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Cytologic findings of malignant vascular neoplasms: a study of twenty-four cases.

Cytologic characterization of malignant vascular neoplasms (MVN) is difficult due to the wide range of differential diagnoses and sampling errors. The objective of this study was to identify criteria helpful in the cytologic diagnosis of MVN. The clinical presentation and cytomorphologic features of 22 angiosarcomas and two hemangioendotheliomas were analyzed. The criteria evaluated included cellularity, cellular arrangement, cell shape and size, pleomorphism, cytoplasmic borders, nuclear shape and number, chromatin pattern, nucleoli, background, and presence of angioformative structures. A previous history of MVN was noted in 18 of 24 patients. Specimens with epithelioid morphology were more cellular and pleomorphic and contained multinucleated cells. Specimens with spindle morphology were usually less cellular and less pleomorphic. Angioformative structures were identified in 11 of 24 cases. Awareness of features suggestive of MVN is necessary to raise the possibility of vascular origin, which can be confirmed with appropriate immunocytochemical studies.

Adult↗

Fine-needle aspiration biopsy of the retroperitoneum: a series of 111 cases not including specific organs.

We report on our experience in fine-needle aspiration (FNA) biopsy of the retroperitoneum: 111 FNA biopsies performed on 99 patients. Cytologic diagnoses were divided into four groups: nondiagnostic (unsatisfactory samples because of a low cellularity and/or improperly prepared smears) aspirates (20%), benign (16%), suspicious for malignancy (13%), and malignant (50%). There were no known false-positive samples. We had two false-negative diagnoses due to sampling errors. Among diagnostic smears, the procedure showed a sensitivity of 97% and a specificity of 100%. The predictive value of a positive result was 100% and the predictive value of a negative result was 90%. The overall accuracy was 98%. Metastatic carcinomas accounted for the largest number of lesions in the group of malignant tumors. A primary tumor site was known for the majority of the cases before the aspiration was performed. In the remaining cases we were unable to suggest an origin. It is therefore important to emphasize the role of ancillary studies in patients that are at the first assessment of the disease or when a second intercurrent malignancy is suspected. In our limited experience, a suggestion of the correct subtype of retroperitoneal sarcoma was not possible. As in the rest of cytopathology, a multidisciplinary approach is mandatory in this setting to improve patient management.

Adult↗

Accuracy of cytological grading of spindle-cell sarcomas.

Spindle-cell sarcomas constitute an important component of soft-tissue sarcomas, where accurate grading may be more important than histologic subtype in order to plan treatment strategies and determine prognosis. To evaluate the applicability and accuracy of grading spindle-cell sarcomas on fine-needle aspiration cytology (FNAC) smears, 54 cases of histologically documented spindle-cell sarcomas, consisting of synovial sarcomas (20 cases), neurofibrosarcomas (12 cases), leiomyosarcomas (9 cases), dermatofibrosarcoma protuberans (DFSP; 6 cases), fibrosarcomas (3 cases), hemangiopericytomas (2 cases), and spindle-cell sarcomas, unclassified (2 cases), were graded according to a three-tier system proposed earlier for FNAC smears, while the histological sections were graded using the French Federation of National Cancer Centers (FNCLCC) grading system. The cytological grading was correlated with the histological grade. There was an overall cytologic and histologic concordance in 40/54 (74%) cases, and concordance in 9/13 (69%) grade I, 19/25 (76%) grade II, and 12/16 (75%) grade III cases. Analysis of grading of individual sarcomas revealed a concordance in 92% of neurofibrosarcomas, 78% of leiomyosarcomas, 70% of synovial sarcomas, 67% of dermatofibrosarcoma protuberans, 67% of fibrosarcomas, 50% of hemangiopericytomas, and 50% of cases of malignant mesenchymal tumors, spindle-cell type unclassified. Major noncorrelation was seen in 10/54 (18.5%) cases. Minor noncorrelation was seen in 4/54 (7.4%) cases. Thus it is possible to accurately predict the grade in 74% of cases of spindle-cell sarcomas. The cytological and histological concordance was better (75%) in high-grade (grades II and III) as compared to grade I sarcomas (69%). Sampling errors due to morphologic heterogeneity in sarcomas may cause noncorrelation in a few cases.

