Do Massive Allograft Reconstructions for Tumors of the Femur and Tibia Survive 10 or More Years after Implantation?

BACKGROUND: Massive bone allografts have been used for limb salvage in patients undergoing bone tumor resections as an alternative to endoprostheses. Although several studies on massive allograft reconstructions for bone tumors reported that most complications occur in the first 3 years after surgery, there are no long-term reports on complications to substantiate this contention. We believe such information is important so that surgeons and patients can make more informed decisions when choosing a reconstructive method after tumor resection. QUESTIONS/PURPOSES: (1) What is the survival of allografts free from removal, amputation, or joint replacement in patients treated for bone tumors in the lower limb with a minimum of 10 years of followup? (2) What complications occur after 10 or more years of followup? (3) Are there factors associated with allograft survival, such as age, sex, the affected bone, reconstruction type (intercalary or osteoarticular allograft), tumor type (malignant or benign), failure type, and chemotherapy use? METHODS: We retrospectively analyzed the records of 398 patients treated in one center with benign or malignant bone tumors in the femur or tibia between 1986 and 2007. During the period in question, our general indications for using allografts (354 patients) included patients with benign or low-grade sarcomas and patients with high-grade sarcomas with clinical and imaging response to neoadjuvant chemotherapy. Other approaches such as endoprostheses (44 patients) were indicated if the patient received radiotherapy, in patients with high-grade sarcomas without clinical and imaging response to neoadjuvant chemotherapy, or with neurovascular tumor involvement. We excluded from the analysis 53 patients treated with allograft-prosthetic composites, 46 with hemicondylar osteoarticular allografts, and 57 with intercalary hemicylindrical allografts. The study was thus performed in 198 patients treated with segmental massive allografts in the long bones of the lower extremity (132 femurs and 66 tibias) after resection of a primary bone tumor, including 120 patients treated with osteoarticular and 78 with segmental intercalary allografts. A total of 32 (16%) of the 198 patients died before 10 years, and graft status was known in all of those patients; these patients were included (mean followup, 192 months; range, 1-370 months). All remaining 166 patients who were not known to have died before 10 years were accounted for at least 10 years after the allograft procedure (mean, 222 months; range, 120-370 months). No patient was lost to followup. The mean age was 22 years (range, 2-55 years); 105 patients were male (53%) and 93 were female. The predominant diagnoses were osteosarcoma (n = 125, 63%), giant cell tumor of bone (n = 27, 14%), and Ewing's sarcoma (n = 19, 10%). In all, 146 patients (74%) underwent chemotherapy. Selected variables were analyzed using multivariate logistic regression analyses to identify risk factors of allograft removal, joint replacement, or amputation. We performed competitive risk analysis with allograft removal, joint replacement, or amputation as the endpoint at 5, 10, and 20 years. Patient function was evaluated using the Musculoskeletal Tumor Society (MSTS)-93 scoring system. RESULTS: The risk of allograft removal, joint replacement, or amputation was 36% at 5 years (95% CI, 30-43), 40% at 10 years (95% CI, 33-47), and 44% at 20 years (95% CI, 37-51). Fractures occurred in 15% (29 patients), infection in 14% (27 patients), nonunion in 12% (23 patients) and tumor recurrence in 7% (13 patients). Thirty-two patients died of disease before 10 years; nine of these patients had a second surgery before death, eight had an amputation, and one underwent graft removal. Of the 166 patients who were still alive 10 years after the allograft procedure, 36 underwent allograft removal, six patients underwent joint replacement, and four had an amputation; however, after 10 years, six more allografts were removed (four due to fractures, one due to infection, and one due to instability), and another patient was amputated due to a second malignancy. After controlling for potentially confounding variables including death, we found that the risk of allograft removal, joint replacement, or amputation in osteoarticular tibial grafts (58% [95% CI, 43-73] at 5, 10, and 20 years) was higher than that of osteoarticular femur allografts (29% [95% CI, 18-39] at 5 years, 30% [95% CI, 19-40] at 10 years, 37% [95% CI, 25-48] at 20 years; p = 0.010) and tibia intercalary allografts (26% [95% CI, 7-45] at 5, 10 and 20 years; p = 0.020). Fractures occurred more frequently in the femur (18% [95% CI, 11-25]) than in the tibia (5% [95% CI, 0-10]; p < 0.010), and infections occurred more frequently in the tibia (24% [95% CI, 14-35]) than in the femur (4% [95% CI, 0-8]; p < 0.001). With the number of patients we had, we found no difference in the proportion of local recurrence in the tibia (12% [95% CI, 4-20]) compared with the femur (5% [95% CI, 1-9]; p < 0.053). CONCLUSIONS: Infections were the most common complications associated with allograft removal in the first 2 to 3 years after reconstruction and were more frequently associated with tibial allograft removal. Fractures were more commonly associated with graft removal with longer term followup and were more frequently associated with femoral allograft removal. Although we cannot directly compare our results with other types of reconstructions, we believe that allografts still have a role in the reconstruction of patients with a benign or low-grade bone tumor. Future studies in femoral allograft with longer followup should be performed to analyze factors that may explain why some grafts fail, such as the percent of the length of the bone resected, type and number of plates and screws used and type of fixation (rods versus plates). There was a higher incidence of graft removal in patients with proximal tibia osteoarticular allografts, which has led us to use this type of reconstruction only in pediatric patients over the last 15 years. LEVEL OF EVIDENCE: Level III, therapeutic study.

