Giant cell tumor of bone: a multicenter epidemiological study in brazil / Tumor de células gigantes ósseas: estudo epidemiológico multicêntrico no brasil

ABSTRACT Introduction: Giant cell tumor of bone (GCTB) mainly affects young adults' long bone epiphyses, threatening bone strength and joint function. Surgery is the primary treatment, although post-surgery recurrence is significant. This study analyzes patient profiles, treatments, and outcomes for GCTB in Brazil. Methods: We retrospectively assessed local recurrence, metastasis, and treatment approaches in 643 GCTB patients across 16 Brazilian centers (1989-2021), considering regional differences. Results: 5.1% (n=33) developed pulmonary metastases, 14.3% (n=92) had pathological fractures, and the local recurrence rate was 18.2% (n=114). Higher rates of pulmonary metastases (12.1%) and advanced tumors (Campanacci III, 88.9%) were noted in lower-income North and Northeast regions. The North also had more pathological fractures (33.3%), extensive resections (61.1%), and amputations (27.8%). These regions faced longer surgical delays (36-39 days) than the South and Southeast (27-33 days). Conclusions: Our findings corroborate international data, underscoring regional disparities in Brazil that may lead to worse outcomes in disadvantaged areas. This highlights the need for improved orthopedic oncology care in Brazil's economically and structurally challenged regions. Level of Evidence III; Retrospective Cohort.

RESUMO Introdução: O tumor de células gigantes do osso (TCG) atinge principalmente epífises de ossos longos em adultos jovens, impactando a resistência óssea e a funcionalidade articular. O tratamento principal é cirúrgico, mas há significativa recorrência pós-operatória. Este estudo analisa o perfil de pacientes e tumores de TCG no Brasil, abordagens de tratamento e resultados. Métodos: Avaliamos retrospectivamente taxas de recorrência, metástase e tratamentos em 643 pacientes tratados em 16 centros brasileiros de 1989 a 2021, considerando a distribuição geopolítica. Resultados: 5,1% desenvolveram metástases pulmonares e 14,3% tiveram fraturas patológicas. A recorrência local foi de 18,2%. Regiões economicamente menos favorecidas, como Norte e Nordeste, mostraram maiores incidências de metástases pulmonares (12,1%) e tumores avançados (Campanacci III, 88,9%). O Norte teve alta ocorrência de fraturas patológicas (33,3%), cirurgias extensas (61,1%) e amputações (27,8%). Nessas regiões, o tempo pré-cirúrgico foi mais longo (médias de 36 e 39 dias) comparado ao Sul e Sudeste (27 e 33 dias, respectivamente). Conclusões: Os resultados refletem disparidades regionais no Brasil, sugerindo que condições socioeconômicas influenciam os desfechos clínicos. Estes achados são importantes para melhorar o cuidado oncológico ortopédico em regiões desfavorecidas do país. Nível de Evidência III; Coorte Retrospectiva.

Argon Beam Coagulation as an Adjuvant for Extended Curettage for Giant Cell Tumors of the Bone: A Study of 50 Cases / Coagulação por plasma de argônio como adjuvante à curetagem estendida em tumores de células gigantes do osso: Um estudo de 50 casos

Abstract Objective Extended curettage with adjuvants of giant cell tumors of bone is associated with a lower rate of recurrence of the tumor while preserving the adjacent joint. The present study was conducted to estimate the recurrence rate and functional outcome after using argon beam as an adjuvant for extended curettage. Methods We selected 50 patients with giant cell tumors, meeting all the inclusion criteria, who underwent extended curettage using high speed burr and argon beam photocoagulation between July 2016 to January 2019. On their follow-up visit, they were assessed for any complaints of pain and signs like tenderness, locally raised temperature, and decreased range of motion of the adjacent joint. Radiologically, the patients were assessed for any increased lucency around the cement mantle and uptake of the subarticular graft. Musculoskeletal Tumor Society Score (MSTS) was administered to the patients, and range of motion of the adjacent joint was compared with the contralateral joint. Results Recurrence was found in 4 patients, that is, an 8% recurrence rate. Twenty-six out of 28 patients with a tumor in the lower limb had a grade-5 weight bearing status 6 months from the surgery, and their range of motion was comparable to contralateral healthy joint with an average MSTS score of 27 (18-30). Conclusion Extended curettage of giant cell tumors using argon beam coagulation is associated with low recurrence rates of the tumor and is an effective modality in the treatment of these tumors besides having a functional outcome comparable to the healthy limb.

Resumo Objetivo A curetagem estendida com adjuvantes de tumores de células gigantes do osso está associada a uma menor taxa de recidiva da neoplasia e à preservação da articulação adjacente. Este estudo foi feito para estimar a taxa de recidiva e o resultado funcional após o uso de plasma de argônio como adjuvante à curetagem estendida. Métodos Cinquenta pacientes com tumores de células gigantes que atendiam a todos os critérios de inclusão foram selecionados para o estudo e submetidos à curetagem estendida com broca de alta velocidade e fotocoagulação com plasma de argônio entre julho de 2016 e janeiro de 2019. À consulta de acompanhamento, os pacientes foram avaliados quanto a quaisquer queixas de dor e sinais como sensibilidade, aumento local da temperatura e diminuição da amplitude de movimento da articulação adjacente. Radiologicamente, os pacientes foram avaliados quanto à presença de qualquer aumento de radiotransparência ao redor do manto de cimento e incorporação do enxerto subarticular. O questionário Musculoskeletal Tumor Society Score (MSTS) foi administrado aos pacientes e a amplitude de movimentação da articulação adjacente foi comparada à articulação contralateral. Resultados Quatro pacientes apresentaram recidiva, o que corresponde a uma taxa de 8%. Seis meses após a cirurgia, 26 de 28 pacientes com tumor no membro inferior tinham capacidade de sustentação de peso de grau 5 e amplitude de movimento comparável à articulação saudável contralateral, com pontuação MSTS média de 27 (intervalo de 18 a 30). Conclusão A curetagem estendida de tumores de células gigantes com coagulação por plasma de argônio está associada a baixas taxas de recidiva da neoplasia; é uma modalidade eficaz no tratamento desses tumores e o resultado funcional é comparável ao do membro saudável.

