Updated prostate imaging reporting and data system (PIRADS v2) recommendations for the detection of clinically significant prostate cancer using multiparametric MRI: critical evaluation using whole-mount pathology as standard of reference.

OBJECTIVES: To evaluate the recommendations for multiparametric prostate MRI (mp-MRI) interpretation introduced in the recently updated Prostate Imaging Reporting and Data System version 2 (PI-RADSv2), and investigate the impact of pathologic tumour volume on prostate cancer (PCa) detectability on mpMRI. METHODS: This was an institutional review board (IRB)-approved, retrospective study of 150 PCa patients who underwent mp-MRI before prostatectomy; 169 tumours ≥0.5-mL (any Gleason Score [GS]) and 37 tumours <0.5-mL (GS ≥4+3) identified on whole-mount pathology maps were located on mp-MRI consisting of T2-weighted imaging (T2WI), diffusion-weighted (DW)-MRI, and dynamic contrast-enhanced (DCE)-MRI. Corresponding PI-RADSv2 scores were assigned on each sequence and combined as recommended by PI-RADSv2. We calculated the proportion of PCa foci on whole-mount pathology correctly identified with PI-RADSv2 (dichotomized scores 1-3 vs. 4-5), stratified by pathologic tumour volume. RESULTS: PI-RADSv2 allowed correct identification of 118/125 (94 %; 95 %CI: 90-99 %) peripheral zone (PZ) and 42/44 (95 %; 95 %CI: 89-100 %) transition zone (TZ) tumours ≥0.5 mL, but only 7/27 (26 %; 95 %CI: 10-42 %) PZ and 2/10 (20 %; 95 %CI: 0-52 %) TZ tumours with a GS ≥4+3, but <0.5 mL. DCE-MRI aided detection of 4/125 PZ tumours ≥0.5 mL and 0/27 PZ tumours <0.5 mL. CONCLUSIONS: PI-RADSv2 correctly identified 94-95 % of PCa foci ≥0.5 mL, but was limited for the assessment of GS ≥4+3 tumours ≤0.5 mL. DCE-MRI offered limited added value to T2WI+DW-MRI. KEY POINTS: • PI-RADSv2 correctly identified 95 % of PCa foci ≥0.5 mL • PI-RADSv2 was limited for the assessment of GS ≥4+3 tumours ≤0.5 mL • DCE-MRI offered limited added value to T2WI+DW-MRI.

Volume-based quantitative FDG PET/CT metrics and their association with optimal debulking and progression-free survival in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery.

OBJECTIVE: Our aim was to evaluate the associations between quantitative (18)F-fluorodeoxyglucose positron-emission tomography (FDG-PET) uptake metrics, optimal debulking (OD) and progression-free survival (PFS) in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery. METHODS: Fifty-five patients with recurrent ovarian cancer underwent FDG-PET/CT within 90 days prior to surgery. Standardized uptake values (SUVmax), metabolically active tumour volumes (MTV), and total lesion glycolysis (TLG) were measured on PET. Exact logistic regression, Kaplan-Meier curves and the log-rank test were used to assess associations between imaging metrics, OD and PFS. RESULTS: MTV (p = 0.0025) and TLG (p = 0.0043) were associated with OD; however, there was no significant association between SUVmax and debulking status (p = 0.83). Patients with an MTV above 7.52 mL and/or a TLG above 35.94 g had significantly shorter PFS (p = 0.0191 for MTV and p = 0.0069 for TLG). SUVmax was not significantly related to PFS (p = 0.10). PFS estimates at 3.5 years after surgery were 0.42 for patients with an MTV ≤ 7.52 mL and 0.19 for patients with an MTV > 7.52 mL; 0.46 for patients with a TLG ≤ 35.94 g and 0.15 for patients with a TLG > 35.94 g. CONCLUSION: FDG-PET metrics that reflect metabolic tumour burden are associated with optimal secondary cytoreductive surgery and progression-free survival in patients with recurrent ovarian cancer. KEY POINTS: • Both TLG and MTV were associated with optimal tumour debulking. • There was no significant association between SUVmax and tumour debulking status. • Patients with higher MTV and/or TLG had significantly shorter PFS. • SUVmax was not significantly related to PFS.

