Cervical false negative cases detected by neural network-based technology. Critical review of cytologic errors

OBJECTIVE: To analyze the cytological errors made in the manual screening of cervical smears and to evaluate the usefulness of neural network-based technology (nnbt) in the detection of different kinds of errors. STUDY DESIGN: We reviewed 1,981 cervical smears by nnbt. Twelve false negatives (FNs) were detected and selected for study. The number of cell images showing atypical keratosis or atypical cells was evaluated on the monitor. The cellular features of the atypical cells (cellularity, cell type, nuclear and cytoplasmic changes, cellular arrangement and location on the slide) were analyzed by optic microscopy. Considering these qualitative and quantitative cytologic parameters and the diagnosis made by manual screening, we classified the errors into two groups: screening and interpretation related. RESULTS: Four FNs were screening errors. Five FNs were classified as errors of interpretation. In three cases the cause of the cytologic errors could not be ascertained. CONCLUSION: Our results confirm previous studies demonstrating that nnbt is useful for detecting screening errors. We also showed that it might be an adjunctive tool in the interpretation of abnormal cells, reducing the number of false negatives.     

Preoperative cytologic morphometry may assist in predicting patient outcome after surgery in papillary thyroid cancer

OBJECTIVE: To evaluate the quantitative estimations of various cytologic nuclear features on smears obtained by preoperative fine-needle aspiration and to examine their correlation with patient outcome after surgery for papillary thyroid cancer. STUDY DESIGN: The subjects consisted of 142 patients with common type papillary thyroid cancer. The aspirated smears were examined quantitatively with a standard microscope connected to a computerized video system, and the mean nuclear area, nuclear perimeter, form factor (FF) and the coefficient of variation of the nuclear area (NACV) were measured and calculated. All of the surgically treated patients were followed through serial clinical evaluations, and correlations between the cytologic parameters and patient outcomes were analyzed. RESULTS: Local relapses or distant metastases were identified in 13 (9.2%) of the 142 patients in the median follow-up period of 160 (range, 108-234) months. Recurred cases had higher FF values than disease-free cases (p = 0.0017), especially in local relapse (p = 0.0015). Distant metastases were frequently observed in the cases with a high NACV value (p = 0.0020). CONCLUSION: Preoperative quantitative estimations of cytologic nuclear features provide preoperative clinical information that may predict patient outcome and be useful for designing individual protocols.     

Prognostic evaluation of breast cancer in cytologic specimens

OBJECTIVE: To evaluate prognostic factors in breast cancer using cytologic samples and to determine the correlation between those factors and ploidy. STUDY DESIGN: Two hundred sixteen fine needle aspirates from patients with primary breast cancer were analyzed for expression of estrogen receptors (ERs), progesterone receptors (PRs), Ki-67 antigen, expression of p53 tumor suppressor gene and overexpression of c-erbB-2 using a standard immunochemical method. Not all subjects had all biomarker information because of the study design (c-erbB2 added later). The specimens were analyzed also for ploidy. We used the SAMBA 4000 image analysis system for quantification of the percent of cells stained positively by the different immunocytochemical stains andfor ploidy. RESULTS: A significant correlation wasfound between ER and PR and between Ki-67 and positive p53. Steroid receptor content was not significantly related to p53, Ki-67 or c-erbB2. No correlation was found between c-erbB2 and the other biomarkers. Ploidy had a significant correlation with all the biomarkers used. CONCLUSION: A reliable and rapid evaluation of markers for breast cancer can be achieved by measuring cells stained positively by immunocytochemical stains, as well as ploidy, by means of an image analysis system. ER, PR Ki-67, p53 and c-erbB2 had a significant correlation with ploidy and overall prognostic value in breast cancer.     

Measurements of a negative ion flux inplasma thruster tests in a vacuum chamber

The dynamics of negative ions created in the interaction of a plasma jet with a target is investigated experimentally. The experiments were carried out with a stationary plasma thruster. A multigrid probe was used to record negative ions.     

Debate on GMOs health risks after statistical findings in regulatory tests

We summarize the major points of international debate on health risk studies for the main commercialized edible GMOs. These GMOs are soy, maize and oilseed rape designed to contain new pesticide residues since they have been modified to be herbicide-tolerant (mostly to Roundup) or to produce mutated Bt toxins. The debated alimentary chronic risks may come from unpredictable insertional mutagenesis effects, metabolic effects, or from the new pesticide residues. The most detailed regulatory tests on the GMOs are three-month long feeding trials of laboratory rats, which are biochemically assessed. The tests are not compulsory, and are not independently conducted. The test data and the corresponding results are kept in secret by the companies. Our previous analyses of regulatory raw data at these levels, taking the representative examples of three GM maize NK 603, MON 810, and MON 863 led us to conclude that hepatorenal toxicities were possible, and that longer testing was necessary. Our study was criticized by the company developing the GMOs in question and the regulatory bodies, mainly on the divergent biological interpretations of statistically significant biochemical and physiological effects. We present the scientific reasons for the crucially different biological interpretations and also highlight the shortcomings in the experimental protocols designed by the company. The debate implies an enormous responsibility towards public health and is essential due to nonexistent traceability or epidemiological studies in the GMO-producing countries.     

