A comparison of two short intensive adjuvant chemotherapy regimens in operable osteosarcoma of limbs in children and young adults: the first study of the European Osteosarcoma Intergroup.

PURPOSE: A randomized pilot study was undertaken to assess the acute and chronic toxicities of two short intensive chemotherapy regimens, and to evaluate the feasibility of conservative surgery in this setting. Additional aims were to determine the clinical and radiologic response and the degree of histologic necrosis after chemotherapy. With extension of the study, eventual accrual was sufficient to compare disease-free survival (DFS) and overall survival (OS). PATIENTS AND METHODS: Between July 1983 and December 1986, the European Osteosarcoma Intergroup (EOI) entered 198 eligible patients with classic high-grade extremity osteosarcoma onto a randomized trial that compared doxorubicin (DOX) 25 mg/m2/d times three, intravenous (IV) bolus plus cisplatin (CDDP) 100 mg/m2, 24 hour infusion, every 3 weeks times six; the same combination was preceded 10 days earlier by high-dose methotrexate (HDMTX) 8 g/m2, 6-hour infusion, every 4.5 weeks times four. In the majority of patients (179), chemotherapy was commenced after biopsy; definitive surgery was scheduled at 9 weeks in both groups. RESULTS: Toxicities for both regimens did not differ substantially from those that occurred in other trials of adjuvant chemotherapy in osteosarcoma. Local recurrence (9%) and surgical complications (18%) after conservative surgery were acceptable. With a median follow-up of 53 months, DFS at 5 years is superior (P = .02) for DOX/CDDP, 57% versus 41%, although OS, 64% versus 50%, is not different significantly (P = .10). In a subset of 66 patients for whom pathologic data on the resected specimen were available, DFS (P = .003) and OS (P = .008) were better for those who demonstrated > or = 90% necrosis. CONCLUSION: A brief intensive chemotherapy regimen of DOX/CDDP has produced excellent long-term results, which are similar to those that have been achieved in cooperative group studies of longer, more complex multiagent chemotherapy, and provide the basis for a direct comparison in the next EOI study.

Principal component and factor analysis to study variations in the aging lumbar spine.

Human spine is a multifunctional structure of human body consisting of bones, joints, ligaments, and muscles which all undergo a process of change with the age. A sudden change in these features either naturally or through injury can lead to some serious medical conditions which puts huge burden on health services and economy. While aging is inevitable, the effect of aging on different areas of spine is of clinical significance. This paper reports the growth and degenerative pattern of human spine using principal component analysis. Some noticeable lumbar spine features such as vertebral heights, disc heights, disc signal intensities, paraspinal muscles, subcutaneous fats, psoas muscles, and cerebrospinal fluid were used to study the variations seen on lumbar spine with the natural aging. These features were extracted from lumbar spine magnetic resonance images of 61 subjects with age ranging from 2 to 93 years. Principal component analysis is used to transform complex and multivariate feature space to a smaller meaningful representation. PCA transformation provided 2-D visualization and knowledge of variations among spinal features. Further useful information about correlation among the spinal features is acquired through factor analysis. The knowledge of age related changes in spinal features are important in understanding different spine related problems.

Protein-binding polyhedral boranes.

A series of polyhedral borane derivatives containing protein-binding functional groups has been synthesized. Problems encountered in earlier studies (low incorporation levels, gross precipitation of conjugates) have been overcome by including a water-solubilizing gluconamide group in the structure. This modification has allowed high levels of boron to be covalently bound to HGG, forming a completely water-soluble conjugate.

Osteogenic sarcoma and Rothmund Thomson syndrome.

Rothmund Thomson syndrome (RTS) is a rare autosomal recessive disorder characterised by poikiloderma, dermal atrophy, dystrophic nails, short stature and hypogonadism. An increased incidence of malignancy has been reported in patients with this syndrome secondary, it is postulated, to DNA repair defects. We report the occurrence of an osteogenic sarcoma in an 11-year-old Irish girl with RTS. Although fibroblast cultures demonstrated enhanced radiosensitivity, there was no undue toxicity associated with treatment, which included methotrexate, cisplatinum and Adriamycin. Following conservative surgery, she is currently off treatment and disease-free 2 years from diagnosis.

