Biomedical subjects

M E Boon

Publications and source records attributed to M E Boon.

At least 19 recordsLinked to original sources

PubMed2006

Unequivocal morphological diagnosis of fungi in morphologically abnormal nails.

AIMS: To analyse the prevalence of fungi in abnormal nails by morphological diagnosis. Prevalence studies of onychomycoses in temperate climate zones have yielded widely varying rates, possibly reflecting the confounding effects of referral bias, sampling specificity and intrinsic sensitivity of the diagnostic techniques employed. METHODS AND RESULTS: The method employed to identify fungi in nails entailed primary fixation using a non-formaldehyde-based coagulative fixative (BoonFix; Finetec, Japan) and microwave-enhanced processing to histology, followed by staining the paraffin sections with periodic acid-Schiff, using haematoxylin as a routine counterstain. The results of 990 nail samples were tabled for statistical analysis related to gender, patient age and diabetes mellitus status. In four of the 990 (< 1%) analysed cases the diagnosis was found to be equivocal using the method employed. These cases were jointly reviewed for definitive diagnosis. The overall prevalence of invasive hyphal structures was found to be 606/990 (approximately 61%). The relative risk for fungal infection in morphologically abnormal nails was found to be higher for persons < 20 years old or diabetic patients aged > or = 71 years. CONCLUSIONS: The 61% positivity rate for fungi found justifies systematic direct submission of samples from abnormal nails for histological confirmation in order to avoid unwarranted treatment.

Adolescent↗

PubMed2005

Koilocytosis and squamous (pre)neoplasia as detected in population-based cervical screening: practice and theory.

INTRODUCTION: Koilocytosis (cavitation of the cytoplasm due to active HPV infection) can be detected in the screening process for cervical carcinoma. OBJECTIVE: To report the practice of detection of koilocytosis and (pre)neoplasia in population screening and to exploit the collected data to propose an explanation for the relationship between HPV infection and nuclear precancerous changes. STUDY DESIGN: Centrally collected and stored (SBBW, Leiden, the Netherlands) data from all smears of six regional pathology laboratories (1995-2002), coded according to KOPAC (the national cervical smear coding system; S1: normal thru S9: invasive carcinoma) were accessed. Prevalences per 100,000 smears were calculated for koilocytosis and for squamous abnormalities after stratification for country of origin of screenees. The relative risk (RR) for the ethnic (age) groups was computed by dividing the prevalence of the relevant ethnic (age) group by the prevalence of all women. RESULTS: Surinamese women featured the highest prevalence of koilocytosis and of all squamous abnormalities. Moroccan women the lowest. The RR for koilocytosis was highest at 30 years (1.84) and lowest at 60 (0.26). RR dependence on age of S5-S9 lesions was similar. Compared to nonkoilocytotic smears, koilocytosis was 104 times more frequent in the 1,500 S4 smears, 36x more frequent in the 6,700 S2-S3 smears, and 24x more frequent in the 1,740 S5-S9 smears. In all three categories this difference is statistically significant. CONCLUSION: High prevalences for both koilocytosis and for preneoplasia were detected in Surinamese immigrants, however, it still does not exclude HPV infection as a confounder linked to sexual lifestyle. The presence of koilocytosis in cervical smears may serve to identify patients with an increased risk for cervical cancer and perhaps warrant more intensive surveillance than what is provided through five-yearly screening.

Adult↗

PubMed2004

[No major difference between population screening for cervical carcinoma at the present screening interval of 5 years and the former interval of 3 years].

