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1.
Clin Orthop Relat Res ; 481(11): 2140-2153, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37768856

RESUMO

BACKGROUND: Liposarcoma is the most commonly diagnosed subtype of soft tissue sarcoma. As these tumors often arise near vital organs and neurovascular structures, complete resection can be challenging; consequently, recurrence rates are high. Additionally, available chemotherapeutic agents have shown limited benefit and substantial toxicities. There is, therefore, a clear and unmet need for novel therapeutics for liposarcoma. Discoidin domain receptor tyrosine kinase 1 (DDR1) is involved in adhesion, proliferation, differentiation, migration, and metastasis in several cancers. However, the expression and clinical importance of DDR1 in liposarcoma are unknown. QUESTIONS/PURPOSES: The purposes of this study were to assess (1) the expression, (2) the association between DDR1 and survival, and (3) the functional roles of DDR1 in liposarcoma. METHODS: The correlation between DDR1 expression in tumor tissues and clinicopathological features and survival was assessed via immunohistochemical staining of a liposarcoma tissue microarray. It contained 53 samples from 42 patients with liposarcoma and 11 patients with lipoma. The association between DDR1 and survival in liposarcoma was analyzed by Kaplan-Meier plots and log-rank tests. The DDR1 knockout liposarcoma cell lines were generated by CRISPR-Cas9 technology. The DDR1-specific and highly selective DDR1 inhibitor 7RH was applied to determine the impact of DDR1 expression on liposarcoma cell growth and proliferation. In addition, the effect of DDR1 inhibition on liposarcoma growth was further accessed in a three-dimensional cell culture model to mimic DDR1 effects in vivo. RESULTS: The results demonstrate elevated expression of DDR1 in all liposarcoma subtypes relative to benign lipomas. Specifically, high DDR1 expression was seen in 55% (23 of 42) of liposarcomas and no benign lipomas. However, DDR1 expression was not found to be associated with poor survival in patients with liposarcoma. DDR1 knockout or treatment of 7RH showed decreased liposarcoma cell growth and proliferation. CONCLUSION: DDR1 is aberrantly expressed in liposarcoma, and it contributes to several markers of oncogenesis in these tumors. CLINICAL RELEVANCE: This work supports DDR1 as a promising therapeutic target in liposarcoma.


Assuntos
Lipoma , Lipossarcoma , Humanos , Receptor com Domínio Discoidina 1/genética , Receptor com Domínio Discoidina 1/metabolismo , Proliferação de Células , Diferenciação Celular , Lipossarcoma/tratamento farmacológico , Lipossarcoma/genética
2.
Cell Tissue Bank ; 24(4): 693-703, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36854877

RESUMO

BACKGROUND: We developed a novel, injectable and decellularized human peripheral nerve-based scaffold, named Micronized Human Neural Tissue (hMINT), designed to be used as a supportive matrix for stem cell transplantation in the context of spinal cord injury (SCI). MATERIALS AND METHODS: Human donated sciatic nerves were micronized at liquid nitrogen temperature prior to decellularization using 3 different procedures of various harshness. hMINT were characterized in terms of particle size, DNA, sulfated glycosaminoglycans (sGAG) and growth factors content. To test the biocompatibility and bioactivity of the various preparations, we used a type of mesenchymal stromal cells (MSCs), termed MIAMI cells, which were placed in contact with hMINT to monitor cell attachment by confocal microscopy and gene expression by RT-qPCR in vitro. RESULTS: The content of DNA, sGAG and growth factors left in the product after processing was highly dependent on the decellularization procedure used. We demonstrated that hMINT are biocompatible and promoted the attachment and long-term survival of MIAMI cells in vitro. Finally, combination with hMINT increased MIAMI cells mRNA expression of pro-survival and anti-inflammatory factors. Importantly, the strongest bioactivity on MIAMI cells was observed with the hMINT decellularized using the mildest decellularization procedure, therefore emphasizing the importance of achieving an adequate decellularization without losing the hMINT's bioactivity. PERSPECTIVES AND CLINICAL SIGNIFICANCE: The capacity of hMINT/stem cells to facilitate protection of injured neural tissue, promote axon re-growth and improve functional recovery will be tested in an animal model of SCI and other neurodegenerative disorders in the future.


