What can We Learn From High-Performing Screening Programs to Increase Bowel Cancer Screening Participation in Australia?

BACKGROUND: Colorectal cancer (CRC) is the second most diagnosed cancer in men and women and second most common cause of cancer death in Australia; Australia's CRC incidence and mortality are among the world's highest. The Australian National Bowel Cancer Screening Program began in 2006; however, only 33% of those approached for the first time by the Program between 2018 and 2019 returned the kit. Of the 5.7 million kits sent during this period, only 44% were returned. Our aim was to identify practices and features of national bowel cancer screening programs in countries with similar programs but higher screening participation, to identify potential interventions for optimising Australian CRC screening participation. METHODS: We searched published and grey literature for CRC screening programs reporting at least 50% screening participation using postal invitation and free return of iFOBT home kits. Interviews were conducted with cancer registry staff and academic researchers, focused on participant and practitioner engagement in screening. RESULTS: National programs in Netherlands, Scotland, Denmark, and Finland reported over 50% screening participation rates for all invitation rounds. Shared characteristics include small populations within small geographic areas relative to Australia; relatively high literacy; a one-sample iFOBT kit; national registration systems for population cancer screening research; and screening program research including randomised trials of program features. CONCLUSIONS: Apart from the one-sample kit, we identified no single solution to persistent Australian low uptake of screening. Research including randomised trials within the program promises to increase participation. IMPACT: This screening program comparison suggests that within-program intervention trials will lead to increased Australian screening participation.

Impact of the veterinary feed directive on Ohio cattle operations.

Widespread use of antibiotics in U.S. livestock operations has been identified as a potential contributor to the rising rates of antibiotic-resistant bacterial infections. In response, the U.S. Food and Drug Administration (FDA) issued new rules in January 2017. GFI (Guide for Industry) #213 banned use of antibiotics for growth promotion and required veterinarian permission, via a revised Veterinary Feed Directive (VFD), to deliver antibiotics through feed. Many stakeholders expressed pre-implementation concerns regarding the rules' potential adverse effects on production and profitability. Our study employed qualitative and quantitative methods to investigate how implementation of GFI #213/VFD impacted Ohio cattle operations. We interviewed over fifty cattle farmers and eight large animal veterinarians to document changes in farm antibiotic use, management practices, and profitability. We also examined published government data for possible effects on overall meat production at the state and national levels. We found that the great majority of Ohio farmers reported little difficulty in complying with the VFD with minimal adverse impacts. Farm responses to the feed directive varied with operation size, type (beef or dairy), and whether producers had previously used fed antibiotics. The most commonly reported changes, by both producers and veterinarians, were more veterinary-client interactions, more paperwork/record-keeping, and decreased use of fed antibiotics. All veterinarians, many beef operators, but no dairy operators reported perceiving the VFD as beneficial; however, dairy operations reported less difficulty with compliance due to established working relationships with veterinarians. We found no evidence that the rules impacted the trajectory of state or national livestock output. In conclusion, GFI #213 was reported as not burdensome enough to prevent compliance, but inconvenient enough to incentivize reduced use of fed antibiotics (when previously used) without significant adverse effects, consistent with its goal of promoting judicious use of medically important antibiotics in order to preserve their effectiveness.

Alemtuzumab-related thyroid disease in people with multiple sclerosis is associated with age and brainstem phenotype at disease onset.

BACKGROUND: Autoimmune thyroid disease (AITD) occurs in 40%-50% of alemtuzumab-treated persons with multiple sclerosis (pwMS), most of whom will develop Graves' Disease (GD). OBJECTIVE: To explore contributory factors for alemtuzumab-related AITD in pwMS. METHODS: A retrospective patient chart review was performed. RESULTS: Sixteen out of 52 (30.8%) pwMS developed AITD. GD occurred in 56.3% (n = 9), the majority (n = 7, 77.8%) symptomatic. All but one (85.7%) pwMS with symptomatic GD developed atypical, large and rapid fluctuations in thyroid hormone levels unexplained by effect of anti-thyroid medication alone. All symptomatic GD cases were age ≤32 years when starting alemtuzumab (ɸ = 0.60, p = 0.03). PwMS who started alemtuzumab at a younger age developed thyroid disease earlier (r = 0.51, p = 0.04). PwMS with clinical and radiological evidence of brainstem involvement at onset of multiple sclerosis were 11 times more likely to develop symptomatic GD compared with those with other phenotypes (p < 0.01). CONCLUSION: Alemtuzumab-induced reconstitution GD may result from early and increased cross-reactivity between antigens common to the brainstem and thyroid, or presence of shared Human Leukocyte Antigen (HLA) alleles that determine brainstem and thyroid involvement. We suggest cautious use of alemtuzumab in younger (≤32 years) pwMS with early brainstem involvement, especially those actively planning pregnancy, where alternative therapies are readily available.

