Bisphosphonates Induce Apoptosis of Stromal Tumor Cells in Giant Cell Tumor of Bone

Giant cell tumour of bone (GCT) is an aggressive primary neoplasm that results in the production of osteolytic lesions. Stromal cells, which form the main neoplastic component of this tumor, regulate the formation of osleoclast-like giant cells that are ultimately responsible for bone destruction. Bisphosphonates prevent bone resorption by inhibiting osteoclast activity and promoting osteoclast apoptosis, and they have been known to induce apoptosis of primary neoplastic cells such as those in breast and prostate cancers. We hypothesized that in bisphosphonates may induce apoptosis not only in osteoclast-like giant cells but also in neoplastic stromal cells of GCT both in vitro and in vivo. Twelve patients with GCT were treated with weekly injections of pamidronate for a period of 6 weeks prior to surgery. GCT specimens were collected at the time of biopsy and during definitive surgery. TUNEL assay was used to evaluate apoptotic DNA fragmentation in cells. In addition, twelve GCT primary cultures from these patients were treated with zoledronate, pamidronate, or alendronate for 48 hours at different doses (3, 30, or 150 M) and subjected to apoptosis assay by flow cytometry following fluorescent Annexin-V labeling. The results showed that pamidronate significantly induced apoptosis in both osteoclast-like giant cells and stromal tumor cells, in vivo. All three bisphosphonates caused substantial apoptosis of stromal tumor cells in cultures. Zoledronate was the most potent reagent, resulting in an average cell death of 27.41% at 150 M, followed by pamidronate (22.23%) and alendronate (15.3%). Our observations suggest that these drugs may be considered as potential adjuvants in the treatment of GCT.Both authors (Y.Y. Cheng and L. Huang) contributed equally to this work.     

骨巨细胞瘤的局部复发与治疗

目的：防止骨巨细胞瘤的局部复发。方法：观察本院１９８１￣１９９８年４０例骨巨细胞瘤患者的术后疗效。结果：２８例骨巨细胞瘤病灶刮除骨水沁填充后,只有１例复发、６例肿瘤病灶刮除自体骨移植后,４例复发。结论：肿瘤病灶刮除后骨水泥填充能减少局部肿瘤复发;对于Ｘ线ＣａｍｐａｎａｃｃｉⅢ级,或者Ｅｎｎｅｃｋｉｎｇ外科分期Ⅰｂ或Ⅱｂ,或者Ｊａｆｆｅ病理分期Ⅲ级患者,应扩大切除肿瘤病灶,近关节处肿瘤可扩大切除术后     

青春期及儿童骨巨细胞瘤14例报告

目的：总结青春期及儿童骨巨细胞瘤（ＧｉａｎｔＣｅｌＴｕｍｏｒｏｆＢｏｎｅ,ＧＣＴ）的临床表现、放射学特点及治疗。方法：１４例青春期及儿童ＧＣＴ选自１９５７～１９９５年我科收治的２１６例ＧＣＴ病人,随访２～１２年,总结其临床表现,放射学特点,治疗及随访结果。结果：青春期及儿童ＧＣＴ占全部ＧＣＴ的６５％,１３／１４发生于１５～１８岁,临床表现以疼痛、肿胀为主,并发病理骨折者较成人ＧＣＴ发生率高;放射学改变为溶骨性改变,位于干骺端者较成年组多见。临床分期２期以下（１１／１４）,行病灶刮除、５０％氯化锌水溶液烧灼瘤腔壁＋植骨,３期行瘤段切除或截肢,全部病人无复发或转移,功能优良率达９１７％。结论：青春期及儿童ＧＣＴ较多位于干骺端,绝大多数属于临床２期,行刮除＋５０％氯化锌烧灼＋植骨的方法可以达到较理想的疗效     