Assuntos
Células-Tronco Mesenquimais , Alicerces Teciduais , Animais , Humanos , Engenharia Tecidual/métodos , Matriz Extracelular/metabolismo , DNA
3.
Pediatr Radiol ; 52(9): 1601-1614, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941207

RESUMO

Aneurysmal bone cyst (ABC) is a benign but locally aggressive lesion that predominantly affects children and young adults. ABC, which accounts for approximately 70% of the cases, is now recognized to be a true neoplasm, whereas ABC-like changes associated to other bone neoplasms (also referred in the literature as secondary ABC) accounts for the remaining 30%. The solid variant of ABC is also considered a true neoplasm but is rare. ABC can involve any bone in the body, and although it has a metaphyseal preference, it can involve any part of a bone and soft tissues. As with any bone tumor, the initial evaluation of ABCs should be done with radiographs followed by magnetic resonance imaging or less frequently computed tomography for further characterization. The imaging appearance of ABC is variable; however, a lytic and expansile lesion with fluid-fluid levels is the most common presentation. The main differential diagnosis of an ABC in the pediatric population is unicameral bone cyst (UBC) and telangiectatic osteosarcoma, therefore a biopsy is recommended before treatment. The therapeutic options of ABC range from curettage with or without adjuncts such as phenol, liquid nitrogen, argon laser and bone grafting or bone substitutes to more recently employed alternatives such as image-guided sclerotherapy with various sclerosing agents and monoclonal antibodies (e.g., Denosumab).


Assuntos
Cistos Ósseos Aneurismáticos , Cistos Ósseos , Neoplasias Ósseas , Osteossarcoma , Cistos Ósseos/diagnóstico por imagem , Cistos Ósseos/terapia , Cistos Ósseos Aneurismáticos/diagnóstico por imagem , Cistos Ósseos Aneurismáticos/terapia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Criança , Humanos , Osteossarcoma/patologia , Tomografia Computadorizada por Raios X , Adulto Jovem
4.
Clin Orthop Relat Res ; 478(11): 2573-2581, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32469487