Volume and landmark analysis: comparison of MRI measurements obtained with an endorectal coil and with a phased-array coil.

AIM: To compare prostate volumes and distances between anatomical landmarks on MRI images obtained with a phased-array coil (PAC) only and with a PAC and an endorectal coil (ERC). MATERIALS AND METHODS: Informed consent was waived for this Health Insurance Portability and Accountability Act-compliant study. Fifty-nine men underwent PAC-MRI and ERC-MRI at 1.5 (n = 3) or 3 T (n = 56). On MRI images, two radiologists independently measured prostate volume and distances between the anterior rectal wall (ARW) and symphysis pubis at the level of the verumontanum; ARW and symphysis pubis at the level of the mid-symphysis pubis; and bladder neck and mid-symphysis pubis. Differences between measurements from PAC-MRI and ERC-MRI were assessed with the Wilcoxon RANK SUM test. Inter-reader agreement was assessed using the concordance correlation coefficient (CCC). RESULTS: Differences in prostate volume between PAC-MRI and ERC-MRI [median: -0.75 mm(3) (p = 0.10) and median: -0.84 mm(3) (p = 0.06) for readers 1 and 2, respectively] were not significant. For readers 1 and 2, median differences between distances were as follows: -10.20 and -12.75 mm, respectively, ARW to symphysis pubis at the level of the verumontanum; -6.60 and -6.08 mm, respectively, ARW to symphysis pubis at the level of the mid-symphysis pubis; -3 and -3 mm respectively, bladder neck to mid-symphysis pubis. All differences in distance were significant for both readers (p ≤ 0.0005). Distances were larger on PAC-MRI (p ≤ 0.0005). Inter-reader agreement regarding prostate volume was almost perfect on PAC-MRI (CCC: 0.99; 95% CI: 0.98-1.00) and ERC-MRI (CCC: 0.99; 95% CI: 0.99-1.00); inter-reader agreement for distance measurements varied (CCCs: 0.54-0.86). CONCLUSION: Measurements of distances between anatomical landmarks differed significantly between ERC-MRI and PAC-MRI, although prostate volume measurements did not.

Thalidomide use: past history and current implications for practice.

PURPOSE/OBJECTIVES: To review the history of thalidomide, examine fears emanating from its renewed usage, and discuss the nurse's critical role in patient education. DATA SOURCES: Published articles, abstracts, books, and clinical experience. DATA SYNTHESIS: In the early 1960s, the teratogenic effects of thalidomide became widely known. The words thalidomide and birth defects became permanently linked as a result of pregnant women who used thalidomide as a sedative, thus giving birth to children with horrific birth defects. As researchers look at novel properties of drugs and new indications in the oncologic setting, thalidomide has made a comeback, particularly in the treatment of multiple myeloma. Patient education is important to combat fear in using and prescribing thalidomide and is essential in preventing birth defects and other side effects associated with thalidomide use. CONCLUSIONS: Nurses are vital in the patient-education process, yet on extensive nursing literature search revealed limited publications regarding thalidomide. Nurses can prevent thalidomide-associated birth defects through comprehensive patient education and can assist patients in decreasing any anxiety related to potential and actual side effects. IMPLICATIONS FOR NURSING PRACTICE: With careful patient monitoring and comprehensive education of physicians, nurses, and patients, it is possible to reap the benefits of thalidomide and avoid the tragedy of misues. Nurses are in the forefront of education, and their expertise will empower patients to use thalidomide responsibly.

Lack of association between the T-->C 267 serotonin 5-HT6 receptor gene (HTR6) polymorphism and prediction of response to clozapine in schizophrenia.

