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Strategies for reoperation after comprehensive epilepsy surgery.

OBJECT: Prior reports of seizure control following reoperation for failed epilepsy surgery have shown good results. These studies included patients who presented during the era preceding magnetic resonance (MR) imaging, and the patients were often not monitored intracranially or underwent subtotal hippocampal resections. In this study, the authors hypothesized that reoperation for recurrent seizures following a more comprehensive initial workup and surgery would not yield such good results. METHODS: The authors examined a consecutive series of patients who underwent two operations at Yale-New Haven Hospital for medically intractable epilepsy and in whom there was a minimum of 1-year follow up after the second surgery. All patients were evaluated and treated according to a standard protocol, including preoperative MR imaging, a low threshold for invasive monitoring, and a radical amygdalohippocampectomy when indicated. Twenty-seven patients were identified (five with mesial temporal sclerosis, 20 with neocortical disease, and two with multifocal sites of seizure onset) of whom six (22%) underwent intentionally palliative second surgery (corpus callostomy or placement of a vagus nerve stimulator [VNS]). Of the remaining 21 patients, only four (19%) became seizure free after a second resective operation. The most common causes of treatment failure were dual pathology, recurrent tumor, limited resection to preserve function, widespread developmental abnormalities, and electrographic sampling error. Successful outcomes resulted from removal of recurrent tumors, completion of a functional hemispherectomy, or repeated invasive monitoring to correct a sampling error. Five (83%) of the six intentionally palliative second operations resulted in more than a 50% decrease in seizure frequency. CONCLUSIONS: If an aggressive preoperative evaluation and surgical resection are performed, reoperation for recurrent seizures has a much lower likelihood of cure than previously reported. Intentionally palliative surgery such as placement of a VNS unit may be considered for patients in whom the initial operation fails to decrease seizure frequency.

Adolescent↗

Concomitant papillary thyroid carcinoma and Hashimoto's thyroiditis.

An association between papillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT) is well recognized. Both entities may often display overlapping morphologic features. The aim of this study was to evaluate the accuracy of fine needle aspiration (FNA) of concomitant PTC and HT. Twenty nine thyroid FNAs with a diagnosis of concomitant PTC and HT on follow-up surgical material were retrospectively reviewed (11% of all HT cases diagnosed in the same period of time). The cytologic specimens were evaluated for the presence of diagnostic features of PTC and HT. In 16 of 29 cases, the diagnosis of PTC was made or suggested; however, only in 3 cases were both entities recognized on the FNA material. The review of the remaining cases (13 cases) showed diagnostic features of PTC in 2 cases (interpretation errors), some features of PTC in 8 cases (insufficient diagnostic features), features of only HT in 2 cases, and 1 case was acellular (sampling errors). Originally, 10 cases with features of PTC were diagnosed as either follicular neoplasm or colloid nodule with or without HT. Histologically, 1 of 13 cases was a cystic variant and 7 of 13 cases were follicular variants of papillary carcinoma. It is important to be aware of the coexistence of PTC and HT. Deliberate search for evidences of PTC in every case of HT may be necessary to improve diagnostic accuracy of the FNA. However, the cytologic diagnosis of follicular variant of PTC coexisting with HT can be challenging. The sampling error may also cause false negative results.

Adult↗

Census error and the detection of density dependence.

1. Studies aiming to identify the prevalence and nature of density dependence in ecological populations have often used statistical analysis of ecological time-series of population counts. Such time-series are also being used increasingly to parameterize models that may be used in population management. 2. If time-series contain measurement errors, tests that rely on detecting a negative relationship between log population change and population size are biased and prone to spuriously detecting density dependence (Type I error). This is because the measurement error in density for a given year appears in the corresponding change in population density, with equal magnitude but opposite sign. 3. This effect introduces bias that may invalidate comparisons of ecological data with density-independent time-series. Unless census error can be accounted for, time-series may appear to show strongly density-dependent dynamics, even though the density-dependent signal may in reality be weak or absent. 4. We distinguish two forms of census error, both of which have serious consequences for detecting density dependence. 5. First, estimates of population density are based rarely on exact counts, but on samples. Hence there exists sampling error, with the level of error depending on the method employed and the number of replicates on which the population estimate is based. 6. Secondly, the group of organisms measured is often not a truly self-contained population, but part of a wider ecological population, defined in terms of location or behaviour. Consequently, the subpopulation studied may effectively be a sample of the population and spurious density dependence may be detected in the dynamics of a single subpopulation. In this case, density dependence is detected erroneously, even if numbers within the subpopulation are censused without sampling error. 7. In order to illustrate how process variation and measurement error may be distinguished we review data sets (counts of numbers of birds by single observers) for which both census error and long-term variance in population density can be estimated. 8. Tests for density dependence need to obviate the problem that measured population sizes are typically estimates rather than exact counts. It is possible that in some cases it may be possible to test for density dependence in the presence of unknown levels of census error, for example by uncovering nonlinearities in the density response. However, it seems likely that these may lack power compared with analyses that are able to explicitly include census error and we review some recently developed methods.

