Role of intravenous zoledronic acid in management of giant cell tumor of bone- A prospective,randomized, clinical,radiological and electron microscopic analysis

BackgroundThe primary treatment of Giant cell tumor of bone is surgical management. Bisphosphonates are antiresorptive drugs which inhibit osteoclast mediated bone resorption and shown to have inhibitory effect on various tumors. The present study aims to establish clinical, ultrastructural and radiological response of intravenous zoledronic acid on giant cell tumor of bone.MethodologyDesign - Prospective randomized controlled study. A group of 30 patients of GCT bone were randomized into two equal groups. Patients in control group did not receive any adjuvant therapy before surgery. Patients in bisphosphonate group received three doses of intravenous zoledronic acid at four weeks interval prior to definitive surgery. The evaluation was done based on size of swelling, VAS score, plain radiograph, MRI and histopathological and Transmission electron microscopic examination findings.ResultsSignificant reduction in VAS score (from mean 5.33 to 1.8), increased mineralization particularly at periphery of lesion in plain radiograph, statistically significant increase in mean apoptotic index, P value < 0.0001 (mean 41.46 in bisphosphonate group and 6.06 in control group) was noted in bisphosphonate group. No significant change in tumor volume is noted in MRI. No significant side effects were noted.DiscussionOne distinctive feature of pathogenesis of GCT bone is osteoclastogenesis which causes extensive bone destruction. Use of intravenous Zoledronic acid counteracts this bone destruction. Further, possible antiangiogenic effect of intravenous bisphosphonates inhibits tumor growth and provides symptomatic improvement.ConclusionIV Zoledronic acid alleviates pain, produce sclerosis and induce apoptosis hence decrease the rate of tumor progression and decrease the rate of local bone destruction, hence they are useful adjuvant to surgery in GCT.     

骨巨细胞瘤治疗进展

骨巨细胞瘤是一种局部具有侵袭性、溶骨活性的良性骨肿瘤,传统治疗手段为囊内刮除植骨,但有很高的局部复发率,通过辅助手段对瘤腔进行处理,有效降低了局部复发;对于不同部位骨巨细胞瘤应依据病变部位、大小、侵犯范围、复发率的高低可选择不同的手术方法,包括假体置换、广泛切除、En bloc切除等;对于特殊部位预计手术风险大、不能完整切除患者可行动脉栓塞,有利于病情得到控制或手术;双磷酸盐、地诺单抗的应用给骨巨细胞瘤的治疗带来新的希望,可有效降低肿瘤复发,目前主要应用于复发、难治、特殊部位、转移性骨巨细胞瘤的治疗。化疗主要应用于转移、恶性骨巨细胞瘤的治疗,放疗对于复发或难以手术切除部位骨巨细胞瘤可控制肿瘤进展,但有恶变可能。双磷酸盐、地诺单抗缺乏长期随访,远期疗效尚不明确,骨巨细胞瘤治疗领域新方法、新药的研发为其带来了更多希望。     

Bisphosphonates may reduce recurrence in giant cell tumor by inducing apoptosis

Giant cell tumor of bone is an aggressive tumor characterized by extensive bone destruction and high recurrence rates. This tumor consists of stromal cells and hematopoietic cells that interact in an autocrine manner to produce tumoral osteoclastogenesis and bone resorption. This autocrine regulation may be disrupted by novel therapeutic agents. Nonspecific local adjuvant therapies such as phenol or liquid nitrogen have been used in the treatment of giant cell tumor, but specific adjuvant therapies have not been described. The bisphosphonates pamidronate and Zoledronate can induce apoptosis in giant cell tumor culture in a dose-dependent manner. We established giant cell tumor cultures from patients with extensive destruction of bone. One of the four cultures formed osteoclastlike giant cells in vitro after more than six passages without exogenous receptor activator of NF-kappaB ligand or macrophage colony stimulating factor. Annexin V staining, presence of active cleaved form of caspase-3, and disappearance of poly (ADP-ribose) polymerase on Western blotting indicated activation of apoptosis by bisphosphonates in giant cell tumor. These results indicate that topical or systemic use of pamidronate or zoledronate can be a novel adjuvant therapy for giant cell tumor by targeting osteoclastlike giant cells, mononuclear giant cell precursor cells, and the autocrine loop of tumor osteoclastogenesis.     

