Bone metastasis ultimately occurs due to a complex multistep process, during which the interactions between cancer cells and bone microenvironment play important roles. Prior to colonization of the bone, cancer cells must succeed through a series of steps that will allow them to gain migratory and invasive properties; epithelial-to-mesenchymal transition (EMT) is known to be integral here. The aim of this study was to determine the effects of G protein subunit alpha Q (GNAQ) on the mechanisms underlying bone metastasis through EMT pathway. A total of 80 tissue samples from patients who were surgically treated during January 2012 to December 2014 were used in the present study. Comparative gene analysis revealed that the GNAQ was more frequently altered in metastatic bone lesions than in primary tumour sites in lung cancer patients. We investigated the effects of GNAQ on cell proliferation, migration, EMT, and stem cell transformation using lung cancer cells with GNAQ-knockdown. A xenograft mouse model tested the effect of GNAQ using micro-CT analyses and histological analyses.Aims
Methods
The use of frozen tumour-bearing autograft combined with a vascularized fibular graft (VFG) represents a new technique for biological reconstruction of massive bone defect. We have compared the clinical outcomes between this technique and Capanna reconstruction. From June 2011 to January 2016 a retrospective study was carried out of patients with primary osteosarcoma of lower limbs who underwent combined biological intercalary reconstruction. Patients were categorized into two groups based on the reconstructive technique: frozen tumour-bearing autograft combined with concurrent VFG (Group 1) and the Capanna method (Group 2). Demographics, operating procedures, oncological outcomes, graft union, limb function, and postoperative complications were compared.Aims
Methods
To assess complications and failure mechanisms of osteoarticular
allograft reconstructions for primary bone tumours. We retrospectively evaluated 38 patients (28 men, 74%) who were
treated at our institution with osteoarticular allograft reconstruction
between 1989 and 2010. Median age was 19 years (interquartile range
14 to 32). Median follow-up was 19.5 years (95% confidence interval
(CI) 13.0 to 26.1) when 26 patients (68%) were alive. In addition, we
systematically searched the literature for clinical studies on osteoarticular
allografts, finding 31 studies suitable for analysis. Results of
papers that reported on one site exclusively were pooled for comparison.Aims
Patients and Methods
We determined the efficacy of a devitalised autograft
(n = 13) and allograft (n = 16) cortical strut bone graft combined
with long-stem endoprosthetic reconstruction in the treatment of
massive tumours of the lower limb. A total of 29 patients (18 men:11
women, mean age 20.1 years (12 to 45) with a ratio of length of
resection to that of the whole prosthesis of >
50% were treated
between May 2003 and May 2012. The mean follow-up was 47 months
(15 to 132). The stem of the prosthesis was introduced through bone
graft struts filled with cement, then cemented into the residual
bone. Bone healing was achieved in 23 patients (86%). The mean Musculoskeletal
Tumour Society functional score was 85% (57 to 97). The five-year
survival rate of the endoprostheses was 81% (95% confidence intervals
67.3 to 92.3). The mean length of devitalised autografts and allografts
was 8.6 cm (5 to 15), which increased the ratio of the the length
of the stem of the prosthesis to that of the whole length of the
prosthesis from a theoretical 35% to an actual 55%. Cortical strut bone grafting and long-stem endoprosthetic reconstruction
is an option for treating massive segmental defects following resection
of a tumour in the lower limb. Patients can regain good function
with a low incidence of aseptic loosening. The strut graft and the
residual bone together serve as a satisfactory bony environment
for a revision prosthesis, if required, once union is achieved. Cite this article:
Avascular necrosis (AVN) is a serious complication
of high-dose chemotherapy for haematological malignancy in childhood.
In order to describe its incidence and main risk factors and to
evaluate the current treatment options, we reviewed 105 children
with a mean age of 8.25 years (1 to 17.8) who had acute lymphoblastic
or acute myeloid leukaemia, or a non-Hodgkin’s lymphoma. Overall,
eight children (7.6%) developed AVN after a mean of 16.8 months (8
to 49). There were four boys and four girls with a mean age of 14.4
years (9.8 to 16.8) and a total of 18 involved sites, 12 of which
were in the femoral head. All these children were aged >
nine years
(p <
0.001). All had received steroid treatment with a mean cumulative
dose of prednisone of 5967 mg (4425 to 9599) compared with a mean
of 3943 mg (0 to 18 585) for patients without AVN (p = 0.005). No
difference existed between genders and no thrombophilic disorders
were identified. Their initial treatment included 11 core decompressions
and two bipolar hip replacements. Later, two salvage osteotomies
were done and three patients (four hips) eventually needed a total
joint replacement. We conclude that AVN mostly affects the weight-bearing
epiphyses. Its risk increases with age and higher steroid doses.
