Helene Wiener

European Guidelines for Quality Assurance in Cervical Cancer Screening. Second Edition—Summary Document

European Guidelines for Quality Assurance in Cervical Cancer Screening have been initiated in the Europe Against Cancer Programme. The first edition established the principles of organised population-based screening and stimulated numerous pilot projects. The second multidisciplinary edition was published in 2008 and comprises ∼250 pages divided into seven chapters prepared by 48 authors and contributors. Considerable attention has been devoted to organised, population-based programme policies which minimise adverse effects and maximise benefits of screening. It is hoped that this expanded guidelines edition will have a greater impact on countries in which screening programmes are still lacking and in which opportunistic screening has been preferred in the past. Other methodological aspects such as future prospects of human papillomavirus testing and vaccination in cervical cancer control have also been examined in the second edition; recommendations for integration of the latter technologies into European guidelines are currently under development in a related project supported by the European Union Health Programme. An overview of the fundamental points and principles that should support any quality-assured screening programme and key performance indicators are presented here in a summary document of the second guidelines edition in order to make these principles and standards known to a wider scientific community.

European guidelines for quality assurance in cervical cancer screening: recommendations for cervical cytology terminology

There are many different systems of cytology classification used in the member states of the European Union (EU) and many different languages. The following short annexe to Chapter 3 of the European Guidelines for Quality Assurance in Cervical Cancer Screening provides a framework that will allow different terminologies and languages to be translated into standard terminology based on the Bethesda system (TBS) for cytology while retaining the cervical intraepithelial neoplasia (CIN) classification for histology. This approach has followed extensive consultation with representatives of many countries and professional groups as well as a discussion forum published in Cytopathology (2005;16:113).

European guidelines for quality assurance in cervical cancer screening: recommendations for cytology laboratories*

The quality of a cervical cytology laboratory depends on adequate handling and staining of the samples, screening and interpretation of the slides and reporting of the results. These guidelines give an overview of procedures recommended in Europe to manage the balance between best patient care possible, laboratory quality assurance and cost effectiveness and will be published as a chapter 4 in the European Guidelines for Quality Assurance in Cervical Cancer Screening. The laboratory guidelines include protocols for personnel and organisation, material requirements, handling and analysing cervical samples, recording of results, quality management and communication. The section on quality management is comprehensive and includes protocols for all aspects of internal and external quality assurance. The guidelines are extensively referenced and as far as possible the recommendations are evidence‐based.

HIGH INCIDENCE OF NEPHROGENIC ADENOMA OF THE BLADDER AFTER RENAL TRANSPLANTATION

BACKGROUND Tumors of the bladder termed nephrogenic adenomas in kidney allograft recipients are believed to develop as urothelial metaplastic proliferations in response to mechanical trauma, chemical noxae, irradiation, and bacterial or viral pathogens. We report on the incidence of nephrogenic adenoma of the bladder in patients who received renal transplants during a period of 7 years and 3 months at the University Hospital of Vienna. METHODS Diagnosis was obtained by cystoscopy and histological analysis. Nephrogenic adenoma was treated by transurethral electroresection and administration of antibiotics in case of urinary tract infections. Follow-up consisted of cytological controls of urine and bladder irrigation fluid as well as of cystoscopy every 3 months. RESULTS In 7 of 1328 renal allograft recipients, nephrogenic adenoma could be detected after 7 to 60 months following renal transplantation. In five patients, recurrence was detected 9 to 23 months after diagnosis of the initial lesion. No evidence of malignant degeneration was observed in any patient. Nephrogenic adenoma was not related to immunosuppressive therapy, cytomegalovirus disease, or gancyclovir therapy. CONCLUSIONS We suggest that after successful transurethral electroresection of nephrogenic adenomas, cytological controls are adequate every 3 months. Only in renal transplant patients with recurrence of voiding disturbances, macrohematuria, or urinary tract infection are cystoscopy and biopsy indicated in the routine follow-up regimen.