Application progress of Ilizarov technique in orthopedics / 中国基层医药

Ilizarov technique is designed based on the "tension-stress principle". Application of the Ilizarov technique can help form a stable mechanical structure through external fixation. It only creates small wounds, without peeling off the surrounding tissue and periosteum. It connects different types of fixation pins and bone or soft tissue to form a traction force, which continuously stimulates the regeneration of bone and tissue and improves the local blood supply and early functional rehabilitation exercises, forming a complete set of minimally invasive orthopedic treatment systems. Ilizarov technique has achieved good results in fracture healing, deformity correction, tissue repair, osteomyelitis, bone nonunion, bone defect, and bone tumor. This paper will summarize the clinical application and research of the Ilizarov technique in orthopedics and explore the key problems of the Ilizarov technique that need to be solved at present.

The correlation of bone metabolism biomarkers in newborn twins and their pregnant mothers / 中国新生儿科杂志

Objective:To study the correlation of bone metabolism biomarkers between newborn twins and their mothers during pregnancy.Methods:From January 1, 2018 to June 30, 2022, newborn twins with mild symptoms admitted to the neonatal department of our hospital were retrospectively reviewed. The clinical data of the twins and their mothers were collected, including bone metabolism biomarkers of the twins within 3 d after birth and their mothers within last month during pregnancy. The twins were assigned into different groups according to gestational age(GA), birth weight(BW), the relationship between BW and GA(appropriate for GA(AGA),small for GA(SGA) and large for GA(LGA), birth season, gender, and the mothers' age, ethnicity, pre-delivery body mass index (BMI), gestational BMI increase, number of births and chorionic properties. The correlations of bone metabolism biomarkers between the twins and their mothers were analyzed.Results:A total of 302 pairs of twins were included. The incidence of insufficient or deficient serum 25-(OH)D 3 was 97.4% among the mothers, and 87.7% among the twins. The levels of blood phosphorus ( r=0.262, P<0.001) and 25-(OH)D 3 ( r=0.239, P=0.002) in mothers were positively correlated with the twin with larger BW. No significant differences existed in 25-(OH)D 3 between genders, AGA,SGA and LGA, birth season, and mothers' age, ethnicity, pre-delivery BMI, gestational BMI increase and chorionic properties( P>0.05). 25-(OH)D 3 in the twins were positively correlated with BW and 25-(OH)D 3 of mothers before delivery ( P<0.05) and negatively correlated with number of births ( P<0.05). Conclusions:In most mothers and their newborn twins, 25-(OH)D 3 are insufficient or deficient. The levels of blood phosphorus and 25-(OH) D 3 are correlated between the newborns and their mothers. The lower the BW of the newborn, the more times the mother give birth and the lower the mother's pre-delivery 25-(OH)D 3 level, the lower the newborn's 25-(OH)D 3 level.

Tumor de células gigantes malignizado: a propósito de un caso

Introducción: La rodilla es la región anatómica donde asientan la mayor cantidad de tumores benignos y malignos que afectan el esqueleto humano, entre ellos se encuentra el tumor de células gigantes. Objetivo: Conocer un paciente con un tumor de células gigantes que sufrió transformación maligna. Caso clínico: Paciente, masculino de 28 años de edad, blanco sin antecedentes mórbidos de salud, que acudió a la consulta externa de la especialidad de Ortopedia y Traumatología por presentar desde hace dos años una tumoración dolorosa a nivel de la rodilla que en los últimos dos meses ha aumentado de tamaño. Se realizaron exámenes imagenológicos mediante radiografía simple, tomografía axial computarizada e imagen de resonancia magnética, además de toma de biopsia incisional para confirmar el diagnóstico. Al analizar los resultados de los exámenes anteriores el equipo multidisciplinario decidió la amputación de la extremidad. Conclusiones: El tumor de células gigantes es una enfermedad que se presenta con mayor frecuencia desde la tercera a quinta décadas de la vida, sus complicaciones principales son la recidiva, las metástasis pulmonares y la transformación maligna. Por lo general, los enfermos con esta última complicación necesitan de procedimientos como la amputación de la extremidad.

Introduction: The knee is the anatomical region where the largest number of benign and malignant tumors that affect the human skeleton settle, among them is the giant cell tumor. Objective: To present a patient with a giant cell tumor that underwent malignant transformation. Clinical case: A 28-year-old white male with no morbid health history, who attended the Orthopedics and Traumatology outpatient clinic for presenting a tumor accompanied by pain at the level of the right knee. It appeared two years ago, but has increased in size rapidly in the last two months. Imaging tests were performed using plain radiography, computed tomography, and magnetic resonance imaging, as well as incisional biopsy to confirm the diagnosis. After analyzing the results of the previous examinations, the multidisciplinary team decided to amputate the limb. Conclusions: The giant cell tumor is an entity that occurs most frequently from the third to fifth decades of life; its main complications are recurrence, lung metastases and malignant transformation. In general, patients with this last complication need procedures such as amputation of the limb.

