[The use of intrauterine device in nulliparous over 18 years: a Belgian consensus]. / La contraception intra-utérine chez la nultlipare de plus de 18 ans: vers un consensus belge.

Under the presidency of prof. H. Depypere (UZ Ghent) and Prof. P. Simon (ULB Erasme) a Belgian panel of thirteen experts (gynecologists, representatives of universities and scientific associations for gynecology-obstetrics) reached a consensus on the use of intrauterine systems, both copper IUDs as hormone IUDs, in nultiparous women.

The Clinical Role of HPV Testing in Primary and Secondary Cervical Cancer Screening.

Traditional population-based cervical screening programs, based on cytology, have successfully reduced the burden of cervical cancer. Nevertheless limitations remain and new screening methods are emerging. Despite vaccination against the 2 most oncogenic types (HPV 16/18), cervical cancer screening will have to continue as an essential public health strategy. As the acquisition of an HR-HPV infection is critical in the progression to (pre-)cancerous cervical lesions, recent research has focused on HR-HPV detection. The sensitivity of HPV testing in primary and secondary prevention outweighs that of cytology, at the cost of slightly lower specificity. Although most of the HR-HPV infections are cleared after conization, new evidence from numerous studies encourages the implementation of HR-HPV testing and genotyping to improve posttreatment surveillance. An HR-HPV test 6 months after conization is a promising useful clinical marker to detect persistence and prevent progression. This review highlights the clinical role of HPV testing in primary and secondary cervical cancer screening.

Efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in women aged 15-25 years with and without serological evidence of previous exposure to HPV-16/18.

In the Phase III PATRICIA study (NCT00122681), the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (Cervarix(®), GlaxoSmithKline Biologicals) was highly efficacious against HPV-16/18 infections and precancerous lesions in women HPV-16/18 deoxyribose nucleic acid (DNA) negative and seronegative at baseline. We present further data on vaccine efficacy (VE) against HPV-16/18 in the total vaccinated cohort including women who may have been exposed to HPV-16/18 infection before vaccination. In women with no evidence of current or previous HPV-16/18 infection (DNA negative and seronegative), VE was 90.3% (96.1% confidence interval: 87.3-92.6) against 6-month persistent infection (PI), 91.9% (84.6-96.2) against cervical intraepithelial neoplasia (CIN)1+ and 94.6% (86.3-98.4) against CIN2+ [97.7% (91.1-99.8) when using the HPV type assignment algorithm (TAA)]. In women HPV-16/18 DNA negative but with serological evidence of previous HPV-16/18 infection (seropositive), VE was 72.3% (53.0-84.5) against 6-month PI, 67.2% (10.9-89.9) against CIN1+, and 68.8% (-28.3-95.0) against CIN2+ [88.5% (10.8-99.8) when using TAA]. In women with no evidence of current HPV-16/18 infection (DNA negative), regardless of their baseline HPV-16/18 serological status, VE was 88.7% (85.7-91.1) against 6-month PI, 89.1% (81.6-94.0) against CIN1+ and 92.4% (84.0-97.0) against CIN2+ [97.0% (90.6-99.5) when using TAA]. In women who were DNA positive for one vaccine type, the vaccine was efficacious against the other vaccine type. The vaccine did not impact the outcome of HPV-16/18 infections present at the time of vaccination. Vaccination was generally well tolerated regardless of the woman's HPV-16/18 DNA or serological status at entry.

Why consider human papillomavirus vaccination in older women?