These high-risk patients may benefit from early screening for AVN. Cite this article:
To date, all surgical techniques used for reconstruction
of the pelvic ring following supra-acetabular tumour resection produce
high complication rates. We evaluated the clinical, oncological
and functional outcomes of a cohort of 35 patients (15 men and 20
women), including 21 Ewing’s sarcomas, six chondrosarcomas, three sarcomas
not otherwise specified, one osteosarcoma, two osseous malignant
fibrous histiocytomas, one synovial cell sarcoma and one metastasis.
The mean age of the patients was 31 years (8 to 79) and the latest
follow-up was carried out at a mean of 46 months (1.9 to 139.5)
post-operatively. We undertook a functional reconstruction of the pelvic ring using
polyaxial screws and titanium rods. In 31 patients (89%) the construct
was encased in antibiotic-impregnated polymethylmethacrylate. Preservation
of the extremities was possible for all patients. The survival rate
at three years was 93.9% (95% confidence interval (CI) 77.9 to 98.4),
at five years it was 82.4% (95% CI 57.6 to 93.4). For the 21 patients
with Ewing’s sarcoma it was 95.2% (95% CI 70.7 to 99.3) and 81.5%
(95% CI 52.0 to 93.8), respectively. Wound healing problems were
observed in eight patients, deep infection in five and clinically
asymptomatic breakage of the screws in six. The five-year implant survival
was 93.3% (95% CI 57.8 to 95.7). Patients were mobilised at a mean
of 3.5 weeks (1 to 7) post-operatively. A post-operative neurological
defect occurred in 12 patients. The mean Musculoskeletal Tumor Society
score at last available follow-up was 21.2 (10 to 27). This reconstruction technique is characterised by simple and
oncologically appropriate applicability, achieving high primary
stability that allows early mobilisation, good functional results
and relatively low complication rates. Cite this article:
It is important to be able to identify patients
with an increased risk of venous thromboembolism (VTE) in order
to minimise the risk of an event. We investigated the incidence
and risk factors for post-operative VTE in 168 consecutive patients
with a malignancy of the lower limb. The period of study included
ten months before and 12 months after the introduction of chemical
thromboprophylaxis. All data about the potential risk factors were identified
and classified into three groups (patient-, surgery- and tumour-related).
The outcome measure was a thromboembolic event within 90 days of
surgery. Of the 168 patients, eight (4.8%) had a confirmed symptomatic
deep-vein thrombosis and one (0.6%) a fatal pulmonary embolism.
Of the 28 variables tested, age >
60 years, higher American Society
of Anesthesiologists grade and metastatic tumour were independent
risk factors for VTE. The overall rate of symptomatic VTE was not significantly
different between patients who received chemical thromboprophylaxis
and those who did not. Knowledge of these risk factors may be of
value in improving the surgical outcome of patients with a malignancy
of the lower limb. Cite this article:
Pathological fractures of the humerus are associated with pain, morbidity, loss of function and a diminished quality of life. We report our experience of stabilising these fractures using polymethylmethacrylate and non-locking plates. We undertook a retrospective review over 20 years of patients treated at a tertiary musculoskeletal oncology centre. Those who had undergone surgery for an impending or completed pathological humeral fracture with a diagnosis of metastatic disease or myeloma were identified from our database. There were 63 patients (43 men, 20 women) in the series with a mean age of 63 years (39 to 87). All had undergone intralesional curettage of the tumour followed by fixation with intramedullary polymethylmethacrylate and plating. Complications occurred in 14 patients (22.2%) and seven (11.1%) required re-operation. At the latest follow-up, 47 patients (74.6%) were deceased and 16 (25.4%) were living with a mean follow-up of 75 months (1 to 184). A total of 54 (86%) patients had no or mild pain and 50 (80%) required no or minimal assistance with activities of daily living. Of the 16 living patients none had pain and all could perform activities of daily living without assistance. Intralesional resection of the tumour, filling of the cavity with cement, and plate stabilisation of the pathological fracture gives immediate rigidity and allows an early return of function without the need for bony union. The patient’s local disease burden is reduced, which may alleviate tumour-related pain and slow the progression of the disease. The cemented-plate technique provides a reliable option for the treatment of pathological fractures of the humerus.
Endoprosthetic reconstruction following resection of 31 tumours of the proximal femur in 30 patients was performed using a Wagner SL femoral revision stem. The mean follow-up was 25.6 months (0.6 to 130.0). Of the 28 patients with a metastasis, 27 died within a mean follow-up period of 18.1 months (0.6 to 56.3) after the operation, and the remaining patient was excluded from the study 44.4 months post-operatively when the stem was removed. The two patients with primary bone tumours were still alive at the latest follow-up of 81.0 and 130.0 months, respectively. One stem only was removed for suspected low-grade infection 44.4 months post-operatively. The worst-case survival rate with removal of the stem for any cause and/or loss to follow-up was 80.0% (95% confidence interval 44.9 to 100) at 130.0 months. The mean Karnofsky index increased from 44.2% (20% to 70%) pre-operatively to 59.7% (0% to 100%) post-operatively, and the mean Merle d’Aubigné score improved from 4.5 (0 to 15) to 12.0 (0 to 18). The mean post-operative Musculoskeletal Tumour Society score was 62.4% (3.3% to 100%). The Wagner SL femoral revision stem offers an alternative to special tumour prostheses for the treatment of primary and secondary tumours of the proximal femur. The mid-term results are very promising, but long-term experience is necessary.