Anti-Histone H3.3 G34W antibody is a sensitive and highly specific immunohistochemistry marker for the diagnosis of Giant cell tumor of bone. A validation based on analysis of 198 cases from a single centre in India

Context: The diagnosis of giant cell tumor of bone (GCTB) is difficult in small biopsies with unusual age of presentation, location, and extensive secondary changes. Most of the GCTBs harbor H3F3A G34W mutations with a subset of cases showing alternate G34V, G34R, and G34L mutations. Objectives: To analyze the expression of anti-histone H3.3G34W antibody in different cellular components of GCTB across different locations and presentations (including the unusual ones) and validate the utility of this antibody in the diagnosis of GCTB and differentiate it from the other osteoclast-like giant-cell-rich lesions. Design: Immunohistochemistry was performed using anti-histone H3.3G34W antibody in the diagnosed cases of GCTB (136 cases of GCTB from 133 patients, including two malignant GCTBs) and other giant cell-containing lesions (62 cases). The presence of unequivocal crisp nuclear staining was considered positive. Results: Immunohistochemistry revealed unequivocal nuclear positivity in the mononuclear cells in 87.3% of the cases of GCTB. Of these, most showed diffuse expression with moderate to strong intensity staining. The positive staining was restricted to the nuclei of mononuclear cells with the nuclei of osteoclastic giant cells being distinctly negative. In addition to conventional GCTBs, two cases each of multicentric and malignant GCTB showed positive staining. The other giant-cell containing lesions were distinctly negative. The present study showed a sensitivity of 87.3% with specificity and positive predictive value of 100%. Conclusion: The anti-histone G34W antibody is a highly sensitive and specific marker for the diagnosis of GCTB and differentiating it from its mimics. The positive staining is restricted to the mononuclear cell component of GCTB with sparing the osteoclastic giant cells further reiterating the fact that the mononuclear stromal cells are the true neoplastic component of GCTB.

Clinical features, diagnostic evaluation and responses to treatment in Paget's disease of bone in a center specialized in bone metabolism / Características clínicas, evaluación diagnóstica y respuestas al tratamiento de la enfermedad de Paget ósea en un centro especializado en metabolismo óseo

Abstract The epidemiology of Paget's disease of bone (PDB) has changed in the last years but there is no update data on its clinical presentation, diagnosis and management in Latin America. Our aim was to describe its clinical features, diagnostic evaluation and responses to treatment in a group of PDB patients treated between June 2012 and December 2019 in an institution specialized in bone diseases, in Buenos Aires, Argentina. The frequency of PDB (180/10 714) was 1.68%. Median age was 67 (range 39-97) years and 59.5% were women. Most patients were asymptomatic (58.6%) and had monostotic disease (54.3%). Favorable responses were obtained in all patients who were treated with zoledronate (n = 36), in 10 out of 14 treated with pamidronate, in 9 out of 10 who received intravenous ibandronate and in 12 out of 13 who received oral bisphosphonates. The response rates were not significantly different when we compared monostotic vs. polyostotic disease. Among the biochemical parameters, mean values of bone specific and total alkaline phosphatase, and C-terminal cross-linked telopeptide of type I collagen decreased significantly after treatment with bisphosphonates. It seems that our results reflect the change in PDB epidemiology towards a more indolent disease. In the future, this would probably allow physicians to use lower doses of bisphosphonates than the ones historically recommended for these patients.

Resumen La epidemiología de la en fermedad de Paget ósea (EPO) ha cambiado en los últimos años. Son necesarios datos actualizados sobre su forma de presentación clínica, diagnóstico y tratamiento en nuestra región. Nuestro objetivo fue describir las características clínicas, evaluación diagnóstica y respuestas al tratamiento de un grupo de pacientes con EPO en un centro especializado en salud ósea de Buenos Aires, Argentina. Se evaluaron todos los pacientes que fueron atendidos en nuestra institución por enfermedades óseas entre junio de 2012 y diciembre de 2019. La frecuencia de EPO (180/10 714) fue de 1.68%. La mediana de edad fue de 67 (rango 39-97) años. El 59.5% eran mujeres. La mayoría se encontraba asintomático (58.6%) y tenían enfermedad monostótica (54.3%). Se objetivaron respuestas favorables en todos los que recibieron zoledronato (n = 36), en 10 de 14 pacientes que recibieron pamidronato, en 9 de 10 que utilizaron ibandronato endovenoso y en 12 de 13 con bifosfonatos orales. Los porcentajes de respuesta no variaron significativamente entre pacientes con formas monostóticas y poliostóticas. Entre los parámetros bioquímicos, los valores de fosfatasa alcalina total y ósea y de β cross-laps disminuyeron significativamente luego del tratamiento con bifosfonatos. Nuestros resultados reflejarían un cambio en la epidemiología de la EPO hacia una forma de presentación más indolente. Esto permitiría probablemente el uso de dosis más bajas de bifosfonatos que las históricamente recomendadas para estos pacientes.

Treatment of Post - traumatic Bone Defects with infection in L ong B ones

Background: Open fractures are a challenging condition to treat because they are frequently compounded by infection and nonunion. Traditional bone defect care strategies are mostly focused on fracture union rather than infection prevention. The goal of this study is t o use the Masquelet approach to examine the outcome of a post - traumatic defect with infection in long bones. This method is a two - step process. Stage I surgery includes debridement and the placement of an antibacterial spacer in the bone defect. Stage II s urgery involved removing the spacer while preserving the induced membrane that had grown on the spacer's surface and filling the bone - gap with morselized iliac crest bone - graft within the membrane sleeve. Methods: There were 22 patients in this study (18 m ales and 4 females), all of them had infected long bone fractures with a bone defect. The average length of the bone defect was 3.5 centimetres. The duration of follow - up varied from 6 to 15 months. Results: After an average of 11.5 weeks following the fir st step of surgery, radiological union was achieved. After stage 1, no patient had any remaining infection. After radiological union, all of the patients were able to mobilise with full weight bearing and a satisfactory range of motion in the adjoining joi nts. Conclusion: With favourable outcomes, this treatment can be used on infected fractures with bone loss on a regular basis. Antibiotic cement spacers, used in conjunction with complete debridement, minimise the risk of infection. The graft is revascular ized through induced biomembrane. In most circumstances, union may be predicted; nonetheless, the length of time it takes to reach an agreement is a constraint. The technique is low - cost and does not necessitate any additional training or equipment. Despit e the fact that it is a two - stage procedure, it does not necessitate several surgeries as in traditional approaches.

