Objective

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.

Methods

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.

Results

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.

Conclusion

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.

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.

Background:

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.

Methods:

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.

Results:

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.

Conclusion:

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.

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.

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.

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.



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.

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.

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.

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.

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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)

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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.

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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)

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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.

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Twenty three children who had been treated for acute lymphoblastic leukaemia (ALL) were evaluated intellectually using the British Ability Scales. Their treatment included early cranial irradiation, intrathecal chemotherapy, and systemic chemotherapy. Nineteen children who had been treated for various types of solid tumours (ST), had undergone related chemotherapy, and had received irradiation to sites of the body other than the cranium were used as controls. In addition, patients' siblings were assessed and their scores statistically corrected to produce a best estimate of the patients' pre-morbid degree of intellectual functioning. The results showed intellectual deficits after treatment in both patient groups, but these were consistently larger in the ALL group, particularly for the higher functions of intelligence. Intellectual deficit in ALL patients did not show immediately after radiotherapy but became progressively more apparent some time afterwards and particularly in younger children. In contrast, in the ST group, intellectual deficits seemed to diminish over time, and the age at radiotherapy was not a critical factor.

In a dialysis centre with a high tap water aluminium content and a known high incidence of dialysis encephalopathy, 29 patients undertaking regular home dialysis, without clinical evidence of encephalopathy, were studied with a battery of psychological tests that have proved useful in detecting early organic intellectual deterioration in other conditions. Full-scale intelligence quotient, as measured by the Wechsler Adult Intelligence Scale, did not differ significantly from that of the normal population, but the patients showed significant deficiencies in three tests of performance--namely, digit symbol, block design, and picture arrangement. The ability to acquire new information in relation to performance was impaired and the abnormality increased with time on dialysis. Such tests should be useful in early detection of dialysis dementia at a reversible stage.