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A retrospective review of 185 mammary phyllodes tumors (105 benign, 51 borderline, 29 malignant) from 4 centers was performed by immunohistochemistry to investigate the expression of vascular endothelial growth factor in the epithelial and stromal cells of mammary phyllodes tumors. The correlation of vascular endothelial growth factor with tumor grade, stromal cell nuclear pleomorphism, cellularity, mitotic rate, margin histomorphology, and the stromal microvessel density was evaluated. Vascular endothelial growth factor expression was found in the epithelium in 29% and in the stromal cells in 31% of cases. There was significant increase of vascular endothelial growth factor expression in the stromal cells with increasing degree of malignancy, but not the epithelium. Microvessel density in the stroma also showed significant correlation with tumor malignancy, and a correlation was shown with the stromal vascular endothelial growth factor expression. Statistical overlap of stromal vascular endothelial growth factor and microvessel density in predicting malignancy suggests that angiogenesis may be an effector mechanism for vascular endothelial growth factor. Assessment of stromal VEGF may be useful as an adjunctive diagnostic criterion in the histologic assessment of malignancy in phyllodes tumors.

Study objectives Scoring of arousals in children is based on an extension of adult criteria, as defined by the American Sleep Disorders Association (ASDA). By this, a minimum duration of 3 seconds is required. A few recent studies utilized modified criteria for the study of children, with durations as short as 1 second. However, the validity and reliability of scoring these shorter arousals have never been verified. Based on studies in adults, we hypothesized that interscorer agreement for scoring arousals shorter than 3 seconds was poor. Design Retrospective review of polysomnograms by 2 experienced sleep practitioners who independently scored arousals according to the ASDA 3-second criteria and modified duration criteria of 1 and 2 seconds. Setting Academic hospital. Patients or participants 20 polysomnographic studies from children aged 3 to 8 years with mild to severe obstructive sleep apnea syndrome, and 16 polysomnographic studies from normal children. Interventions None. Measurements and results The intraclass correlation coefficient for scoring ASDA arousals was 0.90 (95% confidence interval: 0.81-0.95), indicating excellent interscorer agreement. The intraclass correlation coefficient for scoring modified 1-second and 2-second arousals were 0.35 (95% confidence interval: 0.02-0.61) and 0.42 (95% confidence interval: 0.12-0.65) respectively, indicating poor to fair interscorer agreement. Furthermore, modified 1-second and 2-second arousals accounted for less than 15% of all arousals scored. Conclusions We conclude that there is much poorer interscorer agreement for scoring arousals shorter than 3 seconds, when compared to the standard ASDA criteria. We propose that scoring of arousals in children should follow the standard ASDA criteria.

Objectives: The aim of the present systematic review is to critically appraise the current evidence from published medical trials on the role of programmed second endoscopy with appropriate therapy on peptic ulcer re-bleeding. Methods: A systematic review of five prospective randomized controlled trials comparing the effect of programmed second endoscopy against conservative management on peptic ulcer re-bleeding was carried out. Results: From the meta-analysis of the combined results from the five trials on the effect of programmed second endoscopy in ulcer bleeding, we found that a programmed second endoscopy with appropriate therapy reduced the number of recurrent bleeding significantly (Peto odds ratio = 1.97, Mantel Haenszel-Peto P

✓ From the records of The Mount Sinai Hospital, seven cases which met established criteria for radiation-induced meningiomas were identified. This represents the largest series of radiogenic meningiomas documented in North America and includes both intracranial and intraspinal tumors. The records and pathological specimens were reviewed and these data analyzed with other cases retrieved from the world literature. This study reveals that radiation-induced meningiomas can be categorized into three groups based on the amount of radiation administered: 1) low dose; 2) moderate dose and miscellaneous; and 3) high dose. The overwhelming majority of cases had received low-dose irradiation (800 rad) to the scalp for tinea capitis and the second largest group resulted from high-dose irradiation for primary brain tumors (> 2000 rad). The unique features distinguishing radiation-induced meningiomas from other meningiomas are reviewed. Although histologically atypical tumors were common in this series, overt malignancy was not encountered. The preoperative management of these lesions should include angiography to evaluate for large-vessel occlusive vasculopathy, a known association of meningiomas induced by high-dose irradiation. Given the propensity these tumors possess for recurrence, a wide bony and dural margin is recommended at surgical resection.

We examined 186 phyllodes tumors (106 benign, 51 borderline, 29 malignant) for angiogenesis by assessing stromal microvessel density by the hot spot method and assessing p53 protein expression; we correlated these factors with stromal cellularity, margin status, nuclear pleomorphism, mitosis, and stromal overgrowth. Increased degree of malignancy in phyllodes tumors is associated with increased patient age and tumor size. Microvessel density and p53 protein expression also showed a similar increase with malignancy. Using a logistic regression model, microvessel density was shown to be useful in predicting malignancy in phyllodes tumors, independent of key criteria of stromal overgrowth, nuclear pleomorphism, and mitosis. Microvessel density showed correlation with stromal cellularity and margin status, suggesting an interrelationship between these parameters. P53 protein expression showed a positive correlation with microvessel density, suggesting possible overlap in the underlying mechanism of these two factors in the pathogenesis of phyllodes tumors. The numbers of recurrences and metastases are small in our series, and no significant difference was demonstrated in microvessel density and p53 protein expression compared with the primary. We conclude that microvessel density and p53 are useful as independent criteria in evaluating malignancy in phyllodes tumors.

