European consensus statement on expert colposcopy.

BACKGROUND: Following the publication of the European consensus statement on standards for essential colposcopy in 2020, the need for standards relating to more complex and challenging colposcopy practice was recognised. These standards relate to colposcopy undertaken in patients identified through cervical screening and tertiary referrals from colposcopists who undertake standard colposcopy only. This set of recommendations provides a review of the current literature and agreement on care for recognised complex cases. With good uptake of human papillomavirus (HPV) immunisation, we anticipate a marked reduction in cervical disease over the next decade. Still, the expert colposcopist will continue to be vital in managing complex cases, including previous cervical intraepithelial neoplasia (CIN)/complex screening histories and multi-zonal disease. AIMS: To provide expert guidance on complex colposcopy cases through published evidence and expert consensus. MATERIAL & METHODS: Members of the EFC and ESGO formed a working group to identify topics considered to be the remit of the expert rather than the standard colposcopy service. These were presented at the EFC satellite meeting, Helsinki 2021, for broader discussion and finalisation of the topics. RESULTS & DISCUSSION: The agreed standards included colposcopy in pregnancy and post-menopause, investigation and management of glandular abnormalities, persistent high-risk HPV+ with normal/low-grade cytology, colposcopy management of type 3 transformation zones (TZ), high-grade cytology and normal colposcopy, colposcopy adjuncts, follow-up after treatment with CIN next to TZ margins and follow-up after treatment with CIN with persistent HPV+, and more. These standards are under review to create a final paper of consensus standards for dissemination to all EFC and ESGO members.

Mainstream germline genetic testing for patients with epithelial ovarian cancer leads to higher testing rates and a reduction in genetics-related healthcare costs from a healthcare payer perspective.

OBJECTIVE: Germline genetic testing is increasingly offered to patients with epithelial ovarian cancer by non-genetic healthcare professionals, so called mainstream genetic testing. The aim of this study was to evaluate the effect of implementing a mainstream genetic testing pathway on the percentage of newly diagnosed patients with epithelial ovarian cancer to whom genetic testing was offered and the genetics-related healthcare costs. METHODS: The possible care pathways for genetic counseling and testing and their associated costs were mapped. Patient files from all newly diagnosed patients with epithelial ovarian cancer before (March 2016 - September 2017) and after (April 2018 - December 2019) implementing our mainstream genetic testing pathway were analyzed. Based on this analysis, the percentage of newly diagnosed patients to whom genetic testing was offered was assessed and genetics-related healthcare costs were calculated using a healthcare payer perspective based on a Diagnosis-Related Group financing approach. RESULTS: Within six months after diagnosis, genetic testing was offered to 56% of patients before and to 70% of patients after implementation of our mainstream genetic testing pathway (p = 0.005). Genetics-related healthcare costs decreased from €3.511,29 per patient before implementation to €2.418,41 per patient after implementation of our mainstream genetic testing pathway (31% reduction, p = 0.000). CONCLUSION: This study shows that mainstream genetic testing leads to a significantly higher proportion of newly diagnosed patients with epithelial ovarian cancer being offered germline genetic testing. In addition, it significantly reduces genetics-related healthcare costs per patient.

Reasons for guideline non-adherence in older and younger women with advanced stage ovarian cancer.

OBJECTIVE: This study aims to assess the reasons for guideline non-adherence in women with advanced stage ovarian cancer and whether these reasons differ according to age. METHODS: All women diagnosed with advanced stage ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) IIb-IV, between 2015 and 2018 were selected from the Netherlands Cancer Registry. Treatment patterns and reasons for guideline non-adherence were analyzed according to age groups. RESULTS: 4210 women were included, of whom 34%, 33%, 26%, and 8% were aged <65, 65-75, 75-85, and ≥85 years respectively. With advancing age, less women received guideline-adherent treatment (decreasing from 70% to 2% in women aged <65 and ≥85 years respectively) and more women received best supportive care only (ranging from 4% to 69% in women aged <65 and ≥85 years respectively). The most prevalent reasons for guideline non-adherence differed according to age and included patient preference in older women, and functional status and extent of disease in younger women. CONCLUSIONS: Most older women did not receive guideline-adherent care and patient preference was the most common reason for this decision. This knowledge provides insight in the current treatment decision-making process and highlights the importance of eliciting patient treatment preferences. Further prospective research is necessary to study the underlying motivation for women to decline guideline care and the extent to which shared decision-making influences treatment choice.

