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INTRODUCTION: Denosumab has been shown to be highly effective at suppressing the progression of giant cell tumor of bone (GCTB). However, recent studies have observed a potential increased risk of local recurrence after surgery following the use of denosumab, raising concerns on the use of this agent against GCTB in combination with surgery. METHODS: We retrospectively reviewed the medical records of 234 patients with GCTB who were surgically treated at multiple institutions from 1990 to 2017. Patient background, tumor characteristics, treatment methods, local recurrence-free survival rate, distant metastasis rate, oncologic outcome, and limb function at final follow-up were analyzed and compared between cases treated with and without denosumab. RESULTS: The 3-year local recurrence-free survival rate was significantly lower in patients who underwent preoperative denosumab therapy (35.3%) compared with those treated without denosumab (79.9%) (P < 0.001). Among patients who were preoperatively treated with denosumab, those who had a local recurrence all underwent curettage surgery. CONCLUSIONS: Preoperative denosumab therapy in combination with curettage surgery was significantly associated with an increased risk of local recurrence in Campanacci grade 3 tumors. Our data suggest that clinicians seeing GCTB patients should be aware to this increased risk when planning preoperative denosumab therapy.
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Conservadores da Densidade Óssea , Neoplasias Ósseas , Tumor de Células Gigantes do Osso , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Curetagem/efeitos adversos , Denosumab/efeitos adversos , Denosumab/uso terapêutico , Tumor de Células Gigantes do Osso/tratamento farmacológico , Tumor de Células Gigantes do Osso/patologia , Tumor de Células Gigantes do Osso/cirurgia , Humanos , Recidiva Local de Neoplasia/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Due to the wide variations in location, size, local invasiveness, and treatment options, the complications associated with surgery for giant cell tumor of bone have been sporadically reported. For quality assessment, fundamental data based on large-scale surveys of complications under a universal evaluation system is needed. The Dindo-Clavien classification is an evaluation system for complications based on severity and required intervention type and is suitable for the evaluation of surgery in a heterogeneous cohort. METHODS: A multi-institutional retrospective survey of 141 patients who underwent surgery for giant cell tumor of bone in the extremity was performed. The incidence and risk factors of complications, type of intervention for complication control, and impact of complications on functional and oncological outcomes were analyzed using the Dindo-Clavien classification. RESULTS: Forty-six cases (32.6%) had one or more complications. Of them, 18 (12.8%), 11 (7.8%), and 17 (12.1%) cases were classified as Dindo-Clavien classification grade I, II, and III complications, respectively. There were no cases with grade IV or V complications. Progression in Campanacci grading (p = 0.04), resection (over curettage, p < 0.0001), reconstruction with prosthesis (p = 0.0007), and prolonged operative duration (p = 0.0002) were significant risk factors for complications. Complications had a significant impact on function (p < 0.0001). Differences in the impact of complication types and tumor location on function were confirmed. Complications had no impact on local recurrence and metastasis development. CONCLUSION: The Dindo-Clavien classification could provide fundamental information, under a uniform definition and classification system, on postoperative complications in patients with giant cell tumor of bone in terms of incidence, type of intervention for complication control, risk factors, and impact on functional outcome. The data are useful not only for preoperative evaluation for the risk of complications under specific conditions but also for quality assessment of surgery for giant cell tumor of bone.
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Neoplasias Ósseas , Tumor de Células Gigantes do Osso , Procedimentos Ortopédicos , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Extremidades , Tumor de Células Gigantes do Osso/patologia , Tumor de Células Gigantes do Osso/cirurgia , Humanos , Incidência , Procedimentos Ortopédicos/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Surgical treatment for renal cell carcinoma metastases can be an effective modality for improving survival and patients' quality of life. However, it is often difficult to decide on the optimal surgical approach due to the lesion's high vascularity and uncertainty regarding postoperative performance status and survival. PATIENTS AND METHODS: Blood loss, postoperative performance status, overall survival, postoperative complication and related risk factors for surgical treatment were analysed in 61 renal cell carcinoma patients with bone metastases. RESULTS: Pelvic location and impending/pathological fracture in the metastatic lesion were both significant risk factors for increased blood loss. An unresectable primary lesion and poor preoperative performance status were independent risk factors for poor postoperative performance status. A shorter duration from the discovery of primary lesion to bone metastasis, the number of metastases, and unresectable primary lesion were independent risk factors for shorter survival. Postoperative complications were identified in 15 cases (24.6%). CONCLUSION: The preoperative prediction of intraoperative blood loss, performance status and survival in renal cell carcinoma patients with bone metastases may be possible based on the risk factors identified in this study.