Preventive human papillomavirus (HPV) L1 vaccines are safe and efficient to prevent infection and lesions of vaccine- specific HPV types in women from 15 to 26 years, but also in older age groups. Clearly, public health funds are to be spent to organize programs for vaccination of young adolescents. Immunobridging studies and clinical trials have shown that HPV vaccines generate significantly higher plasma antibodies than following natural infections in women up to 55 years and prevent up to 90.5% (95% CI 73.7-97.5) vaccine-specific HPV infections and lesions in women aged 24-45 years who are HPV DNA-negative at the time of vaccination. However, data from clinical trials with HPV L1 vaccines in older women (older than 25 years) are still scarce compared to the amount of evidence from trials in women younger than 26 years. Information from large population-based studies indicates that older women remain at risk of infection by high-risk HPV and the risk of persistent high-risk HPV infection is significantly higher than in young women, leading to a higher risk of progressing disease and carcinoma. The natural history of HPV infection remains enigmatic as we do not know if the immune mechanisms that clear the HPV infection offer prolonged protection. On the contrary, some data indicate that seroconversion after a natural infection only partially protects against re-infection. Given the large proportions of adult men and women that change sexual partners, the protective effects of HPV L1 vaccines may offer an extra benefit against HPV-related genital diseases within a much shorter time period than after vaccination of prepubertal adolescents.

Pregnancy outcome after cervical conisation: a retrospective cohort study in the Leuven University Hospital.

OBJECTIVE: To assess pregnancy outcome after conisation. DESIGN: Retrospective cohort study. SETTING: Belgium, data from a university hospital. POPULATION: Fifty-five pregnancies in 34 women after conisation, and 55 pregnancies in 54 women without a history of conisation or cervical intraepithelial neoplasia (CIN). METHODS: Hospital data were reviewed and questionnaires were collected from 599 women who had a conisation in a 5-year period, among whom subsequent pregnancies were identified. The control group consisted of matched pregnancies of women without a history of conisation. MAIN OUTCOME MEASURES: Gestational age at delivery, neonatal biometry, neonatal condition at birth. RESULTS: Numbers of sexual partners (4.6 +/- 3.4 SD versus 2.5 +/- 2.5 SD) and ex-smokers were significantly higher in the study group compared with the control group. Gestational age at delivery (266 +/- 2 days versus 274 +/- 9 days), neonatal head circumference (33.9 +/- 2.5 cm, versus 34.6 +/- 2.5 cm) and birthweight (3088 +/- 754 g versus 3381 +/- 430 g) were significantly lower in the study group compared with the control group. Numbers of preterm [<37 weeks; 14/55 (25%) versus 2/55 (4%); P = 0.002] and severe preterm (<34 weeks; 6/55 (11%) versus 0/55 (0%); P = 0.031] deliveries in the study group were significantly higher. There were no cases of perinatal mortality. CONCLUSIONS: Conisation affects obstetrical outcome after conisation for CIN. Babies tend to be born earlier and are smaller. It is not clear whether this is related to the procedure or to factors linked with CIN.

Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women.

BACKGROUND: The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine was immunogenic, generally well tolerated, and effective against HPV-16 or HPV-18 infections, and associated precancerous lesions in an event-triggered interim analysis of the phase III randomised, double-blind, controlled PApilloma TRIal against Cancer In young Adults (PATRICIA). We now assess the vaccine efficacy in the final event-driven analysis. METHODS: Women (15-25 years) were vaccinated at months 0, 1, and 6. Analyses were done in the according-to-protocol cohort for efficacy (ATP-E; vaccine, n=8093; control, n=8069), total vaccinated cohort (TVC, included all women receiving at least one vaccine dose, regardless of their baseline HPV status; represents the general population, including those who are sexually active; vaccine, n=9319; control, n=9325), and TVC-naive (no evidence of oncogenic HPV infection at baseline; represents women before sexual debut; vaccine, n=5822; control, n=5819). The primary endpoint was to assess vaccine efficacy against cervical intraepithelial neoplasia 2+ (CIN2+) that was associated with HPV-16 or HPV-18 in women who were seronegative at baseline, and DNA negative at baseline and month 6 for the corresponding type (ATP-E). This trial is registered with ClinicalTrials.gov, number NCT00122681. FINDINGS: Mean follow-up was 34.9 months (SD 6.4) after the third dose. Vaccine efficacy against CIN2+ associated with HPV-16/18 was 92.9% (96.1% CI 79.9-98.3) in the primary analysis and 98.1% (88.4-100) in an analysis in which probable causality to HPV type was assigned in lesions infected with multiple oncogenic types (ATP-E cohort). Vaccine efficacy against CIN2+ irrespective of HPV DNA in lesions was 30.4% (16.4-42.1) in the TVC and 70.2% (54.7-80.9) in the TVC-naive. Corresponding values against CIN3+ were 33.4% (9.1-51.5) in the TVC and 87.0% (54.9-97.7) in the TVC-naive. Vaccine efficacy against CIN2+ associated with 12 non-vaccine oncogenic types was 54.0% (34.0-68.4; ATP-E). Individual cross-protection against CIN2+ associated with HPV-31, HPV-33, and HPV-45 was seen in the TVC. INTERPRETATION: The HPV-16/18 AS04-adjuvanted vaccine showed high efficacy against CIN2+ associated with HPV-16/18 and non-vaccine oncogenic HPV types and substantial overall effect in cohorts that are relevant to universal mass vaccination and catch-up programmes. FUNDING: GlaxoSmithKline Biologicals.

