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      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

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          Abstract

          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.

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          Most cited references30

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          Giant-cell tumor of bone.

          Of 327 patients who had a giant-cell tumor of bone and were seen at the Istituto Rizzoli, 293 were treated at the Institute, and 280 of these were followed for two to forty-four years. The distribution according to sex and age of the patient and site of the tumor was similar to the distributions in major reports of large series. The tumor usually involved the metaphysis and the epiphysis, but was occasionally limited to the metaphysis, and in only 2 per cent of the patients was it adjacent to an open growth plate. The tumor on occasion invaded the articular space, also involving the ligaments and the synovial membrane. Extension to an adjacent bone through the joint occurred in 5 per cent of the tumors. Our radiographic grading, which is roughly comparable with the staging system of Enneking et al., was Grade I in 4 per cent, II in 74 per cent, and III in 22 per cent of 266 patients before treatment. A pathological fracture was apparent on the first radiograph in 9 per cent of the patients. In the 280 patients with adequate follow-up, 331 surgical procedures were performed. The rate of local recurrence was 27 per cent in the 151 intralesional procedures, 8 per cent in the 122 marginal excisions, and zero in the fifty-eight wide or radical procedures. These results did not correlate with the radiographic grade of the lesion. Of the fifty-one local recurrences that were seen after treatment at our institution, 90 per cent appeared in the first three years after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)
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            Giant cell tumor of bone: treatment and outcome of 214 cases.

            Two hundred and fourteen patients with benign giant cell tumor of bone (GCTB), treated from 1980 to 2007 at the Department of Orthopedics of the University of Muenster (Germany), were analyzed in a retrospective study. The mean age was 33.3 years with a female-to-male ratio of 1.2 : 1. The mean follow up was 59.8 months. The recurrence rate of patients who received first treatment at our institution was 16.6%. The most common primary treatment was curettage (188 patients) usually followed by adjuvant local therapy. The effects of bone cement (PMMA), burring and hydrogen peroxide (H(2)O(2)) were statistically analyzed and the influence of a subchondral bone graft on the recurrence rate was evaluated. PMMA alone (n = 52) reduces the likelihood of recurrence by the factor 8.2, additional high-speed burring (n = 39) by the factor 3.9 (compared to PMMA only). H(2)O(2) (n = 42) seems to have an additional effect comparable to that of phenol although it did not reach statistical significance. The combination of all adjuncts (PMMA, burring, H(2)O(2) - n = 42) reduces the likelihood of recurrence by the factor 28.2 compared to curettage only and therefore should be recommended as a standard treatment. If the tumor reaches close to the articulating surface a subchondral bone graft (n = 42) can be performed without risking a higher recurrence rate. We add seven cases of pulmonary metastases and two cases of multicentricity to the literature. Bisphosphonates and interferon alpha may have a beneficial effect.
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              Giant cell tumor of bone: risk factors for recurrence.

              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. 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. 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). 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. 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 III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
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                Author and article information

                Contributors
                Journal
                World J Surg Oncol
                World J Surg Oncol
                World Journal of Surgical Oncology
                BioMed Central
                1477-7819
                2013
                16 July 2013
                : 11
                : 156
                Affiliations
                [1 ]Department of Musculoskeletal Oncology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
                Article
                1477-7819-11-156
                10.1186/1477-7819-11-156
                3717274
                23866921
                7eac1e4b-89be-4787-a2d3-f3f891ebd862
                Copyright ©2013 Zuo et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 December 2012
                : 30 June 2013
                Categories
                Research

                Surgery
                giant cell tumors,recurrence,polymethyl methacrylate,cementation,bone grafting
                Surgery
                giant cell tumors, recurrence, polymethyl methacrylate, cementation, bone grafting

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