Reynaldo Jesus Garcia Filho

Prognostic factors and outcomes for osteosarcoma: an international collaboration

We aimed to evaluate the prognostic significance of traditional clinical predictors in osteosarcoma through an international collaboration of 10 teams of investigators (2680 patients) who participated. In multivariate models the mortality risk increased with older age, presence of metastatic disease at diagnosis, development of local recurrence when the patient was first seen, use of amputation instead of limb salvage/wide resection, employment of unusual treatments, use of chemotherapeutic regimens other than anthracycline and platinum and use of methotrexate. It was also influenced by the site of the tumour. The risk of metastasis increased when metastatic disease was present at the time the patient was first seen and also increased with use of amputation or unusual treatment combinations or chemotherapy regimens not including anthracycline and platinum. Local recurrence risk was higher in older patients, in those who had local recurrence when first seen and when no anthracycline and platinum were used in chemotherapy. Results were similar when limited to patients seen after 1990 and treated with surgery plus combination chemotherapy. This large-scale international collaboration identifies strong predictors of major clinical outcomes in osteosarcoma.

Bone deposition, bone resorption, and osteosarcoma

Bone deposition and bone resorption are ongoing dynamic processes, constituting bone remodeling. Some bone tumors, such as osteosarcoma (OS), stimulate focal bone deposition. OS is the most common primary bone tumor in children and young adults. A complex network of genes regulates bone remodeling and alterations in its expression levels can influence the genesis and progression of bone diseases, including OS. We hypothesized that the expression profiles of bone remodeling regulator genes would be correlated with OS biology and clinical features. We used real‐time PCR to evaluate the mRNA levels of the tartrate‐resistant acid phosphatase (ACP5), colony stimulating factor‐1 (CSF1R), bone morphogenetic protein 7 (BMP7), collagen, type XI, alpha 2 (COL11A2), and protein tyrosine phosphatases zeta 1 (PTPRZ1) genes, in 30 OS tumor samples and correlated with clinical and histological data. All genes analyzed, except CSF1R, were differentially expressed when compared with normal bone expression profiles. In our results, OS patients with high levels of COL11A2 mRNA showed worse overall (p = 0.041) and event free survival (p = 0.037). Also, a trend for better overall survival was observed in patients with samples showing higher expression of BMP7 (p = 0.067). COL11A2 overexpression and BMP7 underexpression could collaborate to OS tumor growth, through its central role in bone remodeling process.

Epidemiology of total hip and knee replacement: a cross-sectional study

ABSTRACT Objective: To describe the epidemiologic characteristics and adverse events of patients submitted to total hip and total knee replacement. Methods: A cross-sectional study retrospectively assessing medical chart data of all total hip and total knee replacements performed at a private hospital, between January 2007 and December 2010 Patients submitted to total hip and total knee replacement, with consent of surgeons were included. Incomplete records and/or missing data of the hospital database were excluded. The categorical variables analyzed were age, gender, type of arthroplasty (primary or secondary), type of procedure, duration of surgery, use of drains, risk of infection, compliance to protocol for prevention of deep venous thrombosis and embolism pulmonary, and compliance to the protocol for prevention of infection. The outcomes assessed were adverse events after surgery. Results: A total of 510 patients were included; in that, 166 admissions for knee replacements (92 male) and 344 admissions for hip replacements (176 female). The mean age of patients was 71 years (range 31-99 years). Adverse events were reported in 76 patients (14.9%); there was no correlation between assessed variables and number of complications. Conclusion: The results showed no individual factors favoring complications in patients submitted to total hip and total knee replacement; hence, surgeons should consider prophylaxis to avoid complications.