Clinicopathological analysis of 105 patients with fibrous dysplasia of cranio-maxillofacial region / 北京大学学报(医学版)

OBJECTIVE@#To compare the clinicopathologic features and prognosis of the different types of fibrous dysplasia (FD) of cranio-maxillofacial region, so as to provide a new reference for clinicians to treat these patients and make prognostic judgement.@*METHODS@#Clinical records, radiographic data and pathological information of 105 patients diagnosed with FD or McCune-Albright syndrome (MAS) at the Department of Oral Pathology, Peking University Hospital of Stomatology from January 2013 to December 2020 were collected. The patients were divided into 4 groups: monostotic FDs, polyostotic FDs, MAS and a specific type called craniofacial fibrous dysplasia (CFD) limited in the craniofacial region. The clinicopathological characteristics, treatment and follow-up data of each type were analyzed.@*RESULTS@#Of all the 105 patients, 46 were males and 59 were females, with a male-to-female ratio of 1 ∶1.3. The onset age ranged from 0 to 56 years and the median age was 12 years. On the basis of different involvement conditions, 4 types were divided. The most common type was monostotic FDs (43 cases, 40.95%), including maxilla (29 cases), mandibular (12 cases) and zygoma (2 cases). 32 cases (30.48%) were diagnosed with polyostotic FDs, 7 cases (6.67%) were MAS, and 23 cases (21.90%) were CFDs confirmed by computed tomography (CT) analysis. CFD was clearly distinct from other types of FD, such as the patient gender and the serum alkaline phosphatase level in peripheral blood before operative surgery. The pathologic findings of various types FD were quite similar, whilst the predominant fibrous tissue hyperplasia could be observed in polyostotic FDs and MAS types.@*CONCLUSION@#The clinicopathologic features of FD in the cranio-maxillofacial region are different from the FD lesions in other parts of the body. The clinicopathological features of CFD are significantly different from those of monostotic and polyostotic FDs in the cranio-maxillofacial region. Therefore, the clinicians should pay attention to distinguish CFD in clinic, imaging and pathology aspects, so as to further clarify its features in clinic management and prognosis.

Analysis of clinical features in children with McCune-Albright syndrome / 中华实用儿科临床杂志

Objective:To summarize and analyze the clinical features of McCune-Albright syndrome (MAS) in 26 children, to improve the understanding of MAS diagnosis and treatment, and to achieve early clinical diagnosis of MAS.Methods:The clinical data of 26 children with MAS treated in Department of Pediatrics, Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from August 2011 to June 2021 were retrospectively analyzed.Their clinical characteristics were summarized and studied. t-test, Mann- Whitney U test, χ 2 test or Fisher′ s exact probability method was used for comparison between groups. Results:(1) Among the 26 MAS patients enrolled, there were 22 females and 4 males.The average onset age of female and male patients was (5.87±2.94) years old and (7.48±3.36) years old, respectively.(2) In female patients, there were 7 cases with the typical triad and 15 cases with the atypical triad.(3) Female patients had the first symptom of vaginal bleeding (8/22) and breast development (14/22). Among the 4 male children, 1 case had " fracture" and 3 cases " lagged behind their peers in height" at the first visit.(4) Compared with the breast development group, the vaginal bleeding group had an earlier onset age[(4.06±1.88) years old vs.(7.82±1.82) years old] ( t=5.023, P<0.001), earlier bone maturation[(1.26±0.07) vs.(1.09±0.13)] ( t=2.933, P<0.05), a greatly lowered predicted adult height[(-2.16±0.98) SDS vs.(-0.96±1.09) SDS]( t=1.352, P<0.05), a lower blood phosphorus level[(1.41±0.14) nmol/L vs.(1.67±0.24) nmol/L] ( t=1.941, P<0.05), and a significantly elevated alkaline phosphatase level[339(313, 656) U/L vs.243(205, 452) U/L] ( U=1.000, P<0.05). All patients (8 cases) in the vaginal bleeding group had fibrous dysplasia of bone.(5) Ten patients progressed to central precocious puberty (CPP). They showed an older average age of onset[(7.27±2.69)years old vs.(4.69±2.68)years old] ( U=44.000, P<0.05), significantly earlier bone maturation at diagnosis[(1.23±0.11) vs.(1.01±0.13)] ( t=1.834, P<0.05), and a lower predicted adult height[(152.00±4.62) cm vs.(162.10±6.91) cm] ( t=3.805, P<0.05), compared with those who did not progress to CPP.(6) Eleven children developed polyostotic fibrous dysplasia of bone, and most common type (8 cases) was polyostotic fibrous dysplasia of bone, primarily at lower limb bones and skulls.(7) Of the 26 children, 20 cases had scattered Café au lait pigments on the skin.The Café au lait pigmented skin lesions in 35% (7/20) cases crossed the midline. Conclusions:With complicated clinical manifestations, MAS is more common and occurs earlier in girls than boys.It is difficult to clinically diagnose MAS in boys due to the insidious onset and atypical symptoms.Female MAS patients with vaginal bleeding as the first symptom usually have an early age of onset, advanced bone age and lower predicted adult height, so they should be monitored and evaluated clinically.Vaginal bleeding is significantly associated with polyostotic fiber dysplasia of bone in MAS patients.Therefore, it is recommended that patients with vaginal bleeding should undergo a routine bone single-photon emission computed tomography scan.This helps understand the situation of occult fiber dysplasia of bone.Patients with later diagnosis and advanced bone age should be aware of the possibility of progression to CPP.

