Acridine orange (AO) demonstrates several biological activities. When exposed to low doses of X-ray radiation, AO increases the production of reactive radicals (radiodynamic therapy (AO-RDT)). We elucidated the efficacy of AO-RDT in breast and prostate cancer cell lines, which are likely to develop bone metastases. We used the mouse osteosarcoma cell line LM8, the human breast cancer cell line MDA-MB-231, and the human prostate cancer cell line PC-3. Cultured cells were exposed to AO and radiation at various concentrations followed by various doses of irradiation. The cell viability was then measured. In vivo, each cell was inoculated subcutaneously into the backs of mice. In the AO-RDT group, AO (1.0 μg) was locally administered subcutaneously around the tumour followed by 5 Gy of irradiation. In the radiation group, 5 Gy of irradiation alone was administered after macroscopic tumour formation. The mice were killed on the 14th day after treatment. The change in tumour volume by AO-RDT was primarily evaluated.Aims
Methods
Patients with soft-tissue sarcoma (STS) who undergo unplanned excision (UE) are reported to have worse outcomes than those who undergo planned excision (PE). However, others have reported that patients who undergo UE may have similar or improved outcomes. These discrepancies are likely to be due to differences in characteristics between the two groups of patients. The aim of the study is to compare patients who underwent UE and PE using propensity score matching, by analyzing data from the Japanese Bone and Soft Tissue Tumor (BSTT) registry. Data from 2006 to 2016 was obtained from the BSTT registry. Only patients with STS of the limb were included in the study. Patients with distant metastasis at the initial presentation and patients with dermatofibrosarcoma protuberans and well-differentiated liposarcoma were excluded from the study.Aims
Methods
Achilles tendon defect is difficult problem for orthopedic surgeon, and therefore the development of new treatments is desirable. Platelet-rich fibrin (PRF), dense fibrin scaffold composed of a fibrin matrix containing many growth factors, is recently used as regenerative medicine preparation. However, few data are available on the usefulness of PRF on Achilles tendon healing after injury. The objective of this study is to examine whether PRF promotes the healing of Achilles tendon defect in vivo and evaluated the effects of PRF on tenocytes in vitro. PRF were prepared from rats according to international guidelines on the literature. To create rat model for Achilles tendon defect, a 4-mm portion of the right Achilles tendon was completely resected, and PRF was placed into the gap in PRF group before sewing the gap with nylon sutures. To assess the histological healing of Achilles tendon defect, Bonar score was calculated using HE, Alcian-blue, and Picosirius-red staining section. Basso, Beattie, Bresnahan (BBB) score was used for the evaluation of motor functional recovery. Biomechanical properties including failure tensile load, ultimate tensile stress, breaking elongation, and elastic modulus were measured. We examined the effects of PRF on tenocytes isolated from rat Achilles tendon in vitro. The number of viable cells were measured by MTS assay, and immunostaining of ki-67 was used for detection of proliferative cells. Migration of tenocytes was evaluated by wound closure assay. Protein or gene expression level of extracellular matrix protein, such as collagen, were evaluated by immunoblotting, immunofluorescence, or PCR. Phosphorylation level of AKT, FGF receptor, or SMAD3 was determined by western blotting. Inhibitory experiments were performed using MK-2206 (AKT inhibitor), FIIN-2 (FGFR inhibitor), SB-431542 (TGF-B receptor inhibitor), or SIS3 (SMAD3 inhibitor). All p values presented are two-sided and p values < 0.05 were considered statistically significant.Introduction and Objective
Materials and Methods
Tocilizumab, an interleukin-6 (IL-6) receptor (IL-6R) targeting antibody, enhances the anti-tumour effect of conventional chemotherapy in preclinical models of cancer. We investigated the anti-tumour effect of tocilizumab in osteosarcoma (OS) cell lines. We used the 143B, HOS, and Saos-2 human OS cell lines. We first analyzed the IL-6 gene expression and IL-6Rα protein expression in OS cells using reverse transcription real time quantitative-polymerase chain reaction (RT-qPCR) analysis and western blotting, respectively. We also assessed the effect of tocilizumab on OS cells using proliferation and invasion assay.Aims
Methods
Pseudotumors have been reported following metal-on-metal total hip arthroplasty (THA); however, the natural history and longitudinal imaging findings of pseudotumors have yet to be fully analyzed. Our hypothesis was that pseudotumor size might change over time following metal-on-metal THA. This hypothesis was studied longitudinally using magnetic resonance imaging (MRI). Screening for pseudotumors was performed using MRI after large-diameter metal-on-metal THA. Initial MRI was conducted at a mean of 36 months postoperatively. Follow-up MRI was performed at a mean of 20 months after the detection of 24 pseudotumors in 20 asymptomatic patients. Pseudotumors were classified as cystic, solid, and mixed types. Fourteen hips were characterized as cystic type and 10 hips were defined as mixed type. There were three men and 17 women with a mean age of 63 years. Pseudotumor size was determined on MRI by manually outlining the greatest size of the mass. Serum cobalt and chromium ion levels were measured in nine patients with unilateral THA at the time of MRI. Statistical analysis was performed using the Kruskal-Wallis test and chi square test to compare age, gender, BMI, head diameter, cup inclination, cup anteversion, and pseudotumor type among changes of pseudotumor size. We compared the pseudotumor size for the three groups (increase in size, no change, decrease in size) using Kruskal-Wallis test and Mann-Whitney U test. Wilcoxon signed-rank test was used to compare median serum metal ion levels over time. A p value < 0.05 was considered significant. This study was approved by the ethics committee of our institution, and all patients provided informed consent.Introduction
Materials and Methods
The aim of this study was to determine whether
the high-sensitivity modified Glasgow prognostic score (Hs-mGPS) could
predict the disease-specific survival and oncological outcome in
adult patients with non-metastatic soft-tissue sarcoma before treatment.
