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Histopathologic Features and Transcriptomic Signatures Do Not Solve the Issue of Magnetic Resonance Imaging-Invisible Prostate Cancers: A Matched-Pair Analysis.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) is pivotal in prostate cancer (PCa) diagnosis, but some clinically significant (cs) PCa remain undetected. This study aims to understand the pathological and molecular basis for csPCa visibility at mpMRI. METHODS: We performed a retrospective matched-pair cohort study, including patients undergoing radical prostatectomy (RP) for csPCa (i.e., ISUP grade group ≥ 2) from 2015 to 2020, in our tertiary-referral center. We screened for inclusion in the "mpMRI-invisible" cohort all consecutive men (N = 45) having a negative preoperative mpMRI. The "mpMRI-visible" cohort was matched based on age, PSA, prostate volume, ISUP grade group. Included patients underwent radiological and pathological open-label revisions and characterization of the tumor mRNA expression profile (analyzing 780 gene transcripts, signaling pathways, and cell-type profiling). We compared the clinical-pathological variables and the gene expression profile between matched pairs. The analysis was stratified according to histological characteristics and lesion diameter. RESULTS: We included 34 patients (17 per cohort); mean age at RP and PSA were 70.5 years (standard deviation [SD] = 7.7), 7.1 ng/mL (SD = 3.3), respectively; 65% of men were ISUP 2. Overall, no significant differences in histopathological features, tumor diameter and location, mRNA profile, pathways, and cell-type scores emerged between cohorts. In the stratified analysis, an upregulation of cell adhesion and motility, of extracellular matrix remodeling and of metastatic process pathways was present in specific subgroups of mpMRI-invisible cancers. CONCLUSIONS: No PCa pathological or gene-expression hallmarks explaining mp-MRI invisibility were identified. Aggressive features can be present both in mpMRI-invisible and -visible tumors.

Humans

[Matched-pair analysis--technic and results demonstrated on the example of breast cancer].

The matched pair analysis is a well-known, but rarely used method. This method is recommended for the following problems: preparation of a controlled clinical experiment based upon the results of a retrospective analysis of results of therapy; analysis of results from a controlled clinical experiment in sub-groups; influence of non-therapeutic factors on the prognosis; epidemiological problems and study of the course of diseases. A matched pair analysis of about 300 female patients with breast carcinoma failed to show significant differences between (a) radical mastectomy alone, (b) radical mastectomy followed by chemotherapy with cyclophosphamide, and (c) preoperative irradiation followed by radical mastectomy.

Breast Neoplasms

Induced abortion and subsequent outcome of pregnancy in a series of American women.

We studied the effect of induced abortion on outcome of subsequent pregnancy in a sample of 4896 parturients in Seattle, Washington, from July, 1972, through June, 1976. We used a matched-pair analysis for 571 women with histories of prior abortions. In addition to analyses involving all women with histories of induced abortions, separate analyses were done for 97 black women and 277 primiparas. Histories of prior induced abortions were not related to low birth weight, premature delivery, stillbirth, neonatal death, miscarriage or congenital malformations in subsequent pregnancies. The termination procedure and weeks of gestation at time of termination were not related to the later occurrence of low birth weight or premature delivery.

Abortion, Induced

Heterozygous alpha-1-antitrypsin deficiency and respiratory function in children.

We evaluated 224 children from Rochester, New York, families in which at least one parent was heterozygous for alpha-1-antitrypsin (AAT) deficiency by protease inhibitor (Pi) typing. The childhood population included, of the two major heterozygote Pi types, 75 Pi type MS children and 37 Pi type MZ children. This population was evaluated by means of a standardized respiratory questionnaire, physical examination, and pulmonary function tests. Maximal expiratory flow volume curves were obtained with subjects breathing both air and a helium-oxygen mixture. Total pulmonary resistance by the method of forced oscillations was measured at 3, 5, 7, and 9 cps. No differences in respiratory symptoms or physical findings were seen in Pi type MZ and MS children compared to Pi type MM children. However, when pulmonary function tests were evaluated by a matched-pair analysis designed to minimize other genetic and environmental risk factors, Pi type MZ subjects demonstrated statistically significant differences in forced expiratory flow rates and in increased frequency-dependent characteristics of total pulmonary resistance. These abnormalities are similar to those previously described in adult Pi type MZ subjects, and suggest that physiologic abnormalities associated with AAT deficiency are present early in life.

Adolescent

The power to detect linkage disequilibrium with quantitative traits in selected samples.

Results from power studies for linkage detection have led to many ongoing and planned collections of phenotypically extreme nuclear families. Given the great expense of collecting these families and the imminent availability of a dense diallelic marker map, the families are likely to be used in allelic-association as well as linkage studies. However, optimal selection strategies for linkage may not be equally powerful for association. We examine the power to detect linkage disequilibrium for quantitative traits after phenotypic selection. The results encompass six selection strategies that are in widespread use, including single selection (two designs), affected sib pairs, concordant and discordant pairs, and the extreme-concordant and -discordant design. Selection of sibships on the basis of one extreme proband with high or low trait scores provides as much power as discordant sib pairs but requires the screening and phenotyping of substantially fewer initial families from which to select. Analysis of the role of allele frequencies within each selection design indicates that common trait alleles generally offer the most power, but similarities between the marker- and trait-allele frequencies are much more important than the trait-locus frequency alone. Some of the most widespread selection designs, such as single selection, yield power gains only when both the marker and quantitative trait loci (QTL) are relatively rare in the population. In contrast, discordant pairs and the extreme-proband design provide power for the broadest range of QTL-marker-allele frequency differences. Overall, proband selection from either tail provides the best balance of power, robustness, and simplicity of ascertainment for family-based association analysis.

