Robin Turner

PURPOSE: To perform a meta-analysis to report pooled estimates for underestimation of invasive breast cancer (where core-needle biopsy [CNB] shows ductal carcinoma in situ [DCIS] and excision histologic examination shows invasive breast cancer) and to identify preoperative variables that predict invasive breast cancer. MATERIALS AND METHODS: Studies were identified by searching MEDLINE and were included if they provided data on DCIS underestimates (overall and according to preoperative variables). Study-specific and pooled percentages for DCIS underestimates were calculated. By using meta-regression (random effects logistic modeling) the association between each study-level preoperative variable and understaged invasive breast cancer was investigated. RESULTS: Fifty-two studies that included 7350 cases of DCIS with findings at excision histologic examination as the reference standard met the eligibility criteria and were included. There were 1736 underestimates (invasive breast cancer at excision); the random-effects pooled estimate was 25.9% (95% confidence interval: 22.5%, 29.5%). Preoperative variables that showed significant univariate association with higher underestimation included the use of a 14-gauge automated device (vs 11-gauge vacuum-assisted biopsy, P = .006), high-grade lesion at CNB (vs non-high grade lesion, P < .001), lesion size larger than 20 mm at imaging (vs lesions ≤ 20 mm, P < .001), Breast Imaging Reporting and Data System (BI-RADS) score of 4 or 5 (vs BI-RADS score of 3, P for trend = .005), mammographic mass (vs calcification only, P < .001), and palpability (P < .001). CONCLUSION: About one in four DCIS diagnoses at CNB represent understaged invasive breast cancer. Preoperative variables significantly associated with understaging include biopsy device and guidance method, size, grade, mammographic features, and palpability.

In Brief Objective: Systematic evidence synthesis of ultrasound-guided needle biopsy (UNB) of axillary nodes in breast cancer. Summary Background Data: Women affected by invasive breast cancer undergo initial staging with sentinel node biopsy, generally progressing to axillary node dissection (AND) if metastases are found. Preoperative UNB can potentially identify and triage women with node metastases directly to AND. Methods: Review and meta-analysis of studies reporting UNB accuracy: we estimated sensitivity, specificity, and PPV, using bivariate random-effects models and examined the effect of covariates; we calculated UNB utility (effect on axillary surgery). Results: Thirty-one studies provided 2874 UNB data from 6166 subjects (median proportion with metastatic nodes 47.2%; IQR 39.5%, 61.2%). Modeled estimates for UNB were: sensitivity 79.6% (95% confidence intervals [CI] 74.1–84.2), specificity 98.3% (95%CI 97.2–99.0), PPV 97.1% (95%CI 95.2–98.3); median UNB insufficiency was 4.1% (IQR0%–10.9%). UNB sensitivity increased with increasing ultrasound sensitivity, and was higher in studies performing UNB for “suspicious” than for “visible” nodes. Specificity was higher in studies of consecutive (vs. selected) subjects, in studies reporting ultrasound data, and in more recent studies. Median proportion of women triaged directly to AND (attributed to UNB) was 19.8% (IQR11.6%–28.1%) or 17.7% (IQR11.6%–27.1%) if restricted to clinically node-negative series. Median proportion of women with metastatic axillary nodes potentially triaged to AND was 55.2% (IQR41.8%–68.2%) and was higher (65.6%; IQR48.9%–69.7%) in the subgroup of studies with median tumor size ≥21 mm. Conclusions: Preoperative UNB of the axilla is accurate for initial staging of women with invasive breast cancer. Meta-analysis indicates that UNB provides better utility in women with average or higher underlying risk of node metastases. Meta-analysis of the accuracy of preoperative ultrasound-guided needle biopsy (UNB) of axillary nodes, based on 31 studies reporting 2,874 UNBs from 6,166 women with breast cancer (median with metastatic nodes 47.2%) shows a modelled sensitivity of 79.6%, specificity of 98.3%, and PPV of 97.1%. The median proportion of women triaged directly to axillary dissection (attributable to UNB) was 19.8%, or 17.7% for clinically node-negative series; the median proportion of women with {metastatic axillary nodes} potentially triaged to axillary dissection was 55.2%.

