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At least 415 records · Page 23Linked to original sources
PubMed2003

Fine-needle aspiration cytology in nonpalpable mammographic abnormalities in breast cancer screening: results from the breast cancer screening programme in Oslo 1996-2001.

Fine-needle aspiration cytology (FNAC) of nonpalpable mammographic lesions has been under attack from two sides for some years. There has been much discussion and controversy as to the ability to differentiate between in situ and invasive carcinomas in cytological material. A further issue is that of optimal sampling to obtain adequate cell material in sufficient quantity. We present the results of FNAC from 832 nonpalpable mammographic abnormalities detected in the course of the breast cancer screening programme in Oslo during 1996-2001. In 11.6% of cases the smears were inadequate, and there were 7% false negatives (FN) and 1.3% false positives. Of the FN, 64% represented microcalcifications and 86% were due to sampling errors. Absolute sensitivity was 74%, complete sensitivity 88% and specificity 88%. In 255 carcinomas a cytological diagnosis of them as in situ or invasive was made. In 93% of the invasive cases (190/205) these had been correctly identified as invasive on FNAC. In 78% of cases proper follow-up could be resolved by cytology/radiology alone. Suboptimal sampling and localization remains the main cause of FN FNAC results. Problems in differentiating between in situ and invasive breast carcinomas can be significantly reduced by applying strict criteria for in situ lesions.

Adult↗
PubMedDate not supplied

Pitfalls in frozen section interpretation: a retrospective study of palpable breast tumors.

AIMS AND BACKGROUND: The use of frozen sections for purposes of diagnosis is recognized to involve a degree of uncertainty. A retrospective study of breast specimen frozen section diagnoses was undertaken in order to analyse the major pitfalls. METHODS: Hard copy files from our archives relating to symptomatic (palpable) breast specimens obtained between 1983 and 1996 were reviewed. RESULTS: The review revealed 23 errors among the diagnoses on 2110 frozen specimens. Twenty-two of them were false-negative and 1 (a case of multiple intraductal papillomatosis with atypical ductal hyperplasia) was false-positive for malignancy. The factors contributing to the pitfalls were: 1) misinterpretation; 2) poor quality of the frozen sections (artifacts making the diagnosis difficult); 3) sampling errors during sectioning; 4) ignorance of the macroscopic features; 5) lesions difficult to interpret; 6) ductal carcinoma in situ as the only lesion in the specimen; and 7) sections not deep enough. Several of the factors sometimes occurred simultaneously. CONCLUSIONS: Although the number of errors is relatively low, more stress should be placed on the preoperative diagnosis of breast lesions. Breast surgery frozen section should be used as rarely as possible for diagnostic purposes, despite the generally good diagnostic accuracy. However, it is reasonable to use frozen sections widely until the given preoperative diagnostic tools allow an appropriate preoperative workup, because it is the only way to keep histopathologists trained to interpret frozen sections.

Breast Neoplasms↗
PubMed1991

Fixed-bin analysis for statistical evaluation of continuous distributions of allelic data from VNTR loci, for use in forensic comparisons.

The detection of DNA polymorphisms by RFLP analysis is having a major impact on identity testing in forensic science. At present, this approach is the best effort a forensic scientist can make to exclude an individual who has been falsely associated with an evidentiary sample found at a crime scene. When an analysis fails to exclude a suspect as a potential contributor of an evidentiary sample, a means should be provided to assess suitable weight to the putative match. Most important, the statistical analysis should not place undue weight on a genetic profile derived from an unknown sample that is attributed to an accused individual. The method must allow for limitations in conventional agarose-submarine-gel electrophoresis and Southern blotting procedure, limited sample population data, possible subpopulation differences, and potential sampling error. A conservative statistical method was developed based on arbitrarily defined fixed bins. This approach permits classification of continuous allelic data, provides for a simple and portable data-base system, and is unlikely to underestimate the frequency of occurrence of a set of alleles. This will help ensure that undue weight is not placed on a sample attributed to an accused individual.

