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1.  Giant-cell tumor of bone, anti-RANKL therapy 
BoneKEy Reports  2012;1:149.
Giant-cell tumor of bone (GCTB) is a rare osteolytic tumor of the bone. Although classified as a benign tumor, GCTB is characterized by local aggressiveness and risk of local recurrence. In addition, GTCB can in some cases lead to the development of so-called 'benign' chest metastases. Surgical resection by intralesional curettage with high-speed burring and polymethylmethacrylate cement is the standard treatment for resectable tumors. In cases of metastatic or unresectable disease (when planned surgical procedure is impossible or would result in severe morbidity), medical treatments such as cytotoxic chemotherapy or interferon-α have limited efficacy. Bisphosphonates have been proposed as a therapeutic option to reduce osteoclast activity. In bone, various pathological states may result from an imbalance in the RANK (receptor activator of nuclear factor kappa-B)/RANKL (receptor activator of nuclear factor kappa-B ligand)/OPG (osteoprotegerin) pathway. Involvement of the RANKL pathway in pathogenesis of GCTB was first proposed in 2000. Denosumab is a fully human monoclonal antibody that binds and inhibits RANKL, thereby preventing the activation of the RANK pathway. As it showed the possibility to counteract osteoclast activation in GCTB and prevent the known physiopathological role of RANKL, denosumab has been under evaluation in the clinic as a treatment for GCTB since 2005. Results of a first Phase II trial demonstrate the therapeutic potential of denosumab to inhibit progressive bone destruction and metastatic progression in patients with unsalvageable giant-cell tumor (GCT), and have also provided key insights into the biology of GCT. Denosumab is currently a therapeutic option for patients with unresectable GCTB but its place in the global therapeutic strategy has not yet been defined.
doi:10.1038/bonekey.2012.149
PMCID: PMC3868728  PMID: 24363925
2.  Giant Cell Tumor of Bone: Risk Factors for Recurrence 
Background
Many surgeons treat giant cell tumor of bone (GCT) with intralesional curettage. Wide resection is reserved for extensive bone destruction where joint preservation is impossible or when expendable sites (eg, fibular head) are affected. Adjuvants such as polymethylmethacrylate and phenol have been recommended to reduce the risk of local recurrence after intralesional surgery. However, the best treatment of these tumors and risk factors for recurrence remain controversial.
Questions/purposes
We evaluated the recurrence-free survival after surgical treatment of GCT to determine the influence of the surgical approach, adjuvant treatment, local tumor presentation, and demographic factors on the risk of recurrence.
Methods
We retrospectively reviewed 118 patients treated for benign GCT of bone between 1985 and 2005. Recurrence rates, risk factors for recurrence and the development of pulmonary metastases were determined. The minimum followup was 36 months (mean, 108.4 ± 43.7; range, 36–233 months).
Results
Wide resection had a lower recurrence rate than intralesional surgery (5% versus 25%). Application of polymethylmethacrylate decreased the risk of local recurrence after intralesional surgery compared with bone grafting; phenol application alone had no effect on the risk of recurrence. Pulmonary metastases occurred in 4%; multidisciplinary treatment including wedge resection, chemotherapy, and radiotherapy achieved disease-free survival or stable disease in all of these patients.
Conclusion
We recommend intralesional surgery with polymethylmethacrylate for the majority of primary GCTs. Because pulmonary metastases are rare and aggressive treatment of pulmonary metastases is usually successful, we believe the potential for metastases should not by itself create an indication for wide resection of primary tumors.
Level of Evidence
Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-010-1501-7
PMCID: PMC3018195  PMID: 20706812
3.  Recurrent Giant Cell Tumor of Long Bones: Analysis of Surgical Management 
Background
Treatment of giant cell tumor of bone (GCT) often is complicated by local recurrence. Intralesional curettage is the standard of care for primary GCTs. However, there is controversy whether intralesional curettage should be preferred over wide resection in recurrent GCTs.
Questions/purposes
We investigated the rerecurrence-free survival after surgical treatment of recurrent GCTs to determine the influence of the surgical approach, adjuvant treatment, local tumor presentation, and demographic factors on the risk of further recurrence.
Patients and Methods
We retrospectively reviewed the medical records of 46 patients with recurrent GCTs of long bones treated with wide resection or intralesional curettage and compared these cohorts. Recurrence rates, risk factors for recurrence, and the development of pulmonary metastases were determined. The minimum followup was 37 months (mean, 134 months; range, 37–337 months).