The affinity of clozapine for 5-HT2A, 5-HT2C, 5-HT6, 5-HT7, and 5-HT1A receptors has been suggested to contribute to various aspects of its complex clinical actions. This study examined the hypothesis that genetic variation in 5-HT1A, 5-HT6, and 5-HT7 receptor genes is involved in the variability observed in response to clozapine. We employed a pharmacogenetic approach in a group (n=185) of schizophrenia patients that have been clinically well characterized for clozapine response. Polymorphisms in the 5-HT6 (HTR6), 5-HT1A (HTR1A) and 5-HT7 (HTR7) receptor genes were genotyped. No evidence for either an allelic or genotypic association of the T-->C 267 HTR6 polymorphism with response to clozapine was found in our sample (allele: chi(2)=0.06, 1 df, P=0.80; genotype: chi(2)=1.21, 2 df, P=0.55). The pro16leu HTR1A polymorphism was not observed in our sample; all individuals genotyped were pro/pro 16 homozygotes. With respect to the pro279leu HTR7 polymorphism, one Caucasian male responder to clozapine was observed to be heterozygous (pro/leu 279 genotype). This individual was clinically similar to the other clozapine responders. Overall, our findings do not support a role for the T-->C 267 polymorphism of the 5-HT6 receptor gene in response to clozapine, although replication is required to confirm this finding.

Are standardized mortality ratios valid for public health data analysis?

Standardized mortality ratios (SMRs) have been criticized as lacking validity, and it has been recommended to use standardized rate ratios (SRRs) instead. A review of the epidemiology literature and standard epidemiology textbooks showed disagreement concerning the validity of SMRs and a lack of data to support claims concerning their validity. Therefore, we sought to determine the validity of SMRs in public health data analysis. Simulations were carried out using widely disparate study population age distributions and disease rates encountered in public health data analysis. We compared SMRs and SRRs as absolute measures of increased mortality in a population, and for ranking mortality in different populations. The simulations showed that SMRs changed by 6 per cent to 8 per cent when the age distribution was changed from that of a 'young' age distribution to that of an 'old' age distribution. In comparison, SRRs changed by 4 per cent to 5 per cent when the age-adjustment standard was changed from the 1940 U.S. Census population to the 1990 U.S. Census population. County rankings by SRR were somewhat more similar among themselves than when compared with rankings by SMR, but the differences were not large. Based on our findings, SMRs are of similar usefulness to SRRs in public health data analysis, will lead to similar conclusions, and may be used to compare different geographic areas.

Improving the quality of care for children in health systems.

OBJECTIVE: To summarize the state of the art in quality improvement, review its application to care for children, and define the information that will be needed so that care for children can be further improved. PRINCIPAL FINDINGS: Health services for children exhibit numerous deficiencies in quality of care. The deficiencies cross all major domains of pediatric care--preventive services, acute care, and chronic care--and provide the opportunity for creative application of improvement strategies with a potential to benefit the health and well-being of children. Approaches to quality improvement have changed over the past two decades from those emphasizing the inspection of structural aspects of care and the imposition of sanctions to more dynamic strategies that emphasize measurement and comparison to motivate change; the use of evidence to specify aims for improvement; and the adoption of a variety of management strategies adapted from business and the social sciences to achieve these aims. These modern approaches to quality improvement have rarely been subjected to rigorous testing of their effectiveness. Moreover, their application in pediatrics has been less widespread than in adult healthcare. For children, several aspects about health services, such as the relative rarity of chronic illness, the important effects of social factors on health, and the limited cost, make some of these approaches even more challenging and may require new approaches or meaningful modifications. RECOMMENDATIONS: Research to understand better the general process of improvement will benefit improvement efforts for children. Research that builds the base of knowledge about best practices for children--effectiveness research--will also result in an enhanced capacity for improvement of those systems that care for children's health. Quality of care for children would be enhanced by targeted research examining ways both to foster improvement across segments of society, and to make recommendations for care more sensitive to children's development and environmental context. Research that supports incorporating the child's perspective into care is both uniquely challenging to perform and central to improving pediatric care.