RESUMO

BACKGROUND: Aseptic loosening is one of the most common causes of revision of distal femoral endoprostheses and is considered a mid- to long-term complication. There are not many reports of 10-year survivorship free from aseptic loosening and all-cause survivorship in cemented stems. To our knowledge, there are no reports on radiographic features that are associated with aseptic loosening of these implants. QUESTIONS/PURPOSES: (1) What is the 5- and 10-year survivorship free from aseptic loosening in patients undergoing reconstruction with a cemented distal femoral endoprosthesis after a tumor resection? (2) What is the all-cause 5- and 10-year survivorship at in these patients? (3) What radiographic features are associated with aseptic loosening at long-term follow-up? METHODS: We performed a multicenter retrospective study reviewing aseptic loosening in cemented prostheses to determine radiographic features associated with long-term implant survivorship. Patients who underwent a cemented distal femoral reconstruction with a modular endoprosthesis after resection of a musculoskeletal tumor between 1997 and 2017 were reviewed. A total of 246 patients were identified from five institutions and met initial inclusion criteria. Of those, 21% (51) were lost to follow-up before 2 years, leaving 195 patients available for us to evaluate and analyze the survivorship and radiologic features associated with long-term implant survival. The mean (range) follow-up was 78 months (22 to 257). At the time of this analysis, 69% (135 of 195) of the patients were alive. Osteosarcoma was the most common diagnosis in 43% of patients (83 of 195), followed by metastatic carcinoma 13% (25 of 195). Fifty-six percent (110 of 195) of patients received chemotherapy; 15% (30 of 195) had radiation therapy. Aseptic loosening was diagnosed radiographically and was defined as a circumferential radiolucent line on all views, or subsidence around the stem in the absence of infection. We present 5- and 10-year Kaplan-Meier survivorship free from aseptic loosening, 5- and 10-year all-cause survivorship, and a qualitative assessment of radiographic features potentially associated with aseptic loosening (including the junctional radiolucent area, and cortical expansion remodeling). The junctional radiolucent area was defined as a radiolucent area of the bone starting at the bone-endoprosthesis junction to the tip of the femoral stem, and cortical expansion remodeling was defined as an increased cortical thickness at the stem tip. Although we wished to statistically analyze radiographic factors potentially associated with aseptic loosening, we did not have enough clinical material to do so (only nine patients developed loosening). Instead, we will report a few preliminary qualitative observations, which necessarily are preliminary, and which will need to be confirmed or refuted by future studies. We urge caution in interpreting these findings because of the very small numbers involved. RESULTS: Kaplan-Meier survivorship free from aseptic loosening of the femoral component at 5 and 10 years were 95% (95% CI 89 to 98) and 93% (95% CI 86 to 97), respectively. Kaplan-Meier survivorship free from revision for any cause at 5 and 10 years were 74% (95% CI 65 to 79) and 64% (95% CI 49 to 70), respectively. Although the numbers were too small to analyze statistically, all patients with aseptic loosening had a junctional radiolucent area more than 20% of the total length of the stem without cortical expansion remodeling at the stem tip. No aseptic loosening was observed if there was cortical ex remodeling, a junctional radiolucent area less than 20%, or curved stems that were 13 mm or greater in diameter. The numbers of patients with aseptic loosening in this series were too small to analyze statistically. CONCLUSIONS: Cemented distal femoral endoprostheses have a relatively low rate of aseptic loosening and acceptable projected first-decade survivorship. The presence of a radiolucent area more than 20% without cortical expansion remodeling at the stem tip may lead to aseptic loosening in patients with these implants. Close radiographic surveillance and revision surgery may be considered for progressive lucencies and clinical symptoms of pain. If revision is contemplated, we recommend using larger diameter curved cemented stems. These are preliminary and provisional observations based on a low number of patients with aseptic loosening; future studies with greater numbers of patients are needed to validate or refute these findings. LEVEL OF EVIDENCE: Level III, therapeutic study.


Assuntos
Cimentos Ósseos , Neoplasias Femorais/diagnóstico por imagem , Neoplasias Femorais/cirurgia , Prótese Articular , Procedimentos de Cirurgia Plástica , Falha de Prótese , Reoperação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
7.
J Foot Ankle Surg ; 56(1): 129-134, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27449524

RESUMO

Peripheral nerve sheath tumors (benign and malignant) usually arise in the soft tissues and are unusual in bone. Intraosseous peripheral nerve sheath tumors are usually benign and constitute approximately 0.2% of all bone tumors. Intraosseous malignant peripheral nerve sheath tumors (MPNSTs) are uncommon and usually result from secondary invasion. Only a few cases of primary intraosseous MPNSTs have been reported in published studies, and these were localized mostly in the mandible (approximately 50%) or maxilla, spine, and, occasionally, in the appendicular skeleton. To the best of our knowledge, we report the first case of primary intraosseous MPNST involving a midtarsal bone (medial cuneiform). The patient was a 62-year-old female who presented with pain and tenderness but without swelling. Imaging revealed nonspecific findings, and the preoperative computed tomography-guided biopsy findings were consistent with MPNST. The patient was treated with neoadjuvant radiotherapy, followed by wide local excision and allograft reconstruction. At the final follow-up examination (24 months), the graft had been incorporated without evidence of local recurrence or distant disease. The patient with primary intraosseous MPNST of the medial cuneiform described in the present report presented with nonspecific clinical and radiologic findings. Thus, a high index of suspicion and histopathologic examination, including immunohistochemistry, are necessary for an accurate diagnosis.