Results
The rate of rerecurrence after wide resection was 6%. Intralesional curettage showed an overall rerecurrence rate of 32%. Implantation of polymethylmethacrylate (PMMA) instead of bone grafting was associated with a lower risk of subsequent recurrence in intralesional procedures (14% versus 50%). Extracompartmental disease did not increase the risk of rerecurrence. Pulmonary metastases occurred in seven patients and appeared independent of the surgical treatment modality chosen.
Conclusions
Intralesional curettage with methylmethacrylate for recurrent GCT provided equivalent tumor control compared with resection in this retrospective study. If joint salvage is possible, we advocate this treatment over resection in recurrent GCTs to preserve the native joint articulation.
Level of Evidence
Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-010-1560-9
PMCID: PMC3048273  PMID: 20857250
4.  Contemporary adjuvant polymethyl methacrylate cementation optimally limits recurrence in primary giant cell tumor of bone patients compared to bone grafting: a systematic review and meta-analysis 
Background
Reports of recurrence following restructuring of primary giant cell tumor (GCT) defects using polymethyl methacrylate (PMMA) bone cementation or allogeneic bone graft with and without adjuvants for intralesional curettage vary widely. Systematic review and meta-analysis were conducted to investigate efficacy of PMMA bone cementation and allogeneic bone grafting following intralesional curettage for GCT.
Methods
Medline, EMBASE, Google Scholar, and Cochrane databases were searched for studies reporting GCT of bone treatment with PMMA cementation and/or bone grafting with or without adjuvant therapy following intralesional curettage of primary GCTs. Pooled risk ratios and 95% confidence intervals (CIs) for local recurrence risks were calculated by fixed-effects methods.
Results
Of 1,690 relevant titles, 6 eligible studies (1,293 patients) spanning March 2008 to December 2011 were identified in published data. Treatment outcomes of PMMA-only (n = 374), bone graft-only (n = 436), PMMA with or without adjuvant (PMMA + adjuvant; n = 594), and bone graft filling with or without adjuvant (bone graft + adjuvant; n = 699) were compared. Bone graft-only patients exhibited higher recurrence rates than PMMA-treated patients (RR 2.09, 95% CI (1.64, 2.66), Overall effect: Z = 6.00; P <0.001), and bone graft + adjuvant patients exhibited higher recurrence rates than PMMA + adjuvant patients (RR 1.66, 95% CI (1.21, 2.28), Overall effect: Z = 3.15, P = 0.002).
Conclusions
Local recurrence was minimal in PMMA cementation patients, suggesting that PMMA is preferable for routine clinical restructuring in eligible GCT patients. Relationships between tumor characteristics, other modern adjuvants, and recurrence require further exploration.
doi:10.1186/1477-7819-11-156
PMCID: PMC3717274  PMID: 23866921
Giant cell tumors; Recurrence; Polymethyl methacrylate; Cementation; Bone grafting
5.  Which Treatment is the Best for Giant Cell Tumors of the Distal Radius? A Meta-analysis 
Background
Intralesional excision and en bloc resection are used to treat giant cell tumors (GCTs) of the distal radius. However, it is unclear whether one provides lower rates of recurrences and fewer complications, and whether the use of polymethylmethacrylate (PMMA) after curettage reduces the risk of recurrence.
Questions/Purposes
We examined whether curettage was associated with lower rates of recurrence and fewer major complications compared with en bloc excision, and whether PMMA resulted in lower rates of recurrence compared with a bone graft.
Methods
We systematically searched the literature using the criteria, “giant cell tumor” AND “curettage” OR “intralesional excision” OR “resection”. Six relevant articles were identified that reported data for 80 curettage cases (PMMA, n = 49; bone graft, n = 26; no PMMA or bone grafts, n = 5) and 59 involving en bloc excision. A meta-analysis was performed using these data.
Results
Overall, patients in the intralesional excision group had a higher recurrence rate (relative risk [RR], 2.80; 95% CI, 1.17–6.71), especially for Campanacci Grade 3 GCTs (RR, 4.90; 95% CI, 1.36–17.66), yet fewer major complications (RR, 0.21; 95% CI, 0.09–0.54) than the en bloc resection group. The use of PMMA versus bone graft did not affect the recurrence rate (RR, 0.98; 95% CI, 0.44–2.17).
Conclusions
Based on data obtained from the limited number of studies available, intralesional excision appears to be more appropriate for the treatment of local lesions (eg, Grades 1 and 2) than Grade 3 GCTs of the distal radius. Moreover, PMMA was not additionally effective as an adjuvant.
Level of Evidence
Level III, therapeutic study (systematic review). See Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-012-2464-7
PMCID: PMC3442009  PMID: 22773395
6.  Giant Cell Tumor With Pathologic Fracture: Should We Curette or Resect? 
Background
Approximately one in five patients with giant cell tumor of bone presents with a pathologic fracture. However, recurrence rates after resection or curettage differ substantially in the literature and it is unclear when curettage is reasonable after fracture.