Application of plasmatrix in horizontal bone augmentation for implant placement / 口腔疾病防治

@#Tooth loss is accompanied by alveolar bone absorption or defect, resulting in insufficient bone and soft tissue. In addition to restoring the masticatory function of missing teeth, implant treatment should also needs to restore the contour and shape of the dental arch. Guided bone regeneration is a common means of bone increase. Xenogeneic granular bone substitute materials are widely used in the field of clinical bone augmentation due to their advantages of long degradation time and low immunogenicity, but other problems, such as inconvenient operation and low osteogenic activity, remain. Plasmatrix can effectively improve the effect of oral tissue regeneration and reduce the occurrence of postoperative complications, and its application in oral tissue regeneration is gradually increasing. This article first introduces the main application forms of plasmatrix in horizontal bone augmentation (mainly solid plasmatrix membrane and plasmatrix bone block), and reclassifies horizontal bone defects according to commonly used decision-making schemes in clinical bone augmentation, in other words, whether the implant can be placed in the ideal position and whether there is bone dehiscence after implantation. Type Ⅰ defects refers to the situation where the bone at the implant site can allow the insertion of an implant with ideal size, and there is no bone dehiscence around the implant, but the alveolar bone contour is not ideal; type Ⅱ defects refers to the situation that when an ideal size implant is placed at the implant site determined by the future prosthesis position, there will be bones on three sides of the implant, but there is bone dehiscence in the buccal bone wall (the length of bone dehiscence is less than 50% of the implant length); type Ⅲ defects refers to the situation where the bone volume at the implant site is not enough to for the placement of the ideal size implant at the ideal position, and bone grafting is required to restore the bone volume before the implant placement. The application of plasmatrix in different types of bone defects is then described. In type Ⅰ bone defects, the solid plasmatrix membrane is used instead of the collagen membrane; in type Ⅱ bone defects, the bone defect around the implant is filled by plasmatrix bone block and then covered with collagen membrane and solid plasmatrix membrane; and in type Ⅲ bone defects, plasmatrix bone block is used to replace autogenous bone block to fill the defect area, and titanium screws are used for fixation. The defect is then covered with a collagen membrane and a solid plasmatrix membrane. This article aims to provide oral clinicians with a comprehensive understanding of plasmatrix and simplify the guidelines for bone regeneration operations.

Single-cell transcriptome reveals features of immune environment and mechanisms of immune escape in giant cell tumor of bone / 中华骨科杂志

Objective:This study aims to reveal the special immune infiltrating environment and possible immune escape mechanism of giant cell tumor of bone through single-cell sequencing data.Methods:The fresh samples obtained from 4 patients with primary giant cell tumor of bone from January 2018 to December 2021 were collected, and single-cell transcriptome sequencing was performed on the 10X platform to explore the characteristics and immune environment of giant cell tumor of bone by using t-distributed stochastic neighbor embedding ( t-SNE). The main cell types and signal pathways of immune cell regulation and function in giant cell tumor of bone were observed by cell communication analysis. Results:Cell clustering, the definition of basic cell types, the classification of immune cells, and the mutual regulatory relationship between cell types were analyzed for 35 643 single-cell data from 4 giant cell tumor samples of bone. It was found that giant cell tumor of bone was composed of 9 basic cell types, in which the immune cells were mainly CD8 + T cells (51%) and the non-immune cells were mainly fibroblast like spindle stromal cells (74%). The immune infiltration of giant cell tumor of bone is dominated by cytotoxic CD8 + T cells and lacks exhausted CD8 + T cells. CD4 + T cells are characterized by high expression of immune checkpoint genes CTLA4 and TIGIT. In giant cell tumor of bone, immune cells mainly act on multinucleated osteoclast like giant cells through PARs and CCL signaling pathways, but not stromal cells. Conclusion:This study defined the main cell types of giant cell tumor of bone through single cell sequencing data, and further revealed the composition characteristics of its immune infiltration, and found that the target of its immune cells was mainly multinuclear osteoclast like giant cells, which provided effective information for further understanding the occurrence and development of giant cell tumor of bone.

An anterolateral thigh perforator chimeric flap combined with calcium sulfate impregnated with vancomycin for treatment of chronic fracture-related infection complicated with extensive soft-tissue defects / 中华创伤骨科杂志

Objective:To investigate the efficacy of an anterolateral femoral chimeric perforator flap combined with vancomycin-loaded calcium sulfate in the treatment of chronic infection after internal fixation of calf fracture with soft tissue defects.Methods:Retrospectively analyzed were the data of 16 patients with chronic infection combined with extensive soft tissue defects after internal fixation of calf fracture who had been admitted to Department of Orthopedics, Shenzhen Hospital Affiliated to Peking University from September 2008 to November 2020. There were 11 males and 5 females, aged from 16 to 62 years (average, 37 years). Infection sites: the upper tibia in 4 cases, the middle and lower tibia in 10 cases, and the middle fibula in 2 cases. According to the Cierny-Mader classification, all patients were anatomical type III and by the host classification, there were 14 cases of type B and 2 cases of type C type. The areas of soft tissue defects ranged from 6 cm × 4 cm to 23 cm × 14 cm. All patients were treated by transplantation of an anterolateral thigh chimeric perforator flap combined with vancomycin-loaded calcium sulfate therapy. At the last follow-up, the curative efficacy was evaluated according to the Paley fracture union scoring.Results:All patients were followed up for 8 to 24 months (mean, 16 months). Complete flap survival was achieved in 15 flaps and partial survival in one. According to the Paley fracture union scoring at the last follow-up, the curative efficacy was evaluated as excellent in 15 cases and as good in one. Both the grafted artificial bone and the tibia and fibula achieved bone union after 6 to 12 months (mean, 8.9 months). Infection with chronic sinus tract pus recurred in one case at post-operative one year. After re-debridement, the infection was controlled and the wound healed. The plate internal fixation was replaced by the unilateral or annular external fixator in 14 patients and retained in 2 patients. The lengths of the bone defects averaged 2.4 cm and the time for the external fixation 10.5 months (from 8 to 14 months).Conclusion:In the treatment of chronic infection after internal fixation of calf fracture with extensive soft tissue defects, the efficacy of an anterolateral femoral chimeric perforator flap combined with vancomycin-loaded calcium sulfate is satisfactory, because the flap can fully cover the bone and soft tissue defects while the vancomycin-loaded calcium sulfate can effectively control the infection.