Animals↗

Operative biopsy of the pancreas using the Trucut needle.

The results of 14 operative biopsies of the pancreas using the Trucut technique are presented. There was no significant complication attributable to the biopsy, and in all cases an adequate tissue specimen was obtained, facilitating either frozen or paraffin section histological diagnosis. One false negative result was obtained which was due to sampling error. This technique is recommended as a good alternative when operative pancreatic biopsy is required. It is technically simple, has an acceptably low sampling error, provides a good tissue specimen for histological examination, and has few complications.

Adenocarcinoma↗

Bacterial content in samples from different sites in the rumen of sheep and cows as determined in two culture media.

Samples of material from the rumen of cattle and of sheep were cultured in both Gall Broth (GB) and Reinforced Clostridium Medium (RCM). Samples were taken, at monthly intervals, from five sites in cattle and two sites in sheep in two series and, at weekly intervals, from two sites in cattle and in sheep in two series. Comparisons were made of the growth of organisms in the media, using the number of fertile tubes per set of six dilutions as a measure of the viable count. RCM gave a greater number of fertile tubes than GB with samples from cattle, but the reverse was the case with samples from sheep. Real differences in the number of fertile tubes from different sites in cattle were found at different times, but there was no consistent pattern. Simultaneous sampling from different sites in the rumen is, therefore, essential to provide an estimate of sampling error within animals. Although no site to site differences were detectable with rumen material from sheep, it is advisable to take more than one sample at a given time to assess sampling error.

Animals↗

Precision of "high-performance" liquid-chromatographic assays with sample pretreatment. Error analysis for the Technicon "FAST-LC" system.

A comprehensive theory has been presented elsewhere (Anal. Chem. 53: 877-884, 1981) for the various contributions to assay imprecision in procedures that are based on sample extraction followed by "high-performance" liquid chromatography. Experimental data (1800 assays, 8400 results) for the Technicon FAST-LC system are used with this theory in an effort to understand and control the precision of clinical-laboratory procedures, both automated and manual. This study provides specific conclusions and recommendations on matters such as: standardization procedures and protocols, physical properties requires in internal standards, the relative importance of different sources of imprecision and means for improving precision, the relative importance of temperature control in pretreatment and liquid-chromatographic analysis, and the precision obtainable with small sample volumes or with samples containing very low concentrations of analyte (e.g., in assays for free drugs). Automation evidently can lead to twofold greater assay precision, other factors being equal, for liquid-chromatographic procedures that include sample pretreatment. Similarly, internal standardization, properly applied, can decrease assay imprecision by twofold.

Anticonvulsants↗

The role of laparoscopy in the diagnosis of cirrhosis.

BACKGROUND: A definitive diagnosis of cirrhosis is important in the prognosis and management of patients with chronic liver disease. The diagnosis of cirrhosis is made either by histologic examination of a biopsy specimen or upon visualization of a diffusely nodular and firm surface of the liver at laparotomy or laparoscopy. A liver biopsy, however, may not demonstrate the histologic features of cirrhosis in some cirrhotic patients. Our goal in this study was to compare the accuracy of liver descriptions made during laparoscopy with liver histology found by laparoscopic biopsy in patients with chronic liver disease. METHODS: A retrospective review of paired laparoscopy and histology reports was performed on 434 consecutive patients who underwent laparoscopy between 1992 and 1994. (M:F ratio, 1.3:1; mean age, 48 +/- 14 years). ETIOLOGY: 52% hepatitis C, 8% hepatitis B, 8% fatty liver, 4% primary biliary cirrhosis, 3% autoimmune hepatitis, and 25% miscellaneous (cancer patients were excluded). RESULTS: One hundred sixty-nine patients had laparoscopic evidence of cirrhosis; 115 were confirmed by histology, representing a 32% sampling error. Two of 265 patients with histologic evidence of cirrhosis (0.8%) had no macroscopic evidence of cirrhosis at laparoscopy. CONCLUSIONS: (1) There was a 32% histologic sampling error among patients documented to have cirrhosis by laparoscopy. (2) Using laparoscopy as a gold standard, the sensitivity of liver biopsy was 68% and the specificity was 99%.