骨巨细胞瘤P21蛋白的表达及意义

目的 探讨骨巨细胞瘤组织中Ras癌基因的蛋白产物P21的表达及生物学意义。方法 采用ABC免疫组织化学方法对69例骨巨细胞瘤组织中P21蛋白表达进行研究。结果 骨巨细胞瘤组织中P21蛋白阳性表达率为48％,其中病理分级Ⅰ、Ⅱ、Ⅲ级P21蛋白阳性表达率分别为43％、44％、86％,Ⅲ级阳性表达率明显高于Ⅰ级和Ⅱ级(P< 0.05);Enneking外科分期1、2、3期阳性表达率分别为33％、36％和73％,3期阳性表达率极显著高于1期和2期(P<0.01)。结论 Ras癌基因产物P21蛋白表达活性在良恶性骨巨细胞瘤中的表达有明显差异,可作为恶性骨巨细胞瘤的标志物;Enneking外科分期3期P21蛋白阳性表达率明显高于1期和2期,说明P21蛋白阳性表达与骨巨细胞瘤的侵袭性有密切关系。     

Stimulated Type I Collagen Turnover in Patients With Giant Cell Tumor of Bone

The aim of this study was to determine type I collagen turnover in giant cell tumor of bone (GCT) by biochemical markers of type I procollagen aminoterminal propeptide (PINP) and type I collagen carboxyterminal telopeptide (ICTP) as synthesis and degradation markers, respectively. The serum concentrations of PINP and ICTP were measured in 11 patients with GCT using radioimmunoassay, and analyzed by the correlation to the grades of GCT progression described by Campanacci. Serum of the 11 healthy subjects was available for comparison. The serum concentration of PINP was significantly higher in patients with GCT (82.4 ± 46.2 ng/ml) than in controls (40.8 ± 12.1 ng/ml) (P < 0.01), and that of ICTP was also significantly higher in GCT (5.3 ± 2.0 ng/ml) than in controls (3.2 ± 0.8 ng/ml) (P < 0.01). In GCT, the PINP concentration of grade 3 (127.6 ± 38.8 ng/ml) was higher than that in grade 1 patients (46.9 ± 4.8 ng/ml) (P < 0.01). ICTP concentration of both grades 2 (7.1 ± 1.4 ng/ml) and 3 (5.8 ± 1.8 ng/ml) patients was significantly higher than that of grade 1 (3.5 ± 0.6 ng/ml) patients (P < 0.01, P < 0.05, respectively). Two cases of serum concentration of PINP and ICTP after resection of GCT demonstrated that these biomarkers decreased to the control levels in the absence of GCT. Our results indicated that type I collagen turnover evaluated by ICTP and PINP was stimulated in the presence of GCT. Moreover, this enhanced metabolic turnover reflects the grade of GCT.     

放射治疗在脊柱骨巨细胞瘤治疗中的价值

作者回顾性评价放射治疗在脊柱骨巨细胞瘤（ＧＣＴ）治疗中的价值。本组１０例（男６例，女４例），年龄１８～３４岁（平均２７岁）。发病部位：颈椎６例，胸腰椎２例，腰、骶椎各１例。Ｊａｆｅ分级：Ⅰ级３例，Ⅰ－Ⅱ级２例，Ⅱ级１例，Ⅲ级２例，未分级２例。治疗方法：（１）单纯放疗治疗颈椎ＧＣＴ３例。（２）先放疗后手术治疗胸腰段ＧＣＴ２例。（３）先手术后放疗治疗颈椎ＧＣＴ３例，腰椎ＧＣＴ１例。（４）手术配合术前与术后放疗治疗骶椎ＧＣＴ１例。随访１．５～２９年（平均１４年）均无复发。５例生活自理，４例恢复工作，１例恢复较差。本组无放疗后恶变。作者认为，脊柱解剖复杂，难以将肿瘤彻底切除，所以手术配合术前术后放疗对脊柱ＧＣＴ的治疗有重要意义。     

膝关节融合治疗股骨远端侵袭性骨巨细胞瘤

目的：探讨应用自体腓骨移植联合膝关节融合治疗股骨远端侵袭性骨巨细胞瘤的应用及临床效果。方法：自2007-2009年对5例股骨远端侵袭性骨巨细胞瘤（Campanacci Ⅲ级）行整块切除术后骨缺损,采用游离腓骨移植联合钢板内固定行膝关节融合术重建下肢功能。结果：所有患者随访20～80个月,疼痛症状消失,MSTS评分21～27分,骨愈合时间6—18个月,无移植骨吸收和骨折,恢复正常工作劳动。所有患者均未出现病变复发及肺转移。结论：肿瘤整块切除联合腓骨移植膝关节融合术是治疗股骨远端侵袭性骨巨细胞瘤的一种良好选择。     