Effects of mindfulness-based stress reduction combined with music therapy on pain, anxiety, and sleep quality in patients with osteosarcoma

Objectives: To evaluate the effects of mindfulness-based stress reduction (MBSR) combined with music therapy (MT) on clinical symptoms in patients with osteosarcoma. Methods: Patients diagnosed with osteosarcoma were assessed for eligibility. A total of 101 patients were ultimately randomized into the intervention and control groups. Both groups received routine care. Eight sessions of MBSR and MT psychotherapy were conducted in the intervention group, while the control group received no psychological intervention. Patients were assessed regarding pain, anxiety, and sleep quality at two distinct stages: before and after the intervention. Results: There were no significant differences in sociodemographic and clinical parameters between the intervention and control groups at baseline. The intervention program significantly alleviated psychological and physiological complications in patients with osteosarcoma. Specifically, the study revealed that 8 weeks of the combined MBSR/MT intervention effectively reduced pain and anxiety scores and improved the quality of sleep in patients. Conclusion: MBSR combined with MT significantly alleviated clinical symptoms, and could be considered a new, effective psychotherapeutic intervention for patients with osteosarcoma.

Plasmocitoma solitario de costilla como presentación inicial de mieloma múltiple: reporte de un caso / Lone rib plasmacytoma as a presentation of initial multiple myeloma: a case report

Resumen Introducción: El 50% de los tumores de pared torácica son malignos, dentro de los que destaca el plasmocitoma de costilla. Objetivo: Presentar un caso clínico que debutó inicialmente como un plasmocitoma de costilla, y que terminó presentándose como mieloma múltiple. Materiales y Método: Registro clínico de un paciente sometido a resección de tumor de parrilla costal. Resultados: Paciente masculino de 58 años, con un año de dolor costal, asociado a aumento de volumen a nivel de la octava costilla derecha en línea media axilar, indurada. TC de tórax que demuestra imagen sugerente de plasmocitoma de 79 × 44 mm. Se realiza resección quirúrgica, con instalación de malla de prolene en el defecto. Biopsia diferida con compromiso neoplásico por lesión monoclonal de células plasmáticas. Se complementa estudio con biopsia de médula ósea confirmando mieloma múltiple. Se inicia tratamiento con quimioterapia adyuvante. Conclusiones: El plasmocitoma óseo solitario es una entidad de baja frecuencia, que se asocia a la presencia de mieloma múltiple. Es por esto que al momento de la sospecha se hace necesario descartar su presencia, con el fin de mejorar el pronóstico del paciente.

Introduction: Up to 50% of chest wall tumors are malignant; among which rib plasmocytoma stand out. Aim: Showcase a clinical case that debuted as a rib plasmacytoma, and that ended up presenting as Multiple Myeloma. Materials and Method: Records of a patient with resection of chest wall tumor. Results: Male patient of 58 years, with one year of costal pain, associated with an indurated increase in volume at the level of the eighth right rib in the mid-axillary line. Chest CT scan demonstrated a suggestive image of plasmacytoma of 79 × 44 mm. Surgical resection was performed, with prolene mesh installation in the defect. Biopsy showed neoplastic compromise due to monoclonal lesion of plasma cells. Study is complemented with bone marrow biopsy confirming multiple myeloma. The patient was treated with adjuvant chemotherapy. Conclusions: Solitary bone plasmacytoma is a low frequency entity, which is associated with the presence of multiple myeloma. At the moment of suspicion, it is necessary to rule out their presence, in order to improve the patient's prognosis.