Cervical spine arthrodesis in rheumatoid arthritis: a long-term follow-up.

Forty-one patients with rheumatoid arthritis involving the cervical spine had a posterior cervical arthrodesis. They were followed for a minimum period of seven years. The diagnoses prior to surgery included cranial settling, atlantoaxial subluxation, subaxial subluxation, and any combination of these three. All patients had posterior arthrodesis, with or without methylmethacrylate, and iliac crest autogenous bone graft. In addition, one patient had an anterior vertebrectomy, and two had transoral resection of the odontoid. Follow-up consisted of a subjective questionnaire, standard radiographs, and physical examination, including a neurologic exam. This information was compared to preoperative data available in the patient''s medical record, postoperative data, and the information obtained in a similar study undertaken in 1987. At the time of follow-up, thirteen patients were known to be dead. One patient could not be located. Of the remaining twenty-six patients, eighteen underwent the full examination, including physical exam and radiographs. The remaining nine patients were contacted and interviewed, but were unavailable for exam and radiographs. All patients considered the operation a success. Only one patient at follow-up had a non-union. This was stable over time. No patient had a deterioration in neurologic function. There was no significant degeneration or instability seen at levels adjacent to the fused segments as compared to the rest of the cervical spine. Posterior cervical spine arthrodesis for rheumatoid involvement of the neck is a safe, efficacious procedure with no significant deterioration of effects over time.     

Cervical cancers diagnosed after negative results on cervical cytology: perspective in the 1980s.

OBJECTIVES--To assess the magnitude of the problem of interval cancers of the cervix (those that are diagnosed within a short time after negative screening test results) in the 1980s, to compare the nature of interval cancers in younger women with that in older women, and, by reviewing negative cervical smears, to determine the proportion of interval cancers that might represent the development of malignancy anew compared with the proportion that might be associated with difficulties in sampling or errors in reporting. DESIGN--An audit of the interval cases of cervical cancer that had been diagnosed within 36 months of a smear having been reported as negative by the Victorian Cytology Gynaecological Service among women registered with cervical cancer during 1982-6. SETTING--The Victorian Cytology Gynaecological Service, a free public sector cytology laboratory in Victoria, Australia. SUBJECTS--138 Women, all of whom had had cervical cancer diagnosed during the 36 months after having had a negative cervical smear. Subjects were divided into two age groups: younger women, aged less than 35; older women, aged 35-69. INTERVENTIONS--Negative slides were reviewed for evidence of optimal sampling and for the presence of cellular abnormalities that had been missed at the time of the original reporting. MAIN OUTCOME MEASURES--The number of interval cases of cancer of the cervix registered during 1982-6. The proportion of interval cases occurring in younger women and the proportion occurring in older women. Division of women into three risk categories based on clinical history and screening history that broadly corresponded to the probability that a diagnosis of cervical cancer might be expected during the 36 months after the issuing of a negative smear report. RESULTS--138 Of 1044 (13.2%) women who had been registered with cervical cancer during 1982-6 had had one or more negative smears during the 36 months preceding the diagnosis of cancer. Interval cancers comprised a larger proportion of registrations of cervical cancer in women aged less than 35 years than in women aged 35-69 (21.1% v 11.0%, p less than 0.01). Women with interval cancer who had had at least three negative smears during the 10 years before the diagnosis of cancer were commoner in the younger age group than in the older age group (7.0% v 2.5%, p less than 0.01). When, however, the number of observed cases of squamous cell carcinoma was related to the number of expected cases in the absence of screening, no significant difference was found between the two age groups (6.8% v 4.8%, p greater than 0.10). The rate of diagnosis of interval cancer per 100,000 negative tests was lower among younger women than among older women (10/100,000 v 16/100,000). Review of the negative slides showed that 11.9% were again considered to be negative with an optimal sample having been obtained as evidenced by the presence of endocervical cells or metaplastic cells, or both. CONCLUSIONS--Interval cancers might comprise a larger proportion of all registered cases of cervical cancer among younger women owing to the larger proportion of such cancers being prevented in this age group. Among women with interval cancer review of the negative slides showed that most were accounted for by suboptimal sampling or by errors of reporting.     

