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Background/aims: The aim of the present study was to investigate whether pancreas cyst fluids should be divided into two for cytological diagnosis and biochemical tests., Materials and Methods: The present study was conducted with fluids aspirated from 12 pancreas cysts. The fluids were divided into two and sent to the cytopathology (fluid 1) and biochemistry (fluid 2) laboratories. Fluid 1 was centrifuged at the cytopathology laboratory. Cytology slides were prepared from the deposit, and the supernatant was sent to the biochemistry laboratory. Fluid 2 was centrifuged at the biochemistry laboratory, and amylase, carcinoembryonic antigen, and cancer antigen 19.9 levels were determined in the supernatant. These procedures were repeated for fluid 1 from the cytopathology laboratory. The remaining fluid 2 was sent to the cytopathology laboratory. Fluid 1-like slides were prepared from fluid 2 in the cytopathology laboratory. Cytological diagnoses of fluid 1 and fluid 2 were compared, and the Pearson correlation coefficient for biochemical test results was identified., Results: 92% of fluid 1 and 50% of fluid 2 were diagnostic. Biochemical test results of fluid 1 and fluid 2 were similar, and the Pearson correlation coefficient was high., Conclusion: Our results showed that pancreatic cyst fluids did not need to be divided into two for cytological diagnosis and biochemical tests. Following centrifugation of the whole fluid at the cytopathology laboratory, the deposit and the supernatant can be used for cytological diagnosis and for biochemical tests, respectively. With this protocol, the sensitivity of cytological diagnoses and biochemical tests of pancreatic cyst fluids may increase.

Background and Objective: Digital scanners are being increasingly adopt-ed in anatomical pathology, but there is still a lack of a standardized whole slide image (WSI) format. This translates into the need for interoperability and knowledge representation for shareable and computable clinical information. This work describes a robust solution, called Visilab Viewer, able to interact and work with any WSI based on the DICOM standard., Methods: Visilab Viewer is a web platform developed and integrated alongside a proposed web architecture following the DICOM definition. To prepare the information of the pyramid structure proposed in DICOM, a specific module was defined. The same structure is used by a second module that aggregates on the cache browser the adjacent tiles or frames of the current user's viewport with the aim of achieving fast and fluid navigation over the tissue slide. This solution was tested and compared with three different web viewers, publicly available, with 10 WSIs., Results: A quantitative assessment was performed based on the average load time per frame together with the number of fully loaded frames. Kruskal-Wallis and Dunn tests were used to compare each web viewer latency results and finally to rank them. Additionally, a qualitative evaluation was done by 6 pathologists based on speed and quality for zooming, panning and usability. The proposed viewer obtained the best performance in both assessments. The entire architecture proposed was tested in the 2nd worldwide DICOM Connectathon, obtaining successful results with all participant scanner vendors., Conclusions: The online tool allows users to navigate and obtain a correct visualization of the samples avoiding any restriction of format and localization. The two strategical modules allow to reduce time in displaying the slide and therefore, offer high fluidity and usability. The web platform manages not only the visualization with the developed web viewer but also includes the insertion, manipulation and generation of new DICOM elements. Visilab Viewer can successfully exchange DICOM data. Connectathons are the ultimate interoperability tests and are therefore required to guarantee that solutions as Visilab Viewer and its architecture can successfully exchange data following the DICOM standard. Accompanying demo video. (Link to Youtube video.)., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: This systematic review aimed to analyze the published evidence for the use of oral brush cytology for the early detection of oral cancer and oral potentially malignant disorders (OPMDs)., Methods: Literature was systematically searched through several databases: MEDLINE, EMBASE, PubMed, SCOPUS, Cochrane Library, and Web of Science. Additional review was performed through cross-checks on the bibliographies of selected articles. The inclusion criteria involved studies assessing the utility of oral brush cytology on human tissues and its applications in the diagnosis, screening, or surveillance of oral cancer or OPMDs., Results: The search strategy resulted in 343 abstracts or full-text articles, of which 36 met the inclusion criteria. The year of publication ranged from 1994 to 2017, and a total of 4302 samples from OPMDs, oral squamous cell carcinoma, and healthy controls have been investigated. Baby toothbrush, cytobrush, OralCDx ® , and Orcellex ® are the brushes that were used to obtain transepithelial mucosal samples for conventional and liquid-based cytology evaluation., Conclusions: Findings from this study indicate that meaningful evidence-based recommendations for the implementation of a minimally invasive technique to be utilized as an adjunctive tool for screening and early detection of oral cancer and OPMDs are complicated from the reported studies in the literature. There is need for well-designed clinical studies to assess the accuracy of oral brush cytology utilizing validated cytological assessment criteria for the diagnosis and prediction of OPMDs., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Mass cytometry allows high-resolution dissection of the cellular composition of the immune system. However, the high-dimensionality, large size, and non-linear structure of the data poses considerable challenges for the data analysis. In particular, dimensionality reduction-based techniques like t-SNE offer single-cell resolution but are limited in the number of cells that can be analyzed. Here we introduce Hierarchical Stochastic Neighbor Embedding (HSNE) for the analysis of mass cytometry data sets. HSNE constructs a hierarchy of non-linear similarities that can be interactively explored with a stepwise increase in detail up to the single-cell level. We apply HSNE to a study on gastrointestinal disorders and three other available mass cytometry data sets. We find that HSNE efficiently replicates previous observations and identifies rare cell populations that were previously missed due to downsampling. Thus, HSNE removes the scalability limit of conventional t-SNE analysis, a feature that makes it highly suitable for the analysis of massive high-dimensional data sets.