Questions/Purposes
We therefore determined: (1) local recurrence rates after curettage with adjuvants or en bloc resection; (2) complication rates after both surgical techniques and whether fracture healing occurred after curettage with adjuvants; and (3) function after both treatment modalities for giant cell tumor of bone with a pathologic fracture.
Methods
We retrospectively reviewed 48 patients with fracture from among 422 patients treated between 1981 and 2009. The primary treatment was resection in 25 and curettage with adjuvants in 23 patients. Minimum followup was 27 months (mean, 101 months; range, 27–293 months).
Results
Recurrence rate was higher after curettage with adjuvants when compared with resection (30% versus 0%). Recurrence risk appears higher with soft tissue extension. The complication rate was lower after curettage with adjuvants when compared with resection (4% versus 16%) and included aseptic loosening of prosthesis, allograft failure, and pseudoarthrosis. Tumor and fracture characteristics did not increase complication risk. Fracture healing occurred in 24 of 25 patients. Mean Musculoskeletal Tumor Society score was higher after curettage with adjuvants (mean, 28; range, 23–30; n = 18) when compared with resection (mean, 25; range, 13–30; n = 25).
Conclusions
Our observations suggest curettage with adjuvants is a reasonable option for giant cell tumor of bone with pathologic fractures. Resection should be considered with soft tissue extension, fracture through a local recurrence, or when structural integrity cannot be regained after reconstruction.
Level of Evidence
Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-012-2546-6
PMCID: PMC3563806  PMID: 22926445
7.  Ethanol as a Local Adjuvant for Giant Cell Tumor of Bone 
Giant cell tumor is an aggressive benign neoplasm of bone. A number of adjuvant agents have been used to supplement intralesional curettage to reduce the otherwise high local recurrence rate. High concentration ethanol is more readily available and less toxic to use than some common alternatives. No report on its use in a group of patients with giant cell tumor is available. Records were retrospectively reviewed for all giant cell tumors treated by intralesional curettage and high concentration ethanol irrigation as the only chemical adjuvant. Twenty-five primary excisional curettages and 12 repeat curettages for giant cell tumors of bone were performed in 31 patients. Patients were followed for a mean of three years and 10 months. There were five recurrences after primary excision procedures, and three after repeat excisions. Only use of a high-speed burr and lower Campanacci staging correlated with reduced recurrence rate, and these were not statistically significant. Most defects were filled with allograft or calcium sulfate. In the 11 patients treated primarily with curettage using a high-speed burr and adjuvant ethanol with minimum two-year follow-up, only one stage 3 lesion in a distal radius recurred. Multiple washes with high concentration ethanol, when used in conjunction with aggressive curettage including high-speed burring, is an effective and safe adjuvant. The necessity of any chemical adjuvant after appropriately aggressive curettage and burring can only be definitively demonstrated with a prospective, randomized, multi-center trial. Until such evidence becomes available, the use of adjuvant ethanol offers a compromise between higher toxicity adjuvants and no chemical adjuvant at all.
PMCID: PMC1888590  PMID: 16789453
8.  Case Report: Reconstruction of the Distal Tibia with Porous Tantalum Spacer after Resection for Giant Cell Tumor 
Treatment options for giant cell tumors of the distal tibia include curettage and cement packing, curettage and bone grafting, or resection and reconstruction for aggressive tumors. Curettage of aggressive tumors often leads to severe bone loss requiring reconstruction. Allograft and autograft may be effective options for reconstruction, but each is associated with drawbacks including the possibility of infection and collapse. We present a case of giant cell tumor of the distal tibia treated with curettage and arthrodesis using a porous tantalum spacer. Complete removal of the tumor and successful arthrodesis of the ankle were accomplished using the spacer. The patient returned to pain-free walking along with eradication of the giant cell tumor. We believe porous tantalum spacers are a reasonable option for reconstructing the distal tibia after curettage of a giant cell tumor with extensive bone loss.
doi:10.1007/s11999-009-1097-y
PMCID: PMC2865625  PMID: 19756900
9.  Local control of long bone giant cell tumour using curettage, burring and bone grafting without adjuvant therapy 
International Orthopaedics  2006;30(6):495-498.
