Three-dimensional-printed porous implant combined with autograft reconstruction for giant cell tumor in proximal tibia.

BACKGROUND: This study is to describe the design and surgical techniques of three- dimensional-printed porous implants for proximal giant cell tumors of bone and evaluate the short-term clinical outcomes. METHODS: From December 2016 to April 2020, 8 patients with giant cell tumor of bone in the proximal tibia underwent intralesional curettage of the tumor and reconstruction with bone grafting and three-dimensional-printed porous implant. Detailed anatomy data were measured, including the size of lesion and thickness of the subchondral bone. Prostheses were custom-made for each patient by our team. All patients were evaluated regularly and short-term clinical outcomes were recorded. RESULTS: The mean follow-up period was 26 months. According to the different defect sizes, the mean size of the plate and mean length of strut were 35 × 35 mm and 20 mm, respectively. The mean affected subchondral bone percentage was 31.5%. The average preoperative and postoperative thickness of the subchondral bone was 2.1 mm and 11.1 mm, respectively. There was no wound infection, skin necrosis, peroneal nerve injury, or other surgical related complications. No degeneration of the knee joint was found. Osseointegration was observed in all patients. The MSTS improved from an average of 12 preoperatively to 28 postoperatively. CONCLUSION: The application of three-dimensional-printed printed porous prosthesis combined autograft could supply enough mechanical support and enhance bone ingrowth. The design and operation management lead to satisfactory subchondral bone reconstruction.

Does a Modified Technique to Achieve Arthrodesis of the Wrist After Resection of the Distal Radius and Translocating the Ipsilateral Ulna as a Vascularized Graft to Reconstruct the Defect Improve Grip Strength and Outcomes Scores?

BACKGROUND: Ten years ago, we reported the results of a procedure in which we translocated the ipsilateral ulna as a vascularized autograft to reconstruct defects of the distal radius after tumor resection, with excellent functional results. At that time, wrist arthrodesis was achieved by aligning the translocated ulna with the scapholunate area of the carpus and usually the third metacarpal. This resulted in wrist narrowing. We then wondered if aligning the translocated ulna with the scaphoid and the second metacarpal would result in ulnar deviation and thereby improve grip strength. We believed lateralization would reduce the wrist narrowing that occurs with fusion to the third metacarpal and would make the cosmesis more acceptable. We also modified the incision to dororadial to make the scar less visible and thus improve the cosmesis. QUESTIONS/PURPOSES: (1) Is there an objective improvement in grip strength and functional scores (Musculoskeletal Tumor Society [MSTS] and Mayo wrist) when the translocated ulna is lateralized and the wrist is fused with the translocated ulna and aligned with the second metacarpal versus when the translocated ulna is aligned with the third metacarpal? (2) Did lateralization caused by the wrist fusion aligned with the second metacarpal minimize wrist narrowing as measured by the circumference compared with the fusion aligned with the third metacarpal? METHODS: From 2010 and 2018, we treated 40 patients with distal radius tumors at our institution, 30 of whom had a distal radius enbloc resection. Twenty-eight patients had an ipsilateral ulna translocation and wrist arthrodesis in which the radius and translocated ulna were aligned with either the second (n = 15) or the third (n = 13) metacarpals. Two patients in the second metacarpal group and three patients in the third metacarpal group were lost to follow-up before 24 months after surgery and were excluded. A retrospective analysis of 23 patients (20 with giant cell tumors and three with malignant bone tumors) included a review of radiographs and institutional tumor database for surgical and follow-up records to study oncologic (local disease recurrence), reconstruction (union of osteotomy junctions, implant breakage or graft fracture, and wrist circumference), and functional outcomes (MSTS and Mayo wrist scores and objective grip strength assessment compared with the contralateral side). The results were compared for each study group (second metacarpal versus third metacarpal). There was no difference in the incidence of local recurrence or the time to union between the two groups. There were no implant breakages or graft fractures noted in either group. RESULTS: Patients in the second metacarpal group lost less grip strength compared with the unoperated side in the third metacarpal group (median 12% [range -30% to 35%] versus median 28% [15% to 42%], difference of medians 16%; p = 0.006). There were no between-group differences in terms of MSTS (median 30 [24 to 30] versus median 26.5 [22 to 30], difference of medians 3.5; p = 0.21) or Mayo wrist scores (median 83 [65 to 100] versus median 72 [50 to 90], difference of medians 11; p = 0.10). The second metacarpal group also had less wrist narrowing as seen from the median difference in circumference between the operated and unoperated wrists (median narrowing 10 mm [3 to 35 mm] in the second metacarpal group versus median 30 mm [15 to 35 mm] in the third metacarpal group, difference of medians 20 mm; p = 0.04). CONCLUSION: Wrist arthrodesis after ulna translocation with alignment of the translocated ulna and the second metacarpal provides a functional position with ulnar deviation that offers some improvement in grip strength but no improvement in the MSTS or Mayo scores. Radialization/lateralization of the translocated ulna achieved from the alignment with the second metacarpal decreases the reduction in the wrist circumference and therefore reduces wrist narrowing. LEVEL OF EVIDENCE: Level III, therapeutic study.