Health-related quality of life of Brazilian children and adolescents with benign and malignant solid tumours: A prospective cohort study during the first year after hospital admission.

INTRODUCTION: This study aims to assess the impact of paediatric benign and malignant solid tumours and its treatment on the health-related quality of life of children and adolescents who were followed up in a Reference Center in Pediatric Oncology in Rio de Janeiro. METHODS: It is a prospective cohort study. Quality of life assessment was performed using the PedsQL™ 4.0 Generic Core Scales and PedsQL™ 3.0 Cancer Module protocols three times: during hospital admission (T1), 6 months after admission (T2) and 1 year after admission (T3). RESULTS: We evaluated 132 patients, 59 men and 73 women, aged 2-17 years. In PedsQL™4.0, the Emotional Functioning scale was the one with the worst scores, while the scores on the Social Functioning scale was the best. In PedsQL™ 3.0, the worst domains were Procedural Anxiety and Worry. Patients with malignant bone tumours had the worst health-related quality of life. The group who received only surgery had better results. Total scores of PedsQL™4.0 and PedsQL™ 3.0 improved between T1 and T3. CONCLUSION: Children and adolescents with malignant and benign neoplasms undergo changes in quality of life as a result of the disease and treatment, but an improvement has been observed over time.

Effects of mindfulness-based stress reduction combined with music therapy on pain, anxiety, and sleep quality in patients with osteosarcoma.

OBJECTIVES: To evaluate the effects of mindfulness-based stress reduction (MBSR) combined with music therapy (MT) on clinical symptoms in patients with osteosarcoma. METHODS: Patients diagnosed with osteosarcoma were assessed for eligibility. A total of 101 patients were ultimately randomized into the intervention and control groups. Both groups received routine care. Eight sessions of MBSR and MT psychotherapy were conducted in the intervention group, while the control group received no psychological intervention. Patients were assessed regarding pain, anxiety, and sleep quality at two distinct stages: before and after the intervention. RESULTS: There were no significant differences in sociodemographic and clinical parameters between the intervention and control groups at baseline. The intervention program significantly alleviated psychological and physiological complications in patients with osteosarcoma. Specifically, the study revealed that 8 weeks of the combined MBSR/MT intervention effectively reduced pain and anxiety scores and improved the quality of sleep in patients. CONCLUSION: MBSR combined with MT significantly alleviated clinical symptoms, and could be considered a new, effective psychotherapeutic intervention for patients with osteosarcoma.

MicroRNA-340-5p modulates cisplatin resistance by targeting LPAATß in osteosarcoma.

MicroRNAs (miRNAs) play an important role in drug resistance and modulate the efficiency of chemotherapy. A recent study indicated that miR-340 functions as a tumor suppressor in various types of cancer. However, the role of miR-340 in chemotherapy has not been reported yet. In this study, we found that miR-340 enhanced cisplatin (CDDP)-induced cell death. Induction of miR-340-5p expression decreased the IC50 of CDDP and increased the apoptosis of CDDP-resistant MG-63 and Saos-2 cells. Moreover, miR-340-5p decreased the accumulation of MRP1 and MDR1. We further explored the mechanism underlying the promoting effects of miR-340-5p on CDDP-induced cell death. We identified a potential target of miR-340 in the 3' untranslated region of lysophosphatidic acid acyltransferase (LPAATß) using the online program Targetscan (http://www.microrna.org). Luciferase reporter assays showed that miR-340 binds to the 3'UTR of LPAATß. Enforced expression of miR-340-5p decreased the accumulation of LPAATß in both MG-63 and Saos-2 cells. Silencing LPAATß decreased the IC50 of CDDP and increased the apoptosis of CDDP-resistant MG-63 and Saos-2 cells, which is consistent with the effect of miR-340-5p on CDDP-induced cell death. Moreover, induced expression of LPAATß compromised the effects of miR-340-5p on CDDP-induced cell death and accumulation of MRP1 and MDR1. Taken together, our data indicated that miR-340-5p enhanced the sensitivity to CDDP by targeting LPAATß.

