Prosthetic joint infection following total hip replacement: results of one-stage versus two-stage exchange.

PURPOSE: Prosthetic hip joint infection remains a challenging socio-economic problem. Curative treatment is usually a one- or two-stage revision surgery, but neither of these options has yet emerged as the treatment of choice. The aim of this study was to evaluate which of these methods produced superior outcomes. METHODS: A retrospective study was performed including 92 patients with deep infections after implantation of primary total hip arthroplasty (THA) who had undergone either one-stage or two-stage revision surgery at a single centre. Infections were classified according to McPherson and we evaluated the rate of persisting infection or reinfection after surgical intervention. RESULTS: The two-stage revision surgery revealed superior outcomes for the analysed infection categories compared to the one-stage procedure except for the least serious category of infections (i.e. McPherson Stage I/A/1, early postoperative infection, no systemic comorbidities, local status uncompromised). Eradication of prosthetic infection was achieved in 94.5 % (n = 52) within the group of two-stage exchange, and 56.8 % (n = 21) of patients treated with a one-stage procedure. Outcome of patients following a one-stage or a two-stage exchange was overall significantly different with p < 0.001. Further deviations between the described two procedures were noted in the subgroups following the classification described by McPherson. CONCLUSIONS: Our results indicate superiority of two-stage revision surgery in case of serious infections. The authors believe that decisions on the surgical approach for the treatment of deep prosthesis infections should be made on the basis of standardized staging systems.

Measurement of the acromiohumeral interval on standardized anteroposterior radiographs: a prospective study of observer variability.

BACKGROUND: An acromiohumeral interval narrower than 6 mm has been considered pathologic and strongly indicative for rotator cuff tears by numerous authors. This prospective study assessed interobserver and intraobserver variability in the radiographic measurement of the acromiohumeral interval. MATERIAL AND METHODS: Five board-certified orthopedic surgeons independently reviewed 58 blinded, standardized anteroposterior shoulder radiographs. The acromiohumeral interval was measured in millimeters. The 5 investigators classified each image a second time in random order. RESULTS: After the same 58 radiographs had been evaluated by the 5 investigators at both examination time points, no significant differences were noted in the interobserver and intraobserver measurements (P < .05). The respective maximum interobserver and intraobserver differences were 4 and 3 mm (range, 0-4 mm). CONCLUSION: The assessment of the acromiohumeral interval using standardized anteroposterior radiographs is a reliable and reproducible method of measurement. LEVEL OF EVIDENCE: Level 1; Investigating a diagnostic test.

The threat of misdiagnosis of primary osteosarcoma over the age of 60: a series of seven cases and review of the literature.

BACKGROUND: Osteosarcoma is the most common, non-haematopoietic, primary malignant bone tumour with an incidence of 0.3-0.5 per 100,000. There is some discrepancy in literature concerning the peaks of incidence of osteosarcoma. Some describe only one peak which arises in adolescence, whilst others report a bimodal age distribution with a second peak over the age of 60. In this retrospective study, we evaluated osteosarcoma patients over age 60 treated at our department and reviewed previous studies from the literature. PATIENTS AND METHODS: Sixty-four patients (40 male, 24 female) with a mean age of 29 years (from 7 to 82) were treated for primary osteosarcomas. At the time of diagnosis, seven patients (two male and five female) were over 60 years of age with a mean follow-up of 46 months after definite diagnosis. RESULTS: Three out of seven osteosarcomas were primarily radiologically or histologically misdiagnosed, but only one was mistreated with intramedullary nailing at a trauma centre. At last follow-up, two patients had died from the disease, three were alive with disease, and two had no evidence of osteosarcoma. CONCLUSIONS: We did not find an increased incidence of primary osteosarcoma in the elderly; yet, older patients had a higher rate of misdiagnosis due to untypical radiological findings in combination with longer times from the onset of first symptoms to definite diagnosis. In cases of pathological fracture, it is essential to assess whether it is caused by mechanical stress or a primary or secondary tumour before leading into mistreatment, especially in older patients.

A common hereditary single-nucleotide polymorphism in the gene of FAS and colorectal cancer survival.

