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Frozen section evaluation of stereotactic brain biopsies: diagnostic yield at the stereotactic target position in 188 cases.

OBJECTIVE: Use of the image-guided stereotactic brain biopsy has facilitated the diagnosis of previously inaccessible lesions with both safety and reliability. However, few studies have assessed the diagnostic yield of frozen section evaluation of the initial stereotactic target (FS-0). We describe our experience with 188 stereotactic brain biopsies in order to evaluate the diagnostic yield of FS-0. DESIGN: Retrospective study of 188 stereotactic brain biopsies from 185 patients. SETTING: Tertiary referral center with a high volume of neurosurgical cases including image-guided stereotactic brain biopsies. PATIENTS: One hundred eighty-five patients who underwent imaged-guided stereotactic brain biopsy over a 58-month period. RESULTS: The patients studied included 107 males and 78 females (mean age 48 years). Eleven (6%) biopsies were nondiagnostic. Diagnoses from FS-0 included a neoplastic condition in 96 (73%) of 131 cases and a nonneoplastic condition in 23 (50%) of 46 cases. In 119 (67%) of 177 cases, a diagnosis was reached at FS-0. A correct diagnosis was made on subsequent frozen section in 28 (16%) of cases, including 21 (16%) of 131 neoplasms and 7 (15%) of nonneoplastic conditions. In 15 (54%) of 28 cases, the correct diagnosis was made on the second frozen section; in 25 (89%) of 28, the correct diagnosis was made by the fourth frozen section. In 14 (11%) of 131 neoplastic cases, a sampling error relative to the lesion resulted in an inaccurate diagnosis at FS-0. A significant error in diagnosis occurred in three cases (1.7%). CONCLUSIONS: We conclude that (1) because 58 (33%) of 177 diagnosed cases in our series would have been potentially misdiagnosed if only one biopsy had been taken at the stereotactic target, frozen section evaluation or cytologic examination of material at the time of surgery should be performed routinely to ensure that adequate tissue has been obtained for purposes of diagnosis; (2) taking up to four biopsies increases the diagnostic yield (from 67% to 89% in this series); and (3) neoplastic lesions are more likely to be definitively diagnosed at FS-0 than non-neoplastic lesions.

Adolescent↗

High-grade dysplasia in Barrett's oesophagus.

BACKGROUND: The management of high-grade dysplasia (HGD) in Barrett's oesophagus is a controversial and challenging problem. METHODS: An up-to-date review of the literature has been made using Index Medicus, the Medline database, and cross-referencing of major articles on this subject. RESULTS: Diagnosis should be confirmed by a second expert pathologist. Repeat multiple jumbo biopsies and brushings need to be taken to reduce sample error and exclude associated invasive cancer. In young fit patients the advantages of surgery outweight the disadvantage of missing an early adenocarcinoma. Continued endoscopic surveillance may be more appropriate in elderly patients. New technology has increased the number of options. Early results of laser and multipolar electrocoagulation ablation of Barrett's epithelium are encouraging. Photodynamic therapy appears to be ideally suited to HGD and early cancers. CONCLUSION: A selective approach to the management of HGD on an individual patient basis should be adopted.

Barrett Esophagus↗

[Combined form of chronic aggressive hepatitis primary biliary cirrhosis].

15 patients with primary biliary cirrhosis (PBC) and 109 patients with chronic aggressive hepatitis (CAH) have been followed. Features of PBC, namely the generalized pruritus, massive rise in alkaline phosphatase, antimitochondrial antibodies and high levels of IgM-globulins, were present in 7 patients with CAH. This group was treated with immunosuppressive drugs for 1-2 years. Clinical, biochemical, immunological and histological parameters were used to assess the therapeutic effect. The pruritus improved and there was a statistically significant reduction in the IgG-hyperglobulinemia. Some resolution of the piecemeal necroses was seen. However, in judging these changes the sampling error must be taken into account. The unknown agent attacks both the hepatocytes and the epithelial cells of the bile ducts. The immunosuppressive treatment protects the liver cells from further damage while the progressive destruction of the bile ducts remains uninfluenced. The results suggest that the smallest possible dose sufficient to suppress the activity of CAH must be selected.

Alkaline Phosphatase↗

The role of the clinical laboratory in occupational medicine.

The pre-analytic, analytic, and post-analytic stages of laboratory testing present challenges to the attainment of accurate and timely information. These include sampling errors, quality control, and interpretation of results. Learning about the benefits and limitations of specific tests allows the physician to use the laboratory more productively and cost-effectively.

Clinical Laboratory Techniques↗

Sensory neuron number in neonatal and adult rats estimated by means of stereologic and profile-based methods.

