A Mayer-Rokitansky-Kuster-Hauser patient with leiomyoma and dysplasia of neovagina: a case report.

BACKGROUND: Most patients with congenital uterus and vaginal aplasia (i.e., Mayer-Rokitansky-Kuster-Hauser [MRKH] syndrome) have rudimentary pelvic uterine structures that contain smooth muscle. Although leiomyomas and dysplasia of vaginal mucosa are relatively common in the general population, they are rare in MRKH patients. Data on the vulnerability of neovaginas to HPV-associated dysplasia are limited. CASE PRESENTATION: A rare case of an MRKH patient with two gynaecological conditions detected during long-term gynaecological follow-up is presented. At the age of 21, the patient was treated for HPV-associated neovaginal dysplasia. At the age of 47, a pelvic leiomyoma was detected with transvaginal ultrasound and confirmed with magnetic resonance imaging. CONCLUSION: A Pap smear or human papillomavirus testing is indicated in sexually active MRKH women. Uterine rudiments contain smooth muscle, which facilitates the development of oestrogen-dependent diseases, such as leiomyomas and adenomyosis. Although magnetic resonance imaging is recommended in cases of a pelvic mass, easily attainable and cost-efficient transvaginal ultrasound offers high diagnostic accuracy in patients with a surgically created neovagina and is suitable for the patients' follow-up. Guidelines for the gynaecological follow-up of MRKH patients are warranted.

Pelvic floor disorders and health-related quality of life in older women: Results from the Women's Gynaecological Health study in Lieto, Finland.

OBJECTIVE: The aim of this study was to analyse the prevalence of pelvic floor disorders and to describe health-related quality of life (HRQoL) among older women. We also compared participants' HRQoL with the age-matched general female population and analysed factors associated with HRQoL. STUDY DESIGN: This is a population-based study of a cohort of women born in 1948 and in 1950 (n = 143) which is also part of the Women's Gynaecological Health study in Lieto, Finland. METHODS: The data were collected by questionnaires which pertained to socio-demographics, health-related variables, pelvic floor disorders and HRQoL (15D). Linear model was conducted to estimate a model of factors that associated with HRQoL. RESULTS: The prevalence of urinary incontinence, faecal incontinence and pelvic organ prolapse was 50%, 13% and 12%, respectively. The overall HRQoL score of the study cohort is broadly similar to that of the agematched general Finnish female population (mean±SD15D scores 0.905±0.084 vs 0.912±0.077). Higher number of medications was the most important explanatory factor for lower HRQoL. CONCLUSION: Urinary incontinence was common; however, the impact on HRQoL was minor. The overall HRQoL score of the study cohort was broadly similar to that of age-matched general female population. Women who used a higher number of medications had lower HRQoL compared to women who used fewer medications.

High-risk human papillomavirus associated with incident cervical intraepithelial neoplasia developing in mothers in the Finnish Family HPV Study cohort.

BACKGROUND: Cofactors of high-risk (HR) human papillomavirus (HPV) in the progression of cervical intraepithelial neoplasia (CIN) are incompletely characterized. In this study these cofactors were investigated in a longitudinal setting. METHODS: A cohort of 329 women (mean age 25.5 y) were enrolled in the Finnish Family HPV Study, and followed-up for 6 y with serial cervical samples for HPV genotyping, virus integration status, and HPV serology. Hospital records were reviewed until March 2010 and linked with HPV detection data. All incident CIN lesions were subjected to HPV genotyping. HPV covariates were studied in an age- and HPV-matched nested case-control (1:4) setting. RESULTS: Twelve of the 329 women developed an incident CIN: 2 CIN1, 3 CIN2, and 7 CIN3. HPV16 was detected most frequently (7/12), followed by HPV58 (2/12), HPV18, HPV31, and HPV42. HPV integration was present in 4/12 cases. Long-lasting persistence of HPV31 and HPV16 preceded incident CIN2 and CIN3. In multivariate conditional logistic regression, the risk for incident CIN increased up to 4-fold with increasing number of deliveries (p = 0.024) and decreased with history of genital warts (p = 0.036). CONCLUSION: Baseline HR-HPV infections and their persistence precede incident CIN by several years. The 2 independent covariates of HR-HPV were (1) number of deliveries (increasing the risk), and (2) history of genital warts (protective effect).

[Update on current care guidelines. Diagnosis, treatment and follow-up of cytological changes in the cervix, vagina and vulva]. / Kohdunkaulan, emättimen ja ulkosynnytinten solumuutokset--diagnostiikka, hoito ja seuranta.

