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1.  Multidisciplinary decisions in breast cancer: does the patient receive what the team has recommended? 
British Journal of Cancer  2013;108(12):2442-2447.
A multidisciplinary team (MDT) approach to breast cancer management is the gold standard. The aim is to evaluate MDT decision making in a modern breast unit.
All referrals to the breast MDT where breast cancer was diagnosed from 1 July 2009 to 30 June 2011 were included. Multidisciplinary team decisions were compared with subsequent patient management and classified as concordant or discordant.
Over the study period, there were 3230 MDT decisions relating to 705 patients. Overall, 91.5% (2956 out of 3230) of decisions were concordant, 4.5% (146 out of 3230), were discordant and 4% (128 out of 3230) had no MDT decision. Of 146 discordant decisions, 26 (17.8%) were considered ‘unjustifiable' as there was no additional information available after the MDT to account for the change in management. The remaining 120 discordant MDT decisions were considered ‘justifiable', as management was altered due to patient choice (n=61), additional information available after MDT (n=54) or MDT error (n=5).
The vast majority of MDT decisions are implemented. Management alteration was most often due to patient choice or additional information available after the MDT. A minority of management alterations were ‘unjustifiable' and the authors recommend that any patient whose treatment is subsequently changed should have MDT rediscussion prior to treatment.
PMCID: PMC3694248  PMID: 23736032
multidisciplinary team; breast cancer; cancer management
3.  Measuring the accuracy of diagnostic imaging in symptomatic breast patients: team and individual performance 
The British Journal of Radiology  2012;85(1012):415-422.
The combination of mammography and/or ultrasound remains the mainstay in current breast cancer diagnosis. The aims of this study were to evaluate the reliability of standard breast imaging and individual radiologist performance and to explore ways that this can be improved.
A total of 16 603 separate assessment episodes were undertaken on 13 958 patients referred to a specialist symptomatic breast clinic over a 6 year period. Each mammogram and ultrasound was reported prospectively using a five-point reporting scale and compared with final outcome.
Mammographic sensitivity, specificity and receiver operating curve (ROC) area were 66.6%, 99.7% and 0.83, respectively. The sensitivity of mammography improved dramatically from 47.6 to 86.7% with increasing age. Overall ultrasound sensitivity, specificity and ROC area was 82.0%, 99.3% and 0.91, respectively. The sensitivity of ultrasound also improved dramatically with increasing age from 66.7 to 97.1%. Breast density also had a profound effect on imaging performance, with mammographic sensitivity falling from 90.1 to 45.9% and ultrasound sensitivity reducing from 95.2 to 72.0% with increasing breast density.
The sensitivity ranges widely between radiologists (53.1–74.1% for mammography and 67.1–87.0% for ultrasound). Reporting sensitivity was strongly correlated with radiologist experience. Those radiologists with less experience (and lower sensitivity) were relatively more likely to report a cancer as indeterminate/uncertain. To improve radiology reporting performance, the sensitivity of cancer reporting should be closely monitored; there should be regular feedback from needle biopsy results and discussion of reporting classification with colleagues.
PMCID: PMC3486650  PMID: 21224304
4.  Quantification of the UK 5-point breast imaging classification and mapping to BI-RADS to facilitate comparison with international literature 
The British Journal of Radiology  2011;84(1007):1005-1010.
The UK 5-point breast imaging scoring system, recently formalised by the Royal College of Radiologists Breast Group, does not specify the likelihood of malignancy in each category. The breast imaging and reporting data system (BI-RADS) is widely used throughout North America and much of Europe. The main purpose of this study is to quantify the cancer likelihood of each of the UK 5-point categories and map them to comparable BI-RADS categories to facilitate comparison with North American and European literature and publication of UK research abroad.
During the 8 year study period, mammogram and ultrasound results were UK scored and the percentage of cancer outcomes within each group calculated. These were then compared with the percentage incidence of the BI-RADS categories.