Postnatal neuron addition, if it occurred, would have profound implications both for the conceptualization of developmental processes and for efforts directed at replacing neurons that were lost to injury or disease. Although dorsal root ganglia (DRGs) offer the advantages of clear boundaries and functional homogeneity, studies comparing neuron number in the DRGs of animals of different ages or sizes have yielded conflicting results. In the present study, neuron number in DRGs L3-L6 was compared in neonatal (approximately 11 days old, mean weight of 24.5 g, mean volume of 25 cm3) and adult (approximately 80 days old, mean weight of 373.5 g, mean volume of 346 cm3) male Sprague-Dawley rats. Estimates of neuron number were derived by using both stereological (physical disector) and profile-counting (one or more nucleoli within a nucleus) methods. The reliability and validity of the two methods were evaluated by comparing estimates of neuron number with those derived from three-dimensional reconstruction of a subset of neurons. The recommended protocol for using the physical disector was found to give accurate estimates of neuron number, but the heterogeneous distribution of neurons in the ganglion led to sampling errors of up to 50%. Reliability was improved by increasing the number of disector pairs examined. Counts of nuclear/nucleolar profiles were more reliable, but introduced a bias that worked against the experimental hypothesis in that estimates of neuron number in neonates exceeded actual values. Nonetheless, both methods indicated that adult rats had more DRG neurons than did neonates. Profile counts were 19% higher in adults (P < .01, two-tailed t-test); and data obtained by using the physical disector showed that adult rats had 28% more neurons than did neonates (P < .05). The difference in neuron number between adults and neonates could be due either to neuron proliferation or to late differentiation of neurons that do not assume a typical appearance until adulthood.

Aging↗

A case study where biology inspired a solution to a computer science problem.

This paper describes how the biological theory of gene duplication described in Susumu Ohno's provocative book, Evolution by Means of Gene Duplication, was brought to bear on a vexatious problem from the domain of automated machine learning, namely the problem of architecture discovery. Six new architecture-altering operations for genetic programming were motivated by the way that new biological structures, functions, and behaviors arise in nature using gene duplication. Genetic programming with the new architecture-altering operations was then applied to the transmembrane protein segment identification problem. The out-of-sample error rate for the best genetically-evolved program achieved was slightly better than that of previously-reported human-written algorithms for this problem.

Amino Acid Sequence↗

Biopsy techniques for pigmented lesions of the skin.

Proper biopsy techniques for pigmented skin lesions are critical to early detection and treatment of malignant melanoma. Complete surgical excision allows evaluation of size, symmetry, circumscription, and maturation, whereas partial biopsies may result in misinterpretation because of sampling error or inadequate architectural detail. The author briefly reviews standard techniques for excisional biopsy and addresses special clinical scenarios in which incisional or partial biopsies may be necessary.

Biopsy↗

T3 prostate cancer: how reliable is clinical staging?

The treatment of locally advanced stage T3 prostate carcinoma remains controversial. The reliability of the clinical assessment of extracapsular extension by digital rectal examination (DRE) is therefore crucial. Results from series of patients with T3 prostate cancer treated by radical prostatectomy indicate that DRE has shown a wide range of accuracy from 44% to 82%. The assessment of capsule perforation on biopsy provides a 96% specificity rate and a positive predictive value of 60%. Furthermore, if the apparent clinical status of the seminal vesicle is incorrect, sampling errors on biopsy may be substantial. Biopsy therefore appears to provide a more accurate assessment of the capsule than of the seminal vesicle. Information regarding the correlation between T3 clinical staging and conventional/endorectal coil magnetic resonance imaging staging is still needed. Finally, the accuracy rate of DRE for T3 staging increases to more than 90% if the prostate-specific antigen level is greater than 15 ng/mL.

Biopsy↗

Cell cycle and proliferation markers in neuroepithelial tumors.

Cell proliferation is characteristic, though non specific, of tumors. The cell cycle is regarded as a clock with ordered activation of protein complexes triggering initiation and advancement through checkpoints. The cell cycle and its control mechanisms are briefly described herein focusing on neuroepithelial tumors. The assessment of cell proliferation in brain tumors is a very important tool in diagnosis and especially in prognosis. It can be performed by different methods: counting mitoses, calculating the labeling index (Ll) of [3H] Thymidine, BrdU, Ki-67, MIB.1, PCNA, cytometry and AgNORs. Each method has its advantages and disadvantages. The main obstacles to the usefulness of different Lls in establishing prognosis in individual cases are sampling error, heterogeneity of the proliferation potential of brains tumors and the wide overlapping of Ll ranges between classic and anaplatic variants. The principal findings are critically described and commented upon.

Biomarkers↗

Difficulties and dilemmas in the management of congenital anomalies in twin pregnancy.

