Interobserver agreement and diagnostic performance of individual MRI criteria for diagnosis of placental adhesion disorders.

AIM: To assess the diagnostic accuracy of several criteria for the diagnosis of placental adhesion disorder (PAD) on magnetic resonance imaging (MRI) and to assess interobserver agreement and reader accuracy based on years of interpretive experience. MATERIALS AND METHODS: Blinded evaluation of the placental MRI studies of 28 randomly selected women, 18 with PADs and 10 without PADs, was undertaken by three radiologists with 10, 5, and 2 years' experience in placental MRI interpretation. The presence of placenta praevia, dark intraplacental bands, heterogeneity, uterine bulging, "shaggy dog" appearance of the uterine serosa, subjective impression of extraplacental invasion, and dark intraplacental bands on diffusion-weighted imaging were assessed. Placental histology was reviewed blinded to the original reports and to MRI interpretation and this, along with clinical information at the time of delivery, formed the reference standard. RESULTS: Dark intraplacental bands on T2-weighted imaging were the most sensitive and specific as well as the most agreed upon (kappa=0.7) criterion for PAD for the three readers. Assessment of uterine bulging (kappa=0.42) and placental heterogeneity (kappa=0.48) did not improve diagnostic accuracy. DWI improved sensitivity but decreased specificity for the least experienced reader and did not change sensitivity or specificity for the more experienced readers. CONCLUSION: Assessment of the placenta for dark bands is the most sensitive, specific, and reproducible criterion for diagnosis of PADs using MRI.

Clinical consequences of upfront pathology review in the randomised PORTEC-3 trial for high-risk endometrial cancer.

Background: In the PORTEC-3 trial, women with high-risk endometrial cancer (HR-EC) were randomised to receive pelvic radiotherapy (RT) with or without concurrent and adjuvant chemotherapy (two cycles of cisplatin 50 mg/m2 in weeks 1 and 4 of RT, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2). Pathology review was required before patient enrolment. The aim of this analysis was to evaluate the role of central pathology review before randomisation. Patients and methods: A total of 1295 cases underwent pathology review to confirm HR-EC in the Netherlands (n = 395) and the UK (n = 900), and for 1226/1295 (95%) matching review and original reports were available. In total, 329 of these patients were enrolled in the PORTEC-3 trial: 145 in the Netherlands and 184 in the UK, comprising 48% of the total PORTEC-3 cohort of 686 participants. Areas of discrepancies were evaluated, and inter-observer agreement between original and review opinion was evaluated by calculating the kappa value (κ). Results: In the 1226 pathology reviews, 6356 selected items were evaluable for both original and review pathology. In 43% of cases at least one pathology item changed after review. For 102 patients (8%), this discrepancy led to ineligibility for the PORTEC-3 trial, most frequently due to differences in the assessment of histological type (34%), endocervical stromal involvement (27%) and histological grade (19%). Lowest inter-observer agreement was found for histological type (κ = 0.72), lymph-vascular space invasion (κ = 0.72) and histological grade (κ = 0.70). Conclusion: Central pathology review by expert gynaeco-pathologists changed histological type, grade or other items in 43% of women with HR-EC, leading to ineligibility for the PORTEC-3 trial in 8%. Upfront pathology review is essential to ensure enrolment of the target trial-population, and to avoid over- or undertreatment, especially when treatment modalities with substantial toxicity are involved. This study is registered with ISRCTN (ISRCTN14387080, www.controlled-trials.com) and with ClinicalTrials.gov (NCT00411138).

Detection of cervical intraepithelial neoplasia in vivo using confocal endomicroscopy.

OBJECTIVE: A high resolution optical imaging device may offer a clinically useful adjunct to colposcopy for the diagnosis and assessment of cervical precancer. This study describes the clinical evaluation of a miniaturised confocal endomicroscope for the quantitative and qualitative assessment of cervical intraepithelial neoplasia (CIN) in vivo. DESIGN: A descriptive study (n = 25) was performed to assess the usability of confocal endomicroscopy to image the cervix. A prospective study (n = 15) then evaluated the diagnostic accuracy of the technique. SETTING AND POPULATION: Patients undergoing colposcopy for treatment of CIN1-CIN3 were examined using confocal endomicroscopy. METHODS: A 5% solution of acetic acid was used to enhance the colposcopic features of the atypical region. Normal and abnormal regions of the cervix were then imaged following topical application of a fluorescent dye (acriflavine). MAIN OUTCOME MEASURES: Confocal images were analysed to develop a scoring system to grade different levels of CIN. Microscopic features were correlated with histology from biopsy. RESULTS: Confocal endomicroscopy enabled microscopic imaging of cellular and subcellular structures in vivo at colposcopy. Imaging at increasing depth showed morphological features including dermal papillae, endocervical glands and the squamo-columnar junction. CIN was characterised by an increase in nuclear density, size and cellular atypia. The sensitivity for detection of CIN was 97%. The specificity for predicting the grade of abnormality was 80% for normal-CIN1 and 93% for CIN2-CIN3. CONCLUSIONS: Confocal endomicroscopy is a sensitive imaging tool for detection and assessment of CIN. The technique enables in vivo imaging of cervical histology and the potential for 'see-and-treat' workflows.