病灶切刮骨水泥填充治疗肢体骨巨细胞瘤125例

目的 探讨病灶切刮骨水泥填充治疗肢体骨巨细胞瘤（ＧＣＴ）的临床应用价值,方法 对１９８０年３月～１９９７年１２月１２５例ＧＣＴ的治疗情况进行回顾分析。患者男６２例,女６３例,年龄１２－７１岁,平均年龄３１．５岁,其中原发ＧＣＴ１０１例,复发ＧＣＴ２４例。发病部位在膝关节周围者１００例（占８０％）。结果 １２５例患者均获随访,随访时间１３－１９４个月,平均９６个月。原发ＧＣＴＦ得,１３例复发,复发率     

Modern Interpretation of Giant Cell Tumor of Bone: Predominantly Osteoclastogenic Stromal Tumor

Owing to striking features of numerous multinucleated cells and bone destruction, giant cell tumor (GCT) of bone, often called as osteoclastoma, has drawn major attractions from orthopaedic surgeons, pathologists, and radiologists. The name GCT or osteoclastoma gives a false impression of a tumor comprising of proliferating osteoclasts or osteoclast precursors. The underlying mechanisms for excessive osteoclastogenesis are intriguing and GCT has served as an exciting disease model representing a paradigm of osteoclastogenesis for bone biologists. The modern interpretation of GCT is predominantly osteoclastogenic stromal cell tumors of mesenchymal origin. A diverse array of inflammatory cytokines and chemokines disrupts osteoblastic differentiation and promotes the formation of excessive multi-nucleated osteoclastic cells. Pro-osteoclastogenic cytokines such as receptor activator of nuclear factor kappa-B ligand (RANKL), interleukin (IL)-6, and tumor necrosis factor (TNF) as well as monocyte-recruiting chemokines such as stromal cell-derived factor-1 (SDF-1) and monocyte chemoattractant protein (MCP)-1 participate in unfavorable osteoclastogenesis and bone destruction. This model represents a self-sufficient osteoclastogenic paracrine loop in a localized area. Consistent with this paradigm, a recombinant RANK-Fc protein and bisphosphonates are currently being tried for GCT treatment in addition to surgical excision and conventional topical adjuvant therapies.     

Oncologic and functional results after treatment of giant cell tumors of bone

Surgical treatment of giant cell tumor of bone has always been a difficult problem because of its local aggressive behavior. Oncologic results and functional outcome are reported here in a retrospective study of 36 patients, treated by various surgical procedures. The average age at the time of diagnosis was 34 years, and the median follow-up period was 7 years. Twenty-three patients were treated by intralesional excision with local adjuvant therapy, and 11 patients by extralesional excision. Two patients received radiotherapy only. Seven local tumor recurrences (30%) were encountered after intralesional procedures, while local tumor control was the rule after extralesional excision. Intralesional excision with local adjuvant therapy resulted in significantly better functional results compared with extralesional excision. Wide excision was associated with a poor functional outcome and marginal excision with a good functional outcome. For the treatment of giant cell tumor of bone, intralesional excision with local adjuvant therapy is recommended because of a good functional outcome. When applying cryosurgery as the local adjuvant, more vigorous freezing may be necessary to improve local tumor control.     

骨盆和骶骨骨巨细胞瘤的治疗策略

目的 探讨骨盆和骶骨骨巨细胞瘤(GCT)外科治疗的手术方法、局部复发率、并发症.方法 1997年12月至2005年12月我院共收治骶骨、骨盆GCT 46例,其中男性25例,女性21例.年龄17～64岁,平均32岁.骶骨GCT 24例、骨盆GCT 22例.骨盆Ⅰ区GCT(髂骨)8例,Ⅱ区(髋臼)10例,Ⅲ区(坐骨耻骨)4例.S1-5 GCT 2例,S1-4 4例,S1-3 12例,S1-2 5例,S3-5 1例.手术方法:行3次手术者2例,行2次手术者7例.骶骨GCT患者的治疗方式包括19例患者进行了病灶内边缘切除术,2例患者同时进行了病灶内边缘切除术和放疗,3例患者进行了广泛边缘切除术.骨盆22例GCT患者中,除2例坐骨及1例髂骨GCT患者采用刮除术外,其余19例均行大块切除术.结果 1例患者在外院手术后复发,肿瘤巨大、表面溃烂,再次手术后2周死于严重感染.余45例患者,随访时间12个月至8年,平均随访时间37个月.2例患者1年后死亡.1例骶骨GCT患者术后2年出现肺转移,化疗1周期,随访1年,肺部病灶无明显增大.1例髋臼部GCT患者刮除术后2年出现肺转移、局部复发,行肺部照射、髋臼部肿瘤广泛切除、人工半骨盆置换术,肺部病灶随访1年,控制良好.局部复发:骶骨:9/24(37.5%),其中复发2次的患者2例,复发1次的患者7例;骨盆:2/22(9.1%),2例坐骨GCT刮除后均局部复发;行大块切除的19例GCT均未复发.结论 对于骶骨GCT,由于刮除术后局部复发率高,治疗应该更具侵袭性.肿瘤广泛边缘切除术可能会引起骶神经损害,但由于局部复发率降低,所以仍为治疗的最佳选择.     