Globally altered epigenetic landscape and delayed osteogenic differentiation in H3.3-G34W-mutant giant cell tumor of bone.

The neoplastic stromal cells of giant cell tumor of bone (GCTB) carry a mutation in H3F3A, leading to a mutant histone variant, H3.3-G34W, as a sole recurrent genetic alteration. We show that in patient-derived stromal cells H3.3-G34W is incorporated into the chromatin and associates with massive epigenetic alterations on the DNA methylation, chromatin accessibility and histone modification level, that can be partially recapitulated in an orthogonal cell line system by the introduction of H3.3-G34W. These epigenetic alterations affect mainly heterochromatic and bivalent regions and provide possible explanations for the genomic instability, as well as the osteolytic phenotype of GCTB. The mutation occurs in differentiating mesenchymal stem cells and associates with an impaired osteogenic differentiation. We propose that the observed epigenetic alterations reflect distinct differentiation stages of H3.3 WT and H3.3 MUT stromal cells and add to H3.3-G34W-associated changes.

The functional outcomes and complications of different reconstruction methods for Giant cell tumor of the distal radius: comparison of Osteoarticular allograft and three-dimensional-printed prosthesis.

BACKGROUND: En bloc excision has been increasingly used for the management of giant cell tumors (GCTs) in the distal radius. An osteoarticular allograft has been used extensively for decades, and custom-made prosthesis reconstruction has been more recently applied. We aimed to compare the clinical outcomes of the two procedures. METHODS: We retrospectively analyzed 30 patients with Campanacci III or recurrent GCTs of the distal radius for follow-up at a mean of 33.2 months. In total, 15 underwent osteoarticular allograft reconstruction (allograft group) and 15 received cementless three-dimensional (3D)-printed prosthesis reconstruction (prosthesis group) between March 18, 2013, and May 20, 2018. All patients underwent by clinical and radiological examinations, including pre- and postoperative active range of motion (ROM) of the wrist, VAS score, grip strength, degenerative change of wrist, Mayo wrist score and Musculoskeletal Tumor Society (MSTS) score. Complications were evaluated using the Henderson classification. RESULTS: Both groups showed significantly increased ROM, grip strength, Mayo score and MSTS score postoperatively. Furthermore, the extension, flexion, MSTS, and Mayo score were significantly higher in the prosthesis group. There was no significant difference in grip strength and VAS between the groups. In allograft group, one patient had a late infection one had resorption of allograft without allograft bone fracture. and four had wrist subluxation. All patients had degenerative changes (mean 9 months). In the prosthesis group, three patients developed wrist subluxation, three had separation of the distal radioulnar joint, and none of the patients developed wrist degeneration. CONCLUSIONS: Our study compared the objective functional outcomes and complications of two reconstructive methods for Campanacci III or recurrent GCT in the distal radius. 3D-printed prosthesis replacement can partially preserve wrist function better than allograft reconstruction in the short-term. During the design of 3D-printed prosthesis, preoperative morphological assessment of the affected proximal row carpal is helpful to control postoperative dislocation. After allograft reconstruction, wrist degeneration, which has been demonstrated in all patients, severely influence their wrist function. Therefore, compared to allograft reconstruction, 3D-printed prosthesis reconstruction has irreplaceable advantages at early-stage application, especially in wrist function, however, further studied with a larger number of cases and longer follow-up.

Stromal Cell-Derived CCL20 Promotes Tumor Progression and Osteolysis in Giant Cell Tumor of Bone.

