Robin M. Turner

Preoperative Ultrasound-Guided Needle Biopsy of Axillary Nodes in Invasive Breast Cancer: Meta-Analysis of Its Accuracy and Utility in Staging the Axilla

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.

Preoperative Magnetic Resonance Imaging in Breast Cancer: Meta-analysis of Surgical Outcomes

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.

Ductal Carcinoma in Situ at Core-Needle Biopsy: Meta-Analysis of Underestimation and Predictors of Invasive Breast Cancer

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.

An Individual Person Data Meta-Analysis of Preoperative Magnetic Resonance Imaging and Breast Cancer Recurrence

PURPOSE There is little consensus regarding preoperative magnetic resonance imaging (MRI) in breast cancer (BC). We examined the association between preoperative MRI and local recurrence (LR) as primary outcome, as well as distant recurrence (DR), in patients with BC. METHODS An individual person data (IPD) meta-analysis, based on preoperative MRI studies that met predefined eligibility criteria, was performed. Survival analysis (Cox proportional hazards modeling) was used to investigate time to recurrence and to estimate the hazard ratio (HR) for MRI. We modeled the univariable association between LR (or DR) and MRI, and covariates, and fitted multivariable models to estimate adjusted HRs. Sensitivity analysis was based on women who had breast conservation with radiotherapy. RESULTS Four eligible studies contributed IPD on 3,180 affected breasts in 3,169 subjects (median age, 56.2 years). Eight-year LR-free survival did not differ between the MRI (97%) and no-MRI (95%) goups (P = .87), and the multivariable model showed no significant effect of MRI on LR-free survival: HR for MRI (versus no-MRI) was 0.88 (95% CI, 0.52 to 1.51; P = .65); age, margin status, and tumor grade were associated with LR-free survival (all P < .05). HR for MRI was 0.96 (95% CI, 0.52 to 1.77; P = .90) in sensitivity analysis. Eight-year DR-free survival did not differ between the MRI (89%) and no-MRI (93%) groups (P = .37), and the multivariable model showed no significant effect of MRI on DR-free survival: HR for MRI (v no-MRI) was 1.18 (95% CI, 0.76 to 2.27; P = .48) or 1.31 (95% CI, 0.76 to 2.27; P = .34) in sensitivity analysis. CONCLUSION Preoperative MRI for staging the cancerous breast does not reduce the risk of LR or DR.

Absolute and relative accuracy of rapid urine tests for urinary tract infection in children: a meta-analysis

Rapid urine tests, such as microscopy, for bacteria and white cells, and dipsticks, for leucocyte esterase and nitrites, are often used in children that are unwell to guide early diagnosis and treatment of urinary tract infection. We aimed to establish whether these tests were sufficiently sensitive to avoid urine culture in children with negative results and to compare the accuracy of dipsticks with microscopy. Medline, Embase, and reference lists were searched. Studies were included if urine culture results were compared with rapid tests in children. Data were analysed to obtain absolute and relative accuracy estimates. Data from 95 studies in 95 703 children were analysed. Summary estimates for sensitivity and specificity for microscopy for Gram-stained bacteria were 91% (95% CI 80-96) and 96% (92-98), for unstained bacteria were 88% (75-94) and 92% (84-96), for urine white cells were 74% (67-80) and 86% (82-90), for leucocyte esterase or nitrite positive dipstick were 88% (82-91) and 79% (69-87), and for nitrite-only positive dipstick were 49% (41-57) and 98% (96-99). Microscopy for bacteria with Gram stain had higher accuracy than other laboratory tests with relative diagnostic odds ratio compared with bacteria without Gram stain of 8.7 (95% CI 1.8-41.1), white cells of 14.5 (4.7-44.4), and nitrite of 22.0 (0.7-746.3). Microscopy for white cells should not be used for the diagnosis of urinary tract infection because its accuracy is no better than that of dipstick, laboratory facilities are needed, and results are delayed. Rapid tests are negative in around 10% of children with a urinary tract infection and cannot replace urine culture. If resources allow, microscopy with Gram stain should be the single rapid test used.

