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A radiochemical oestrogen receptor assay on cytosol was correlated with a radiochemical and an immunohistochemical oestrogen receptor assay using cryostat sections from 50 breast cancer specimens. Oestrogen receptors were reliably quantitated in 6 micron cryostat sections with Scatchard analysis using radiolabelled oestradiol, and a good quantitative and qualitative relation with cytosol oestrogen receptor assay was found. Parallel sections were used for routine histological tissue verification and for direct comparison with immunohistochemistry for oestrogen receptor. Specific immunoperoxidase staining with a rat monoclonal antibody was scored by semiquantitative evaluation of the staining intensity of cancer cell nuclei. Oestrogen receptor scoring was highly reproducible when performed by the same observer. The semiquantitative immunohistochemical oestrogen receptor score correlated significantly better with the radiochemical assay on sections than with cytosol assay. Oestrogen receptor in breast cancer can be reliably assayed by semiquantitative evaluation of cryostat sections immunostained for oestrogen receptor, but only if the procedure is adequately standardised. The results underline the importance of cellular heterogeneity as a cause of variation in oestrogen receptor assay evaluation in breast cancer. [ABSTRACT FROM PUBLISHER]

Background: The use of multidetector computed tomography (CT) in lung-cancer screening trials involving subjects with an increased risk of lung cancer has highlighted the problem for the clinician of deciding on the best course of action when noncalcified pulmonary nodules are detected by CT., Methods: A total of 7557 participants underwent CT screening in years 1, 2, and 4 of a randomized trial of lung-cancer screening. We used software to evaluate a noncalcified nodule according to its volume or volume-doubling time. Growth was defined as an increase in volume of at least 25% between two scans. The first-round screening test was considered to be negative if the volume of a nodule was less than 50 mm(3), if it was 50 to 500 mm(3) but had not grown by the time of the 3-month follow-up CT, or if, in the case of those that had grown, the volume-doubling time was 400 days or more., Results: In the first and second rounds of screening, 2.6% and 1.8% of the participants, respectively, had a positive test result. In round one, the sensitivity of the screen was 94.6% (95% confidence interval [CI], 86.5 to 98.0) and the negative predictive value 99.9% (95% CI, 99.9 to 100.0). In the 7361 subjects with a negative screening result in round one, 20 lung cancers were detected after 2 years of follow-up., Conclusions: Among subjects at high risk for lung cancer who were screened in three rounds of CT scanning and in whom noncalcified pulmonary nodules were evaluated according to volume and volume-doubling time, the chances of finding lung cancer 1 and 2 years after a negative first-round test were 1 in 1000 and 3 in 1000, respectively. (Current Controlled Trials number, ISRCTN63545820.), (2009 Massachusetts Medical Society)

The present study aimed to assess the interobserver variation in histopathological grading of 88 slides by four experienced pathologists who, before the start of the study, reached consensus about the method of grading through a joint session behind a discussion microscope. The results were compared with two previous studies, the first assessing the observer variation under normal conditions, the second doing the same after theoretical agreement about which morphological characteristics were relevant for grading. In the present study the pathologists first made a provisional diagnosis on low power view, followed by a final diagnosis on high power view, scoring various morphological characteristics as in the second study. The unweighted and weighted group kappa values for the final diagnosis were 0.41 and 0.71 respectively in the present study (after the consensus meeting), compared to 0.33 and 0.70 respectively in the second study (after only theoretical consensus), and 0.28 and 0.55 in the first study (without consensus). We conclude that a consensus meeting appears to be useful to improve the interobserver agreement.

The present study aimed to assess where the interobserver variation in grading cervical dysplasia stems from. Four experienced pathologists examined 93 histological slides, after they agreed on which morphological characteristics should be considered relevant for grading. They scored 6 morphological characteristics for each slide and assigned it to a degree of dysplasia. Compared to a previous study, the interobserver variation showed a statistically significant improvement: the weighted group kappa value increased from 0.55 to 0.69. For the scores of the individual characteristics considerable interobserver variation was observed: weighted group kappa values ranged from 0.28 to 0.49. The pathologists slightly differed in which characteristics they considered most important for their grading. The agreement on the degree of dysplasia turned out to be better than the agreement on the morphological characteristics on which this diagnosis is based. In the discussion, a few explanations for this paradoxical finding are put forward.