BACKGROUND/AIMS: Giant cell tumor of bone (GCTB), one of the most common primary bone tumors, leads to extensive bone destruction. However, the mechanisms underlying GCTB progression remain elusive and prognostic factors and treatment targets are required. In the current study, we explored the function of the chemokine family member CCL20 in GCTB progression. METHODS: We explored the expression of CCL20 in stromal cells (GCTSCs) using microarray. Clinical analyses of the role of CCL20 in tumor progression were performed based on the patient cohort of our institution. The role of CCL20 in tumor proliferation was evaluated by MTS assay, migration ability was measured by a Transwell assay, and osteoclastogenesis was induced by CCL20 or GCTSC-conditioned medium. Quantitative PCR and western blot were used to measure the expression levels of mRNAs and proteins related to tumor progression. RESULTS: CCL20 was upregulated in GCTSCs and correlated with tumor progression and prognosis. CCL20 induced GCTSC proliferation and migration in an autocrine manner. In addition, CCL20 recruited mononuclear cells and induced osteoclastogenesis by overactivating the AKT and NF-κB signaling pathways. Antibody blockade of CCL20 abolished the exacerbated osteoclastogenesis. CONCLUSION: Taken together, our data indicate that GCTSC secretion of CCL20 acts as a key modulator in the pathological progression of GCTB. It can promote GCTSC proliferation and migration in an autocrine manner and can recruit bone marrow monocytes to the tumor microenvironment and enhance osteoclastogenesis in a paracrine manner. These findings strongly indicate the potential prognostic and therapeutic value of CCL20 in GCTB.

Reliability and Validity of the Musculoskeletal Tumor Society Scoring System for the Upper Extremity in Japanese Patients.

BACKGROUND: The Musculoskeletal Tumor Society (MSTS) scoring system developed in 1993 is a widely used disease-specific evaluation tool for assessment of physical function in patients with musculoskeletal tumors; however, only a few studies have confirmed its reliability and validity. QUESTIONS/PURPOSES: The aim of this study was to validate the MSTS scoring system for the upper extremity (MSTS-UE) in Japanese patients with musculoskeletal tumors for use by others in research. Does the MSTS-UE have: (1) sufficient reliability and internal consistency; (2) adequate construct validity; and (3) reasonable criterion validity in comparison to the Toronto Extremity Salvage Score (TESS) or SF-36? METHODS: Reliability was performed using test-retest analysis, and internal consistency was evaluated with Cronbach's alpha coefficient. Construct validity was evaluated using a scree plot to confirm the construct number and the Akaike information criterion network. Criterion validity was evaluated by comparing the MSTS-UE with the TESS and SF-36. RESULTS: The test-retest reliability with intraclass correlation coefficient (0.95; 95% CI, 0.91-0.97) was excellent, and internal consistency with Cronbach's α (0.7; 95% CI, 0.53-0.81) was acceptable. There were no ceiling and floor effects. The Akaike Information Criterion network showed that lifting ability, pain, and dexterity played central roles among the components. The MSTS-UE showed substantial correlation with the TESS scoring scale (r = 0.75; p < 0.001) and fair correlation with the SF-36 physical component summary (r = 0.37; p = 0.007). Although the MSTS-UE showed slight correlation with the SF-36 mental component summary, the emotional acceptance component of the MSTS-UE showed fair correlation (r = 0.29; p = 0.039). CONCLUSIONS: We can conclude that the MSTS is not an adequate measure of general health-related quality of life; however, this system was designed mainly to be a simple measure of function in a single extremity. To evaluate the mental state of patients with musculoskeletal tumors in the upper extremity, further study is needed.

Sarcoma survivors' perspectives on their body image and functional quality of life post-resection/limb salvage surgery.

Sarcomas often occur in patients' extremities and treatment typically involves bone resection/limb salvage surgery. Such treatments leave survivors with physical disfigurements, functional disabilities, and/or emotional traumas. Our post-surgery psychological intervention investigated how these experiences impinge on sarcoma survivors' lives. Twenty-three survivors aged 19-60 years (M = 36 years) participated in a tri-disciplinary (rehabilitative exercise, plastic surgery and psychological) intervention. Of these, 17 participated in psychodynamic counselling, 10 completed a mental-health questionnaire and seven kept a reflective journal. An exemplar case study research design was employed and data were subjected to interpretative phenomenological analysis. The findings reveal that survivors typically experience a number of body image issues and mobility difficulties, which they are reluctant to share with their oncologist in case they are viewed as being ungrateful or vain. In instances where such issues remain unaddressed, then sarcoma survivors have a tendency to adopt avoidant coping strategies and social isolation practices. These practices negatively impact on their mental health and functional quality of life. Hence, it is suggested that a short three part (body image, mobility, and coping strategy) screen be devised and used at all sarcoma 2-year follow-up assessment consults to identify which survivors are in need of psychological assistance.