Optimizing the Frequency of Follow-Up Visits for Patients Treated for Localized Primary Cutaneous Melanoma

PURPOSE To develop more evidence-based guidelines for the frequency of patient follow-up after treatment of localized (American Joint Committee on Cancer [AJCC] stage I or II) melanoma. METHODS We used data from Melanoma Institute Australia on an inception cohort of 3,081 consecutive patients first diagnosed with stage I or II melanoma between January 1985 and December 2009. Kaplan-Meier curves and Cox models were used to characterize the time course and predictors for recurrence and new primaries. We modeled the delay in diagnosis of recurrence or new primary as well as the number of monitoring visits required using two monitoring schedules: first, according to 2008 Australian and New Zealand guidelines and, second, with fewer visits, especially for those at lowest risk of recurrence. RESULTS For every 1,000 patients beginning follow-up, 229 developed recurrence and 61 developed new primary within 10 years. There was only a small difference in modeled delay in diagnosis (extra 44.9 and 9.6 patients per 1,000 for recurrence and new primary, respectively, with delay greater than 2 months) using a schedule that requires far fewer visits (3,000 fewer visits per 1,000 patients) than recommended by current guidelines. AJCC substage was the most important predictor of recurrence, whereas age and date of primary diagnosis were important predictors of developing new primary. CONCLUSION By providing less intensive monitoring, more efficient follow-up strategies are possible. Fewer visits with a more focused approach may address the needs of patients and clinicians to detect recurrent or new melanoma.

Too much medicine in older people? Deprescribing through shared decision making

Jansen and colleagues explore the role of shared decision making in tackling inappropriate polypharmacy in older adults

Psychosocial outcomes of three triage methods for the management of borderline abnormal cervical smears: an open randomised trial

Objective To assess which of three triage strategies for women with borderline abnormal cervical smear results in the best psychosocial outcomes. Design Pragmatic, non-blinded, multicentre, randomised controlled trial. Setting 18 family planning clinics across Australia, covering both urban and rural areas, between January 2004 and October 2006. Participants Women aged 16-70 years (n=314) who attended routine cervical screening and received a borderline cervical smear. Interventions Patients were randomly assigned to human papillomavirus (HPV) DNA testing (n=104), a repeat smear test at six months (n=106), or the patient’s informed choice of either test supported by a decision aid (n=104). Psychosocial outcomes were assessed at multiple time points over 12 months by postal questionnaire. Main outcome measures We assessed health related quality of life (SF36 mental health subscale), cognitive effects (such as perceived risk of cervical cancer, intrusive thoughts), affective outcomes (general anxiety [state-trait anxiety inventory]), specific anxiety about an abnormal smear (cervical screening questionnaire), and behavioural outcomes (sexual health behaviour and visits to the doctor) over 12 months of follow-up. Results At two weeks, some psychosocial outcomes were worse for women allocated to HPV testing compared with those in the smear testing group (SF36 vitality subscale: t=−1.63, df=131, P=0.10; intrusive thoughts χ2=8.14, df=1, P<0.01). Over 12 months, distress about the abnormal smear was lowest in women allocated to HPV testing and highest in the repeat smear testing group (t=−2.89, df=135, P<0.01). Intrusive thoughts were highest in patients allocated to HPV testing (25%, compared with 13% in the informed choice group; difference=12%, 95% CI −1.1% to 25.1%). Women in the HPV DNA group and the informed choice group were more satisfied with their care than women allocated to repeat smear testing. Conclusions Although the psychosocial effect was initially worse for women allocated to HPV triage, over the full year of follow-up this intervention was better for women’s psychosocial health than repeat smear testing. Offering informed choice could have a small advantage for cognitive outcomes, but in view of the additional effort and logistical complexity that this intervention requires, HPV testing alone can be justified for most women.Trial Registration actr.org.au Identifier: 12605000111673

Patients who plan for conservative care rather than dialysis: a national observational study in Australia.