Giant cell tumour (GCT) is a benign, but aggressive, primary tumour of the bone. The recurrence rate after surgical treatment has been reported to be as high as 50%. Many surgical techniques have been employed in the treatment of this tumour. More aggressive interventions, such as en bloc resection and bulk allograft or prosthetic reconstruction, are generally understood to be associated with lower rates of local recurrence. However, because of lessened morbidity, intralesional techniques have come to be favoured for this condition. In addition to curettage, various adjuvant procedures and packing materials have been advocated in order to control and reconstruct long bone defects secondary to this neoplasm. We report our experience with 40 long bone GCT patients treated with curettage, burring, bone grafting and no adjuvants between 1997 and 2002. There was a local recurrence rate of 32.5%, with most recurrences noted within the first 30 months after surgery. Minor complications were found in 18% of patients. The risk of local recurrence in this study is acceptable (within the range that has been historically reported for curettage and bone grafting). In cases where more resources are available, the addition of adjuvant therapies, as noted in the recent literature, may be beneficial. The results of this study should be considered when designing multicenteric studies in the future.
doi:10.1007/s00264-006-0146-3
PMCID: PMC3172751  PMID: 16896875
10.  Giant cell tumor: Curettage and bone grafting 
Indian Journal of Orthopaedics  2007;41(2):121-123.
Background:
Curettage and wide resection are accepted methods of treatment of giant cell tumor (GCT) of bone. The success rate with curettage in different reports varies widely. There is a paucity in the literature regarding selection of cases for curettage. Present study is an analysis of outcome of 34 cases treated by curettage and bone grafting.
Materials and Methods:
Thirty-four cases of GCT of bone, 28 fresh and six with recurrence were treated by curettage and bone grafting. All cases of Campanancci grade 1, 2 and grade 3 which on computerized tomography scan showed break in the cortex confined to one surface and cortical break less than one third of circumference were treated by curettage and bone grafting.
Results:
4 (14%) of these lesions treated primarily by us showed recurrence after one and half year.
Conclusion:
Curettage and bone grafting is a reliable method in the treatment of GCT, provided guidelines regarding selection of cases and principles of tumor surgery are strictly adhered to.
doi:10.4103/0019-5413.32042
PMCID: PMC2989134  PMID: 21139763
Computerized tomography scan; curettage and bone grafting; wide resection
11.  Similar Local Control between Phenol- and Ethanol-treated Giant Cell Tumors of Bone 
Background
Giant cell tumors (GCTs) of bone often are treated with curettage, adjuvant therapy, and cementation. Phenol is a commonly used adjuvant associated with local control rates ranging from 9% to 25%. However, it is corrosive to the eyes, skin, and respiratory tract. Ethanol is readily available and does not cause chemical burns on contact, but it is unclear whether ethanol can achieve similar local control rates as phenol for treating GCTs.
Questions/purposes
We evaluated (1) the recurrence rate and recurrence-free Kaplan-Meier survival function, (2) Musculoskeletal Tumor Society (MSTS) functional score (1993 version), and (3) complications of two groups of patients with GCTs treated with extensive curettage, local adjuvant therapy with phenol or ethanol, and cement reconstruction, to determine if ethanol was a reasonable alternative to phenol.
Patients and Methods
We retrospectively reviewed all 26 patients with GCTs in the long bones of extremities treated with curettage, high-speed burring, phenolization, and cementation between May 1995 and November 2001, and 35 patients treated with the same protocol, except phenol was replaced with 95% ethanol, between November 2001 and November 2007. The recurrence rates, Kaplan-Meier recurrence-free survival curves, and MSTS functional scores of these two treatment groups were compared with Fisher’s exact test, Tarone-Ware test, and Mann-Whitney U test, respectively. The minimum followup was 36 months (mean, 58 months; range, 36–156 months).
Results
Local recurrence rates were similar in the two groups: 11% in the ethanol group and 12% in the phenol group. The survival curves (using local recurrence as an endpoint) of the two groups were similar. The mean MSTS functional score was 27.3 (91%) for the ethanol group and 26.9 (90%) for the phenol group.
Conclusions
Ethanol is a reasonable alternative to phenol when adjuvant therapy is considered in the treatment of GCTs of long bones.
Level of Evidence
Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-011-1962-3
PMCID: PMC3183197  PMID: 21732023
12.  Bisphosphonate treatment of aggressive primary, recurrent and metastatic Giant Cell Tumour of Bone 
BMC Cancer  2010;10:462.
Background
Giant cell tumour of bone (GCTB) is an expansile osteolytic tumour which contains numerous osteoclast-like giant cells. GCTB frequently recurs and can produce metastatic lesions in the lungs. Bisphosphonates are anti-resorptive drugs which act mainly on osteoclasts.
Method
In this study, we have examined clinical and radiological outcomes of treatment with aminobisphosphonates on 25 cases of aggressive primary, recurrent and metastatic GCTB derived from four European centres. We also analysed in vitro the inhibitory effect of zoledronic acid on osteoclasts isolated from GCTBs.