Cellular cannibalism in giant cells of central giant cell granuloma of jaw bones and giant cell tumors of long bones.

AIM: The aim of the present study was to investigate the relationship of central giant cell granuloma (CGCG) and giant cell tumor of long bones (GCT) with respect to cannibalistic giant cells (GCs). METHOD: Sixteen cases each of CGCG and GCT were histopathologically analyzed for cannibalistic GCs. One hundred GCs were examined in each section, and the number of cannibalistic GCs was expressed in percentage. RESULTS: Cannibalistic GCs were seen in all cases of CGCG and GCT (100%). GCT showed significantly higher mean cannibalistic GC frequency (44.81 ± 1.013) than CGCG (32.06 ± 1.398), aggressive CGCG (38.17 ± 1.579), non-aggressive CGCG (28.40 ± 0.6360), non-recurrent CGCG (30.42 ± 1.417), and recurrent CGCG (37.00 ± 2.483). In aggressive CGCG, the mean cannibalistic GC frequency was significantly higher (38.17 ± 1.579) than the non-aggressive variant (28.40 ± 0.6360). Recurrent CGCG cases showed significantly higher mean cannibalistic GC frequency (37.00 ± 2.483) than non-recurrent cases (30.42 ± 1.417). Similarly, recurrent GCT showed significantly higher mean cannibalistic GC frequency (47.4 ± 4.97) than non-recurrent GCT (43.63 ± 3.1). CONCLUSION: The distinctness of CGCG and GCT was observed in terms of mean cannibalistic GC count. The assessment of cannibalistic GC in CGCG and GCT could help in predicting the biological behavior and grading of the tumor.

Does Wrist Arthrodesis With Structural Iliac Crest Bone Graft After Wide Resection of Distal Radius Giant Cell Tumor Result in Satisfactory Function and Local Control?

BACKGROUND: Many techniques have been described for reconstruction after distal radius resection for giant cell tumor with none being clearly superior. The favored technique at our institution is total wrist fusion with autogenous nonvascularized structural iliac crest bone graft because it is structurally robust, avoids the complications associated with obtaining autologous fibula graft, and is useful in areas where bone banks are not available. However, the success of arthrodesis and the functional outcomes with this approach, to our knowledge, have only been limitedly reported. QUESTIONS/PURPOSES: (1) What is the success of union of these grafts and how long does it take? (2) How effective is the technique in achieving tumor control? (3) What complications occur with this type of arthrodesis? (4) What are the functional results of wrist arthrodesis by this technique for treating giant cell tumor of the distal radius? METHODS: Between 2005 and 2013, 48 patients were treated for biopsy-confirmed Campanacci Grade III giant cell tumor of the distal radius. Of those, 39 (81% [39 of 48]) were treated with wrist arthrodesis using autogenous nonvascularized iliac crest bone graft. Of those, 27 (69% [27 of 39]) were available for followup at a minimum of 24 months (mean, 45 months; range, 24-103 months). During that period, the general indications for this approach were Campanacci Grade III and estimated resection length of 8 cm or less. Followup included clinical and radiographic assessment and functional assessment using the Disabilities of the Arm, Shoulder and Hand (DASH) score, the Musculoskeletal Tumor Society (MSTS) score, grip strength, and range of motion at every followup by the treating surgeon and his team. All functional results were from the latest followup of each patient. RESULTS: Union of the distal junction occurred at a mean of 4 months (± 2 months) and union of the proximal junction occurred at a mean of 9 months (± 5 months). Accounting for competing events, at 12 months, the rate of proximal junction union was 56% (95% confidence interval [CI], 35%-72%), whereas it was 67% (95% CI, 45%-82%) at 18 months. In total, 11 of the 27 patients (41%) underwent repeat surgery on the distal radius, including eight patients (30%) who had complications and three (11%) who had local recurrence. The mean DASH score was 9 (± 7) (value range, 0-100, with lower scores representing better function), and the mean MSTS 1987 score was 29 (± 1) (value range, 0-30, with higher scores representing better function) as well as 96% (± 4%) of mean MSTS 1993 score (value range, 0%-100%, with higher scores representing better function). The mean grip strength was 51% (± 23%) of the uninvolved side, whereas the mean arc of forearm rotation was 113° (± 49°). CONCLUSIONS: Reconstruction of defects after resection of giant cell tumor of the distal radius with autogenous structural iliac crest bone graft is a facile technique that can be used to achieve favorable functional results with complications and recurrences comparable to those of other reported techniques. We cannot show that this technique is superior to other options, but it seems to be a reasonable option to consider when other reconstruction options such as allografts are not available. LEVEL OF EVIDENCE: Level IV, therapeutic study.