Alleles↗
PubMed1997

Modelling of mortality data from a multi-centre study in Japan by means of Poisson regression with error in variables.

BACKGROUND: Death rates of particular categories in epidemiological studies are often based on a small number of occurrences which can be well described by a Poisson distribution. METHOD: We applied this model for the analysis of a multi-centre study in five Japanese counties where the death rates of stomach cancer (ICD-9 code 151) in four age groups are known. In our example some covariates of the cases (e.g. plasma lycopene levels) are unknown values and are estimated from a randomly chosen collective. Therefore these values are subject to a sampling error. The inclusion of errors in variables (e-i-v) into the statistical model can adequately describe such a situation. The model is estimated in a Bayesian framework by means of resampling techniques. RESULTS: Based on the posterior distribution of the parameters the relative risk of stomach cancer is 0.46 (95% confidence interval: 0.23-0.79) comparing the maximum of the population medians of lycopene with the minimum. The estimated overdispersion is close to zero indicating only minor interference with other possible explanatory variables. In addition, we show that inclusion of e-i-v can give more accurate estimates of the parameters even from small sample sizes. CONCLUSIONS: Appropriate statistical methods allow the accurate estimation of relative risks from small sample sizes and from low number of cases. Lycopene plasma levels are good predictors for stomach cancer.

Adult↗
PubMed1996

Cytological vs microhistological diagnosis of hepatocellular carcinoma: comparative accuracies in the same fine-needle biopsy specimen.

There is still debate over the relative merits of cytology and histology in diagnosing hepatocellular carcinoma in cirrhotic livers. Previous comparisons of the diagnostic accuracies of these two methods may have been biased by sampling errors due to multiple punctures. We compared the diagnostic accuracies of cytology and microhistology using tissue and cells from the same point in liver nodules subsequently proved to be hepatocellular carcinoma. A single ultrasound-guided liver-nodule biopsy was obtained with a 20- to 21-G cutting needle from 131 cirrhotic patients. The solid portion of samples was used for microhistology; the remainder was subjected to smear cytology. The results of each type of examination were expressed as true positive, nonspecific malignancy, false negative, or inadequate for diagnosis. No false-positive diagnoses were made in 13 benign lesions. In 118 HCC nodules (particularly those <30 mm in diameter), cytology provided a significantly higher percentage of correct diagnoses (85.6%) that was only slightly inferior to that based on results of both studies (89.8%). The single-biopsy technique generally provides adequate tissue for histology and cytology specimens with a high cellularity. It reduces both the cost and the risks of fine-needle biopsy diagnosis of hepatocellular carcinoma.

Adult↗
PubMed2005

Genetic monitoring of wild and repatriated populations of endangered razorback sucker (Xyrauchen texanus, Catostomidae, Teleostei) in Lake Mohave, Arizona-Nevada.

The Native Fishes Work Group, formed in 1991, developed and implemented a protocol to enhance the dwindling razorback sucker population in Lake Mohave, Arizona-Nevada. This large, genetically diverse population is severely reduced in size as a result of recruitment failure associated with predation on larvae. To circumvent this problem, wild larvae are captured, reared in protective custody until they are large enough to escape predation, and then released back into the lake. We present results of a monitoring program designed to assess the effectiveness of the sampling design in transmitting the high genetic diversity found in wild adults. Variation in a fragment from the mitochondrial DNA gene cytochrome b was examined by analysis of single-stranded polymorphisms and direct sequencing. Samples were characterized from three life history stages. Characterization of wild adults verified previous results that identified considerable diversity and provided baseline data. Samples of larvae from several temporal collections from throughout the spawning season and four geographical areas were characterized for 7 years (1997-2003) to assess the transmission of genetic variation from wild adults to larvae. Several analyses identified significant differences among temporal collections, resulting from sampling errors associated with finite number of females spawning at a given time and place. Comparisons among areas and years failed to identify significant variation, indicating that pooled collections for each year possess the same levels and patterns of genetic variation. Examination of repatriates representing 11 years (1992-2002) also failed to identify significant differences among cohorts; however, some sample sizes were small and the amova may lack sufficient power to detect differences. Contrasts of wild adults, larvae, and repatriates identified statistically significant differences among collections within these three groups; however, levels of variation are small and not biologically meaningful. More importantly, this analysis failed to detect significant differences among adults, larvae, and repatriates indicating that the program has been achieving its goal of transmitting variation from adults through the larvae and into the repatriate population. The reproductive capability of repatriates has not been examined, so it is unknown if the program will maintain genetic variation found in the original adult population. This will be most easily achieved by periodic monitoring of genetic variation in larval samples. If levels of variation become reduced in repatriates, levels and patterns of diversity in larvae are also expected to become reduced, and deviations in estimates of genetic diversity may become larger and more frequent. If this is the case, intervention may be necessary to ensure that certain individuals are not over-represented in the repatriate population.