OBJECTIVE: To assess the effect of extending the screening interval from 3 to 5 years on the detection of premalignant changes and invasive cervical carcinoma in the restructured population screening programme. DESIGN: Retrospective follow-up study. METHOD: The results were collected of the 1st round (1996-2000; 277, 377 women) and a part of the 2nd round (2001; 49,622 women; screening interval: 5 years) of the screening programme in Region West, the Netherlands. Histoscores for cervical intraepithelial neoplasia (CIN) 3 and squamous cell carcinoma (n/100 women investigated) and the hit count (sum of the histoscores for CIN 3, adenocarcinoma in situ and (micro)invasive cervical carcinoma) were calculated. Data of women with adenocarcinoma in situ and endocervical (adeno)carcinoma were recorded separately. The results of the 1st and 2nd round of the current screening programme (commenced in 1996) were compared with those of the historical screening programme that commenced in 1976 (screening interval: 3 years). RESULTS: From the 1st to the 2nd round of the historical screening programme that commenced in 1976, the histoscores for CIN 3 (3.33, 1.88) and squamous cell carcinoma (0.53, 0.19) and the hit count (3.92, 2.15) all diminished significantly. The current restructured programme, which commenced in 1996, showed low starting values for all three parameters, comparable to those in the 2nd round of the 1976 programme; a further reduction (0.16, 0.08; p < 0.01) was seen only in the histoscore for squamous cell carcinoma. In both rounds of both programmes, the histoscores for adenocarcinoma in situ (0.02, 0.02, 0.05, 0.04, respectively) and endocervical adenocarcinoma (0.04, 0.06, 0.05, 0.04) remained stable. CONCLUSION: In the current cervical carcinoma screening programme, with a screening interval of 5 years, the hit count of serious abnormalities remained constant while the incidence of squamous cell carcinoma decreased; this is in contrast to the historical screening programme (commenced in 1976), when both the hit count and the histoscore for CIN 3 diminished significantly. There were indications that cervical screening has no beneficial effect on the prevention of cervical adenocarcinoma.

Carcinoma↗

PubMed2002

How to improve cytologic screening for endocervical adenocarcinoma?

AIM: A retrospective study was undertaken to investigate how to improve the diagnosis of endocervical adenocarcinoma in screening programs. MATERIAL AND METHODS: The study group consisted of 29 slides of women diagnosed with cancer but who had negative smears. The slides were subdivided in 12 smears taken less than one year before diagnosis by histology and 17 smears taken between one and 10 years prior to diagnosis. A hundred smears of healthy women were used for comparison. All smears were studied macroscopically after which both groups of smears were scanned by the Neural Network Scanner (NNS). Differences between groups were studied for statistical significance using Pearson's Chi-squared test. FINDINGS: The macroscopic parameter of these smears found to be present most frequently was a heavy admixture of blood. The presence of blood (lysed or not) in the smears was equally consistently highlighted by the NNS. Statistical significance of the association of this parameter, with the presence of cancer, was demonstrated. CONCLUSION: The awareness of blood as a background feature of adenocarcinoma of the cervix will help to select cases needing special attention. These difficult bloody smears, studied by light microscopy and by NNS images can also be selected for additional MiB-1 staining. With this approach, blood in smears, otherwise frequently leading to a compromise of classification, can become a blessing in disguise. The diagnosis of endocervical adenocarcinoma in screening smears will therefore be improved.

Adenocarcinoma↗

PubMed2001

Less medical intervention after sharp demarcation of Grade 1-2 cervical intraepithelial neoplasia smears by neural network screening.

BACKGROUND: Neural network technology has been used for the daily screening of cervical smears in The Netherlands since 1992. The authors believe this method might have the potential to demarcate diagnoses of Grade 1-2 cervical intraepithelial neoplasia (CIN 1-2). METHODS: Of 133,196 women who were screened between 1992-1995, there were 2236 CIN 1-2 smears; 1128 of which were detected by means of neural network screening (NNS) (n = 83,404 women) and 1108 of which were diagnosed by conventional screening (n = 49,792 women). Cytologic and clinical outcomes (first cytologic or histologic follow-up diagnosis) were retrieved for all the women in the study population (n = 1920). Stratification based on clinical outcome resulted in the cases being grouped as overdiagnosed, concordant, or underdiagnosed. The smears were performed by general practitioners, whereas the biopsies were obtained by gynecologists. RESULTS: The prevalence rate for CIN 1-2 was 1.15% (95% confidence interval [95% CI], 1.08-1.23%) for NNS and 1.92% (95% CI, 1.80-2.04%) for conventional diagnosis (P < 0.001). Concordance with histology was significantly higher for NNS (53.9%; 95% CI, 50.7-57.0%) compared with conventional screening (29.2%; 95% CI, 26.4-32.2%). In addition, overdiagnosis was significantly lower for cases diagnosed by NNS (39.4%; 95% CI, 36.3-42.4%) compared with cases diagnosed by conventional screening (62.4%; 95% CI, 59.3-65.5%). CONCLUSIONS: Neural network-based screening can lead to fewer women being burdened unnecessarily with a cytologic diagnosis of CIN 1-2 by resulting in a sharp demarcation in these diagnoses and a corresponding reduction in unnecessary medical interventions. [See editorial on pages 171-172, this issue.]