Does topical instillation therapy influence chromosomal aberrations in superficial bladder cancer

PURPOSE Patients with a high risk for superficial bladder cancer are treated by topical immuno-or chemotherapy after transurethral resection to reduce the chance of recurrence and/or progression. The aim of this study was to analyse if cytogenetical abnormalities, which are known to be constantly related to bladder cancer, are modified or eliminated by topical immuno- or chemotherapy. MATERIALS AND METHODS Using fluorescence in situ hybridization (FISH), the influence of topical instillation therapy with Bacillus Calmette-Gúerin (BCG) and Mitomycin C (MMC) on numerical aberrations of chromosomes 7, 9 and 17 was investigated in 25 patients with transitional cell cancer (TCC) of the bladder. Data were compared with histological and clinical outcome. Fifteen TCC patients with similar histological criteria without instillation therapy served as controls. Median follow-up was 30 +/- 2 months. RESULTS After BCG treatment 10 of 15 patients (66.6%) developed recurrent and 2/15 (13.3%) progressive disease. Three of 15 patients (20.0%) had no evidence of disease. Numerical aberrations did not change in 8 of the 15 BCG patients (53.3%) and changed to a more aggressive pattern in 40.0% (6/15). Five of 10 MMC treated patients (50.0%) developed a recurrent tumor, 2/10 (20.0%) progressed and 3/10 (30.0%) had no evidence of disease. Four of 10 (40.0%) of these patients showed stable and 5/10 (50.0%) progressive chromosomal patterns. Only one patient in each group with primary chromosomal alterations changed to a regular diploid chromosomal pattern after therapy according to a complete clinical remission. CONCLUSION Even though topical immuno- and chemotherapy may be useful to delay recurrence and progression, chromosomal patterns remain basically unstable.

Survey of medical training in cytopathology carried out by the journal Cytopathology

Anshu, A. Herbert, B. Cochand‐Priollet, P. Cross, M. Desai, R. Dina, J. Duskova, A. Evered, A. Farnsworth, W. Gray, S. S. Gupta, K. Kapila, I. Kardum‐Skelin, V. Kloboves‐Prevodnik, T. K. Kobayashi, H. Koutselini, W. Olszewski, B. Onal, M. B. Pitman, Ž. Marinšek, T. Sauer, U. Schenck, F. Schmitt, I. Shabalova, J. H. F. Smith, E. Tani, L. Vass, P. Vielh and H. Wiener
Survey of medical training in cytopathology carried out by the journal Cytopathology

European guidelines for quality assurance in cervical histopathology.

Abstract The current paper presents Chapter 5 of the second edition of the European Guidelines for Quality Assurance in Cervical Cancer Screening, which deals with the histopathological diagnosis of lesions of the uterine cervix. It completes a series of publications in journals containing the contents of other parts of the European Guidelines. Histopathology provides the final diagnosis on the basis of which treatment is planned, and serves as the gold standard for quality control of cytology and colposcopy. It is also the source of the diagnostic data stored at the cancer registry and used for evaluation of screening programmes. It is therefore important that histopathology standards are monitored and based on agreed diagnostic criteria. Histology is required to diagnose the degree of abnormality in women with persistent low-grade abnormalities including HPV-lesions, as well as high-grade lesions. Cytology may also suggest either glandular abnormalities or be suggestive of high-grade CIN, AIS or invasive cancer. Histopathologists should be aware of, and familiar with, the nature of cytological changes which may be relevant to their reports. The accuracy of the histopathological diagnosis of tissue specimens depends on adequate samples, obtained by colposcopically directed punch biopsies (with endocervical curettage if necessary) or excision of the transformation zone or conisation. An accurate histological diagnosis further depends on appropriate macroscopic description, technical processing, microscopic interpretation and quality management correlating cytological and histological diagnosis. This paper proposes guidelines for sampling and processing of cervical tissue specimens obtained by biopsy, excision and/or curettage.