Locally administered zoledronic Acid therapy for giant cell tumor of bone

Giant cell tumor of bone is locally aggressive and occurs in the meta-epiphyseal region of long bones. Because of its high recurrence rate, local adjuvant therapies such as phenol or liquid nitrogen have been recommended. In the present study, zoledronic acid, a nitrogen-containing bisphosphonate, was administered locally as an adjuvant during a biopsy. An otherwise healthy 43-year-old man presented with pain and swelling in the right knee. Plain radiographs showed an osteolytic lesion of the right proximal tibia. An open biopsy was performed and the intraoperative pathologic diagnosis was giant cell tumor of bone. Following biopsy, the defect was filled with betatricalcium phosphate, and 4 mg of zoledronic acid was locally administered into the tumor lesion. Two months after the biopsy, curettage and bone grafting were performed. Sections were obtained during the curettage for histology to evaluate the response to bisphosphonate treatment. Histologic examination revealed massive tumor cell death in the lesion in which both stromal cells and osteoclast-like giant cells were necrotic. Curettage was performed and the defect was filled with a commercial preshaped hydroxyapatitetricalcium phosphate bone substitute. Eighteen months after curettage, the patient had regained full range of motion and good function of the knee, and radiographs at 18 months after curettage revealed no recurrence of giant cell tumor of bone.     

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.     

Surgical treatment of giant cell tumour of long bone with anhydrous alcohol adjuvant

This study was designed to evaluate the feasibility and effectiveness of the use of anhydrous alcohol as an adjuvant treatment for giant cell tumours (GCTs) of long bone. Between October 1989 and January 2004, 42 GCT patients were treated and followed up for an average of 4.1 years (range 1-13 years). Mean patient age was 34 years (range 17-67 years). After curettage and additional burring, anhydrous alcohol was used as an adjuvant therapy in all patients before the bone defect was filled with bone graft or cement. Four patients (9.5%) experienced local recurrence. There were no alcohol-related complications. Recurrence-free probability was 87.6% at final follow-up (13 years) after index surgery by Kaplan-Meyer analysis. Our data suggest that anhydrous alcohol can be used as an effective safe adjuvant for the treatment of GCT of long bone.     

Higher local recurrence rates after intralesional surgery for giant cell tumor of the proximal femur compared to other sites

Purpose

The treatment of giant cell tumor (GCT) of bone remains controversial. Intralesional surgery (curettage) results in a higher rate of local recurrence, but better functional results compared to resection. The aim of this study was to assess whether the use of curettage was successful in the treatment of GCT of long bones. We evaluated the influence of adjuvant treatment, local tumor presentation, and demographic factors on the risk of recurrence.

Methods

We retrospectively reviewed the records of patients treated for GCT of long bones between 1990 and 2013, using curettage. No patient had any treatment other than surgery. After detailed curettage, the bone cavity was filled with bone allografts and/or cement. Recurrence rates, risk factors for recurrence and the development of pulmonary metastases were determined. The minimum follow-up was 24 months.

Results

We enrolled 210 patients with GCT of long bones treated by curettage. The rate of local recurrence was 16.2% (34/210 patients). The median follow-up was 89.2 months. In the multivariate analysis, no significant statistical effect on the local recurrence rate could be identified for gender, patient’s age, Campanacci’s grading, or cement versus bone allografts. The only independent risk factor related to the local recurrence was the site, with a statistically significant higher risk for patients with GCT of the proximal femur.

Conclusions

Our observation on the correlation of tumor location and risk of local recurrence is new. We suggest that patients with GCT of bone in the proximal femur should be followed closely soon after surgery to identify any possible recurrence.