Language differences in interpretation of breast cancer health messages.

BACKGROUND: Little is known about how women interpret terminology used in breast cancer messages. The authors assessed the understanding of common cancer terms and whether understanding differed by language of interview. METHODS: In interviews, low-income women 50 years old or older were asked open-ended questions about the meanings of specific terms and phrases in commonly used health messages. RESULTS: Of 232 completed interviews, 167 were conducted in English and 65 in Spanish. Both English- and Spanish-speaking women poorly understood the terms "risk factors," "at risk," and "cancer." Spanish speakers were less likely to provide technical definitions of "diagnosed" and "mammogram" and had different interpretations of several cancer terms compared with English speakers. CONCLUSIONS: Cancer terms mean different things to English and Spanish speakers. Client education could be vastly improved if these cultural differences in interpretation were addressed.

Validity of Pap smear and mammogram self-reports in a low-income Hispanic population.

This study measures the validity of self-reported mammography and Pap smear usage in Mexican-American women. We compared Pap smear and mammography reports in medical records to self-reports obtained in a household survey of 450 women in El Paso, Texas. The women were generally low-income, older, and Spanish-speaking. Forty-six percent of self-reported Pap smears in the previous year were verified (60.8% within previous two years, 67.1% within previous three years). Forty-nine percent of self-reported mammograms within the previous year were verified (74.7% within previous two years). For both Pap smears and mammograms, twice as many tests in the past five years were reported as were documented. Self-reports of Pap smears at a public health clinic were more valid than those at other sites. Denials of mammography within the past five years were more accurate (97.5%) than denials of Pap smears (81.8%). We conclude that self-reports of mammograms and Pap smears in Mexican-American women greatly overestimate the prevalence of screening. Intensive cancer prevention activities in this population are needed to approach the Year 2000 Objectives set by the U.S. Department of Health and Human Services.

Survey of El Paso physicians' breast and cervical cancer screening attitudes and practices.

One hundred and ninety-eight primary care physicians in El Paso, Texas, were surveyed for their practices and attitudes concerning breast and cervical cancer screening. The response rate was 83%. For women 40-49 years old, 77% of respondents stated that they ordered a screening mammogram at least every two years. For women 50-74 years old, 73% said they ordered an annual screening mammogram. For women 75 years and older, 61% stated they ordered an annual screening mammogram. For women 40 years or older, 89% of respondents said they performed annual or more frequent clinical breast examinations. Eighty-four percent of respondents stated they ordered a Pap smear every 1-3 years, both for pre- and post-menopausal women. The most common reasons given for not ordering or doing a breast or cervical screening exam were patient refusal, knowledge that other doctor performs exam, high price, inadequate insurance, patient not under regular care, do not see patient for gynecologic care, and patient being seen for different reason. Seventy percent of respondents do vaginal smears on women who have had a total hysterectomy for a benign condition, and 38% use a cytobrush for endocervical sampling. Respondents were generally more comfortable with their ability to do Pap smears (72% comfortable, 1% uncomfortable) than they were in performing clinical breast examinations (52% comfortable, 4% uncomfortable). Obstetricians and gynecologists were more likely than other physicians to do vaginal smears, use a cytobrush, and feel comfortable with their Pap smear technique.

The EPIGRAM computer program for analyzing mortality and population data sets.

