Treatment delay and radiological errors in patients with bone metastases

During routine investigations, we are surprised to find that therapy for bone metastases is sometimes delayed for a considerable period of time. To determine the extent of this delay and its causes, we reviewed the medical records of symptomatic patients seen at our hospital who had been recently diagnosed as having bone metastases for the last four years. The treatment delay was defined as the interval between presentation with symptoms and definitive treatment for bone metastases. The diagnostic delay was defined as the interval between presentation with symptoms and diagnosis of bone metastases. The results of diagnostic radiological examinations were also reviewed for errors. The study population included 76 males and 34 females with a median age of 66 years. Most bone metastases were diagnosed radiologically. Over 75% of patients were treated with radiotherapy. The treatment delay ranged from 2 to 307 days, with a mean of 53.3 days. In 490 radiological studies reviewed, we identified 166 (33.9%) errors concerning 62 (56.4%) patients. The diagnostic delay was significantly longer for patients with radiological errors than for patients without radiological errors (P < 0.001), and much of it was due to radiological errors. In conclusion, the treatment delay in patients with symptomatic bone metastases was much longer than expected, and much of it was caused by radiological errors. Considerable efforts should therefore be made to more carefully examine the radiological studies in order to ensure prompt treatment of bone metastases.

Phlebotomine fauna, natural infection rate and feeding habits of Lutzomyia cruzi in Jaciara, state of Mato Grosso, Brazil

Visceral leishmaniasis (VL) in Brazil is transmitted by the phlebotomine Lutzomyia longipalpis and in some midwestern regions by Lutzomyia cruzi. Studies of the phlebotomine fauna, feeding habits and natural infection rate by Leishmania contribute to increased understanding of the epidemiological chain of leishmaniases and their vectorial capacity. Collections were performed in Jaciara, state of Mato Grosso from 2010-2013, during which time 2,011 phlebotomines (23 species) were captured (68.70% Lu. cruzi and 20.52% Lutzomyia whitmani). Lu. cruzi females were identified by observing the shapes of the cibarium (a portion of the mouthpart) and spermatheca, from which samples were obtained for polymerase chain reaction to determine the rates of natural infection. Engorged phlebotomines were assessed to identify the blood-meal host by ELISA. A moderate correlation was discovered between the number of Lu. cruzi and the temperature and the minimum rate of infection was 6.10%. Twenty-two females were reactive to the antisera of bird (28%), dog (3.30%) and skunk (1.60%). We conclude that Lu. cruzi and Lu. whitmani have adapted to the urban environment in this region and that Lu. cruzi is the most likely vector of VL in Jaciara. Moreover, maintenance of Leishmania in the environment is likely aided by the presence of birds and domestic and synanthropic animals.

Prevalence of exclusive lower extremity metastases at 18F-NaF PET/CT

AbstractObjective:To evaluate the prevalence of exclusive lower extremity metastases, specifically in the femur and below the knee, observed at 18F-NaF PET/CT.Materials and Methods:One thousand consecutive PET/CT studies were retrospectively evaluated for the presence of exclusive uptake in lower extremities suggesting metastatic involvement. The presumptive diagnoses based on such uptakes were subsequently obtained by evaluation of other imaging studies.Results:No exclusive uptake suggestive of metastasis below the femur was observed in the present series. Exclusive uptake was observed in the proximal femur with a presumptive diagnosis of metastasis in two patients.Conclusion:The prevalence of exclusive metastasis below the femur is low and scanning from head to knees is appropriate in most cases.

Widespread hematogenous metastases and Trousseau's syndrome in gastric adenocarcinoma

A case of widespread hematogenous metastases and Trousseau's syndrome is reported in a 40 year-old white housewife with gastric cancer, presenting subdural hematoma, ecchymoses, epistaxis, stomach and uterine bleeding. After undergoing hematoma drainage, she was unsuccessfully treated with platelets, red blood cells, plasma cryoprecipitate transfusions, and antibiotics. Necropsy disclosed gastric ring-signet adenocarcinoma invading the serous layer, with massive disseminated intravascular coagulation and systemic neoplastic embolism. Multiple old and recent hyaline (rich in fibrin and platelets) microthrombi, and tumor emboli were observed in the bone marrow, meninges, liver, lungs, kidneys, lymph nodes, adrenals, thyroid, heart, pancreas, and ovaries (Krukenberg tumor).