This review tackles the issues related to disease burden caused by cervical cancer (CC) and its precursor (CIN) lesions in Brazil. A special focus is given to new technologies with potential to interfere with the development of CC by reducing the high-risk human papillomavirus (hr-HPV)-induced lesions that remain a major public health burden in all developing countries where organized screening programs do not exist. Globally, 85% of all incident CC and 50% of CC deaths occur in the developing countries. Unfortunately, most regions of Brazil still demonstrate high mortality rates, ranking CC as the second most common cancer among Brazilian women. Recently, CC screening programs have been tailored in the country to enable early detection of CC precursor lesions and thereby reduce cancer mortality. A combination of HPV testing with liquid-based cytology (LBC) seems to be a promising new approach in CC screening, with high expectation to offer an adequate control of CC burden in this country.

Microscopy (skill of using a microscope) and the concepts of cytology (study of cells) and histology (study of tissues) are most often taught in professional veterinary medicine programs through the traditional method of glass slides and light microscopes. Several limiting factors in veterinary training programs are encouraging educators to explore innovative options for teaching microscopy skills and the concepts of cytology and histology. An anonymous online survey was administered through the Colorado Veterinary Medical Association to Colorado veterinarians working in private practice. It was designed to assess their current usage of microscopes for cytological and histological evaluation of specimens and their perceptions of microscope use in their veterinary education. The first part of the survey was answered by 183 veterinarians, with 104 indicating they had an onsite diagnostic lab. Analysis pertaining to the use of the microscope in practice and in veterinary programs was conducted on this subset. Most respondents felt the amount of time spent in the curriculum using a microscope was just right for basic microscope use and using the microscope for viewing and learning about normal and abnormal histological sections and clinical cytology. Participants felt more emphasis could be placed on clinical and diagnostic cytology. Study results suggest that practicing veterinarians frequently use microscopes for a wide variety of cytological diagnostics. However, only two respondents indicated they prepared samples for histological evaluation. Veterinary schools should consider these results against the backdrop of pressure to implement innovative teaching techniques to meet the changing needs of the profession.

Background: The use of immunocytochemistry as an important ancillary technique for the workup of fine-needle aspiration (FNA) specimens is an important component in the daily practice of cytopathology. Although cell block preparations are commonly used, immunocytochemistry cannot be completed if the cell blocks are hypocellular. As an alternative approach when conventional cell blocks fail, immunocytochemistry can be performed on cell-transferred direct smears. Multiple immunostains can be applied to a single direct smear using the cell transfer technique (CTT)., Methods: A retrospective review of all FNA cases performed at the study institution over a 3-year period was conducted. All cases in which CTT was used for immunocytochemistry were identified. The contribution of CTT to the final diagnosis in these cases was assessed., Results: CTT was used in 152 of the 11,259 FNAs performed. A total of 431 immunocytochemistry stains, including 46 different antibodies, were performed using CTT. In 118 of 150 cases, the immunocytochemistry results contributed significantly to the final diagnosis. It provided no added value in the remaining 32 cases and failed in 2 cases., Conclusions: CTT is a very useful tool for the workup and diagnosis of FNA specimens when conventional cell blocks lack adequate cellularity. Although CTT was used in only 1.4% of FNA cases in the current study, it contributed to the final diagnosis in 79% of the cases in which it was used. For these patients, CTT reduced the need for repeat FNAs, thereby reducing potential patient morbidity and health care costs., (© 2014 American Cancer Society.)

Objective: Women treated for high-grade cervical disease (cervical intraepithelial neoplasia grade 2 or grade 3 [CIN2/3]) face a significant risk of developing post-treatment disease. Therefore, in most European countries, they are monitored by cytologic testing at 6, 12, and 24 months after treatment. Although testing for high-risk types of the human papillomavirus (hrHPV) in the follow-up seems to be a valuable supplementary method, its use is not yet fully explored., Methods: Besides reviewing the literature, we completed a long-term follow-up study describing the cumulative risk for CIN2/3 or cancer (CIN2+) of different hrHPV and cytology test results after treatment., Conclusions: High-risk HPV testing improves the sensitivity to detect posttreatment CIN2/3 (relative sensitivity=1.15, 95% confidence interval [CI]=1.06-1.25), but the highest sensitivity (95%, 95% CI=91%-98%) is reached by performing cotesting (both cytology and hrHPV). The CIN2+ risk after a single negative cotesting result taken 6 months after treatments was similar to the risk after 3 consecutive negative cytologic test results (5-y CIN2+ risk being 3.0% [95% CI=1.5%-6.1%] and 2.9% [95% CI=1.2%-7.1%], respectively). Women who test negative for cotesting at both 6 and 24 months after treatment have a minimal risk of developing CIN3+ in the next 5 years (0.0%, 95% CI=0.0%-3.0%)., Recommendations: We propose a new posttreatment surveillance protocol, consisting of combined testing with both cytology and hrHPV at 6 and 24 months after treatment. After 2 negative cotesting results, women should be retested after 5 years.