EPIGRAM is a computer program designed to improve access to State-level underlying cause mortality data. The program produces results for population, deaths, death rate, age-adjusted death rate, years of potential life lost (YPLL), YPLL rate, and confidence intervals. Results can be compared variously among age groups, counties, causes of death, races, regions, and years. The program's menu-driven interface facilitates the selection or modification of analysis parameters. Current selections are retained so the user can modify one parameter at a time. Based on the parameters that the user selects, the program produces a series of tables, one for each instance of a particular parameter. Each output table has columns for male, female, and both sexes combined, and an indefinite number of user-defined rows for age groups, causes of death, counties, races, regions, or years. EPIGRAM has major advantages over other methods for analyzing mortality and population data. The program uses relatively small amounts of memory and disk space, executes rapidly, is flexible, can be used by inexperienced computer users, provides online help screens and tutorials, and runs under DOS or UNIX without modification. The program currently is used to analyze mortality and population data for Texas. Although it is not currently available for distribution, support is being sought for its evaluation and possible implementation in State health departments to analyze data for other States, or other data sets, such as hospital discharge data or cancer incidence data.

Multiple realities. Teaching rounds in an inpatient pediatric service.

Teaching rounds are a mainstay of most educational programs for interns and residents, but little is known about how they are conducted and the role they play in house staff members' learning. We performed a qualitative study of teaching rounds in an inpatient adolescent service using five data sources: observations, interviews, house staff ratings, results of a house staff retreat, and documents outlining faculty responsibilities. Interns, senior residents, and faculty members expressed differing views regarding the purpose, process, and content of rounds; mutual roles and expectations; and time management. An interactive teaching format focused around the visit of a patient to the conference room stimulated house staff interest and learning to a greater extent than did more traditional case presentations and lectures. These results suggest a need to develop a consensus among faculty and house staff regarding the purpose, content, and process of rounds.

Coordinate expression of lactase-phlorizin hydrolase mRNA and enzyme levels in rat intestine during development.

The development of rat intestinal lactase-specific activity displays a well-known post-weaning decline. In contrast, total lactase activity increases to reach maximal levels around weaning, and remains high subsequently. In order to elucidate the molecular basis for these patterns, a rat lactase cDNA was isolated and characterized, and used in the quantification of lactase mRNA during development. This lactase cDNA uniquely hybridized to a 6.8-kilobase mRNA in the small intestine. To assess the amount of lactase mRNA encoding for lactase enzyme activity in the small intestine, total intestinal RNA was isolated and analyzed by Northern and dot-blot hybridization. The pattern of total lactase mRNA during development followed that of total lactase activity, suggesting that over this time span the level of lactase activity is primarily controlled at the transcriptional level. However, the magnitude of increase of total lactase activity during lactation compared to that of total lactase mRNA suggests that additional mechanisms are involved in regulating lactase levels. Analysis of the regional distribution of lactase mRNA along the small intestine at 14 days revealed that mRNA was high in the proximal three regions, but was dramatically lower in the distal regions. Total lactase activity, in contrast, displayed maximum activity in the mid-intestine with decreased levels both proximally and distally. Thus, lactase activity in the intestine appears to be regulated during development predominantly by transcriptional mechanisms, while alterations during lactation, and along the proximal to distal gradient, are the result of other control mechanisms.

Definition and identification of homology domains.

A method is described for identifying and evaluating regions of significant similarity between two sequences. The notion of a 'homology domain' is employed which defines the boundaries of a region of sequence homology containing no insertions or deletions. The relative significance of different potential homology domains is evaluated using a non-linear similarity score related to the probability of finding the observed level of similarity in the region by chance. The sensitivity of the method is demonstrated by simulating the evolution of homology domains and applying the method to their detection. Several examples of the use of homology domain identification are given.

Group C streptococcal surgical wound infections transmitted by an anorectal and nasal carrier.

Streptococcus equisimilis (Lancefield group C), an unusual cause of nosocomial surgical infection, was isolated from two orthopedic postoperative wound infections. Both operations had been performed by the same surgeon within a three-day period. Examination of the surgeon revealed perianal dermatitis from which S. equisimilis was isolated. The organism was also recovered from the surgeon's nose and rectum. The wound infections responded to treatment with penicillin derivatives. The surgeon was successfully treated with topical bacitracin and oral penicillin and vancomycin. This report documents the pathogenicity of the C Streptococcus in postoperative infection and suggests a possible nosocomial source of the organism.