Treatment decision-making in elderly women with ovarian cancer: an age-based comparison.

OBJECTIVE: To investigate treatment choices and outcomes in women with ovarian cancer, comparing elderly (≥75 years) and younger patients (<75 years). METHODS: A single-center retrospective analysis of patients diagnosed with ovarian cancer between 2010 and 2015. The initial treatment plan and course of treatment were extracted from medical files. RESULTS: Of 128 included patients, 34% were aged ≥75 years. The initial treatment plan consisted of the combination of cytoreductive surgery and platinum-based doublet chemotherapy (ie, standard treatment) in only 10% of the elderly patients with an indication for this treatment. 5% of these patients completed this treatment without adaptations (compared with 85% and 48%, respectively, in younger patients). 38% of the elderly patients with an indication for cytoreductive surgery and chemotherapy received best supportive care only. Patient preference was an important reason to withhold standard treatment. Surgery- and chemotherapy-related complications and hospital admissions did not differ between groups. Median survival was lower in the elderly (p=0.002) and in patients receiving best supportive care (p<0.001). CONCLUSIONS: Elderly patients were less frequently treated in accordance with the treatment guideline. To select those older patients who may benefit from (adapted) treatment is challenging. Future studies should evaluate determinants associated with treatment completion to improve outcomes in this vulnerable population.

The performance of Dynamic Spectral Imaging colposcopy depends on indication for referrals.

OBJECTIVE. A previous study has shown that Dynamic Spectral Imaging (DSI) colposcopy increases the sensitivity of the colposcopic examination in women referred with abnormal cytology. In this study we have reanalyzed the performance of DSI and conventional colposcopy for new referral conditions and for low-grade cytology referrals versus high-grade cytology referrals. METHOD. Data from a previous validation trial was used to assess the performance of DSI in different cytology groups:Women referred with BMD (borderline and mild dyskaryosis) cytology and women referred with NBMD cytology either hrHPV positive or negative were separately analyzed. Furthermore, we tried to assess the clinical performance by appropriate filtering of patients to replicate two different referral strategies. RESULTS. The sensitivity of DSI and conventional colposcopy to detect CIN2+ lesions in women referred with BMD cytology is 82% and 44% respectively (p= 0.001) and in the NBMD group 77% and 64% respectively (p= 0.24). If the two techniques are combined the sensitivity is 85%.When the conditions of new screening strategies are applied DSI colposcopy has a higher sensitivity to detect CIN2+ than conventional colposcopy. Findings are similar when CIN3+ is used as a threshold. CONCLUSION. We found that in most cases DSI colposcopy has a higher sensitivity than conventional colposcopy, even when referral criteria are changed. Unlike conventional colposcopy, the sensitivity of colposcopy with DSI in low-grade cytology referrals was found similar to the sensitivity in high-grade cytology referrals. This suggests that a baseline colposcopy sensitivity may be possible with the adjunctive use of the DSI map, irrespective of referral cytology.

Women's Preferences of Dynamic Spectral Imaging Colposcopy.

