Lichen sclerosus and risk of cancer Halonen, Pia; Jakobsson, Maija; Heikinheimo, Oskari ...
International journal of cancer,
1 May 2017, Letnik:
140, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Malignant potential of lichen sclerosus (LS) has been suspected, but evidence is sparse. We used the population‐based Finnish Cancer Registry data to further study this connection.
We identified all ...women with the diagnosis of LS (n = 7,616) listed in the Finnish Hospital Discharge Registry from 1970 to 2012. The cohort was followed through the Finnish Cancer Registry for subsequent cancer diagnoses until 2014. Standardized incidence ratios (SIRs) were calculated for different cancers by dividing the observed numbers of cancers by expected ones. The expected numbers were based on national cancer incidence rates.
During the follow‐up period, we found 812 cancers among patients with LS (SIR: 1.13, 95% CI 1.05–1.21). LS was associated with an increased risk of vulvar (182 cases, SIR: 33.6, 95% CI 28.9–38.6) and vaginal cancer (4 cases, SIR: 3.69, 95% CI 1.01–9.44). The risk of cancers of the uterine cervix and lung was significantly decreased.
LS is associated with an increased risk for vulvar and vaginal cancer. These data are important when designing the care of women diagnosed with LS.
What's new?
Does it or doesn't it? Evidence is scant on whether the skin condition lichen sclerosus leads to cancer. These authors conducted the largest study to date, looking at 7,600 patients for nearly a decade. Among these patients, 800 cancer cases arose. Analysis showed that lichen sclerosus does increase one's risk of developing vulvar or vaginal cancer, but decreases the risk of cervical cancer, although the numbers were few due to the rarity of LS and these cancers.
Mifepristone is a steroidal antiprogestin and antiglucocorticoid acting at the receptor level. The aromatic dimethylaminophenyl side chain in position 11 of the steroid structure is essential for the ...antagonistic properties of mifepristone. The pharmacokinetics of mifepristone are characterised by rapid absorption, a long half-life of 25 to 30 hours and micromolar serum concentrations following ingestion of doses currently in clinical use. The serum transport protein alpha 1-acid glycoprotein (AAG) regulates the serum kinetics of mifepristone. Binding to AAG limits the tissue availability of mifepristone, explaining the low metabolic clearance rate of 0.55 L/kg/day and the low volume of distribution of mifepristone. Also, similar serum concentrations of mifepristone following ingestion of single doses exceeding 100mg can be explained by saturation of the binding capacity of serum AAG. Following oral intake, mifepristone is extensively metabolised by demethylation and hydroxylation, the initial metabolic steps are catalysed by the cytochrome P450 (CYP) enzyme CYP3A4. The 3 most proximal metabolites, namely the monodemethylated, didemethylated and hydroxylated metabolites of mifepristone, all retain considerable affinity toward the human progesterone and glucocorticoid receptors; in addition, the serum concentrations of these 3 metabolites are in a similar range as those of the parent drug. Thus, the combined pool of mifepristone, as well as that of the metabolites, seems responsible for the biological actions of mifepristone. Combination therapy with mifepristone and low dose prostaglandin is currently in clinical use for termination of early pregnancy in China, France, Sweden and the UK. The combined regimen is well tolerated and highly efficacious with a 95% rate of complete pregnancy terminations. Recent clinical studies on pregnancy termination have focused on dose optimisation of mifepristone and evaluation of the orally active prostaglandin derivative misoprostol. In addition, several other indications for the clinical use of mifepristone, such as induction of labour, contraception, as well as treatment of various hormone dependent disorders, are emerging. The major obstacles currently inhibiting further evaluation and distribution of mifepristone are political rather than clinical. However, it is hoped that the eventual introduction of new antiprogesterone molecules by several manufacturers will enhance the availability of this important class of new drugs.
To evaluate whether a public program providing long-acting reversible contraceptive (LARC) methods free of charge increases the LARC initiation rate and reduces the unintended pregnancy rate in the ...general population.