MicroRNA-340-5p modulates cisplatin resistance by targeting LPAATβ in osteosarcoma

MicroRNAs (miRNAs) play an important role in drug resistance and modulate the efficiency of chemotherapy. A recent study indicated that miR-340 functions as a tumor suppressor in various types of cancer. However, the role of miR-340 in chemotherapy has not been reported yet. In this study, we found that miR-340 enhanced cisplatin (CDDP)-induced cell death. Induction of miR-340-5p expression decreased the IC50 of CDDP and increased the apoptosis of CDDP-resistant MG-63 and Saos-2 cells. Moreover, miR-340-5p decreased the accumulation of MRP1 and MDR1. We further explored the mechanism underlying the promoting effects of miR-340-5p on CDDP-induced cell death. We identified a potential target of miR-340 in the 3′ untranslated region of lysophosphatidic acid acyltransferase (LPAATβ) using the online program Targetscan (http://www.microrna.org). Luciferase reporter assays showed that miR-340 binds to the 3′UTR of LPAATβ. Enforced expression of miR-340-5p decreased the accumulation of LPAATβ in both MG-63 and Saos-2 cells. Silencing LPAATβ decreased the IC50 of CDDP and increased the apoptosis of CDDP-resistant MG-63 and Saos-2 cells, which is consistent with the effect of miR-340-5p on CDDP-induced cell death. Moreover, induced expression of LPAATβ compromised the effects of miR-340-5p on CDDP-induced cell death and accumulation of MRP1 and MDR1. Taken together, our data indicated that miR-340-5p enhanced the sensitivity to CDDP by targeting LPAATβ.

Survival, recurrence, and function after epiphyseal preservation and allograft reconstruction in osteosarcoma of the knee.

BACKGROUND: Bone tumor resections for limb salvage have become the standard treatment. Recently, intercalary tumor resection with epiphyseal sparing has been used as an alternative in patients with osteosarcoma. The procedure maintains normal joint function and obviates some complications associated with osteoarticular allografts or endoprostheses; however, long-term studies analyzing oncologic outcomes are scarce, and to our knowledge, the concern that a higher local recurrence rate may be an issue has not been addressed. QUESTIONS/PURPOSES: We wanted to assess (1) the overall survival in patients treated with this surgical technique; (2) the percentage of local recurrence and limb survival, specifically the incidence of recurrence in the remaining epiphysis; (3) the frequency of orthopaedic complications, and, (4) the functional outcomes in patients who have undergone intercalary tumor resection. METHODS: We analyzed all 35 patients with osteosarcomas about the knee (distal femur and proximal tibia) treated at our center between 1991 and 2008 who had resection preserving the epiphysis and reconstruction with intercalary allografts. Minimum followup was 5 years, unless death occurred earlier (mean, 9 years; range, 1-16 years), and no patients were lost to followup. During the study period, our indications for this approach included patients without metastases, with clinical and imaging response to neoadjuvant chemotherapy, that a residual epiphysis of at least 1 cm thickness could be available after a surgical margin width in bone of 10 mm was planned, and 16% of patients (35 of 223) meeting these indications were treated using this approach. Using a chart review, we ascertained overall survival of patients, oncologic complications such as local recurrence and tumor progression, limb survival, and orthopaedic complications including infection, fracture, and nonunion. Survival rates were estimated using the Kaplan-Meier method. Patient function was evaluated using the Musculoskeletal Tumor Society (MSTS)-93 scoring system. RESULTS: Overall survival rate of the patients was 86% (95% CI, 73%-99%) at 5 and 10 years. Five patients died of disease. No patient had a local recurrence in the remaining bony epiphysis, but three patients (9%; 95% CI, 0%-19%) had local recurrence in the soft tissue. The limb survival rate was 97% (95% CI, 89%-100%) at 5 and 10 years. Complications treated with additional surgical procedures were recorded for 19 patients (54%), including three local recurrences, two infections, 11 fractures, and three nonunions. In 10 of these 19 patients, the allograft was removed. Only five of the total 35 study patients (14%) lost the originally preserved epiphysis owing to complications. The mean functional score was 26 points (range, 10-30 points, with a higher score representing a better result) at final followup. CONCLUSIONS: Although the recurrence rate was high in this series, the small sample size means that even one or two fewer recurrences might have resulted in a much more favorable percentage. Because of this, future, larger studies will need to determine whether this is a safe approach, and perhaps should compare epiphyseal preservation with other possible approaches, including endoprosthetic reconstruction and/or osteoarticular allografts. LEVEL OF EVIDENCE: Level IV, therapeutic study.