[Should the antipapillomavirus vaccination after the age of 25 be advised?]. / Place de la vaccination antipapillomavirus après 25 ans.

Antipapillomavirus vaccination of young girls before their first sexual encounter is now a common practice. However, this prophylactive measure could also be extended to older patients. The HPV infection is indeed not limited to teenagers even if the highest incidence rate is noticed between the age of 18 and 30, it can also be found in older women. These older women show a sustained prevalence due to the longer persistence of the infection. This is clearly illustrated by the incidence of cervical cancer after the age of 50. Moreover, phase 3 studies in large unselected populations have shown the effectiveness of HPV vaccination in patients who had previously been infected by HPV (and got cured of it) as well as with patients who had never had any papillomavirus contact. Actually, less than 1 % of women who present simultaneously a HPV 16 and a HPV 18 infection will not derive any benefit from a HPV vaccination. Therefore, it seems logical to positively consider a HPV prophylaxis in patients who are above the age of 25 and who do not present any papillomavirus induced cervical lesion.

Prediction of recurrence after treatment for high-grade cervical intraepithelial neoplasia: the role of human papillomavirus testing and age at conisation.

OBJECTIVES: The aim of this study was to examine the accuracy of the presence of high-risk human papillomavirus (HR-HPV) DNA (HR-HPV DNA test) postconisation as prediction of recurrent or residual cervical intraepithelial neoplasia (CIN) after treatment of high-grade cervical intraepithelial lesions (CIN2+) in a prospective study and to compare this with follow-up cytology and the marginal status of the excised tissue. DESIGN: Prospective follow-up study. SETTING: Unselected women presenting at colposcopy clinic of University Hospital Gasthuisberg, Leuven. POPULATION: Seventy-two women treated with conisation for CIN2 or CIN3. METHODS: Women were followed by HR-HPV DNA test (Hybrid Capture II test of Digene) every 3 to 6 months. The same vial was used for cytology and the HR-HPV DNA test (SurePath). All women were further followed by colposcopy and cytology for 24 months at 6-month intervals. The outcome of the study was presence of >CIN2, proven with colposcopy-directed biopsy occurring within 24 months after treatment. HR-HPV status was correlated with recurrent or residual CIN2+. MAIN OUTCOME MEASURES: Sensitivity, specificity, predictive values and diagnostic odds ratios to predict treatment failure or cure were computed for HR-HPV testing, marginal status and follow-up cytology. HR-HPV status was also correlated with section margins postconisation and with the first cervical smear. RESULTS: In 6 of the 72 treated women (8%), residual or recurrent CIN occurred. Women with recurrence were significantly older than women without a recurrence (51.5 +/- 9.6 versus 39.8 +/- 12.2 years, P= 0.007). All six women with recurrence were HR-HPV positive, four had a positive follow-up smear (>or=atypical squamous cells of uncertain significance = ASCUS+) and only two had involved section margins. Among the 66 cured women, 15 were HR-HPV positive, 6 had an abnormal smear and 12 had positive section margins. Sensitivity of cytology, positive section margins and HR-HPV DNA positivity was 66.7, 33.3 and 100% to predict treatment failure. Specificity of the three tests was, respectively, 90.9, 81.8 and 77.3%. Women with HR-HPV DNA at 3 to 6 months showed recurrent or residual CIN in 15% (2/13) if they had normal follow-up Pap smears and in 50% (4/8) if they had abnormal Pap smears. Margin status was not statistically significantly associated with human papillomavirus status. CONCLUSION: Persistence or clearance of HR-HPV DNA is an early valid prognostic marker of failure or cure after treatment for CIN2+ and is more accurate than cytology or section margin status at the time of conisation. The absence of HR-HPV DNA has a 100% negative predictive value. Higher age at conisation may be a previously unrecognised risk factor for recurrence.