Assuntos
Artrodese/métodos , Neoplasias Ósseas/cirurgia , Transplante Ósseo/métodos , Imagem Multimodal/métodos , Neoplasias de Bainha Neural/cirurgia , Ossos do Tarso/cirurgia , Biópsia por Agulha , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Terapia Combinada , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Neoplasias de Bainha Neural/diagnóstico por imagem , Neoplasias de Bainha Neural/patologia , Tomografia por Emissão de Pósitrons/métodos , Radiografia/métodos , Doenças Raras , Medição de Risco , Ossos do Tarso/patologia , Resultado do Tratamento
8.
AJR Am J Roentgenol ; 207(1): 150-6, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27070373

RESUMO

OBJECTIVE: Lodwick's well-established grading system of lytic bone lesions has been widely used in predicting growth rate for lytic bone lesions. We applied a Modified Lodwick-Madewell Grading System as an alternative means to categorize lytic bone tumors into those with low, moderate, and high risks of malignancy. MATERIALS AND METHODS: A retrospective review of the radiographs of 183 bone lesions was performed. Cases were selected to include a broad range of benign and malignant tumors. Readers applied our Modified Lodwick-Madewell Grading System, and consensus was reached in all cases. This modified system consists of grade I, which is composed of grades IA and IB as listed in the Lodwick system; grade II, which is grade IC in the Lodwick system; and grade III, which is composed of IIIA (changing margination), IIB (moth-eaten and permeative patterns), and IIIC (radiographically occult). Grading was correlated with the final diagnosis. RESULTS: Of the 183 tumors, 81 were classified as grade I, 54 as grade II, and 48 as grade III. When correlating grade with pathology, we found that 76 of 81 (94%) grade I lesions were benign and 39 of 48 grade III lesions (81%) were malignant. A nearly equal number of grade II lesions proved to be benign (29/54; 54%) and malignant (28/54; 53%). CONCLUSION: By expanding Lodwick's grading system to include two additional patterns of disease described by Madewell and colleagues (changing margination and radiographically occult) and by reclassifying them into three distinct grades, we propose a modified system-the Modified Lodwick-Madewell Grading System. Application of this system shows correlation of tumor grade with tumor biologic activity and with risk of malignancy: Grade I lesions are usually benign, grade II lesions carry moderate risk of malignancy, and grade III lesions possess a high likelihood of malignancy.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Gradação de Tumores/métodos , Adolescente , Adulto , Idoso , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Skeletal Radiol ; 45(10): 1365-73, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27502790

RESUMO

OBJECTIVE: Imaging criteria for measuring the response of desmoid fibromatosis to systemic therapy are not well established. We evaluated a series of patients with desmoids who underwent systemic therapy to document magnetic resonance imaging (MRI) features associated with a positive clinical response. MATERIALS AND METHODS: This Institutional Review Board-approved retrospective study included 23 patients (mean age 40.5) with 29 extra-abdominal tumors. Therapeutic regimens included cytotoxic chemotherapy (n = 19), targeted therapy (n = 3), and nonsteroid anti-inflammatory drugs (NSAIDS; n = 1). Clinical effects were categorized as progressive disease, stable, or partial response. Maximum tumor dimension (Dmax), approximate tumor volume (VTumor), and quantitative tumor T2 hyperintensity and contrast enhancement (relative to muscle) for pre- and post-treatment MRIs were compared. RESULTS: Three lesions progressed, 5 lesions were stable, whereas 21 showed a clinical response. Dmax decreased more in responders (mean -11.0 %) than in stable/progressive lesions (mean -3.6 and 0 % respectively, p = 0.28, ANOVA); by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) 27 out of 29 lesions were "stable," including the 3 progressive lesions. In responders, VTumor change averaged -29.4 %, but -19.2 % and +32.5 % in stable and progressive lesions respectively (p = 0.002, ANOVA); by 3D criteria 14 out of 29 lesions showed a partial response. T2 hyperintensity decreased by 50-54 % in partial response/stable disease, but only by 10 % in progressive lesions (p = 0.049, t test). Changes in contrast enhancement ranged from -23 % to 0 %, but were not statistically significant among response groups (p = 0.37). Change in T2 hyperintensity showed a positive correlation with volumetric change (r = 0.40). CONCLUSION: Decreases in volume and T2 hyperintensity reflect the positive response of desmoid fibromatosis to systemic therapy; RECIST 1.1 criteria are not sensitive to clinically determined tumor response.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Antineoplásicos/administração & dosagem , Monitoramento de Medicamentos/métodos , Fibromatose Agressiva/diagnóstico por imagem , Fibromatose Agressiva/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento , Adulto Jovem
12.
Clin Orthop Relat Res ; 473(2): 742-50, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25212962