Apoptosis plays an important role in embryogenesis, autoimmunity and tumourigenesis. Cell surface death receptors such as TNFRSF6 (FAS) confer a major apoptotic effect. A single-nucleotide polymorphism in the FAS promoter gene, -670A/G, modulates apoptotic signalling and has been related to susceptibility and progression of a variety of cancers. The present study aimed to evaluate the role of this polymorphism for survival of patients with colorectal cancer. We performed a retrospective analysis including 433 patients with histologically confirmed colorectal cancer. A Cox regression model including FAS -670 genotypes, age at diagnosis, tumour grading, primary tumour size, number of lymph nodes examined, number of metastatic lymph nodes, tumour stage and application of fluorouracil-based adjuvant chemotherapy was used to estimate the effect of the FAS genotype on survival. FAS -670A/G genotype frequencies were 24.2% (AA), 46.3% (AG) and 29.5% (GG). Forty-nine patients were excluded from the Cox regression analysis because of missing values. Out of the remaining 384 patients, 69 (18%) died during a follow-up of maximum 10 years. Mean follow-up time was 58 +/- 34 months (median 55 months). Carriers of the homozygous FAS -670GG genotype had a significantly lower survival rate compared with AA/AG genotype carriers (relative risk 1.76, 95% confidence interval 1.08-2.87; P= 0.023). The FAS -670A/G polymorphism may be associated with overall survival time of patients with colorectal cancer.

Common single nucleotide polymorphisms in the vascular endothelial growth factor gene and colorectal cancer risk.

PURPOSE: Tumor growth requires the formation of new blood vessels, a phenomenon known as angiogenesis. The most important regulator of angiogenesis is vascular endothelial growth factor (VEGF). Several common polymorphisms in the VEGF-gene have been associated with different VEGF expression, production and plasma levels according to allele status, and influence the risk of developing different types of cancer. Therefore, these variants might be risk factors for colorectal cancer (CRC). METHODS: In the present case-control study, VEGF genotypes of the +936 C>T, -2578 C>A and -634 G>C polymorphisms were determined in 427 patients with histologically verified CRC and 427 age and sex-matched healthy control subjects. Genotypes were analyzed by a fluorogenic exonuclease assay (TaqMan). P-value for age at diagnosis was analyzed by student's t test, P-values for tumor characteristics were determined by Pearson's Chi-square test. Threshold for significance was P<0.05. RESULTS: At the time of diagnoses, patients were between 29 and 83 years of age, with a mean age of 61+/-10.9 years. VEGF -2578 C>A and VEGF -634 G>C genotype frequencies were similar among patients and controls. Carriers of the 936T-allele were found slightly more frequent among controls (27.2%) than among patients (22.5%), but this difference did not reach statistical significance (P=0.07). Furthermore, no correlation was found between all these variants and tumor characteristics like size, histological grading, positive regional lymph node metastases or tumor stage. CONCLUSION: We conclude that the investigated polymorphisms are not associated with individual susceptibility to colorectal cancer.

Survival analysis of 254 patients after manifestation of spinal metastases: evaluation of seven preoperative scoring systems.

STUDY DESIGN: Retrospective study. OBJECTIVE: This study analyzed the predictive value of the scoring systems of Bauer, Bauer modified, Tokuhashi, Tokuhashi revised, Tomita, van der Linden, and Sioutos as well as the parameters included in these systems. SUMMARY OF BACKGROUND DATA: Metastases of the spinal column are a common manifestation of advanced cancer. Severe pain, pathologic fracture, and neurologic deficit due to spinal metastases need adequate treatment. Besides oncologic aspects and quality of life, treatment decisions should also include the survival prognosis. METHODS: Two hundred fifty-four patients with confirmed spinal metastases were investigated retrospectively (treatment 1998-2006; 62 underwent surgery and 192 had conservative treatment only). Factors related to survival, such as primary tumor, general condition (Karnofsky Performance Status Scale), neurologic deficit, number of spinal and extraspinal bone metastases, visceral metastases, and pathologic fracture, were analyzed. The survival period was calculated from date of diagnosis of the spinal metastases to date of death or last follow-up (minimum follow-up: 12 months). For statistical analysis, univariate and stepwise multivariate Cox regression analyses were performed. RESULTS: Median overall survival for all patients was 10.6 months. The following factors showed significant influence on survival in multivariate analysis: primary tumor (P < 0.0001), status of visceral metastases (P < 0.0001), and systemic therapy (P < 0.0001). Using the recommended group assignment for each system, only Bauer and Bauer modified showed significant results for the distinction between good, moderate, and poor prognosis. The other systems failed to distinguish significantly between good and moderate prognosis. The hazard ratio of the absolute score of all analyzed systems was, however, statistically significant, with a better score leading to lower risk of death. CONCLUSION: According to this analysis, the Bauer and the Bauer modified scores are the most reliable systems for predicting survival. Since the Bauer modified score furthermore consists of only four positive prognostic factors, we emphasize its impact and simplicity.