     

Giant cell tumor of bone. An evaluation of 87 patients

AIM: Giant cell tumor (GCT) of bone is a very peculiar and interesting tumor due to of its biological behavior and the phenomenon of pulmonary metastases of a histologically benign tumor. We present the results of a retrospective study. METHODS: Between 1965 and 2002 we treated 87 patients, 54 women and 33 men, for a GCT of bone. The average age of the patients was 28.2 (range 8-72) years. The median follow-up time was 91 months. 63 patients (72.4%) were hospitalized with a primary tumor. Twelve of these patients (19 %) had a pathological fracture. 24 patients (27.6%) presented with local recurrence. 7 tumors were malignant GCT of bone, 80 tumors were benign. According to the classification of Campanacci, 9 patients (10.3%) were diagnosed in stage I, 42 (48.3%) in stage II, and 36 (41.4%) in stage III. Surgical procedures were intralesional curettage and packing with cement in 36 patients, and bone-grafting in 7. In 35 cases we performed a wide resection, and in nine an amputation. RESULTS: Local recurrence was observed in 11 patients (12.6%), all of them were benign GCT. Local recurrences were followed by an intralesional curettage and bone-grafting in three cases (42.8%), packing with cement in seven (19.4%). Three patients with local recurrence (27.3%) also had synchronous pulmonary metastases. All patients diagnosed with benign GCT are still alive. 3 out of 7 patients with malignant GCT died from progression of metastatic disease. CONCLUSION: To reduce the risk of local recurrence and pulmonary metastases, we recommend an adjuvant therapy of GCT.     

Giant cell tumor of bone: Is curettage the answer?

Background:

Giant cell tumors (GCT) are neoplasms of mesenchymal stromal cells with varied manifestations. There is no uniform accepted treatment protocol for these tumors,

Materials and Methods:

49 cases of proven giant cell tumors of appendicular skeleton, 27 prospective and 22 retrospective constituteed this study. The retrospective cases were collected by using computerized data base collection method. The patients were evaluated clinically, radiologically and by histology. Companacci grading and Enneking staging was used in the study. Two treatment modalities were used a) extended curettage (with/ without bone grafting/ cementation) or b) wide excision and reconstruction with a prosthesis or arthrodesis. Functional evaluation was done by Enneking''s system. Chi square tests, mann-whitney test and ANOVA were used for statistical analysis.

Results:

The average age was 26.82 years (16-50 years). 25 patients (51%) were recurrent GCT at presentation. The commonest site was lower end of femur (16 cases, 32.65%) and upper end of tibia (13 cases, 26.53%). 40 (81.63%) tumors had less than 5 mm of subchondral bone free of tumor. 35 (71.43%) tumors were Enneking''s surgical stage III and companacci grade III. Pathological fractures were seen in 12 (24.49%) cases. Intra-lesional currettage was used in 28 and enbloc excision in 19 patients and 2 (4.08%) underwent amputation. The average follow up period was 18.6 months (range 2-84). One recurrence was seen in a grade III recurrent distal radial lesion in the intralesional curettage group (3.57%) Enneking''s functional score with intralesional curettage (25.41) was better than enbloc excision (21.37). Enbloc excision had higher rates of infections (36.84 % Vs 25%) and soft tissue coverage problems (21.05% Vs 0).

Conclusion:

Intralesional therapy has a better functional outcome and less complications than enbloc excision, albeit with a high recurrence rate which can however be effectively treated with repeat extended curettage.     

The management of diffuse-type giant cell tumour (pigmented villonodular synovitis) and giant cell tumour of tendon sheath (nodular tenosynovitis)

Giant cell tumours (GCT) of the synovium and tendon sheath can be classified into two forms: localised (giant cell tumour of the tendon sheath, or nodular tenosynovitis) and diffuse (diffuse-type giant cell tumour or pigmented villonodular synovitis). The former principally affects the small joints. It presents as a solitary slow-growing tumour with a characteristic appearance on MRI and is treated by surgical excision. There is a significant risk of multiple recurrences with aggressive diffuse disease. A multidisciplinary approach with dedicated MRI, histological assessment and planned surgery with either adjuvant radiotherapy or systemic targeted therapy is required to improve outcomes in recurrent and refractory diffuse-type GCT. Although arthroscopic synovectomy through several portals has been advocated as an alternative to arthrotomy, there is a significant risk of inadequate excision and recurrence, particularly in the posterior compartment of the knee. For local disease partial arthroscopic synovectomy may be sufficient, at the risk of recurrence. For both local and diffuse intra-articular disease open surgery is advised for recurrent disease. Marginal excision with focal disease will suffice, not dissimilar to the treatment of GCT of tendon sheath. For recurrent and extra-articular soft-tissue disease adjuvant therapy, including intra-articular radioactive colloid or moderate-dose external beam radiotherapy, should be considered.     

