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Detailed histologic scoring systems have been developed for the assessment of disease activity in ulcerative colitis. Literature from adult patients has shown some correlation between endoscopy and histology, and reproducibility of histologic scoring systems has also been supported. The effectiveness of endoscopic appearance at predicting histologic scores in pediatric patients has not been well studied, and none of the histologic scoring systems used in adults have had interobserver reproducibility assessed in pediatric patients. We reviewed endoscopic images and concurrent biopsies using Mayo and Geboes scores from the distal colon and rectum in untreated pediatric patients at the presentation of presumed ulcerative colitis based on clinical and endoscopic findings. Interobserver concordance was calculated by weighted-kappa statistic. The averaged histologic scores were compared to endoscopy scores using Spearman’s coefficient. Correlation between endoscopic score and each histologic score was weakly to moderately positive, whereas interobserver agreement for histologic scores was fair to moderate, suggesting that the Geboes scoring system has value in pediatric patients. For each histologic parameter, the average score was lower than the average endoscopic score. Examination of larger pediatric cohorts, treated patients, correlations of clinical outcomes with individual histologic parameters, and alternate scoring systems may contextualize these findings.

AimsHaemophagocytic lymphohistiocytosis (HLH) is divided into paediatric (primary) and adult (secondary) types. While paediatric-HLH has been extensively characterised, similar studies in adults are limited. This study aims to evaluate the significance of the HLH diagnostic criteria as well as other clinical parameters in adults with bone marrow evidence of haemophagocytosis.MethodsWe conducted a 10-year retrospective search of the pathology archives of two institutions for cases with bone marrow haemophagocytosis. We included those cases that fulfilled the currently established HLH diagnostic criteria. For the 29 cases that met inclusion criteria, we assessed clinical features, co-morbidities, therapy and clinical outcome. The effect of 19 clinical variables on mortality outcomes was assessed using logistic and hazard regression analyses.ResultsOf cases for which an aetiology could be identified, infectious diseases were the most common association (14 of 19, 74%). Fever and elevated ferritin were the most frequently available criteria used to establish HLH. The overall mortality rate was 61% despite HLH-specific therapy, which had been initiated in 48% of the cases. The remaining cases were treated with supportive therapy and antibiotics. The most statistically significant marker of mortality was an elevated absolute neutrophil count (ANC), a feature not typical of HLH.ConclusionsSince elevated ANC correlates with poor outcomes in sepsis, and not HLH, we postulate that many of the patients fulfilling HLH diagnostic criteria in this study likely had sepsis/systemic inflammatory response syndrome rather than HLH. Our results highlight the need to define HLH diagnostic criteria specific to the adult population.

BACKGROUND Relative risks are the most common statistics used to quantify the risk of mortal or morbid outcomes associated with different patient groups and therapeutic interventions. However, absolute risks are of greater value to both patient and physician in making clinical decisions. METHODS The relationship between relative and absolute risks is explained using graphical aids. A program to estimate absolute risks from relative risks is available on the Internet (see ftp://ftp.vanderbilt.edu/pub/biostat/absrisk.txt). This program uses a competing hazards model of morbidity and mortality to derive these estimates. RESULTS When a patient's absolute risk is low, it can be approximated by multiplying her relative risk by the absolute risk in the reference population. This approximation fails for higher absolute risks. The relationship between relative and absolute risk can vary dramatically for different diseases. This is illustrated by breast cancer morbidity and cardiovascular mortality in American women. The accuracy of absolute risk estimates will be affected by the accuracy of relative risk estimates, by the appropriateness of the reference groups used to calculate relative risks, by the stability of cross-sectional, age-specific morbidity and mortality rates over time, by the influence of individual risk factors on multiple causes of mortality, and by the extent to which relative risks may vary over time. CONCLUSIONS Valid absolute risk estimates are valuable when making treatment decisions. They can often be obtained over time intervals of 10 to 20 years when the corresponding relative risk estimates have been accurately determined. Cancer 1996;77:2193-9.

A double-blind, randomized controlled trial over 5 years compared the safety, immunogenicity, and efficacy of cold-adapted and inactivated influenza A vaccines in 5210 normal subjects. Both vaccines were well tolerated. Inactivated vaccine significantly increased hemagglutination inhibition antibody titers. Significant titer rises were also noted after cold-adapted vaccine but of lesser magnitude than with inactivated vaccine. The efficacy of inactivated vaccine in preventing culture-positive influenza was 76% (95% confidence interval [CI], 58%-87%) for H1N1 disease and 74% (95% CI, 52%-86%) for H3N2; for cold-adapted vaccine, 85% (95% CI, 70%-92%) and 58% (95% CI, 29%-75%), respectively. The efficacy of inactivated vaccine in preventing a four-fold rise in antibody titer over the influenza season was 69% (95% CI, 61%-76%) for H1N1 and 73% (95% CI, 65%-79%) for H3N2; for cold-adapted vaccine, 54% (95% CI, 44%-62%) and 32% (95% CI, 17%-44%), respectively. Cold-adapted and inactivated influenza vaccines are safe and effective for preventing influenza A disease.

Methods of sample size and power calculations are reviewed for the most common study designs. The sample size and power equations for these designs are shown to be special cases of two generic formulae for sample size and power calculations. A computer program is available that can be used for studies with dichotomous, continuous, or survival response measures. The alternative hypotheses of interest may be specified either in terms of differing response rates, means, or survival times, or in terms of relative risks or odds ratios. Studies with dichotomous or continuous outcomes may involve either a matched or independent study design. The program can determine the sample size needed to detect a specified alternative hypothesis with the required power, the power with which a specific alternative hypothesis can be detected with a given sample size, or the specific alternative hypotheses that can be detected with a given power and sample size. The program can generate help messages on request that facilitate the use of this software. It writes a log file of all calculated estimates and can produce an output file for plotting power curves. It is written in FORTRAN-77 and is in the public domain.