BACKGROUND It is unclear how many incident patients with stage 5 chronic kidney disease (CKD) referred to nephrologists are presented with information about conservative care as a treatment option and how many plan not to dialyze. STUDY DESIGN National observational survey study with random-effects logistic regression. SETTING & PARTICIPANTS Incident adult and pediatric pre-emptive transplant, dialysis, and conservative-care patients from public and private renal units in Australia, July to September 2009. PREDICTORS Age, sex, health insurance status, language, time known to nephrologist, timing of information, presence of caregiver, unit conservative care pathway, and size of unit. OUTCOMES & MEASUREMENTS The 2 main outcome measures were information provision to incident patients about conservative care and initial treatment regardless of planned conservative care. RESULTS 66 of 73 renal units (90%) participated. 10 (15%) had a formal conservative-care pathway. Of 721 incident patients with stage 5 CKD, 470 (65%) were presented with conservative care as a treatment option and 102 (14%) planned not to dialyze; median age was 80 years. Multivariate analysis for information provision showed that patients older than 65 years (OR, 3.40; 95% CI, 1.97-5.87) and those known to a nephrologist for more than 3 months (OR, 6.50; 95% CI, 3.18-13.30) were more likely to receive information about conservative care. Patients with conservative care as planned initial treatment were more likely to be older than 65 years (OR, 4.71; 95% CI, 1.77-12.49) and women (OR, 2.23; 95% CI, 1.23-4.02) than those who started dialysis therapy. Those with private health insurance were less likely to forgo dialysis therapy (OR, 0.40; 95% CI, 0.17-0.98). LIMITATIONS Cross-sectional design prohibited longer term outcome measurement. Excluded patients with stage 5 CKD managed in the community. CONCLUSIONS 1 in 7 patients with stage 5 CKD referred to nephrologists plans not to dialyze. Comprehensive service provision with integrated palliative care needs to be improved to meet the demands of the aging population.

Reduced Estimated GFR and Cancer Mortality

BACKGROUND Chronic kidney disease is associated with an increased risk of cancer, but whether reduced kidney function also leads to increased cancer mortality is uncertain. The aim of our study was to assess the independent effects of reduced kidney function on the risk of cancer deaths. STUDY DESIGN Prospective population-based cohort study. SETTING & PARTICIPANTS Participants of the Blue Mountains Eye Study (n=4,077; aged 49-97 years). PREDICTOR Estimated glomerular filtration rate (eGFR). OUTCOMES Overall and site-specific cancer mortality. RESULTS During a median follow-up of 12.8 (IQR, 8.6-15.8) years, 370 cancer deaths were observed in our study cohort. For every 10-mL/min/1.73 m(2) reduction in eGFR, there was an increase in cancer-specific mortality of 18% in the fully adjusted model (P<0.001). Compared with participants with eGFR ≥ 60 mL/min/1.73 m(2), the adjusted HR for cancer-specific mortality for those with eGFR<60 mL/min/1.73 m(2) was 1.27 (95% CI, 1.00-1.60; P=0.05). This excess cancer mortality varied with site, with the greatest risk for breast and urinary tract cancer deaths (adjusted HRs of 1.99 [95% CI, 1.05-3.85; P=0.01] and 2.54 [95% CI, 1.02-6.44; P=0.04], respectively). LIMITATIONS Residual confounding, such as from unmeasured socioeconomic factors and the potential effects of erythropoiesis-stimulating agents on cancer deaths, may have occurred. CONCLUSIONS eGFR<60 mL/min/1.73m(2) appears to be a significant risk factor for death from cancer. These effects appear to be site specific, with breast and urinary tract cancers incurring the greatest risk of death among those with reduced kidney function.