A total of 139 patients treated between 2001 and 2012 were retrospectively reviewed.
The Hs-mGPS varied between 0 and 2. Patients with a score of 2 had
a poorer disease-specific survival than patients with a score of
0 (p <
0.001). The estimated five-year rate of disease-specific
survival for those with a score of 2 was 0%, compared with 85.4%
(95% CI 77.3 to 93.5) for those with a score of 0. Those with a
score of 2 also had a poorer disease-specific survival than those
with a score of 1 (75.3%, 95% CI 55.8 to 94.8; p <
0.001). Patients
with a score of 2 also had a poorer event-free rate than those with
a score of 0 (p <
0.001). Those with a score of 2 also had a
poorer event-free survival than did those with a score of 1 (p =
0.03). A multivariate analysis showed that the Hs-mGPS remained
an independent predictor of survival and recurrence. The Hs-mGPS
could be a useful prognostic marker in patients with a soft-tissue
sarcoma. Cite this article:
Salubrinal is a synthetic agent that elevates phosphorylation
of eukaryotic translation initiation factor 2 alpha (eIF2α) and
alleviates stress to the endoplasmic reticulum. Previously, we reported
that in chondrocytes, Salubrinal attenuates expression and activity
of matrix metalloproteinase 13 (MMP13) through downregulating nuclear
factor kappa B (NFκB) signalling. We herein examine whether Salubrinal
prevents the degradation of articular cartilage in a mouse model
of osteoarthritis (OA). OA was surgically induced in the left knee of female mice. Animal
groups included age-matched sham control, OA placebo, and OA treated
with Salubrinal or Guanabenz. Three weeks after the induction of
OA, immunoblotting was performed for NFκB p65 and p-NFκB p65. At
three and six weeks, the femora and tibiae were isolated and the sagittal
sections were stained with Safranin O.Objectives
Methods
The aim of this study was to define the incidence
of venous thromboembolism (VTE) and risk factors for the development
of deep-vein thrombosis (DVT) after the resection of a musculoskeletal
tumour. A total of 94 patients who underwent resection of a musculoskeletal
tumour between January 2003 and December 2005 were prospectively
studied. There were 42 men and 52 women with a mean age of 54.4
years (18 to 86). All patients wore intermittent pneumatic compression
devices and graduated compression stockings. Ultrasound examination
of the lower limbs was conducted to screen for DVT between the fifth
and ninth post-operative days. DVT was detected in 21 patients (22%). Of these, two were symptomatic
(2%). One patient (1%) had a fatal pulmonary embolism. Patients
aged ≥ 70 years had an increased risk of DVT (p = 0.004). The overall incidence of DVT (both symptomatic and asymptomatic)
after resection of a musculoskeletal tumour with mechanical prophylaxis
was high. It seems that both mechanical and anticoagulant prophylaxis
is needed to prevent VTE in patients who have undergone the resection
of a musculoskeletal tumour. Cite this article:
We evaluated the risk of late relapse and further
outcome in patients with soft-tissue sarcomas who were alive and event-free
more than five years after initial treatment. From our database
we identified 1912 patients with these pathologies treated between
1980 and 2006. Of these 1912 patients, 603 were alive and event-free
more than five years after initial treatment and we retrospectively
reviewed them. The mean age of this group was 48 years (4 to 94)
and 340 were men. The mean follow-up was 106 months (60 to 336).