RNA silencing of single and multiple members in a gene family of rice

RNA silencing with inverted repeat (IR) constructs has been used to suppress gene expression in various organisms. However, the transitive RNA-silencing effect described in plants may preclude the use of RNA silencing for a gene family. Here, we show that, in rice (Oryza sativa), transitive RNA silencing (spreading of double-stranded RNA along the target mRNA) occurred with the green fluorescent protein transgene but not with the endogenous phytoene desaturase gene. We fused IR copies of unique 3' untranslated regions derived from the rice OsRac gene family to a strong promoter and stably introduced them into rice. Each of the seven members of the OsRac gene family was specifically suppressed by its respective IR construct. We also examined IR constructs in which multiple 3' untranslated regions were fused and showed that three members of the OsRac gene family were effectively suppressed by a single construct. Using highly conserved regions of the two members of the OsRac gene family, we also suppressed the expression of all members of the gene family with variable efficiencies. These results suggest that RNA silencing is a useful method for the functional analysis of gene families in rice and other plants.     

Intraoperative cytologic diagnosis of sentinel node metastases in breast cancer

OBJECTIVE: To clarify the usefulness of imprint cytology for intraoperative investigations of sentinel lymph nodes in breast cancer, comparing the results with those of examinations using frozen and permanent sections. STUDY DESIGN: The material consisted of 303 sentinel lymph nodes from 124 cases of clinically node negative breast cancer. Touch imprint cytologic slides and frozen sections were obtained from the same cut surface of the sentinel nodes. Correlations with the final histopathologic results in paraffin sections were evaluated. RESULTS: The sensitivity, specificity and accuracy of imprint cytology were 70.3%, 99.6% and 96.0%, and those of frozen sections were 83.8%, 100%, 98.0%, respectively. The values were improved when the 2 methods were combined (89.2%, 99.6%, 98.3%), though the concordance between imprint cytology and frozen section was 91.9%. CONCLUSION: Both imprint cytology and frozen section are useful for evaluating sentinel lymph node status in breast cancer. However, the 2 techniques should be combined to improve the diagnostic sensitivity.     

Prognostic markers in histologic and cytologic specimens of breast cancer

OBJECTIVE: To correlate histologic and cytologic specimens of breast cancer by the expression of prognostic factors, such as estrogen receptor (ER), progesterone receptor (PR) and c-erbB-2, with immunochemical staining. STUDY DESIGN: Cytologic and histologic specimens from 83 patients were analyzed for expression of ER and PR, and 30 cases were analyzed for overexpression of c-erbB-2 using a standard immunochemical method. The material used for immunocytochemical staining was taken from the needle and syringe after each aspiration and smear preparation. The material was washed into a small container with preservative solution. Immunohistochemical staining was performed on paraffin-embedded specimens. RESULTS: A significant association was found between the histologic specimens and cytologic specimens by means of the expression of immunochemical markers. The best correlation between cytologic and histologic specimens was found when using c-erbB-2. CONCLUSION: A reliable and rapid evaluation of markers for breast cancer can be achieved by immunocytochemical staining on cytologic material. A good association was found between histologic and cytologic specimens using immunostaining.     

100% rapid rescreening for quality assurance in a quality control program in a public health cytologic laboratory

OBJECTIVE: To verij5 the efficacy of the quality control (QC) program in a cytologic laboratwy with a rapid rescreening (RR) protocol. STUDY DESIGN: RR, according to the Turret RR method, of all samples initially screened as negative at the Laboratory of Cytology, Adolfo Lutz Institute, was performed. The slides were reviewed for 60 seconds. Suspect smears were fully checked by 2 reviewers to determine the final diagnoses. A total of 2954 sequential cytologic results were considered in this study. Of the 2954, 2568 (86.9%) were considered initially negative according to our internal QC, and these cases underwent RR. Also, 10% were randomly selected from these negative cases for full reviewing. The internal QC in our laboratory includes review of cases selected according to clinical and cytomorphologic criteria. RESULTS: Among the 2954 total cases, QC detected 386 (13%) atypias with final diagnoses reported according to The Bethesda System 2001 as follows: 82 (2.18%) low grade squamous intraepithelial lesions (LSILs), 35 (1.18%) high grade squamous intraepithelial lesions (HSILs), 2 (0.06%) squamous cell carcinomas, 105 (3.5%) atypical cells of undetermined significance (ASC-US), 4 (0.12%) atypical endocervical cells (AECs) and 158 (5.3%) unsatisfactory samples. RR of 2568 smears initially considered negative selected 194 (7.5%) slides. Of the 194, 146 (75.3%) were negative, 28 (14.4%) ASC-US, 5 (2.6%) AEC, 1 (0.5%) LSIL and 14 (7.2%) unsatisfactory. Full review of a 10% random fraction of the 2568 cases interpreted as negative did not detect lesions but did detect 5 (1.95%) unsatisfactory samples. CONCLUSION: Internal QC used in our laboratory based on clinical and cytomorphologic criteria to select cases for review proved to be an efficient method of detecting HSIL and cervical cancer. The consensus basis of this program strongly limits the false positive and false negative rates and also provides subjects with continuing education. One hundred percent RR is more efficient than 10% full reviewing in detecting cervical abnormalities.