Animals↗
PubMed1986

Estrogen receptor content in breast cancer: correlation between biochemical and immunohistochemical methods.

Estrogen receptor content of 26 consecutive cases of ductal breast carcinoma was evaluated by using both biochemical and immunohistochemical methods. Agreement was present in 20/26 cases (76.9%). The analysis of discordant cases shows that in 5 cases disagreement is due to sampling error or to prolonged storage before biochemical evaluation. Such cases may reasonably be excluded when correlating results. Linear regression of the remaining 21 cases shows a significant relationship (r = 0.931; p less than 0.001) between biochemical and immunohistochemical values. Results show that immunohistochemical and biochemical assays are largely comparable, and stress the important role of the pathologist in tumor sampling.

Adult↗
PubMed1984

Tumors of the salivary glands. Comparison of frozen-section diagnosis with final pathologic diagnosis.

Of the 256 cases of salivary gland tumors subjected to frozen-section diagnosis, the error rate in diagnosis for malignant disease was one of four cases, and in benign disease, it was one of ten cases. Six of the 52 malignant tumors were erroneously labeled as benign, while four of the 204 benign tumors were diagnosed as malignant neoplasms. The occurrence of concurrent benign and malignant disease, nonneoplastic alterations of salivary gland tissue, and sampling errors militated against total reliance on frozen-section diagnosis in the management of salivary gland neoplasms.

Child↗
PubMed2004

Quantification of variability and uncertainty using mixture distributions: evaluation of sample size, mixing weights, and separation between components.

Variability is the heterogeneity of values within a population. Uncertainty refers to lack of knowledge regarding the true value of a quantity. Mixture distributions have the potential to improve the goodness of fit to data sets not adequately described by a single parametric distribution. Uncertainty due to random sampling error in statistics of interests can be estimated based upon bootstrap simulation. In order to evaluate the robustness of using mixture distribution as a basis for estimating both variability and uncertainty, 108 synthetic data sets generated from selected population mixture log-normal distributions were investigated, and properties of variability and uncertainty estimates were evaluated with respect to variation in sample size, mixing weight, and separation between components of mixtures. Furthermore, mixture distributions were compared with single-component distributions. Findings include: (1). mixing weight influences the stability of variability and uncertainty estimates; (2). bootstrap simulation results tend to be more stable for larger sample sizes; (3). when two components are well separated, the stability of bootstrap simulation is improved; however, a larger degree of uncertainty arises regarding the percentiles coinciding with the separated region; (4). when two components are not well separated, a single distribution may often be a better choice because it has fewer parameters and better numerical stability; and (5). dependencies exist in sampling distributions of parameters of mixtures and are influenced by the amount of separation between the components. An emission factor case study based upon NO(x) emissions from coal-fired tangential boilers is used to illustrate the application of the approach.

Journal Article↗
PubMed1996

Experience with quantitative PCR for the management of HCMV disease.