RESUMO

BACKGROUND: Fibrous dysplasia is a benign fibroosseous bone tumor that accounts for 5% to 10% of benign bone tumors. It can present as monostotic fibrous dysplasia (70% to 80%), polyostotic fibrous dysplasia (20% to 30%), McCune-Albright syndrome (2% to 3%), or Mazabraud's syndrome in rare cases. Bone lesions in fibrous dysplasia arise in the medullary canal and usually are confined to the bone. Cortical destruction and extension into soft tissue usually indicates malignant transformation or secondary aneurysmal bone cyst formation. Locally aggressive fibrous dysplasia with cortical destruction and extension into soft tissue in the absence of these two possibilities is extremely rare. It is important for the treating physician to distinguish this entity from more aggressive or malignant tumors to avoid overtreating the patient for a benign condition or inattention to a malignant tumor. CASE DESCRIPTIONS: We report four unusual cases of fibrous dysplasia with an aggressive radiographic appearance. They occurred in the rib (1), ilium (2), and distal femur (1). Two patients had pain and two had swelling. Radiologically, all were associated with cortical destruction and an associated soft tissue mass, and initially they were interpreted as potentially malignant. Three patients underwent biopsy and one patient did not have a biopsy. Histopathologic analysis by an experienced bone pathologist confirmed fibrous dysplasia in all patients. Two patients were treated surgically; one patient with zoledronic acid and one patient currently is being followed by observation alone. LITERATURE REVIEW: There are only a few reports in the literature that describe the locally aggressive variant of fibrous dysplasia that presents with pain and progressive swelling clinically and with cortical destruction and soft tissue extension on imaging which suggest malignancy. We could not find any article that describes the use of bisphosphonates in such lesions or the response to bisphosphonates clinically, on laboratory parameters or imaging. To our knowledge, this is the largest case report published regarding locally aggressive fibrous dysplasia arising outside the craniofacial skeleton. CLINICAL RELEVANCE: The locally aggressive variant of fibrous dysplasia may be confused with a malignant tumor or malignant degeneration of fibrous dysplasia. It is important to properly evaluate these lesions to ensure that a proper diagnosis is made, especially with respect to a malignant versus benign mass.


Assuntos
Neoplasias Ósseas/diagnóstico , Displasia Fibrosa Óssea/diagnóstico , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Fêmur/patologia , Displasia Fibrosa Óssea/diagnóstico por imagem , Displasia Fibrosa Óssea/patologia , Humanos , Ílio/patologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Ossos Pélvicos/diagnóstico por imagem , Costelas/patologia , Tomografia Computadorizada por Raios X
13.
Cell Tissue Bank ; 16(4): 623-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26006785