Dosimetria de pacientes submetidos a exames de PET/CT cerebral para diagnóstico de comprometimento cognitivo leve

Objetivo: O objetivo deste trabalho é avaliar a dose em pacientes submetidos a PET/CT para diagnóstico de comprometimento cognitivo leve. Materiais e Métodos: Para as medidas da dose absorvida proveniente da modalidade CT utilizaram-se detectores TLD-100 inseridos em um simulador Alderson Rando®. Os simuladores antropomórficos (versões masculina e feminina) foram submetidos aos mesmos protocolos técnicos para aquisição das imagens dos pacientes. A dose absorvida resultante da injeção do radiofármaco foi estimada por meio do modelo proposto pela ICRP 106. Resultados: A dose efetiva a que foram submetidos os pacientes com esta técnica diagnóstica foi, aproximadamente, (5,34 ± 1,99) mSv. Conclusão: Protocolos otimizados para cálculo de atividade radioativa que será injetada em cada paciente podem contribuir para a redução da dose efetiva nos pacientes durante a realização do diagnóstico de comprometimento cognitivo leve com PET/CT.

Receiver operating characteristic (ROC) curve for classification of18F-NaF uptake on PET/CT

Abstract Objective: To assess the cutoff values established by ROC curves to classify18F-NaF uptake as normal or malignant. Materials and Methods: PET/CT images were acquired 1 hour after administration of 185 MBq of18F-NaF. Volumes of interest (VOIs) were drawn on three regions of the skeleton as follows: proximal right humerus diaphysis (HD), proximal right femoral diaphysis (FD) and first vertebral body (VB1), in a total of 254 patients, totalling 762 VOIs. The uptake in the VOIs was classified as normal or malignant on the basis of the radiopharmaceutical distribution pattern and of the CT images. A total of 675 volumes were classified as normal and 52 were classified as malignant. Thirty-five VOIs classified as indeterminate or nonmalignant lesions were excluded from analysis. The standardized uptake value (SUV) measured on the VOIs were plotted on an ROC curve for each one of the three regions. The area under the ROC (AUC) as well as the best cutoff SUVs to classify the VOIs were calculated. The best cutoff values were established as the ones with higher result of the sum of sensitivity and specificity. Results: The AUCs were 0.933, 0.889 and 0.975 for UD, FD and VB1, respectively. The best SUV cutoffs were 9.0 (sensitivity: 73%; specificity: 99%), 8.4 (sensitivity: 79%; specificity: 94%) and 21.0 (sensitivity: 93%; specificity: 95%) for UD, FD and VB1, respectively. Conclusion: The best cutoff value varies according to bone region of analysis and it is not possible to establish one value for the whole body.

Morphology and morphometry of feline bone marrow-derived mesenchymal stem cells in culture

Mesenchymal stem cells (MSC) are increasingly being proposed as a therapeutic option for treatment of a variety of different diseases in human and veterinary medicine. Stem cells have been isolated from feline bone marrow, however, very few data exist about the morphology of these cells and no data were found about the morphometry of feline bone marrow-derived MSCs (BM-MSCs). The objectives of this study were the isolation, growth evaluation, differentiation potential and characterization of feline BM-MSCs by their morphological and morphometric characteristics. in vitro differentiation assays were conducted to confirm the multipotency of feline MSC, as assessed by their ability to differentiate into three cell lineages (osteoblasts, chondrocytes, and adipocytes). To evaluate morphological and morphometric characteristics the cells are maintained in culture. Cells were observed with light microscope, with association of dyes, and they were measured at 24, 48, 72 and 120h of culture (P1 and P3). The non-parametric ANOVA test for independent samples was performed and the means were compared by Tukey's test. On average, the number of mononuclear cells obtained was 12.29 (±6.05x10(6)) cells/mL of bone marrow. Morphologically, BM-MSCs were long and fusiforms, and squamous with abundant cytoplasm. In the morphometric study of the cells, it was observed a significant increase in average length of cells during the first passage. The cell lengths were 106.97±38.16µm and 177.91±71.61µm, respectively, at first and third passages (24 h). The cell widths were 30.79±16.75 µm and 40.18±20.46µm, respectively, at first and third passages (24 h).The nucleus length of the feline BM-MSCs at P1 increased from 16.28µm (24h) to 21.29µm (120h). However, at P3, the nucleus length was 26.35µm (24h) and 25.22µm (120h). This information could be important for future application and use of feline BM-MSCs.

