Prostate Cancer Risk Inflation as a Consequence of Image-targeted Biopsy of the Prostate: A Computer Simulation Study

Background

Prostate biopsy parameters are commonly used to attribute cancer risk. A targeted approach to lesions found on imaging may have an impact on the risk attribution given to a man.

Objective

To evaluate whether, based on computer simulation, targeting of lesions during biopsy results in reclassification of cancer risk when compared with transrectal ultrasound (TRUS) guided biopsy.

Design, setting, and participants

A total of 107 reconstructed three-dimensional models of whole-mount radical prostatectomy specimens were used for computer simulations. Systematic 12-core TRUS biopsy was compared with transperineal targeted biopsies using between one and five cores. All biopsy strategies incorporated operator and needle deflection error. A target was defined as any lesion ≥0.2 ml. A false-positive magnetic resonance imaging identification rate of 34% was applied.

Outcome measurements and statistical analysis

Sensitivity was calculated for the detection of all cancer and clinically significant disease. Cases were designated as high risk based on achieving ≥6 mm cancer length and/or ≥50% positive cores. Statistical significance (p values) was calculated using both a paired Kolmogorov-Smirnov test and the t test.

Results and limitations

When applying a widely used biopsy criteria to designate risk, 12-core TRUS biopsy classified only 24% (20 of 85) of clinically significant cases as high risk, compared with 74% (63 of 85) of cases using 4 targeted cores. The targeted strategy reported a significantly higher proportion of positive cores (44% vs 11%; p < 0.0001) and a significantly greater mean maximum cancer core length (7.8 mm vs 4.3 mm; p < 0.0001) when compared with 12-core TRUS biopsy. Computer simulations may not reflect the sources of errors encountered in clinical practice. To mitigate this we incorporated all known major sources of error to maximise clinical relevance.

Conclusions

Image-targeted biopsy results in an increase in risk attribution if traditional criteria, based on cancer core length and the proportion of positive cores, are applied. Targeted biopsy strategies will require new risk stratification models that account for the increased likelihood of sampling the tumour.     

Interleukin-3 treatment of rhesus monkeys leads to increased production of histamine-releasing cells that express interleukin-3 receptors at high levels

To understand the hematopoietic and nonhematopoietic responses to interleukin-3 (IL-3), expression of cell-surface IL-3 receptors (IL-3R) was examined on bone marrow (BM) cells and peripheral blood (PB) cells of rhesus monkeys during the course of in vivo IL-3 treatment. Whereas IL-3R expression is low in untreated monkeys, IL-3 administration led to a gradual increase in both low- and high-affinity binding sites for IL-3. This increase reflected the total number of cells expressing IL- 3Rs, as detected by flow cytometry using biotinylated IL-3. Most of these IL-3R+ cells in both BM and PB could be characterized as basophilic granulocytes that contained high levels of histamine. In contrast to the effect on these differentiated cells, IL-3 administration did not significantly alter the low level IL-3R expression on immature, CD34+ cells. Further flow cytometric analysis using biotinylated growth factors showed that the IL-3R+ basophils also expressed receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), but not for IL-6 or Kit ligand. These findings indicated that the IL-3R+ cells included neither monocytes, which express GM-CSFRs and IL-6Rs abundantly, nor mast cells, which express c- kit. By combining flow cytometric and Scatchard data, it was calculated that the basophils contain as many as 1 to 2 x 10(3) high-affinity IL- 3Rs and 15 to 30 x 10(3) low-affinity sites. The finding that in vivo IL-3 treatment leads to the production of large numbers of cells that express high levels of IL-3R and are capable of producing histamine provides an explanation for the often severe allergic reactions that occur during prolonged IL-3 administration. It also indicates that IL- 3, in addition to its direct effects on hematopoietic cells, may also stimulate hematopoiesis through the release of secondary mediators such as histamine by IL-3-responsive mature cells.     