BACKGROUND: The focus of testing the dynamic spectral imaging (DSI) colposcope has been on the technical characteristics and clinical performance. However, aspects from a patient's perspective are just as important. METHODS: This study was designed as a substudy of the DSI validation study, a prospective comparative, multicenter clinical trial to assess the clinical performance of DSI colposcopy. All women included in this study were asked to complete two questionnaires: a patient characteristics questionnaire and a patient satisfaction questionnaire. RESULTS: In the initial study a total of 239 women were included in the intention-to-treat cohort. Of these, 230 women (96.2%) completed both questionnaires. When assessing the women's preferences for some of the possible uses of DSI colposcopy, a high level of agreement was noted for all potential implementations. In general, women found the additional time DSI colposcopy took acceptable: just 15 women (6.5%) thought the time DSI colposcopy took made them feel uncomfortable. Furthermore, women ranked test accuracy as the most important characteristic, followed by (more) rapid testing and comfort. Quick notification of the results and costs were considered the least important characteristics. CONCLUSION: Women are willing to accept discomfort in the form of an additional or longer test if there is clinical benefit.

Long-term CIN3+ risk in women with abnormal cytology; role of hrHPV testing.

BACKGROUND: Many studies have examined the short-term value of high-risk human papillomavirus (hrHPV) testing in predicting cumulative risk of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+). This study focuses on long-term CIN3+ risk after initial wait and see policy. METHODS: A total of 342 women with abnormal cytology of borderline/mild dyskaryosis (BMD) or worse (>BMD), included between 1990 and 1992, were followed-up by cytology and hrHPV testing until 1996 and monitored by cytology thereafter. Primary endpoint was cumulative CIN3+ risk by December 2009. RESULTS: Women with BMD had a 5-year CIN3+ risk of 22.5% (95% confidence interval (CI) 17.0-29.1) and of 0.7% (0.1-4.5) in the subsequent 5 years. High-risk human papillomavirus-negative women with BMD had a 5-year risk of <0.01% (95% CI 0.0-5.1) and of <0.01% (0.0-5.7) in the following 5 years, while for hrHPV-positive women these risks were 37.5% (29.0-46.9) and 1.6% (0.2-9.5), respectively. Women with >BMD had a 5-year risk of 45.1% (36.4-54.1) and of 3.5% (0.9-12.2) in the subsequent 5 years. High-risk human papillomavirus-negative women with >BMD had a 5-year risk of 7.3% (2.0-23.6) and hrHPV-positive women of 56.6% (46.4-66.3). CONCLUSION: Women with BMD have an elevated CIN3+ risk for 5 years only; afterwards their risk is similar to the general population. High-risk human papillomavirus-negative women with BMD may return to regular screening directly. All other women with BMD should be referred for additional testing and/or colposcopy.

Agreement between colposcopic impression and histological diagnosis among human papillomavirus type 16-positive women: a clinical trial using dynamic spectral imaging colposcopy.

OBJECTIVE: To investigate the agreement between conventional colposcopic impression, dynamic spectral imaging (DSI) colposcopy and histology, for human papillomavirus type 16-positive (HPV16(+)) and non-16 high-risk (hr) HPV(+) women. DESIGN: Prospective, comparative, multicentre clinical trial. SETTING: Three colposcopy clinics in the Netherlands. POPULATION: Women (n = 177) aged 18 years or over with an intact cervix, referred for colposcopy. METHODS: The colposcopist graded the lesion by using the DSI colposcope as a regular video colposcope. Subsequently the DSI impression was displayed and biopsies were taken from all abnormal areas as well as from a random (normal) site. A cervical smear was taken for HPV typing. MAIN OUTCOME MEASURES: Histologically confirmed high-grade cervical intraepithelial neoplasia or cancer (CIN2(+)), positive for HPV16 or for any other hrHPV type. RESULTS: The DSI colposcope identified more CIN2(+) cervical lesions among HPV16(+) women than in non-16 hrHPV(+) women (P = 0.032 regardless of final histology and P = 0.009 among women with CIN2(+)). Consequently, the sensitivity of the DSI colposcope for detecting CIN2(+) lesions was higher in HPV16(+) women than in non-16 hrHPV(+) women (97% versus 74%, P = 0.009). No such differences were seen for the colposcopist impression. In addition, mainly smaller cervical lesions are missed by the colposcopist. CONCLUSIONS: The sensitivity of DSI colposcopy for CIN2(+) is higher in HPV16(+) than in non-16 hrHPV(+) women. Furthermore, regardless of HPV16 status, the sensitivity of DSI for CIN2(+) is higher than that of the colposcopist, probably because colposcopists tend to miss smaller cervical lesions.