Electronic ordering systems have the potential to enhance the efficient utilisation of pathology services. The aim of this study was to assess the effect of electronic pathology ordering on repeat test ordering for paediatric patients (ages 0 to 18 years) who were in intensive care units (ICUs) and non-ICU wards. The dataset described 85,728 pathology tests ordered for 5,073 children before and after the implementation of electronic ordering. This study showed that, for children in ICUs, the repeat test order rate was significantly lower for electronic orders than for paper-based orders. Similarly, the rate of repeat tests ordered within short intervals (up to 23-hours), for children older than one-year in non-ICU wards, was lower for electronic ordering than for paper ordering. The proportion of repeat tests occurring within one-hour of the previous test was consistently lower for tests ordered using electronic ordering than it was for tests ordered using the paper based system for patients older than one-year in all wards and for patients under one-year in ICUs. These results suggest that features of the electronic system, including alerts about previously ordered tests and the availability of information about previous orders, can help clinicians to identify and reduce unnecessary repeat tests.

Background: The National Cervical Screening Program in Australia currently recommends that women aged 18-69 years are screened with conventional cytology every 2 years. Publicly funded HPV vaccination was introduced in 2007, and partly as a consequence, a renewal of the screening program that includes a review of screening recommendations has recently been announced. This study aimed to provide a baseline for such a review by quantifying screening program resource utilisation and costs in 2010., Methods: A detailed model of current cervical screening practice in Australia was constructed and we used data from the Victorian Cervical Cytology Registry to model age-specific compliance with screening and follow-up. We applied model-derived rate estimates to the 2010 Australian female population to calculate costs and numbers of colposcopies, biopsies, treatments for precancer and cervical cancers in that year, assuming that the numbers of these procedures were not yet substantially impacted by vaccination., Results: The total cost of the screening program in 2010 (excluding administrative program overheads) was estimated to be A$194.8M. We estimated that a total of 1.7 million primary screening smears costing $96.7M were conducted, a further 188,900 smears costing $10.9M were conducted to follow-up low grade abnormalities, 70,900 colposcopy and 34,100 histological evaluations together costing $21.2M were conducted, and about 18,900 treatments for precancerous lesions were performed (including retreatments), associated with a cost of $45.5M for treatment and post-treatment follow-up. We also estimated that $20.5M was spent on work-up and treatment for approximately 761 women diagnosed with invasive cervical cancer. Overall, an estimated $23 was spent in 2010 for each adult woman in Australia on cervical screening program-related activities., Conclusions: Approximately half of the total cost of the screening program is spent on delivery of primary screening tests; but the introduction of HPV vaccination, new technologies, increasing the interval and changing the age range of screening is expected to have a substantial impact on this expenditure, as well as having some impact on follow-up and management costs. These estimates provide a benchmark for future assessment of the impact of changes to screening program recommendations to the costs of cervical screening in Australia.

Microarrays are promising tools for cell isolation and detection. However, they have yet to be widely applied in biology. This stems from a lack of demonstration of their sensitivity and compatibility with complex biological samples, and a lack of proof that their use does not induce aberrant cellular effects. Herein, we characterized and optimized a recently developed technology associating antibody microarrays with surface plasmon resonance imaging (SPRi). Using a murine macrophage cell line we demonstrate the binding specificity of our antibody-microarrays and the correlation between SPRi signals and both the number of bound cells, and the level of expression of cell surface markers. Confocal microscopy reveals that cell binding to the chip through antibody-antigen interactions underwent morphological changes reflecting the density of the relevant cell surface marker without affecting cell viability as shown by fluorescent microscopy. The detection threshold of the microarray-SPRi system is lowered 10-fold by applying a polyethylene oxide film to the gold surface of the chip. This increased sensitivity allows the detection of cells representing as little as 0.5% of a mixed population. The potential of this method is illustrated by two applications: characterization of ligand-cell receptor interactions, allowing determination of receptor specificity, and analysis of peripheral blood mononuclear cells, demonstrating the suitability of this tool for the analysis of complex biological samples., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: To determine whether high-risk patients with hematuria receive evaluation according to guideline recommendations., Methods: We recently performed a screening study for bladder cancer using a urine-based tumor marker in 1502 subjects at high risk based on aged > or = 50 years, > or = 10-year smoking history, and/or a 15-year or more environmental exposure. We evaluated use of urinalysis (UA) within 3 years preceding the screening study. Chart review was performed to determine if this subset with microhematuria received any additional evaluation., Results: Of 1502 study participants, routine urinalysis was performed in 73.2% and 164 (14.9%) subjects had documented hematuria (>3 red blood cells / high-power field) before inclusion. Of these, 42.1% had no further evaluation. Additional testing included repeat urinalysis (36%), urine culture (15.2%), cytology (10.4%), imaging (22.6% overall: 15.9% computed tomography, 4.3% intravenous pyelography; 2.4% magnetic resonance imaging), and cystoscopy (12.8%). Three subjects with microscopic hematuria (2%) were subsequently found to have bladder cancer during the screening study but were not referred for evaluation based on their hematuria. The source of hematuria was unknown in 65%, infection in 22%, benign prostatic enlargement in 10%, and renal stone disease in 4%, but these results are based on incomplete evaluation since only 12.8% underwent cystoscopy., Conclusions: Subjects at high risk for bladder cancer based on > or = 10 years of smoking or environmental exposure with microscopic hematuria are rarely evaluated thoroughly and only 12.8% were referred for urologic evaluation. Further studies are needed to evaluate both the utilization and effectiveness of guidelines for hematuria.