Results
Treatment protocols differed with several different aminobisphosphonates being employed, but stabilisation of disease was achieved in most of these cases which were refractory to conventional treatment. Most inoperable sacral/pelvic tumours did not increase in size and no further recurrence was seen in GCTBs that had repeatedly recurred in bone and soft tissues. Lung metastases did not increase in size or number following treatment. Zoledronic acid markedly inhibited lacunar resorption by GCTB-derived osteoclasts in vitro.
Conclusion
Our findings suggest that bisphosphonates may be useful in controlling disease progression in GCTB and that these agents directly inhibit GCTB - derived osteoclast resorption. These studies highlight the need for the establishment of standardised protocols to assess the efficacy of bisphosphonate treatment of GCTB.
doi:10.1186/1471-2407-10-462
PMCID: PMC2940802  PMID: 20799989
13.  Long-term outcome of giant cell tumor of bone involving sacroiliac joint treated with selective arterial embolization and curettage: a case report and literature review 
Background
Giant cell tumor of the sacrum, especially involving the sacroiliac joint, is rare, but is particularly challenging to treat. The long term outcome of a patient was studied with giant cell tumor involving the sacroiliac joint treated with selective arterial embolization and curretage.
Method
One patient with giant cell tumor involving the sacroiliac joint was treated with selective arterial embolization and curettage in our hospital in October 2002. The curettage and bone grafting was done after two times of selective arterial embolization;1600 ml of blood were transfused and no complications developed during the operation.
Results
At the final follow-up of 9 years after the operation, no local recurrence and metastasis developed and she retained normal activity in daily life.
Conclusion
We think it is an optimal treatment for giant cell tumor involving the sacroiliac joint, with repeated selective arterial embolization and curettage, which has the advantage of less injury, less blood loss and fewer complications.
doi:10.1186/1477-7819-11-72
PMCID: PMC3615942  PMID: 23497322
Giant cell tumor of bone; Sacrum; Pelvis; Selective arterial embolization; Curettage; Long term outcome
14.  Treatment of giant cell tumor of bone: Current concepts 
Indian Journal of Orthopaedics  2007;41(2):101-108.
Giant cell tumor (GCT) of bone though one of the commonest bone tumors encountered by an orthopedic surgeon continues to intrigue treating surgeons. Usually benign, they are locally aggressive and may occasionally undergo malignant transformation. The surgeon needs to strike a balance during treatment between reducing the incidence of local recurrence while preserving maximal function.
Differing opinions pertaining to the use of adjuvants for extension of curettage, the relative role of bone graft or cement to pack the defect and the management of recurrent lesions are some of the issues that offer topics for eternal debate.
Current literature suggests that intralesional curettage strikes the best balance between controlling disease and preserving optimum function in the majority of the cases though there may be occasions where the extent of the disease mandates resection to ensure adequate disease clearance.
An accompanying treatment algorithm helps outline the management strategy in GCT.
doi:10.4103/0019-5413.32039
PMCID: PMC2989131  PMID: 21139760
Curettage; giant cell tumor; treatment
15.  Argon Beam Coagulation as Adjuvant Treatment after Curettage of Aneurysmal Bone Cysts: A Preliminary Study 
The optimal treatment of aneurysmal bone cysts remains an area of debate. Curettage, with or without adjuvant therapy, has been advocated for tumors in most locations. To evaluate argon beam coagulation as adjuvant therapy to curettage, we retrospectively analyzed the complication and recurrence rates in 40 consecutive patients with a diagnosis of aneurysmal bone cyst. For our analysis of recurrence, we excluded six of the 40 patients who were lost to followup or had less than 18 months followup; five patients treated with resection also were excluded. Of the remaining 29 patients, 17 were treated with curettage and argon beam coagulation and 12 were treated with curettage with or without phenol. None of the 17 patients treated with curettage and argon beam coagulation had a recurrence, whereas four patients treated without argon beam coagulation had recurrences. There were no differences between patients treated with or without argon beam coagulation regarding frequencies of intraoperative complications, neurovascular injury, or bone graft incorporation. Argon beam coagulation seems to offer favorable control rates when compared with curettage with or without phenol. No complications have been experienced thus far with its use.
Level of Evidence: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-009-0914-7
PMCID: PMC2795835  PMID: 19495896
16.  Local recurrences after curettage and cementing in long bone giant cell tumor 
Indian Journal of Orthopaedics  2011;45(2):168-173.
Background
Giant cell tumor of bone (GCT) is a benign lesion with great propensity for local recurrence. This study aimed to analyse the rates of local recurrence and its possible predisposing factors in Campanacci’s Grade III and II GCT of long bones following intralesional curettage and bone cementing.