MAPK7 and MAP2K4 as prognostic markers in osteosarcoma

Osteosarcoma is a class of cancer originating from the bone, affecting mainly children and young adults. Cytogenetic studies showed the presence of rearrangements and recurrent gains in specific chromosomal regions, indicating the possible involvement of genes located in these regions during the pathogenesis of osteosarcoma. These studies investigated expression of 10 genes located in the chromosomal region involved in abnormalities in osteosarcoma, 1p36, 17p, and chromosome 19. The purpose of this study was to investigate the expression profile of genes located in regions involved in chromosomal rearrangements in osteosarcoma. We used quantitative real-time polymerase chain reaction to investigate the expression of 10 genes located in 1p36.3 (MTHFR, ERRFI1, FGR, E2F2), 17p (MAPK7, MAP2K4), and chromosome 19 (BBC3, FOSB, JUND, and RRAS), in 70 samples taken from 30 patients (30 prechemotherapy, 30 postchemotherapy, and 10 metastases specimens) and 10 healthy bones as a control sample. The most interesting results showed a strong association between the expression levels of MAPK7 and MAP2K4 genes and clinical parameters of osteosarcoma. Overexpression of these genes was significantly associated to a poor response to treatment (P = .0001 and P = .0049, respectively), tumor progression, and worse overall survival (P = .0052 and P = .0085, respectively), suggesting that MAPK7 and MAP2K4 could play an important role in osteosarcoma tumorigenesis. Thus, these genes could be good markers in assessing response to treatment and development of osteosarcoma.

The metastatic behavior of osteosarcoma by gene expression and cytogenetic analyses

Osteosarcoma is a malignant bone tumor with high metastatic potential. Metastasis at diagnosis is the most significant prognostic factor in predicting the clinical outcome of osteosarcoma. We compared the gene expression of metastases that were present at the time of initial diagnosis to those developed later in the course of the disease. We used quantitative real-time polymerase chain reaction to evaluate the gene expression of MDM2, CXCR4, RANKL, RB1, and OSTERIX in 98 samples of osteosarcoma taken from 47 patients (74 metastases and 24 primary tumors) and 30 nonmalignant lung tissues surrounding osteosarcoma metastases. In addition, we investigated the copy number changes of RB1 and MDM2 genes in 12 primary cultures of pulmonary metastases of osteosarcoma, using interphase fluorescence in situ hybridization. Metastases from metastatic patients at diagnosis were characterized by low expression of RB1 and RANKL (P = .0009 and P = .0109, respectively) and overexpression of CXCR4 and MDM2 (P = .0389 and P = .0325, respectively). The loss of RANKL and gain of CXCR4 could also be detected in the primary tumors of metastatic patients at diagnosis (P = .0121 and P = .0264, respectively). Thus, some early genetic events such as the loss of RANKL and the gain of CXCR4 expressions probably facilitate the metastatic progression concomitant with the primary tumor establishment, supporting the role of the CXCR4 receptor in directing osteosarcoma metastases to the lung. On the other hand, late events such as the loss of RB1 and gain of MDM2, crucial regulators of cell cycle, appear to be related to the final mechanisms contributing to the metastatic establishment of osteosarcoma.

Computed tomography-guided percutaneous trephine removal of the nidus in osteoid osteoma patients: experience of a single center in Brazil

Objective To report the results of computed tomography (CT)-guided percutaneous resection of the nidus in 18 cases of osteoid osteoma. Materials and Methods The medical records of 18 cases of osteoid osteoma in children, adolescents and young adults, who underwent CT-guided removal of the nidus between November, 2004 and March, 2009 were reviewed retrospectively for demographic data, lesion site, clinical outcome and complications after procedure. Results Clinical follow-up was available for all cases at a median of 29 months (range 6–60 months). No persistence of pre-procedural pain was noted on 17 patients. Only one patient experienced recurrence of symptoms 12 months after percutaneous resection, and was successfully retreated by the same technique, resulting in a secondary success rate of 18/18 (100%). Conclusion CT-guided removal or destruction of the nidus is a safe and effective alternative to surgical resection of the osteoid osteoma nidus.