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Perda Sanguínea Cirúrgica/estatística & dados numéricos , Neoplasias Ósseas/secundário , Neoplasias Ósseas/cirurgia , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/patologia , Complicações Pós-Operatórias/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Estudos Retrospectivos , Medição de RiscoRESUMO
BACKGROUND: Although intensive studies have been conducted to clarify the incidence, risks, and management methods of deep infection of tumor endoprostheses, limited data have been published in respect of the impact of such deep infection on the function of the corresponding limb. METHODS: Clinical data of 125 patients (infection group 57, control group 68) with malignant bone and soft tissue tumors around the knee enrolled with the Japanese Musculoskeletal Oncology Group were collected. We analyzed the impact of deep infection of tumor endoprostheses on the limb salvage status together with that on the function of the salvaged limb. The definition of deep infection was based on the recommendations of the Centers for Disease Control and Prevention. The functional evaluation was based on the functional classification system established by the International Society of Limb Salvage and the Musculoskeletal Tumor Society. RESULTS: Infection together with extracapsular resection was demonstrated to be a risk factor for late amputation. There were no significant differences in the functional scores for "pain," "support," "walking," or "gait" between the infection and control groups. The risk factors identified for a loss of score for "functional activities" were deep infection, age, duration of operation, and extracapsular resection. The infection group also showed a significant lower score loss in "emotion". As for the overall functional scores, the risk factors identified for lower scores were deep infection and age. The mean scores for the infection group and control group were 19.3 (64.3 %) and 21.6 (72 %), respectively. Although the difference was confirmed to be statistically significant, the actual difference was only 2.3 (10.6 % reduction). CONCLUSIONS: Infection was a major risk factor for late amputation. Limbs salvaged by management of deep infection may show loss of function; however, the impact may be limited.
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Neoplasias Ósseas/cirurgia , Articulação do Joelho , Prótese do Joelho/efeitos adversos , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Adulto , Amputação Cirúrgica , Feminino , Humanos , Joelho , Salvamento de Membro , Masculino , Recuperação de Função Fisiológica , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) is usually a solitary adipocytic tumor. ALT/WDLPS shows no potential for metastasis unless it undergoes dedifferentiation. No case of multiple ALT/WDLPS has been reported in recent years. We present a rare case of multiple recurrent liposarcomas. A 71-year-old man with a history of scrotal ALT/WDLPS at 61 years presented with multiple large tumors spread throughout the body. The patient was bedridden and severely limited in his activities of daily living (ADL) due to multiple large tumors in the trunk and lower extremities. Radiological examination revealed multiple adipocytic tumors, mainly in the soft tissues of the trunk and extremities, with several visceral lesions. Tumors were resected in stages, starting with large tumors directly related to disability. Repeated palliative resections improved the patient's ADL; he regained ambulation and was discharged 18 months after admission. Twelve surgeries were performed to remove 44 adipocytic tumors from the testis, left chest wall, perigastric area, ileum, left inguinal region, both buttocks, thighs, and lower legs. Histological examination revealed dedifferentiated components in five tumors, while 39 tumors were diagnosed as ALT/WDLPS. At the age of 76 years, the patient developed an unresectable dedifferentiated liposarcoma between the heart and aorta, leading to fatality at 79 years. The patient's clinical course suggested multiple metastases of ALT/WDLPS of scrotal origin or ALT/WDLPS of multicentric origin. Although multicentric ALT/WDLPS or ALT/WDLPS metastases are rare, they should be considered when multiple large adipocytic tumors are found throughout the body. Despite the presence of numerous large malignant tumors, surgical treatments of the lesions can improve ADL and prolong life if the tumors are of low-grade malignancy.