Carbonic Anhydrase IX as a Diagnostic Urinary Marker for Urothelial Bladder Cancer

UNLABELLED Urinary biomarkers are needed to improve the management and reduce the cost of urothelial bladder cancer (UBC); however, none have been recommended yet for clinical practice. This study evaluated carbonic anhydrase IX (CAIX) as a diagnostic urinary biomarker for UBC. CAIX was analyzed by quantitative polymerase chain reaction in urine samples of 196 patients with UBC and 123 controls with hematuria. Paired samples from urine and tumor tissue were evaluated in 16 cases. Data were validated in 155 independent samples. The sensitivity and specificity of CAIX for UBC detection were 86.2% and 95.1%, respectively (area under the curve [AUC]: 90.5%). There was a significant association of CAIX expression between the paired urine and tumor specimens (p=0.002). CAIX showed a significantly higher predictive accuracy than urinary cytology (90.5% vs 71.7%), specifically in low-grade tumors (90.0% vs 61.8%). CAIX expression decreased with increasing tumor stage and grade. Analyses in an independent validation cohort confirmed the high accuracy of CAIX for diagnosing UBC (AUC: 88.3%). PATIENT SUMMARY We evaluated carbonic anhydrase IX (CAIX) as a urinary marker for bladder cancer (BCa) using a large series of patients from a single hospital. We found that urinary CAIX has a high sensitivity and specificity for diagnosing BCa.

The value of transurethral bladder biopsy after intravesical bacillus Calmette-Guérin instillation therapy for nonmuscle invasive bladder cancer: a retrospective, single center study and cumulative analysis of the literature.

PURPOSE We evaluated the need of routine transurethral biopsies after an induction course of intravesical bacillus Calmette-Guérin for high grade nonmuscle invasive bladder cancer. MATERIALS AND METHODS This retrospective study included 180 patients with high grade nonmuscle invasive bladder cancer who underwent a 6-week induction course of bacillus Calmette-Guérin. Cystoscopic findings, urinary cytology and pathological results of transurethral biopsy were evaluated. For cumulative meta-analysis we systematically reviewed studies indexed in MEDLINE®, EMBASE® and Web of Science®. The records of 740 patients from a total of 7 studies were finally analyzed. RESULTS Biopsy was positive in 58 patients (32%). Cystoscopy appeared normal in 75 patients (42%) and showed only erythema in 51 (28%) and tumor in 54 (30%), of whom 6 (8%), 11 (22%) and 41 (76%), respectively, showed positive findings at biopsy. The positive predictive value of erythema was 15% with negative cytology and 56% with positive cytology. The positive predictive value of a tumor with negative and positive cytology was 63% and 89%, respectively. A combination of negative cytology and normal cystoscopy was associated with a negative biopsy in 94% of cases. A total of 970 bladder biopsies were taken, of which 137 (14%) were positive, including 20 of 125 erythematous lesions (16%), 73 of 107 tumors (68%) and 44 of 738 normal-appearing areas (6%). Cumulative analysis findings were comparable. CONCLUSIONS Routine transurethral bladder biopsies after a bacillus Calmette-Guérin induction course are not necessary. An individually approach is recommended, tailored from cystoscopic findings and cytology.

Cytophotometry in the monitoring of bladder cancer under intravesical chemotherapy.

OBJECTIVE We evaluated the DNA cytophotometry in 446 bladder washing samples from 64 patients under mitomycin C after superficial bladder cancer during an observation period of up to 5 years. The aim of the study was to identify patients at high risk of recurrence despite chemotherapy-induced atypical, hence noninformative cytology. METHODS The prognostic value of cytology and ploidy during chemotherapy was compared with regard to recurrence rates and the median time to recurrence. RESULTS Aneuploidy identified 8 of 10 patients recurring within 12 months out of 17 patients with atypia at first presentation after surgery, whereas no recurrence was seen after atypia and diploid histograms (p = 0.005, mean follow-up period 62 months). Aneuploidy was the most accurate indicator of short-time recurrence (p < 0.001 by multivariate analysis). Follow-up data showed a relative risk of recurrence of 12.7 following histogram shifts towards aneuploidy and of 1.6 for positive shifts in cytology. CONCLUSION Cytophotometry is superior to cytology in predicting the outcome in patients under chemotherapy for superficial transitional cell cancer of the bladder.