Since 2013, all women in Vantaa, Finland, have been entitled to 1 LARC method free of charge. With time-series analysis between 2000 and 2015, we assessed whether this public program was associated with changes in steady-state mean rates of LARC initiation and abortions.
The initiation rate of LARCs (1/1000 women) increased 2.2-fold from 1.9 to 4.2 after the intervention (P < .001). Concomitantly, the abortion rate (1/1000 women) declined by 16% from 1.1 to 0.9 in the total sample (P < .001), by 36% from 1.3 to 0.8 among those aged 15 to 19 years (P < .001), and by 14% from 2.0 to 1.7 among those aged 20 to 24 years (P = .01).
The LARC program was associated with increased uptake of LARC methods and fewer abortions in the population. Public Health Implications. Entitling the population to LARC methods free of charge is an effective means to reduce the unmet need of contraception and the need for abortion, especially among women younger than 25 years.
OBJECTIVE:To assess the risks of gynecologic cancer according to the type of endometriosis in women with surgically verified endometriosis.
METHODS:This is a population-based study of women with ...surgically verified endometriosis retrieved from the Finnish Hospital Discharge Register 1987–2012 (N=49,933); the subtypes of ovarian (n=23,210), peritoneal (n=20,187), and deep infiltrating (n=2,372) endometriosis were analyzed separately. Gynecologic cancers were obtained from the Finnish Cancer Registry. The outcome measure was the standardized incidence ratio (95% CI) calculated as the ratio between the observed to the expected number of cancers and defined for each gynecologic cancer and further stratified according to the histology, follow-up time since surgery, and age at follow-up. The follow-up was 838,685 person-years, and the Finnish female population served as the reference.
RESULTS:Endometriosis was associated with increased risk of ovarian cancer (standardized incidence ratio 1.76 95% CI 1.47–2.08), especially with endometrioid (3.12 2.15–4.38) and clear cell (5.17 3.20–7.89) histologic type and to a lesser extent with serous type (1.37 1.02–1.80). The risk of ovarian cancer was highest among women with ovarian endometriosis and especially for endometrioid (4.72 2.75–7.56) and clear cell (10.1 5.50–16.9) ovarian cancer, occurring 5–10 years after the index surgery. The overall risk of ovarian cancer was not increased among women with peritoneal and deep infiltrating endometriosis. However, peritoneal endometriosis was associated with a twofold increase in risk of endometrioid histology. The risk of endometrial cancer was not altered in the entire cohort. The standardized incidence ratio for precancerous cervical lesions was 0.81 (0.71–0.92) and for invasive squamous cell carcinoma of the cervical cancer 0.46 (0.20–0.91).
CONCLUSION:The excess risk of ovarian cancer among women with ovarian endometriosis translates into two excess cases per 1,000 patients followed for 10 years. Acknowledging these risks is important when planning long-term management of women with endometriosis.
Uterine leiomyomas are common benign smooth muscle tumors that impose a major burden on women’s health. Recent sequencing studies have revealed recurrent and mutually exclusive mutations in ...leiomyomas, suggesting the involvement of molecularly distinct pathways. In this study, we explored transcriptional differences among leiomyomas harboring different genetic drivers, including high mobility group AT-hook 2 (HMGA2) rearrangements, mediator complex subunit 12 (MED12) mutations, biallelic inactivation of fumarate hydratase (FH), and collagen, type IV, alpha 5 and collagen, type IV, alpha 6 (COL4A5-COL4A6) deletions. We also explored the transcriptional consequences of 7q22, 22q, and 1p deletions, aiming to identify possible target genes. We investigated 94 leiomyomas and 60 corresponding myometrial tissues using exon arrays, whole genome sequencing, and SNP arrays. This integrative approach revealed subtype-specific expression changes in key driver pathways, including Wnt/β-catenin, Prolactin, and insulin-like growth factor (IGF)1 signaling. Leiomyomas with HMGA2 aberrations displayed highly significant up-regulation of the proto-oncogene pleomorphic adenoma gene 1 (PLAG1), suggesting that HMGA2 promotes tumorigenesis through PLAG1 activation. This was supported by the identification of genetic PLAG1 alterations resulting in expression signatures as seen in leiomyomas with HMGA2 aberrations. RAD51 paralog B (RAD51B), the preferential translocation partner of HMGA2, was up-regulated in MED12 mutant lesions, suggesting a role for this gene in the genesis of leiomyomas. FH-deficient leiomyomas were uniquely characterized by activation of nuclear factor erythroid 2-related factor 2 (NRF2) target genes, supporting the hypothesis that accumulation of fumarate leads to activation of the oncogenic transcription factor NRF2. This study emphasizes the need for molecular stratification in leiomyoma research and possibly in clinical practice as well. Further research is needed to determine whether the candidate biomarkers presented herein can provide guidance for managing the millions of patients affected by these lesions.