Objective: The purpose of this study was to examine the utility of SurePath-liquid-based cytology (LBC) compared to conventional cytological preparations (CCP) in the identification of endometrial carcinoma., Methods: During a 13-month period, direct endometrial samples were collected from 120 patients using the Uterobrush. The material comprised 30 cases each of endometrial carcinoma, proliferative endometrium, secretory endometrium and atrophic endometrium. The following points were investigated:(i) the frequency of cell clumps in endometrial carcinoma; (ii) the area of cell nuclei; (iii) overlapping nuclei., Results: (i) Comparison of the frequency of cell clumps with irregular protrusion pattern and papillo-tubular pattern showed no statistically significant difference in either type of cell clump between CCP and LBC. (ii) Comparison of the nuclear area of cells showed a sequential decrease from endometrial carcinoma to secretory endometrium, to proliferative endometrium and to atrophic endometrium, which was significant in CCP and LBC. (iii) Nuclear area was significantly lower with LBC compared with CCP in endometrial carcinoma, secretory endometrium and proliferative endometrium but not atrophic endometrium. (iv) Comparison of the degree of overlapping nuclei showed a sequential decrease from endometrial carcinoma to proliferative endometrium, to secretory endometrium and to atrophic endometrium, which was significant in both CCP and LBC. (v) Comparison of the degree of overlapping nuclei between CCP and LBC showed no significant difference for normal types of endometrium, but LBC had significantly higher values (P < 0.0001) in endometrial carcinoma than in CCP., Conclusions: The results of this study revealed that applying diagnostic criteria used in CCP to LBC was easy to achieve, because LBC had excellent cytoarchitectural preservation and cells were well presented. Although we have not examined all cytological features of malignancy and have not considered atypical hyperplasia, we believe that this method may be a useful tool in the diagnosis of endometrial cytology.

Background: P16(INK4a) is a biomarker for transforming HPV infections that could act as an adjunct to current cytological and histological assessment of cervical smears and biopsies, allowing the identification of those women with ambiguous results that require referral to colposcopy and potentially treatment., Material and Methods: We conducted a systematic review of all studies that evaluated the use of p16(INK4a) in cytological or histological specimens from the uterine cervix. We also estimated the mean proportion of samples that were positive for p16(INK4a) in cytology and histology, stratified by the grade of the lesion., Results: Sixty-one studies were included. The proportion of cervical smears overexpressing p16(INK4a) increased with the severity of cytological abnormality. Among normal smears, only 12% (95% CI: 7-17%) were positive for the biomarker compared to 45% of ASCUS and LSIL (95% CI: 35-54% and 37-57%, respectively) and 89% of HSIL smears (95% CI: 84-95%). Similarly, in histology only 2% of normal biopsies (95% CI: 0.4-30%) and 38% of CIN1 (95% CI: 23-53%) showed diffuse staining for p16(INK4a) compared to 68% of CIN2 (95% CI: 44-92%) and 82% of CIN3 (95% CI: 72-92%)., Conclusion: Although there is good evidence that p16(INK4a) immunostaining correlates with the severity of cytological/histological abnormalities, the reproducibility is limited due to insufficiently standardized interpretation of the immunostaining. Therefore, a consensus needs to be reached regarding the evaluation of p16(INK4a) staining and the biomarker needs to be assessed in various clinical settings addressing specific clinical questions.

Objectives: To establish the proportion of cytology samples sent to a commercial veterinary laboratory that yields diagnostically useful information in the context of current use and perceptions of cytology., Methods: Nine hundred and forty-five cytology submissions were retrospectively collected and categorised according to diagnostic utility. A survey into the use and perceptions of cytology was distributed at the British Small Animal Veterinary Association Congress 2008., Results: A specific diagnosis was reached in 23.1 per cent of samples and a cytological diagnosis in 35.3 per cent. 22.4 per cent of samples yielded some useful information, but 19.2 per cent were unacceptable. Seventy-four participants in the survey took an average of 3.9 cytological samples per week, of which they examined 27.0 per cent in-house only, 21.6 per cent in-house before sending to an external laboratory and 51.4 per cent were sent externally without prior examination. "To obtain a definitive diagnosis" was the principal reason cited for performing cytology., Clinical Significance: Results suggest that cytology is underused and may be applied in an inappropriate context in the UK. It is hoped that illustrating the diagnostic outcome of samples received by a commercial laboratory will encourage increased, appropriate use of cytology.

Background: Tumor budding along the advancing front of colorectal adenocarcinoma is an early event in the metastatic process. A reproducible, prognostic budding scoring system based on outcomes in early stage colorectal cancer has not been established., Design: One hundred twenty-eight T3N0M0 colorectal carcinoma patients with known outcome were identified. Tumor budding was defined as isolated tumor cells or clusters of <5 cells at the invasive tumor front. Tumor bud counts were generated in 5 regions at 200x by 2 pathologists (conventional bud count method). The median bud count per case was used to divide cases into low (median=0) and high budding (median > or =1) groups. Forty cases were reevaluated to assess reproducibility using the conventional and a novel rapid bud count method., Results: Fifty-seven (45%) carcinomas had high and 71 (55%) had low budding scores. High budding was associated with an infiltrative growth pattern (P<0.0001) and lymphovascular invasion (P=0.005). Five-year cancer-specific survival was significantly poorer in high compared with low budding groups: 63% versus 91%, respectively, P<0.0001. Multivariate analysis demonstrated tumor budding to be independently prognostic (hazard ratio=4.76, P<0.001). Interobserver agreement was at least equivalent comparing the conventional to the rapid bud count methods: 87.5% agreement (kappa=0.75) versus 92.5% agreement (kappa=0.85), respectively., Conclusions: Tumor budding is a strong, reproducible, and independent prognostic marker of outcome that is easily assessed on hematoxylin and eosin slides. This may be useful for identifying the subset of T3N0M0 patients at high risk of recurrence who may benefit from adjuvant therapy.