Cytogenetic Analysis↗

PubMed2001

Presence of proliferating (MiB-1-positive) cells in cervical smears of women infected with HIV is associated with clinical outcome: a study of Brazilian women.

The hypothesis tested was that there is an association between the presence of proliferating (MiB-1-positive) cervical cells and clinical outcome of women infected with human immunodeficiency virus (HIV). Female partners (attending the Gynecology Outpatients Clinic of the University Hospital of Rio Grande, Brazil) of known HIV-positive (HIV+) men were used for this pilot study. Among these women, 25 were also HIV+. Papanicolaou smears of these 25 HIV+ women and of 44 HIV- women were graded as negative, CIN I, CIN II, or CIN III, using neural network screening. MiB-1 grading and HPV identification were also performed. The immune status of patients was determined using the current Centers for Disease Control classification. In agreement with the scientific literature, in these Brazilian women both CIN and HPV were associated with HIV. In the HIV+ women, the immune status tends to correlate with MiB-1 grading. Also, in the one case in whom progression from CIN I to invasive cervical carcinoma was observed, the smear contained many MiB-1-positive cells. Staining cervical smears of HIV+ women is a simple procedure to get an indication of clinical outcome of the patient.

Adult↗

PubMed2001

Neural network-based screening (NNS) in cervical cytology: no need for the light microscope?

Neural network-based screening (NNS) of cervical smears can be performed as a so-called "hybrid screening method," in which parts of the cases are additionally studied by light microscope, and it can also be used as "pure" NNS, in which the cytological diagnosis is based only on the digital images, generated by the NNS system. A random enriched sample of 985 cases, in a previous study diagnosed by hybrid NNS, was drawn to be screened by pure NNS. This study population comprised 192 women with (pre)neoplasia of the cervix, and 793 negative cases. With pure NNS, more cases were recognized as severely abnormal; with hybrid NNS, more cases were cytologically diagnosed as low-grade. For a threshold value > or = HSIL (high-grade squamous intraepithelial lesions), the areas under the receiver operating characteristic (ROC) curves (AUC) were 81% (95% CI, 75-88%) for pure NNS vs. 78% (95% CI, 75-81%) for hybrid NNS. For low-grade squamous intraepithelial lesions (LSIL), the AUC was significantly higher for hybrid NNS (81%; 95% CI, 77-85%) than for pure NNS (75%; 95% CI, 70-80%). Pure NNS provides optimized prediction of HSIL cases or negative outcome. For the detection of LSIL, light microscopy has additional value.

Cervix Uteri↗

PubMed2000

Consecutive quantitative cytology in bladder cancer.

OBJECTIVES: Quantitative cytology (Quanticyt) provides an objective reproducible alternative for routine cytology. To increase the sensitivity of cytology, we studied the application of consecutive cytology in patients in follow-up for superficial bladder cancer. METHODS: Between 1991 and 1998, a set of five or more bladder wash samples was obtained from 614 patients. These patients were retrospectively studied for follow-up data. Each sample was scored according to the Quanticyt risk score. RESULTS: In 614 patients (508 men, 106 women), 5832 bladder wash samples were taken. The mean interval between the first and fifth sample per patient was 21.5 months (SD 13.8 months). The mean number of tumor recurrences per patient was 2.17 (SD 1.82). The risk score of the first sample was not predictive of recurrence. Invasive disease was found in 0%, 0%, and 0.8% of patients with one low, intermediate, and high-risk sample, respectively. After five samples, the corresponding rate was 0%, 0%, and 10%. A comparison of visual cytology and quantitative cytology revealed that the false-negative rate was significantly different (17% versus 3.8%). The positive predictive value was highest for visual cytology (17% versus 9.2%). CONCLUSIONS: Adding consecutive quantitative cytology to urine cytopathologic evaluation improves the detection rate of high-grade lesions. Combining quantitative cytology and visual cytology provided a more accurate prediction of tumor stage.