Family history-based colorectal cancer screening in Australia: A modelling study of the costs, benefits, and harms of different participation scenarios.

BACKGROUND: The Australian National Bowel Cancer Screening Programme (NBCSP) was introduced in 2006. When fully implemented, the programme will invite people aged 50 to 74 to complete an immunochemical faecal occult blood test (iFOBT) every 2 years. METHODS AND FINDINGS: To investigate colorectal cancer (CRC) screening occurring outside of the NBCSP, we classified participants (n = 2,480) in the Australasian Colorectal Cancer Family Registry (ACCFR) into 3 risk categories (average, moderately increased, and potentially high) based on CRC family history and assessed their screening practices according to national guidelines. We developed a microsimulation to compare hypothetical screening scenarios (70% and 100% uptake) to current participation levels (baseline) and evaluated clinical outcomes and cost for each risk category. The 2 main limitations of this study are as follows: first, the fact that our cost-effectiveness analysis was performed from a third-party payer perspective, which does not include indirect costs and results in overestimated cost-effectiveness ratios, and second, that our natural history model of CRC does not include polyp sojourn time, which determines the rate of cancerous transformation. Screening uptake was low across all family history risk categories (64%-56% reported no screening). For participants at average risk, 18% reported overscreening, while 37% of those in the highest risk categories screened according to guidelines. Higher screening levels would substantially reduce CRC mortality across all risk categories (95 to 305 fewer deaths per 100,000 persons in the 70% scenario versus baseline). For those at average risk, a fully implemented NBCSP represented the most cost-effective approach to prevent CRC deaths (AUS$13,000-16,000 per quality-adjusted life year [QALY]). For those at moderately increased risk, higher adherence to recommended screening was also highly cost-effective (AUS$19,000-24,000 per QALY). CONCLUSION: Investing in public health strategies to increase adherence to appropriate CRC screening will save lives and deliver high value for money.

Mesenteric-Based Surgery Exploits Gastrointestinal, Peritoneal, Mesenteric and Fascial Continuity from Duodenojejunal Flexure to the Anorectal Junction--A Review.

INTRODUCTION: It is now well established that mesenteric-based colorectal surgery is associated with superior outcomes. Recent anatomic observations have demonstrated that the mesenteric organ is contiguous from the duodenojejunal to the anorectal junction. This led to similar observations in relation to associated peritoneum and fascia. The aim of this review was to demonstrate the relevance of the contiguity principle to resectional colorectal surgery. METHODS: All literature in relation to mesenteric anatomy was reviewed from 1873 to the present, without language restriction. RESULTS: Mesenteric-based surgery (i.e. complete mesocolic excision, total mesocolic and mesorectal excision) requires division of the peritoneal reflection (i.e. peritonotomy), and mesenteric mobilisation in the mesofascial plane. These are the fundamental technical elements of mesenterectomy. Mesenteric, peritoneal and fascial contiguity mean that in resectional surgery, these technical elements can be reproducibly applied at all levels from the origin at the superior mesenteric root, to the anorectal junction. CONCLUSIONS: The goals of complete mesocolic, total mesocolic and mesorectal excision can be universally achieved at any level from duodenojejunal flexure to anorectal junction, by adopting technical elements based on mesenteric, peritoneal and fascial contiguity.

The AC-OK Cooccurring Screen: Reliability, Convergent Validity, Sensitivity, and Specificity.