Background: The impact of meningeal dissemination in primary CNS lymphoma (PCNSL) is debated, and the reported frequency varies. We prospectively evaluated the diagnostic value of PCR in comparison with CSF cytomorphology and MRI for diagnosing meningeal dissemination in PCNSL., Methods: We evaluated 282 patients from a multicenter therapy study for PCNSL for the presence of meningeal dissemination: 205 with CSF cytomorphology, 171 with PCR of the rearranged immunoglobulin heavy-chain genes in CSF, and 217 with cranial MRI., Results: Meningeal dissemination was found in 33 of 205 patients (16%) by cytomorphology, in 19 of 171 (11%) patients evaluated by PCR, and in 8 of 217 patients (4%) by MRI. Considering either of these methods, the relative frequency of meningeal dissemination was 17.4% (49 of 282 patients). PCR was monoclonal in 6 of 19 (32%) samples with positive cytomorphology, 1 of 13 samples (8%) with suspicious cytology, and in 10 of 105 (10%) cytologically negative samples. In 11 samples with positive and 12 with suspicious cytology, PCR showed only a polyclonal pattern. The probability of meningeal dissemination detection was higher in cases with CSF pleocytosis (>5/microL) with an OR of 2.48 (95% CI 1.15-5.34, p = 0.018). CSF protein had no predictive value for meningeal dissemination detection., Conclusions: We found a low rate of meningeal dissemination in primary CNS lymphoma in this large prospective study. The rate of discordant PCR and cytomorphologic results was high. Thus, the methods should be regarded as complementary. CSF pleocytosis had predictive value for meningeal dissemination detection.

Objective: To determine the utility of imprint cytology (IC) in providing an early presumptive diagnosis of clinically suspected cervical carcinoma., Study Design: A total of 219 clinically suspicious cervical cancer cases underwent Pap test, punch biopsy and IC at the same sitting. Correlations were performed between these diagnostic modalities to determine the sensitivity and specificity of IC in diagnosis of cervical cancer., Results: The overall accuracy of IC in detecting cervical cancers was 96.2%. About 78% of squamous cell carcinomas (SCC), 60% of adenocarcinomas and 100% of small cell carcinoma could be accurately typed on imprints. Twelve malignant lesions were diagnosed on IC among 26 unsatisfactory biopsies. Although there was no false positive result, 3.5% false negative diagnoses were given on IC. The sensitivity and specificity of imprint smear cytology to detect malignancy was 96.2% and 100%. Agreement between imprint cytology and Pap smear diagnosis of malignancy was 95.3%. kappa Statistics revealed excellent agreement between imprints and biopsies and between imprints and Pap smears in diagnosis of malignant lesions., Conclusion: IC can be used as an adjunctive technique for an early and reliable preliminary presumptive diagnosis of cancer of the uterine cervix.

The human superior parietal cortex (SPC; Brodmann areas [BA] 5 and 7) comprises the superior parietal lobule and medial wall of the intraparietal sulcus (mIPS) laterally and the posterior paracentral lobule and precuneus medially. Receptor autoradiographic and functional studies indicate more complex segregations in the SPC than suggested by Brodmann (1909). Differences to other historical maps may be due to anatomical variability between brains and different definition criteria for areas. To provide a reliable anatomical reference of the SPC, we performed an observer-independent cytoarchitectonic mapping of this region in 10 human postmortem brains. Cytoarchitecture was analyzed in cell-body-stained brain sections using gray-level index profiles. Multivariate statistical analysis of profile shape allowed the exact localization of cytoarchitectonic borders and quantification of interareal differences. We identified 3 areas in BA 5 (5L, 5M, and 5Ci), 4 in BA 7 (7PC, 7A, 7P, and 7M), and 1 in the anterior mIPS (hIP3). Locations of their borders relative to macroanatomical landmarks varied considerably between brains and hemispheres. Cytoarchitectonic profiles of areas 5Ci and hIP3 differed most from those of the remaining areas, and differences between subareas were stronger in BA 5 than in BA 7. These areas are possible structural correlates of functional segregations within the SPC.

This study aimed to document current cervical cancer screening practices of physicians in Korea. Questionnaires were distributed to 852 Korean obstetricians and gynecologists, who attended the 91st Conference of the Korean Society of Obstetrics and Gynecology held during May, 2005. Questionnaires were returned by 30.6% (260/852) of the recipients and 254 of these were eligible for analysis. Sixty-seven percent started cervical cancer screening women at age 20, and 65% replied that they would continue annual screening in a 35-yr-old woman with three consecutive normal cytologic tests. Over 65% of respondents preferred conventional cytologic screening to liquid-based cytology. The cost was a major determinant for selecting screening method. Fifty-three percent used the human papillomavirus DNA test as a triage for atypical squamous cells of undetermined significance. Our findings suggest that majority of Korean obstetricians and gynecologists in hospital prefer annual conventional cytologic testing to liquid-based cytology for financial reason.

