LY3023414 is a novel oral phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitor designed for advanced cancers, for which a phase II clinical study was completed in March 2020; however, little is known about its effect on bone modelling/remodelling. In this study, we aimed to explore the function of LY3023414 in bone modelling/remodelling. The function of LY3023414 was explored in the context of osteogenesis (bone formation by osteoblasts) and osteoclastogenesis (osteoclast formation and bone resorption). Murine preosteoblast MC3T3-E1 cell line and murine bone marrow-derived macrophage cells (BMMs) were subjected to different treatments. An MTS cell proliferation assay was used to examine the cytotoxicity. Thereafter, different induction conditions were applied, such as MCSF and RANKL for osteoclastogenesis and osteogenic media for osteogenesis. Specific staining, a bone resorption assay, and quantitative real-time polymerase chain reaction (qRT-PCR) were subsequently used to evaluate the effect of LY3023414. Moreover, small interfering RNA (siRNA) was applied to knockdown Akt1 or Akt2 for further validation. Lastly, western blot was used to examine the exact mechanism of action.Aims
Methods
The aim of this study was to present the long-term surgical outcomes, complications, implant survival, and causes of implant failure in patients treated with the modified Harrington procedure using antegrade large diameter pins. A cohort of 50 consecutive patients who underwent the modified Harrington procedure for periacetabular metastasis or haematological malignancy between January 1996 and April 2018 were studied. The median follow-up time for all survivors was 3.2 years (interquartile range 0.9 to 7.6 years).Aims
Patients and Methods
This study aimed to evaluate the incidence and prognosis of patients with spinal metastasis as the initial manifestation of malignancy (SM-IMM). We retrospectively reviewed the electronic medical records of 338 patients who underwent surgical treatment for metastatic spinal disease. The enrolled patients were divided into two groups. The SM-IMM group included patients with no history of malignancy whose site of primary malignancy was diagnosed after the identification of spinal metastasis. The other group included patients with a history of treatment for primary malignancy who then developed spinal metastasis (SM-DTM). The incidence of SM-IMM by site of primary malignancy was calculated. The difference between prognoses after surgical treatment for SM-IMM and SM-DTM was established.Aims
Patients and Methods
Aims
Patients and Methods
This study aims to assess first, whether mutations in the epidermal
growth factor receptor (EGFR) and Kirsten rat sarcoma (kRAS) genes
are associated with overall survival (OS) in patients who present
with symptomatic bone metastases from non-small cell lung cancer
(NSCLC) and secondly, whether mutation status should be incorporated into
prognostic models that are used when deciding on the appropriate
palliative treatment for symptomatic bone metastases. We studied 139 patients with NSCLC treated between 2007 and 2014
for symptomatic bone metastases and whose mutation status was known.
The association between mutation status and overall survival was
analysed and the results applied to a recently published prognostic
model to determine whether including the mutation status would improve
its discriminatory power.Aims
Patients and Methods
We analyzed the long-term outcomes of patients observed over ten years after resection en bloc and reconstruction with extracorporeal irradiated autografts This retrospective study included 27 patients who underwent resection en bloc and reimplantation of an extracorporeal irradiated autograft. The mean patient age and follow-up period were 31.7 years (9 to 59) and 16.6 years (10.3 to 24.3), respectively. The most common diagnosis was osteosarcoma (n = 10), followed by chondrosarcoma (n = 6). The femur (n = 13) was the most frequently involved site, followed by the tibia (n = 7). There were inlay grafts in five patients, intercalary grafts in 15 patients, and osteoarticular grafts in seven patients. Functional outcome was evaluated with the Musculoskeletal Tumor Society (MSTS) scoring system.Aims
Patients and Methods
During the last decades, several research groups have used bisphosphonates for local application to counteract secondary bone resorption after bone grafting, to improve implant fixation or to control bone resorption caused by bone morphogenetic proteins (BMPs). We focused on zoledronate (a bisphosphonate) due to its greater antiresorptive potential over other bisphosphonates. Recently, it has become obvious that the carrier is of importance to modulate the concentration and elution profile of the zoledronic acid locally. Incorporating one fifth of the recommended systemic dose of zoledronate with different apatite matrices and types of bone defects has been shown to enhance bone regeneration significantly
Surgical intervention in patients with bone metastases from breast
cancer is dependent on the estimated survival of the patient. The
purpose of this paper was to identify factors that would predict
survival so that specific decisions could be made in terms of surgical
(or non-surgical) management. The records of 113 consecutive patients (112 women) with metastatic
breast cancer were analysed for clinical, radiological, serological
and surgical outcomes. Their median age was 61 years (interquartile
range 29 to 90) and the median duration of follow-up was 1.6 years
(standard deviation (Aims
Methods
The purpose of this study was to develop a prognostic model for
predicting survival of patients undergoing surgery owing to metastatic
bone disease (MBD) in the appendicular skeleton. We included a historical cohort of 130 consecutive patients (mean
age 64 years, 30 to 85; 76 females/54 males) who underwent joint
arthroplasty surgery (140 procedures) owing to MBD in the appendicular
skeleton during the period between January 2003 and December 2008.