The principal barriers to universal screening for the cooccurring disorders of mental illness and substance abuse are training, time, cost, and a reliable and valid screen. Although many of the barriers to universal screening still remain intact, the lack of a cooccurring screen that is effective and can be administered in a cost efficient way is no longer an obstacle. This study examined the reliability, factor structure, and convergent validity of the 15-item AC-OK Cooccurring Screen. A total of 2,968 AC-OK Cooccurring Screens administrated to individuals who called or went to one of the nine participating mental health and substance abuse treatment facilities were administrated and analyzed. Principal axis factor (PAF) analysis was used in the confirmatory factor analysis to identify the common variance among the items in the scales while excluding unique variance. Cronbach's Alpha was used to establish internal consistency (reliability) of each subscale. Finally, the findings from the AC-OK Cooccurring Screen were compared to individual scores on two standardized reference measures, the addiction severity index and the Client assessment record (a measure of mental health status) to determine sensitivity and specificity. This analysis of the AC-OK Cooccurring Screen found the subscales to have excellent reliability, very good convergent validity, excellent sensitivity, and sufficient specificity to be highly useful in screening for cooccurring disorders in behavioral health settings. In this study, the AC-OK Cooccurring Screen had a Cronbach's Alpha of .92 on the substance abuse subscale and a Cronbach's Alpha of .80 on the mental health subscale.

Acid suppression increases rates of Barrett's esophagus and esophageal injury in the presence of duodenal reflux.

BACKGROUND: The contribution of gastric acid to the toxicity of alkaline duodenal refluxate on the esophageal mucosa is unclear. This study compared the effect of duodenal refluxate when acid was present, decreased by proton pump inhibitors (PPI), or absent. METHODS: We randomized 136 Sprague-Dawley rats into 4 groups: group 1 (n = 33) were controls; group 2 (n = 34) underwent esophagoduodenostomy promoting "combined reflux"; group 3 (n = 34) underwent esophagoduodenostomy and PPI treatment to decrease acid reflux; and group 4, the 'gastrectomy' group (n = 35) underwent esophagoduodenostomy and total gastrectomy to eliminate acid in the refluxate. Esophaguses were examined for inflammatory, Barrett's, and other histologic changes, and expression of proliferative markers Ki-67, proliferating cell nuclear antigen (PCNA), and epidermal growth factor receptor (EGFR). RESULTS: In all reflux groups, the incidence of Barrett's mucosa was greater when acid was suppressed (group C, 62%; group D, 71%) than when not suppressed (group B, 27%; P = 0.004 and P < .001). Erosions were more frequent in the PPI and gastrectomy groups than in the combined reflux group. Edema (wet weight) and ulceration was more frequent in the gastrectomy than in the combined reflux group. Acute inflammatory changes were infrequent in the PPI group (8%) compared with the combined reflux (94%) or gastrectomy (100%) groups, but chronic inflammation persisted in 100% of the PPI group. EGFR levels were greater in the PPI compared with the combined reflux group (P = .04). Ki-67, PCNA, and combined marker scores were greater in the gastrectomy compared with the combined reflux group (P = .006, P = .14, and P < .001). CONCLUSION: Gastric acid suppression in the presence of duodenal refluxate caused increased rates of inflammatory changes, intestinal metaplasia, and molecular proliferative activity. PPIs suppressed acute inflammatory changes only, whereas chronic inflammatory changes persisted.

The Extent of Axillary Lymph Node Clearance Required Following Detection of Sentinel Node Micrometastases.

Sentinel node (SN) micrometastases are an indication to proceed to axillary clearance. The aim of this study is to determine the extent and level of axillary clearance required for patients with SN micrometastases. All patients with SN micrometastases which were followed by axillary clearances from 1999 to 2007 were identified. Slides were reviewed by a histopathologist to detail characteristics of SN micrometastases including size and site. The SN micrometastases and primary tumor characteristics were correlated with the presence and level of non-SN micrometastases. Fifty patients who had micrometastases followed by axillary clearances were identified. Of those 18% (n = 9) had non-SN metastases.Seven patients had metastases to level I, one patient had metastases to level I and III and one patient had non-SN metastases to level III only. No patient had metastases to level II. Patients with non-SN metastases had very limited number of non-SNs involved (maximum 2 non-SNs). No variable, including site of the micrometastasis, was predictive of non-SN metastases. In patients with SN micrometastases, a limited level I axillary clearance can be justified in view of the low number of additional nodes involved and in particular, the low (4%) rate of spread to level II / III nodes.

The value of level III clearance in patients with axillary and sentinel node positive breast cancer.