HrHPV-testing in a university hospital gynecology outpatient clinic: recommendations for clinical practice.

OBJECTIVE: To study the effect of hrHPV-testing on the detection of CIN2/3+ in women referred to a gynecology outpatient clinic, and to assess a useful risk profile in relation to the referral reason to identify who should be tested for cervical pathology. METHODS: This study was designed as an observational cohort study. In the first six months of 2007, we categorized the referral reason of 1149 consecutive women who visited our gynecology outpatient clinic and assessed the risk for CIN2/3+ as found by cytology or co-testing with a hrHPV-test and cytology. RESULTS: Three different categories of referral reasons were identified; women with presumed cervix pathology, women with presumed endometrial pathology and women with other referral indications. The cumulative 18-month CIN2+ and CIN3+ risks were highest in the group with presumed cervical disease (adjusted risks 11.1% and 5.4% respectively) and lowest in the miscellaneous group with no suspicion of cervical and/or endometrial pathology (adjusted risks 4.1% and 1.8% respectively). HrHPV-testing detected significantly more CIN2/3+ lesions than cytology (relative detection rate: 1.42 (95%CI 1.05-1.92) and 1.38 (95%CI 0.95-2.05) respectively). CONCLUSIONS: The high (>2%) cumulative 18-month CIN2/3+ risk in patients with presumed cervical and/or endometrial pathology warrants routine cervical testing. In these women a hrHPV-test should be added to cytology because this identifies a significant number of additional women with a substantial risk of CIN2/3+ lesions who would not be identified with cytology alone. Women referred for other reasons should not have cervical testing beforehand, because of their low risk of CIN2/3+.

Digital colposcopy: ready for use? An overview of literature.

The aims of this review were to summarise the various methods of digital colposcopy and to provide an overview of their efficacy. We conducted a literature search and focused on papers that described a technique for colposcopy, other than conventional colposcopy, and compared this with conventional colposcopy and/or histology and included digitalisation of the process. All papers have been classified in one of the following categories: digital imaging and telecolposcopy, spectroscopy, computerised colposcopy, optical coherence tomography and confocal microcolposcopy. Among the most promising developments is spectroscopy, allowing a more or less automated analysis and interpretation of the colposcopic image.

Fear of blushing: effects of task concentration training versus exposure in vivo on fear and physiology.

Patients with fear of blushing as the predominant complaint (N = 31) were randomly assigned to (1) exposure in vivo (EXP), or (2) task concentration training (TCT), in order to test the effect of redirecting attention above exposure only. In addition, it was investigated whether treatment reduced actual blush behavior; therefore, physiological parameters of blushing were measured during two behavioral tests. Half of the patients served as waiting-list controls first. Assessments were held before and after treatment, at 6-weeks, and at 1-year follow-up. Both treatments appeared to be effective in reducing fear of blushing and realizing cognitive change. Yet, at posttest, TCT tended to produce better results with respect to fear of blushing. At 6-weeks follow-up, TCT produced significantly more cognitive change. At 1-year follow-up, patients further improved, while differential effects had disappeared. The reduction in fear of blushing was not paralleled by a reduction in actual blush behavior during the behavioral assessments. Thus, it seems that fear of blushing reflects a fearful preoccupation, irrespective of actual facial coloration.

Exclusion of vanA, vanB and vanC type glycopeptide resistance in strains of Lactobacillus reuteri and Lactobacillus rhamnosus used as probiotics by polymerase chain reaction and hybridization methods.