地诺单抗通过STAT3信号通路抑制骨巨细胞瘤的初步研究

目的 研究STAT3信号通路及其下游相关分子在地诺单抗治疗骨巨细胞瘤过程中的表达变化及其意义。方法 收集我院2013年1月至2018年12月手术治疗的31例骨巨细胞瘤病人,其中28例未经地诺单抗治疗（对照组）,3例经地诺单抗治疗（研究组）。通过苏木素-伊红（hematoxylin and eosin, HE）染色检测骨巨细胞瘤组织经地诺单抗治疗前后的病理学变化;通过免疫组化法检测研究组和对照组的骨巨细胞瘤组织中RANKL、STAT3及其下游分子Bcl-2、Cyclin D1分子的表达差异;通过TUNEL法检测上述两组石蜡切片组织中肿瘤细胞的凋亡情况。结果 HE染色结果：对照组中骨巨细胞瘤组织主要由肿瘤基质细胞和多核破骨样巨细胞组成;研究组中破骨样巨细胞消失,残留部分细长形肿瘤基质细胞,大量网状纤维组织及编织骨形成并替代肿瘤组织;免疫组化检测结果：RANKL主要表达于肿瘤基质细胞;STAT3主要表达于多核破骨细胞胞浆和肿瘤基质细胞胞膜;Bcl-2主要表达于多核破骨样巨细胞胞浆、散在分布于细胞核;Cyclin D1表达于多核破骨样巨细胞的细胞核中。RANKL、STAT3、Bcl-2和Cyclin D1在对照组肿瘤组织中的阳性表达率分别为70%、53%、77%、73%;研究组肿瘤组织中多核破骨样巨细胞消失,残留的肿瘤基质细胞中RANKL表达量明显减少,未见STAT3、Bcl-2、Cyclin D1分子表达;TUNEL法凋亡结果：对照组中仅有少量的肿瘤细胞凋亡,研究组中可见残留的肿瘤细胞明显凋亡。结论 地诺单抗可能通过抑制STAT3 信号通路抑制多核破骨样巨细胞的形成及促进肿瘤基质细胞凋亡。     

The Influence of Adjuvants on Local Recurrence Rate in Giant Cell Tumour of the Bone

Introduction: Intralesional surgery of giant cell tumour of the bone (GCT) may result in a high rate of local recurrence. The introduction of local adjuvants, such as cementation, cryosurgery or phenolization, has proved to be successful in the reduction of recurrence rates. This study presents the results of a single institution in surgery of GCT with an evolution in treatment strategies.

Material & Methods: Forty primary and 25 recurrent surgical procedures in 46 patients with GCT of the bone with a median follow-up of 72 months were reviewed retrospectively. The mean age was 32.6 years (range 13.6–57.9 years). Forty-seven curettages and 18 resections were performed. For the curettages, a large bone window was cut followed by high speed burring and bone grafting or cementation. In 34 of 47 curettages and 7 of 18 resections, phenol was additionally applied.

Results: Two patients showed pulmonary metastasis, one died due to metastatic disease. In total, a third of the patients developed local recurrence (32.3%). This was evenly spread among primary and recurrent diesease (32.5% vs. 32%). Seven of 13 curettages without adjuvant recurred (53.9%), compared to 11 of 34 curettages with adjuvant phenol (32.4%). Three of 18 resections developed a recurrence (16.7%). No complications in respect to the use of phenol were seen. Discussion: Phenolization is a safe local adjuvant therapy for GCT. Although the recurrence rate was lower with the use of phenol, this drop was not significant. The comparable high recurrence rate in our study, even if phenol was used, might be due to the fact that curettage was our favoured treatment, even in cases with an extensive juxta-articular tumour. We recommend adjuvant phenolization in the treatment of GCT of the bone after thorough curettage in applicable cases, including where cementation is used for defect filling.     

An unusual tumor of rib diaphysis—report of a giant cell tumor and a brief review of literature

Giant Cell Tumor of bone (GCT) is a benign but aggressive tumor, which forms about 4?C5% of primary bone tumors and 1?C2% of all chest wall tumors. It arises in the epiphysis of bones. The epiphysis of a rib is in its head and tubercle posteriorly and hence a GCT arising in a rib??s anterior aspect, its diaphysis, is rare. In this unusual position, it can be mistaken for other more common diaphyseal pathologies. Radiological images are often diagnostic. A needle biopsy is best avoided and a wide excision biopsy is the treatment of choice. Microscopically, multinucleated giant cells are seen amidst stromal cells. Giant cells like these are also seen in other diseases like the brown tumor of primary hyperparathyroidism. Giant cell lesions are never caused by secondary hyperparathyroidism. We present a case of a diaphyseal GCT of rib in a patient with secondary hyperparathyroidism who was successfully treated.     