BACKGROUND: The value of level III axillary clearance is contentious, with great variance worldwide in the extent and levels of clearance performed. OBJECTIVE: To determine rates of level III positivity in patients undergoing level I-III axillary clearance, and identify which patients are at highest risk of involved level III nodes. METHODS: From a database of 2850 patients derived from symptomatic and population-based screening service, 1179 patients who underwent level I-III clearance between the years 1999-2007 were identified. The pathology, surgical details, and prior sentinel nodes biopsies of patients were recorded. RESULTS: Eleven hundred seventy nine patients had level I-III axillary clearance. Of the patients, 63% (n = 747) were node positive. Of patients with node positive disease, 23% (n = 168) were level II positive and 19% (n = 141) were level III positive. Two hundred fifty patients had positive sentinel node biopsies prior to axillary clearance. Of these, 12% (n = 30) and 9% (n = 22) were level II and level III positive, respectively. On multivariate analysis, factors predictive of level III involvement in patients with node positive disease were tumor size (P < 0.001, OR = 1.36; 95% CI: 1.2-1.5), invasive lobular disease (P < 0.001, OR = 3.6; 95% CI: 1.9-6.95), extranodal extension (P < 0.001, OR = 0.27; 95% CI: 0.18-0.4), and lymphovascular invasion (P = 0.04, OR = 0.58; 95% CI: 0.35-1). Lobular invasive disease (P = 0.049, OR = 4.1; 95% CI: 1-16.8), extranodal spread (P = 0.003, OR = 0.18; 95% CI: 0.06-0.57), and having more than one positive sentinel node (P = 0.009, OR = 4.9; 95% CI: 1.5-16.1) were predictive of level III involvement in patients with sentinel node positive disease. CONCLUSION: Level III clearance has a selective but definite role to play in patients who have node positive breast carcinoma. Pathological characteristics of the primary tumor are of particular use in identifying those who are at various risk of level III nodal involvement.

Coassociation of estrogen receptor and p160 proteins predicts resistance to endocrine treatment; SRC-1 is an independent predictor of breast cancer recurrence.

PURPOSE: This study investigates the role of the p160 coactivators AIB1 and SRC-1 independently, and their interactions with the estrogen receptor, in the development of resistance to endocrine treatments. EXPERIMENTAL DESIGN: The expression of the p160s and the estrogen receptor, and their interactions, was analyzed by immunohistochemistry and quantitative coassociation immunofluorescent microscopy, using cell lines, primary breast tumor cell cultures, and a tissue microarray with breast cancer samples from 560 patients. RESULTS: Coassociation of the p160s and estrogen receptor alpha was increased in the LY2 endocrine-resistant cell line following treatment with tamoxifen in comparison with endocrine-sensitive MCF-7 cells. In primary cultures, there was an increase in association of the coactivators with estrogen receptor alpha following estrogen treatment but dissociation was evident with tamoxifen. Immunohistochemical staining of the tissue microarray revealed that SRC-1 was a strong predictor of reduced disease-free survival (DFS), both in patients receiving adjuvant tamoxifen treatment and untreated patients (P < 0.0001 and P = 0.0111, respectively). SRC-1 was assigned a hazard ratio of 2.12 using a Cox proportional hazards model. Endocrine-treated patients who coexpressed AIB1 with human epidermal growth factor receptor 2 had a significantly shorter DFS compared with all other patients (P = 0.03). Quantitative coassociation analysis in the patient tissue microarray revealed significantly stronger colocalization of AIB1 and SRC-1 with estrogen receptor alpha in patients who have relapsed in comparison with those patients who did not recur (P = 0.026 and P = 0.00001, respectively). CONCLUSIONS: SRC-1 is a strong independent predictor of reduced DFS, whereas the interactions of the p160 proteins with estrogen receptor alpha can predict the response of patients to endocrine treatment.

Cyclooxygenase-2 predicts adverse effects of tamoxifen: a possible mechanism of role for nuclear HER2 in breast cancer patients.

