The role of (18)F-FDG PET in the differentiation between lung metastases and synchronous second primary lung tumours.

PURPOSE: In lung cancer patients with multiple lesions, the differentiation between metastases and second primary tumours has significant therapeutic and prognostic implications. The aim of this retrospective study was to investigate the potential of (18)F-FDG PET to discriminate metastatic disease from second primary lung tumours. METHODS: Of 1,396 patients evaluated by the thoracic oncology group between January 2004 and April 2009 at the Radboud University Nijmegen Medical Centre, patients with a synchronous second primary lung cancer were selected. Patients with metastatic disease involving the lungs served as the control group. Maximum standardized uptake values (SUVs) measured with (18)F-FDG PET were determined for two tumours in each patient. The relative difference between the SUVs of these tumours (∆SUV) was determined and compared between the second primary group and metastatic disease group. Receiver-operating characteristic (ROC) curve analysis was performed to determine the sensitivity and specificity of the ∆SUV for an optimal cut-off value. RESULTS: A total of 37 patients (21 metastatic disease, 16 second primary cancer) were included for analysis. The ∆SUV was significantly higher in patients with second primary cancer than in those with metastatic disease (58 vs 28%, respectively, p < 0.001). The area under the ROC curve was 0.81 and the odds ratio for the optimal cut-off was 18.4. CONCLUSION: SUVs from (18)F-FDG PET images can be helpful in differentiating metastatic disease from second primary tumours in patients with synchronous pulmonary lesions. Further studies are warranted to confirm the consistency of these results.

Can orthopedic trials change practice?

BACKGROUND AND PURPOSE: The impact of large, randomized trials in orthopedic surgery on surgeons' preferences for a particular surgical approach remains unclear. We surveyed surgeons to assess whether they would change practice based upon results of a large, multicenter randomized controlled hip fracture trial. METHODS: We conducted a cross-sectional survey among International Hip Fracture Research Collaborative (IHFRC) surgeons and surgeons who were members of Arbeitsgemeinschaft fuer Osteosynthesefragen - Association for the Study of Internal Fixation (AO/ASIF) to determine the likelihood that they would change practice based on findings of a proposed large, multicenter randomized controlled trial (the Hip Fracture Evaluation with Alternatives of Total Hip Arthroplasty versus Hemi-Arthroplasty (HEALTH) study). We asked surgeons their current preferences for the management of displaced femoral neck fractures and whether a trial that definitively revealed a substantial improvement in function and quality of life with no difference in risk of revision surgery was important and would cause them to change practice. RESULTS: Of 883 surgeons surveyed, 210 responded from IHFRC and 586 from AO/ASIF (a response rate of 90%). Most surgeons (61%) preferred hemiarthroplasty (HA) for treating displaced femoral neck fractures. 72% of responding surgeons believed that a substantial improvement in patient function with total hip arthroplasty (THA) and no adverse effects on revision surgery would be an important finding. Moreover, of 483 surgeons who preferred hemiarthroplasty, 62% would change their practice based upon the findings of the trial. INTERPRETATION: Large clinical trials in orthopedics are worthwhile endeavors, as they have the potential to change practice among surgeons. Surgeons seem willing to adopt alternative surgical approaches if the evidence is compelling and sound.

The impact of clinical data on the evaluation of tibial fracture healing.

BACKGROUND: Radiographic healing is a common outcome measure in orthopedic trials and adjudication by outcome assessors is often conducted on the basis of plain films alone. The degree to which this process reflects clinical practice, in which both plain films and clinical notes are available, is uncertain. We explored the effect of adding clinical notes to radiographs in the adjudication process of a feasibility trial of tibial shaft fractures. METHODS: Radiographic and clinical data from a multicenter randomized controlled trial of 51 patients with operatively treated tibial fractures formed the basis of the study data. At the completion of the trial, serial radiographs (anteroposterior and lateral) were independently evaluated for progression of fracture healing, defined as bridging of at least 3 of 4 cortices, by an adjudication committee comprised of 3 blinded orthopaedic trauma surgeons. Immediately after determination of radiographic time to healing, each surgeon was provided with clinical notes associated with each radiographic follow up visit and asked to re-visit their initial impression. Consensus was achieved for both adjudications. We calculated the percentage of time to healing consensus decisions that changed after evaluation of clinical notes. We further examined the contents of clinical notes and their relative influence on the committee's decisions. RESULTS: 47 of 51 patients were determined to have healed radiographically during the trial follow-up period, and consideration of clinical notes resulted in a change of 40% (19 of 47) of time to healing consensus decisions; however, revised decisions were equally likely to support an earlier or a later time to healing. Clinical notes that resulted in a change to either a 'healed' or a 'not healed' decision contained significantly more comments of either pain resolution or deterioration, respectively, resumption of or failure to resume weightbearing, or either return or no return to work/pre-injury activities (p < 0.001). CONCLUSIONS: The addition of clinical notes to the adjudication of radiographic fracture healing changed the outcome decision in a substantial number of cases. Orthopedic trialists should consider the addition of clinical notes to adjudication material in studies of fracture healing in order to enhance the generalizability of their results. TRIAL REGISTRATION: The TRUST trial was registered [ID NCT00667849] at http://clinicaltrials.gov/ct2/show/NCT00667849.

Prospectively screening for eligible patients was inaccurate in predicting patient recruitment of orthopedic randomized trials.