Genetic polymorphisms in the vascular endothelial growth factor gene and breast cancer risk. The Austrian "tumor of breast tissue: incidence, genetics, and environmental risk factors" study.

PURPOSE: Vascular endothelial growth factor (VEGF) is a key regulator of tumor-induced angiogenesis and is required for growth of tumors. We tested the hypothesis that VEGF gene polymorphisms may be associated with breast cancer. EXPERIMENTAL DESIGN: We performed a case-control study including 804 female incident breast cancer patients and 804 female age-matched healthy control subjects. We selected seven VEGF candidate polymorphisms and determined genotypes by 5'-nuclease (TaqMan) assays. Furthermore, VEGF plasma levels and genotypes were analyzed in a group of 81 healthy volunteers (64 men and 17 women). RESULTS: Haplotype analysis showed two separate blocks of high-linkage disequilibrium, formed by five polymorphisms upstream of the coding sequence (promoter and 5' untranslated region) and two polymorphisms downstream of the coding sequence. None of the single polymorphisms or haplotypes was significantly associated with the presence of breast cancer. After Bonferroni correction for multiple testing, only one statistical signifcant association between VEGF genotypes and haplotypes and tumor characteristics was observed (-634C allele and small tumor size; p < 0.001). In a multivariate regression analysis including sex, age, VEGF genotypes, and haplotypes as covariates and VEGF plasma level as dependent variable, none of the VEGF polymorphism or haplotypes was a significant predictor of VEGF plasma levels. CONCLUSIONS: Our findings do not support the hypothesis that VEGF polymorphisms are associated with breast cancer risk. The association of the VEGF -634C allele with small tumor size is in clear contrast to a previous publication and should be interpreted with caution until replicated by additional studies.

The Glu228Ala polymorphism in the ligand binding domain of death receptor 4 is associated with increased risk for prostate cancer metastases.

BACKGROUND: Death receptor 4, encoded by the TNFRSF10A gene, is an important mediator of apoptosis and its dysfunction may be related to cancer development and distant tumor spread. A single nucleotide polymorphism in TNFRSF10A (Glu228Ala, rs20576) within a conserved region of the extracellular cysteine-rich domain of death receptor 4 has been associated with an increased risk for a variety of tumor entities. Aim of the present study was to evaluate the role of the TNFRSF10A polymorphism in metastatic progression of prostate cancer after radiation therapy. METHODS: We carried out a prospective study including 702 prostate cancer patients from the Austrian PROCAGENE (Prostate Cancer Genetics) study. Development of metastases was examined in regular follow-up investigations. TNFRSF10A genotypes were determined by a 5'-nuclease assay (TaqMan). RESULTS: Within a median follow-up time of 10 months (range 0-60 months), 24 (3.4%) patients developed metastases. In a Cox regression model including age at diagnosis and risk group as potential confounders, carriage of an 228Ala allele was associated with a relative risk of 2.47 (95% CI 1.10-5.54; P=0.028) for metastases. TNFRSF10A genotypes were not associated with tumor stage, grade, risk group or age at diagnosis. CONCLUSION: We conclude that the TNFRSF10A Glu228Ala polymorphism may be a novel independent risk factor for prostate cancer metastases after radiation therapy.

Volar plate fixation of AO type C2 and C3 distal radius fractures, a single-center study of 55 patients.