Cyclooxygenase-2 (COX-2) is associated with breast tumour progression. Clinical and molecular studies implicate human epidermal growth factor receptor 2 (HER2) in the regulation of COX-2 expression. Recent reports raise the possibility that HER2 could mediate these effects through direct transcriptional mechanisms. The relationship between HER2 and COX-2 was investigated in a cohort of breast cancer patients with or without endocrine treatment. A tissue microarray comprising tumours from 560 patients with 10-year follow-up was analysed for HER2, ERK1/2, polyoma enhancer activator 3 (PEA3) and COX-2 expression. Subcellular localisation of HER2 was assessed by immunofluorescence and confocal microscopy. Expression of markers examined was analysed in relation to classic clinicopathological parameters and disease-free survival in the presence and absence of tamoxifen. COX-2 expression associated with both membranous and nuclear expression of HER2 (P=0.0033 and P<0.00001 respectively). No association was detected between COX-2 and either ERK1/2 or PEA3 (P=0.7 and P=0.3 respectively). None of the markers were found to be independently prognostic. Membrane HER2, nuclear HER2 and COX-2, however, were all found to predict poor disease-free survival in patients on endocrine treatment (P=0.0017, P=0.0003 and P=0.0202 respectively). Moreover, patients who were positive for COX-2 predicted adverse effects of tamoxifen (P=0.0427). These clinical ex vivo data are consistent with molecular observations that HER2 can regulate COX-2 expression through direct transcriptional mechanisms. COX-2 expression correlates with disease progression on endocrine treatment. This study supports a role for COX-2 as a predictor of adverse effects of tamoxifen in breast cancer patients.

Needle core biopsy characteristics identify patients at risk of compromised margins in breast conservation surgery.

Selection of patients for breast-conserving surgery relies on inexact parameters such as the preoperative estimation of lesion size. This study investigates the value of needle core biopsy findings, in particular, the relative quantity of DCIS, in improving patient selection for breast conservation. Patients undergoing breast-conserving surgery for invasive ductal carcinoma from 1999 to 2004 were identified. Only patients who had a preoperative diagnosis of carcinoma (DCIS and invasive) on core biopsy were included. All core biopsies were reviewed by a breast histopathologist to document the quantity and characteristics of the DCIS component. Of a total of 281 patients, 46% (n=129) had invasive disease on core biopsy (group 1) and 54% (n=152) had either invasive disease with an accompanying DCIS component or DCIS only on core biopsy (group 2). The compromised margin rate for group 1 was 23% compared to 39% for group 2 (P=0.004). The rate of compromised margins increased progressively as the core biopsy DCIS component increased until a rate of 75% (n=18/24) was reached in patients with DCIS only on core biopsy. In patients with a DCIS component on core biopsy, the presence of necrosis (P=0.002), solid type architecture (P=0.008), high grade DCIS (P=0.007), calcification (P=0.003), and the relative proportion of DCIS present (P<0.001) were associated with compromised margins on univariate analysis. On multivariate analysis of this subgroup, the proportion of DCIS in this subgroup (P=0.048) was an independent predictor of compromised margins. The presence and relative proportion of DCIS on core biopsy provides important information as to whether patients are at risk of compromised margins. Documentation of these parameters may assist patient selection for breast-conserving surgery or identify patients who may benefit from wider margins at the time of initial operation.

Analysis of patients with false negative mammography and symptomatic breast carcinoma.

AIM: False-negative mammograms may result in a delay in breast carcinoma diagnosis and have important implications for patient care. In this study, the characteristics of symptomatic patients with false-negative mammograms were analysed. METHODS: Patients with symptomatic breast carcinoma were identified over a 10-year period (1994-2004). One hundred and twenty-four patients had false-negative preoperative mammograms and 1241 patients had abnormal preoperative mammograms. Clinical presentation, diagnostic methods and pathology were analysed. False-negative mammograms were reviewed by a specialist breast radiologist. RESULTS: Following retrospective review, 42% of false-negative mammograms were re-categorised as suspicious. The most commonly misinterpreted lesion was architectural distortion/asymmetrical density. Adjuvant ultrasound, where performed (n = 27), raised the level of suspicion in 93% of cases. Patients with false-negative mammograms were more likely to be younger (P < 0.0001), present with nipple discharge (P = 0.002) and have smaller tumours (P < 0.0001). Their tumours were more frequently located outside the upper outer quadrant (P = 0.002). False-negative mammography led to a delay in diagnosis of >2 months in 12 patients. CONCLUSION: Symptomatic patients with false-negative mammograms often demonstrate definite abnormalities on imaging, the most common of which is architectural distortion/asymmetrical density. Those at particular risk were younger patients, those with nipple discharge, and patients with lesions located outside the upper outer quadrant.