Primary malignant giant cell tumor of bone: a series of three rare cases

The purpose of this research was to study incidence; clinical, histological, and radiological features; and outcome of primary malignant giant cell tumor (PMGCT). The authors retrospectively reviewed all cases of giant cell tumor (GCT) in which a diagnosis of GCT was related to sarcoma treated in their department between 1997 and 2004. Three cases of PMGCT were found according to the criterion of Hutter and Dahlin. Histological and radiological records of all the three cases were reviewed. In these three cases of PMGCT, the initial clinical and radiological findings were the same as those for benign giant cell tumor. Wide excision of the tumor was performed in all three cases. In two cases, knee arthrodesis was performed, and in one case a custom-made total knee replacement was performed. PMGCT was diagnosed on initial biopsy in one patient, in the second patient it was diagnosed in the excised specimen, and in third case it was only diagnosed after local recurrence 6 months after initial treatment. All the patients died within 5 months of detection of recurrence and metastasis. PMGCT has a very poor prognosis. Histological examination is highly significant in such cases. Awareness about this entity, adequate biopsy, and sampling of specimen can aid in early diagnosis, which may improve the overall prognosis.     

复杂性骨巨细胞瘤的外科治疗初步随访分析

目的提出复杂性骨巨细胞瘤的定义并回顾分析其治疗方法和结果，为减少其术后复发提供临床依据。方法2001年4月～2005年4月共治疗22例复杂性骨巨细胞瘤患者。男11例，女11例。年龄15～60岁。肿瘤位于股骨下段10例，胫骨上段5例，股骨近端2例，肱骨近端2例，髋骨2例和桡骨远端l例。所有患者按Campanicci’s分级，Ⅱ级4例，余均为Ⅲ级。行肿瘤边缘性切除或扩大性切除加大段同种异体骨与关节移植14例，肿瘤型人工关节置换8例。结果将骨巨细胞瘤已穿破骨皮质和／或侵犯至关节软骨下，已发生病理性骨折，瘤组织活检显示肿瘤细胞具有较强的侵袭性和肿瘤已有一次或多次复发定义为复杂性骨巨细胞瘤。所有患者获随访6～48个月，平均23个月。2例患者分别于术后8个月和11个月复发，分别经截肢和放射治疗后好转，复发率为9％。人工关节置换的关节功能优于同种异体骨移植；不带关节的同种异体骨移植的关节功能优于带关节的同种异体骨移植。所有移植的同种异体骨均获得不同程度的骨愈合。结论对定义为复杂性骨巨细胞瘤患者采用上述方法进行治疗，可获得较低的肿瘤复发率和一定范围的关节功能，是临床上治疗复杂性骨巨细胞瘤可采用的一种方法。     

PTHrP increases RANKL expression by stromal cells from giant cell tumor of bone

Giant cell tumor of bone (GCT) presents with numerous osteoclast-like multinucleated giant cells that are principally responsible for the extensive bone resorption by the tumor. Although the precise etiology of GCT remains uncertain, the accumulation of giant cells is partially due to the high expression of the receptor activator of nuclear factor-κB ligand (RANKL) from the neoplastic stromal cells. Here, we have investigated whether parathyroid hormone-related protein (PTHrP) plays a role in the pathogenesis of GCT. Immunohistochemistry results revealed PTHrP expression in the stromal cells of the tumor, and that its receptor, the parathyroid hormone type 1 receptor (PTH1R), is expressed by both the stromal cells and giant cells. PCR and Western blot analyses confirmed the expression of PTHrP and PTH1R by isolated stromal cells from five patients presenting with GCT. Treatment of GCT stromal cells with varying concentrations of PTHrP (1-34) significantly increased both RANKL gene expression and the number of multinucleated cells formed from RAW 264.7 cells in co-culture experiments, whereas inhibition of PTHrP with a neutralizing antibody decreased RANKL gene expression. These results suggest that PTHrP is expressed within GCT by the stromal cells and can contribute to the abundant RANKL expression and giant cell formation within the tumor.