Of 23 741 separate assessment episodes, 15 288 mammograms and 10 642 ultrasound examinations were evaluated. There was a direct correlation between UK scoring and BI-RADS for categories 1 and 5. UK Score 2 lipomas and simple cysts correlated with BI-RADS 2, with the remaining UK Score 2 lesions (mostly fibroadenomas) assigned to BI-RADS 3. BI-RADS 4 incorporates a wide range of cancer risk (2–95%) with subdivisions a, b and c indicating increasing, but unspecified, likelihood of malignancy. UK Score 3 correlated with BI-RADS 4 a/b and UK Score 4 corresponded with BI-RADS 4c.
This study quantifies the cancer likelihood of the UK scoring and maps them to parallel BI-RADS categories, with equivalent cancer risks. This facilitates the ability to share UK research data and clinical practice on an international scale.
PMCID: PMC3473699  PMID: 22011830
5.  Incidental breast lesions detected on CT: what is their significance? 
The British Journal of Radiology  2010;83(987):233-240.
An increasing number of breast lesions are being detected incidentally on CT. The aim of this study was to investigate the rate of referrals to the breast unit for assessment of lesions identified on CT and the resulting yield of previously undiagnosed breast malignancies from this pathway. A retrospective review was undertaken of CT examinations conducted over a period of 14 years. All patients (with no previous history of breast cancer) whose report contained the keyword “breast” and who were referred to a specialist breast unit for assessment were reviewed. CT lesion morphology and enhancement pattern were identified and compared with the final diagnostic outcome. 70 patients were identified by retrospective analysis, yielding 78 incidental breast lesions, of which 22 (28.2%) were malignant (category B5). This gave a positive predictive value (PPV) for malignancy of 28.2%. The best morphological predictor of malignancy was spiculation (PPV, 76%) and irregularity (PPV, 58%), whereas calcification patterns (PPV, 36%) were diagnostically unhelpful. Malignant lesions were likely to be larger (mean, 28.5 mm) than benign lesions (mean, 20.2 mm; p<0.05). In conclusion, 30% of incidental breast lesions in this large series of patients proved to be unsuspected breast cancers, particularly irregular spiculated masses. Referral for formal triple assessment of CT-diagnosed breast lesions is worthwhile, and careful examination of the breast should be a routine part of CT examinations.
PMCID: PMC3473543  PMID: 19546179
6.  Radiological staging in breast cancer: which asymptomatic patients to image and how 
British Journal of Cancer  2009;101(9):1522-1528.
Approximately 4% of patients diagnosed with early breast cancer have occult metastases at presentation. Current national and international guidelines lack consensus on whom to image and how.
We assessed practice in baseline radiological staging against local guidelines for asymptomatic newly diagnosed breast cancer patients presenting to the Cambridge Breast Unit over a 9-year period.
A total of 2612 patients were eligible for analysis; 91.7% were appropriately investigated. However in the subset of lymph node negative stage II patients, only 269 out of 354 (76.0%) investigations were appropriate. No patients with stage 0 or I disease had metastases; only two patients (0.3%) with stage II and ⩽3 positive lymph nodes had metastases. Conversely, 2.2, 2.6 and 3.8% of these groups had false-positive results. The incidence of occult metastases increased by stage, being present in 6, 13.9 and 57% of patients with stage II (⩾4 positive lymph nodes), III and IV disease, respectively.
These results prompted us to propose new local guidelines for staging asymptomatic breast cancer patients: only clinical stage III or IV patients require baseline investigation. The high specificity and convenience of computed tomography (chest, abdomen and pelvis) led us to recommend this as the investigation of choice in breast cancer patients requiring radiological staging.
PMCID: PMC2778507  PMID: 19861999
radiological staging; asymptomatic; breast cancer; CT
7.  One-stop diagnostic breast clinics: how often are breast cancers missed? 
British Journal of Cancer  2009;100(12):1873-1878.
The aim of this study was to estimate the number of patients discharged from a symptomatic breast clinic who subsequently develop breast cancer and to determine how many of these cancers had been ‘missed' at initial assessment. Over a 3-year period, 7004 patients were discharged with a nonmalignant diagnosis. Twenty-nine patients were subsequently diagnosed with breast cancer over the next 36 months. This equates to a symptomatic ‘interval' cancer rate of 4.1 per 1000 women in the 36 months after initial assessment (0.9 per 1000 women within 12 months, 2.6 per 1000 women within 24 months). The lowest sensitivity of initial assessment was seen in patients of 40–49 years of age, and these patients present the greatest imaging and diagnostic challenge. Following multidisciplinary review, a consensus was reached on whether a cancer had been missed or not. No delay occurred in 10 patients (35%) and probably no delay in 7 patients (24%). Possible delay occurred in three patients (10%) and definite delay in diagnosis (i.e., a ‘missed' cancer) occurred in only nine patients (31%). The overall diagnostic accuracy of ‘triple' assessment is 99.6% and the ‘missed' cancer rate is 1.7 per 1000 women discharged.