Of the original cohort, 582 (97%) were alive at final follow-up.
The disease-specific survival was 96.4% (95% confidence interval
(CI) 94.4 to 98.3) at ten years and 92.9% (95% CI 89 to 96.8) at
15 years. The rate of late relapse was 6.3% (38 of 603). The ten-
and 15-year event-free rates were 93.2% (95% CI 90.8 to 95.7) and
86.1% (95% CI 80.2 to 92.1), respectively. Multivariate analysis
showed that tumour size and tumour grade remained independent predictors
of events. In spite of further treatment, 19 of the 38 patients
died of sarcoma. The three- and five-year survival rates after the
late relapse were 56.2% (95% CI 39.5 to 73.3) and 43.2% (95% CI
24.7 to 61.7), respectively, with a median survival time of 46 months.
Patients with soft-tissue sarcoma, especially if large, require
long-term follow-up, especially as they have moderate potential
to have their disease controlled. Cite this article:
The aim of this study was to determine whether
the level of circulating C-reactive protein (CRP) before treatment predicted
overall disease-specific survival and local tumour control in patients
with a sarcoma of bone. We retrospectively reviewed 318 patients who presented with a
primary sarcoma of bone between 2003 and 2010. Those who presented
with metastases and/or local recurrence were excluded. Elevated CRP levels were seen in 84 patients before treatment;
these patients had a poorer disease-specific survival (57% at five
years) than patients with a normal CRP (79% at five years) (p <
0.0001). They were also less likely to be free of recurrence (71%
at five years) than patients with a normal CRP (79% at five years)
(p = 0.04). Multivariate analysis showed the pre-operative CRP level
to be an independent predictor of survival and local control. Patients
with a Ewing’s sarcoma or chondrosarcoma who had an elevated CRP
before their treatment started had a significantly poorer disease-specific
survival than patients with a normal CRP (p = 0.02 and p <
0.0001, respectively).
Patients with a conventional osteosarcoma and a raised CRP were
at an increased risk of poorer local control. We recommend that CRP levels are measured routinely in patients
with a suspected sarcoma of bone as a further prognostic indicator
of survival. Cite this article:
Standard surgical exposure reduces blood flow to the patella during total knee arthroplasty (TKA). Reduction of patellar blood flow has resulted in patellofemoral complications including osteonecrosis and patellar fracture, necessitating revision surgery. Eversion of the patella is typically used to gain access to the knee joint in most TKA surgical approaches. More recently, the development of minimally invasive surgery (MIS) techniques has avoided patellar eversion by subluxing the patella. The present study is the first to measure patellar blood flow during MIS TKA with the knee in both extension and 90 degrees of flexion followed by lateral retraction and then eversion of the patella. Patellar blood flow was measured using laser Doppler flowmetry in 40 patients during MIS TKA. Patients included 32 women and 8 men who had a mean age of 73 years (range, 52 to 88 years) and a mean weight of 59 kg (39 to 85 kg). The pre-operative diagnoses were osteoarthritis in 36 patients and rheumatoid arthritis in four patients. All patients underwent MIS TKA using the mini-midvastus approach. After initial blood flow was assessed with the leg in full extension, further measurements were performed after lateral retraction and after eversion of the patella. Then, blood flow was assessed with the knee in 90 degrees of flexion followed by lateral retraction and then eversion of the patella.Introduction
Methods
Limb salvage involving wide resection and reconstruction is now well established for managing musculoskeletal sarcomas. However, involvement of major nerves and vessels with a large volume of muscle and skin may result in a useless limb, contributing to depression and a low quality of life. We have been studying alternative treatments for musculoskeletal sarcoma since 1990, and have recently established a regime using photodynamic surgery with cells labelled with acridine orange, photodynamic therapy with cells treated similarly and radiodynamic treatment using the effect of X-rays on such cells. These techniques have been used after marginal or intralesional resection of tumours since 1999 and have enabled maintenance of excellent limb function in patients with sarcomas.