Protein-binding polyhedral boranes II: DL-S-(10-dimethylsulfidooctahydrodecaborane)methionine.

An analog of methionine, DL-S-(10-dimethylsulfidooctahydrodecaborane)methionine, was synthesized from fully protected homoserine. A protected dipeptide with glycine is described.

Computed tomographic appearances of the pelvis following hindquarter amputation.

Bilateral and midline symmetry of the normal pelvic anatomy is an aid to the interpretation of computed tomographic (CT) examinations. Following hindquarter amputation (HQA) or partial hemipelvectomy (PHP) the normal anatomical relationships are disturbed. The CT examinations of 15 patients who had undergone either an HQA or a PHP for an advanced musculoskeletal malignancy are reviewed. The new "normal" anatomy revealed displacement of the bladder and small bowel to the side of surgery in one third of patients, more commonly in the PHP cases. There were varying degrees of wasting of the ipsilateral musculature, gluteus maximus muscle flap, erector spinae and psoas muscles, etc., because of partial denervation and disruption of their origin or insertion. Recurrent tumour was identified in eight of 10 cases in which it was clinically suspected prior to the CT examination. Invariably the recurrence arose within the muscle flap at the resection margin. Bone involvement by direct tumour spread was present in three cases. Pitfalls in differentiating recurrent tumour from scar tissue are discussed.

Fatigue fractures of the femoral diaphysis in the skeletally immature simulating malignancy.

The clinical and radiological features of three fatigue fractures developing along the medial aspect of the distal femoral diaphysis are described. All three patients were skeletally immature and were referred with the radiographic diagnosis of a probable sarcoma of bone. The plain radiographic findings consisted of an uninterrupted single lamella of periosteal new bone arising medially from the distal femoral diaphysis. Bone scans showed no evidence of hyperaemia on the vascular phase and revealed a fusiform focus of increased uptake in the postero-medial cortex of the lower femoral diaphysis on the 3-h images. Computed tomography showed increased attenuation of the medulla due to fibrosis and an absence of a soft-tissue mass. Periosteal callus was present and a cortical fracture through the medial femoral cortex was identified in two cases. The features that distinguish a fatigue fracture of the femur from a sarcoma are discussed.

Endoprosthetic replacement of the humerus and elbow joint.

Between 1969 and 1985 26 patients with destructive lesions of the distal humerus were treated by endoprosthetic replacement; each implant was custom-made and incorporated part of the distal humerus or the entire bone as well as a hinged total elbow replacement. Recurrence occurred in three of the patients with tumours, and three prostheses were removed because of deep infection in patients with previously compound injuries of the elbow. Another three loosened without infection, but none needed revision or removal and no amputations resulted. Other complications included nerve palsies, but the only deaths were from metastases. A useful range of elbow movement, with a stable arm and good hand function, was achieved in every patient.

Prosthetic replacement of the distal femur for primary bone tumours.

Over a 16-year period, 135 custom-made distal femoral prostheses, based on a fully constrained Stanmore-type knee replacement, were used in the treatment of primary malignant or aggressive benign tumours. Survivorship analysis showed a cumulative success rate of 72% at five years and 64% at seven years. Intact prostheses in 91% of the surviving patients gave good or excellent functional results. Deep infection was the major complication, occurring in 6.8% of cases; clinical aseptic loosening occurred in 6.0%. Revision surgery was carried out for loosening and infection, and the early results are encouraging. We conclude that prosthetic replacement of the distal femur can meet the objectives of limb salvage surgery.

Reconstruction of the hemipelvis after the excision of malignant tumours. Complications and functional outcome of prostheses.

We treated 35 patients with primary malignant tumours of the periacetabular area by resection and prosthetic reconstruction of the defect. At a mean follow-up of 84 months, 15 patients (43%) were free from disease. The most common complications were deep infection (26%), local recurrence (24%) and recurrent dislocation of the hip (17%). The surviving patients achieved an average of 70% of their premorbid function. This method of reconstruction has a high morbidity and should be performed only at specialist centres, but the functional and oncological outcomes are satisfactory.

Hindquarter amputation for tumours of the musculoskeletal system.

