[Should I treat or prevent a pathologic fracture?]. / Hoidanko vai ehkäisenkö patologisen murtuman?

Many cancer diseases will eventually spread to the bones. Fracture-prone metastases should as far as possible be treated preemptively, in which case the operation will be easier both for the surgeon and the patient. Intramedullary nailing, often strengthened with bone cement, is the most commonly utilized method.

Ewing's sarcoma family of tumors in Finland during 1990-2009: a population-based study.

BACKGROUND: Ewing's sarcoma family of tumors (ESFTs) are rare bone and soft tissue tumors characterized by specific genetic alterations. Our aim was to carry out a nationwide analysis of ESFT, to survey the treatments used and to report the five-year disease specific and event-free survival rates (EFS and DSS). MATERIAL AND METHODS: The study data was gathered from the Finnish National Cancer Registry and all five University Hospitals and consisted of 76 bone and soft tissue ESFT patients diagnosed during 1990-2009. Their medical records were reviewed and data on their disease, treatments, complications and outcome were analyzed. RESULTS: The five-year EFS and DSS of patients with localized disease at diagnosis (n = 57) were 70% and 60%, respectively. Factors contributing to DSS and EFS were the axial vs. peripheral site of primary tumor and adequate surgical resection of the primary tumor. DSS was also affected by patient's age at diagnosis and the treatment employed. The five-year DSS of patients with metastatic disease at diagnosis (n = 19) was 33% and both preoperative and high dose chemotherapy were associated with improved survival. CONCLUSION: Population-based studies including both bone and soft tissue ESFTs are few. In this nationwide, population-based study on Finnish bone and soft tissue ESFT patients, we find their treatment successful and results comparable to those previously published. Absence of metastases, young age at diagnosis and a peripheral primary tumor site were associated with a better prognosis. It seems that surgical resection of the primary tumor should be performed whenever adequate resection margins can be achieved. The role of high dose chemotherapy merits further studies in this setting.

Homozygous deletions of cadherin genes in chondrosarcoma-an array comparative genomic hybridization study.

Chondrosarcoma is a malignant bone tumor that is often resistant to chemotherapy and radiotherapy. We applied high resolution oligonucleotide array comparative genomic hybridization to 46 tumor specimens from 44 patients with chondrosarcoma and identified several genes with potential importance for the development of chondrosarcoma. Several homozygous deletions were detected. The tumor suppressor genes CDKN2A and MTAP were each homozygously deleted in four of the cases, and the RB1 gene was homozygously deleted in one. Two homozygous deletions of MTAP did not affect CDKN2A. Deletions were also found to affect genes of the cadherin family, including CDH4 and CDH7, each of which had a targeted homozygous loss in one case, and CDH19, which had a targeted homozygous loss in two cases. Loss of the EXT1 and EXT2 genes was uncommon; EXT1 was homozygously deleted in none and EXT2 in two of the cases, and large heterozygous losses including EXT1 and/or EXT2 were seen in three cases. Targeted gains and amplifications affected the MYC, E2F3, CDK6, PDGFRA, KIT, and PDGFD genes in one case each. The data indicate that chondrosarcomas develop through a combination of genomic imbalances that often affect the RB1 signaling pathway. The inactivation of cadherin genes may also be critical in the pathogenesis of the tumor.

[Psychoactive drugs and accident risk in road traffic]. / Psykoaktiiviset aineet ja onnettomuusriski tieliikenteessä.

In the DRUID (Driving under the influence of drugs, alcohol and medicines) study, the risk of injury and death was calculated for different psychoactive substances on the basis of samples collected from drivers in road traffic and in various accident situations. The number of persons having used alcohol or drugs with negative effects on the ability to drive was lower in Finland than in Europe on the average. Aggravated drunk drivers and mixed substance abusers pose an accident risk that can be several hundredfold higher compared with sober drivers. More attention should be focused on traffic risks due to mixed use of drugs and alcohol.

Incidence, epidemiology and treatment results of osteosarcoma in Finland - a nationwide population-based study.