PMCID: PMC2714235  PMID: 19455145
breast cancer; breast diseases; diagnosis; diagnostic errors
9.  Screen-detected vs symptomatic breast cancer: is improved survival due to stage migration alone? 
British Journal of Cancer  2008;98(11):1741-1744.
This paper examines whether screen-detected breast cancer confers additional prognostic benefit to the patient, over and above that expected by any shift in stage at presentation. In all, 5604 women (aged 50–70 years) diagnosed with invasive breast cancer between 1998 and 2003 were identified by the Eastern Cancer Registration and Information Centre (ECRIC) and mammographic screening status was determined. Using proportional hazards regression, we estimated the effect of screen detection compared with symptomatic diagnosis on 5-year survival unadjusted, then adjusted for age and Nottingham Prognostic Index (NPI). A total of 72% of the survival benefit associated with screen-detected breast cancer can be accounted for by age and shift in NPI. Survival analysis by continuous NPI showed a small but systematic survival benefit for screen-detected cancers at each NPI value. These data show that although most of the screen-detected survival advantage is due to a shift in NPI, the mode of detection does impact on survival in patients with equivalent NPI scores. This residual survival benefit is small but significant, and is likely to be due to differences in tumour biology. Current prognostication tools may, therefore, overestimate the benefit of systemic treatments in screen-detected cancers and lead to overtreatment of these patients.
PMCID: PMC2410118  PMID: 18506175
breast cancer; breast screening; survival
12.  Can breast MRI help in the management of women with breast cancer treated by neoadjuvant chemotherapy? 
British Journal of Cancer  2004;90(7):1349-1360.
PMCID: PMC2409692  PMID: 15054453
breast cancer; breast MRI; disease response; diagnostic impact; neoadjuvant chemotherapy
15.  Attentional ability among survivors of leukaemia 
Archives of Disease in Childhood  1999;80(4):318-323.
Attentional ability in 19 survivors of acute lymphoblastic leukaemia and 19 sibling controls was assessed using a neuropsychological model of attention. Analysis revealed that children who had received treatment for leukaemia exhibited significantly poorer performance on measures of the "focus encode" and "focus execute" elements of attention and on measures of the ability to respond to external cues and feedback. No significant differences in performance were found for measures of sustained attention and the ability to shift attention. These results indicate that children who have received treatment for leukaemia may experience highly specific attentional deficits that could have an impact on academic performance, particularly mathematical and reading skills. It is suggested that this underlying attentional deficit might be the source of the neuropsychological sequelae associated with the disease. Future attempts at remediation should incorporate activities specifically designed to ameliorate focusing difficulties.

PMCID: PMC1717894  PMID: 10086934
17.  Replication and packaging of coronavirus infectious bronchitis virus defective RNAs lacking a long open reading frame. 
Journal of Virology  1996;70(12):8660-8668.