Objective: To evaluate the performance of the conventional Pap test and liquid-based cytology (LBC) in an ongoing multicenter trial testing optional screening tools (cytology, screening colposcopy, visual inspection with acetic acid, visual inspection with Lugol's Iodine, cervicography and Hybrid Capture II [HCII] (Digene Brazil, São Paulo, Brazil) conventional and self-sampling), for cervical cancer in Brazil and Argentina., Study Design: A cohort of 12,107 women attending four clinics (Campinas, São Paulo, Porto Alegre, Buenos Aires) were randomized into the 8 diagnostic arms. Women testing positive with any of the tests were referred for colposcopy, and cervical biopsies were used as the gold standard to assess performance characteristics of the diagnostic tests. Conventional Pap smears were sampled by all clinics (n = 10,240), and LBC (Autocyte PREP, [TriPath Imaging, Burlington, North Carolina, U.S.A.], n=320, and DNA-Citoliq [Digene Brazil], n =1,346) was performed by 1 of the clinics., Results: Conventional Pap smears showed no squamous intraepithelial lesions (normal) in 8,946 (87.4%) and LBC in 1,373 (82.4%). Using high grade squamous intraepithelial lesions (HSIL) as the cutoff, Pap smears predicted high grade (cervical intraepithelial neoplasia [CIN] 3) with OR 63.0 (95% CI, 36.90-107.70), standard error (SE) 59%, SP 97.8%, positive predictive value (PPV) 68.1% and negative predictive value (NPV) 96.7%. The same figures for Autocyte PREP were: OR 9.0 (95% CI, 2.43-33.24), sensitivity (SE) 33.3%, specificity (SP) 100%, PPV 100% and negative PV (NPV) 88.8%. DNA-Citoliq detected CIN 3 as follows: OR 11.8 (95% CI 2.60-53.26), SE 40.0%, SP 94.6%, PPV 40.0% and NPV 94.6%. Lowering the cutoff to low grade squamous intraepithelial lesions increased SE and NPV but compromised SP and PPV. The detection rates for high grade lesions after an atypical squamous cells of undetermined significance diagnosis were similar with the 3 techniques. In our settings, the 3 methods of cervical cytology were slightly different in performance. The conventional Pap smear had the highest SE, while Autocyte PREP had 100% SP and PPV in detecting CIN3 with the HSIL cutoff. All 3 tests had lower SE but higher SP as compared to HCII.

There is no uniformly accepted definition of a positive margin in breast conserving surgery. In 1999, the Japanese Breast Cancer Society created the Guidelines for Breast-Conserving Treatment (GBCT). At that time, we did a questionnaire survey about the definition of margin status. Although 57.1% of hospitals/institutes used the definition of cancer cells present at the surface, the GBCT adopted the definition of cancer cells present within 5 mm of the surface. Moreover, the GBCT required that the distance between the edge of the cancer cells and the surface be recorded in millimeters when cancer cells were present within 5 mm of the surface. The risk factors for local recurrence after breast-conserving treatment were studied. From 1986 to 1995, 391 patients were treated with breast-conserving surgery at Osaka Medical Center for Cancer and Cardiovascular Diseases. Of these, 35 patients developed local recurrence. Multivariate analysis showed that positive margin (p=0.0002), high degree of ductal proliferative change around the tumor (p=0.0035) and high histological grade (p=0.0041) were significant independent risk factors for local recurrence, while radiation therapy (p=0.0327) significantly reduced local recurrence. There was no significant difference in the risk of local recurrence between the two different definitions of positive margin (tumor present at the surface and tumor present within 5 mm from the surface). It is hoped that more hospitals/institutes will adopt the definition of margin positivity presented by the GBCT and that a practical definition of margin positivity will be established.

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.

Objective: To compare the sputum smear cytology and cell block methods for specimen adequacy, cytology quality and diagnostic accuracy in the diagnosis of lung cancer., Study Design: We assessed 2,524 sputum specimens from 768 patients. The specimens were prepared as smears and cell blocks for cytopathologic examination between March 1, 1992, and December 31, 1998. The smear and cell block slides were evaluated both separately and together, and the results were compared with radiologic and histopathologic diagnoses., Results: The sensitivity of the smear method was 69.4% and specificity was 99.5%. The sensitivity of the cell block method was 84.4% and specificity, 100%. The sensitivity of the smear and cell block together was 87.6% and specificity, 99.5%., Conclusion: The cell block method increases the sensitivity and specificity of sputum cytology, and when smear and cell block slides are evaluated together, sensitivity reaches its highest value. Therefore, application of smear and cell block methods together seems most useful in the diagnosis of lung cancer.

Data from five different Institution of Pathological Anatomy Hospital Services are presented in order to show one (the benchmark) of the multiple existing ways to approach the budget problem and the macroeconomic management of our Services. The aim of this work is not to show the "best" way to work in terms of cost-efficacy but only a methods to compare our results with others. Nevertheless from this study is possible also to make some considerations about medical and technical workload in different services with different habits.

Objective: To study the cellularity of liquid-based preparations (LBPs) for normal, abnormal and false negative cervical cytology cases., Study Design: A series of 1,875 LBPs obtained by a split-sample protocol was examined. Slides had been examined by at least one cytotechnologist. All abnormals were reviewed by at least two cytopathologists. The cellular objects were counted using a fully automated microscope. Cellularity was evaluated for the entire population, normal (< LSIL) slides, abnormal (LSIL+) slides and "false negative" slides. False negatives were identified as those with an initial impression of < LSIL and (1) the reference pathologist's impression of the slide was LSIL+, (2) the simultaneous conventional smear was LSIL+, or (3) a cervical biopsy was LSIL+. Descriptive statistics and graphic comparisons were used., Results: There were 192 confirmed abnormal cases and 1,683 normal cases, of which 53 were false negative. The frequency distributions of cellularity for the entire population and each category were skewed-right nonnormal. Median cell counts of the entire series, normals, abnormals and false negatives were 60,510, 59,822, 70,523 and 64,036 respectively. Cell counts at 2.5 percentiles were 8,677, 7,891, 11,864 and 6,009, respectively. The population of abnormal slides tended to have higher cellularity. The population of false negative slides could not be distinguished by their cellularity., Conclusion: Cellularity does not provide assurance of adequacy. Any cellularity criterion should be based on measurement of the prevalence of abnormal cells on abnormal slides.