We describe the management of nonunion combined with limb-length discrepancy following vascularised fibular grafting for the reconstruction of long-bone defects in the lower limb after resection of a tumour in skeletally immature patients. We operated on nine patients with a mean age of 13.1 years (10.5 to 14.5) who presented with a mean limb-length discrepancy of 7 cm (4 to 9) and nonunion at one end of a vascularised fibular graft, which had been performed previously, to reconstruct a bone defect after resection of an osteosarcoma. Reconstruction was carried out using a ring fixator secured with correction by half pins of any malalignment, compression of the site of nonunion and lengthening through a metaphyseal parafocal osteotomy without bone grafting. The expected limb-length discrepancy at maturity was calculated using the arithmetic method. Solid union and the intended leg length were achieved in all the patients. Excessive scarring and the distorted anatomy from previous surgery in these patients required other procedures to be performed with minimal exposures and dissection in order to avoid further compromise to the vascularity of the graft or damage to neurovascular structures. The methods which we chose were simple and effective in addressing these complex problems.
We present a retrospective study of patients suffering from a variety of benign tumours in whom external fixators were used to treat deformity and limb-length discrepancy, and for the reconstruction of bone defects. A total of 43 limbs in 31 patients (12 male and 19 female) with a mean age of 14 years (2 to 54) were treated. The diagnosis was Ollier’s disease in 12 limbs, fibrous dysplasia in 11, osteochondroma in eight, giant cell tumour in five, osteofibrous dysplasia in five and non-ossifying fibroma in two. The lesions were treated in the tibia in 19 limbs, in the femur in 16, and in the forearm in eight. The Ilizarov frame was used in 25 limbs, the Taylor Spatial Frame in seven, the Orthofix fixator in six, the Monotube in four and the Heidelberg fixator in one. The mean follow-up was 72 months (22 to 221). The mean external fixation period was 168 days (71 to 352). The mean external fixation index was 42 days/cm (22.2 to 102.0) in the 22 patients who required limb lengthening. The mean correction angle for those with angular deformity was 23° (7° to 45°). At final follow-up all patients had returned to normal activities. Four patients required a second operation for recurrent deformity of further limb lengthening. Local recurrence occurred in one patient, requiring further surgery.
The outcome of tibial allograft reconstruction after resection of a tumour is inconsistent and has a high rate of failure. There are few reports on the use of tibial allografts in children with open growth plates. We performed 21 allograft reconstructions (16 osteoarticular, five intercalary) in 19 consecutive patients between seven and 17 years of age. Two had Ewing’s sarcoma, one an adamantinoma and 16 osteosarcoma, one with multifocal disease. Five patients have died; the other 14 were free from disease at the time of follow-up. Six surviving patients (eight allograft reconstructions) continue to have good or excellent function at a mean of 59 months (14 to 132). One patient has poor function at 31 months. The other seven patients have a good or excellent function after additional procedures including exchange of the allograft and resurfacing or revision to an endoprosthesis at a mean of 101 months (43 to 198). The additional operations were performed at a mean of 47 months (20 to 84) after the first reconstruction. With the use of allograft reconstruction in growing children, joints and growth plates may be preserved, at least partially. Although our results remain inconsistent, tibial allograft reconstruction in selected patients may restore complete and durable function of the limb.
We reviewed 29 patients who had undergone intercalary resection for malignant tumours. Of these, 14 had received segmental allograft reconstruction and 15 extracorporeally-irradiated autograft. At a mean follow-up of 71 months (24 to 132), 20 were free from disease, five had died and four were alive with pulmonary metastases. Two patients, one with an allograft and one with an irradiated autograft, had a local recurrence. Reconstruction with extracorporeally-irradiated autograft has a significantly lower rate of nonunion (7% Extracorporeally-irradiated autograft could be an acceptable alternative for reconstruction after intercalary resection, especially in countries where it is difficult to obtain allografts.
We describe a method of reconstruction using tumour-bearing autograft treated by liquid nitrogen in 28 patients. The operative technique consisted of The limb function was rated as excellent in 20 patients (71.4%), good in three (10.7%), fair in three (10.7%), and poor in two (7.1%). At the final follow-up six patients had died at a mean of 19.8 months after the operation, while 21 remained free from disease with a mean follow-up of 28.1 months (10 to 54). One patient is alive with disease. Bony union was seen at a mean of 6.7 months after the operation in 26 patients. Complications were encountered in seven patients, including three deep infections, two fractures, and two local recurrences. All were managed successfully. Our results suggest that this is a simple and effective method of biological reconstruction.