Nitroimidazole-resistant vaginal trichomoniasis treated with paromomycin.

A 33-year old woman with nitroimidazole-resistant vaginal trichomoniasis is described. She was treated with intravaginal paromomycin (500 mg daily for 2 days). This cured the trichomoniasis but resulted in severe local side effects. Paromomycin may be useful for difficult cases of nitroimidazole-resistant Trichomonas vaginalis vaginitis. The exact dosage still has to be determined.

An intracranial tumour--an uncommon cause of hyperemesis in pregnancy.

Brain tumours in pregnancy are rare. In this case vomiting and headache were the only signs. An assessment of the patient with vomiting in pregnancy to help reach a diagnosis when faced with vomiting in pregnancy is given. Following the diagnosis of a brain tumour during pregnancy, management should be tailored to the individual patient.

Postoperative day 3 serum human chorionic gonadotropin decline as a predictor of persistent ectopic pregnancy after linear salpingotomy.

OBJECTIVE: To evaluate the ability of preoperative clinical, ultrasonographic, intraoperative findings and pre-postoperative serum human chorionic gonadotropin (hCG) levels to predict persistent ectopic pregnancy (EP). STUDY DESIGN: Retrospective cohorts study. SETTING: Tertiary care, university hospital. In all, 61 women with EP treated with laparoscopic linear salpingostomy between January 1995 and December 1999. RESULT: Out of 61 patients, 10 (9%) were diagnosed with a persistent EP. When compared with 51 (91%) successfully treated patients there were no differences in preoperative clinical and ultrasonographic findings, preoperative serum hCG levels and intraoperative findings. The postoperative decline of hCG levels were different in both groups. No case of persistent EP was found if the postoperative day 3 decline of hCG was more than 55%. CONCLUSION: Postoperative serum hCG follow-up is important after salpingotomy to prevent persistent EP. A decline of less than 55% at day 3 predicts persistent EP and may select early cases for second line methotrexate therapy.

Lymphocytes and dendritic cells in the normal uterine cervix. An immunohistochemical study.

OBJECTIVE: Assessment of the appearance, distribution and numerical density of immune cell populations in the normal human uterine cervix. SETTING: University Hospital Gasthuisberg. SUBJECTS: 29 healthy women undergoing total hysterectomy for non-cervical benign uterine disease. ANALYSIS: Immunohistochemistry and morphometrical analysis on histological sections containing ectocervix, transformation zone and endocervix, using antibodies against the following antigens: HLA-DR, CD4, CD22, CD1a and CD8. STATISTICAL ANALYSIS: Wilcoxon rank sum test. RESULTS: Lymphocytes in the epithelial and stromal compartments are predominantly T-lymphocytes. Intraepithelial T-lymphocyte and Langerhans' cell densities and their distribution are not influenced by the menstrual cycle and are the same in both ectocervix and transformation zone. CONCLUSION: The wide variation of T lymphocyte subpopulations and Langerhans' cell densities in the normal epithelium of the uterine cervix is stressed. We are the first to present a large and well-defined control series, which is indispensable to study the effect of smoking and other factors on the cervical immune system.

