytology. We report a patient with a history of prostate cancer, status post radiation, and hormonal therapy 4 years before, who presented with a new, single adrenal mass on abdominal imaging studies. The ultrasound‐guided FNA cytology of the adrenal mass revealed cytomorphological features that were suggestive of a primary adrenal cortical neoplasm, but overlapped with those of a prostate metastasis. To our knowledge, FNA findings of metastatic prostate cancer simulating an adrenal cortical neoplasm have not been previously reported in the English literature. The purpose of our study is to discuss the differential diagnosis of these entities. The accurate diagnosis is important because of different prognosis and treatment implications for the various diseases. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Expression of parathyroid hormone-related protein and its receptor in bone metastases from prostate cancer

Studies of breast cancer suggest that parathyroid hormone-related protein (PTHrP) is important in the development of bone metastases. To determine whether PTHrP expression is important in prostate cancer metastasis, immunohistochemistry and in situ hybridization were used to assess the expression of PTHrP and its receptor in primary prostate cancer and bone metastases from both prostate and non-prostate cancers. PTHrP was expressed in more prostate primary tumours than bone metastases (p=0.003, Fisher's exact test). All bone metastases from non-prostate cancers expressed PTHrP. In contrast, PTHrP receptor was expressed in all bone metastases, but in only 19% of primary prostate tumours (p=0.001). The receptor to PTHrP was found to be highly expressed in bone metastases from prostate and other primaries, whereas PTHrP protein was found to have lower expression in the bone metastases than in the primary tumours. In conclusion, the expression of the receptor to PTHrP is increased in bone metastases from prostate cancer and may play an important role in their formation.     

Differential expression of osteopontin and bone sialoprotein in bone metastasis of breast and prostate carcinoma

Breast and prostate cancer often metastasise to the skeleton. Interestingly, the histopathological characteristics of the bone lesions that arise from these two cancer types differ. Breast tumours give rise to metastases in the skeleton with a mixed lytic/sclerotic pattern, whereas a predominantly sclerotic pattern is seen in metastases from prostate tumours. Osteopontin (OPN) and bone sialoprotein (BSP) are bone matrix proteins that have been implicated in the selective affinity of cancer cells for bone. In the present study, 21 patient cases with skeletal metastasis and their respective primary tumours (12 with breast cancer, 9 with prostate cancer) were investigated by immunohistochemistry in order to assess the level of OPN and BSP. Moderate to strong OPN expression was found in 42% of all breast tumours and in 56% of all prostate tumours. Significantly more breast cancer bone metastases exhibited high OPN expression, 83%, as compared with prostate tumour bone metastases, 11% (P=0.0019). In contrast, moderate to strong BSP expression was found in 33% of breast tumours and in 89% of prostate tumours. In the bone lesions, only 33% of breast tumour metastases showed moderate/strong BSP expression compared to 100% of prostate tumour metastases (P=0.0046). This divergent pattern of OPN/BSP expression could be an important determinant for the different characteristics of these two types of bone metastasis, i.e., lytic vs. sclerotic, consistent with the proposed role of OPN in differentiation and activation of osteoclasts and of BSP as a stimulator of bone mineralisation. This revised version was published online in July 2006 with corrections to the Cover Date.     

Bone histology at autopsy and matched bone scintigraphy findings in patients with hormone refractory prostate cancer: the effect of bisphosphonate therapy on bone scintigraphy results

Bisphosphonates (BisP) are non-metabolized compounds with high bone affinity used in bone metastasis diagnosis and treatment. Currently, BisP are used to treat hypercalcemia of malignancy as well as to prevent, minimize, or delay skeletal morbidity. These compounds have a long half-life in bone. Thus long-term BisP treatment might saturate bone and interfere with a single-dose scanning agent used for bone scintigraphy when visualizing bone metastases. In an effort to answer this question, this study evaluated the concordance of histology and Technetium⁹⁹ methylene diophosphonate (Tc⁹⁹ MDP) bone scintigraphy in the diagnosis of bone metastases in prostate cancer patients. We assessed the concordance of findings between bone scintigraphy and histology using 188 bone biopsies from 11 autopsied patients who died with metastatic prostate cancer, 5 of whom were treated with pamidronate for 2 to 13 months before death. Overall agreement between histology and bone scintigraphy was 84%, 86% in non-pamidronate-treated patients and 82% in pamidronate-treated patients. Scintigraphic bone metastases without histological metastasis (false negatives = 12.7%) were observed in 24 anatomic locations; half of these were in one patient who had been treated with pamidronate and had no histological bone response to the carcinoma. There were only 4 sites where a positive bone scan was not associated with histologic metastasis (false positives = 2.21%). There was no statistical difference between the treated and non-treated group for concordance, specificity, sensitivity, positive and negative predictive values of bone scintigraphy and prevalence of histological abnormality. Long-term pamidronate treatment of prostate cancer bone metastases does not generally affect the ability to detect bone metastases with Tc⁹⁹ MDP bone scintigraphy. This revised version was published online in July 2006 with corrections to the Cover Date.     