Adult↗

Magnetic resonance imaging of the knee: diagnostic performance studies.

OBJECTIVES: To review and reassess the published diagnostic performance statistics for MRI of the menisci and cruciate ligaments. To illustrate the potential sources and effects of bias in the evaluation of this widely accepted diagnostic technique. METHODS: Published evaluations of knee MRI were identified from the literature. Criteria for inclusion in the review were a total sample size > or = 35, arthroscopic correlation of MRI findings and presentation of complete results. Diagnostic performance statistics were then recalculated for each published study. RESULTS: Twenty-two studies were identified with sample sizes between 35 and 1014. The overall sensitivity for MRI of the menisci and cruciates was 0.88 (95% confidence interval 0.86-0.90). The overall specificity was 0.94 (0.93-0.94). Sampling error varied widely amongst studies and was rarely quantified. CONCLUSIONS: Diagnostic performance statistics are widely used. It is still not well appreciated that these are subject to sampling error. Such errors make meaningful comparisons between published studies more difficult. Nevertheless, the results for meniscal and cruciate lesions are consistently high and support the use of MRI for these common problems. The diagnostic performance of other applications of MRI should be subjected to similar critical review.

Anterior Cruciate Ligament↗

Detection of abnormal E-cadherin expression by simulated prostate biopsy.

PURPOSE: Sampling error is an inherent problem of prostate biopsy. Consequently the determination of whether a given carcinoma is clinically significant based on biopsy results is problematic. We assess the dimensions of sampling error and, thereby, provide insight into the potential value of prognostic markers applied to needle biopsies. MATERIALS AND METHODS: We constructed 3-dimensional computer models of 21 prostatectomy specimens, including outlines of carcinomas, regions of abnormal E-cadherin expression and individual Gleason patterns. The 6 random systematic core biopsy technique and modifications were simulated using a computer algorithm. RESULTS: In 6 of 21 cases the area of abnormal E-cadherin expression and/or high grade carcinoma was not sampled on 6 random systematic core biopsy. The areas missed were either small or inconsistently under sampled regions of the prostate. Modifying the placement of biopsy needles improved the detection of these features. In addition, percent tumor in the needle appeared to be well correlated to percent tumor in the prostate (r = 0.891, r2 = 0.642). CONCLUSIONS: To avoid underestimating the aggressiveness of prostatic carcinoma at least 6 biopsies should be taken from each patient. A more extensive sampling is probably not warranted in all patients but it may prove useful in those in whom extent of disease is unclear or whose general health makes treatment decisions difficult. A reliable estimate of tumor volume in the prostatectomy specimen can be made based on relative amount of tumor in the biopsy specimen on an individual basis.

Aged↗

The intraclass covariance matrix.

Introduced by C.R. Rao in 1945, the intraclass covariance matrix has seen little use in behavioral genetic research, despite the fact that it was developed to deal with family data. Here, I reintroduce this matrix, and outline its estimation and basic properties for data sets on pairs of relatives. The intraclass covariance matrix is appropriate whenever the research design or mathematical model treats the ordering of the members of a pair as random. Because the matrix has only one estimate of a population variance and covariance, both the observed matrix and the residual matrix from a fitted model are easy to inspect visually; there is no need to mentally average homologous statistics. Fitting a model to the intraclass matrix also gives the same log likelihood, likelihood-ratio (LR) chi2, and parameter estimates as fitting that model to the raw data. A major advantage of the intraclass matrix is that only two factors influence the LR chi2--the sampling error in estimating population parameters and the discrepancy between the model and the observed statistics. The more frequently used interclass covariance matrix adds a third factor to the chi2--sampling error of homologous statistics. Because of this, the degrees of freedom for fitting models to an intraclass matrix differ from fitting that model to an interclass matrix. Future research is needed to establish differences in power-if any--between the interclass and the intraclass matrix.