Alleles

Matched-pairs study of reserpine use and breast cancer.

This paper reports on an analysis of psychiatric population. 55 female patients with breast cancer were matched with non-cancer patients on age, year of admission, psychiatric diagnosis, race, and religion. Reserpine use was examined for yearly use by each year preceding the diagnosis of breast cancer, by cumulative yearly use, and by other defined time periods. Regardless of the definition of reserpine user, there were no significant increased relative risks of breast cancer for those women on reserpine. There was a fairly low proportion of patients from each group who were on the drug in any given year, and a fairly wide range of total dosage received. Over half of the women used reserpine at some time during their hospital stay.

Aged

Bottle feeding as a risk factor for cholera in infants.

To determine risk factors for cholera in infants, a retrospective matched-pair study of 42 cases and their controls was undertaken during an outbreak of El Tor cholera in Bahrain in the autumn of 1978. The highest attack-rate of cholera (125/10 000) occurred in infants in the 6--11 month age-group, which corresponds to the weaning age in this community. Significantly more cases than controls were principally bottle fed (greater than 50% milk intake by bottle) than principally breast fed during the week before onset of illness (p=0.004). Analysis of various patterns of breast and bottle feeding did not determine whether the protection afforded by breast feeding was a negative effect (due to the lack of exposure to contaminated bottle feedings for breast fed infants) or a positive effect (due to protective functions of constituents of human breast milk). Cholera infection (with or without symptoms) among mothers of either case or control infants was uncommon (case mothers 3, control mothers 5), and mean serum vibriocidal and antitoxic antibody levels were similar for the two groups of mothers. These observations suggest that maternal infection did not affect the relative risk of infants having symptomatic cholera.

Antibodies, Bacterial

Induced abortion and subsequent outcome of pregnancy. A matched cohort study.

The effect on subsequent pregnancy outcome related to abortion was studied in a sample of 26,000 births in Taiwan. When no adjustment was made for confounding maternal variables, significant relationships were found between previous abortion and various problems of outcome of subsequent pregnancies. However, in a matched-pair cohort study controlling for relevant maternal characteristics, all such relationships disappeared. It is concluded that the deleterious effects of abortion on subsequent pregnancy outcome reported by others may be a consequence of the failure to adjust for maternal factors which are related both to abortion status and pregnancy outcome, and not to abortion itself.

Abortion, Induced

Health of workers exposed to 1, 1, 1,-trichloroethane: a matched-pair study.

An epidemiologic study of 151 matched pairs of employees was conducted in two adjacent textile plants, one of which used inhibited 1,1,1-trichloroethane as a general cleaning solvent. Employees in the study population had exposures to the solvent for 6 yrs or less at varying concentrations which were measured by breathing zone sampling and personal monitoring. While cardiovascular and hepatic observations were of primary interest, other health parameters were also studied. Application of sensitive statistical techniques and careful examination of all data did not reveal any clinically pertinent findings that were associated with exposure to 1,1,1-trichloroethane. The statistically significant associations that were observed between health measures and nonexposure factors emphasize the need to consider age, sex, race, and other variables in designing epidemiologic studies.

Adolescent

Immunoglobulin concentrations in serum and nasal secretions in chronic obstructive pulmonary disease. A matched-pair study.

Immunoglobulin concentrations were determined in the sera and nasal washes of 111 patients with chronic obstructive pulmonary disease who were 45 to 60 years of age and in 111 control subjects matched with the patients for age, sex, occupation, and smoking history who demonstrated normal 1-sec forced expiratory volume. Serum IgA, IgM, IgG, nad IgE were not significantly different in the 2 groups. Serum IgD was significantly higher in subjects with chronic obstructive pulmonary disease. Nasal wash IgD and IgM, expressed as percentages of total protein, were higher in index cases, but nasal wash IgA and IgG were comparable in both groups. The finding of relatively high concentrations of IgA, expressed as fractions of total protein, in respiratory secretions compared to serum is consistent with earlier findings that IgA is actively secreted from the respiratory epithelium and is not deficient locally in subjects with chronic obstructive pulmonary disease. In contrast, IgM and IgG expressed as proportions of total protein were consistently higher in sera than secretions. The IgE in nasal secretions was detected so seldom in this study that too few matched pairs were available for statistical analysis. The higher concentration of IgD in the serum and nasal secretions of patients with chronic obstructive pulmonary disease compared with their matched pairs and the associated higher frequency of low IgD in control subjects suggests that low IgD may be protective against the development of chronic obstructive pulmonary disease. Further studies on the biologic role of IgD may provide better understanding of these findings.

Humans