Approximately 150 cervical cancer cases are diagnosed in Finland annually. Both incidence and mortality have decreased by 80% since organised screening began. Recently, screening based on primary HPV-testing with Pap-smear triage has been shown to be more sensitive and more specific among women over 35 years old in randomised studies and thus may be implemented in routine. Abnormal findings in Pap smears indicate management. Confirmed CIN1 lesions are followed up and CIN2 and worse lesions treated. Follow-up after treatment should be reliably arranged, because elevated risk of cancer remains over 20 years after treatment. Quality control is of utmost importance.

Radiation-induced effects on telomerase in gynecological cancer cell lines with different radiosensitivity and repair capacity.

PURPOSE: Telomerase activation in response to irradiation might enhance the radioresistance of cells. Thus, we have investigated radiation-induced effects on telomerase in six gynecological cancer cell lines, with different intrinsic radiosensitivity and capacity for sublethal damage repair (SLDR). MATERIALS AND METHODS: Three endometrial adenocarcinoma (UM-EC-1, UT-EC-2B and UT-EC-3) and three vulvar squamous cell carcinoma (A431, UM-SCV-2 and UM-SCV-7) cell lines were irradiated with doses of 5, 10 and 25 Gy and the effects on telomerase were evaluated at 0.5, 6, 24 and 48 h post-irradiation. Telomerase activity was quantitatively measured by SYBR Green real-time telomeric repeat amplification protocol. RESULTS: The most radioresistant cell line A431 had the strongest stimulatory effects (approximately 2.0 - 2.5-fold) on telomerase activity 24 and 48 h post-irradiation with the highest radiation doses. In contrast to that, telomerase activities in the highly radiosensitive cell line UT-EC-2B remained below the basal level throughout the 48-h period of post-irradiation with the highest doses, and even a decline to approximately 50% of the basal level was found 24 h after exposure. In other cell lines being either moderately or highly radiation resistant, telomerase activity levels in response to irradiation remained mainly at the basal level or gradually increased. CONCLUSIONS: The present findings indicate that there might be a connection between the radiation-induced telomerase response and radiosensitivity. However, no correlation was found between the radiation-induced effects on telomerase and the sublethal damage repair capacity of the cells.

Characterization of 10 vulvar carcinoma cell lines by karyotyping, comparative genomic hybridization and flow cytometry.

OBJECTIVE AND METHODS: Ten vulvar squamous cell carcinoma cell lines established at the University of Michigan (UM-SCV-1A, -1B, -2, -3, -4, -6, -7) and at the University of Turku (UT-SCV-1, -2, -3) were characterized by G-banding karyotyping, comparative genomic hybridization (CGH), and deoxyribonucleic acid (DNA) flow cytometry. RESULTS: All cell lines had hyperdiploid DNA content as measured by flow cytometry. The DNA index (DI) remained relatively stable through different passages in 9 of 10 cases. DIs of UM-SCV-3 and UT-SCV-2 were near-diploid, as were the corresponding karyotypes. The 10 SCVs showed remarkable genetic similarities with respect to consistent chromosome rearrangements. Loss of 3p, noted in 8/10 SCVs, was narrowed to the smallest common region at 3p11-3p13. Loss of 8pter-p11 was observed in 10/10 cell lines. Loss of 11qter-q23 was present in UM-SCV-1 and -2, and in all four recently karyotyped SCVs. Other consistent losses include Xpter-p11 in 6/10, and 18qter-q11 in 7/10 cell lines. Common gains included gain of 8q in 8/10 and 3q in 6/10. Consistent copy number imbalances were confirmed by CGH; concerning loss of 3p, in 63%, to loss of 8p in 70%, to gain of 3q in 83%, and to gain of 8q in 75% of the cell lines. CONCLUSIONS: CGH and karyotyping showed concordance in defining copy number imbalances, thus supporting the accuracy of CGH to detect chromosome imbalances in tumors that cannot be karyotyped.

Does skin fibroblast radiosensitivity predict squamous cancer cell radiosensitivity of the same individual?

Individualization of radiation doses is presumed to result in better radiotherapy outcome. Success rate in measuring radiosensitivity is probably the most limiting factor for present radiosensitivity assays to be introduced into clinical routine. To find a simpler predictive parameter, we compared the radiosensitivity of dermal fibroblasts and head and neck squamous cell carcinoma (SCC) cell lines established from the same individuals. The radiosensitivity was tested using the clonogenic 96-well plate assay. The surviving fraction at 2.0 Gy (SF2) was determined, as well as the mean inactivation dose (AUC) of cancer cells. SF2 of SCC cell lines and skin fibroblasts were 0.25-0.44 and 0.11-0.43, respectively. AUC of SCC cells was 1.4-2.1 Gy. Dermal fibroblasts were more radiosensitive than SCC cells in 14 of 15 cases. In 1 patient (UT-SCC-8), cancer cells were found to be more radiosensitive than corresponding dermal fibroblasts. There was a clear tendency to a correlation between radiosensitivities of these 2 cell types, but statistical significance was reached only when the data of UT-SCC-8 was excluded. In our material, the intrinsic radiosensitivity of head and neck SCC cells could in most cases be predicted from the intrinsic radiosensitivity of dermal fibroblasts established from the same individual.