Adult↗

Radiologically guided percutaneous fine-needle aspiration biopsy of pelvic and retroperitoneal masses: a retrospective study of 68 cases.

Fine-needle aspiration (FNA) of the pelvis and retroperitoneum (excluding the pancreas, kidney, and adrenal masses) has not achieved its full potential as a diagnostic modality. We reviewed 68 percutaneous, radiologically guided FNAs from these locations to assess the clinical utility and complication rate of this procedure. Satisfactory material was obtained in 66 cases (97.1%), of which 37 were deemed positive (55%), 3 suspicious (4%), 4 atypical (6%), and 22 negative (32%) for malignancy; two cases (3%) were unsatisfactory. Compared to biopsy (36 patients) and clinical information, the sensitivity and specificity of FNA for malignancy were 90.2% and 100%, respectively, yielding a positive predictive value of 100% and a negative predictive value of 86.6%. The four false-negative cases (5.9%) were due to sampling error. One patient had a minor complication (hematoma) from the procedure. We conclude that FNA is the procedure of choice for detecting most malignancies in these two locations.

Biopsy, Needle↗

Fine-needle aspiration cytology of the thyroid: ten years experience in a community teaching hospital.

We present our experience of fine-needle aspiration (FNA) cytology of the thyroid in a community hospital setting and discuss the cancer probability of the indeterminate FNA results. There were 1,621 FNAs, 401 of which have follow-up thyroidectomies during a 10-yr period. The initial FNA diagnoses of these 401 cases were benign non-neoplastic (BNN) 159, malignant 34, atypical 33, suspicious 19, follicular neoplasm (FN) 88, follicular lesion (FL) 51, and inadequate 17. There were no false-positive cases. Cancer was found in 11 cases diagnosed as BNN (7%), 6 cases were due to sampling errors (incidental microcarcinomas), and 5 cases were due to failure to identify focal atypia in the smears of a follicular variant of papillary carcinoma. The false-negative rate was 3%, with the exclusion of cases of incidental microcarcinomas. Among the indeterminate FNA results, the follow-up operations revealed malignant tumors in 16 of 33 (48%) cases of atypical, 13 of 19 (68%) cases of suspicious, 29 of 88 (33%) cases of FN, and 7 of 51 (14%) cases of FL. Malignant tumors were also found in 2 of 17 (12%) of inadequate specimens with follow-up. When compared to the cancer rate (3%) for FNA diagnosis of BNN, the likelihood of finding cancer in the thyroidectomy is 5 times more for a FL, 11 times more for a FN, 16 times more for atypical, and 23 times more for suspicious. The sensitivity and specificity are 87 and 100%, respectively.

Adult↗

CT-guided stereotactic biopsy of intracranial lesions: correlation between core biopsy and aspiration smear.

Computerized tomography (CT)-guided stereotactic biopsies of intracranial lesions in 29 patients were analyzed, paying particular attention to the correlation between core biopsies and aspiration smears. Seven percent were nondiagnostic due to sampling error. Discrepancies occurred between core biopsies and aspiration smears in 10% of the cases. In two instances of such discrepancies, cytologic findings on the aspiration smear yielded the diagnosis of metastatic tumor. One patient, with herpetic encephalitis, was diagnosed by electron microscopic review of the core biopsy only. One patient died of an intraoperative hemorrhage, a complication of the fine-needle technique.

Biopsy↗

Fine-needle aspiration of breast lesions: role and accuracy in a review of 7,495 cases.

In the past 10 years, 7,495 cytological breast fine-needle aspirations (FNAs) were performed (4,756 FNAs of solid nodes and 2,739 of cystic nodes). Of these, 2,099 cases underwent surgery; 650 (31%) had histologically proven carcinoma. Sensitivity was 83.9%, specificity was 99.5%, the predictive value for negative results was 93.2% and for positive results was 98.6%, and the accuracy was 94.6%. Inadequate (13.3%) and doubtful samples (8.1%) were excluded from calculation. False-negative results (82 cases) mainly resulted from sampling errors. False suspicious results (six cases) lessened with increasing experience in breast pathology and with the application of strict diagnostic criteria, but most likely they will never reach zero. Frozen-section diagnosis could be bypassed only in selected cases. Guidelines on the role of FNA in management of solid breast lesions are given. FNA deserves further evaluation in diagnosing early stages of breast carcinoma: sensitivity was 7.5% in 57 carcinomas in situ, 67.5% in 55 minimally invasive carcinoma, and 92.7% in 538 nonminimally invasive carcinomas.