We reviewed 34 hindquarter amputations performed for malignant tumours around the hip from 1971 to 1988, classifying them as palliative or curative according to the resection margins or the presence of disseminated disease at the time of surgery. There were three peri-operative deaths, 12 palliative and 19 curative procedures. Ten patients died of disseminated disease within a year of surgery, eight of whom had had a palliative operation. Three patients died between one and five years after palliative surgery. One died of unrelated disease at nine years. Seventeen patients are disease free an average of 31 months from surgery, 16 after curative procedures. The median survival after palliative amputations was six months and the 5-year survival rate for curative cases was 83%.

Aseptic loosening in cemented custom-made prosthetic replacements for bone tumours of the lower limb.

We have made a retrospective study of 1001 custom-made prostheses used as replacements after surgery for bone tumours. There were 493 distal femoral, 263 proximal femoral and 245 proximal tibial prostheses. Aseptic loosening was shown to be the principal mode of failure of the implants, and 71 patients had revision for aseptic loosening of a cemented intramedullary stem. The probability of a patient surviving aseptic loosening for 120 months was 93.8% for a proximal femoral replacement, 67.4% for a distal femoral prosthesis and 58% for a proximal tibial implant. In patients with distal femoral replacements the age of the patient at the time of operation and the percentage of bone resected were related to the risk of aseptic loosening. Young patients with distal femoral prostheses in whom a high percentage of the femur had been replaced had the poorest prognosis for survival without aseptic loosening. The percentage of bone removed had a significant effect in the proximal tibial replacement group, but the age of the patient did not. By contrast, neither the age nor the percentage of bone removed was a factor after proximal femoral replacement. The significance of these findings is discussed in relation to mechanical factors.

Endoprosthetic replacement of the proximal tibia.

We have performed endoprosthetic replacement after resection of tumours of the proximal tibia on 151 patients over a period of 20 years. During this period limb-salvage surgery was achieved in 88% of patients with tumours of the proximal tibia. Both the implant and the operative technique have been gradually modified in order to reduce complications. An initial rate of infection of 36% has been reduced to 12% by the use of a flap of the medial gastrocnemius, to which the divided patellar tendon is attached. Loosening and breakage of the implant have been further causes of failure. We found that the probability of further surgical procedures being required was 70% at ten years and the risk of amputation, 25%. The development of a new rotating hinge endoprosthesis may lower the incidence of mechanical problems. Limb salvage for tumours of the proximal tibia is fraught with complications, but the good functional outcome in successful cases justifies its continued use.

Endoprosthetic replacement of the proximal femur and acetabulum. A survival analysis.

A series of 81 patients has been reviewed to determine the value of endoprosthetic replacement of the proximal femur and hip in the treatment of bone tumours. Standard statistical methods were used to evaluate the survival of the replacements and the patients. Taking removal of the prosthesis, irrespective of the cause, as the criterion for failure the survival of the replacements was found to be 63 per cent after 10 years. If deaths are regarded as failures, then the survival value falls to 48 per cent. The survival of patients with chondrosarcoma and osteoclastoma treated by endoprosthetic replacement compares favourably with survival after amputation or excision of the tumour.

Potential for ammonia recapture by farm woodlands: design and application of a new experimental facility.

There has been increasing pressure on farmers in Europe to reduce the emissions of ammonia from their land. Due to the current financial climate in which farmers have to operate, it is important to identify ammonia control measures that can be adopted with minimum cost. The planting of trees around farmland and buildings has been identified as a potentially effective and low-cost measure to enhance ammonia recapture at a farm level and reduce long-range atmospheric transport. This work assesses experimentally what fraction of ammonia farm woodlands could potentially remove from the atmosphere. We constructed an experimental facility in southern Scotland to simulate a woodland shelterbelt planted in proximity to a small poultry unit. By measuring horizontal and vertical ammonia concentration profiles within the woodland, and comparing this to the concentration of an inert tracer (SF6) we estimate the depletion of ammonia due to dry deposition to the woodland canopy. Together with measurements of mean ammonia concentrations and throughfall fluxes of nitrogen, this information is used to provide a first estimate of the fraction of emitted ammonia that is recaptured by the woodland canopy. Analysis of these data give a lower limit of recapture of emitted ammonia, at the experimental facility, of 3%. By careful design of shelterbelt woodlands this figure could be significantly higher.

Endoprosthetic replacement for bony metastases.