Aged↗

PubMed2000

Analysis of three-dimensional architecture in Feulgen-stained fine-needle liver aspirates, using confocal scanning laser microscopy.

Early and accurate diagnosis of hepatocellular carcinoma in liver nodules using fine-needle aspiration biopsy can still pose difficulties, particularly in cirrhotic nodules containing dysplastic hepatocytes. Loss of architectural clues, which may aid diagnosis, can be overcome by using confocal scanning laser microscopic examination of tissue fragments in smears without the need for further processing of slides. The basic fuchsin of the Feulgen method resulted in excellent confocal images without the need for further processing of the smears. Clear morphological differences in three-dimensional reconstructions of optically sectioned tissue fragments were demonstrated in normal, hyperplastic, and malignant smears as an aid to diagnosis.

Biopsy, Needle↗

PubMed2000

Neural network-based digitized cell image diagnosis of bladder wash cytology.

In this pilot study, we tested whether it is possible to apply neural network-based diagnostics on bladder washings to detect urothelial cell carcinoma of the bladder. Eighty-five bladder wash (BW) samples were chosen at random from our own database. Cystoscopy, histology, and follow-up data concerning tumor recurrence were available. Each slide was scanned by the neural network-based digitized cell image system. The neural network-based diagnosis (NNBD) was based on 128 digitized cell images provided by the system. The light microscopic diagnosis (LMD) was rendered by an experienced cytopathologist using the same terminology, i.e., negative, low-grade tumor, and high-grade tumor. Finally, an automatic QUANTICYT analysis was performed on the same material, with as classification low, intermediate, and high risk. The sensitivity for diagnosing a histologically confirmed tumor was for NNBD 92%, for LMD 50%, and for QUANTICYT 69%. For the three methods, receiver operating characteristic (ROC) curves were made for the thresholds low grade/intermediate risk and high grade/high risk. For the prediction of a positive cystoscopy, the highest area under the curve (AUC) was found for NNBD, being 0.71. The AUC for LMD was 0.58. QUANTICYT analysis had the highest AUC value (0.62) for predicting tumor recurrence after a negative cystoscopy, with a lower value for NNBD (0.50). These findings indicate that neural network-based diagnosis of bladder washing samples is highly promising.

Area Under Curve↗

PubMed2000

Cytological recognition of invasive squamous cancer of the uterine cervix: comparison of conventional light-microscopical screening and neural network-based screening.

Cytologic recognition of invasive or microinvasive cancer of the uterine cervix may present substantial difficulties. In this study, we compared conventional light-microscopical screening of 109,104 cervical smears and neural network-based screening (NNS) of 245,527 smears, all obtained by the spatula-Cytobrush method. Two populations of Dutch women were included in the study: those receiving smears within the framework of the Dutch population screening program ("routine smears") and those receiving smears for other reasons, discussed in the text ("interval smears"). There were 71 smears, from an equal number of biopsy-confirmed invasive squamous carcinomas, 28 of which were microinvasive. The "interval smears" yielded a statistical valid higher prevalence of invasive cancer than "routine smears." Except for 5 smears that contained no evidence of abnormality ("sampling errors"), no false-negative errors occurred in the 52 NNS cases, whereas 4 such errors occurred in the 19 conventionally screened cases. By measuring the amount of cancerous material present in each smear (mapping), it could be documented that NNS was effective even in smears with a small number of cancer cells, whereas the 4 conventional false-negative screening errors occurred in smears of this type. The study showed that cells derived from invasive cancer of the cervix may have large bland nuclei that do not fit the images commonly associated with squamous cancer cells. Neural network-based screening of cervical smears was more effective than conventional screening in the diagnosis of invasive squamous cancer of the uterine cervix.

Carcinoma, Squamous Cell↗

PubMed2000

Presence of carcinoma in situ and high 2C-deviation index are the best predictors of invasive transitional cell carcinoma of the bladder in patients with high-risk Quanticyt.