Cervical cotinine and macrophage-Langerhans cell density in the normal human uterine cervix.

Cotinine levels in blood and cervical fluid of smokers and non-smokers were analysed using capillary-column gas chromatography. These levels were not related to numerical cell densities of intraepithelial S100-protein- and LN2-positive Langerhans cells or to MAC-387-positive macrophages in the stroma of the transformation zone of normal uterine cervices. A decrease in the number of Langerhans cells was noted in smokers, especially in those using oral contraceptives (OCs). Macrophages were more numerous in the endocervical stroma of smokers, suggesting a local response to smoke constituents. These findings may indicate a synergistic suppression of local cervical immunity by smoking and OCs.

Langerhans' cells and L1 antigen expression in normal and abnormal squamous epithelium of the cervical transformation zone.

This study evaluates the presence of Langerhans' cells and expression of L1 antigen in squamous epithelium of the normal and dysplastic transformation zone of the cervix uteri and determines the influence of tobacco smoking and pregnancy. Women who smoked and pregnant women showed a decrease of Langerhans' cell counts in normal epithelium. In cervical intraepithelial neoplasia (CIN) 1 lesions, decreased Langerhans' cell counts were noted. L1 antigen expression was significantly less in CIN of all grades. Normal squamous epithelium of smokers showed weaker staining for L1 antigen but total staining scores were not significantly different. These data suggest a decrease in epithelial cell-mediated immune response in smokers, pregnant women and in low-grade CIN. Dysplastic squamous cells probably have intracellular regulatory problems independent of other immune cells.

Carbon dioxide laser for laparoscopic enterocele repair.

The use of the carbon dioxide (CO2) laser for laparoscopic enterocele repair was evaluated in four women with an enterocele as the only pathology. Three women had a large enterocele after earlier hysterectomy, and one young woman had a congenital enterocele. The technique consists of vaporizing the peritoneum of the enterocele; however, it is important first to delineate carefully the lesion's circumference because of the strong retraction during vaporization. Subsequently, a posterior culdotomy is performed taking care to restore the horizontal position of the upper vaginal axis by shortening the uterosacral ligaments, which are sutured together on the midline and the posterior vaginal wall. The (CO2) laser has the advantage that the superficial vaporization it produces is rapid (<5 min), safe, and completely bloodless. The shrinking during vaporization facilitates subsequent repair. Postoperative morbidity and recovery were uneventful for all patients. The (CO2) laser seems to have some advantages over sharp endoscopic resection of enteroceles. The relative simplicity of technique and the low postoperative morbidity suggest that endoscopy could become routine in pelvic floor surgery, improving diagnosis and complementing vaginal surgery while avoiding laparotomy.

Tobacco smoking impairs the local immunosurveillance in the uterine cervix. An immunohistochemical study.

Previous reports have supported an association between tobacco smoking and cervical neoplasia. Our observations show an association between smoking and a reduction of the numerical densities of Langerhans cells and of helper/inducer T lymphocytes in the squamous epithelia of the transformation zone of the uterine cervix. This suggests a local impairment of cell-mediated immunity by smoking. This immunosuppressive effect could support the concept that smoking is an independent risk factor for cervical neoplasia.

Tobacco smoking and the uterine cervix: cotinine in blood, urine and cervical fluid.

Cotinine levels in blood, urine and cervical fluid of smokers and nonsmokers were analyzed by capillary-column gas chromatography. The sensitivity of this method appeared to be 100%. The specificity was lower (87.5% in blood, 25% in urine and 75% in cervical fluid). Nonsmokers exposed to smoke by others had low but detectable cotinine levels in the three body fluids. The highest cotinine levels in cervical fluid were detected during the proliferative phase of the cycle. Cotinine levels in cervical fluid and blood correlated well, but the correlation was less during the proliferation phase. Cotinine measurement in cervical fluid proves to be a reliable method to quantify exposure to tobacco smoke, even when induced by others.