The construction of a full-length clone of the avian coronavirus infectious bronchitis virus (IBV) defective RNA (D-RNA), CD-91 (9,080 nucleotides [Z. Penzes et al., Virology 203:286-293]), downstream of the bacteriophage T7 promoter is described. Electroporation of in vitro T7-transcribed CD-91 RNA into IBV helper virus-infected primary chick kidney cells resulted in the production of CD-91 RNA as a replicating D-RNA in subsequent passages. Three CD-91 deletion mutants were constructed--CD-44, CD-58, and CD-61--in which 4,639, 3,236, and 2,953 nucleotides, respectively, were removed from CD-91, resulting in the truncation of the CD-91 long open reading frame (ORF) from 6,465 to 1,311, 1,263, or 2,997 nucleotides in CD-44, CD-58, or CD-61, respectively. Electroporation of in vitro T7-transcribed RNA from the three constructs into IBV helper virus-infected cells resulted in the replication and packaging of CD-58 and CD-61 but not CD-44 RNA. The ORF of CD-61 was further truncated by the insertion of stop codons into the CD-61 sequence by PCR mutagenesis, resulting in constructs CD-61T11 (ORF: nucleotides 996 to 1,058, encoding 20 amino acids), CD-61T22 (ORF: nucleotides 996 to 2,294, encoding 432 amino acids), and CD-61T24 (ORF: nucleotides 996 to 2,450, encoding 484 amino acids), all of which were replicated and packaged to the same levels as observed for either CD-61 or CD-91. Analysis of the D-RNAs showed that the CD-91- or CD-61-specific long ORFs had not been restored. Our data indicate that IBV D-RNAs based on the natural D-RNA, CD-91, do not require a long ORF for efficient replication. In addition, a 1.4-kb sequence, corresponding to IBV sequence at the 5' end of the 1b gene, may be involved in the packaging of IBV D-RNAs or form part of a cis-acting replication element.
PMCID: PMC190960  PMID: 8970992
18.  Investigation of the control of coronavirus subgenomic mRNA transcription by using T7-generated negative-sense RNA transcripts. 
Journal of Virology  1995;69(10):6219-6227.
The subgenomic mRNAs of the coronavirus transmissible gastroenteritis virus (TGEV) are not produced in equimolar amounts. We have developed a reporter gene system to investigate the control of this differential subgenomic mRNA synthesis. Transcription of mRNAs by the TGEV polymerase was obtained from negative-sense RNA templates generated in situ from DNA containing a T7 promoter. A series of gene cassettes was produced; these cassettes comprised the reporter chloramphenicol acetyltransferase (CAT) gene downstream of transcription-associated sequences (TASs) (also referred to as intergenic sequences and promoters) believed to be involved in the synthesis of TGEV subgenomic mRNAs 6 and 7. The gene cassettes were designed so that negative-sense RNA copies of the CAT gene with sequences complementary to the TGEV TASs, or modified versions, at the 3' end would be synthesized in situ by T7 RNA polymerase. Using this system, we have demonstrated that CAT was expressed from mRNAs derived from the T7-generated negative-sense RNA transcripts only in TGEV-infected cells and only from transcripts possessing a TGEV negative-sense TAS. Analysis of the CAT mRNAs showed the presence of the TGEV leader RNA sequence at the 5' end, in keeping with observations that all coronavirus mRNAs have a 5' leader sequence corresponding to the 5' end of the genomic RNA. Our results indicated that the CAT mRNAs were transcribed from the in situ-synthesized negative-sense RNA templates without the requirement of TGEV genomic 5' or 3' sequences on the T7-generated negative-sense transcripts (3'-TAS-CAT-5'). Modification of the TGEV TASs indicated (i) that the degree of potential base pairing between the 3' end of the leader RNA and the TGEV negative-sense TAS was not the sole determinant of the amount of subgenomic mRNA transcribed and (ii) that other factors, including nucleotides flanking the TAS, are involved in the regulation of transcription of TGEV subgenomic mRNAs.
PMCID: PMC189519  PMID: 7666523
19.  Memory after treatment for acute lymphoblastic leukaemia. 
Archives of Disease in Childhood  1992;67(3):266-268.
Long term survivors of acute lymphoblastic leukaemia (ALL) often experience cognitive difficulties, which may be related to impairment of memory function. Memory ability has been studied in a group of survivors of ALL along with sibling controls and in children who have received treatment for other forms of cancer. Children in the ALL group were found to have significant deficits in memory function in tasks which required the application of strategic planning behaviour. These deficits are potentially remediable by educational strategies.
PMCID: PMC1793661  PMID: 1575545
20.  Cognitive function after two doses of cranial irradiation for acute lymphoblastic leukaemia. 
Archives of Disease in Childhood  1991;66(10):1245-1246.
The cognitive function of 23 children given cranial irradiation in a dose of 24 Gy was compared with that of 41 given 18 Gy. No significant differences were found in intellectual function or in mean number of intelligence quotient points lost between patients in the two treatment groups. A reduction in the dose of cranial irradiation does not seem to alleviate long term neuropsychological deficits.