Human cytomegalovirus (HCMV) is a major pathogen in newborn children and immunosuppressed individuals. There are various diagnostic methods for HCMV, but all test systems either suffer from limited sensitivity and specificity or are prone to sampling errors. Due to its unequaled sensitivity, strong hopes were pinned on the polymerase chain reaction (PCR) for the early diagnosis of active HCMV infections. However, when monitoring immunocompromised patients, unwanted positive results are often obtained without further evidence of active HCMV infection. To better discriminate between latent and active infections, different methods for the quantitation of viral genomes in clinical samples by PCR have been devised in the past years. Here we discuss the current standing of quantitative PCR in HCMV diagnostics.

Cytomegalovirus Infections↗
PubMed1997

A bootstrap approach to medical decision analysis.

In economic evaluations of health treatments, the sensitivity of a cost-benefit (CB), cost-effectiveness (CE) or cost-utility (CU) analysis to changes in modeling assumptions, variation in data, and sampling error is important. The typical approach to this problem is ad hoc experimentation; namely, a few parameters of particular interest are changed, either separately or in combination, over plausible ranges. The impact of random variation in the data is seldom explored beyond parametric tests of the statistical significance of estimated coefficients. This note suggests a systematic approach to sensitivity analysis. Bootstrap sampling is used to determine to what extent the patients' response to treatment and economic consequences might vary due to many replications of a clinical trial.

Clinical Medicine↗
PubMed1994

The effect of exposure variance and exposure measurement error on study sample size: implications for the design of epidemiologic studies.

A small variability of exposure in a population, for example small variance in nutrient intake, limits the power of an epidemiologic study. McKeown-Eyssen and Thomas (J Chron Dis 1985; 38:559-568) have shown that by selecting a population with larger exposure variance vs one with smaller variance, the study sample size can be reduced by a factor equal to the ratio of the smaller to larger variance. The authors show that this benefit may be even greater for exposures measured with error. When there is measurement error, the sample size requirements are greatly increased. However, the proportional reduction in sample size from selecting a population with larger variance may be even greater when there is error than when there is not. Under certain assumptions, the validity of the exposure (correlation coefficient of the mismeasured exposure with the true exposure) is enhanced in the population with larger exposure variance, which provides the additional sample size benefit. Simple equations are presented that demonstrate quantitatively the substantial benefit of selecting a population with larger exposure variance when there is moderate or large measurement error. For example, selecting a population with a 30% greater standard deviation of exposure could reduce sample size requirements by 41% when the exposure is perfectly measured, but when the exposure is poorly measured with a validity coefficient of 0.6, the savings could be 56% if a population with 30% greater standard deviation of exposure could be studied. Applications of these results as well as the limitations of the assumptions are discussed.

Bias↗
PubMedDate not supplied

Analysis of false results in a series of 835 fine needle aspirates of breast lesions.

OBJECTIVE: To analyze cases of false diagnoses from a large series to help increase the accuracy of fine needle aspiration of palpable breast lesions. STUDY DESIGN: The results of FNA of 835 palpable breast lesions were analyzed to determine the reasons for false positive, false negative and false suspicious diagnoses. RESULTS: Of the 835 aspirates, 174 were reported as positive, 549 as negative and 66 as suspicious or atypical but not diagnostic of malignancy. Forty-six cases were considered unsatisfactory. Tissue was available for comparison in 286 cases. The cytologic diagnoses in these cases were reported as follows: positive, 125 (43.7%); suspicious, 33 (11.5%); atypical, 18 (6.2%); negative, 92 (32%); and unsatisfactory, 18 (6.2%). There was one false positive diagnosis, yielding a false positive rate of 0.8%. This lesion was a case of fibrocystic change with hyperplasia, focal fat necrosis and reparative atypia. There were 14 false negative cases, resulting in a false negative rate of 13.2%. Nearly all these cases were sampling errors and included infiltrating ductal carcinomas (9), ductal carcinomas in situ (2), infiltrating lobular carcinomas (2) and tubular carcinoma (1). Most of the suspicious and atypical lesions proved to be carcinomas (35/50). The remainder were fibroadenomas (6), fibrocystic change (4), gynecomastia (2), adenosis (2) and granulomatous mastitis (1). CONCLUSION: A positive diagnosis of malignancy by FNA is reliable in establishing the diagnosis and planning the treatment of breast cancer. The false-positive rate is very low, with only a single case reported in 835 aspirates. Most false negatives are due to sampling and not to interpretive difficulties. The category "suspicious but not diagnostic of malignancy" serves a useful purpose in management of patients with breast lumps.