Algorithms↗

Adenocarcinoma in situ of the uterine cervix: screening and diagnostic errors in Papanicolaou smears.

BACKGROUND: Little attention has been given to the reasons for failure to detect adenocarcinoma in situ (AIS) of the uterine cervix in Papanicolaou (Pap) smears. In the current study, the authors examined a series of screening or diagnostic errors in cases in which the final histologic diagnosis was either AIS or AIS combined with a high-grade squamous intraepithelial lesion (AIS + HSIL). METHODS: Smears obtained in the 3 years before histologically proven AIS or AIS + HSIL was diagnosed and within a specified 6-year period (1993-1998) were reviewed and reclassified. All were conventional Pap smears. The smears studied were those with a review diagnosis of possible or definite high-grade epithelial abnormality that initially were reported by a cytotechnologist to be negative (screening error) or that were reported by a pathologist to be negative, unsatisfactory, or indicative of a low-grade epithelial abnormality (diagnostic error). A semiquantitative, blinded assessment of the frequency of cytologic criteria for the diagnosis of AIS was made for smears with erroneous diagnoses compared with a series of smears that yielded true-positive findings. RESULTS: Sampling errors, which were defined as cases in which smears did not have sufficient evidence for a diagnosis of possible or definite AIS or HSIL on review, accounted for 35.1% and 36% of all smears from patients with a biopsy diagnosis of AIS and patients with a biopsy diagnosis of AIS + HSIL, respectively. With regard to AIS, there were 3 screening errors and 5 diagnostic errors, accounting for 10.4% of 77 smears. Minimal, poorly preserved material was evident in four smears, including three smears with only one sheet of abnormal glandular cells. In four other smears, there was a moderate amount of adequately preserved glandular material, mainly in large sheets, with varying degrees of crowding and hyperchromasia. With regard to AIS + HSIL, there were 6 screening errors and 6 diagnostic errors, accounting for 13.5% of 89 smears. In those smears, there generally was a moderate amount of abnormal material in the form of crowded groups of suboptimally preserved, hyperchromatic squamous cells. Only two of those smears yielded findings of possible abnormal glandular cells. Only 3 of 20 errors occurred in smears that were examined during the last 3 years of the study. In the semiquantitative assessment, smears with erroneous findings were shown to contain far less abnormal material than true-positive smears and to exhibit a corresponding paucity of diagnostic criteria. CONCLUSIONS: Sampling errors were the main cause of false-negative reports in cases of AIS and AIS + HSIL. The primary factors that contributed to screening or diagnostic errors in AIS were minimal, poorly preserved abnormal material and an overly conservative approach to the assessment of unusual large sheets or aggregates of glandular cells. With regard to AIS + HSIL, most laboratory errors were related to the presence of crowded groups of squamous epithelial cells. There were fewer errors in the last 3 years of the study, raising the possibility of improvement over time.

Adenocarcinoma↗

Estrogen and progesterone hormone receptor status in breast carcinoma: comparison of immunocytochemistry and immunohistochemistry.

We evaluated the correlation between histologic and cytologic specimens in the determination of estrogen receptor (ER) and progesterone receptor (PR) status in breast carcinoma and investigated the causes of clinically significant discrepancies. We analyzed 70 immunoassays for ER and 60 for PR from 71 patients with breast carcinoma. Concordance between cytology and histology was 89% for ER and 63% for PR using scores from pathology reports. Concordance between cytology and histology was 98% for ER and 91% for PR using consensus scores (obtained after reevaluation by the team of pathologists). Thirty of 130 (23%) tests had clinically relevant discrepancies, 53% of which were caused by wrong interpretation of cytologic findings, 10% by wrong interpretation of histologic findings, 17% by sampling error and 20% were not available for reevaluation. Wrong interpretation of the results for ER and PR status in cytology was a far more frequent cause of clinically relevant discrepancies than sampling errors. The use of strict criteria is recommended.

Adenocarcinoma, Mucinous↗

Accuracy and consistency in application of a probabilistic approach to reporting breast fine needle aspiration.