Materials and Methods:
32 cases of either sex with Campanacci’s Grade II (n= 14), and Grade III (n=18) with intact articular surface, operated between 1995 and 2007 in form of intralesional curettage and bone cementing were studied. All the cases were followed up for 2.5-12 years (mean, 6.5), after primary treatment. The mean age at operation was 32.4 years (range, 18.5-40 years). The proximal tibia was involved in 13 cases (40.6%), followed by distal femur (n=11)34.4% distal tibia (n=3) 9.4%, proximal femur (n=2) 3.2% and distal radius (n=3) 9.4%.
Results:
Eleven patients (34.4%) had local recurrence, of which eight were of Campanacci’s Grade III. The mean recurrence time was 14 months (range, 3-34 months). The two-year recurrence-free survivorship was 71.9% (n=23/32). Post-recurrence mean follow-up was 4.2 years (range, 2-6.5 years).
Conclusion:
We observed higher rate of local recurrence with Campanacci’s Grade III GCTs. We recommend selective use of this procedure in Grade III lesions, particularly with extensive soft tissue involvement.
doi:10.4103/0019-5413.77138
PMCID: PMC3051125  PMID: 21430873
Bone cementing; GCT; recurrence
17.  Giant-cell tumors of bone: an analysis of 87 cases 
International Orthopaedics  2004;28(4):239-243.
We reviewed 87 patients with giant-cell tumor treated between 1992 and 2001. The mean follow-up was 62 (28–138) months. Fifty-six lesions were treated with intralesional curettage with adjunctive phenol treatment and reconstructed with autograft and allograft. Thirty-one lesions were treated with wide resection and reconstructed with prosthesis, osteochondral allograft, or alloprosthetic composite. Overall recurrence was 12%. Recurrence rate after curettage was 18% and 3% after wide excision. Complication rate after wide excision was higher than that after curettage. Functional outcome was evaluated using the Enneking scoring system. Average rating was 86% for the lower extremity and 83% for the upper extremity. The overall satisfactory rate was 88%.
doi:10.1007/s00264-004-0564-z
PMCID: PMC3456930  PMID: 15160253
18.  Phenol levels during intralesional curettage and local adjuvant treatment of benign and low-grade malignant bone tumours 
Background
Phenol is widely used for years as local adjuvant treatment for bone tumours. Despite its use for a long time, no information is available about the local concentration of phenol that is achieved in an individual patient, and the most sufficient and safe procedure to wash out the phenol after using it as local adjuvant.
Questions/purposes
1. What is the initial local concentration of phenol in the tissue of the cavity wall after the application of phenol? 2. How quickly is phenol 85% diluted by washing the bone cavity with ethanol 96% solution? 3. Is the degree and speed of dilution influenced by the size of the cavity? 4. How many times should the cavity be rinsed to obtain sufficient elimination of phenol?
Methods
A basic science study was performed at respectively 16 and 10 patients, treated by intralesional curettage and adjuvant therapy for low-grade central chondrosarcoma of bone. Test 1:in 16 patients ten samples were collected of the mixture of phenol and ethanol from the bone cavity. Test 2:in ten patients, two biopsy samples were taken from the cavity wall in the bone during surgery.
Results
Phenol concentrations had wide variety in different patients, but all decreased by rinsing with ethanol.
Conclusions
Ethanol 96% is effective to wash out local applicated phenol, by rinsing the bone cavity six times. The local concentration of phenol diminishes to an acceptable concentration of 0.2%. This study provides new insights to safely further improve the surgical technique of intralesional treatment of bone tumours.
doi:10.1186/2045-3329-2-10
PMCID: PMC3351749  PMID: 22588078
19.  Clinical outcomes of giant cell tumor of bone treated with bone cement filling and internal fixation, and oral bisphosphonates 
Oncology Letters  2012;5(2):447-451.