[Denosumab may be a supplement to the surgical treatment of giant cell tumours of bone].

Giant cell tumour of bone (GCTB) is an aggressive bone tumour causing bone destruction. GCTB requires surgical treatment, and severe cases have a high risk of functional morbidity. GCTB consists of receptor activator of nuclear factor kappa-B (RANK)-positive osteoclast-like giant cells. The formation and activity of these cells are mediated by the interaction with RANK ligand (RANKL) released from neoplastic stromal cells. Denosumab is a human monoclonal antibody which inhibits RANKL and impairs the growth of the GCTB. Several studies have described the ability of denosumab to downgrade the extent of surgical treatment and improve the functional outcome.

What are the Functional Results, Complications, and Outcomes of Using a Custom Unipolar Wrist Hemiarthroplasty for Treatment of Grade III Giant Cell Tumors of the Distal Radius?

PURPOSE: A giant cell tumor (GCT) of bone presenting in the distal radius is rare, however, when they occur, Campanacci Grade III tumors can present formidable reconstructive challenges. They are associated with a high local recurrence rate with intralesional treatment, therefore approaches to reconstruct the wrist after en bloc resection warrant study. QUESTIONS: We asked: (1) What are the functional outcomes after en bloc resection and reconstruction of the wrist with a unipolar prosthesis in patients with Grade III GCT of the distal radius? (2) What complications occur with use of a unipolar prosthesis in these patients? (3) What are the oncologic outcomes with using en bloc resection and reconstruction with a custom unipolar wrist hemiarthroplasty for Grade III GCTs of the distal radius? METHODS: We retrospectively analyzed 10 patients with Campanacci Grade III GCTs of the distal radius treated by a unipolar prosthesis after wide resection of the tumor between January 2008 and October 2013. During that period, all patients at our medical group who presented with a Grade III GCT of the distal radius were treated with wide resection and reconstruction using a custom unipolar implant. Pre- and postoperative pain at rest were assessed according to a 10-cm VAS score. The functional outcomes of the wrist were assessed using the modified Mayo wrist score, and the degenerative changes were evaluated radiographically by a new rating system based on the Knirk and Jupiter scale. We also analyzed tumor recurrence, metastases, and complications associated with the reconstruction procedure. All patients were available for followup at a mean of 52 months (range, 24-90 months). RESULTS: Although the complication rate associated with prosthetic arthroplasty was relatively high (six of 10), none of our patients experienced severe complications. Two patients reported having occasional pain of the involved wrist at the time of final followup (VAS, preoperative versus postoperative: 0 versus 3; 5 versus 2, respectively). The mean modified Mayo wrist score was 68 (range, 45-90). Degenerative changes were found in three wrists (Grade 1, two patients; Grade 2, one patient). Aseptic loosening occurred in one patient and wrist subluxation occurred in two patients. Lung metastases or local tumor recurrence were not observed. CONCLUSIONS: Because of the proportion of patients who had complications and progressive degeneration with this approach, we recommend first exploring alternatives to reconstruction with custom unipolar wrist hemiarthroplasty after resection of Grade III GCTs of the distal radius, such as fibular autografting. However, this technique provides an alternative for patients with concerns regarding possible morbidity associated with autografting, and for situations when allograft is not available. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Case of a Missed Giant Cell Tumor of Bone: An Opportunity to Observe its Natural History Disease.