OBJECTIVE: To compare the accuracy of estimates of potential recruitment from a prospective 8-week screening study compared with a retrospective chart review across sites participating in two fracture management trials. STUDY DESIGN AND SETTING: During the planning phase of two large, multicenter, randomized controlled fracture management trials, 74 clinical sites provided estimates of the annual recruitment rate both retrospectively (based on chart reviews) and prospectively. The prospective estimate was generated by screening, for 8 weeks, all incoming patients for eligibility in the concerning trial, without actually enrolling any patient. We compared these prospective and retrospective estimates with one another (for 74 sites in the two trials) and with actual 1-year recruitment rates in the definitive trial (for nine sites in one trial). RESULTS: There was a median difference of four patients (interquartile range: -14 to 18 patients; P=0.89) between a center's prospective estimate and its retrospective estimate. Both predictions were overestimations of recruitment in the definitive trial; only 31% (95% confidence interval [CI]: 28, 35) of retrospectively estimated patients, and 31% (95% CI: 27, 35) of prospectively estimated patients were recruited in the definitive trials. CONCLUSION: Compared with relatively simple chart reviews, prospectively screening for eligible patients at clinical sites, which is associated with substantial costs, did not result in more accurate predictions of accrual in large, multicenter, randomized controlled trials.

EUS-FNA for the detection of left adrenal metastasis in patients with lung cancer.

In patients with lung cancer, enlarged or (18)Fluoro-deoxyglucose positron emission tomography ((18)FDG-PET) positive left adrenal glands are suspected for distant metastases and require tissue confirmation for a definitive assessment. The aim of this study was to assess the sensitivity of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for left adrenal metastases in lung cancer patients with a suspect adrenal gland based on imaging. EUS-FNA findings of patients with (suspected) lung cancer and CT enlarged or (18)FDG-PET positive left adrenal glands were retrospectively evaluated. In the absence of metastases at EUS, clinical and radiological follow-up was obtained. In 85 patients, EUS-FNA demonstrated left adrenal metastases of lung cancer in 53 (62%), benign adrenal tissue in 25 (29%), a metastasis from colon carcinoma in 1 (1%) and a primary adrenocortical carcinoma in 1 (1%) patient. In five patients (5.9%), the aspirates contained non-representative material. EUS outcomes were false negative in two patients. Sensitivity and negative predictive value (NPV) for EUS-FNA of the left adrenal gland were at least 86% (95% CI 74-93%) and 70% (95% CI 50-85%). No complications occurred. EUS-FNA is a sensitive, safe and minimally invasive technique to provide tissue proof of left adrenal metastases in patients with (suspected) lung cancer and enlarged or (18)FDG-PET positive adrenal glands. Therefore, EUS-FNA qualifies as the staging test of choice for patients with lung cancer with suspected left adrenal metastases.

When is a fracture healed? Radiographic and clinical criteria revisited.

Selecting the most appropriate outcome measures can be especially burdensome in trials studying fracture healing, because the process of fracture healing is subjective and without a gold standard. Although a wide variety of radiographic modalities are available, plain radiography remains the most common approach for healing assessment. Radiographic criteria, however, do not correlate well with fracture strength and stiffness. Additional challenges include a lack of consensus in what radiographic measures are most appropriate in the assessment of healing. In this article, we provide an overview of the most commonly used radiographic and clinical criteria for defining fracture healing. The validity and reliability of alternative approaches is also discussed.

The radiographic union scale in tibial fractures: reliability and validity.

Radiographic assessment of tibial fracture healing continues to pose significant challenges to both routine fracture care and clinical research. Orthopaedic surgeons fail to achieve sufficient agreement on fracture healing when using conventional radiographic measures such as their general impression or the number of cortices bridged by callus. Moreover, the extent to which radiographic assessment of healing corresponds to patient-important outcomes is largely unknown. In an attempt to improve the former (ie, reliability) and inform the latter (ie, validity), recent studies have explored a novel radiographic assessment for tibial shaft fractures, the Radiographic Union Scale for Tibial fractures (RUST). The RUST score assesses the presence of bridging callus and that of a fracture line on each of 4 cortices seen on 2 orthogonal radiographic views. A recent study has found that RUST scores have greater inter-rater reliability when compared with surgeon's general impression or the number of cortices bridged by callus. This may increase the utility of radiographs as a standardized measure of treatment efficacy in the follow-up of tibial fractures.

Twenty years of meta-analyses in orthopaedic surgery: has quality kept up with quantity?

BACKGROUND: As the number of studies in the literature is increasing, orthopaedic surgeons highly depend on meta-analyses as their primary source of scientific evidence. The objectives of this review were to assess the scientific quality and number of published meta-analyses on orthopaedics-related topics over time. METHODS: We conducted, in duplicate and independently, a systematic review of published meta-analyses in orthopaedics in the years 2005 and 2008 and compared them with a previous systematic review of meta-analyses from 1969 to 1999. A search of electronic databases (MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews) was performed to identify meta-analyses published in 2005 and 2008. We searched bibliographies and contacted content experts to identify additional relevant studies. Two investigators independently assessed the quality of the studies, using the Oxman and Guyatt index, and abstracted relevant data. RESULTS: We included forty-five and forty-four meta-analyses from 2005 and 2008, respectively. While the number of meta-analyses increased fivefold from 1999 to 2008, the mean quality score did not change significantly over time (p = 0.067). In the later years, a significantly lower proportion of meta-analyses had methodological flaws (56% in 2005 and 68% in 2008) compared with meta-analyses published prior to 2000 (88%) (p = 0.006). In 2005 and 2008, respectively, 18% and 30% of the meta-analyses had major to extensive flaws in their methodology. Studies from 2008 with positive conclusions used and described appropriate criteria for the validity assessment less often than did those with negative results. The use of random-effects and fixed-effects models as pooling methods became more popular toward 2008. CONCLUSIONS: Although the methodological quality of orthopaedic meta-analyses has increased in the past twenty years, a substantial proportion continues to show major to extensive flaws. As the number of published meta-analyses is increasing, a routine checklist for scientific quality should be used in the peer-review process to ensure methodological standards for publication.