Optimum web viewer application for DICOM whole slide image visualization in anatomical pathology.

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.).

Should pancreas cyst fluids be divided into two for cytological diagnosis and biochemical tests?

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.

The utility of oral brush cytology in the early detection of oral cancer and oral potentially malignant disorders: A systematic review.

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.

Visual analysis of mass cytometry data by hierarchical stochastic neighbour embedding reveals rare cell types.

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.

Resultados de la citología cervicovaginal en población universitaria. Un estudio descriptivo / Results of Papanicolaou tests in university population. A descriptive study

Objetivo: Caracterizar los resultados de las CCV (citología cervicovaginal) de estudiantes atendidas en los servicios de Bienestar Universitario de la Universidad Industrial de Santander UIS (Bucaramanga). Material y método: Estudio descriptivo, de corte transversal. Población: estudiantes de la UIS en el periodo comprendido entre julio de 2004 y julio de 2010. Tamaño de muestra 1543 universitarias. Para obtener la información se tuvo acceso al sistema de información de los servicios de salud de Bienestar Universitario-UIS correspondientes a los resultados de las CCV tomadas en el periodo mencionado, sistema del cual se obtuvieron las variables relacionadas con características sociodemográficas, resultados citológicos entre otras Fueron calculadas frecuencias absolutas y relativas para cada variable. Se calculó la prevalencia de anormalidad en la CCV, sus intervalos de confianza del 95%. Todos los análisis fueron realizados en Stata 12. Resultados: Conocimiento de las alteraciones en los resultados de las citologías: anormalidad: 33%; principal microorganismo cándida albicans: 13.7%, presencia de ASCUS:11%, VPH: 2.5%, cambios celulares reactivos:15.2%. El 43.9% inició sus relaciones sexuales entre los 17 y 18 años, y el 23.8% inició a los 16 o menos años, el 93% manifestó que el rango de compañeros sexuales está entre 0 y 1 y el 46% de las estudiantes utilizan métodos anticonceptivos, los más utilizados son los anovulatorios Conclusiones: Se hallaron más factores protectores que predisponentes para presentar alteraciones citológicas y cáncer de cérvix, pero los resultados de anormalidad son significativos en la población joven, que ameritan continuar el fortalecimiento de programas enfocados a la salud sexual y reproductiva (AU)

Objective: Characterize the results of pap tests realized in students catered in the universitary welfare of the Universidad Industrial de Santander UIS (Bucaramanga). Material and methods: descriptive study, of cross-section. Population: UIS students between the time frame of July 2004 and July 2010. The sample size was 1543 students. To get the information, access to the information system of universitary welfare UIS services was provided corresponding to the results of pap tests made during the time frame mencionated before. Variables related to sociodemographic characteristics, results and others were obtained too. Absolute and relative frequencies were calculated for each variable. The prevalence of abnormality was calculated and the Confidence Interval was 95%. All the analysis was made in Stata 12. Results: Alterations in the results of pap tests: Abnormality: 33%; main microorganism candida albicans: 13.7%, presence of ASCUS: 11%, HPV: 2.5%, reactive cellular changes: 15.2%. 43.9% began sexual relationships between the ages of 17 and 18, 23.8% said they began at the age of 16 or less, 93% manifest the range of sexual partners was between 0 and 1 and 46% of students utilize contraception methods, the most used was anovulatory. Conclusions: More protective factors than predisposing factors to present cytological abnormalities and cervical cancer were found. But the abnormality results were significant, this deserves to continue the strengthen of programs related to sexual and reproductive health (AU)

Cribado de cáncer de cérvix: ¿merece la pena la búsqueda activa? / Cervical cancer screening: Is active recruitment worth the effort?

OBJETIVOS: Conocer el porcentaje de mujeres que han realizado una citología en los últimos 5 años y el ámbito de realización. Detectar alteraciones citológicas precursoras de cáncer de cérvix en mujeres sin cribado o con cribados inadecuados y conocer la prevalencia de determinaciones de VPH positivas. DISEÑO: Estudio descriptivo transversal. Emplazamiento: Centro de Salud de Natahoyo, Gijón. PARTICIPANTES: Mujeres de 40 a 50 años residentes en la zona básica y adscritas al centro de salud. MÉTODOS: Recogida de información en bases de datos, telefónicamente y por encuestas en domicilios. Captación activa, en atención primaria, de mujeres sin cribado o con cribado inadecuado para realizar citología y determinación de VPH. RESULTADOS: De las 1.420 mujeres de 40 a 50 años 1.236 (87%) habían realizado una citología en los últimos 5 años y 184 (13%) nunca habían hecho una citología o llevaban más de 5 años sin hacerla. De las 184 mujeres sin cribado o con cribados inadecuados 108 (el 58,7%) accedieron a realizar citología y determinación de VPH. En las citologías realizadas no se diagnosticó ninguna displasia de alto grado. El 8,3% de las determinaciones de VPH fueron positivas. CONCLUSIONES: En nuestra población existe una alta cobertura del cribado oportunista de cáncer de cérvix. La captación activa de mujeres que se encontraban fuera del programa de cribado no resultó rentable

OBJECTIVES: To determine the percentage of women who have had a Pap smear in the last 5 years, and the place where it was carried out. To detect cytological abnormalities and precursors of cervical cancer in un-screened or inadequately screened women and the prevalence of HPV-positive determinations. DESIGN: Cross sectional study. SETTING: Natahoyo Health Centre, Gijón (Spain). PARTICIPANTS: Women aged 40-50 years living in the area and assigned to the Health Centre. METHODS: The information was collected from databases, telephone and home surveys. There was active recruitment of unscreened women or inadequately screened in Primary Care as well as offering to perform cytology and HPV determination. RESULTS: Of the 1420 women aged 40 to 50 years, 1236 (87%) had cytology in the last 5 years, and 184 women (13%) had no screening or it was inadequate. Of these 184 women, 108 (58.7%) agreed to have cytology and HPV test performed. No high-grade cervical dysplasia was diagnosed. The prevalence of HPV-positive was 8.3%. CONCLUSIONS: In our population there is a high coverage of opportunistic screening for cervical cancer. The active recruitment of women who were not in the screening program was not useful

Human papillomavirus (HPV) screening and cervical cancer burden. A Brazilian perspective.

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.

Microscope use in clinical veterinary practice and potential implications for veterinary school curricula.

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.

The usefulness of the cell transfer technique for immunocytochemistry of fine-needle aspirates.

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.

What is the effect of electronic pathology ordering on test re-ordering patterns for paediatric patients?

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.

Posttreatment assessment of women at risk of developing high-grade cervical disease: proposal for new guidelines based on data from the Netherlands.

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.

Expenditure and resource utilisation for cervical screening in Australia.

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.

Biosensor for direct cell detection, quantification and analysis.

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.

High-risk patients with hematuria are not evaluated according to guideline recommendations.

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.

Utility of liquid-based cytology in endometrial pathology: diagnosis of endometrial carcinoma.

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.

The perceived and actual diagnostic utility of veterinary cytological samples.

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.

p16(INK4a) immunostaining in cytological and histological specimens from the uterine cervix: a systematic review and meta-analysis.

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.

Tumor budding is a strong and reproducible prognostic marker in T3N0 colorectal cancer.

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.

Meningeal dissemination in primary CNS lymphoma: prospective evaluation of 282 patients.

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.

Utility of imprint cytology for early presumptive diagnosis in clinically suspicious cervical cancer.

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.