OBJECTIVES: We hypothesized that volar locked plate fixation of AO type C2 or C3 fractures could effectively maintain radiographic reduction as shown by comparison of immediate postoperative alignment and that seen after more than 12 months' follow-up. DESIGN: Prospective cohort study. SETTING: Level II trauma center located in a suburban area. PATIENTS: Fifty-five adult patients with intra-articular fractures of the distal radius. INTERVENTION: Open reduction and internal fixation with a locked volar plate and screws. MAIN OUTCOME MEASUREMENTS: Volar tilt, radial inclination, radial length, and articular incongruity were radiologically assessed immediately postoperatively and at the time of final follow-up (mean follow-up: 29 +/- 7 months). RESULTS: At final radiographic examination, the average loss of volar tilt was 1.9 +/- 3.3 degrees (P < 0.001) and the average loss of radial inclination was 1.4 +/- 2.8 degrees (P < 0.001). Four patients had more than 5 degrees loss of radial inclination (7.8%), and 22 patients (43.1%) had more than 5 degrees loss of volar tilt. Radial shortening was not statistically significant (P > 0.05). CONCLUSIONS: The treatment of intra-articular fractures of the distal radius with a volar locked plating system is associated with a small but statistically significant loss of volar tilt and radial inclination upon comparison of immediate postoperative alignment with that seen after more than 12 months' follow-up.

Mesothelioma mortality in Europe: impact of asbestos consumption and simian virus 40.

BACKGROUND: It is well established that asbestos is the most important cause of mesothelioma. The role of simian virus 40 (SV40) in mesothelioma development, on the other hand, remains controversial. This potential human oncogene has been introduced into various populations through contaminated polio vaccines. The aim of this study was to investigate whether the possible presence of SV40 in various European countries, as indicated either by molecular genetic evidence or previous exposure to SV40-contaminated vaccines, had any effect on pleural cancer rates in the respective countries. METHODS: We conducted a Medline search that covered the period from January 1969 to August 2005 for reports on the detection of SV40 DNA in human tissue samples. In addition, we collected all available information about the types of polio vaccines that had been used in these European countries and their SV40 contamination status. RESULTS: Our ecological analysis confirms that pleural cancer mortality in males, but not in females, correlates with the extent of asbestos exposure 25 - 30 years earlier. In contrast, neither the presence of SV40 DNA in tumor samples nor a previous vaccination exposure had any detectable influence on the cancer mortality rate in neither in males (asbestos-corrected rates) nor in females. CONCLUSION: Using the currently existing data on SV40 prevalence, no association between SV40 prevalence and asbestos-corrected male pleural cancer can be demonstrated.

Integrin alpha-2 and beta-3 gene polymorphisms and breast cancer risk.

Integrins are cell surface receptors, which mediate cell-to-cell and cell-to-extracellular matrix adhesion. Some of them, e.g. alpha(V)beta(3), alpha(IIb)beta(3) and alpha(2)beta(1), have been suggested as key players for cancer development and tumor metastasis. Two polymorphisms in the gene for the alpha(2) component, ITGA2 807C>T and 1648G>A, have been associated with the cell-surface density of integrin alpha(2)beta(1). The 176T>C polymorphism in the ITGB3 gene, encoding the beta(3) subunit of integrins alpha(IIb)beta(3) and alpha(V)beta(3), modifies a variety of traits of beta(3) expressing cells. To analyze the role of ITGA2 and ITGB3 polymorphisms for breast cancer risk and prognosis, we performed a case-control study including 500 female breast cancer patients and 500 healthy female age-matched control subjects. All study participants were of Caucasian origin (Austria, Middle-Europe). The ITGA2 1648_AA genotype was significantly associated with breast cancer (odds ratio 3.12; 95% confidence interval 1.11-8.77). Carriers of the most common ITGA2 haplotype (807C_1648G, 'wildtype') were at decreased risk for breast cancer (odds ratio 0.72; 95% confidence interval 0.53-0.98). A histological grade of 3 or 4 was found more often in ITGA2 807TT subjects (p=0.039 compared to CC+CT genotypes) and carriers of an ITGA2 1648A allele (p=0.017 compared to GG genotype). Carriers of the ITGA2 807C_1648G haplotype were less likely to have a histological grade 3 or 4 compared to non-carriers (p=0.003). The ITGB3 176T>C polymorphisms was not associated with breast cancer susceptibility. In a Cox-regression analysis, carriers of the homozygous ITGB3 176-CC genotype had a higher risk for metastasis (relative risk 2.3; 95% CI 1.3-4.2; p=0.005). We conclude that functional polymorphisms in integrin genes ITGA2 and ITGB3 influence the development and progression of breast cancer, respectively. The precise mechanism remains to be determined, but likely involves dysregulated signaling pathways.