Supra-additive effect with concurrent paclitaxel and cisplatin in vulvar squamous cell carcinoma in vitro.

The effect of concurrent paclitaxel and cisplatin was tested in vitro in 5 vulvar squamous cell carcinoma (SCC) cell lines (UM-SCV-1A, -2, -4 and -7 and UT-SCV-3). Chemosensitivity was tested using the 96-well plate clonogenic assay. Paclitaxel concentrations used varied between 0.4 and 1.6 nM, and cisplatin concentrations varied between 0.1 and 0.9 microg/ml. These drug concentrations are clinically achievable. Survival data were fitted to the LQ model, and the area under the curve (AUC) value was obtained with numerical integration. The type of interaction was determined by comparing the AUC ratio of the 2 drugs with the survival fraction (SF) of paclitaxel alone. With all cell lines tested the growth-inhibitory effect of simultaneous paclitaxel and cisplatin was at least additive. The effect of the tested combination on the UM-SCV-1A and UT-SCV-3 cell lines was clearly supra-additive with all paclitaxel concentrations tested, and the UM-SCV-4 and UM-SCV-7 cell lines exhibited a supra-additive effect with increasing paclitaxel concentrations. The degree of supra-additivity was dose-dependent in the UM-SCV-7 cell line with increasing synergy at higher paclitaxel doses. In the current study the combination of paclitaxel and cisplatin had a clear additive or supra-additive cytotoxic effect on the vulvar SCC cell lines, and it has been successfully used in other gynecologic malignancies; therefore concurrent paclitaxel and cisplatin also deserves further testing in clinical settings in advanced-stage vulvar carcinoma, which has a poor prognosis.

Docetaxel does not impair cardiac autonomic function in breast cancer patients previously treated with anthracyclines.

The effects of docetaxel treatment on autonomic cardiac function was studied with 24-h ECG recordings in breast cancer patients pretreated with anthracyclines. Twenty-four women were evaluated before docetaxel treatment and after 3-4 courses of docetaxel 100 mg/m(2). The heart rate, cardiac extrasystoles and heart rate variability (HRV) in both the time and frequency domain were assessed from 24-h ECG recordings. The acute effects of docetaxel were calculated from 1-h recordings immediately prior to, during and after infusion. Long-term effects were evaluated from 24-h recordings performed before treatment and after 3-4 courses of docetaxel. There was no increase in the number of cardiac extrasystoles during docetaxel infusion. The number of ventricular extrasystoles decreased from 14 (23) to 7 (14) during and 5 (10) after the first infusion (p=0.02). The heart rate, HRV and extrasystoles were similar before and after 3-4 courses of docetaxel. The treatment did not abolish circadian variability of the heart rate. Docetaxel did not deteriorate autonomic cardiac function. In conclusion, our findings suggest that docetaxel does not have harmful cumulative effects on autonomic control of the heart and is therefore unlikely to be cardiotoxic.

Paclitaxel combined with fractionated radiation in vitro: a study with vulvar squamous cell carcinoma cell lines.

Concurrent paclitaxel and radiation has given promising results in the treatment of a variety of solid tumors. We wanted to test the efficacy of this combination for vulvar carcinoma, which currently has a poor outcome in advanced stages. The radiation sensitivity, sublethal damage repair (SLDR) capacity and effect of paclitaxel during fractionated radiation were assessed in our study on 7 vulvar inherently radioresistant squamous cell carcinoma (SCC) cell lines. The 96-well plate clonogenic assay was used. Survival data were fitted to the linear quadratic model. The area under the curve (AUC), equivalent to mean inactivation dose (D), was obtained with numerical integration. AUC ratios between single-dose radiation and fractionated radiation with or without paclitaxel were used to determine the SLDR of the cell lines and the effect of paclitaxel on it. Seven currently tested vulvar SCC cell lines were found to have a limited capacity of repairing sublethal damage (SLD). Only 3 of them presented SLDR of significance. The effect of concurrent radiation and paclitaxel was clearly additive when the radiation dose was fractionated in most of the cell lines. In addition, 2 of the cell lines having SLDR exhibited a trend toward losing the repair capacity when paclitaxel was present during the irradiation. In addition, the survival curve of the UM-SCV-1A cell line gave the impression of a true paclitaxel effect on SLDR. Paclitaxel used concurrently with fractionated radiation showed effectiveness on vulvar carcinoma. The effect was at least additive and could even be expected to abrogate the SLDR during split-dose radiation.