OBJECTIVES: Karyometric analysis (Quanticyt) has proved of value as a cytologic marker for bladder cancer. This study was conducted to identify diagnostic and prognostic factors in a high-risk Quanticyt population to predict the prognosis of transitional cell carcinoma (TCC) of the bladder. METHODS: Quanticyt is a karyometric system for quantitative bladder wash cytologic findings based on two nuclear features: the 2c-deviation index (2cDI) and the mean of nuclear shape. Samples are scored as low, intermediate, or high risk. Before 1995, 109 patients with high-risk quantitative bladder wash cytologic findings were identified at our clinic. Four patients with previous invasive tumors were excluded. RESULTS: Histologically proven malignancy was found in 54 of 105 patients at first high-risk quantitative bladder wash cytologic findings. Invasive TCC was found in 16 patients, and another 10 patients had progression during a median follow-up of 3.7 years. In univariate analysis, the presence of carcinoma in situ (CIS), highest tumor grade, 2cDI, and highest tumor stage were significant predictors of progression. The presence of CIS proved to be the only predictor of progression in the multivariate analysis. A 2cDI of 2.00 c(2) or higher was a significant predictor of CIS, invasive TCC, and progression. At follow-up analysis after negative cystoscopy, 2cDI showed a tendency toward predicting progression. CONCLUSIONS: These data confirm earlier findings that CIS is an important marker of progression. 2cDI as assessed by quantitative cytology is a practical tool to predict CIS, invasive TCC, and subsequent progression. A 2cDI of 2. 00 c(2) can be used to further stratify high-risk quantitative bladder wash cytologic findings.

Adult↗

PubMed2000

PCR based high risk HPV testing is superior to neural network based screening for predicting incident CIN III in women with normal cytology and borderline changes.

BACKGROUND/AIMS: To improve the accuracy of conventional cytology in cervical cancer screening, high risk human papillomavirus (HPV) testing and neural network based screening have been developed. This study assessed the power of both techniques to detect women at risk of developing incident CIN III; that is, CIN III detected during the follow up of women with normal cytology and borderline nuclear changes. METHODS: A cohort of 2250 women, 34-54 years of age, who attended population based cervical cancer screening from 1988 to 1991 and had normal smears or borderline nuclear changes was followed. All smears were tested for high risk HPV and the smears were rescreened using neural network based screening. The value of neural network based screening for predicting incident CIN III during a mean follow up period of 6.4 years was compared with that of high risk HPV testing. In addition, morphological markers presumed to be related to HPV were correlated with HPV status. RESULTS: Thirteen (0.6%) women had incident CIN III. Both high risk HPV positivity and abnormal cytology were associated with an increased risk for incident CIN III (odds ratio, 240 and 22, respectively) and high risk HPV positivity was associated with abnormal cytology. The sensitivity of high risk HPV testing for predicting incident CIN III was much higher than that of neural network based screening (92% and 46%, respectively). None of the morphological markers assessed, including koilocytosis, was correlated with high risk HPV status. CONCLUSION: High risk HPV testing is superior to neural network based screening in identifying women at risk of developing CIN III. For women with normal cytology and borderline changes and a negative high risk HPV test, the screening interval can be considerably prolonged.

Adult↗

PubMed1999

Potentially difficult smears of women with squamous cell carcinoma pose fewer problems when PAPNET is used for primary screening.

The diagnosis of squamous cell carcinoma (SCC) on a cervical smear is often far from easy. This study reports the analysis of 40 true-positive SCC smears detected in primary PAPNET screening and eight false-negative (FN) conventionally screened smears. All FN cases contained sparse abnormal material (< 10% of the slide). In these potentially difficult cases the diagnosis on the PAPNET images was not hard. Statistical analysis of the quantitative data indicated that the PAPNET images of the FN cases and the true-positive cases differed in some aspects. PAPNET highlighted the importance of background information (old blood, fibrin and necrosis). In addition, all FN smears contained cancer cells in the PAPNET images, allowing a correct diagnosis.

Analysis of Variance↗

PubMed1999

Pretreatment in a high-pressure microwave processor for MIB-1 immunostaining of cytological smears and paraffin tissue sections to visualize the various phases of the mitotic cycle.