PMCID: PMC1793513  PMID: 1953013
21.  Protein A gold identification of ureaplasmas on the bovine zona pellucida. 
The object of this study was to develop a prefixation protein A gold labelling technique for Ureaplasma diversum and to apply this to bovine embryos. Sixteen hour cultures of Ureaplasma diversum strain 2312 were incubated with either specific antiserum or nonimmune serum, followed by exposure to protein A gold and negative staining. The ureaplasmas which were incubated with specific antiserum were labelled with gold particles while those ureaplasmas which were incubated with nonimmune serum were not labelled. Twenty-three unhatched, day 7 bovine embryos were then incubated in either embryo culture medium (ECM) alone, ECM with sterile ureaplasma broth added or ECM with 1.7 X 10(6) colony forming units of Ureaplasma diversum strain 2312 per embryo. After 16 hours, the embryos were washed twice and incubated with either specific antiserum or nonimmune serum. The embryos were then incubated with medium containing protein A gold and examined by electron microscopy. No ureaplasmas were identified on the zona pellucida of the control embryos. Ureaplasmas were identified on the outer surface of the zona pellucida of 13 of the 17 embryos which had been exposed to the organism. Of these, the embryos which were incubated with specific antiserum had labelled ureaplasmas while the embryos which were incubated with nonimmune serum had unlabelled ureaplasmas on the zona pellucida. It was concluded that the protein A gold method was a suitable technique for the identification of ureaplasmas in EM preparations. The presence of ureaplasmas on the outer surface of the bovine zona pellucida following in vitro exposure to the organism was confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)
PMCID: PMC1255543  PMID: 2469532
22.  Adolescent-type Tillaux fracture of the ankle: two case reports. 
Archives of Emergency Medicine  1988;5(3):180-183.
Fracture of the lateral portion of the distal end of the tibia in adults is known as the fracture of Tillaux (Tillaux, 1872). The fracture line extends vertically from the distal articular surface of the tibia upwards to the lateral cortex. The fragment is roughly quadrangular in shape. The analogous epiphyseal injury is less common and two such cases are presented here, both were fixed internally. There now appears to be a consensus of opinion that for fractures of the lateral portion of the distal tibial epiphysis open reduction should be performed, and that closed reduction should be reserved for undisplaced or minimally displaced fractures only.
PMCID: PMC1285524  PMID: 3178979
24.  In vitro exposure of bovine morulae to Ureaplasma diversum. 
Ureaplasma diversum has been associated with infertility in the cow experimentally and in naturally occurring cases. However, the pathogenic mechanism is undetermined. The purpose of this study was to determine whether ureaplasmas are pathogenic for bovine morulae in vitro. Twenty-one morulae were recovered from three superovulated, mature, Holstein cows six or seven days postestrus. The embryos were divided into three groups (A,B,C) and incubated for 16 hours at 37 degrees C in humidified air with 10% CO2. Group A was incubated in embryo culture medium alone, Group B was incubated in culture medium with sterile ureaplasma broth added and Group C was incubated in culture medium containing 1.7 X 10(6) colony forming units Ureaplasma diversum strain 2312. After incubation, the morulae were examined using an electron microscope. Structures morphologically identical to U. diversum were present on the outer surface of the zonae pellucidae of all the morulae exposed to the organism and none were present on the unexposed control embryos. No other morphological differences were observed in either the ureaplasma-exposed embryos or the two groups of control embryos. Ureaplasma diversum was isolated from three of the five embryos incubated in culture medium with sterile ureaplasma broth added. These three embryos were recovered from one donor cow which cultured positive for U. diversum from the vulva and flush fluid. This finding suggests that the contaminating organisms entered the embryo culture wells either in the embryo collection medium or attached to the embryos.(ABSTRACT TRUNCATED AT 250 WORDS)
PMCID: PMC1255303  PMID: 3607652
25.  Intellect after malignancy. 
Archives of Disease in Childhood  1986;61(7):700-702.
A previous study has shown that significant intellectual deficits exist in children treated for leukaemia but not in those with solid tumours. Unexpectedly, the deficits had not increased in the two years since the original study, suggesting that the nadir had already been reached five years after diagnosis.
PMCID: PMC1777891  PMID: 3461748

Results 1-25 (27)