We used immunohistochemical analysis to detect the presence of estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR) protein expression in the epithelial and stromal cells of 143 phyllodes tumors (PTs). Expression of epithelial ER and PR proteins was common, occurring in 43% to 84% of PTs. Expression of epithelial AR protein and stromal ER, PR, and AR proteins was low (5% or less) in all tumors. An inverse relationship of epithelial ER and PR protein expression with degree of malignancy in PT was found (P < .05), and ER expression also correlated with mitotic count (P < .05). When considering PT with the expression of ER or PR proteins and the coexpression of both, the inverse relationship with tumor grade also was significant (P < .05). As the hormonal receptor protein expression shows a consistent decrease with increasing malignancy, we infer that the epithelium has a crucial role in the pathogenesis or progression of PT. Mammary phyllodes tumor (PT) is an uncommon stromal-epithelial neoplasm with a reported incidence of 0.3% to 0.5% of female breast tumors. 1-5 The median and mean ages of patients are 45 years, and the average tumor size is 4 to 5 cm. Rarely these lesions can occur in young or elderly women or in men. Pathologically, PTs are divided into benign, borderline, and malignant categories based on assessment of a combination of histologic features, namely mitotic count, cellularity and nuclear pleomorphism of the stromal cells, stromal overgrowth, and circumscription of the tumor border. 2,6 While borderline and malignant PTs can rarely metastasize, all PTs can recur locally. This propensity to recur makes proper and adequate treatment imperative, even in benign cases. Currently the mainstay of treatment of mammary PT remains surgical, and this also applies to recurrences and metastases. The expression of estrogen receptor (ER) and progesterone receptor (PR) in mammary neoplasms is well documented, particularly in carcinoma of the breast. The evaluation of hormonal receptors in breast carcinoma is useful as a predictor of response to endocrine manipulation therapy and as a prognostic index of the course of the disease. 7 While the usefulness of hormone receptor status of mammary PT is unknown, potentially this may offer similar therapeutic and prognostic information. We evaluated the expression of hormonal receptor proteins (ER, PR, and androgen receptor [AR]) in mammary PTs by immunohistochemical analysis with the aim of documenting the hormone receptor status of a large cohort of tumors from 3 centers in the Oceania region in an attempt to gain further insight into the pathobiology of these uncommon tumors.

The authors reviewed 143 cases (87 benign, 37 borderline, and 19 malignant) of mammary phyllodes tumors (PTs) and used immunohistochemistry to detect p53 protein product semi-quantitatively as negative, weak, moderate and strong (scored 0 to 3). For all PTs, an increasing trend of tumor size and malignancy was detected with increasing age. For p53 staining, 60 cases (42%) were negative, 55 (38%) stained weakly, 28 (13%) stained moderately, and 10 (7%) stained strongly. Of the 87 benign PTs, 41 (47%) were negative, 37 (43%) stained weakly, and 9 (10%) stained moderately. For the 37 borderline PTs, 16 (43%) were negative, 14 (38%) stained weakly, 6 (16%) stained moderately, and 1 (3%) stained strongly. Of the 19 malignant PTs, 3 (16%) were negative, 4 (21%) stained weakly, 3 (16%) stained moderately, and 9 (47%) stained strongly. The mean intensity score for p53 staining increased progressively from benign to borderline to malignant PT, with established statistical significance (P < .0001). This is significantly correlated with mitotic count but not stromal cellularity, pleomorphism, margin, and stromal overgrowth. When considering strong staining alone (score, 3), 47% of malignant, 3% of borderline, and none of the benign PTs were positive. The use of strong positive staining for diagnosing malignant PT gave positive and negative predictive values, specificity, and sensitivity of 90%, 92.5%, 99%, and 47%, respectively. Thus diffuse strong p53 protein staining can be used as a soft sign in assisting the diagnosis of malignant PT. Conversely, negative or weak staining of p53 protein in PT is of little discriminatory value. The role of p53 gene mutation in the malignant transformation of PT is unclear; but this may not be the sole mechanism as many malignant PT were p53 protein negative.

PURPOSE A meta-analysis of the effect of antihypertensive drug treatment on mortality and morbidity in elderly patients. DATA SOURCES A literature search of published articles from January 1980 to February 1992. STUDY SELECTION Randomized controlled trials of drug treatment of hypertension with end points for elderly patients reported separately. DATA EXTRACTION Mortality or morbidity end points or both in patients older than 59 years were pooled by determination of typical odds ratio. A meta-regression was used to study heterogeneity. RESULTS Nine major trials with 15,559 patients older than 59 years were identified. Death rates in the control group varied between 2.7% and 77.2%; stroke and coronary mortality increased with the severity-of-illness rank (P < 0.001). Overall, treated patients had an approximately 12% reduction in all-cause mortality (odds ratio, 0.88; 95% CI, 0.80 to 0.97; 953 events compared with 1069 events, P = 0.009). There was a 36% reduction in stroke mortality (odds ratio, 0.64; CI, 0.49 to 0.82; 94 events compared with 149 events, P < 0.001) and a 25% reduction in coronary heart disease mortality (odds ratio, 0.75; CI, 0.64 to 0.88; 263 events compared with 350 events, P < 0.001). Coronary morbidity was reduced 15% (odds ratio, 0.85; CI, 0.73 to 0.99; 325 events compared with 379 events, P = 0.036), and stroke morbidity was reduced 35% (odds ratio, 0.65; CI, 0.55 to 0.76; 247 events compared with 382 events, P < 0.001). CONCLUSION Overall, treatment of hypertension in elderly patients produces a significant benefit in total mortality and cardiovascular morbidity and mortality. However, this benefit may be reduced in the oldest age groups.