Biopsy, Needle↗

Aspiration cytology of neuroendocrine tumors below the diaphragm.

In a series of 630 transabdominal fine-needle aspirates, 24 neuroendocrine tumors (NETs) presenting below the diaphragm were encountered. Of these, 10 were classic small-cell undifferentiated carcinomas (SCUCs). Recognition of SCUC in abdominal aspirates has major directive value, pointing to bronchogenic origin, possibly unsuspected, in most cases (eight of 10 in this series). The other 14 NETs were 10 pancreatic islet-cell tumors and four intestinal carcinoids, both diagnosed more frequently in metastatic than in primary sites (10 of 14 in the liver in this series). The cytologic presentation of these non-SCUC neoplasms has received little literature attention, and it is described and illustrated here, with discussion of cytologic pitfalls and differential diagnoses. Diagnostic specificity was 100%, and sensitivity was also 100%, exclusive of two sampling errors. The purpose of this article is to establish a broader view of the range of morphological features of the extended neuroendocrine group of tumors in aspiration cytology.

Adenoma, Islet Cell↗

Cytospins--an alternative method for fine-needle aspiration cytology of the breast: a study of 148 cases.

The aim of this study was to evaluate the cytospin technique as an alternative method to prepare fine-needle aspiration (FNA) specimens of the breast. To do so, the cytology of 148 breast FNAs that had been prepared by the cytospin technique and that had histologic correlation, was reviewed. All the cases that were diagnosed as malignant by cytology were proved malignant after surgical excision, and there were no false-positive results. All but two cases diagnosed as benign by cytology proved to be benign on excision. The two false-negative cases were missed due to sampling error. The cytological features seen on cytospins were similar to those seen on conventional direct smears. The major advantage of this method is that no aspirate is unsatisfactory due to unskilled direct smear technique. This, along with its good correlation with histology, proves that the cytospin method is an effective alternative to conventional direct smears for breast FNA.

Biopsy, Needle↗

Cost prediction models for the comparison of two groups.

For trial-based economic evaluation where patient-specific cost data are not routinely available, cost prediction models are commonly used to estimate total cost for each patient. Typically, multiple regression techniques are used on data from diagnosis-matched, non-trial patients (where patient-level cost data are available) to model cost as a function of covariates that are observed on the trial subjects (e.g. length of hospital stay, procedures, etc.). The estimated beta coefficients provide a means of estimating the total cost for each patient in the trial. However, the variability of the beta coefficients due the measurement and sampling error is seldom included in the overall variance expression for mean costs by treatment group. In this paper we provide a method for estimating this variance and provide an example application

Angina, Unstable↗

Frozen section during parotid surgery revisited: efficacy of its applications and changing trend of indications.

BACKGROUND: Efficacy of frozen sections was assessed in terms of its various applications. The changing role of frozen sections in parotid surgery was examined. METHOD: Records of parotid operations over a 15-year period in a University Department of Head & Neck Surgery were reviewed. RESULTS: Of 241 operations, frozen sections were performed on 32. Applications of frozen sections included diagnosis, margin clearance, and checking suspicious lymph nodes and nerve invasion. The false-positive rate for malignancy was 12.5%. Margins may still be involved despite correct tissue diagnosis from sampling error. No inappropriate surgery resulted from the information obtained. With the advent of fine-needle aspiration, frozen sections were less often called for and a shift from a diagnostic role to margin checking was seen. Frozen sections picked up all unsuspected malignant tumors. CONCLUSION: Frozen sections are helpful when interpreted cautiously, but clinical assessment and fine-needle aspiration are also important components in the workup.

Aged↗

Clinical utility of intraoperative frozen section diagnosis in head and neck surgery: a quality assurance perspective.