Both the incidence of twin pregnancy and the demand for prenatal diagnosis are increasing. Unfortunately, biochemical screening and ultrasound scanning are less reliable for prenatal diagnosis in twin pregnancies than in singletons. Amniocentesis and chorionic villous biopsy are usually diagnostic in singleton pregnancies but may be marred by sampling errors in twin gestations. Where a congenital anomaly has been diagnosed in a twin pregnancy, difficult decisions may have to be made, especially if one twin is unaffected. In these cases, special skills are required to ensure that adequate information, psychological support and optimal medical care are provided.

Abortion, Induced↗

The value of a reverse transcriptase polymerase chain reaction assay in preoperative staging and followup of patients with prostate cancer.

PURPOSE: The reverse transcriptase polymerase chain reaction (RT-PCR) assay is an extremely sensitive technique of detecting cells expressing prostate specific antigen (PSA). Controversy exists regarding the ability of peripheral blood PSA RT-PCR testing to reflect pathological staging or treatment outcome. We examine the phenomenology of RT-PCR results in patients with prostate cancer, with particular emphasis on the RT-PCR test before and after radical prostatectomy, and correlations with pathological staging and treatment outcome. MATERIALS AND METHODS: Peripheral blood was obtained from a wide variety of patients with and without prostate cancer, including before and after radical prostatectomy. After ribonucleic acid isolation, complementary deoxyribonucleic acid was generated and amplified with a hot-start technique. RT-PCR results were compared with pathological stage, Gleason score, tumor volume and disease-free status. Correlations between preoperative and postoperative RT-PCR tests were also made. RESULTS: The RT-PCR test was positive in 1 of 56 controls (1.8%) without suspicion of prostate cancer. A positive test was obtained in 12 of 65 men (18.5%) with a suspicion of prostate cancer but a negative biopsy. Before radical prostatectomy a positive test was obtained in 13 of 75 men (17.3%) with pT2 disease versus 10 of 46 (21.7%) with pT3 disease. There was no significant difference in serum PSA, Gleason score or tumor volume between the men with positive or negative results. With repetitive testing an increasing percentage of men had at least 1 positive test preoperatively. With a median followup of 8 months 6 of the 7 patients in whom radical prostatectomy failed had had negative RT-PCR before treatment. Of patients with known metastatic disease or failed primary treatment a positive test was obtained in 32 to 75%. Radical prostatectomy and prostate needle biopsy appeared to have a negligible effect on RT-PCR tests immediately following these procedures. Following radical prostatectomy results were variable but many men who are RT-PCR positive preoperatively become RT-PCR negative postoperatively. CONCLUSIONS: The PSA RT-PCR test in our laboratory cannot be used preoperatively to predict pathological stage of prostate cancer or treatment failure. Most cases that are positive preoperatively become negative postoperatively. While increasing tumor burden increases the likelihood of positive tests, there appears to be significant sampling error associated with the use of this test in the peripheral blood.

Adult↗

Listening to parents. A national survey of parents with young children.

OBJECTIVE: To document the child-rearing needs and pediatric health care experiences of parents with children from birth to 3 years old. DESIGN: A nationally representatives sample of 2017 parents with children younger than 3 years using a 25-minute structured telephone questionnaire. Interviews were completed by 68% of the screened eligible respondents. The margin of sampling error for results at the 95% confidence level was +/- 3 percentage points. RESULTS: Seventy-six percent of children younger than 3 years were reported by parents to be in excellent health; 88% had a regular source of pediatric health care. Seventy-one percent of parents who received special pediatric services rated their child's physician as excellent in providing good health care. Seventy-nine percent of parents reported they could use more information in at least 1 of 6 areas of child rearing, and 53% wanted information in at least 3 areas. Forty-two percent had talked with their child's physician about "nonmedical" concerns; 39% of parents read to or looked at a picture book with their child on a daily basis; 51% of parents set daily routines for meals, naps, and bedtime. Breast-feeding and reading to the child on a daily basis were much more likely if a physician encouraged parents to do so. CONCLUSIONS: Most parents view the pediatric health care system as meeting the physical health needs of their young children. Parents want more information and support on child-rearing concerns, yet pediatric clinicians often fail to discuss nonmedical questions with them. The interventions of pediatric clinicians can positively affect parental behavior. Pediatric practices should consider creative ways to reconstitute and augment their current services and systems of care.

Adult↗

Mammographic-histopathologic correlation of large-core needle biopsies of the breast.