BACKGROUND: People with chronic kidney disease (CKD) have an increased risk of stroke but the magnitude of increased risk and the independent effects of glomerular filtration rate (GFR) and albuminuria are unclear. We aimed to quantify the association between the independent and combined effects of GFR and albuminuria on stroke risk. METHODS: We searched MEDLINE and EMBASE (February 2014) for cohort studies or randomized controlled trials (RCTs) which reported stroke incidence in adults with a baseline measurement of GFR and/or albuminuria. We extracted study and participant characteristics, risk of bias and relative risks (RR, with confidence interval; CI) of stroke associated with GFR and/or quantity of albuminuria, synthesized data using random effects meta-analysis and explored heterogeneity using meta-regression. RESULTS: We identified 83 studies; 63 cohort studies (2 085 225 participants) and 20 RCTs (168 516 participants) reporting 30 392 strokes. There was an inverse linear relationship between GFR and risk of stroke, with risk of stroke increasing 7% (RR: 1.07, CI: 1.04-1.09) for every 10 mL/min/1.73 m(2) decrease in GFR. A 25 mg/mmol increase in albumin-creatinine ratio was associated with a 10% increased risk of stroke (RR: 1.10, 95% CI: 1.01-1.20). The effect of albuminuria was independent of GFR. Results were not different across subtypes of stroke, sex and varying prevalence of cardiovascular risk factors. CONCLUSIONS: Stroke risk increases linearly and additively with declining GFR and increasing albuminuria. CKD staging may also be a useful clinical tool for identifying people who may benefit most from interventions to reduce cardiovascular risk.

Too much medicine is an increasingly recognised problem, and one manifestation is inappropriate polypharmacy in older people. Polypharmacy is usually defined as taking more than five regular prescribed medicines. It can be appropriate (when potential benefits outweigh potential harms) but increases the risk of older people experiencing adverse drug reactions, impaired physical and cognitive function, and hospital admission.There is limited evidence to inform polypharmacy in older people, especially those with multimorbidity, cognitive impairment, or frailty. Systematic reviews of medication withdrawal trials (deprescribing) show that reducing specific classes of medicines may decrease adverse events and improve quality of life

In Brief Background and Objective: The role of breast magnetic resonance imaging (MRI) in women newly diagnosed with breast cancer (BC) is controversial. This meta-analysis examines the effect of preoperative MRI compared with standard preoperative assessment on surgical outcomes, focusing on studies that used a controlled design. Methods: Using random-effects logistic meta-regression modeling, we estimated the proportion of women with each outcome in the MRI versus no-MRI groups, and calculated the odds ratio (OR) and adjusted OR (adjusted for study-level median age, and, where appropriate, for temporal effect) for each model. Results: There were 9 eligible studies (2 randomized trials; 7 comparative cohorts). Outcomes in 3112 patients with BC (any histological tumor type) for MRI versus no-MRI (referent) were as follows: initial mastectomy 16.4% versus 8.1% [OR, 2.22 (P < 0.001); adjusted OR, 3.06 (P < 0.001)]; re-excision after initial breast conservation 11.6% versus 11.4% [OR, 1.02 (P = 0.87); adjusted OR, 0.95 (P = 0.71)]; overall mastectomy 25.5% versus 18.2% [OR, 1.54 (P < 0.001); adjusted OR, 1.51 (P < 0.001)]. In 766 patients with invasive lobular cancer (ILC), outcomes were as follows: initial mastectomy 31.1% versus 24.9% [OR, 1.36 (P = 0.056); adjusted OR, 2.12 (P = 0.008)]; re-excision after initial breast conservation 10.9% versus 18.0% [OR, 0.56 (P = 0.031); adjusted OR, 0.56 (P = 0.09)]; overall mastectomy 43.0% versus 40.2% [OR, 1.12 (P = 0.45); adjusted OR, 1.64 (P = 0.034)]. Conclusions: Our summary of the evidence showed that MRI significantly increased mastectomy rates and suggests an unfavorable harm-benefit ratio for routine use of preoperative MRI in BC. We found weak evidence that MRI reduced re-excision surgery in patients with ILC —although this was at the expense of increased mastectomies—and overall patient benefit from MRI in ILC is not clear from this study. Meta-regression modeling of studies using a controlled design to examine the effect of preoperative magnetic resonance imaging (MRI) in breast cancer (3112 patients) showed that using MRI versus standard preoperative assessment (no-MRI) increased the overall mastectomy rate [25.5% vs 18.2%; odds ratio (OR), 1.54 (P < 0.001); adjusted OR, 1.51 (P < 0.001)] and did not reduce re-excision surgery in those with initial breast conservation [11.6% vs 11.4%; OR, 1.02 (P = 0.87); adjusted OR, 0.95 (P = 0.71)].