Osteoporosis is one of the most common diseases in modern aging society. Receptor activator of nuclear factor-κB ligand (RANKL) plus macrophage colony stimulating factor (M-CSF)-mediated osteoclastogenesis has been recently implicated in the pathogenesis of this disease. Among other causes, the anticoagulant drug heparin is a notable inducer of secondary osteoporosis, although the molecular pathway underlying this process, particularly in human model, has not been clarified yet. Recently, we reported the differentiation of two subtypes of osteoclasts starting from human peripheral blood CD14-positive monocytes (Monocytes), respectively fusion regulatory protein-1 (FRP-1/CD98)-mediated osteoclasts and RANKL+M-CSF-mediated osteoclasts. We, therefore, investigated in details effects of heparin on differentiation and activation using a simple system of human osteoclastogenesis. When Monocytes were cultured with osteoclastogenesis-relating factors and a high dose of heparin, heparin suppressed osteoclastogenesis in both pathways. However, a proper quantity of heparin enhanced tartrate-resistant acid phosphatase-positive multinucleated giant cell formation. There were significant differences in fusion indices between control osteoclasts and osteoclasts stimulated by moderate concentrations of heparin in two systems (P<
0.05). As a result of osteoclastic activity, FRP-1-mediated osteoclasts treated with a proper quantity of heparin formed larger pits on Ca plates. Moreover, lacunae on dentin surfaces induced by FRP-1-mediated osteoclasts were enhanced with moderate concentration of heparin. In contrast, heparin did not increase pit-formation area on Ca plates and on dentin surfaces by RANKL+M-CSF-mediated osteoclasts. Evaluating the relation between the concentration of heparin and the osteolytic areas on Ca plates, Pearson’s correlation coefficient of the FRP-1 and the RANKL+M-CSF were −0.973 (P<
0.05) and −0.695 (P=0.19), respectively. In present study, although moderate doses of heparin stimulated differentiation in both systems, in osteoclastic activity, heparin promoted only to the FRP-1 system, not to RANKL+M-CSF system. Our results suggested FRP-1-induced osteoclastogenesis mainly contributes to development of heparin osteoporosis and also that the onset mechanism after long-term administration of heparin may be affected by the characteristic bone resorption ability of FRP-1osteoclasts.
Transient osteoporosis of the hip is a disorder characterised by pain, and associated with temporary osteopaenia. Although osteopaenia is the essence of the condition, data do not exist about the local bone density of the femoral neck if no medication is administered. We describe three patients who were treated with limitation of weight-bearing only. Repeated bone mineral density measurements were obtained, and that at the femoral neck was lowest two months after the onset of the condition. The mean reduction in bone mineral density when compared with an age-matched control group was 13% (3% to 24%). Spontaneous recovery was observed in all patients.
A modular layered acetabular component (metal-polyethylene-ceramic) was developed in Japan for use in alumina ceramic-on-ceramic total hip replacement. Between May 1999 and July 2000, we performed 35 alumina ceramic-on-ceramic total hip replacements in 30 consecutive patients, using this layered component and evaluated the clinical and radiological results over a mean follow-up of 5.8 years (5 to 6.5). A total of six hips underwent revision, one for infection, two for dislocation with loosening of the acetabular component, two for alumina liner fractures and one for component dissociation with pelvic osteolysis. There were no fractures of the ceramic heads, and no loosening of the femoral or acetabular component in the unrevised hips was seen at final follow-up. Osteolysis was not observed in any of the unrevised hips. The survivorship analysis at six years after surgery was 83%. The layered acetabular component in our experience, has poor durability because of unexpected mechanical failures including alumina liner fracture and component dissociation.
Antibiotic-impregnated polymethylmethacrylate beads, which are used to deliver antibiotic directly to infected sites in the musculoskeletal system has been evaluated most widely. The disadvantages include reduced biocompatibility with bone, short duration of drug release, very low release rate and thermal damage to the antibiotics. For solving this problem, we developed the antibiotic-impregnated calcium hydroxyapatite ceramic implant (HA) as a new drug delivery system. This study is to evaluate the clinical results of the antibiotic-impregnated HA used for the treatment of infected total hip and knee arthroplasty. Twenty-two patients with infected arthroplasty treated antibiotic-impregnated HA were evaluated. There were 5 men and 17 women with a median age of 65 (range, 54–86 years). The study included 14 hips and 8 knees. The duration from the initial arthroplasty to the detection of the infection was 16 years at the longest (median of 2 years and 2 months). The most common microorganism was Staphylococcus aureus, presented in 13 patients. Antibiotic most frequently impregnated was Vancomycin. In five patients, debridement without removal of the prosthesis was performed with antibiotic-impregnated HA implanted in surrounding bone. In another three patients, one-stage revision was performed with antibiotic-impregnated HA. In fourteen patients, antibiotic-impregnated HA was used to fill the dead space after removal of the prosthesis (two-stage revision was performed in 9 patients). No patients developed evidence of recurrent infection at an average follow-up of 18.7 months. Antibiotic-impregnated HA is an excellent drug delivery system for the infected total hip and knee arthroplasty.