Factors affecting successful breast conservation for ductal carcinoma in situ.

BACKGROUND: Successful breast-conserving therapy in DCIS is restricted by high rates of residual disease resulting in the need for radiotherapy and/or re-excision. This study identifies patients with DCIS who are most at risk of compromised margins and of residual disease. METHODS: All patients undergoing breast-conserving surgery for DCIS over a 6-year period were included. Method of diagnosis, mammographic size, pathological size, DCIS-margin distance and residual disease on re-excision were analysed. RESULTS: One hundred and thirty-five patients underwent initial breast-conserving surgery for DCIS. The compromised margin rate was 72%, and the rate of residual disease on re-operation was 54%. On univariate analysis, underestimation of pathological size by mammography by >1 cm occurred in 40% of those with compromised margins undergoing a therapeutic operation compared to only 14% of those with clear margins (P = 0.02). However, on multivariate analysis only pathological size (P < 0.0001, OR = 1.0,95% CI 1.037-1.128) and lack of a preoperative diagnosis by core biopsy (P < 0.0001, OR = 5.3,95% CI 1.859-15.08) were predictive of compromised margins. The presence of residual disease on re-excision was associated with increasing pathological size (P < 0.0001, OR = 1.085,95% CI 1.038-1.134) and decreasing DCIS-margin distance (P = 0.03, OR = 6.694,95% CI 1.84-37.855). Twenty-nine percent (n = 13/45) of lesions < or =3 cm compared to 84% (n = 27/32) of lesions >3 cm had residual disease on re-operation (P < 0.0001). Residual disease was present in 62% (n = 34/55), 64% (n = 7/11) and 17% (n = 2/12) of patients with DCIS-margin distances < or =1, 1-2 and 2-5 mm, respectively. CONCLUSION: Considerable underestimation of DCIS extent by mammography occurs in a high proportion of patients with compromised margins in breast conservation. Patients at particularly high risk of residual disease on re-excision are those with lesions >3 cm and those with DCIS-margin distances of < or = 2mm.

Interfacing with Community Mental Health Services: Opportunities for Occupational Therapy and Level II Fieldwork Education.

A three-year $54,000 grant has provided an opportunity for students in the Master of Occupational Therapy Programs at The University of Findlay to complete Level II fieldwork experiences in a community mental health setting. Occupational Therapy Program faculty and Level II fieldwork students were involved in the evaluation and intervention process for individuals who have severe mental illness and were participating in a supported employment program. After the first year of completion with the addition of these occupational therapy services, results indicate a 69% increase in secured competitive employment for individuals who have participated in this grant project.

Predictive value of breast lesions of "uncertain malignant potential" and "suspicious for malignancy" determined by needle core biopsy.

BACKGROUND: The optimum management of patients whose needle core biopsy (NCB) results are of "uncertain malignant potential" (B3) or "suspicious for malignancy" (B4) is unclear. This study correlates B3 and B4 NCB findings with excision histology to determine associated rates of malignancy. METHODS: All NCBs categorized as B3 or B4 were identified from a series of 3729 NCBs. Results of biopsies were reported as normal/nondiagnostic (B1), benign (B2), uncertain malignant potential (B3), suspicious but not diagnostic of malignancy (B4), or malignant (B5) according to the B classification system. B3 lesions included atypical intraductal epithelial proliferations (AIEPs), lobular neoplasia, papillary lesions, radial scars, and potential phyllodes tumors. Histological concordance between NCB and excision specimen was analyzed. RESULTS: A total of 211 B3 lesions and 51 B4 lesions were identified during the study period. The open biopsy rate after a B3/B4 finding was 86% (n = 226). The overall rate of malignancy for B3 lesions after excision was 21%. The B3 lesion-specific rates of malignancy were 6% for radial scars, 14% for papillomas, 35% for AIEP, and 44% for lobular neoplasia. Of the patients with a B4 categorization, 90% (44 of 49) were diagnosed with carcinoma after surgery. Those that were "suspicious for ductal carcinoma-in-situ" and "suspicious for invasion" correlated accurately with excision findings in 81% and 89% of patients, respectively. CONCLUSIONS: Management of lesions in the B3 categorization must be tailored to the patient because the specific lesion types are associated with highly variable rates of malignancy. A repeat biopsy or a therapeutic wide local excision should be undertaken in lesions with a B4 NCB categorization because such lesions are associated with a particularly high risk of malignancy at excision.