Multicenter evaluation of Iso-ALP test kit for measurement of bone alkaline phosphatase activity in serum and plasma.

A test kit (Iso-ALP, Boehringer Mannheim) for measuring human bone alkaline phosphatase activity in serum or plasma was evaluated in five laboratories in three countries. The assay is based on the principle described by Rosalki and Foo (Clin Chem 1984;30:1182-6) and uses wheat germ lectin to precipitate bone alkaline phosphatase. Residual ALP in the supernate in comparison with total ALP is used to quantify the bone fraction. The imprecision of residual ALP measurement was low (median between-run CV 4.9%) and comparable with that of total ALP. Linearity of precipitation was demonstrable up to a bone ALP activity (diethanolamine buffer 37 degrees C) of 2000 U/L, though a matrix effect was observed for dilutions of high-activity sera in saline or bovine serum albumin. For assaying patients' samples, different batches of lectin demonstrated excellent comparability. Taking electrophoresis as a basis for standardization, we determined that the lectin precipitated approximately 90% of bone ALP, but < 5% of nonbone ALP. From this we derived serum/plasma upper reference limits for bone ALP activity in adults and children.

[Diagnosis of chronic pancreatitis. Studies of duodenal juice after stimulation with the secretin-ceruletide test. Decision limits and evaluation of various parameters]. / Diagnostik der chronischen Pankreatitis. Untersuchungen im Duodenalsaft nach Stimulation mittels Sekretin-Ceruletid-Test. Entscheidungsgrenzen und Bewertung verschiedener Messgrössen.

187 patients were checked up over 4 years by the secretin-ceruletide test. Independently of the test results they were assigned to various disease groups on the basis of clinical assessment. 131 subjects were divided in a pilot investigation into: subjects with a healthy pancreas (n = 55); subjects with chronic pancreatitis (n = 50); subjects whose pancreatic condition could not be classified clearly (n = 26). 8 parameters were compared by univariate and multivariate statistical procedures in order to confirm or rule out the presence of chronic pancreatitis. The discriminatory power of the following parameters in duodenal fluid proved to be sufficiently high, with less than 15% frequency of misclassification: chymotrypsin (activity) and/or; lipase (activity) and/or; amylase (activity); viscosity. Under routine conditions measurement of the activity of two of these enzymes is sufficient. Their contribution to discrimination proved to be approximately equal. The diagnostic sensitivity and specificity of the parameters bicarbonate, lipase (concentration), trypsin (activity) and volume of duodenal fluid are lower. The classification rules derived from the above pilot group were confirmed by a diagnostic study under routine condition in a test group of 38 patients. Limitation to examining only volume and a maximum of 3 parameters which proved best in distinguishing between patients with chronic pancreatitis and healthy subjects, together with the omission of the first-hour samples after a secretin bolus, considerably reduced laboratory workload without altering the discriminatory power of the secretin-ceruletide test.

[Problems of electroconvulsive treatment in advanced age--its possible applications and necessities, indications criteria, method and effectiveness]. / Probleme der Elektroheilkrampfbehandlung (EKB) im höheren Lebensalter--ihre Einsatzmöglich- und -notwendigkeiten, Indikationskriterien, Methodik und Effektivität.

After a critical discussion with antiquated and actual problems to the electroconvulsive therapy the problem-important peculiarities of progress and treatment of the psychosis in the higher age are exhibited. In search of satisfactoring solutions we used Dexamethazon as a supplemental premedication in the electroconvulsive therapy and by this way we found out a remarkable minimize of complications which allowed to put in more frequently the electroconvulsive therapy during the psychosis in the higher age. This leads to a general optimation of prognosis of the late psychical diseases. Beside the method itself the urgency of indications and exclusion of standards are described in the same way, also there are shown the few complications in comparison with the successes of therapy of 2010 electricalconvulsive therapies from 433 patients.