Large-core (14g) needle biopsy (CNB) of the breast is a new diagnostic modality increasingly being used to evaluate patients with mammographic abnormalities. Two hundred twenty-four CNBs were performed on 198 patients. Surgical follow-up was available in 64 cases (28.6%). Overall concordance rate was 93.8% (60 of 64 cases). Of the four discordant cases, two were diagnosed as atypical ductal hyperplasia (ADH) on CNB; on excision, these cases showed cribriform ductal carcinoma in situ (DCIS); two remaining cases, diagnosed on CNB as ADH versus DCIS, showed invasive carcinoma (DCIS with invasive component and infiltrating cribriform carcinoma, respectively) on excisional biopsy. Malignancy, primary (52) or metastatic (5), was identified in 57 cases (25.4%); 47 of these patients underwent surgical excision, and the diagnosis was confirmed in all of these cases. Of 51 cases with radiographic evidence of microcalcifications, 48 (94%) had microcalcifications in the CNB: 30 (62.5%) were benign, 11 (22.9%) were malignant, and 7 (14.6%) were diagnosed as ADH. In the remaining three cases (1.3%), only benign breast tissue without microcalcifications was seen, and the lesion was considered to have been missed. Biopsy specimens were obtained from 173 lesions because of the presence of a mass: 125 (72.3%) were benign, 45 (26%) were malignant, and 3 (1.7%) were diagnosed as ADH. Follow-up was available in 118 patients with benign lesions: all were mammographically stable or decreased at 6 or 12 months; no follow-up was available for the remaining patients. CNB of the breast is a highly sensitive (96.9%) and specific (100%) technique for management of patients with mammographic abnormalities. The histologic findings should be correlated with the mammographic appearance, and an attempt should be made to achieve a specific diagnosis in all lesions, particularly masses. The diagnosis of ADH should always prompt excisional biopsy because of a high frequency of false-negative results caused by sampling errors or underestimation.

Adolescent↗

[HIV infection. Diagnosis in the national network of laboratories in Chile].

A national network including 114 blood banks and laboratories performs screening for HIV infection on approximately 250,000 blood donors a year. This represents 100% coverage of blood transfusions performed in Chile. Up to December 1990. 4956 samples had been sent to the National Reference Center for AIDS for supplementary studies. HIV infection was confirmed in 1465 (29.6%). A prior study covering the first semester of 1989 showed a 26.9% confirmation rate for HIV infection on 845 serum samples. Technical errors including sample contamination, poor cleaning, decreasing titers of controls and erratic criteria regarding the need for supplementary studies may explain the low confirmation rate reported in this study.

Blood Donors↗

Changes of bone histology during maintenance hemodialysis at various levels of dialyzate Ca concentration.

Bone histology (iliac crest biopsies; undecalcified sections; micromorphometry) was studied by repeated biopsies in 19 patients on maintenance hemodialysis. Sampling error was assessed by taking two biopsies at one time. After an initial biopsy, patients were dialyzed either against 3.6 mEq Ca/l dialyzate or 3.9 mEq Ca/l dialyzate for 9-16 months before a second biopsy was taken. Bone histology failed to normalize irrespective of the dialyzate Ca concentration. Surface density of endosteal fibrosis diminished in a considerable proportion of the patients (9/19). Volumetric density of osteoid fell in 5 and rose in 4 of the patients.

Adolescent↗

The impact of ignoring measurement error when estimating sample size for epidemiologic studies.

The author presents two examples illustrating the bias in sample-size estimates that can result from ignoring measurement error among study variables. The first example examines the impact of ignoring misclassification of the study's outcome variable on the accuracy of sample-size estimates. In addition, the author outlines a simple yet effective means of adjusting sample-size estimates to account for outcome misclassification. In the second example, the author illustrates the potential for severe underestimation of required sample size in studies using linear regression to evaluate associations between the outcome of interest and an independent variable subject to classical measurement error. The author concludes with a discussion of pertinent literature that might be helpful to study planners interested in adjusting sample-size estimates to account for measurement errors in both outcome and predictor variables.

Epidemiologic Studies↗

Sheep lactate entry-rate measurements: error due to sampling jugular blood.

Carotid arterial and jugular venous blood samples were taken simultaneously during primed continuous infusions of L-[U-14C]lactate in four sheep. The mean rate (n = 4) of total net formation of lactate (0.394 +/- 0.047 mg C/min per kg) calculated from the results obtained by analyzing the jugular blood samples for lactate concentration and specific radioactivity was significantly higher (0.01 greater than P greater than 0.005) than the mean rate (n = 4) calculated from the results of analysis of the arterial samples (0.302 +/- 0.036 mg C/min per kg). The error in the estimation of the rate of total net formation of lactate due to jugular sampling resulted from the negative arteriovenous difference found for lactate across the tissues of the head. These results illustrate the general need for examination of the suitability of venous sampling in experiments that make use of the continuous infusion isotope-dilution method.

Animals↗