Clinical analysis of 8 cases of desmoplastic fibroma of the jaw / 口腔疾病防治

Objective @#To improve the dentist's understanding of desmoplastic fibroma of the jaw, we investigated the clinical manifestations, pathological features, treatment and prognosis of this disease.@*Methods@#The clinical data of 8 patients with desmoplastic fibroma of the jaw who were admitted to Nanjing Stomatological Hospital from 2011 to 2021 were retrospectively reviewed.@* Results @#The male-female ratio in this group was 3:1, the age of first onset was 32.13±15.00, and the lesions were mainly in the mandible. Histologically, the lesions was composed of mildly atypical fibroblasts and a large number of collagen fibers. The positive rates of Vimentin, α-SMA and β-catenin in the cytoplasm were 100%, 62.5% and 62.5%, respectively. The Ki-67 level in the initial patients was lower than 5%, and the S-100 protein level was 100% negative. The imaging manifestations were single-room or multichamber light-transmitting lesions with clear or irregular boundaries, with or without peripheral sclerosis. Five patients were treated with curettage for the first time; among them, two patients relapsed with poor prognosis. Three patients underwent extended resection, and all had no recurrence.@*Conclusions @# The clinical and imaging features of desmoplastic fibroma of the jaw are not specific. We mainly rely on histopathology to diagnose the disease. It has a high recurrence rate after surgery. At present, the best treatment is to extend surgical resection. Local curettage is easy to relapse and has a poor prognosis.

Application of plasmatrix in vertical bone augmentation for implant placement / 口腔疾病防治

@#Vertical bone augmentation surgery still faces considerable challenges in clinical practice due to various problems, such as difficulty in restoring the ideal alveolar bone height and biological complications, and because it is highly technically sensitive. Plasmatrix is derived from patients’ own blood, and it can effectively promote the vascularization of the regenerated area, recruit stem cells, and reduce inflammation when used in vertical bone augmentation. Based on studies published worldwide, this article first divides vertical bone augmentation into 3 categories according to the height of the expected alveolar ridge, namely, type Ⅰ, the required vertical bone gain is less than 4 mm; type Ⅱ, the required vertical bone gain is between 4-8 mm; and type Ⅲ, the required vertical bone gain is greater than 8 mm. In the type Ⅰ vertical bone augmentation, the plasmatrix bone block is directly placed in the defect area and covered with the plasmatrix membrane before tension-free suturing; in the type Ⅱ vertical bone augmentation, the plasmatrix bone block should be placed in the defect area and fixed with titanium nails and then covered with an absorbable collagen membrane and plasmatrix membrane with a tension-free suture; in the type Ⅲ vertical bone augmentation, additional active ingredients (such as bone morphogenetic protein, autologous bone, etc.) should be added to the plasmatrix bone block and strong fixation (such as titanium nails) should be used. Absorbable collagen and plasmatrix membranes should be used to cover the surface of the bone block, and the flap should be sutured. According to different types of vertical bone augmentation categories, the above methods optimize the vertical bone augmentation effect. This article aims to provide a reference and guidelines for oral clinicians to fully understand plasmatrix and simplify the classification and operation of vertical bone augmentation.

Epidemiological and Clinical Characteristics of Fibrous Dysplasia of Bone / 肿瘤防治研究

Objective To describe the epidemiological and clinical characteristics of fibrous dysplasia of bone admitted to a single center in the past 30 years. Methods We analyzed the clinical features of 744 patients with bone fibrous dysplasia diagnosed by pathology, including age, gender, disease location, monostotic or polyostotic lesions, pathological fracture and malignant transformation. Results There were 1183 lesions in 744 patients. The mean age at admission was 31.1±13.5 years old. The ratio of male to female was close to 1:1. The most common site was the lower extremities (916(77.4%)), followed by the upper extremities (106(9.0%)). The most common sites of lower extremities were the femur (645(54.5%)) and the tibia (224(18.9%)). Polyostotic cases accounted for 25.4%, and monostotic cases accounted for 74.6%. Pathological fracture occurred in 163 (13.8%) patients. There were 6 (0.8%) patients with malignant transformation. The mean age was 40.5 years old. The mean time of malignant transformation was 7.7 years. Conclusion Fibrous dysplasia of bone is a rare group of benign bone tumors, with typical epidemiological and clinical features.

Is periostin useful as a biomarker for fibrous dysplasia? / ¿Es útil periostina como biomarcador de displasia fibrosa?

Fibrous dysplasia (FD) is an infrequent non-hereditary bone disease caused by a somatic mutation of the GNAS gene. Periostin is a novel marker that increases during tissue healing and fibrous or inflammatory diseases. We conducted an exploratory case-control study to evaluate sensitivity of periostin as a biomarker of FD. The study comprised 15 patients with FD, and healthy age- and sex-matched subjects (controls). Serum periostin levels were assessed and comparisons were established between FD patients and controls, and between patients with the monostotic and the polyostotic form of FD. No statistically significant differences in serum periostin levels were observed between the cohort of FD patients studied here and the control group (FD: 51.1±10ng/ml vs. control: 44.2±15ng/ml; p=0.15), or between the clinical forms of FD (polyostotic: 51.8±9.1ng/ml vs. monostotic: 49.6±13 ng/ml; p=0.66). A sub-analysis performed to compare serum levels of periostin in FD patients with and without a history of fractures showed no statistically significant differences [fracture patients (n=4): 41.2±17ng/ml vs. non-fracture patients (n=11): 49.9±11 ng/ml; p=0.47].Lastly, sensitivity of periostin as a biomarker of FD was analyzed, and was found to have low sensitivity to estimate disease activity [ROC curve; cut-off points: 39.625(0.867-0.467)]. To conclude, in the cohort of FD patients studied here, periostin serum levels did not differ significantly from those of the control group or between the two forms of the disease, and showed low sensitivity as a biomarker of the disease. (AU)