Fibroadenomas are benign breast tumors that are commonly diagnosed in young women and are associated with a slight increase in the risk of breast cancer. These lesions vary considerably in their histologic characteristics. We assessed the correlation between the histologic features of fibroadenomas and the risk of subsequent breast cancer.We conducted a retrospective cohort study of a consecutive series of patients with fibroadenoma diagnosed between 1950 and 1968. Follow-up data were obtained for 1835 patients (90 percent of those eligible). Fibroadenomas with cysts, sclerosing adenosis, epithelial calcifications, or papillary apocrine changes were classified as complex. The rate of subsequent breast cancer among the patients was compared with the rates in two control groups, women listed in the Connecticut Tumor Registry and women chosen from among the patients' sisters-in-law.The risk of invasive breast cancer was 2.17 times higher among the patients with fibroadenoma than among the controls (95 percent confidence interval, 1.5 to 3.2). The relative risk increased to 3.10 among patients with complex fibroadenomas (95 percent confidence interval, 1.9 to 5.1) and remained elevated for decades after diagnosis. Patients with benign proliferative disease in the parenchyma adjacent to the fibroadenoma had a relative risk of 3.88 (95 percent confidence interval, 2.1 to 7.3). Patients with a family history of breast cancer in whom complex fibroadenoma was diagnosed had a relative risk of 3.72, as compared with controls with a family history (95 percent confidence interval, 1.4 to 10). Two thirds of the patients had noncomplex fibroadenomas and no family history of breast cancer and did not have an increased risk.Fibroadenoma is a long-term risk factor for breast cancer. The risk is increased in women with complex fibroadenomas, proliferative disease, or a family history of breast cancer.

Abstract #3090 Background: A large number of genes encode components of complex growth factor signaling networks and may contribute to breast cancer risk. Prominent among these candidates are protein phosphatases that counter kinases of signaling cascades. We explored the role of a set of candidate genes encoding subunits of the major cellular protein phosphatase 2A (PP2A) in a cohort of women with a history benign breast disease. Women with a history of benign proliferative breast disease are at increased risk of subsequently developing breast cancer. Materials and Methods: We evaluated genetic variation in a set of 49 candidate genes of signal transduction pathways for potential contributions to breast cancer risk. The study was conducted as a nested case-control investigation of a cohort of women with a history of benign breast disease. DNA prepared from the original archival benign breast biopsy was available for 301 women diagnosed with breast cancer on follow-up, and for 545 of their 602 matched controls. Controls were women who remained free of breast cancer, matched to cases in a 2:1 ratio by race, age, and year of entry biopsy. Results: We observed that a PP2A structural subunit gene, PPP2R1A, and two regulatory subunit genes, PPP2R2A and PPP2R5E, each appeared to modify breast cancer risk with both risk-elevating and risk-reducing genetic variants. Only PPP2R2A was significantly associated with breast cancer after correction for multiple comparisons, with significant risk and protective haplotypes (OR = 1.79, study-wide P = 0.015, and OR = 0.62, study-wide P = 0.025, respectively). These variants interact with a history of proliferative breast disease to modify risk for breast cancer. In a dose model that included all three genes, breast cancer risk ranged from a 5.1-fold decrease to a 3.9-fold increase in risk, depending on the portfolio of variants inherited by a woman (study-wide P = 0.02). Discussion: If confirmed by independent studies, PP2A may play a key role as a tumor suppressor in breast cancer that is able to augment as well as to nullify elevated risk associated with early benign proliferative breast disease. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3090.

Results of renal revascularization for retrieval of function in poorly functioning kidneys are variable, but criteria for prediction of benefit and patient selection for operation are ill-defined. This report examines preoperative parameters in 64 hypertensive patients who underwent successful revascularization of poorly functioning kidneys as defined by creatinine clearance less than or equal to 15 ml/min (measured by preoperative split renal function studies [SRFS]) or preoperative serum creatinine greater than or equal to 3.5 mg/dl (range: up to 8.9 mg/dl) to identify markers of value in prediction of a beneficial response in renal function. Ages ranged from 35 to 75 years. There were 35 men and 29 women. The renovascular lesion was atherosclerotic in 58 patients and fibrodysplastic in six. Total renal artery occlusion was present in 32 cases. No urine flow was detectable before surgery on SRFS from 13 kidneys. Kidney lengths ranged from 7.7 cm to 15.1 cm. Fifty-four unilateral and 10 bilateral revascularizations were performed. A beneficial blood pressure response to operation was observed in 94%. Benefit in excretory function was determined by comparison of preoperative and postoperative data which included SRFS parameters, renal length, serum creatinine, isotopically derived split functioning renal mass, and glomerular filtration rates. Overall, 56 patients could be classified in regard to functional response. Twenty-two patients received no or minimal benefit; nine patients received modest improvement, and 25 patients exhibited more marked improvement. Statistical evaluation of preoperative anatomic and functional parameters as predictors of functional response suggested that multiple variables influence the probability of function retrieval by revascularization. Useful among these predictive variables are the status of the distal vessel beyond the occlusion, the bilaterality of reconstructable disease in azotemic patients, the amount of residual renal mass available for revascularization, and the degree of hyperconcentration of nonreabsorbable solutes from the involved kidney after surgery.