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Myxoid/round cell liposarcoma (MRCL), unlike other soft tissue sarcomas, has been associated with unusual pattern of metastasis to extrapulmonary sites. In an attempt to elucidate the clinical features of MRCL with metastatic lesions, 58 cases, from the medical database of Keio University Hospital were used for the evaluation. 47 patients (81%) had no metastases, whereas 11 patients (11%) had metastases during their clinical course. Among the 11 patients with metastatic lesions, 8 patients (73%) had extrapulmonary metastases and 3 patients (27%) had pulmonary metastases. Patients were further divided into three groups; without metastasis, with extrapulmonary metastasis, and with pulmonary metastasis. When the metastatic patterns were stratified according to tumor size, there was statistical significance between the three groups (P = 0.028). The 8 cases with extrapulmonary metastases were all larger than 10 cm. Similarly, histological grading had a significant impact on metastatic patterns (P = 0.027). 3 cases with pulmonary metastatic lesions were all diagnosed as high grade. In conclusion, large size and low histological grade were significantly associated with extrapulmonary metastasis.
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BACKGROUND: We have previously reported that recombinant human plasminogen-related protein B (rPRP-B), a putative 9-kDa protein that closely resembles the activation peptide of plasminogen, has shown significant inhibition of tumor growth through inhibition of angiogenesis. Based on recent reports suggesting a close relationship between rheumatoid arthritis (RA) and angiogenesis, we hypothesized that this compound would regulate inflammatory conditions in RA. The present study therefore tested the effects of rPRP-B in the treatment of collagen-induced arthritis (CIA) to elucidate the mechanisms underlying these effects. METHODS: DBA/1J mice immunized with type II collagen to induce CIA were monitored to assess the effects of rPRP-B on clinical severity of the disease. Pathological changes in joints, including vessel formation and vascular endothelial growth factor (VEGF) production, were examined histologically. Bone destruction was radiologically evaluated. In vitro studies on the effects of rPRP-B on cell proliferation and production of VEGF in interleukin (IL)-1ß or basic fibroblast growth factor (bFGF)-stimulated human synoviocytes were also performed. RESULTS: Development of CIA was effectively inhibited by rPRP-B. Radiological examinations revealed that the protein reduced bone destruction in CIA. CIA-induced vessel formation and VEGF expression in vivo were also reduced. In vitro mechanistic studies demonstrated that rPRP-B affected human synoviocyte proliferation and VEGF production stimulated by IL-1ß and bFGF. CONCLUSIONS: Given the ability to effectively promote multistep anti-angiogenic activities, including cell growth inhibition and cytokine regulation, rPRP-B represents a promising candidate for a novel therapeutic agent against RA.