Ensaio clínico randomizado, duplo-cego, comparativo entre a associação de cafeína, carisoprodol, diclofenaco sódico e paracetamol e a ciclobenzaprina, para avaliação da eficácia e segurança no tratamento de pacientes com lombalgia e lombociatalgia agudas

OBJECTIVE: To evaluate the efficacy and safety of the combination of diclofenac, paracetamol, carisoprodol, and caffeine in the treatment of acute low back pain and lumboischialgia, compared to the efficacy and safety of cyclobenzaprine. STUDY DESIGN: Single-center, comparative, randomized, double-blind clinical trial. METHOD: Drugs were administered t.i.d. for a period of 7 days. STUDY POPULATION: 108 patients with a diagnosis of acute low back pain and lumboischialgia in the last 7 days were randomized, being included 54 patients in each group. ENDPOINTS: The primary efficacy endpoints selected for the study were the pain visual analog scale and the Roland-Morris questionnaire, the results of which were compared before and after treatment. The secondary endpoints were the patients and the investigators overall assessment of the treatment, as well as the use of the analgesic rescue medication. The safety criteria were the tolerability analysis, the medication discontinuation due to adverse events, and laboratory tests. RESULTS: There were no statistically significant differences among the groups regarding efficacy in any of the endpoints examined. Both medications have been shown to be safe and tolerable in the treatment of acute low back pain and lumboischialgia. The thorough statistical analysis revealed a difference between the two groups only concerning adverse events, which were more frequent in the group treated with cyclobenzaprine.

Sarcoma de Ewing: epidemiologia e prognóstico dos pacientes tratados no Instituto de Oncologia Pediátrica, IOP-GRAACC-UNIFESP

OBJECTIVE: To outline the epidemiological profile and prognosis for Ewings sarcoma in the Brazilian population. Material and METHODS: The medical records of 64 patients with intraosseous Ewings sarcoma who were treated at the Pediatric Oncology Institute, IOP-GRAACC-Unifesp, between 1995 and 2010, were retrospectively evaluated. RESULTS: The statistical analysis on the data obtained did not correlate factors such as sex, trauma, pathological fracture and time taken for case diagnosis with the treatment outcome. Factors such as initial metastasis, lung metastasis, tumor site, age, recurrence and type of surgery showed results corroborating what has been established in the literature. CONCLUSION: The prognosis in cases of Ewings sarcoma was mainly influenced by the presence of metastases at the time of diagnosis.

Clinicopathologic study and Ki-67 proliferative marker evaluation in human osteosarcomas

Background: Osteosarcoma is a relatively uncommon malignant neoplasm and little information has been reported on its cell proliferation using Ki-67. Objectives: Evaluate histological, clinical and immunohis- tochemical parameters using Ki-67 labeling index (LI), correlate one to another and with follow-up. Material and method: Fifty-seven patients with available clinicopathological data submitted to the study of cell proliferation as determined by Ki-67 expression measured by immunohistochemistry (IHC) staining using formalin-fixed paraffin embedded sections. In each sample, positive cells were quantified on at least a thousand nuclei and expressed as Ki-67 LI according to median value. Results and discussion: Non-significant correlations were observed in metastatic and non-metastatic cases when variables as surgery, tumor size, death and relapse were compared with Ki-67 LI values (cut-off of 45%). In the group of non-metastatic cases there was a direct correlation between higher values of Ki-67 index and better overall survival. Metastatic patients overall survival curve and LI high and low Ki-67 did not show significant differences. Conclusion: Based on our results the Ki-67 LI could be useful as a prognostic marker in patients without metastasis at diagnosis.

Complicações das endopróteses em pacientes com tumores ósseos do joelho

Non-conventional endoprostheses (NCE) are frequently used in orthopedic oncology. The complications associated with this procedure have prompted research, due to the fact that it is commonly performed on young patients, with a higher survival rate. We conducted a systematic review of the literature, searching for the best scientific evidence on the subject. The research was carried out in the following databases: MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of randomized controlled trials (CCTR), seeking to identify studies that report complications, and compare patellar resurfacing versus retention. The studies were selected according to the best methodological quality that exists for the subject. One hundred and forty six (146) studies were evaluated. No randomized clinical trial was found. We conducted a qualitative and quantitative evaluation of the work found (evidence levels IV and V). We used the Mann-Whitney U test for the statistical analysis. The results indicate a need for further studies that will enable us to reach a more solid conclusion. The rate of complications after NCE can be considered high, despite the low quality of the studies, as demonstrated by the studies that exist in the literature.