BACKGROUND: Patients diagnosed with osteosarcoma in Finland during 1991-2005 were retrospectively analyzed in a nationwide, population-based study. We focused on the incidence, treatment and outcome of osteosarcoma patients. We also evaluated the value of known prognostic parameters. MATERIAL AND METHODS: Osteosarcomas were retrieved from the files of the national Finnish Cancer Registry. Only patients with histologically confirmed osteosarcoma were included in the analysis. Histological review was performed. RESULTS: The study consists of 144 osteosarcoma patients with a mean follow-up of 9.8 years for survivors. Mean annual incidence of histologically confirmed osteosarcoma was 1.8 new osteosarcomas per million. The 10-year sarcoma-specific survival for the whole population was 63% and 73% for patients with local disease at presentation. Overall limb-salvage rate was 73% and local control was 84% for patients with a peripheral tumor. Development of local recurrence and major deviation from the chemotherapy protocol were significant adverse factors for sarcoma-specific survival in multivariate analysis. CONCLUSION: The present nationwide and population-based study is our second report of treatment and prognosis of osteosarcoma in Finland. With modern chemotherapy the prognosis of local osteosarcoma has improved in Finland from 47% during 1971-1980 and 65% during 1981-1990 at five years to the present 73% during 1991-2005 at 10 years. The 10-year sarcoma-specific survival of 73% is excellent and comparable to results reported with contemporary treatment protocols in high-volume centers. However, improvement in limb-salvage rate and local control probably requires centralization of treatment of this rare disease.

PET imaging of blood flow and glucose metabolism in localized musculoskeletal tumors of the extremities.

INTRODUCTION: Little is known about blood flow in sarcomas. Our purpose was to study glucose metabolism and blood flow in untreated localized musculoskeletal tumors of the extremities using [(18)F]fluorodeoxyglucose (FDG), oxygen-15 labeled water ([15O]H(2)O) and positron emission tomography (PET). METHODS: Six patients with high-grade osteosarcoma (OS), two with soft-tissue sarcoma (STS) and one with aneurysmal bone cyst had PET studies with [15O]H(2)O and FDG. Arterial blood sampling and autoradiography calculation method were used to define blood flow as milliliters per 100 g times minutes. Tumor FDG uptake was measured as standardized uptake values (SUVs) and regional metabolic rates for FDG (rMRFDG). Two patients also had FDG PET studies during (one patient) and after (two patients) preoperative chemotherapy. All patients underwent dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). The PET findings were compared with the clinical follow-up data and results of DCE-MRI. RESULTS: Blood flow in bone tumors was 31.7-75.2 ml/(100 g×min) and in STS 9.0-45.9 ml/(100 g×min). [(18)F]-Fluorodeoxyglucose uptake and rMRFDG in untreated bone tumors were 5.4-18.4 and 10.9-57.4 µmol/100 g/min, respectively. [(18)F]-Fluorodeoxyglucose uptake and rMRFDG in STS were 2.6-11.5 and 5.6-32.2 µmol/100 g/min, respectively. Four of five sarcomas with SUV>9.0 have already relapsed. High blood flow in untreated OS was related to long overall survival, while the predictive power of glucose metabolism was less apparent. Good histopathological response to therapy was not associated with long survival. CONCLUSIONS: Measurement of blood flow in musculoskeletal tumors appears to be feasible by PET and [(15)O]H(2)O. The influence of tumor blood flow and glucose metabolism on the final outcome in sarcoma is variable and needs further research.

Chemoradiotherapy in the treatment of inoperable high-grade osteosarcoma.

Radical surgery is not feasible for all osteosarcoma patients. Overall survival for non-extremity osteosarcoma, as well as for patients with metastatic disease at diagnosis remains poor. For such patients, radical radiotherapy combined with chemotherapy may present an effective treatment approach. This report describes the results of conservative treatment for osteosarcoma patients not suitable for surgery. Seven out of 71 consecutive osteosarcoma patients were treated non-surgically at the Helsinki University Central Hospital either due to the inoperability of the tumour or the patient's choice of therapy. Staging procedures and measurement of tumour size were performed using computed tomography and magnetic resonance imaging. Six patients were treated with chemo-radiotherapy, and one patient received radiotherapy alone. Five patients received computer-assisted dose-planned radiotherapy with curative intent (total dose 60-70.5 Gray), and two patients received radiotherapy as palliation. Radiotherapy relieved symptoms efficiently. Median time to local failure was 2.6 years (range 0.5-16.9+ years). Five year after treatment termination four patients were alive, and one of them remained disease-free. For selected patients not suitable for surgery, radiotherapy combined with chemotherapy provides an option to reduce symptoms caused by the primary tumour and improve quality of life. For some patients, this approach may (even) produce long-term remission.