RESUMO

This study assessed the relationship of non-injected illicit drug use and infectious disease seropositivity for human immunodeficiency virus (HIV-1), hepatitis B virus (HBV), hepatitis C virus (HCV), and Syphilis. In a retrospective review of 986 donor charts recovered from 2009 to 2011 at a single tissue bank, the absence of reported non-injected illicit drug use corresponded with seropositivity in 6.61 %, of recovered donors while reported illicit drug use in the medical and social history corresponded with seropositivity in 11.25 %, representing a 70 % increased risk. There was no significant difference noted for overall seropositivity rates between types on noninjected illicit drugs, although donors that used cocaine had a higher incidence of HIV, while marijuana use was associated with a higher rate of HBV, HCV, and syphilis positivity. Toxicology screening results were not an accurate predictor of seropositivity (PPV = 3.77 %; NPV = 91.56 %). Further, the degree of relationship between the donor and the next of kin had no bearing on the veracity of actual drug use when comparing the response of the medical-social history and the toxicology screen.


Assuntos
Drogas Ilícitas , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Sífilis/epidemiologia , Bancos de Tecidos/estatística & dados numéricos , Doadores de Tecidos/estatística & dados numéricos , Viroses/epidemiologia , Adulto , Florida/epidemiologia , Soropositividade para HIV/epidemiologia , Humanos , Incidência , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco
15.
Clin Orthop Relat Res ; 471(3): 891-8, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22968531

RESUMO

BACKGROUND: Core needle biopsies of sarcomas allow a diagnosis in a high percentage of patients with few complications. However, it is unclear whether the tract needs to be excised to prevent recurrences. QUESTIONS/PURPOSES: We therefore determined the rates of recurrence and metastases in patients with Stage III extremity sarcomas, who underwent wide local resection without excision of the needle tract and also received adjuvant treatment. METHODS: We retrospectively reviewed 59 adult patients with deep, larger than 5 cm, high-grade soft tissue sarcomas of the upper or lower extremity treated between January 1999 and April 2009. All the patients underwent a core needle biopsy. Resection was performed with wide margins. The biopsy tract was not resected during the definitive surgery. Fifty-seven patients (97%) received preoperative and/or postoperative radiation, whereas 49 patients (83%) received chemotherapy. Local recurrence and distant recurrence rates were determined. The minimum followup was 24 months (median, 56 months; range, 24-122 months). RESULTS: The local recurrence rate was 9%. Fifteen patients (25%) developed metastasis after diagnosis. Seven of the 59 patients (12%) had microscopic positive margins at resection. CONCLUSIONS: Our data demonstrate no increase in local recurrence rates or rates of metastatic disease compared with previously published studies when resection of the core biopsy tract was not performed. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.


Assuntos
Biópsia com Agulha de Grande Calibre/efeitos adversos , Recidiva Local de Neoplasia/patologia , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Adulto , Idoso , Quimioterapia Adjuvante , Extremidades , Feminino , Humanos , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Neoplasia Residual , Radioterapia Adjuvante , Reoperação , Estudos Retrospectivos , Sarcoma/secundário , Neoplasias de Tecidos Moles/patologia , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral
16.
Arthroscopy ; 29(4): 756-65, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23369445