Bilateral hip reconstruction in severe whole-body cerebral palsy: ten-year follow-up results.

The results of a functional, clinical and radiological study of 30 children (60 hips) with whole-body cerebral palsy were reviewed at a mean follow-up of 10.2 years (9.5 to 11). Correction of windsweep deformity of the hips was performed by bilateral simultaneous combined soft-tissue and bony surgery at a mean age of 7.7 years (3.1 to 12.2). We were able to recall 22 patients; five had died of unrelated causes and three were lost to follow-up. Evaluation involved interviews with patients/carers and clinical and radiological examination. The gross motor functional classification system was used to assess overall motor function and showed improvement in seven patients. Of the 12 patients thought to have pain pre-operatively, only one had pain post-operatively. Improved handling was reported in 18 of 22 patients (82%). Those with handling problems were attributed by the carers to growth of the patients. All patients/carers considered the procedure worthwhile. The range of hip movements improved, and the mean windsweep index improved from 50 pre-operatively to 36 at follow-up. The migration percentage and centre-edge angle were assessed on plain radiographs. Radiological containment improved, the mean migration percentage improved from 50 pre-operatively to 20 at follow-up and the mean centre-edge angle improved from -5 degrees to 29 degrees . No statistical difference was noted between the three-year and ten-year follow-up results, indicating that the improvements in clinical and radiological outcome had been maintained.

Bilateral hip surgery in severe cerebral palsy a preliminary review.

When cerebral palsy involves the entire body pelvic asymmetry indicates that both hips are 'at risk'. We carried out a six-year retrospective clinical, radiological and functional study of 30 children (60 hips) with severe cerebral palsy involving the entire body to evaluate whether bilateral simultaneous combined soft-tissue and bony surgery of the hip could affect the range of movement, achieve hip symmetry as judged by the windsweep index, improve the radiological indices of hip containment, relieve pain, and improve handling and function. The early results at a median follow-up of three years showed improvements in abduction and adduction of the hips in flexion, fixed flexion contracture, radiological containment of the hip using both Reimer's migration percentage and the centre-edge angle of Wiberg, and in relief of pain. Ease of patient handling improved and the satisfaction of the carer with the results was high. There was no difference in outcome between the dystonic and hypertonic groups.

Investigation of 100 consecutive negative cone biopsies.

OBJECTIVE: To investigate the reasons for cone biopsies reported as not containing intraepithelial or invasive malignancy and thereby find ways to decrease their incidence. DESIGN: One hundred cone biopsies reported as negative were identified out of a total of 436 consecutive cone biopsies. The patients' cytology, colposcopy and histology reports and cytology and histology slides were reviewed. Further opinions in cases of doubt were obtained in cytology and histology. In cone biopsies still considered negative after reviews, deeper levels were cut, exhausting all paraffin blocks. Follow up cytology, colposcopy and histology were reviewed. SETTING: Gynaecological oncology unit in a university teaching hospital. RESULTS: After re-evaluation the final diagnoses of cone biopsies initially reported as negative were positive (n = 21), unsatisfactory (n = 27) and true negative (n = 51), with one case excluded because of insufficient material for review. The positive cases were diagnosed on review (n = 11) or extra levels (n = 10). The unsatisfactory cases were all due to denudation. The 51 true negative cases were divided into those which never had had histologic confirmation by punch biopsy or endocervical curettage (n = 47) and those with a previously confirmed histological abnormality (n = 4). CONCLUSIONS: The number of negative cone biopsies can be reduced by: 1. taking Pap smears after correction of atrophy and inflammation; 2. more scrupulous colposcopy aimed at reducing the number of unsatisfactory colposcopies or misinterpreted colposcopic findings; this through examination should include the vagina and vulva; 3. confirmation of smear and colposcopic findings by biopsy prior to cold-knife conisation and performing a large loop excision of the transformation zone (LLETZ) for cases where there is a discrepancy between the smear abnormality and colposcopy/biopsy findings; 4. good quality cone biopsies using a technique that does not handle the mucosa and is performed after the mucosa has had time to regenerate following the colposcopic investigations; and 5. exhausting all blocks with multiple levels before reporting a cone biopsy as negative.

Changes in cardiovascular homeostasis after injury are mediated by tissue damage and not haemorrhage.

During treatment of the injured patient it is assumed that the cardiovascular responses follow recognized physiological principles. Studies in humans have shown that injury causes a profound suppression of arterial baroreflex function which alters the normal relationship between heart rate and blood pressure and casts doubt on this assumption. To investigate the mechanism of baroreflex suppression, we have studied the effects of the two major components of injury, blood loss and tissue damage, on baroreflex function in healthy volunteers. Baroreflex function was assessed using suction stimulation of the carotid sinus. The loss of 500 ml blood had no effect on baroreflex sensitivity. A human laboratory model of tissue injury reduced the ability of the baroreflex to compensate for a rise in blood pressure (P less than 0.05, Wilcoxon signed rank test). We conclude that tissue damage, rather than hypovolaemia, appears to mediate the effect of injury on baroreflex function in the injured. Blockade of neural signals from damaged tissue may have a role in the treatment of injury.