Giant cell tumor (GCT) of the bone is a relatively common primary bone tumor. Treatment with simple curettage often results in a high local recurrence rate. Tumor resection and reconstruction with prosthesis or an allograft has a low rate of local recurrence; however, the patient’s native joint function becomes significantly impaired. With the development and usage of aggressive curettage, it is a priority to treat GCT with a method that reduces the local recurrence rate and preserves the native joint. To evaluate the feasibility of treating GCT with aggressive curettage and cement filling using internal fixation and oral bisphosphonates, 16 patients with GCT of the bone located in the distal femur and treated in our department from January 2008 to June 2011, were followed up. The patients had received aggressive curettage, bone cement filling, internal fixation and oral administration of bisphosphonates.There were seven males and nine females in total, with a mean age of 38 years. All patients were carefully assessed prior to surgery in order to determine the integrity of the tumor cavity. Subsequently, patients were treated with aggressive curettage by high-speed burring and cementation with internal fixation, and were administered postoperative oral alendronate sodium tablets (10 mg/day) for two years. The median follow-up time was 25 months. None of the patients were lost to follow-up. No local recurrence or metastasis was observed in the last follow-up. The Enneking limb function score range of the affected limb was 24–29 (average, 26.7). At the last follow-up, all patients exhibited solid fixation without fracture of the subchondral bone in plain radiographs. Based on these data, we suggest that patients with distal femoral GCT may be treated with aggressive curettage and cement filling, with internal fixation and oral bisphosphonates. The advantages of this method are its safety and efficacy. However, the long-term outcomes require further investigation.
doi:10.3892/ol.2012.1036
PMCID: PMC3573151  PMID: 23420680
giant cell tumor; cement filling; internal fixation; bisphosphonate
20.  Cytotoxic effect and tissue penetration of phenol for adjuvant treatment of giant cell tumours 
Oncology Letters  2013;5(5):1595-1598.
Local adjuvant treatment of giant cell tumours (GCTs) of the bone with phenol has led to a significant reduction in recurrence rates. In the current study, the optimal phenol concentration and duration of intralesional exposure were evaluated. Specimens of GCTs were exposed to various concentrations of phenol solution (6, 60 and 80%) for either 1 or 3 min. Following embedding in glutaraldehyde, the tumour cell layers were examined by transmission electron microscopy. Destroyed cell organelles indicated the penetration depth as a sign of denaturation. Incubation of GCT specimens with 6% phenol solution for 3 min resulted in the most tissue damage and the deepest tissue penetration of ∼200 μm. Incubation with 60 and 80% phenol solution reached a penetration depth of only ∼100 μm. Phenol instillation may be used for the treatment of small scattered cellular debris following intralesional curettage; however, it is not suitable for treatment of remaining solid tumour tissue of GCT. The use of high phenol concentrations has no benefit and increases the risk of local or systemic intoxication.
doi:10.3892/ol.2013.1244
PMCID: PMC3678778  PMID: 23760940
phenol; tissue penetration; giant cell tumour; GCT; cytotoxic; denaturation
21.  High-Speed Burring with and without the Use of Surgical Adjuvants in the Intralesional Management of Giant Cell Tumor of Bone: A Systematic Review and Meta-Analysis 
Sarcoma  2010;2010:586090.
Local control rates for Giant Cell Tumor of Bone (GCT) have been reported in a large number of retrospective series. However, there remains a lack of consensus with respect to the need for a surgical adjuvant when intralesional curettage is performed. We have systematically reviewed the literature and identified six studies in which two groups from the same patient cohort were treated with intralesional curettage and high-speed burring with or without a chemical or thermal adjuvant. Studies were evaluated for quality and pooled data was analyzed using the fixed effects model. Data from 387 patients did not indicate improved local control with the use of surgical adjuvants. Given the available data, we conclude that surgical adjuvants are not required when meticulous tumor removal is performed.
doi:10.1155/2010/586090
PMCID: PMC2913811  PMID: 20706639
22.  Solid variant of aneurysmal bone cyst in the tibia treated with simple curettage without bone graft: a case report 
The solid variant of aneurysmal bone cyst (solid ABC) is rarely encountered in long bones and appropriate treatment for this disease remains unclear. We experienced a 13-year-old boy suffering from pain in his left knee caused by solid ABC. Simple curettage of the bone lesion without any adjuvant therapy and a bone graft gave immediate pain relief. Histological examination of the surgical specimen showed typical features of solid ABC, and cycloxygenase-2 (COX-2) expression was confirmed in giant cells with a background of spindle cells by immunohistochemistry. Magnetic resonance imaging showed that soft tissue edema surrounding the lesion was improved two months after surgery and there was no indication of recurrence two years after surgery.
If COX-2 secreted from the tumor induces soft tissue edema, simple curettage of the bone lesion seems to be a reasonable treatment for solid ABC and is able to minimize invasive treatment of the patients.
doi:10.1186/1477-7819-10-45
PMCID: PMC3296629  PMID: 22348469
aneurismal bone cysts; curettage; cyclooxygenase 2
23.  A Systematic Review and Meta-Analysis of En-Bloc vs Intralesional Resection for Giant Cell Tumor of Bone of the Distal Radius 
Introduction:
Surgical management of Giant Cell Tumor of Bone of the distal radius (GCTDR) remains controversial due to risk of local recurrence (LR) offset by functional limitations which result from en-bloc resection. This study aims to determine the oncologic and functional outcomes of wide excision (WE) vs intralesional curettage (IC) of GCTDR.