A series of 38 patients with long bone metastases treated at the Birmingham Bone Tumour Treatment Service with resection of the metastatic lesion and replacement of the bone defect with an endoprosthesis was reviewed. The majority of cases had pathological fractures due to a massive destructive lesion. Two-thirds of the patients had a solitary metastasis. Metastases from hypernephroma and breast carcinoma accounted for the majority of cases. All the patients were independently mobile after the endoprosthetic replacement and were pain free. The average survival rate after the endoprosthetic replacement was 14.7 months and this varies with the primary tumour. The indications for endoprosthetic replacement for the treatment of long bone metastases are outlined and the results and complications are discussed. It is concluded that endoprosthetic replacement for bony metastases is an effective palliative procedure for a selected group of patients.

In vivo distraction forces in extendible endoprosthetic replacements--a study of 34 patients.

Using an instrumented distraction tool 34 extendible endoprosthetic replacements were lengthened to measure total resistance to extension. The study consisted of 19 distal femoral, 2 proximal femoral, 1 total femoral, 8 proximal tibial, 1 distal humeral, 2 proximal humeral and 1 total humeral replacements. Among these prostheses a total of 76 measurements were made. The initial load on the prosthesis due to soft tissues and muscles varied between 0 and 578 N with an overall mean of 128 N. There was a linear relationship between extension and load. At 6 mm extension the load varied between 42 and 1513 N with a mean of 476 N. There was very little difference between the means of femoral and tibial measurements. There was very little resistance to extension in the total humeral replacement due to the absence of glenoid and muscle attachment. In the distal humeral replacement all three measurements were comparable with the forces in proximal tibial replacements. Two cases showed very high resistance to extension, which was mainly attributed to the presence of large amounts of scar tissues observed at surgery. During one lengthening operation a 30 s pause at 1 mm increments from 0 to 9 mm showed load recovery of approximately 10 per cent for up to 3 mm, beyond which there appeared to be stiffening of tissues.

Hydrogen sulphide removal by activated sludge diffusion.

Odours from wastewater treatment plants comprise a mixture of various gases, of which hydrogen sulphide (H2S) is the main constituent. Microorganisms commonly found in wastewater can degrade sulphurous compounds. Therefore, the use of activated sludge (AS) for odour control offers an alternative to traditional waste gas treatment processes, such as biofilters, bioscrubbers and biotrickling filters, both in practical terms (use of existing facilities) and economically (minimal capital cost). The performance of AS diffusion as a bioscrubber for removing H2S at concentrations at 25, 75 and 150 ppmv was evaluated. Pilot-scale trials were undertaken using parallel 60-L aeration tanks and 20-L clarifier reactors at the Bedford Sewage Treatment Works, Carington, UK. Olfactometry measurements were also carried out to determine whether there was any increase in odour concentration owing to H2S diffusion. Hydrogen sulphide removal rates of 100% were obtained, with no noticeable increase in odour concentration throughout the trials as measured by olfactometry. Odour concentration was highest at the beginning of the trials and lowest during the high H2S dosing period, with similar values being obtained for test and control. It was concluded that AS diffusion is an effective bioscrubber for the removal of H2S odour.

Reduction of ammonia and odour emissions from pig slurry under slats using oil and foam layers.

In Europe, new legislation on environmental protection requires reductions in emissions of ammonia and odour from animal production. Animal housing is identified as one of the biggest ammonia emission sources in pig production, but abatement techniques for animal houses often require high initial cost. The aims of this study were to investigate the use of layers of oil and foam on slurry under slats. It was found that relatively low-cost, used frying oil (mainly rapeseed oil) could reduce ammonia and odour emissions by about 50% in weaner accommodation. The cost for this technique was Pound Sterling 2.60 per pig place per year. Foam showed poor ammonia abatement potential. The oil was biodegradable, so increasing methane emissions from stored pig slurry by about 60%.

[Chondrosarcoma in a patient with osteopoikilosis. Apropos of a case]. / Chondrosarcome chez un patient porteur d'ostéopoïkilie. A propos d'un cas.

A twenty-nine year old man with osteopoikilosis developed a chondrosarcoma from which he subsequently died. The association of osteopoikilosis with a chondrosarcoma has not previously been reported.