Paullinia cupana Mart var. sorbilis, guaraná, reduces cell proliferation and increases apoptosis of B16/F10 melanoma lung metastases in mice

We showed that guaraná (Paullinia cupana Mart var. sorbilis) had a chemopreventive effect on mouse hepatocarcinogenesis and reduced diethylnitrosamine-induced DNA damage. In the present experiment, we evaluated the effects of guaraná in an experimental metastasis model. Cultured B16/F10 melanoma cells (5 x 10(5) cells/animal) were injected into the tail vein of mice on the 7th day of guaraná treatment (2.0 mg P. cupana/g body weight, per gavage) and the animals were treated with guaraná daily up to 14 days until euthanasia (total treatment time: 21 days). Lung sections were obtained for morphometric analysis, apoptotic bodies were counted to calculate the apoptotic index and proliferating cell nuclear antigen-positive cells were counted to determine the proliferation index. Guaraná-treated (GUA) animals presented a 68.6% reduction in tumor burden area compared to control (CO) animals which were not treated with guaraná (CO: 0.84 ± 0.26, N = 6; GUA: 0.27 ± 0.24, N = 6; P = 0.0043), a 57.9% reduction in tumor proliferation index (CO: 23.75 ± 20.54, N = 6; GUA: 9.99 ± 3.93, N = 6; P = 0.026) and a 4.85-fold increase in apoptotic index (CO: 66.95 ± 22.95, N = 6; GUA: 324.37 ± 266.74 AB/mm², N = 6; P = 0.0152). In this mouse model, guaraná treatment decreased proliferation and increased apoptosis of tumor cells, consequently reducing the tumor burden area. We are currently investigating the molecular pathways of the effects of guaraná in cultured melanoma cells, regarding principally the cell cycle inhibitors and cyclins.

Women with primary ovarian insufficiency have lower bone mineral density

The aim of the present study was to assess the prevalence of osteoporosis in a sample of 32 patients with spontaneous primary ovarian insufficiency (POI) in comparison to reference groups of 25 pre- and 55 postmenopausal women. Hip (lumbar) and spinal bone mineral density (BMD) measurements were performed by dual-energy X-ray absorptiometry in the three groups. The median age of POI patients at the time of diagnosis was 35 years (interquartile range: 27-37 years). The mean ± SD age of postmenopausal reference women (52.16 ± 3.65 years) was higher than that of POI (46.28 ± 10.38 years) and premenopausal women (43.96 ± 7.08; P = 0.001) at the time of BMD measurement. Twenty-seven (84.4%) POI women were receiving hormone replacement therapy (HRT) at the time of the study. In the postmenopausal reference group, 30.4% were current users of HRT. Lumbar BMD was significantly lower in the POI group (1.050 ± 0.17 g/cm²) compared to the age-matched premenopausal reference group (1.136 ± 0.12 g/cm²; P = 0.040). Moreover, 22 (68.7%) POI women had low bone density (osteopenia/osteoporosis by World Health Organization criteria) versus 47.3% of the postmenopausal reference group (P = 0.042). In conclusion, the present data indicate that BMD is significantly lower in patients with POI than in age-matched premenopausal women. Also, the prevalence of osteopenia/osteoporosis is higher in POI women than in women after natural menopause. Early medical interventions are necessary to ensure that women with POI will maintain their bonemass.