In many pathology laboratories, both microwave ovens and pressure cookers are used for pretreatment of cytologic smears and paraffin sections to allow MIB-1 staining. For both methods there are two problems. First, the results cannot be used for quantitation because standardization is impossible. Second, the staining results are often suboptimal, resulting in negative staining of cells in the G(1)- and S-phases. When pretreatment is performed in a microwave processor, allowing microwave heating under pressure, precise temperature monitoring becomes possible. In addition, the importance of the pH of the buffer was studied using a test battery series. Optimal staining is achieved at a temperature of 115C, 10 min, pH 6. This method proved to be highly reproducible. Because the immunostaining results are optimal, the various phases of the cell cycle can be defined in the sections and smears. In addition, the perinucleolar staining of the late G(1)-phase is optimally visualized and nuclei of the stable pKi-67 pathway can be identified. Under suboptimal conditions, in particular, the number of cells in the late G(1)-phase are underestimated in the MIB-1 counts.

Antigens, Nuclear↗

PubMed1998

Combining QUANTICYT karyometric analysis with architectural confocal-aided cytology to prognosticate superficial bladder cancer.

For this study, bladder washings of 923 patients with a follow-up for superficial bladder cancer were used. For the prognostication of each case (follow-up period up to 20 mo), two parameters were used: tumor recurrence and the event of (progressing) invasive growth. Each sample was classified as negative, low grade or high grade, based on confocal-aided architectural cytology. The feature architecture was based on the images of the epithelial fragments as seen in the Feulgen stain, which also could be visualized in confocal microscopy. The same three classes were also used for grading the samples according to the QUANTICYT system, in which DNA and morphometry of nuclei were automatically assessed. The 532 cases graded as QUANTICYT high had a worse prognosis than the 391 cases with QUANTICYT low. In addition, architectural cytology contributed significantly for the prognostication of cases classified as QUANTICYT high, the 228 nonconcording cases faring better than the 304 concording ones. For QUANTICYT low, the 156 nonconcording cases had also a lower recurrence rate than the 235 concording ones, but this difference was only significant in patients followed for up to 8 mo. These findings indicate that QUANTICYT grading supplemented by architectural cytology supplies the clinician with valuable prognostic information which can be used to limit cystoscopies.

Automation↗

PubMed1998

New paradigm for ASCUS diagnosis using neural networks.

It was tested whether it was possible to reduce the atypical squamous cells of undetermined significance (ASCUS) scores in a meaningful way by exploiting the cells selected by the neural networks of the PAPNET system. For this test, 2,000 routine smears were screened once by means of PAPNET and once conventionally in a laboratory in Amsterdam. From these 2,000 smears, 168 were diagnosed as ASCUS. In the second phase of the study, the diagnosis was based solely on the PAPNET images, and in addition, cases with immature cells (bare nuclei and cells with very little cytoplasm) in the PAPNET images were classified as ASCUS. Although, in this second phase, 75.6% of the cases were revised to negative, the cases with positive follow-up were all still classified as ASCUS. The negative predictive value remained at 100%, whereas the positive predictive value increased from 14.3 to 30%. By using the new paradigm (focusing on immature cells selected by the neural networks) for routine primary PAPNET screening in a laboratory in Leiden, the ASCUS scores were reduced from 10% (June of 1996) to 1.0% (early 1998), with promising follow-up results for the first half of 1997.

Cervix Uteri↗

PubMed1998

Microwave-stimulated Jones-Marres method for staining fungi in brain tissue of immunocompromised patients.

Life-threatening fungal infections have increased significantly in the past decade due to the rising number of immunocompromised patients. Serological diagnosis of most fungal infections is unreliable and blood cultures are positive in only 50% of premortem cases; therefore, tissue sampling together with fast, reliable staining of fungi should be carried out to reach the correct, timely diagnosis. We developed, partly serendipitously, a microwave silver staining method for fungi in histological sections. During a differentiation step in periodic acid, background staining is removed. This rapid staining method can be combined with immunostaining, for example, the alpha smooth muscle actin method, to visualize blood vessels. Silver staining results were optimized using the recently developed MicroMED BASIC microwave labstation for histology (Milestone srl, Italy), featuring no-touch temperature measurements and PC control.

Aspergillosis↗