Mouse intracerebral hemorrhage models produce different degrees of initial and delayed damage,axonal sprouting,and recovery

The mechanisms of delayed damage and recovery after intracerebral hemorrhage (ICH) remain poorly defined. Two rodent models of ICH are commonly used: injection of the enzyme collagenase (cICH) and injection of autologous blood (bICH). In mice, we compared the effects of these two models on initial and delayed tissue damage, motor system connections, and behavioral recovery. There is no difference in lesion size between models. Injection of autologous blood causes greater mass effect and early mortality. However, cICH produces greater edema, inflammation, and cell death. Injection of the enzyme collagenase causes greater loss of cortical connections and secondary shrinkage of the striatum. Intracerebral hemorrhage occurs within the motor system connections of the striatum. Mapping of the projections of the forelimb motor area shows a significant sprouting in motor cortex projections only in cICH. Both models of ICH produce deficits in forelimb motor control. Behavioral recovery occurs by 5 weeks in cICH and 9 weeks in bICH. In summary, cICH and bICH differ in almost every facet of initial and delayed stroke pathophysiology, with cICH producing greater initial and secondary tissue damage and greater motor system axonal sprouting than bICH. Motor recovery occurs in both models, suggesting that motor system axonal sprouting in cICH is not causally associated with recovery.     

Residual Periodontal Ligament in Extracted Teeth – Is It Associated With Indication for Extraction?

BackgroundPeriodontal disease is a major cause of tooth loss. Few studies have evaluated the residual area of the periodontal ligament in extracted teeth and, to the best of our knowledge, none from Latin America have done so regarding indications for extraction. The aim of this study was to evaluate the residual periodontal ligament (RPL) with respect to indication for extraction in a sample of teeth from a Brazilian Public Health Service district.Materials and methodsAll teeth extracted within the Public Health Service district of Santa Maria, Brazil, over a 5-month period were requested for analysis. A total of 414 teeth eligible for measurement were stained and evaluated for RPL using a stereo microscope. Participating Public Health Service dentists completed a questionnaire detailing demographic variables and indication for each extracted tooth. The percentage of RPL was determined for each tooth. Comparisons of RPL between teeth extracted on periodontal versus other indications were made using the Mann-Whitney test.ResultsRPL averaged 34.8% for teeth extracted on periodontal indications versus 79.5% for other teeth (P ≤ 0.001). When considering teeth with an RPL ≥ 30% as possible to maintain, 189 (76%) of the teeth extracted on periodontal indications could have been maintained. When RPL cut-off limits of ≥ 40% or ≥ 50% are applied, 93 (37%) and 43 (17%) teeth, respectively, could have been maintained.ConclusionThis study suggests that strictly based on RPL, a large number of teeth extracted on periodontal indications conceivably could be maintained.Key words: Cross-sectional studies, Prognosis, Tooth extraction, Tooth loss     

Anxiety,depression, and stress in caregivers of children and adolescents with mental disorders in Ghana and implications for medication adherence

ObjectiveThis study assessed levels of anxiety, depression, and stress among family caregivers of children and adolescents with mental disorders in Ghana and the implication on medication adherence.DesignA cross-sectional study.SettingThe study was conducted at the outpatient departments of the three main public psychiatric hospitals in Ghana.ParticipantsTwo hundred and ten non-paid family caregivers of children and adolescents with mental disorders were recruited for this study.Main Outcome MeasureThe study assessed symptoms of anxiety, depression and stress among the caregivers and estimated caregiver-reported medication adherence.ResultsAbout 56.2%, 66.2% and 78% of the caregivers experienced severe anxiety, severe depression and moderate to severe stress symptoms respectively. From the multiple logistic regression model, while anxiety was significantly affected by religion and education, depression was influenced by sex, age, marital status, proximity to facility, and employment status. Female caregivers had about four times higher odds of being depressed compared to male caregivers (aOR: 3.81, 95% CI: 1.66 – 8.75). The caregiver-reported medication adherence was 11.9%. Anxiety was significantly predictive of medication adherence.ConclusionMost family caregivers of children and adolescents with mental disorders experienced symptoms of anxiety, depression and stress with anxiety having implications for medication adherence. The study findings underscore the need to consider psychological characteristics of caregivers and the provision of mental health support for them, as part of the routine health care for children and adolescents with mental disorders.FundingNone indicated