The technical and professional issues that affect the clinical utility of intraoperative frozen section diagnosis in head and neck surgery are addressed from a quality assurance perspective. The most common reasons for sampling errors and interpretive errors are discussed. We offer several recommendations for head and neck surgeons and pathologists which will optimize the clinical utility of intraoperative frozen section consultation.

Clinical Protocols↗

Comparison and validation of simple noninvasive tests for prediction of fibrosis in chronic hepatitis C.

Liver biopsy is recommended before antiviral treatment, particularly for patients with hepatitis C virus (HCV) genotype 1 infection, but it may cause complications and is limited by sampling error. Several non-invasive tests comprising routine laboratory parameters (simple fibrosis tests) have been proposed to predict fibrosis in chronic HCV. The aim of the current study was to validate and compare the diagnostic accuracies of the simple fibrosis tests, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), cirrhosis discriminant score (CDS), age-platelet (AP) index, Pohl score, AST-to-platelet ratio index (APRI), and platelet count per se. Staging was performed in liver biopsy specimens of 194 treatment-naive patients with chronic HCV according to Ishak et al. by two independent pathologists. Receiver operating characteristic curve analysis showed comparable diagnostic accuracies of CDS, AP index, APRI, and platelet count for prediction of significant fibrosis (F3-F6) (area under the ROC curve [AUROC], 0.71, 0.74, 0.80, and 0.71, respectively; pathologist A) and for prediction of cirrhosis (F5-F6) (AUROC, 0.91, 0.91, 0.90, and 0.89, respectively; pathologist A). Diagnostic accuracy of APRI for prediction of significant fibrosis was superior to that of AAR (P < .05). Significant fibrosis was reliably predicted by APRI > or = 1.5 and platelet count <150 x10(9)/L in 24% and 22% of the patients, respectively, whereas cirrhosis was reliably excluded by APRI <2.0 and platelet count > or = 150 x10(9)/L in 85% and 78% of the patients, respectively. In conclusion, simple fibrosis tests may render liver biopsy unnecessary only in a minority of patients with chronic HCV. Improved serum fibrosis markers with greater sensitivity for severe fibrosis or cirrhosis are needed.

Adult↗

Prostate cancer association studies: pitfalls and solutions to cancer misclassification in the PSA era.

Widespread screening of American men for elevated PSA has changed the characteristics of prostate cancer cases in the U.S. The influence of the changed nature of prostate cancer cases in the PSA era and the need for careful consideration of who is a "case" and who is a "control" on the ability to detect associations of risk factors with prostate cancer in etiologic epidemiologic studies merits discussion. Issue 1: prostate cancer cases diagnosed in the PSA era are enriched with a pool of early lesions, which may differ in etiology, and are deficient in advanced lesions, which are the most likely to be the product of promotion and progression events. By admixing the two types of cases (i.e., imperfect specificity), the associations previously detected using epidemiologic designs when the majority of cases were clinically detected may no longer be apparent in the PSA era when the majority of cases are now detected in the pre-clinical phase. Researchers must now tailor hypotheses such that they are testable using early stage cases or specifically augment the number of advanced cases when testing hypotheses related to extraprostatic growth and progression. Issue 2: even when controls are screened for elevated PSA to rule out the presence of prostate cancer, some proportion of those controls currently will have one or more foci of prostate cancer. The imperfect sensitivity of the PSA test coupled with diagnostic work-up may in part result from (a) lack of PSA elevation in some men with prostate cancer or (b) failure of biopsy to sample the tumor focus in men with elevated PSA. Misclassification of men with undetected prostate cancer as controls usually produces a bias that tends to deflate associations. Given this type of disease misclassification, whether an association still can be statistically detected depends on the extent of misclassification, the magnitude of the true association, the prevalence of the exposure in the true controls, and the sample size, although in general moderate nondifferential misclassification does not lead to profound attenuation. However, under the same scenario attenuation does not occur in cohort or case-cohort studies in which the rate or risk ratio (RR) is calculated. That prostate cancer cases diagnosed in the PSA era are enriched with early stage, minimally invasive disease in our opinion is likely to pose a far more serious obstacle to epidemiologic research on the etiology of clinically important prostate cancer than the issue of inclusion as controls some men who have undiagnosed prostate cancer because of imperfect sensitivity of PSA screening and biopsy sampling error.