Objective: To inventory the diagnostic methods used in patients with clinically occult, radiologically suspect breast lesions., Design: Enquiry., Method: The departments of radiology of all Dutch hospitals were sent a list in January 2000 containing questions concerning the number of thread localizations in 1999 and the use of cytological or histological needle diagnostics with image monitoring prior to surgical intervention in clinically occult, radiologically suspect breast lesions. Of the 120 questionnaires mailed, 74 (62%) were completed and returned by clinics throughout the country., Results: Fifty-one of the 74 hospitals (69%) had prior to operation carried out histological or cytological examinations and in these 51 hospitals this was done in 1743 of the 2857 lesions (61%): fine-needle aspiration cytology was performed in 1046 (/1743 = 60%; /4140 lesions in all 74 hospitals = 25%) and/or histological needle biopsy in 784 (45%; /4140 = 19%)., Conclusion: In less than half of all non-palpable breast abnormalities non-surgical methods of diagnosis are used, histological needle biopsy less often than fine needle aspiration cytology.

The effect of some steroid hormones and their synthetic analogs--dexamethasone, estradiol, progesterone, testosterone, and cytostatics--on the fibroblast nuclei in a monolayer culture was studied. Their proliferation was studied at the same time by the radioindicator method. The method of computerized morphodensitometry with the use of the apparatus-programmer complex DiaMorf (Russia) showed that the compounds under study induce reorganization of interphase chromatin of fibroblast nuclei over the molecules, the amount of which may be recorded by means of the computer system of analysis of cell and tissue images.

The estimation of the malignancy-associated changes in oral mucosa of patients with benign and malignant processes in mammary and thyroid gland is carried out on the basis of textural and densitometric indices of the interphase nuclei of the epitheliocytes with the help of the methods of mathematical statistics.

Our aim was to characterize epithelial cell proliferative activity within the oral cavity and to find out if there were differences between sites with high and low incidence of cancer. A total of 105 samples of clinically normal mucosa were harvested from various intra-oral sites. Excised specimens were incubated in vitro with tritiated thymidine and bromodeoxyuridine to 'double label' cells undergoing DNA synthesis, and enable calculation of the duration of S phase and estimation of variables of cell flux to and from S. Mean labelling indices (percentage of cells within the S phase of the cell cycle) were highest in the floor of mouth (12.3%) and ventral tongue (10.1%), while activity was lowest in the dorsum of tongue (4.3%) and the palate (7.2%), P<0.001. In general, both cell influx and the duration of S increased proportionally to the labelling index. Sites with a high incidence of cancer were characterized by high labelling indices, increased cell influx and a prolonged S phase.

Accurate, predictive assessment of the clinical behaviour and progression of individual oral cancers and premalignant lesions requires reproducible and quantitative analyses of diseased tissue. In this paper we describe the use of in vitro double labelling (sequential tritiated thymidine and bromodeoxyuridine staining of proliferating epithelial cells) to calculate S phase labelling indices (LIs), estimation of S phase duration (tS), and measurement of variables of flux to and from S for excised specimens of oral squamous cell carcinoma, premalignant lesions, and clinically normal mucosa from patients with oral cancer. There was a significant increase in mean LIs in buccal mucosa leukoplakias (14.5%) compared with normal mucosa (10.3%); P = 0.03. LIs were also increased in patients with cancers of the floor of mouth and ventral tongue but neither these changes nor alterations in flux parameters or S Phase durations were significant. Twenty-one kinetic profiles of dysplastic and malignant tissue were compared with conventional histopathological results, however, and these showed a 2.2% increase in LIs with each increase in grade of dysplasia (P = 0.004) and a 12% increase in LIs with each reduction in tumour differentiation (P = 0.02).

Age changes of microstructure of granular layer of the cortex of human cerebellum superior lobe (the area of clivus, posterior lateral regions of right and left tetrangular lobules) were studied in annual intervals from birth up to 20 yrs using computer analysis of optic images. Enlargement of the area of profile fields of cell groups in apical and basal regions of cerebellar folia from birth up to 14-15 yrs and differences between hemispheres in clasterization of granular layer were demonstrated. The data on age changes of cellular aggregations obtained allowed to formulate a hypothesis on autonomic local sensory networks of human cerebellar cortex associated with granular layer of cerebellar cortex that are considered as structural elements of module organization of the latter.