Strains of Lactobacillus reuteri and Lact. rhamnosus are used as probiotics in man and animal. The aim of this study was to determine whether the glycopeptide resistance in these lactobacilli has a similar genetic basis as in enterococci. Five Lact. reuteri strains and one Lact. rhamnosus, as well as four Enterococcus control strains, were probed for the vanA gene cluster, the vanB gene and the vanC gene by PCR and Southern hybridization, and DNA/DNA hybridization. Their resistance and plasmid patterns were also investigated. All Lactobacillus strains were resistant to vancomycin but susceptible to a broad range of antibiotics. Four of the Lactobacillus strains (including the Lact. rhamnosus strain) did not harbour any plasmid and two of them contained five and 6 plasmid bands respectively. None of the Lactobacillus strains possessed the vanA, vanB or vanC gene. These findings indicate that the glycopeptide resistance of the Lactobacillus strains analysed is different from the enterococcal type. The study provides reassurance on the safety of the Lactobacillus strains used as probiotics with regard to their vancomycin resistance.

Peritonitis associated with vancomycin-resistant Lactobacillus rhamnosus in a continuous ambulatory peritoneal dialysis patient: organism identification, antibiotic therapy, and case report.

A case of Lactobacillus rhamnosus-associated peritonitis in a patient undergoing continuous ambulatory peritoneal dialysis is reported. The patient was treated with vancomycin after isolation of glycopeptide-susceptible coagulase-negative staphylococci. After a skin rash developed, vancomycin was discontinued and replaced with teicoplanin. Seven weeks after the glycopeptide therapy was discontinued, a Lactobacillus strain was isolated in pure cultures. The isolate was identified first incorrectly as L. acidophilus but later correctly as L. rhamnosus. Antibiotic susceptibility testing showed that the isolate was resistant to glycopeptides but susceptible to several other antibiotics. The antibiotic treatment was then switched to imipenem and was successful.

[Suitability of sampling methods for environmental studies in meat rendering and processing plants with European Community licenses]. / Eignung von Probenahmemethoden zur Umgebungsuntersuchung in fleischgewinnenden und -verarbeitenden Betrieben mit EU-Zulassung.

In EC-licensed meat rendering and processing plants microbiological test results obtained through contact slides and a highly precise swab method were compared. It was revealed that when using contact slides the absolute cfu can be determined only after prior verification with a reference method. The key provided by the manufacturer for data interpretation does not always match with results obtained by swab technique. Nevertheless, contact plates are suitable to determine the microbiological status. However, their technical deficiencies must be compensated. A simple swab method is well suited for use in meat rendering and processing plants. It is very economical due to low material costs and easy to apply by plant hygienists. The use of a seven step scale listing results up to 10(3) cfu/cm2 enables even non-experts to interpret their results reasonably.

[Microbiological quality of fresh and stored ground meat from commercial production]. / Mikrobiologische Qualität von frischem und gelagertem Hackfleisch aus industrieller Herstellung.

In the last quarter of 1993 we investigated 295 samples of minced meat on 59 days of production (5 samples each day). EC-regulations (88/657/EEC, changed by 92/110/EEC) were considered. We looked for the total aerobic count, E. coli, Staph. aureus and Salmonella. Factors that could influence the results were examined as day of sampling, storage under defined conditions, ph-value etc. Most important for the microbiological quality of the product was the quality of the processed meat. In most cases samples fulfilled the strict microbiological requirements of the EC-regulation. After storage for 2 days at 2 degrees C there was no detectable alteration of the microflora of minced meat. Beginning with the third day total aerobic count increased significantly explainable by the increase of pseudomonads. There were problems with minced meat produced from beef, that was of lower quality and not fresh. EC-regulations can be fulfilled and are reasonable in case of industrial production when considering the quality of the processed meat and seasonal differences. Therefore microbiological quality control is justified.