In order to gain insight into the causality of the relation between beta-carotene and cancer, we performed a randomized placebo-controlled trial in which the effect of beta-carotene on the regression and progression rates of cervical dysplasia were examined. The experimental group (n = 137) received a supplemental dose of 10 mg of beta-carotene daily for 3 months. The control group (n = 141) received placebo capsules. As the outcome parameter, two definitions of regression and progression were used, which were based on the degree of dysplasia before and after the medication period. The number of patients who showed progression was too small to allow conclusions. No effect of beta-carotene on the regression percentages was observed: OR = 0.68 (95% CI: 0.28-1.60) using the broad definition; and OR = 1.22 (95% CI: 0.43-3.41) with the strict definition. A secondary analysis, in which the effect of the total intake of beta-carotene (diet + medication) on the regression percentages of cervical dysplasia was studied, did not show a positive effect either. The paper discusses to what extent issues in the study design may have masked a potential effect and how our results affect the evidence for a causal relation between beta-carotene and cancer.

Deficiencies of antioxidants and increased free radical generation may explain the high incidence of bronchopulmonary dysplasia in premature infants. Long-acting antioxidants such as polyethylene glycol (PEG) conjugated superoxide dismutase (SOD), and catalase might modify this process. We delivered 32 premature lambs, 16 pairs of twins, by cesarean section at 125-141 days of gestation (term 146 days) and stabilized them on ventilators in normocapnic hyperoxia for a period of 8 h. One lamb of each twin pair received an intravenous dose of 7,500-50,000 IU/kg of PEG-SOD and of 37,500-1,000,000 IU/kg of PEG-catalase at birth. Their siblings acted as controls. Mean airway pressure, arterial pressure, and heart rate were recorded continuously. Arterial blood gases and pH were obtained every 30 min. After sacrifice, standardized lung biopsies were prepared for quantitative morphometrics and electron microscopy. Administration of PEG antioxidants at birth reduced the influx of neutrophils and macrophages into the lung and damage to arterioles, bronchiolar mucosa, and type II pneumocytes without major changes in alveolar surface area or pulmonary function. These effects were dose-related and detectable even at the lowest doses of PEG antioxidants administered.

In order to assess the variability among histopathologists in grading cervical dysplasia, four experienced histopathologists examined the same set of 106 biopsy specimens and assigned them to one of five diagnostic categories. These were: no dysplasia, mild dysplasia, moderate dysplasia, severe dysplasia and carcinoma in situ. The histopathologists did not discuss the grading criteria beforehand. There was considerable disagreement among the pathologists: unweighted group kappa 0.28, weighted group kappa 0.56. It appeared that all grades of dysplasia were equally difficult to distinguish from adjacent categories. Various explanations for this interobserver variation are put forward.

9 healthy volunteers were examined by magnetic resonance imaging in order to describe the anatomy of the normal female genital tract as seen by this technique. The visualization of the bony and pelvic skeleton and the muscles surrounding these structures is excellent. Due to high contrast resolution relatively small structures like the femoral blood vessels can be positively identified. Imaging of the small bowel is disappointing. Visualization of the rectum and sigmoid colon is relatively good. In the uterine wall three distinct layers can be identified. An interpretation of the origin of these layers based on comparison with macroscopic and microscopic examination of sections of uterine tissue is given. Further research is needed to demonstrate possible cyclic changes in the appearance of the uterus. The ovaries could not be identified with certainty.