Giant cell tumor of bone (GCT) is a benign neoplasm that most commonly presents with pain and is rarely diagnosed as an incidental finding. We present the report of a young woman whose pre-operative MRI was only noted to have a tear of the anterior cruciate ligament (ACL). Subsequently, the patient underwent anACL reconstruction. A second MRI, performed four years later, demonstrated an enlarged mass in the same location. A retrospective evaluation of the initial MRI revealed an eccentric metaphyseal lesion. Histology obtained from the lesion demonstrated a giant cell tumor of bone. We present the case of an asymptomatic GCT discovered retrospectively as an incidental finding and reevaluated four years later. 'Ihis case serves as a reminder of the importance for the critical review of routine preoperative imaging and also offers a unique perspective on the natural history of giant cell tumor of bone.

The multidisciplinary management of giant cell tumor of bone.

Giant cell tumor of bone is a locally aggressive lesion with a predilection for local recurrence, and in a small proportion of patients, metastatic disease can develop. Surgery is the mainstay of management for extremity-based lesions. For tumors located in challenging anatomical locations such as the sacrum and spine however, surgery may be associated with unacceptable functional morbidity. There are limited data regarding other treatment modalities such as radiation therapy, cytotoxic chemotherapy, interferon and bisphosphonates. Serial arterial embolization can be effective in some cases. Recent evidence has demonstrated denosumab to be a promising agent in the treatment of unresectable or metastatic disease.

Pamidronate, farnesyl transferase, and geranylgeranyl transferase-I inhibitors affects cell proliferation, apoptosis, and OPG/RANKL mRNA expression in stromal cells of giant cell tumor of bone.

Giant cell tumor (GCT) is the most common nonmalignant primary bone tumor reported in Hong Kong. It usually affects young adults between the ages of 20 and 40. This tumor is well known for its potential to recur following treatment. To date no effective adjuvant therapy exists for GCT. Our project aimed to study the effects of pamidronate (PAM), farnesyl transferase inhibitor (FTI-277), geranylgeranyl transferase inhibitor (GGTI-298), and their combinations on GCT stromal cells (SC). Individual treatment with PAM, FTI-277, and GGTI-298, inhibited the cell viability and proliferation of GCT SC in a dose-dependent way. Combination of FTI-277 with GGTI-298 caused synergistic effects in reducing cell viability, and its combination index was 0.49, indicating a strong synergism. Moreover, the combination of FTI-277 with GGTI-298 synergistically enhanced cell apoptosis and activated caspase-3/7, -8, and -9 activities. PAM induced cell-cycle arrest at the S-phase. The combination of PAM with GGTI-298 significantly increased OPG/RANKL mRNA ratio and activated caspase-3/7 activity. Our findings support that the combination of bisphosphonates with GGTIs or FTIs with GGTIs may be used as potential adjuvants in the treatment of GCT of bone.

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.

Could MTA be a novel medicine on the recurrence therapy for GCTB?

Giant cell tumor of bone (GCTB) is a benign locally aggressive bone tumor with a shown clinical behavior of local recurrences and rare distant metastases. Surgical treatment of GCTB is associated with high morbidity, and local recurrence. Due to the high rate of pulmonary metastases recurrent GCTB may be considered as a severe disease. If the tumor reaches close to the articulating surface a subchondral bone graft can be performed without risking a higher recurrence rate. Mineral trioxide aggregate (MTA) has been widely used to repair various kinds of tooth perforations. MTA is a powder aggregate containing mineral oxides with a good biological action and may facilitate the regeneration of the periodontal ligament and formation of bone. MTA used was able to induce bone regeneration and had its action optimized. Study has showed that, in the presence of MTA, cells grow faster and produce more mineralized matrix gene expression in osteoblasts. We hypothesize that MTA may has anti-recurrence properties. For the clinical point of view, we can apply MTA in the GCTB to induce bone production, then to inhibit the recurrent of the cases. MTA may be the therapy of choice for primary as well as recurrent giant cell tumors of bone.