TGF-β and BMP7 interactions in tumour progression and bone metastasis

The skeleton is the second most frequent site of metastasis. However, only a restricted number of solid cancers, especially those of the breast and prostate, are responsible for the majority of the bone metastases. Metastatic bone disease is a major cause of morbidity, characterised by severe pain and high incidence of skeletal and haematopoietic complications (fractures, spinal cord compression and bone marrow aplasia) requiring hospitalisation. Despite the frequency of skeletal metastases, the molecular mechanisms for their propensity to colonise bone are poorly understood and treatment options are often unsatisfactory. TGF-β and the signalling pathway it controls appears to play major roles in the pathogenesis of many carcinomas, both in their early stages, when TGF-β acts to arrest growth of many cell types, and later in cancer progression when it contributes, paradoxically, to the phenotype of tumour invasiveness. Here we discuss some novel insights of the TGF-β superfamily—including BMPs and their antagonists—in the formation of bone metastasis. Increasing evidence suggests that the TGF-β superfamily is involved in bone homing, tumour dormancy, and development of micrometastases into overt bone metastases. The established role of TGF-β/BMPs and their antagonists in epithelial plasticity during embryonic development closely resembles neoplastic processes at the primary site as well as in (bone) metastasis. For instance, the tumour-stroma interactions occurring in the tissue of cancer origin, including epithelium-to-mesenchyme transition (EMT), bear similarities with the role of bone matrix-derived TGF-β in skeletal metastasis formation.     

Prostate cancer presenting as an endobronchial mass: a case report with literature review

Endobronchial metastasis from a prostate cancer is uncommon. Diagnosis of prostate carcinoma after primary presentation with an endobronchial mass is very rare. The authors describe the case of an 84-year-old man with endobronchial metastases from prostatic carcinoma presenting primarily with pulmonary symptoms. The diagnosis of prostate cancer and endobronchial metastases was made by a bronchoscopic bronchial biopsy and confirmed by immunohistological staining with prostate-specific antigen. The importance of this manifestation along with clinical and therapeutic implications is discussed here.     

The relationship of TMPRSS2-ERG gene fusion between primary and metastatic prostate cancers

Recent studies have revealed the presence of TMPRSS2-ERG gene fusion in both primary and metastatic prostate cancers. However, the relationship between primary and corresponding metastatic prostate cancers with respect to the status of this gene fusion remains unclear. Using fluorescence in situ hybridization, we evaluated the rearrangement of the ERG gene in the radical prostatectomy specimens and corresponding lymph node metastases from 19 patients with prostate cancer. The mean age of the patients was 61 years, and the median Gleason score in the radical prostatectomy specimens was 7 (4 + 3). Prostate cancer was unifocal in 6 cases and multifocal in 13 cases, including 10 with 2 foci and 3 with 3 foci. In the primary prostate cancers, rearrangement of the ERG gene was observed in 13 cases and associated with deletion of the 5' ERG gene in 8 cases. In the metastases, the ERG rearrangement was present in 10 cases and associated with deletion of the 5' ERG gene in 6 cases. In unifocal prostate cancers, the status of the ERG rearrangement was concordant between the primary prostate cancer and metastasis in 5 of 6 cases. In multifocal prostate cancer, despite a significant interfocal discordance, the status of the ERG rearrangement was concordant between the index (largest) primary tumor focus and metastasis in all 13 cases. Our study demonstrates a close relationship of the TMPRSS2-ERG gene fusion status between primary and metastatic prostate cancer. The concordance of the ERG gene rearrangement status between the index primary tumor focus and metastasis suggests that metastasis most likely arises from the index tumor focus in multifocal prostate cancer.