Prostate-specific membrane antigen can promote in vivo osseous metastasis of prostate cancer cells in mice

Reports remain insufficient on whether and how prostate-specific membrane antigen (PSMA) can influence in vivo osseous metastasis of prostate cancer (PCa). In the present study, the authors induced stable expression of PSMA in mouse PCa cell line RM-1. In vivo osseous metastasis was induced in 37 6-week-old female C57BL/6 mice weighing 22.45 ± 0.456 g. RM-1 cells were actively injected into the femoral bone cavity, leading to bilateral dissymmetry of bone density in the femoral bone. Tumor cells were also detected in bone tissue by pathological examination. The impact on bone density was demonstrated by the significant difference between animals injected with RM-PSMA cells (0.0738 ± 0.0185 g/cm²) and animals injected with RM-empty plasmid cells (0.0895 ± 0.0241 g/cm²). The lytic bone lesion of the RM-PSMA group (68.4%) was higher than that of the control group (27.8%). Immunohistochemistry showed that the expression of both vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) was distinctly higher in the RM-PSMA group than in the control group, while ELISA and Western blot assay indicated that VEGF and MMP-9 were higher in the RM-PSMA group compared to the control group (in vitro). Thus, the present study proposed and then confirmed for the first time that PSMA can promote in vivo osseous metastasis of PCa by increasing sclerotic destruction of PCa cells. Further analyses also suggested that PSMA functions positively on the invasive ability of RM-1 by increasing the expression of MMP-9 and VEGF by osseous metastases in vivo

Serum 25-hydroxyvitamin D and biochemical markers of bone metabolism in patients with juvenile idiopathic arthritis

Our objective was to evaluate the concentrations of serum 25-hydroxyvitamin D [25(OH)D], serum calcium, serum phosphorus, alkaline phosphatase, and parathormone (PTH) in patients with polyarticular juvenile idiopathic arthritis (JIA) and to associate them with disease duration and activity, bone mineral density and use of medications. In a cross-sectional and controlled study, 30 patients with polyarticular JIA were evaluated and compared to 30 healthy individuals matched for age and gender. Clinical status, anthropometry, laboratory markers in both patients and controls, and bone mineral density, only in the patients, were measured. Of the 30 patients included in the study, 23 (76.7%) were female and 16 (53.3%) non-Caucasian; mean age was 14 years (range = 4 to 20 years). Mean disease duration was 5 years (range = 1 to 12 years). The mean concentrations of serum albumin-corrected calcium (9.04 ± 0.41 mg/dL) and alkaline phosphatase (153.3 ± 100.1 IU) were significantly lower in patients with JIA than in controls (P < 0.0001 and P = 0.001, respectively). No differences in 25(OH)D, PTH or serum phosphorus were observed between JIA and control subjects. Regarding 25(OH)D concentration, 8 patients (26.7%) and 5 controls (16.7%) had 25(OH)D concentrations compatible with deficiency (lower than 20 ng/mL) and 14 patients (46.7%) and 18 controls (60%) had concentrations compatible with insufficiency (20-32 ng/mL). These values were not associated with disease activity, use of medications or bone mineral density. We observed a high frequency of 25(OH)D insufficiency and deficiency in the study sample. The compromised bone metabolism emphasizes the importance of follow-up of JIA patients.

Association between indoxyl sulfate and bone histomorphometry in pre-dialysis chronic kidney disease patients

Introduction: Experimental studies have suggested that indoxyl sulfate (IS), a protein-bound uremic toxin, may be involved in the development of renal osteodystrophy. Objective: evaluate the association between IS levels and biochemical parameters related to mineral metabolism and bone histomorphometry in a cohort of pre-dialysis chronic kidney disease (CKD) patients. Methods: This is a post-hoc analysis of an observational study evaluating the association between coronary calcification and bone biopsy findings in 49 patients (age: 52 ± 10 years; 67% male; estimated glomerular filtration rate: 36 ± 17 ml/min). Serum levels of IS were measured. Results: Patients at CKD stages 2 and 3 presented remarkably low bone formation rate. Patients at CKD stages 4 and 5 presented significantly higher osteoid volume, osteoblast and osteoclast surface, bone fibrosis volume and bone formation rate and a lower mineralization lag time than CKD stage 2 and 3 patients. We observed a positive association between IS levels on one hand and the bone formation rate, osteoid volume, osteoblast surface and bone fibrosis volume on the other. Multivariate regression models confirmed that the associations between IS levels and osteoblast surface and bone fibrosis volume were both independent of demographic and biochemical characteristics of the study population. A similar trend was observed for the bone formation rate. Conclusion: Our findings demonstrated that IS is positively associated with bone formation rate in pre-dialysis CKD patients.