促凋亡基因bax在骨巨细胞瘤中的表达及分化调控意义

目的：研究促凋亡基因ｂａｘ在骨巨细胞瘤中的表达及其与Ｊａｆｅ分级和预后的关系。方法：采用兔抗人Ｂａｘ多克隆抗体及免疫组织化学ＳＡＢＣ法。结果：７３例骨巨细胞瘤中,Ｂａｘ阳性４７例（６４４％）;其中Ｊａｆｅ病理分级中Ⅰ级２７例中,阳性２２例（８１５％）,Ⅱ级３８例中阳性２３例（６０５％）,Ⅲ级８例中,２例阳性（２５０％）,Ｐ＜００５。在不同预后分组中Ｂａｘ阳性率间无显著差异（Ｐ＞００５）。结论：促凋亡基因在骨巨细胞瘤中不同程度的表达可能参与骨巨细胞瘤凋亡的调节,并与肿瘤分化程度有关。单一Ｂａｘ表达不能反应预后。     

Giant Cell Tumor of Tendon Sheath: Case Series and Review of Literature

Recurrence of Giant cell tumor of the tendon sheath (GCTTS) is an unresolved issue, though it is a non malignant condition. The authors operated on fourteen cases of GCTTS, after fine needle aspiration cytology confirmation and using a magnifying loupe for complete excision of the lesion including the satellite nodules. In only one case recurrence was noted which was successfully managed by a second wide excision. Preoperative diagnosis and meticulous surgical technique were found the only predictive factor of recurrence. During the 5 year period from 2002, 12 patients [11 females, 1 male, mean age 29.5, ranging from 10–53 years] underwent excision of giant cell tumor of tendon sheath of the hand. The lesions were found over the thumb [n = 7], ring finger [n = 1], index finger [n = 1], and over the hand [n = 2]. The lesions were classified using the Al-Qattan classification. The most common presentation was with a mass over the hand, with a predilection to the thumb [n = 7]. Radiological changes in the form of bony indentation was seen in only 2 cases. FNAC was inconclusive in 2 out of the 12 cases. Due to the high incidence of recurrence, pre-operative planning aided by a tissue diagnosis with fine needle aspiration cytology, wide surgical exposure, and meticulous dissection with help of magnification are imperative for a successful outcome in GCTTS.     

高温灭活骨粒骨水泥填充骨缺损治疗骨巨细胞瘤

目的：总结和评价高温灭活、骨粒骨水泥填充骨缺损治疗骨巨细胞瘤的疗效。方法：对20例骨巨细胞瘤采用高温灭活肿瘤组织，保留骨的原有结构，用自体或异体骨粒复合骨水泥填充骨缺损，恢复患者肢体的完整结构和功能。结果：经过2－3年随访，按Enneking's肢体功能评价优良率85％，并发症为10％，关节退变为10％，局部肿瘤原发率为0％，无转移，结论：高温灭活、骨粒骨水泥填充骨缺损是治疗骨巨细胞瘤的有效方法。     

Central Giant Cell Lesion

A classic case of central giant cell lesion (CGCL) is presented with emphasis on clinical, radiologic, and histologic features. The differential is discussed including peripheral giant cell granuloma, brown tumor of hyperparathyroidism, and giant cell tumor of bone. The molecular pathway of osteoclastogenesis is selectively reviewed and applied to suggest possible etiologies of the giant cell lesions. CGCL syndromes and treatment are also discussed.     

Telomerase Activity in Giant Cell Tumors of Bone

Background A giant cell tumor of bone (GCT) is a histologically benign neoplasma that has an unpredictable pattern of biological aggressiveness. In the present study, we investigated whether there was a correlation between telomere length or the levels of telomerase activity and other clinical features of GCTs, for the possible use of these factors as parameters of aggressiveness or prognosis. Methods In 16 surgically resected GCTs specimens, telomere length was assessed by terminal restriction fragments by Southern blot analysis. Telomerase activity was measured by a semiquantitative polymerase chain reaction–based telomeric repeat amplification protocol assay. Results Telomere length reduction was observed in 69% of the GCT samples. The telomere lengths of tumors were significantly shorter than those of normal tissue (P = .008). The mean telomere length of grade 3 tumors was significantly shorter than those of grade 1 and 2 tumors (P = .038). Telomerase activity was detected in 81% of tumor samples. The level of telomerase activity in tumors with local recurrence was significantly higher than in tumors without local recurrence (P = .011). Conclusions These results suggest that telomere length correlates with roentgenographic grade as a result of the frequency of cell division, and high telomerase activity indicates the aggressiveness of GCTs.     