Methods:
A complete search of the applicable literature was done. Included studies reported on patients from the same cohort who were surgically treated for GCTDR with WE or IC. Two reviewers independently assessed all papers. The primary outcome measure was LR.
Results:
One-hundred-forty-one patients from six studies were included: 60 treated with WE, and 81 with IC. Five WE patients (8%) suffered LR whereas 25 IC patients (31%) did. The odds of LR were three times less in the WE group vs the IC group. MSTS1993 scores, where available, were on average 'good' with WE and 'excellent' with IC.
Conclusions:
Within statistical limitations the data support an attempt, where feasible, at wrist joint preservation and superior function with IC. Intralesional curettage is reasonable when the functional benefit outweighs the risk of recurrence as is the case in many cases of GCT of the distal radius.
doi:10.2174/1874325001307010103
PMCID: PMC3664443  PMID: 23730371
Curettage; excision; giant cell tumor; meta-analysis; radius; surgery.
24.  Giant Cell Tumor of Bone: A Neoplasm or a Reactive Condition? 
Giant cell tumor of bone (GCTB) is a benign but locally aggressive bone tumor of young adults. It typically presents as a large lytic mass at the end of the epiphysis of long bones. Grossly it is comprised of cystic and hemorrhagic areas with little or no periosteal reaction. Microscopically areas of frank hemorrhage, numerous multinucleated giant cells and spindly stromal cells are present. Telomeric fusions, increased telomerase activity and karyotypic aberrations have been advanced as a proof of its neoplastic nature. However such findings are not universal and can be seen in rapidly proliferating normal cells as well as in several osseous lesions of developmental and/or reactive nature, and the true neoplastic nature of GCTB remains controversial. The ancillary studies have generally not reached to the point where these alone can be taken as sole diagnostic and discriminatory criteria. While giant cells and stromal cells have been extensively studied, little attention has been paid to the overwhelming hemorrhagic component. If examined carefully intact and partially degenerated red blood cells are almost invariably seen in many giant cells as well as in the stroma. While hemorrhage in many patients may be resolved without leaving any trace over time, in some it gives rise to giant cell formation, and in others it may lead to proliferation of fibroblasts and histiocytes. At times one sees xanthomatous cells due to intracytoplasmic cholesterol deposits and sharp cholesterol clefts. Individual genetic makeup, local tissue factors as well as the amount of hemorrhage may play a key role in the final effects and outcome. Malignancy usually does not occur in GCTB and when discover, it usually represents primary bone sarcomas missed at original diagnosis. Embolization therapy to curtail hemorrhage and insertion of cement substance to support matrix are helpful in reducing recurrences. Aneurysmal bone cyst (ABC) shares many features with GCTB. There had been unique karyotypic changes in some aneurysmal bone cysts making it distinct from GCTB. However these changes may be in the endothelial cells which are quite different from stromal or giant cells. It had been concluded that the poor matrix support to the vessels may lead to frequent and profuse intraosseous hemorrhage attracting blood-derived monocytes with active conversion into osteoclasts, resulting in GCTB formation. On the other hand, dilatation of the thin-walled blood vessels results in formation of ABCs. If hemorrhagic foci are replaced by proliferation of fibroblasts and histiocytes, then a picture of fibrous histiocytic lesion is emerged. Enhanced telomerase activity and karyotypic aberrations may be necessary for rapid division of the nuclei of the giant cells in order to be able to deal with significant in situ intraosseous hemorrhage.
PMCID: PMC2480584  PMID: 18787633
Giant cell tumor; bone; osteoclastoma; aneurysmal bone cyst; osteoclast; hemorrhage; bone matrix; telomerase
25.  Denosumab Chemotherapy for Recurrent Giant-Cell Tumor of Bone: A Case Report of Neoadjuvant Use Enabling Complete Surgical Resection 
Giant-cell tumor of the bone (GCTB) is a rare neoplasm that affects young adults. The tumor is generally benign but sometimes can be locally aggressive. There are no standardized approaches to the treatment of GCTB. Recently, the RANKL inhibitor denosumab has shown activity in this tumor type. We present the case of a young female who presented with locally advanced disease and was successfully managed with the neoadjuvant use of denosumab allowing for surgical resection of the tumor that was previously deemed unresectable. Following surgery, the patient is being managed with continued use of denosumab as ‘maintenance,' and she continues to be free of disease. Our case highlights a novel approach for the management of locally advanced and aggressive giant cell tumor of the bone.
doi:10.1155/2013/496351
PMCID: PMC3745896  PMID: 23984138

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