Particulate bioglass in the regeneration of alveolar bone in dogs: clinical, surgical and radiographic evaluations

Bone loss, either by trauma or other diseases, generates an increasing need for substitutes of this tissue. This study evaluated Bioglass as a bone substitute in the regeneration of the alveolar bone in mandibles of dogs by clinical, surgical and radiological analysis. Twenty-eight adult dogs were randomly separated into two equal groups. In each animal, a bone defect was created on the vestibular surface of the alveolar bone between the roots of the fourth right premolar tooth. In the treated group, the defect was immediately filled with bioglass, while in the control, it remained unfilled. Clinical evaluations were performed daily for a week, as well as x-rays immediately after surgery and at 8, 14, 21, 42, 60, 90 and 120 days post-operative. Most animals in both groups showed no signs of inflammation and wound healing was similar. Radiographic examination revealed a gradual increase of radiopacity in the region of the defect in the control group. In the treated group, initial radiopacity was higher than that of adjacent bone, decreasing until 21 days after surgery. Then it gradually increased until 120 days after surgery, when the defect became undetectable. The results showed that Bioglass integrates into bone tissue, is biocompatible and reduced the period for complete bone regeneration.

Bone mineral density of rat femurs after hindlimb unloading and different physical rehabilitation programs

Bone weakening can occur due to the absence of load on the skeleton or even short periods of decreased physical activity. Therefore, musculoskeletal diseases that involve temporary immobilization by casts, inactivity or tension increases the risk of fractures. Physical activity is the most studied procedure both to prevent damage and to restore bone structure. The present study aimed at evaluating, by bone densitometry on rat femurs, the influence of hindlimb unloading and later running activity on treadmill or free movement. Sixty-four Wistar rats were used, aged 65 days with a mean corporal mass of 316.11g, randomly divided into eight experimental groups: group 1, the suspended control with seven animals under hindlimb unloading regimen for 28 days, then euthanized; groups 2 and 3, the trained suspended comprising of 7 and five animals, respectively, subjected to hindlimb unloading for 28 days, followed by treadmill exercise for 28 days (group 2) or 56 days (group 3), then euthanized; groups 4 and 5, designated free suspended, comprised of 7 animals each under hindlimb unloading regimen for 28 days followed by free activity in cages for 28 days (group 4) or 56 days (group 5), then euthanized; groups 6, 7 and 8, negative controls, each with 8 animals allowed to free activity in cages and euthanized at the ages of 93, 121 and 149 days, respectively. Bone mineral density (BMD) of the left femur was analyzed by bone densitometry. Unloading by tail-suspension decreased BMD while treadmill training and free activity in cages promoted its recovery in a similar way and over time.

Ractopamina em dietas sem ajustes aminoacídicos para suínos machos castrados em terminação

Este estudo teve o objetivo de avaliar planos de suplementação com ractopamina, em dietas sem ajustes aminoacídicos, para suínos machos castrados, em terminação. Foram utilizados 72 suínos machos castrados, com peso inicial de 68,61 ± 3,89 kg, distribuídos em seis planos de suplementação com duração de 30 dias (0 ppm; 5 ppm; 10 ppm; 20 ppm; 5 ppm, durante 15 dias, seguidos por 10 ppm durante 15 dias; e 10 ppm durante 15 dias seguidos por 20 ppm durante 15 dias), com seis repetições e dois animais por unidade experimental. A suplementação com ractopamina melhorou a conversão alimentar. A suplementação com 5 ppm de ractopamina aumentou o ganho de peso diário. Os níveis de 10 e 20 ppm e as suplementações graduais reduziram o consumo de ração diário e de nutrientes. Não houve influência da suplementação sobre o peso de carcaça quente e o comprimento de carcaça. A ractopamina reduziu a espessura de toucinho e aumentou a profundidade de músculo, o percentual de carne magra, a quantidade de carne magra e o índice de bonificação das carcaças. A suplementação de 5 ppm de ractopamina em dietas sem ajustes aminoacídicos melhora o desempenho e as características de carcaça de suínos em terminação, nos 30 dias pré-abate.