RESUMO

PURPOSE: The purpose of this study was to thoroughly characterize the fan-folded iliotibial band (FITB) allograft and compare it with anterior tibialis tendons (ATs) and native anterior cruciate ligaments (ACLs) to determine whether it measures up to those tissues. METHODS: We compared the histologic structure, tensile strength to failure, creep, and stress-relaxation properties of FITBs with those of ATs and ACLs. In vitro cytotoxicity and biocompatibility of FITBs were also compared with ATs. RESULTS: No structural difference was observed between the tissues studied. FITB ultimate tensile strength (3,459 ± 939 N) was not significantly different (P > .9999) from ultimate tensile strength of ATs (3,357 ± 111 N) and was significantly greater (P = .0005) than that of ACLs (886 ± 254 N). No significant difference (P > .9999) was observed in the increase in length resulting from creep testing between FITBs (9.5 ± 3.0 mm) and ATs (9.7 ± 4.0 mm). During stress-relaxation testing, FITBs reached 181 ± 46 N, which was not significantly different (P > .9999) from ATs (166 ± 40 N). Finally, we showed that cytotoxicity of FITBs and ATs was negligible. In vitro biocompatibility of FITBs and ATs was very good, whereas FITBs had a higher propensity to favor the attachment and infiltration of cells that proliferated for at least 4 weeks on their contact. CONCLUSIONS: We found that FITBs, ACLs, and ATs shared a similar structure made of aligned collagen fibers. No significant difference was observed between FITB and AT ultimate tensile strength, creep, and stress-relaxation viscoelastic properties. Ultimate tensile strength to failure of ACLs was lower than that of FITBs and ATs, whereas ACLs were superior to both FITBs and ATs during creep and stress-relaxation testing. FITBs and ATs showed low cytotoxicity and excellent biocompatibility in vitro, with a somewhat higher propensity of FITBs to favor cell attachment and infiltration over time. CLINICAL RELEVANCE: This study suggests that FITBs have the potential to perform as well as ATs for ACL reconstruction.


Assuntos
Reconstrução do Ligamento Cruzado Anterior/métodos , Ligamento Cruzado Anterior/cirurgia , Fáscia/transplante , Tendões/transplante , Adolescente , Adulto , Ligamento Cruzado Anterior/anatomia & histologia , Ligamento Cruzado Anterior/fisiologia , Lesões do Ligamento Cruzado Anterior , Fenômenos Biomecânicos , Cadáver , Fáscia/anatomia & histologia , Fáscia/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tendões/anatomia & histologia , Tendões/fisiologia , Transplante Homólogo , Adulto Jovem
17.
Cancer Manag Res ; 15: 113-122, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36776730

RESUMO

Purpose: To report a case of large extremity soft tissue sarcoma (2933 cc), safely treated with a novel approach of interdigitating high-dose LATTICE radiation therapy (LRT) with standard radiation therapy as a neoadjuvant treatment to surgery. Patients and Methods: Four sessions of high-dose LRT were delivered in a weekly interval, interdigitated with standard radiation therapy. The LRT plan consisted of 15 high-dose vertices receiving a dose >12 Gy per session, with 2-3 Gy to the peripheral margin of the tumor. The patient underwent surgical excision 2 months after the new regimen of induction radiation therapy. Results and Discussion: The patient tolerated the radiation therapy regimen well. The post-operative assessment revealed a negative surgical margin and over 95% necrosis of the total tumor volume. The post-surgical wound complication was mitigated by outpatient wound care. Interdigitating multiple sessions of high-dose LATTICE radiation treatments with standard neoadjuvant radiation therapy as a neoadjuvant therapy for soft tissue sarcoma was feasible and did not incur additional toxicity in this clinical case. A phase-I/II trial will be conducted to further evaluate the toxicity and efficacy of the new treatment strategy with the intent to increase the rate of pathologic necrosis, which has been shown to positively correlate with the overall survival.