Osteosarcoma in Finland from 1971 through 1990: a nationwide study of epidemiology and outcome.

BACKGROUND AND PURPOSE: There have only been a few nationwide studies on the epidemiology and outcome of osteosarcoma. We report the clinical features, treatment, and prognosis of osteosarcoma in Finland for the period 1971-1990. METHODS: The study material was derived from population-based data from the national Finnish Cancer Registry. 302 osteosarcomas were reported during the study period. Histological slides could be retrieved for 199 cases and from histological re-examination, 139 (83%) of these cases were confirmed as osteosarcoma and were included in the analysis. The mean length of follow-up was 8 (0.1-28) years. RESULTS: The overall 5-year survival for the whole study population was 58%, with an improvement in survival during 1981-1990 (65%) compared to the period 1971-1980 (47%) (p=0.01). More chemotherapy was administered in the later time period. For metastasis-free survival, diagnosis in the 1970s as opposed to the 1980s (p=0.01) and large tumor size worsened outcome in univariate analysis. Patients who developed metastatic relapse within 10 months of the diagnosis had worse sarcoma-specific survival than those who developed metastases later. Limb-salvage surgery increased from 12% to 23% for patients with a peripheral tumor, with no increase in local relapses. INTERPRETATION: We recommend aggressive approach to treat recurrent disease, with a view to further improving survival. In a small country such as Finland it is necessary to concentrate treatment to only a few centers, to ensure a high quality of treatment.

Observational failures/distraction and disease attack/incapacity as cause(s) of fatal road crashes in Finland.

OBJECTIVE: To study the incidence of health-related conditions and observational failures/distraction (OFD) as an immediate cause for fatal motor vehicle accidents (FMVA) and to correlate them with driver's age. METHODS: Retrospective study of all FMVA in Finland secondary to OFD from January 1995 to December 2005 and FMVA secondary to a disease attack/incapacity (DA) from January 2003 to December 2004. The data were based on the final investigation reports of the Finnish Motor Insurers' Centre. The cases were categorized into the three following groups: 1) vehicle crashes due to OFD of the driver, 2) pedestrian-vehicle accidents due to the driver's OFD, and 3) pedestrian-vehicle accidents due to the pedestrian's OFD. In the second part, 54 autopsy reports from FMVA resulting from a DA of the driver between the years 2003-2004 were revisited and the health-related causes of the accident were investigated. RESULTS: Oldest age group (> 65 years) had the highest prevalence of FMVA secondary to an OFD. We estimated that in 20-30% of all FMVA affecting subjects > 65 years an impairment of cognitive functions might have played a role. Analysis of the DA that the inspection teams had concluded to have been the immediate risk factor for the FMVA revealed that these accidents accounted for 10.3% of all FMVA in 2003-2004. Cardiovascular diseases were most often involved. CONCLUSIONS: OFD as an immediate cause of FMVA began to play a role from the age of 60 years onwards. The role of health conditions as a cause of FMVA was higher than expected. Cardiovascular disease (70%) was found to be the leading medical condition that inhibited the driving task among the DA related to FMVA in Finland.

Cement is recommended in intralesional surgery of giant cell tumors: a Scandinavian Sarcoma Group study of 294 patients followed for a median time of 5 years.

BACKGROUND: Giant cell tumors of bone rarely metastasize but often recur locally after surgery. There is limited knowledge about the risk of recurrence related to different types of treatment. PATIENTS AND METHODS: We analyzed factors affecting the local recurrence rate in 294 patients with giant cell tumors of the extremities using prospectively collected material from 13 centers. The median follow-up time was 5 (0.2-18) years. RESULTS: A local recurrence was diagnosed in 57 of 294 patients (19%). The overall 5-year local recurrence rate was 0.22. Univariate analysis identified young age and intralesional surgery to be associated with a higher risk of recurrence. Based on multivariate analysis, the relative risk was 2.4-fold for intralesional surgery compared to more extensive operative methods. There was no correlation between tumor size, tumor extension, sex of the patient, tumor location, or fracture at diagnosis and outcome. In the subgroup of 200 patients treated with intralesional surgery, the method of filling (cement or bone) was known for 194 patients and was statistically highly significant in favor of the use of cement. INTERPRETATION: Intralesional surgery should be the first choice in most giant cell tumors, even in the presence of a pathological fracture. After thorough evacuation, the cavity should be filled with cement.