Objective: To determine the feasibility and utility of thin-layer cytology preparations for morphometric analysis of nuclear and cytoplasmic area in cells from nongynecologic cytology specimens., Study Design: Identical paired samples from nongynecologic specimens (bronchial aspirate, urine, pleural and peritoneal fluid) were used to prepare thin-layer preparations and corresponding traditional membrane filter preparations. The paired preparations were analyzed by static image morphometry measuring eight nuclear and cytoplasmic parameters that allowed calculation of nuclear area, cytoplasmic area and total cell size. Hepatocytes and bronchial columnar, mesothelial, squamous and transitional cells were studied, as was a single case of high grade transitional cell carcinoma. Sufficient numbers of each cell type were measured to allow statistical analysis., Results: Both thin-layer and membrane filter preparation techniques yielded individual cells suitable for morphometric analysis, and there were no consistent morphologic measurement differences between the two methods. The thin-layer preparation had the following significant technical advantages: more numerous easily measured single cells, lack of interfering background and superior specimen stability. Benign oval to round nuclei from a variety of cell types have a mean nuclear area in a narrow range from 29 to 55 microns 2. The mean nuclear area of malignant cells studied was significantly larger (78 microns 2), and there was a significant decrease in absolute cytoplasmic profile area in the malignant population studied., Conclusion: Thin-layer cytology preparations have significant advantages for morphometric studies over traditional membrane filter cytologic preparations. The morphometric measurement of nuclear area in benign and malignant cell populations has great potential as a generic screening tool for malignancy in cytologic specimens. Simultaneous measurement of cytoplasmic area adds a powerful dimension. The subsequent calculation of a true nuclear/cytoplasmic ratio may yield a sensitive and specific discriminator for detecting malignant cell populations in human nongynecologic cytology specimens.

Cytologic evaluation of nongynecologic tissues is a widely accepted diagnostic modality commonly used in the clinical evaluation of living patients. Fine needle aspiration (FNA) of superficial masses and touch preparations of surgical specimens often yield diagnostic results. The adjunctive role of these two techniques during postmortem examination has not been adequately addressed. A prospective study was carried out on a series of 13 patients undergoing postmortem examination. FNA was performed in a standard manner to obtain tissue fragments from superficial masses in three cases. Visceral lesions grossly suspicious for cancer were scraped and smeared onto glass slides to create a "touch prep" in 10 cases. Cytologic evaluation of alcohol-fixed, hematoxylin and eosin (H&E)-stained slides was performed in each case. Cytologic diagnoses were subsequently correlated with histologic sections. In the majority of cases, cytologic material was diagnostic. Touch prep slides, in combination with gross findings, were diagnostic of primary and metastatic carcinoma in visceral lesions. FNA of superficial masses accurately assessed local recurrences of carcinoma and nodal metastases. Both methods yielded diagnoses within minutes, in contrast to the time required to process routine histologic sections. Cytologic evaluation of tissues obtained at autopsy provides accurate, inexpensive, and rapid diagnostic information. The touch prep is an inexpensive adjunct to histologic sections in documenting the presence of carcinoma or the extent of metastatic disease found at autopsy, and its further application can strengthen the standard applied in clinicopathologic diagnosis.

This survey describes the results of a questionnaire on the methodology of sperm morphology assessment. A questionnaire form was sent to 410 fertility centres. A total of 170 answer forms (41.5%) from 40 different countries was evaluated. Most responding centres (147 or 86.5%) treat more than 200 new couples per year. According to our results, a wide and complex variation in different methods of sperm preparation, staining procedures and classification systems is observed world wide. WHO recommendations for sperm preparation seem to be poorly followed. Only 86 centres (50.6%) reported the use of a single approach to both semen preparation and sperm morphology evaluation. Our results indicate an urgent need for standardization and consensus on sperm morphology methodology to regain the power of this important sperm parameter.

Objective: To assess the effect of modifications made in the Micro-Cell sperm counting chamber on the motility of washed human spermatozoa., Design: In a 2 x 2 experimental design, human sperm samples were washed with or without protein supplementation, loaded into modified or unmodified Micro-Cell chambers, and assessed by automated semen analysis for changes associated with sperm adhesion to the glass chamber surfaces., Participants: Twenty-one men who were undergoing semen analysis and presented with > or = 50% motile sperm, or normal donors., Main Outcome Measures: Reduced motility and elevated lateral head displacement associated with sperm adhesion to glass surfaces were compared using a doubly repeated measures analysis of variance., Results: Addition of protein to the sperm washing solution partially reversed the adhesion of spermatozoa to the glass of unmodified Micro-Cell chambers. Chambers manufactured to reduce cell adhesion to glass surfaces yielded the highest motility and lowest lateral head displacement, whether the sperm were washed in a solution supplemented with or without protein., Conclusion: These findings indicate that, as in raw semen, kinematics of washed sperm can be measured reliably in the modified Micro-Cell chamber.

Endoscopic retrograde brush cytology is useful for the evaluation of biliary strictures. Access across a stricture can be maintained by removing the cytology brush while leaving the sheath in the bile duct. We examined the potential for loss of diagnostic cellular material in this setting using the canine biliary system. Twenty consecutive samples were randomly collected by (1) pushing the brush from the end of the sheath or (2) pulling the brush through the length of the sheath. Slides prepared from cell suspensions were scored by a cytopathologist blinded to the collection method. Pulling the brush resulted in a significant loss of cellular material (p < 0.001). In a second phase, 23 consecutive samples were randomly obtained in the same fashion. Combining salvage cytology of material from the sheath with cytology of the pulled-brush specimens produced cellular yields similar to those of specimens obtained by pushing the brush from the sheath. If the brush is pulled from the sheath during bile duct brush cytology, we suggest that salvage cytology be performed in order to maximize the diagnostic sensitivity.

Deformation properties of erythrocytes have been studied using osmotic gradient ectacytometric procedure in rats with spontaneous hereditary hypertension (SHR), normal tension rats from Wistar-Kyoto strain and albino rats from Wistar strain. It was shown that high intrinsic viscosity and, to a less extent, changes in their form account for the increased rigidity of the erythrocytes from SHR rats. No significant changes in visco-elastic properties of the membrane were found. The degree of hydration of haemoglobin significantly increases in the order SHR-WKY-Wistar.