OBJECTIVE: To determine the application of a probabilistic/categorical approach for reporting breast fine needle aspiration (FNA) and its dependence on the cytopathologist's level of experience. STUDY DESIGN: All breast surgical specimens that had preoperative breast FNA at our institution during a 3-year period were identified. The cytologic results were reported as 1 of 6 categories: positive, suspicious, atypical, epithelial proliferative, unremarkable and nondiagnostic, according to well-defined criteria. Five cytopathologists were responsible for all cytology sing-out during the study period. The histologic and cytologic diagnoses were correlated. RESULTS: A total of 297 cases were identified. Overall, there were no false positive cases (positive predictive value [PPV] = 100%). Two false negative cases (negative predictive value [NPV] = 96%) were due to sampling error. This indicates that the PPV and NPV for each of the 5 pathologists were also all 100% except for the 1 pathologist who had two false negative cases due to sampling errors. The probability of finding carcinoma on histology for suspicious and atypical cytologic categories ranged from 67% to 100% and 8% to 31%, respectively, for the individual pathologists. Fifteen cases were signed out by > or = 2 pathologists. The involvement of consultants was significantly associated with diagnosis (P = .02). Ten of the 15 cases were in the suspicious (5) or atypical (5) category. CONCLUSION: The probabilistic approach with defined diagnostic criteria is an accurate method and can be consistently applied in reporting breast FNA. Although use of the indeterminate (suspicious and atypical) categories is variable, a definite and considerable difference in the probability of carcinoma between these 2 categories was observed for all pathologists. The involvement of consultants did not move the cases out of these indeterminate categories.

Biopsy, Fine-Needle↗

[Quality assessment of intraoperative frozen sections in a teaching hospital: an analysis of 847 consecutive cases].

We evaluated the accuracy of 847 consecutive frozen section diagnoses in order to develop a quality control. We also evaluated the time needed to perform them. Frozen sections and final diagnoses agreed in 92.6% and disagreed in 1.7% (14 cases). 5.8% of the cases were deferred. The only case of false-positive frozen sections (0.1%) was due to a pathologist's misinterpretation. False-negative frozen sections were due to sampling errors: in 5 cases, diagnostic tissue was present only in permanent sections of the frozen block and in 8 cases diagnostic tissue was present only in the portion of the specimen not sampled by the frozen section. One hundred and ninety two frozen sections concerned thyroid neoplasms. Thirteen cancers were diagnosed on frozen sections, 2 cancers were considered as benign and 9 cancers had a differed diagnosis. The mean duration to perform the frozen sections was 21 minutes. In conclusion, intra operative frozen section diagnosis is rapid and reliable. Discrepancies are more often false negatives due to sampling errors. Although a high rate of differed diagnosis was observed in thyroid neoplasms, frozen sections remain useful for these lesions. Imprint cytology of thyroid nodules is advisable.

Biopsy↗

Modified H & E staining technique for fine needle aspiration cytology (FNAC) smears.

Papanicolaou (Pap) staining procedure has achieved worldwide acceptance in cytology practice due to its crisp cytological details. There are many centres or private laboratories in our country which cannot fulfill the economic requirement of Pap staining and hence employ comparatively cheaper haematoxylin and eosin (H & E) stain. Although routine H & E cannot replace Pap, this study is an attempt to modify H & E staining that would offer comparable diagnostic results. The present study is restricted to FNAC material from palpable lesions i.e.breast and lymph nodes. For this purpose 50 lymph nodes ( LN) and 18 breasts were aspirated. Out of two fixed smears, 1 was stained by Pap technique for routine reporting and other by modified H & E method which was examined and reported by other pathologist, Dr. Sangeeta B. Desai ( SBD) The diagnosis of both the techniques were compared. Emphasis was also given on cytomorphological characteristics. Out of fifty lymph node aspirates from various sites, no diagnostic discrepancy was observed in 46 cases. Three out of 4 had sampling errors whereas, poor nuclear staining was noticed in a single case. Out of eighteen breast aspirates concordant diagnosis was achieved in 16 cases. Out of two discrepant diagnosis 1 was due to sampling error, and the other was an interpretative error. All the cases were confirmed histologically. In conclusion, modified H & E staining is useful for common sites of aspirations of superficial lesions.

Biopsy, Fine-Needle↗