During the past 20 years, there have been prolonged vendace (Coregonus albula) recessions in several Finnish lakes. Hypotheses have been proposed that predation by brown trout (Salmo trutta m. ...lacustris) or perch (Perca fluviatilis) on young-of-the-year vendace could prevent the recovery of the vendace stocks from a low-density state. In this study, dynamic modelling was applied to examine the effect of predation, assuming a dome-shaped spawning stockrecruitment relationship for vendace, type II or III functional responses to predation by brown trout and perch, and a constant rate of fishing. The results showed that the form of the functional response is crucial in determining the significance of the predation on vendace stocks that have a steep dome-shaped stockrecruitment relationship. In all cases, however, predation by perch had more effect than that by brown trout, probably due to perch occupying the pelagic zone when the vendace stock is sparse. This may make the mortality of vendace increase with decreasing population density (depensatory mortality) at certain density levels.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
Women undergoing an induced abortion are highly fertile and at risk of subsequent unplanned pregnancy. We recently completed a randomized clinical trial showing that routine provision of ...intrauterine device (IUD) at the time of abortion significantly reduced the risk of subsequent abortion during a 5‐year follow up. As the use of highly effective contraception may affect all subsequent pregnancies, we analyzed the rate and distribution of all subsequent pregnancies (deliveries, miscarriages, and abortions), and the risk factors for these various pregnancy outcomes in the above‐mentioned randomized clinical trial.
Material and methods
We enrolled adult women requesting first‐trimester induced abortion and candidates for IUD for post‐abortion contraception. Women (n = 751) were randomized to receive an IUD (either levonorgestrel‐releasing IUD or copper IUD) by the clinic responsible for abortion care vs. routine care of IUD provision in primary health care with oral contraceptives for interval contraception. In the present secondary analysis, we identified all deliveries, miscarriages, and abortions in the intervention (n = 375) and control (n = 373) cohorts during the 5‐year follow up using the Finnish national registries. The trial is registered at Clinical Trials (NTC01223521).
Results
The overall delivery, miscarriage, and abortion rates were 42.0, 12.0 and 32.1/1000 years of follow up (yFU). Any new pregnancy occurred in 98 women in the intervention and in 129 women in the control cohort (hazard ratio 0.73, 95% confidence interval 0.56–0.95, p = 0.023). The effect of routine IUD provision in reducing pregnancies was limited to the first 2 yFU. The number of subsequent induced abortions and of women undergoing it were significantly reduced, and time to abortion was prolonged by the intervention. However, the overall number, the number of women with subsequent delivery or miscarriage, and the times to these events were not significantly affected. History of previous pregnancy (delivery or abortion) and smoking were risk factors for subsequent induced abortion, but not for delivery or miscarriage.
Conclusions
Routine provision of IUD as part of abortion care did not reduce the rates of delivery or miscarriage during the 5‐year follow up. The rates of all pregnancies and the need of subsequent induced abortion were reduced by IUD provision during the first 2 yFU.
Routine provision of IUD for post‐abortion contraception decreased the rate of all pregnancies and that of induced abortions during 5‐year follow up. However, no significant differences emerged in the rates of delivery or miscarriage. The duration of effect of the intervention was limited to the first 2 years.