Papel de la radioterapia en tumores óseos benignos de células gigantes / Role of radiotherapy for benign giant cell tumors of bone

El papel de la radioterapia (RT) en los tumores de células gigantes es incierto. El tratamiento estándar es la cirugía, y el uso de adyuvancia es controvertido. Tras la presentación de un caso clínico se analiza la indicación de la RT en estos tumores y se lleva a cabo una revisión retrospectiva, con historias clínicas de pacientes diagnosticados en el Hospital General Universitario Gregorio Marañón con informe de tumor de células gigantes, análisis y discusión de la literatura. En los tumores de células gigantes en los que éstos se presentan en localizaciones difíciles de realizar una resección amplia, la RT debe ser el tratamiento estándar posterior a la biopsia, alcanzando excelentes tasas de respuesta local. La RT de rescate tras recidiva proporciona una alta tasa de control local sin añadir una morbilidad importante, por lo que debería indicarse como tratamiento en los casos mencionados o como tratamiento paliativo(AU)

The rol of the radiotherapy (RT) in the giant-cell tumor is unknown. The standart treatment is surgery and the use of adjuvant therapy is controversial. After a presentation of a clinical case, the indication of the RT is analyzed in these tumors, and a retrospective review is carried out with patients clinical histories diagnosed in the Hospital General Universitario Gregorio Marañón with report of tumor of giant cells, with analysis and discussion of the literature. In giant cells tumors in which the tumor appears in locations difficult to realize a wide resection, the radiotherapy must be the standard treatment after biopsy, reaching excellent rates of local response. Rescue RT, after recurrence, provides a high rate of local control without adding an additional important morbidity, by it should be indicated as treatment in the mentioned cases or as palliative treatment(AU)

Gap junctional communication in human osteoclasts in vitro and in vivo.

Bone-forming cells are known to be coupled by gap junctions, formed primarily by connexin43 (Cx43). The role of Cx43 in osteoclasts has so far only been studied in rodents, where Cx43 is important for fusion of mononuclear precursors to osteoclasts. Given the potential importance for human diseases with pathologically altered osteoclasts, we asked whether a similar influence of Cx43 can also be observed in osteoclasts of human origin. For this purpose, Cx43 mRNA expression was studied in a time course experiment of human osteoclast differentiation by RT-PCR. Localization of Cx43 in these cells was determined by immunohistochemistry and confocal microscopy. For the assessment of the effect of gap junction inhibition on cell fusion, gap junctions were blocked with heptanol during differentiation of the cells and the cells were then evaluated for multinuclearity. Paraffin sections of healthy bone and bone from patients with Paget's disease and giant cell tumour of the bone were used to study Cx43 expression in vivo. We found mRNA and protein expression of Cx43 in fully differentiated osteoclasts as well as in precursor cells. This expression decreased in the course of differentiation. Consistently, we found a lower expression of Cx43 in osteoclasts than in bone marrow precursor cells in the histology of healthy human bone. Blockade of gap junctional communication by heptanol led to a dose-dependent decrease in multinuclearity, suggesting that gap junctional communication precedes cell fusion of human osteoclasts. Indeed, we found a particularly strong expression of Cx43 in the giant osteoclasts of patients with Paget's disease and giant cell tumour of the bone. These results show that gap junctional communication is important for fusion of human mononuclear precursor cells to osteoclasts and that gap junctional Cx43 might play a role in the regulation of size and multinuclearity of human osteoclasts in vivo.

Giant cell tumor of the spine.

Giant cell tumors are benign but locally aggressive neoplasms that typically affect the extremities. When involving the spine, the tumors occur predominantly in the sacrum. Gross total resection of the tumor with wide margins yields good results in terms of survival. However, it carries a significant potential for morbidity and disability. Subtotal resection with adjuvant radiation carries a risk for recurrence or, more concerning, sarcomatous malignant transformation. Endovascular tumor embolizations have also been attempted to control unresectable tumors, and have been performed with moderate degrees of success. Outcomes are analyzed outcomes following surgery, radiation therapy, and tumor embolization.

Impending fractures in giant cell tumours of the distal femur: incidence and outcome.

Giant cell tumours are rare bone tumours that are characteristically benign but locally aggressive, most frequently occurring in the distal femur with pathological fractures being common. This paper investigates relationships between tumour size and cortical breach on initial X-rays and subsequent treatment. The X-rays of 54 patients with distal femoral giant cell tumours were reviewed. The volumes of the tumour, distal femur and a ratio between the two parameters were estimated. The presence of a cortical breach, discrete fracture and Campanacci grade was recorded. X-rays revealed intact cortical rim in 20 patients (37%), cortical breach in 22 patients (41%) and discrete fracture in 12 patients (22%). There was a significant difference in the ratio of tumour volume to distal femoral volume between the discrete fracture group and the cortical breach group. No significant differences in rates of local recurrence were demonstrated. Extended curettage was effective for intact and cortical breach groups; however, patients in the fracture group often required radical treatment.