Biopsy, Needle↗
PubMed2004

Heterozygote excess in small populations and the heterozygote-excess effective population size.

It has been proposed that effective size could be estimated in small dioecious population by considering the heterozygote excess observed at neutral markers. When the number of breeders is small, allelic frequencies in males and females will slightly differ due to binomial sampling error. However, this excess of heterozygotes is not generated by dioecy but by the absence of individuals produced through selfing. Consequently, the approach can also be applied to self-incompatible monoecious species. Some inaccuracies in earlier equations expressing effective size as function of the heterozygote excess are also corrected in this paper. The approach is then extended to subdivided populations, where time of sampling becomes crucial. When adults are sampled, the effective size of the entire population can be estimated, whereas when juveniles are sampled, the average effective number of breeders per subpopulations can be estimated. The main limitation of the heterozygote excess method is that it will only perform satisfactorily for populations with a small number of reproducing individuals. While this situation is unlikely to happen frequently at the scale of the entire population, structured populations with small subpopulations are likely to be common. The estimation of the average number of breeders per subpopulations is thus expected to be applicable to many natural populations. The approach is straightforward to compute and independent of equilibrium assumptions. Applications to simulated data suggest the estimation of the number of breeders to be robust to mutation and migration rates, and to specificities of the mating system.

Biological Evolution↗
PubMed1996

Immediate assessment of fine needle aspiration cytology of lung.

AIMS: To assess the value of immediate assessment of cytology in percutaneous fine needle aspiration (FNA) cytology of lung. METHODS: FNA specimens from 75 consecutive patients with suspected pulmonary neoplasms were subjected to immediate cytology assessment. Direct smears were prepared in the radiology department and stained using the Diff Quik method. The cellular content was assessed and, if possible, a provisional diagnosis offered. A second FNA was requested if the initial aspirate seemed of doubtful adequacy. The diagnostic accuracy was examined by review of clinical and radiological data in all patients, and by correlation with other histological or cytological material in 25 patients. Complications of the procedure were identified during the clinical review. RESULTS: Two of 75 specimens were inadequate for diagnosis. Satisfactory diagnostic material was obtained in 51 patients on a single aspirate and following a second FNA in 22 patients. Of the 73 satisfactory aspirates, 58 were malignant, one highly suspicious of malignancy and 14 reported as negative for malignancy. All malignant diagnoses were confirmed on clinical or pathological review. FNA accurately distinguished primary small cell and large cell carcinomas in those patients with pathological follow up. There were two false negative reports, one due to sampling error and the other due to misinterpretation of aspirate material. The diagnostic specificity was 100% and sensitivity 96.6%. Complications were recorded in seven (9.3%) patients, five of whom developed pneumothorax; a chest drain was required in one patient. CONCLUSIONS: Percutaneous FNA cytology provides safe and accurate diagnosis in the investigation of pulmonary lesions. Immediate cytology assessment ensures that aspirate material is handled optimally, and those patients requiring further sampling or ancillary investigation identified rapidly. The number of unsatisfactory and false negative lung FNA are therefore reduced. The complication rate is minimised by decreasing the number of pleural punctures.

Adult↗
PubMed2000

[Preanalytical errors on the determination of arterial O(2)-partial pressure and their impact on the AaDO(2)].