A mathematical model for describing the metastasis of cancer in bone tissue.

Metastasis is the rapid proliferation of cancer cells (secondary tumour) at a specific place, generally leading to death. This occurs at anatomical parts providing the necessary environment for vascularity, oxygen and food to hide their actions and trigger the rapid growth of cancer. Prostate and breast cancers, for example, use bone marrow for their proliferation. Bone-supporting cancer cells thus adapt to the environment, mimicking the behaviour of genetic and molecular bone cells. Evidence of this has been given in Cecchini et al. (2005, EAU Update Ser. 3:214-226), providing arguments such as how cancer cell growth is so active during bone reabsorption. This paper simulates metastasis activation in bone marrow. A mathematical model has been developed involving the activation of molecules from bone tissue cells, which are necessary for cancer to proliferate. Here, we simulate two forms of secondary tumour growth depending on the type of metastasis: osteosclerosis and osteolysis.

Tumor de células gigantes da extremidade distal do fêmur: um desafio de tratamento / Giant cell tumor of femoral distal end: a challenge in treatment

Apresentamos aqui um caso de tumor de células gigantes na extremidade distal do fêmur direito tratado com ressecção da massa tumoral em bloco com remoção aguda da extremidade proximal e distal e fixado com hastes longas em K atravessando o joelho, do fêmur à tíbia. Após a consolidação / união completa das extremidades, foi feita a remoção da haste em K, seguida pela corticotomia juntamente com a osteogênese da distração com o auxílio do anel fixador de Ilizarov. O comprimento foi alcançado com este processo. O resultado final foi muito bom neste caso. Revisamos as opções de tratamento para tumor maligno de células gigantes na extremidade distal do fêmur e as dificuldades de tratá-lo.

We present a case of malignant giant cell tumor of distal end of right femur treated with resection of the tumor mass en block with acute docking of proximal and distal end and fixed with long K-nail across knee from femur to tibia. After complete consolidation/ union of the ends, removal of K nail was done followed by corticotomy along with distraction osteogenesis with the help of Ilizarov ring fixator. The length was achieved with this process. The end result was very good in this case. We reviewed the treatment options for malignant giant cell tumor of femoral distal end and the challenges in its treatment.

Functional and radiographic evaluation of 214 aggressive benign bone lesions treated with curettage, cauterization, and cementation: 24 years of follow-up.

PURPOSE: Treatment with curettage, cauterization, and methylmethacrylate of aggressive benign bone lesions is a method now widely accepted in most orthopedic oncology centers. However, one of the controversies regarding this technique is the possible complications that may arise from the use of methylmethacrylate, which has caused some authors to remove it 2 years after the surgery and replace it with bone graft. The objective of this paper is to present a functional and radiographic evaluation of 214 patients presenting with aggressive benign bone lesions treated with curettage, cauterization, and methylmethacrylate from 1974 to 1998, with some of them having 24 years of follow-up. These patients were clinically and radiographically evaluated for the incidence of late osteoarthrosis, range of motion, and pain in the involved joint. METHOD: This study comprised 214 patients, with an average follow-up duration of 10.6 years (range: 2 to 24 years. All cases involved aggressive benign lesions. The patients were evaluated according to the Musculoskeletal Tumor Society Score (MSTS) functional evaluation system, and the complications are described. RESULTS: The MSTS functional evaluation was excellent in 166 cases (78%), good in 26 (12%), fair in 11 (5%), and poor in 11 (5%). The following complications were observed: late osteoarthrosis, 25 cases (12%); infection, 12 (6%); pathologic fracture, 11 (5%); and local recurrence, 19 (9%). CONCLUSION: Based on clinical assessment, no significant deleterious effects directly related to the use of methylmethacrylate were observed. The functional evaluation performed in 1998 (up to 24 years of follow-up) did not show significant change when compared to the evaluation performed in 1985.