Primary cancer, pre-operative haemoglobin, fracture Aims
Methods
Instability of the hip is the most common mode of failure after
reconstruction with a proximal femoral arthroplasty (PFA) using
an endoprosthesis after excision of a tumour. Small studies report
improved stability with capsular repair of the hip and other techniques,
but these have not been investigated in a large series of patients.
The aim of this study was to evaluate variables associated with
the patient and the operation that affect post-operative stability.
We hypothesised an association between capsular repair and stability. In a retrospective cohort study, we identified 527 adult patients
who were treated with a PFA for tumours. Our data included demographics,
the pathological diagnosis, the amount of resection of the abductor
muscles, the techniques of reconstruction and the characteristics
of the implant. We used regression analysis to compare patients
with and without post-operative instability.Aims
Patients and Methods
Skeletal metastases from hepatocellular carcinoma are highly destructive vascular lesions which severely reduce the quality of life. Pre-existing liver cirrhosis presents unique challenges during the surgical management of such lesions. We carried out a retrospective study of 42 patients who had been managed surgically for skeletal metastases from hepatocellular carcinoma affecting the appendicular skeleton between January 2000 and December 2006. There were 38 men and four women with a mean age of 60.2 years (46 to 77). Surgery for a pathological fracture was undertaken in 30 patients and because of a high risk of fracture in 12. An intralesional surgical margin was achieved in 36 and a wide margin in six. Factors influencing survival were determined by univariate and multivariate analyses. The survival rates at one, two and three years after surgery were 42.2%, 25.8% and 19.8%, respectively. The median survival time was ten months (95% confidence interval 6.29 to 13.71). The number of skeletal metastases and the Child-Pugh grade were identified as independent prognostic factors by Cox regression analysis. The method of management of the hepatocellular carcinoma, its status in the liver, the surgical margin for skeletal metastases, the presence of a pathological fracture and adjuvant radiotherapy were not found to be significantly related to the survival of the patient, which was affected by hepatic function, as represented by the Child-Pugh grade.
Deep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing. The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets. DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory. We present a new biphasic ceramic bone substitute consisting of hydroxyapatite and calcium sulphate for local antibiotic delivery in combination with bone regeneration. Gentamicin release was measured in four setups: 1) Objectives
Materials and Methods
The December 2015 Oncology Roundup360 looks at: Amputation may not be the best option; Growing golf balls bad news!; How close is safe? Radiotherapy and surgery; Lymphocyte: monocyte ratio in osteosarcoma; Are borderline cartilage tumours really borderline?; Boosting algorithms improves survival estimates; CT better than Mirels?
In 1999, we developed a technique for biological
reconstruction after excision of a bone tumour, which involved using
autografts of the bone containing the tumour treated with liquid
nitrogen. We have previously reported the use of this technique
in 28 patients at a mean follow up of 27 months (10 to 54). In this study, we included 72 patients who underwent reconstruction
using this technique. A total of 33 patients died and three were
lost to follow-up, at a mean of 23 months (2 to 56) post-operatively,
leaving 36 patients available for a assessment at a mean of 101
months 16 to 163) post-operatively. The methods of reconstruction included
an osteo-articular graft in 16, an intercalary in 13 and, a composite
graft with prosthesis in seven. Post-operative function was excellent in 26 patients (72.2%),
good in seven (19.4%), and fair in three (8.3%) according to the
functional evaluation system of Enneking. No recurrent tumour occurred
within the grafts. The autografts survived in 29 patients (80.6%),
and the rates of survival at five and ten years were 86.1% and 80.6
%, respectively. Seven of 16 osteo-articular grafts (44%) failed
because of fracture or infection, but all the composite and intercalary
grafts survived. The long-term outcomes of frozen autografting, particularly using
composite and intercalary grafts, are satisfactory and thus represent
a good method of treatment for patients with a sarcoma of bone or
soft tissue. Cite this article:
