Background Whether the genomic rearrangement TMPRSS2:ERG has prognostic value in prostate cancer is unclear. Methods Among men with prostate cancer in the prospective Physicians’ Health and Health Professionals Follow-Up Studies, we identified rearrangement status by immunohistochemical assessment of ERG protein expression. We used Cox models to examine associations of ERG overexpression with biochemical recurrence and lethal disease (distant metastases or cancer-specific mortality). In a meta-analysis including 47 additional studies, we used random effects models to estimate associations between rearrangement status and outcomes. Results The cohort consisted of 1,180 men treated with radical prostatectomy between 1983 and 2005. During a median follow-up of 12.6 years, 266 men experienced recurrence, and 85 men developed lethal disease. We found no significant association between ERG overexpression and biochemical recurrence (HR: 0.99; 95% CI: 0.78-1.26) or lethal disease (HR: 0.93; 95% CI: 0.61-1.43). The meta-analysis of prostatectomy series included 5,074 men followed for biochemical recurrence (1,623 events), and 2,049 men followed for lethal disease (131 events). TMPRSS2:ERG was associated with stage at diagnosis (RR≥T3 vs. T2: 1.23; 95% CI: 1.16-1.30) but not with biochemical recurrence (RR: 1.00; 95% CI: 0.86-1.17) or lethal disease (RR: 0.99; 95% CI: 0.47-2.09). Conclusions These results suggest that TMPRSS2:ERG, or ERG overexpression, is associated with tumor stage but does not strongly predict recurrence or mortality among men treated with radical prostatectomy. Impact This is the largest prospective cohort study to examine associations of ERG overexpression and lethal prostate cancer among men treated with radical prostatectomy.
The purpose of this study was to examine institutional trends in the volume of clavicle fractures in children and adolescents. Medical records were retrospectively reviewed to identify patients aged 10-18 years treated for a clavicle fracture between 1999 and 2011 at a single tertiary-care pediatric hospital. There were significant increases in the number of clavicle fractures seen annually, of midshaft clavicle fractures, and of midshaft clavicle fractures treated operatively. The percentage of midshaft clavicle fractures treated with fixation also increased significantly. The volumes of clavicle fractures and midshaft clavicle fractures treated operatively appear to be increasing. Despite a lack of evidence-based support, the frequency of fixation of midshaft clavicle fractures appear to be increasing in the pediatric population.
A variety of strategies are utilized for management of pediatric diaphyseal femur fractures, depending chiefly on the age of the patient. Other factors that can influence the selection of a technique-which range from skeletal traction with spica casting to immediate spica casting, flexible intramedullary nailing, rigid intramedullary rodding, or plate fixation-are weight, fracture severity, associated injuries, and underlying medical or musculoskeletal conditions. The available evidence regarding technique, outcomes, and complications of the aforementioned treatment options remains largely insufficient, and, at times, conflicting, which contributes to the challenges in management decisions. Considerable controversy has arisen over several topics, particularly the optimal treatment for patients aged 5 to 12 years and accepted standards of treatment. This review is designed to provide perspective for some of the most recent influential literature on pediatric diaphyseal femur fracture treatment in light of established evidence and evolving controversies.
Background Although obesity is an established modifiable risk factor for multiple myeloma (MM), several nuanced aspects of its relation to MM remain unelucidated, limiting public health and prevention messages. Methods We analyzed prospective data from the Nurses’ Health Study and Health Professionals Follow-Up Study to examine MM risk associated with 20-year weight patterns in adulthood, body shape trajectory from ages 5 to 60 years, and body fat distribution. For each aforementioned risk factor, we report hazard ratios (HRs) and 95% confidence intervals (CIs) for incident MM from multivariable Cox proportional-hazards models. Results We documented 582 incident MM cases during 4 280 712 person-years of follow-up. Persons who exhibited extreme weight cycling, for example, those with net weight gain and one or more episodes of intentional loss of at least 20 pounds or whose cumulative intentional weight loss exceeded net weight loss with at least one episode of intentional loss of 20 pounds or more had an increased MM risk compared with individuals who maintained their weight (HR = 1.71, 95% CI = 1.05 to 2.80); the association was statistically nonsignificant after adjustment for body mass index. We identified four body shape trajectories: lean-stable, lean-increase, medium-stable, and medium-increase. MM risk was higher in the medium-increase group than in the lean-stable group (HR = 1.62, 95% CI = 1.22 to 2.14). Additionally, MM risk increased with increasing hip circumference (HR per 1-inch increase: 1.03, 95% CI = 1.01 to 1.06) but was not associated with other body fat distribution measures. Conclusions Maintaining a lean and stable weight throughout life may provide the strongest benefit in terms of MM prevention.
Objectives:Apophyseal avulsion fractures of the hip and pelvis occur almost exclusively in the adolescent population, with greater numbers being seen recently as the popularity and intensity of youth sports increases. Limited evidence exists detailing the demographics or distribution of these fractures by injury site. The goal of the current study was to present a comprehensive perspective on 437 of these fractures, including the indications and clinical course of 25 cases that underwent surgical intervention.Methods:All cases of an apophyseal avulsion fracture of the hip or pelvis between the years of 1981-2012 at a tertiary care pediatric center underwent radiographic and chart review, including operative details for that sub-population. Demographic data was analyzed, along with radiographic displacement, healing times, and return to sports for both groups.Results:413 patients underwent definitive non-operative treatment, 72% of which were male. The mean age was 14.5 years. The anatomic site of injury was well-distributed: AIIS 29%, ASIS 27%, ischial tuberosity 17%, lesser trochanter 15%, and iliac crest 11%. Half of all injuries occurred during one of three different athletic activities (soccer 26%, track 13%, baseball/softball 11%), with a wide range of sports in the overall cohort. In the 287 nonop cases with adequate follow up data to confirm mean radiographic union and time of return to sports (RTS), healing occurred at 2.7 months and RTS at 2.8 months respectively. The mean age of the cohort of 25 patients who ultimately required operative treatment was 15.7 years, with 72% of cases being initially treated with nonoperative measures. The ischial tuberosity was the most common (64%) anatomic site with others including AIIS 16%, iliac crest 16%, and ASIS 4%. Excision of the apophyseal fragment was the intervention pursued for 48% of cases, with the mean time to union of 4.8 months in 11 cases which underwent fixation and had adequate follow up data.Conclusion:In over 400 cases of apophyseal avulsion fractures in an adolescent population, 94% were successfully treated nonoperatively, with mean times of healing and return to sports under 3 months. Most cases requiring surgery failed primary conservative care, many of which underwent fragment excision, rather than fixation, due to the chronic nature of their preoperative period. Better understanding of the rare indications for early fixation and functional outcome measures of both nonoperative and operative management of these injuries is warranted, particularly given their increasing frequency paralleling a rise in overuse and youth sports injuries.
Background: Multiple myeloma (MM) is a lethal malignancy with a poorly understood etiology. Adult body mass index (BMI) is a recently identified risk factor for MM, but the etiologic roles of body fatness at different ages and adult weight cycling have not been assessed. We prospectively examined body shape during childhood, adolescence, and adulthood, as well as weight cycling over a 20-year period, in relation to MM risk in the Nurses' Health Study (NHS) cohort. Methods: The NHS was formed in 1976 among 121,700 female registered nurses ages 30–55 years from the United States who returned the enrollment questionnaire on lifestyle and medical history. Biennial follow-up questionnaires have subsequently updated lifestyle and medical information. A validated somatogram-depicted body shape (current and at ages 5, 10, 20, 30, and 40 years) was queried in 1988. The 1992 questionnaire characterized weight change over the prior 20 years (when most NHS participants were middle-aged adults). The present analyses included women who completed the 1988 (somatogram) or 1992 (weight cycling) questionnaires and had no cancer history at that time. Women were followed through the earliest among a cancer diagnosis, death, or June 2008. We classified body shapes as relatively lean, medium, and heavier at the specified ages and for the average shape at ages 5 and 10 (“childhood”) and ages 10 and 20 years (“adolescent”). We classified women's 20-year weight cycling patterns as weight loser/maintainer, gainer (i.e., only weight gain), light cycler (i.e., net loss or gain of ≥5 lbs. with ≥1 episode of voluntary 5–9 lb. change), or heavy cycler (i.e., net loss or gain of ≥5 lbs. with ≥1 episode of voluntary ≥20 lb. change). We computed hazard ratios (HR) and 95% confidence intervals (CI) in Cox proportional hazard models to assess the association of body shape and weight cycling with MM risk. Models included only one body shape or weight cycling variable and controlled for potential confounding by age and baseline BMI. Results: We confirmed 126 incident diagnoses of MM over 1,049,600 person-years for the somatogram analyses and 96 incident diagnoses of MM over 749,578 person-years for the weight cycling analyses. We observed suggestive increases in MM risk among women who reported heavier average body shapes in childhood (v. those with a relatively lean childhood shape; HR=1.8; 95% CI=0. 8–4.2) and adolescence (HR=1.6; CI=0.6–4.1). Body shape at specific ages and at baseline did not appear to predict MM risk. In the 20-year weight cycling analysis, we observed a suggested modest increase in MM risk among women who were weight gainers (HR=1.2; 95% CI=0.5–3.0) or light (HR=1.2; 95% CI=0.5–2.8) or heavy cyclers (HR=1.4; 95% CI=0.6–3.2) compared to those who lost weight or maintained stable weight. Discussion: These first prospective studies of body shape at various ages and long-term adult weight cycling are consistent with existing evidence that obesity is positively associated with risk of MM. Obesity in adulthood has consistently predicted an increased risk of MM in published studies and is thus a potentially modifiable risk factor for MM. Obesity at younger ages or an inability to maintain stable adult weight may be predictors of adult obesity, or may indicate an etiologic role for earlier life exposures in MM. Confirmation of the present findings in men and in other large populations is warranted, as are studies to explore potential biologic correlates of these lifestyle factors. If confirmed, these data would suggest that maintenance of a healthy weight from an early age, in addition to conferring other health benefits, may help to diminish risk of MM. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A79.
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