18.
Front Oncol ; 13: 1286807, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38188297

RESUMO

Objectives: Because size-based imaging criteria poorly capture biologic response in desmoid-type fibromatosis (DF), changes in MRI T2 signal intensity are frequently used as a response surrogate, but remain qualitative. We hypothesized that absolute quantification of DF T2 relaxation time derived from parametric T2 maps would be a feasible and effective imaging biomarker of disease activity. Methods: This IRB-approved retrospective study included 11 patients with DF, managed by observation or systemic therapy, assessed by 3T MRI. Tumor maximum diameter, volume, and T2-weighted signal intensity were derived from manual tumor segmentations. Tumor:muscle T2 signal ratios were recorded. Two readers measured tumor T2 relaxation times using a commercial T2 scanning sequence, manual ROI delineation and commercial calculation software enabling estimation of reader reliability. Objective response rates based on RECIST1.1 and best responses were compared between size-based and signal-based parameters. Results: Median patient age was 52.6 years; 8 subjects were female (73%). Nine patients with longitudinal assessments were followed for an average of 314 days. Median baseline tumor diameter was 7.2 cm (range 4.4 - 18.2 cm). Median baseline T2 was 65.1 ms (range 40.4 - 94.8 ms, n=11); median at last follow-up was 44.3 ms (-32% from baseline; range 29.3 - 94.7 ms, n=9). T2 relaxation times correlated with tumor:muscle T2 signal ratios, Spearman p=0.78 (p<0.001). T2 mapping showed high inter-reader reliability, ICC=0.84. The best response as a percentage change in T2 values was statistically significant (mean -17.9%, p=0.05, paired t-test) while change in diameter was not (mean -8.9%, p=0.12). Conclusions: Analysis of T2 relaxation time maps of DF may offer a feasible quantitative biomarker for assessing the extent of response to treatment. This approach may have high inter-reader reliability.

19.
Curr Opin Oncol ; 24(4): 404-8, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22572726

RESUMO

PURPOSE OF REVIEW: Giant cell tumor of tendon sheath and pigmented villonodular synovitis are synovial-based diseases that are generally treated by surgery. For aggressive and recurrent tumors, treatment alternatives are needed. This review explores a targeted therapeutic strategy. RECENT FINDINGS: Imatinib, a tyrosine kinase inhibitor, blocks expression of colony stimulating factor 1 (CSF1) by a small subpopulation of tumor cells that recruit CSF1-bearing nonneoplastic cells. Limited clinical data support the efficacy and side effect profile of imatinib in stabilizing disease in most patients. SUMMARY: Imatinib along with other such inhibitors and monoclonal antibodies to CSF1R are putative drugs that may play an important role in the treatment of these tumors.


Assuntos
Fator Estimulador de Colônias de Macrófagos/antagonistas & inibidores , Sinovite Pigmentada Vilonodular/tratamento farmacológico , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Benzamidas , Humanos , Mesilato de Imatinib , Fator Estimulador de Colônias de Macrófagos/imunologia , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Receptor de Fator Estimulador de Colônias de Macrófagos/imunologia , Sinovite Pigmentada Vilonodular/imunologia
20.
J Surg Oncol ; 106(7): 850-5, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22623216

RESUMO

BACKGROUND: Renal cell carcinoma is the seventh leading cause of cancer deaths. Studies have shown patients with solitary osseous metastases have a better prognosis; however, methods of resection are not well defined. The purpose of this study was to review factors associated with survival and assess the impact of wide versus intralesional management on function and disease-specific outcomes in patients with renal cell carcinoma metastases. METHODS: Sixty-nine patients with 86 osseous renal cell metastases were reviewed. Potential factors associated with survival were evaluated with Kaplan-Meier curves. ANOVA was performed to compare means between groups. RESULTS: One year survival for the group was 77% and 32.5% at 5 years. The absence of metastatic disease at presentation, nephrectomy, and pre-operative status were associated with improved survival. There was a lower rate of local recurrence with wide resection (5%) versus intralesional procedures (27%). CONCLUSIONS: Improved pre-operative status, nephrectomy, and metachronous lesions had better overall survival. Wide resection results in decreased local recurrence and revision surgeries. However, it did not reliably predict improved survival. Our recommendation is for individual evaluation of each patient with osseous renal cell carcinoma metastases. Wide excision may be used for resectable lesions to prevent local progression and subsequent surgeries.


Assuntos
Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Neoplasias Renais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/terapia , Carcinoma de Células Renais/terapia , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/terapia , Masculino , Pessoa de Meia-Idade , Nefrectomia , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Taxa de Sobrevida , Resultado do Tratamento
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