Biopsy↗

Prostate cancer tumor location as predicted by digital rectal examination transferred to ultrasound and ultrasound-guided prostate needle biopsy.

The advent of transrectal ultrasound (TRUS) and the Biopty instrument (Bard Urologic) has revolutionized prostate biopsy (PNB). Theoretically the systematic multiple biopsy approach offers the advantage of less sampling error with respect to presence of carcinoma, grade of carcinoma and sites of tumor within the gland. These parameters may be important in selecting the therapeutic approach and, if radical prostatectomy is contemplated, in modifying the operation as indicated based on tumor location. In the present investigation, we received specimens obtained from 100 men with clinically localized prostatic carcinoma who had previously undergone ultrasound-guided systematic random biopsy (TRUSPNB) along with TRUS and digital rectal exam (DRE). Among the 372 sectors with carcinoma identified in the 100 radical prostatectomy specimens, significant underrepresentation by TRUSPNB was noted (39% false negative). When an abnormality on either DRE, TRUS or TRUSPNB was observed, the sensitivity was 65%. The specificity was 89% when all three tests were abnormal. It would appear that preoperative assessment of tumor location is inadequate with the current modalities available. There may, however, be subsets of patients which would benefit by tumor location utilizing DRE, TRUS and TRUSPNB.

Biopsy, Needle↗

Tissue autofluorescence as an intermediate endpoint in cancer chemoprevention trials.

Intermediate endpoints which reflect responsiveness to chemopreventive agents are needed in clinical trials. A potential problem in the assessment of these endpoints is their requirement for invasive biopsies. Secondly, their expression within the aerodigestive tract is doubtfully uniform. Without clinically definable disease, the potential for biopsy sampling error is significant. Our approach to this problem is the analysis of intrinsic tissue fluorescence. Various cellular components exist within tissues with the innate capacity to emit a characteristic spectral signature when excited at a particular wavelength of light. It can be postulated that cells in varying stages of progression towards malignancy will differ in both the qualitative and quantitative nature of these intrinsic cellular fluorophores which include folate derivatives and cytokeratins, as well as various vitamins and coenzymes. Using current bioptical technology, we have tested the applicability of tissue autofluorescence to chemoprevention studies through various model systems. In an N-nitroso-N-methylbenzylamine (NMBA)-induced rat esophageal cancer model, alteration of the 380 nm emission pattern corresponded to disease progression from normal mucosa through dysplasia to invasive cancer. In a multicellular tumor spheroid model, trans-retinoic acid (RA) altered autofluorescent profiles at multiple wavelengths including intensities at 340 nm, 450 nm, and 520 nm. Such RA-induced alterations corresponded to changes in the state of spheroid differentiation. In vivo human studies are in progress which suggest that aerodigestive mucosal neoplasias can be discriminated from normal mucosa by their autofluorescent profile. Because aerodigestive mucosa can be scanned without the need for invasive biopsies, the assessment of tissue autofluorescence as an intermediate endpoint may prove valuable.

Animals↗

MR measurements of pulsatile pressure gradients.

A magnetic resonance (MR) imaging method for evaluating pulsatile pressure gradients in laminar blood flow is presented. The technique is based on an evaluation of fluid shear and inertial forces from cardiac-gated phase-contrast velocity measurements. The technique was experimentally validated by comparing MR and manometer pressure gradient measurements performed in a pulsatile flow phantom. Analyses of random noise propagation and sampling error were performed to determine the precision and accuracy of the method. The results indicate that a precision of 0.01-0.03 mmHg/cm and an accuracy of better than 8% can be achieved by using standard clinical pulse sequences in tubes exceeding 6 mm in diameter. The authors conclude that MR measurement of pressure gradients is feasible and that additional hemodynamic information may be derived from conventional phase-contrast imaging studies.

Algorithms↗

Clinical measurement of tremor.

Multidimensional evaluations are recommended for the assessment of tremor severity in clinical trials. The precise method of measuring a particular tremor influences the results of the measurement. Furthermore, complex natural tremor amplitude perturbations introduce the potential for sampling errors.

Disability Evaluation↗