La displasia fibrosa (DF) es una enfermedad infrecuente del hueso, no hereditaria producida por una mutación somática del gen GNAS. Periostina (Postn) es un novedoso marcador, cuyos niveles séricos se encuentran elevados en los procesos de reparación tisular, enfermedades fibrosas o inflamatorias. Llevamos a cabo un estudio exploratorio caso-control para evaluar la sensibilidad de Postn como biomarcador de DF. Se incluyeron en el estudio 15 pacientes con DF apareados por edad y género con sujetos sanos (controles) en los cuales se evaluó los niveles séricos de Postn en pacientes con DF y controles y según forma de presentación clínica. No observamos diferencias estadísticamente significativas en los niveles séricos de Postn y el grupo control (DF: 51.1±10ng/ml vs. control: 44.2±15ng/ml; p=0.15) como así tampoco por forma clínica de DF (poliostótica: 51.8±9.1ng/ml vs. monos-tótica: 49.6±13 ng/ml; p=0.66). Posteriormente realizamos un sub-análisis para evaluar los niveles séricos de Postn en los pacientes con DF y antecedentes de fracturas no observan-do diferencias estadísticamente significativas [fracturados (n=4): 41.2±17ng/ml vs. no frac-turados (n=11): 49.9±11 ng/ml; p=0.47]. Por último analizamos la sensibilidad Postn como biomarcador de DF, mostrando este poseer escasa sensibilidad para estimar actividad de la enfermedad [curva ROC; puntos de corte: 39.625 (0.867-0.467)]. En conclusión, los ni-veles séricos de Postn en nuestra cohorte de pacientes con DF no mostraron diferencias estadísticamente significativas comparadas con el grupo control o por forma clínica de presentación, mostrando una baja sensibilidad como biomarcador de enfermedad. (AU)

Long-term use of denosumab in giant cell tumors and vertebral aneurysmal bone cysts / Uso prolongado de denosumab no tumor de células gigantes e cistos ósseos aneurismáticos vertebrais / Uso prolongado de denosumab en tumor de células gigantes y quistes óseos aneurismáticos vertebrales

ABSTRACT Introduction: Denosumab is a human monoclonal antibody that binds to the receptor activator of nuclear factor kB (RANKL), it is used in the treatment of Osteoporosis. The Giant Cell Tumor (GCT) and the Aneurysmal Bone Cyst (ABC) use the same RANKL, and for this reason this drug began to be used for its treatment. There is consensus on the use, dose-time and 12-month duration for Denosumab treatment of GCT. Not so for ABC. In unresectable, disabling or recurrent tumors, its use could be for life. The adverse events of the habitual use of the drug are known, but it is not known if these increase with time. The objective of the present work is to identify the possible adverse events of treatment with Denosumab for more than 12 months. Material and Method: Series of cases with a diagnosis of GCT or ABC in spine, treated with Denosumab for more than 12 months. Adverse events are: arthralgia, fatigue, spinal pain, pain in extremities, headache, hypokalaemia, hypocalcemia, osteonecrosis of the jaw, malignant transformation, pathological fractures. Results: Eight patients, 6 TCG and 2 ABC, with a mean age at diagnosis of 25,6 years; presenting a mean treatment of 4.18 years (range 1.7 - 8.7). Of 6 operated patients, 4 had recurrence (2 to 36 months after surgery). One patient had to suspend treatment due to necrosis of the jaw, another hypocalcemia, both returned to treatment when stabilized. Conclusions: A minor adverse event (hypocalcemia) and a major adverse event (jaw bone necrosis) were observed. Level of Evidence IV; Original.

RESUMO Introdução: O denosumab é um anticorpo monoclonal humano que se liga ao receptor ativador do fator nuclear kB (RANKL), sendo utilizado no tratamento da Osteoporose. O Tumor de Células Gigantes (TCG) e o Cisto Ósseo Aneurismático (CAO) utilizam o mesmo RANKL, por isso esse medicamento passou a ser utilizado para seu tratamento. Há consenso sobre o uso, o tempo de dosagem e a duração de 12 meses para o tratamento com Denosumabe de TCG. Não é assim para CAO. Em tumores irressecáveis, incapacitantes ou recorrentes, seu uso pode ser vitalício. Os eventos adversos do uso habitual do medicamento são conhecidos, mas não se sabe se aumentam com o tempo. O objetivo do presente trabalho é identificar os possíveis eventos adversos do tratamento com Denosumabe por mais de 12 meses. Material e Método: Série de casos com diagnóstico de TCG ou CAO na coluna, tratados com Denosumabe por mais de 12 meses. Os eventos adversos são: artralgia, fadiga, dor na coluna, dor nas extremidades, cefaleia, hipocalemia, hipocalcemia, osteonecrose da mandíbula, transformação maligna, fraturas patológicas. Resultados: Oito pacientes, 6 TCG e 2 LRA, com média de idade ao diagnóstico de 25,6 anos; apresentando um tratamento médio de 4,18 anos (variação 1,7 - 8,7). Dos 6 pacientes operados, 4 tiveram recorrência (2 a 36 meses após a cirurgia). Um paciente teve que suspender o tratamento por necrose da mandíbula, outro hipocalcemia, ambos voltaram ao tratamento quando estabilizados. Conclusões: Um evento adverso menor (hipocalcemia) e um evento adverso maior (necrose óssea da mandíbula) foram observados. Nível de Evidência IV; Original.