Functional and radiographic evaluation of 214 aggressive benign bone lesions treated with curettage, cauterization, and cementation: 24 years of follow-up

OBJETIVO: O tratamento com curetagem cauterização e metilmetacrilato de lesões ósseas benignas agressivas é o método agora amplamente aceito em quase todos os Centros Ortopédicos Oncológicos, entretanto uma das controvérsias com relação a esta técnica são as possíveis complicações que podem sugerir com o uso do metilmetacrilato fazendo com que alguns autores o removam dos anos depois da cirurgia e os substituam com o enxerto ósseo. O objetivo deste trabalho é apresentar a avaliação radiográfica e funcional de 214 pacientes apresentando lesões ósseas benignas agressivas tratadas com curetagem, cauterização e metilmetacrilato de 1974 a 1998, sendo que alguns deles tem 12 anos de seguimento. Esses pacientes foram avaliados clínica e radiograficamente para a ocorrência de osteoartrose tardia, amplitude de movimento e dor na articulação envolvida. MÉTODO: Este estudo é constituído de 214 pacientes, com seguimento médio de 10,6 anos (2 a 24 anos). Todos os casos correspondem as lesões benignas agressivas. Os pacientes foram avaliados de acordo com Muscolskeletal Tumor Society Score sendo descritas as complicações. RESULTADOS: A avaliação funcional da (MSTS) foi excelente em 166 casos (78%), bom em 26 (12%), regular em 11(5%) e mal 11 (5%). Foram observadas as seguintes complicações: osteoartrose tardia 25 casos (12%), infecção 12(6%), fratura patológica 11(5%) e rescindiva local 19(9%). CONCLUSÃO: Baseado na abordagem clínica não foi observado efeitos deletérios diretamente relacionados ao uso do metilmetacrilato. A avaliação funcional realizada em 1998 (até 24 anos de seguimento) não apresentou alterações significantes quando comparadas a avaliação realizada em 1985.

Linfoma ósseo em cão / Bone lymphoma in a dog

It was reported one case of primary bone lymphoma in eight year-old bitch, Fila, with history of anterior limbs paralysis and side lied. A cervical vertebrae neoplasm was suspected and in view of the poor prognosis, the animal was euthanatized. Based on the anatomopathological and histological findings it was firmed the diagnosis of primary bone lymphoma.

Osteossarcoma periosteal: estudo de quatro casos / Periosteal osteosarcoma: study of four cases

Os autores estudam quatro casos de uma entidade pouco conhecida até recentemente - o osteossarcoma periosteal. A casuística analisada é comparada com o descrito na literatura pertinente em relaçäo aos aspectos anatomopatológico e terapêutico.

Linfangioma óseo: presentación de dos pacientes / Bone lymphangioma: report of 2 cases

Se presentan las historias clínicas de dos pacientes con diagnóstico de Linfangioma óseo, el cual es un tumor benigno formado por vasos linfáticos, cuya etiología es desconocida. Las lesiones muestran variabilidad en cuanto a tamaño, sitio y hueso afectado, ya que involucra desde los huesos de la calota, huesos largos y cortos. la evolución de las lesiones puede ser estacionaria o avanzar hasta la total desaparición del hueso

Tumores óseos. Estadio clínico / Bone tumors. Clinical staging

Se presenta una revisión retrospectiva de 100 casos clínicos con lesiones óseas primarias tumorales, diagnosticados, tratados y seguidos clínicamente por un lapso promedio de 24 meses, que se usaron para utilizar y evaluar el sistema de estadio clínico de neoplasias esqueléticas propuesto por Enneking. Toda la información clínica fué codificada en el lenguaje del sistema de Enneking, determinándose en cada uno de los casos el estado clínico correspondiente. Los elementos que se consideraron para su evaluación fueron la verificación de las correlaciones: clínico-radiológica-histopatológica del diagnóstico, y la del margen quirúrgico y tratamiento complementario con el estadio clínico, así como la concordancia de ambas correlaciones con su seguimiento. En nuestro estudio el sistema de Enneking demostró que es una metodología eficaz y confiable para el diagnóstico y tratamiento de los pacientes con neoplasias esqueléticas primarias.