Needle core biopsy in the diagnosis of phyllodes neoplasm.

BACKGROUND: Accurate identification of phyllodes neoplasms without surgical intervention is difficult, reducing the ability to manage "benign" lumps non-operatively and impacting on the open benign biopsy rate. Needle core biopsy is considered to be a highly accurate technique in the diagnosis of breast carcinoma. Its accuracy in the diagnosis of phyllodes neoplasm has not been established. METHODS: A series of 3729 core biopsies performed between January 1999 and July 2005 were examined. All core biopsies followed by surgical excision were identified. Histologic concordance between core biopsy and excision specimen was analyzed. RESULTS: Twenty-three patients had phyllodes neoplasm on excisional biopsy with prior core biopsy findings as follows: phyllodes neoplasm (n=2), "equivocal" for phyllodes neoplasm (n=12), fibroadenoma (n=3), benign (n=6). The false negative rate for phyllodes neoplasm was therefore 39% (n=9/23). Of the total biopsy series, 35 patients had a core biopsy suggesting the possibility of phyllodes neoplasm. Of these, 32% (n=11) were found to be phyllodes neoplasm on excision, 3% (n=1) phyllodes neoplasm with breast carcinoma, 6% (n=2) breast carcinoma, and 3% (n=1) sarcoma. When a preference for phyllodes neoplasm (n=4) was stated on the equivocal core biopsies, excision correlated with the stated preference; this correlation also occurred in 90% (n=9/10) of core biopsies where fibroadenoma was favored. CONCLUSIONS: Needle core biopsy rarely produces a definite preoperative diagnosis of phyllodes neoplasm. A diagnosis of fibroadenoma or equivocal phyllodes neoplasm on core biopsy should not prevent excision if clinical suspicion remains.

Population-based retrieval of newborn dried blood spots for researching paediatric cancer susceptibility genes.

We have demonstrated the feasibility of linking newborn blood spots, population-based cancer incidence data and birth certificate data. Incident cases of acute lymphocytic leukaemia and population-based controls were ascertained. We retrieved dried blood spot specimens, isolated and amplified DNA, and assayed the cancer susceptibility genes GSTT1 and GSTM1. The double null genotype was over-represented in the cases, consistent with previous reports based on other epidemiological methods. The design avoids issues of participation bias by cases and controls and can be used to investigate interactions of susceptibility genes and xenobiotics in semi-ecological studies. It can be useful for generating or testing hypotheses on associations of other paediatric illness and environmental contaminants.

The role of major duct excision and microdochectomy in the detection of breast carcinoma.

BACKGROUND: The association of nipple discharge with breast carcinoma has resulted in numerous women undergoing exploratory surgery to exclude malignancy. The aim of this study was to determine whether pre-operative factors can identify those patients that are most at risk of carcinoma. METHODS: All patients over a 14-year period (1991-2005) who had a microdochectomy or subareolar exploration for the evaluation of nipple discharge were assessed. Patient characteristics, pre-operative imaging and pathological findings were analysed. RESULTS: Of the 211 patients included in this study, 116 patients had pathological (unilateral, uniductal serous or bloody) discharge. On excision, 6% (n = 7) of patients with pathological discharge and 2.4% (n = 2) of patients with non-pathological discharge were diagnosed with carcinoma. Overall, major duct excision resulted in the diagnosis of carcinoma in 4.3% (n = 9), ADH/LCIS in 4% (n = 8), papilloma in 39% (n = 83), and duct ectasia or non-specific benign disease in 53% (n = 111) of patients. In the patients determined to have malignancy, 44% (n = 4) were premenopausal. No patient with a non-bloody discharge in the total population analysed (28%; n = 59/211), or in the population with a pathological discharge (21%; n = 24/116) was found to have carcinoma upon excision. CONCLUSION: Microdochectomy or major duct excision performed for nipple discharge resulted in a low rate of malignancy on excision. Conservative management of non-bloody nipple discharge can be considered in patients with no other clinical or radiological signs of malignancy.