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Inibidores da Angiogênese/uso terapêutico , Artrite Experimental/tratamento farmacológico , Plasminogênio/uso terapêutico , Animais , Masculino , Camundongos , Camundongos Endogâmicos DBA , Proteínas Recombinantes/uso terapêuticoRESUMO
Osteosarcoma is the most common malignant primary bone tumor that occurs most frequently in the second decade of life but rarely in patients over 40 years of age. The most common primary sites of osteosarcoma are the distal femur followed by proximal tibia and proximal humerus, and involvement of the wrist is extremely rare. Moreover, dedifferentiated osteosarcoma is also a rare condition that progresses to high-grade osteosarcoma from low-grade osteosarcoma, usually central low-grade osteosarcoma or parosteal osteosarcoma that bears MDM2 and/or CDK4 gene amplifications. We herein report an extremely rare case of dedifferentiated osteosarcoma arising in the distal ulna of an adult over 40 years of age. The patient was a 46-year-old man with a 2-month history of pain in his left swollen wrist. The initial radiological findings suggested a benign bone tumor in the distal ulna, and the lesion was marginally excised at the nearby hospital. Although the pathological diagnosis at the nearby hospital suggested a benign cartilaginous tumor, the tumor recurred in an aggressive manner 8 months after the initial surgery. The patient was referred to our hospital, and an incisional biopsy showed a high-grade osteosarcoma. The primary tumor was retrospectively re-evaluated at our hospital and diagnosed as low-grade osteosarcoma. Since neoadjuvant chemotherapy failed to shrink the tumor, the patient had to undergo below the elbow amputation to cure the disease. Although the tumor was negative for MDM2 nor CDK4, the definitive diagnosis of dedifferentiated osteosarcoma was made according to the clinical course and the histological findings. Lung metastases were found 10 months after the amputation, which were successfully treated by neoadjuvant chemotherapy and surgery. The patient has been doing well with no evidence of disease for 1 year and 6 months. Surprisingly, the literature review revealed that many low-grade osteosarcomas of the distal ulna progressed to high-grade dedifferentiated osteosarcomas. One should bear in mind that the diagnosis and treatment for bone-forming tumors of the distal ulna should be made very carefully because, although rare, it is possible that the tumor may initially appear as a benign or low-grade malignant tumor and may progress to high-grade osteosarcoma.
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BACKGROUND: Although deep infection remains one of the most difficult complications to manage in the treatment of musculoskeletal tumor reconstructed with an endoprosthesis, limited information with respect to its incidence and risk factors has been reported. METHODS: This multicenter, retrospective, uncontrolled study reviewed the medical records of 82 patients who underwent reconstruction with an endoprosthesis or temporary spacer for bone-immature patients after resection of malignant bone tumor around the knee. Risk factors for deep infection and the impact of deep infection on prosthesis survival and oncological outcomes were analyzed. Deep infection was defined according to the Centers for Disease Control and Prevention (CDC) guidelines with minor modification. RESULTS: Deep infection occurred in 14 cases (17%), identified at a mean of 10.9 months (range <1 to 48 months) after initial surgery. Univariate analysis identified surface infection (P < 0.001) and skin necrosis (P < 0.001) as risk factors associated with deep infection. Conversely, tumor origin, chemotherapy, number of postoperative antibiotics, and length of bone resection were not associated with infection. Subclass analysis in femur cases identified a correlation between infection and the extent of partial resection of the quadriceps muscle (P = 0.04). In the multivariate analysis, surface infection represented an independent risk factor for deep infection (P = 0.03). Deep infection was a risk for endoprosthesis survival (P = 0.003) but did not affect the oncological outcome. CONCLUSIONS: A strong correlation between the condition of soft tissue and establishment of deep infection is suggested in this study. Although practical options for preventing deep infection seem limited, the present data allow a form of perioperative evaluation for patients with a higher risk of deep infection.
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Neoplasias Ósseas/cirurgia , Joelho/cirurgia , Implantação de Prótese/efeitos adversos , Infecção da Ferida Cirúrgica/etiologia , Idoso de 80 Anos ou mais , Pré-Escolar , Feminino , Fêmur/cirurgia , Humanos , Estimativa de Kaplan-Meier , Salvamento de Membro , Masculino , Estudos Retrospectivos , Tíbia/cirurgiaRESUMO
Metastases of dedifferentiated sarcoma usually contain a dedifferentiated component. We report a rare case of dedifferentiated parosteal osteosarcoma (dd-POS) with well-differentiated multiple metastases in a 65-year-old woman with a painful firm mass on her thigh. Radiological examination revealed that the mass arose from the surface of her femur without medullary involvement. Multiple intramuscular metastases were detected in her lower leg on MR imaging. Small subcutaneous palpable masses were identified on her left lower leg, buttock, chest wall and head. An open biopsy and above-the-knee amputation were performed, and the mass on her femur was diagnosed as a dd-POS. However, histological examination on the subcutaneous lesions in her lower leg, buttock and head showed low-grade conventional POS without dedifferentiated components. To the best of our knowledge, this is the first report of a dd-POS with multiple metastases that do not contain any dedifferentiated components.