应用综合评估法术前评估骨巨细胞瘤的侵袭性

应用穿刺活检进行病理诊断和分级,同时作DNA含量图象法分析,结合X线平片表现对骨巨细胞瘤的侵袭性进行综合评价,结果显示,在综合分级中,Ⅰ与Ⅱ级的复发率有显著性差异,而病理和X线分级则无显著性差异。提示综合分级对评估骨巨细胞瘤的侵袭性具有合理性和全面性,有助于指导治疗。     

Giant Cell Tumor of the Pelvis: a Systematic Review

This is a systematic review of articles concerning the morbidity, recurrence rate, treatment and treatment complications of pelvic giant cell tumors (GCTs). The key words “giant cell tumor, pelvis” were used to identify articles which included data on patients with pelvic GCTs in English and Chinese databases of published reports from 1949–2012. The articles were filtered by title, abstract and full text. Thirty‐eight articles and 165 patients were identified for this review. Data on all identified patients were studies; data in different articles on the same patients was not used repeatedly. The following patient data were collected where possible and subjected to systematic analysis; age, location of GCT, treatment, follow‐up, complications, recurrence and whether alive or dead. The mean age of onset was 33.2 years (range, 14–73 years), the peak ages of onset being between 21 and 40 years. A pronounced sex difference was identified, the male : female ratio being 1:1.7. The acetabulum was the commonest area for pelvic GCTs. Forty‐eight tumors were primarily located in the iliac, 60 in the acetabular and 31 in the ischiopubic area. Twenty‐seven patients experienced complications of treatment. Patients who had been treated by wide resection had the most complications; these included incisional infection and delayed healing of incisions. Local recurrence was common, having occurred in 39/158 patients (24.6%), comprising 24/72 (33.3%) who had undergone intralesional surgery only; 9/20 (45.0%) who had undergone radiotherapy only; 1/51 (2.0%) who had undergone wide resection; and 5/14 patients (35.7%) who had undergone radiation therapy or cryotherapy plus intralesional surgery. Mortality was low (3.2%, 5/158). Pelvic GCT is not common, the acetabular area appears to the most frequent site and the peak age is the third and fourth decades. Although the recurrence rate is high for all pelvic GCTs, the mortality is low. Treatment has a critical influence on recurrence. In spite of the associated complications, the lower local recurrence rate makes wide resection a reasonable option for patients with extensive and/or aggressive GCTs.     

人工膝关节置换治疗近膝部骨巨细胞瘤

目的：探讨人工膝关节置换治疗近膝部骨巨细胞瘤的效果。方法：对10例人工全膝关节置换术进行临床分析和总结。结果：人工全膝关节置换术治疗骨巨细胞10例，随访1-3年，平均1年4个月，无1例复发，无感染、松动和断裂现象。应用HSS膝关节评分进行分析，优8例，良2例，优良率为100％。结论：近膝关节部骨巨细胞瘤采用瘤段截除，人工全膝关节置换术的手术方法，效果满意。     

自体腓骨移植治疗桡骨远端骨巨细胞瘤

目的：探讨白体近端腓骨移植重建在桡骨远端骨巨细胞瘤临床治疗中的应用及效果。方法：对4例桡骨远端骨巨细胞瘤复发（Campanacci Ⅲ级）患者在行桡骨远端瘤段切除的同时,行自体近端腓骨移植重建手术。结果：所有患者随访27～50个月,疼痛症状消失,骨愈合时间5～9个月,平均愈合时间为6．5个月,无移植骨吸收和骨折,腕关节功能握持力为对侧手的55％（40～80％）,背伸活动度可达对侧50％（10～80％）,掌屈达40％（15～70％）,无神经血管损伤症状,恢复正常工作劳动。所有患者均未出现骨巨细胞瘤的复发及肺转移。结论：桡骨远端骨巨细胞瘤经广泛切除后,用自体近端腓骨移植进行保肢治疗,可较好地保留腕关节功能,是一种有效的治疗方法。