The association between Lichen planus (LP) and cancer has been under debate for decades. We studied the connection via population‐based Finnish register data. All women with the diagnosis of LP (n = ...13,100) were identified from the Finnish Hospital Discharge Registry from 1969–2012. These patients were linked with subsequent cancer diagnoses from the Finnish Cancer Registry until 2014. Standardized incidence ratios (SIRs) were counted for different cancers by dividing the observed numbers of cancers by expected numbers, which were based on national cancer incidence rates. In total, 1,520 women with LP were diagnosed with cancer (SIR 1.15, 95% confidence interval CI 1.09–1.20). LP was associated with an increased risk of cancer of lip (SIR 5.17, 95% CI 3.06–8.16), cancer of tongue (SIR 12.4, 95% CI 9.45–16.0), cancer of oral cavity (SIR 7.97, 95% CI 6.79–9.24), cancer of esophagus (SIR 1.95, 95% CI 1.17–3.04), cancer of larynx (SIR of 3.47, 95% CI 1.13–8.10) and cancer of vulva (SIR 1.99, 95% CI 1.18–3.13). The risk of cancer was not increased in other locations where LP manifests (pharynx and skin). Patients with diagnosed LP have an increased risk of developing cancer of lip, tongue, oral cavity, esophagus, larynx and vulva. These data are important when considering treatment and follow‐up of patients with LP diagnosis.
What's new?
Lichen planus (LP) is a chronic disease of the skin and mucous membranes that is likely autoimmune in origin. Owing to its inflammatory nature, it is also suspected of causing certain cancers. Whether LP possesses malignant potential, however, remains uncertain. Here, in a cohort of 13,100 women diagnosed with LP between 1969 and 2012 in Finland, some 1,520 were eventually diagnosed with cancer. Malignancies with significant increases in incidence in LP patients included those of the lip, tongue, oral cavity, esophagus, larynx and vulva. The findings suggest that LP patients could benefit from multidisciplinary approaches to care.
Contraceptive use in the Nordic countries Lindh, Ingela; Skjeldestad, Finn E.; Gemzell‐Danielsson, Kristina ...
Acta obstetricia et gynecologica Scandinavica,
January 2017, 2017-Jan, 2017-01-00, 20170101, 2017, Letnik:
96, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Introduction
The aim was to compare contraceptive use in the Nordic countries and to assess compliance with recommendations from the European Medicines Agency regarding the use of combined oral ...contraception containing low‐dose estrogen and levonorgestrel, norethisterone or norgestimate.
Material and methods
Data on hormonal contraceptive prescriptions and sales figures for copper intrauterine devices were obtained from national databases and manufacturers in Denmark, Finland, Iceland, Norway and Sweden in 2010–2013.
Results
Contraceptive use was highest in Denmark (42%) and Sweden (41%), followed by Finland (40%). Combined oral contraception was the most used method in all countries, with the highest use in Denmark (26%). The second most used method was the levonorgestrel‐releasing intrauterine system, with the highest use in Finland (15%) and ≈10% in the other countries. Copper intrauterine devices (7%) and the progestin‐only pill (7%) were most often used in Sweden. Combined oral contraception use decreased with increasing age and levonorgestrel‐releasing intrauterine system and progestin‐only pills use increased. The use of long‐acting reversible methods of contraception (=levonorgestrel‐releasing intrauterine system, copper intrauterine devices, and implants) increased with time and was highest in Sweden (20%) and Finland (18%). The highest use of European Medicines Agency recommended combined oral contraception was in Denmark, increasing from 13 to 50% between 2010 and 2013. In Finland, recommended combined oral contraception remained below 1%.
Conclusions
Contraceptive use was highest in Denmark and Sweden, levonorgestrel‐releasing intrauterine system use was highest in Finland and all long‐acting methods were most common in Sweden. The use of combined oral contraception recommended by the European Medicines Agency was highest in Denmark.
PDF