Malignant fibrous histiocytoma of bone: analysis of genomic imbalances by comparative genomic hybridisation and C-MYC expression by immunohistochemistry.

Malignant fibrous histiocytoma (MFH) of bone is a rare, highly malignant tumour. As very little is known about its genetic alterations, 26 bone MFHs were analysed by comparative genomic hybridisation (CGH). Twenty-three tumours (89%) had DNA sequence copy number changes (mean, 7.2 changes per sample). Gains were more frequent than losses (gains:losses=2.5:1). Minimal common regions for the most frequent gains were 8q21.3-qter (35%), 9q32-qter (35%), 7q22-q31 (35%), 1q21-q23 (31%), 7p12-pter (31%), 7cen-q11.2 (31%) and 15q21 (31%). Minimal common regions for the most frequent losses were 13q21-q22 (42%) and 18q12-q22 (27%). High-level amplifications were detected in 8 out of the 26 tumours (31%). The only recurrent amplifications, 1q21-q23 and 8q21.2-q22, were present in two samples (8%). As copy number increase at 8q24 (the locus of C-MYC) was frequent, the expression of C-MYC was studied by immunohistochemistry. Increased levels of c-myc protein were detected in 7 out of 21 tumours studied (33%). 81% of the samples studied both by CGH and immunohistochemistry showed concordant results. Furthermore, the findings of the present study were compared to previous publications on osteosarcoma, soft tissue MFH and fibrosarcoma of bone. Clear differences were detected in CGH aberration patterns, further supporting the concept of bone MFH as an individual bone tumour entity. Finally, the findings of the present study reflect well the high malignancy and aggressive nature of bone MFH.

Gene amplifications in osteosarcoma-CGH microarray analysis.

Little is known about the genomic alterations underlying osteosarcoma. We performed a genomewide high-resolution gene copy number analysis of 22 osteosarcoma samples using comparative genomic hybridization on a cDNA microarray that contained cDNA clones of about 13,000 genes. Nineteen of the 22 cases had amplifications that on average spanned more than 1 Mb and contained more than 10 genes. Numerous regions of gain and loss were identified, and their boundaries were defined at high resolution. Novel amplicons were found at 14q11, 17q25, and 22q11-q13. Earlier-known large amplified regions were detected at 12q11-q15, 8q24, 6p12-p13, and 17p11-p13 in 8, 6, 5, and 4 of the 22 samples, respectively. Amplification of 12q was observed more frequently (36% of the cases) than previously reported. Previously known small amplicons at 1p34-p36, 1q21, 19q13, and 21q22 were seen in at least three cases. Our results implicate TOM1L2 and CYP27B1 as having roles as novel targets for the 17p and 12q amplicons, respectively. Details (www.helsinki.fi/cmg) of the amplified genes in each amplicon provide valuable raw data for further in silico studies.

Radicular lower extremity pain as the first symptom of primary hyperparathyroidism.

Clinical symptoms of hyperparathyroidism are generally nausea, vomiting, fatigue, constipation, and hypotonicity of the muscles and ligaments; bone pain and tenderness are also seen but are more common in secondary hyperparathyroidism. We report a histologically confirmed case of a 28-year-old man whose sole symptom of primary hyperparathyroidism was lower extremity radicular pain due to a vertebral brown tumor. Magnetic resonance imaging demonstrated brown tumor to be hyperintense on T2-weighted and slightly hypointense on T1-weighted sequences; it showed intense contrast enhancement with gadolinium. Because brown tumors usually contain hemosiderin a short T2 should have been expected, but this was not seen in our case. Healing resulted in decreasing contrast enhancement on T1-weighted sequences and increasingly short T2. To our knowledge, this is the first report of a lumbar vertebral brown tumor associated with primary hyperparathyroidism.