OBJECTIVES: The paO(2) and AaDO(2) are routinely measured for evaluating pulmonary gas exchange. The normal value of the AaDO(2) amounts 10 mmHg when breathing atmospheric air and is said to increase with rising FIO(2). This increase is discussed controversially. One possible reason for incongruities in AaDO(2) measurement may be the impact of so called preanalytical errors during paO(2) measurement, which are often neglected. Therefore, the aim of this study was to evaluate the relevance of preanalytical errors on the AaDO(2) under hyperoxic conditions. METHODS: Arterial blood gas analysis was performed on twenty patients without known pulmonary disease after tracheal intubation and 30 min of ventilation with pure oxygen. All preanalytical paO(2) errors (sampling technique, transport and storage of samples, aspirated air bubbles) were assessed and all paO(2) measurements were corrected by applying respective predetermined correction factors. Calculation of the AaDO(2) was performed with corrected and uncorrected paO(2) values. RESULTS: The average amount of the AaDO(2) under ventilation with FIO(2)=1.0 was 118.9+/-41.1 mmHg, calculated from uncorrected paO(2) values, and 13.4+/-7.5 mmHg calculated from paO(2) values corrected for preanalytical errors, respectively. CONCLUSION: The present results show that the assumption of an increasing AaDO(2) with rising FIO(2) is questionable. It could be proved that neglecting preanalytical paO(2) errors leads to a significant overestimation of the AaDO(2). The consequence would be a misinterpretation of the patient's condition in relation to a reduced pulmonary gas exchange, which should in fact be attributed solely to the preanalytical errors.

Adult↗
PubMed2005

Colonoscopic surveillance in inflammatory bowel disease.

PURPOSE OF REVIEW: To describe recent findings in the literature aimed at decreasing systematic error in dysplasia surveillance in inflammatory bowel disease. RECENT FINDINGS: Despite great promise, colonoscopic surveillance in inflammatory bowel disease has yet to be demonstrated to reduce colorectal cancer mortality. In part, this stems from a number of inherent systematic troubles, including low rates of observer agreement among pathologists; lack of consensus on the natural history of dysplasia, particularly low-grade dysplasia; the patchy nature of dysplasia, which leads to sampling error caused by insufficient biopsy by endoscopists; and incomplete patient follow-up. Recent publications that have focused on defining better the natural history of different levels of dysplasia and improving dysplasia identification at the time of colonoscopy may aid in overcoming the flaws of surveillance. The key recent findings include conflicting evidence on the relative danger of flat low-grade dysplasia, the safety of treating polypoid low-grade dysplasia as a benign adenoma in the absence of flat dysplasia in the rest of the colon or the surrounding mucosa, and preliminary support of chromoendoscopy to target dysplasia better during colonoscopy and to limit unnecessary nontargeted biopsies. SUMMARY: These and other advances stand a reasonable chance of making surveillance a more accurate tool to discriminate between patients with chronic colitis likely to progress to advanced pathology and those less likely to do so. Such advances may result in effective surveillance in which both colorectal cancer mortality and unnecessary colectomy may be limited.

Colonoscopy↗
PubMed2001

[Telepathology--applications of an emerging technology].

Due to the development of modern telecommunication by means of high speed data transfer either by normal telephone lines or the internet we are faced with new possibilities and chances in pathology. Instead of mailing slides, today images can be transferred electronically within seconds around the world, a second opinion of a highly skilled specialist can be available within the same day or even the same hour. Beside teleconsultation, telediagnostics is the most sophisticated application of telepathology. This means the evaluation of freshly prepared cryosections obtained during surgery by a pathologist using a remotely controlled microscope in a location deprived of pathological expertise. Since the technology applied has become very reliable, problems encountered by using this technology are mainly caused by either microscopic or macroscopic sampling errors. A correct diagnosis can not be obtained if the images mailed are not containing the necessary information. The same is true for telediagnostics, if the biopsy taken for cryosection does not contain the relevant lesion, a correct diagnosis will not be possible. However, these problems are not specific for telepathology, but are encountered in routinely processed specimens as well. Thus, protocols need to be developed assuring sufficient and reproducible image sampling for teleconsultation.

Biotechnology↗