RESUMEN Introducción: El Denosumab es un anticuerpo humano monoclonal que se une al receptor activador del factor nuclear kB (RANKL), se lo utiliza en el tratamiento de Osteoporosis. El Tumor de Células Gigantes (TCG) y el Quiste Óseo Aneurismático (QOA), utilizan los mismos RANKL, y por ello se comenzó a utilizar esta droga para su tratamiento. Existe consenso en la utilización, dosis-tiempo y 12 meses de duración para el tratamiento con Denosumab del TCG. No así para el QOA. En tumores irresecables, incapacitantes o con recidiva, su uso podría ser de por vida. Se conocen los eventos adversos de la utilización habitual de la droga, pero no se sabe si estas aumentan con relación al tiempo. El objetivo del presente trabajo, es identificar los posibles eventos adversos del tratamiento con Denosumab por más de 12 meses. Material y Método: Serie de casos con diagnóstico de TCG o QOA de columna, tratados con Denosumab por más de 12 meses. Los eventos adversos son: artralgias, fatiga, raquialgia, dolor en extremidades, cefalea, hipopotasemia, hipocalcemia, osteonecrosis de mandíbula, transformación maligna, fractura patológica. Resultados: Ocho pacientes, 6 TCG y 2 QOA, con promedio de edad al diagnóstico de 25,6 años; presentando una media de tratamiento de 4.18 años (rango 1,7 - 8,7). De 6 pacientes operados, 4 presentaron recidiva (2 a 36 meses después de la cirugía). Un paciente se debió suspender el tratamiento al presentar una necrosis de mandíbula, otro hipocalcemia, ambos retornaron al tratamiento al estabilizarse. Conclusiones: Se observa un evento adverso menor (hipocalcemia) y un evento adverso mayor (necrosis ósea de mandíbula). Nivel de Evidencia IV; Original.

Denosumab como tratamiento neoadyuvante del tumor de células gigantes del hueso. Indicaciones, resultados y efectos adversos / Denosumab as a neoadjuvant treatment for giant cell tumor of bone. Indications, results and side effects

Resumen El tumor de células gigantes óseo es una neoplasia de agresividad local intermedia, que raramente metastatiza. En los últimos años el denosumab, anticuerpo monoclonal humano, surgió como una alternativa de tratamiento para esta enfermedad, al bloquear el comportamiento lítico tumoral. El objetivo de este trabajo fue determinar sus indicaciones y efectos adversos, analizando también los resultados oncológicos, y las tasas de recurrencia local en pacientes con diagnóstico de tumor de células gigantes óseo que recibieron denosumab como tratamiento neoadyuvante. Entre 2010 y 2018 se analizaron 80 pacientes con tumor de células gigantes, de los cuales 14 recibieron denosumab como tratamiento neoadyuvante. El seguimiento mínimo fue 12 meses. En 8 pacientes se trató de un tumor primario, mientras que 6 fueron pacientes con recidiva tumoral. En todos los casos se evidenció una mejoría clínica. Trece presentaron cambios radiográficos, y 11 respuesta histológica completa. En 6 de 14 pacientes se evidenció una recurrencia local y en 7 se identificó al menos un efecto adverso relacionado con el denosumab (incluyendo una malignización tumoral). A pesar de ser una herramienta útil para el tratamiento del tumor de células gigantes, el uso de denosumab está asociado a mayor tasa de recurrencias locales y no está exento de efectos adversos.

Abstract Giant cell tumor of bone is an intermediate, locally aggressive and rarely metastasiz ing, primary bone neoplasia. In recent years denosumab emerged as a treatment alternative for this pathology. The objective of this work was to analyze its indications as well as the clinical outcomes, side effects and local recurrence rates in patients diagnosed with giant cell tumor of bone, who received denosumab as neoadjuvant treatment. Between 2010 and 2018, 80 patients with giant cell tumor were analyzed, of whom 14 received deno sumab as a neoadjuvant treatment. The minimum follow-up was 12 months. In 8 patients it was a primary tumor, while 6 showed tumor recurrence. In all cases, clinical improvement was evident. Thirteen patients presented radiographic changes, and 11 showed complete histological response. A local recurrence was evidenced in 6 of 14 patients, and at least one adverse effect related to denosumab (including tumor malignancy) was identified in 7. Despite being a useful tool for treating giant cell tumor, the use of denosumab is associated with a higher rate of local recurrences and is not free of adverse effects.

Rehabilitación de un paciente con fractura femoral distal izquierda con pérdida de sustancia ósea, fractura patelar y tibial izquierda: a propósito de un caso / Rehabilitation of a patient with a left distal femoral fracture with loss of bone substance, a left patellar and tibial fracture: about a case

La rehabilitación de un paciente con fractura es progresivos y secuenciales para la mejora del foco de fractura, en especial en este tipo de fracturas con pérdida de sustancia ósea ya que suelen ser agresivas y de difícil resolución, por tanto, el tratamiento ortopédico es cuidadoso y complejo como la recuperación es prolongada sujeta a varios pasos según la progresión del paciente. El objetivo de este artículo es la de describir la secuencia de pasos en la rehabilitación de este tipo de fracturas, ya que no hay un manual claro para el manejo en rehabilitación de casos similares. El seguimiento y recuperación de este caso dura 8 meses dividida en 3 etapas de rehabilitación en un total de 122 sesiones, teniendo 4 evaluaciones en base a los tres parámetros de evaluación de ingreso: dolor, movimiento, postura y fuerza muscular, mejorando progresivamente estos aspectos.

The rehabilitation of a fractured patient is progressive and sequential for the improvement of the fracture focus, especially in this type of fractures with loss of bone substance since they are usually aggressive and difficult to resolve, so orthopedic treatment is careful and complex. as the recovery is prolonged subject to several steps depending on the patient's progression. The objective of this article is to describe the sequence of steps in the rehabilitation of this type of fractures, since there is no clear manual for the management in rehabilitation of similar cases. The follow-up and recovery of this case lasts 8 months divided into 3 stages of rehabilitation in a total of 122 sessions, having 4 evaluations based on the three parameters of admission assessment: pain, movement, posture and muscular strength, progressively improving these aspects.