Disruption of the BM can be found in metastasizing neoplasms. It has been suggested that also in some patients with endometriosis the BM is lacking, depending on the severity of disease. Thus studying the aspect of the BM would enable characterization of the disease and possibly have a prognostic value with respect to (medical) treatment. We studied the aspect of the BM in 16 patients with endometriosis, 4 in each of the stages of the rAFS classification, and demonstrated all endometriosis lesions in all patients to be surrounded by a continuous and intact BM. We conclude that studying the BM in endometriosis offers no advantage in determining the prognosis of the disease and its possible response to therapy.

Benign tumors of the extrahepatic biliary ducts are rare. The high recurrence rate following local resection of these benign tumors is well known, but the development of one into a malignant tumor has received little attention. The recurrence 4 years after local excision of a benign periampullary tumor that developed into a well-differentiated papillar adenocarcinoma is described in this case report. Radical resection was performed by means of a pancreatoduodenectomy. The literature concerning the progression of benign extrahepatic tumors to adenocarcinomas is reviewed.

Three cases of granular cell tumor of the breast are reported. Granular cell tumor of the breast is a rare benign tumor with a malignant appearance both clinically, radiologically and macroscopically. The cytology is quite characteristic although the tumor clinically often resembles a carcinoma. Frozen section can be misinterpreted, unnecessary mastectomy or axillary dissection can be prevented by careful cytological examination.

Twenty-six premature lambs were treated by tracheal instillation of [14C]labeled natural sheep surfactant before the onset of breathing or after the establishment of respiratory distress syndrome 30 min after birth. Half of both groups were subsequently ventilated for 3 h with 100% O2 by conventional mechanical ventilation (CMV) and half by high frequency oscillation superimposed onto backup mechanical ventilation (HFOV). Mean airway pressure, arterial blood pressures, and heart rate were recorded continuously. Arterial blood gases and pH were obtained every 15 min. After sacrifice, the distribution of radiolabeled surfactant was quantified and alveolar expansion was evaluated by morphometrics. At comparable oxygenation, mean airway pressures were significantly lower in the lambs treated with surfactant at birth (groups CMV-B and HFOV-B) than in lambs on CMV and treated with surfactant during RDS (group CMV-R). Mean airway pressures in both groups of lambs on HFOV (groups HFOV-B and HFOV-R) were comparable at values lower than in group CMV-R and higher than in group CMV-B. The distribution of radiolabeled surfactant was more homogeneous in lambs treated at birth and not different for both types of ventilatory assistance. Morphometrics demonstrated significantly better expansion of the alveoli of lambs ventilated with HFOV than of those on CMV, irrespective of the timing of surfactant administration. These results indicate that prophylactic surfactant administration at birth leads to a better distribution of surfactant than rescue treatment with surfactant after the establishment of respiratory distress syndrome and is not affected by a subsequent type of ventilatory assistance.(ABSTRACT TRUNCATED AT 250 WORDS)

The use of high oxygen concentrations and high mean airway pressures during mechanical ventilation of premature newborn infants with respiratory distress syndrome leads in 20%-30% of the survivors to chronic lung disease. This study explores if exogenous polyethylene glycol conjugated superoxide dismutase (PEG-SOD) and catalase (PEG-CAT) mitigate oxygen toxicity in premature lambs with respiratory distress syndrome. Six pairs of premature lambs were delivered by cesarean section and treated by tracheal instillation of 60 mg natural sheep surfactant/kg/body weight. After birth, all lambs were ventilated with 100% oxygen, and one of each pair received a single intravenous injection of 1 million U/kg PEG-CAT and 50,000 U/kg PEG-SOD. At 8 h of age or after respiratory failure was established, the lambs were killed and the lungs were removed intact. Lung damage was assessed by microscopy. The arterial blood gases, pH, and mean airway pressures of the lambs treated with PEG-SOD/PEG-CAT did not differ from those of the controls. Mean PaO2 was greater than 140 mmHg during the first 4 h of the experiments. In the lambs treated with PEG-SOD/PEG-CAT, SOD and CAT levels were very high during the study period and less bronchiolar epithelial damage and lung hemorrhages were found at microscopy.