Munanjohdinsyöpä : esiintyvyys, riski- suoja- sekä ennustetekijät

The aim of the study was to clarify the occurrence, and etiological and prognostic factors of primary fallopian tube carcinoma (PFTC). We studied the sociodemographic determinants of the incidence of PFTC in Finland and the role of chlamydial infections and human papillomavirus infections as risk factors for PFTC. Serum tumor markers were studied as prognostic factors for PFTC. We also evaluated selected reproductive factors (parity, sterilization and hysterectomy) as risk or protective factors of PFTC. The risks of second primary cancers after PFTC were also studied. The age-adjusted incidence of PFTC in Finland increased to 5.4 / 1,000,000 in 1993 97. The incidence rate was higher in the cities, but the relative rise was higher in rural areas. Women in the two highest social classes showed a 1.8 fold incidence compared with those in the lowest. Women in agriculture and those not working outside the home showed only half the PFTC incidence of those in higher socioeconomic occupations. Pretreatment serum concentrations of hCGβ, CA125 and TATI were evaluated as prognostic markers for PFTC. Elevated hCGβ values (above the 75th percentile, 3.5 pmol/L; OR 2.49, 95% CI 1.22 5.09), stage and histology were strong independent prognostic factors for PFTC. The effects of parity, sterilization and hysterectomy on the risk of PFTC were studied in a case control-study with 573 PFTC cases from the Finnish Cancer Registry. In multivariate analysis parity was the only significant protective factor as regards PFTC, with increasing protection associated with increasing number of deliveries. In univariate analysis sterilization gave borderline protection against PFTC and the protective effect increased with time since the operation. In multivariate analysis the protection did not reach statistical significance. Chlamydial and human papillomavirus (HPV) infections were studied in two separate seroepidemiological case-control studies with 78 PFTC patients. The incidence of women with positive HPV or chlamydial serology was the same in PFTC patients and in the control group and was not found to be a risk factor for PFTC. Finally, the possible risk of a second primary cancer after diagnosis and treatment of PFTC in a cohort of 2084 cases from 13 cancer registries followed for second primary cancers within the period 1943 2000 was studied. In PFTC patients, second primary cancers were 36% more common than expected (SIR 1.36, 95% CI 1.13 1.63). In conclusion, the incidence of PFTC has increased in Finland, especially in higher social classes and among those in certain occupations. Elevated serum hCGβ reflect a worsened prognosis. Parity is a clear protective factor, as is previous sterilization. After PFTC there is a risk of second primary cancers, especially colorectal, breast, lung and bladder cancers and non-lymphoid leukemia. The excess of colorectal and breast cancers after PFTC may indicate common effects of earlier treatments, or they could reflect common effects of lifestyle or genetic, immunological or environmental background.Sydän- ja verisuonisairaudet ovat Suomessa naisten yleisin kuolinsyy, syöpä on toiseksi yleisin. Vuonna 2005 uusia naisten gynekologisia syöpiä todettiin 1503; näistä 30 oli munanjohdinsyöpiä. Munanjohdinsyöpä on monietiologinen tauti ja harvinaisena vähän tutkittu; sen epidemiologiasta ei juurikaan ole tietoa. Väitöstutkimuksessa selvitettiin munanjohdinsyövän esiintyvyyttä sekä siihen vaikuttavia riski, suoja- ja ennustetekijöitä. Lisäksi monikansallisessa syöpärekisteritutkimuksessa selvitettiin riskiä sairastua uuteen syöpään sairastetun munanjohdinsyövän jälkeen. Munanjohdinsyövän esiintyvyyden todettiin lisääntyneen Suomessa lähes viisinkertaiseksi vuodesta 1953 vuoteen 1997, jolloin, insidenssi oli 5.4/1 000 000. Insidenssi on korkein kaupungeissa, mutta lisääntyi eniten maaseudulla. Ylemmissä sosiaaliluokissa munanjohdinsyöpää esiintyi 1.8-kertaisesti verrattuna alempiin sosiaaliluokkiin. Tietyissä ammattiryhmissä kuten akateemisissa sekä hallintoammateissa insidenssi oli korkeampi. Munanjohdinsyövän ennustetekijöistä todettiin koholla olevan seerumin kasvainmerkkiaine hCGß:n (> 3.5 pmol/l), taudin levinneisyyden sekä histologian (muu kuin seröösi carcinoma) olevan vahvoja huonon ennusteen tekijöitä. Synnyttäneisyyden, aiemman sterilisaation sekä kohdunpoiston mahdollista suojavaikutusta tutkittiin, kuten myös sairastettua Chlamydia trachomatis- tai ihmisen papillomavirus (HPV) -infektiota mahdollisena munanjohdinsyövän riskitekijänä. Synnyttäneisyys on vahva suojatekijä munanjohdinsyövälle ja suojavaikutus kasvaa synnytysten lukumäärän lisääntyessä. Myöhäisempi ensisynnytysikä lisäsi suojavaikutusta. Univariaattianalyysissä aiempi sterilisaatio suojasi munanjohdinsyövältä ja suojavaikutus lisääntyi, mitä nuoremmalla iällä toimenpide oli tehty ja mitä kauemmin toimenpiteestä oli aikaa kulunut. Multivarianttianalyysissä suojavaikutus ei ollut tilastollisesti merkittävä. Aiempi kohdunpoisto ei suojannut munanjohdinsyövältä. Aiemmin sairastetut Chlamydia trachomatis- tai HPV-infektiot eivät lisänneet riskiä sairastua munanjohdinsyöpään. Monikansallisessa syöpärekisteritutkimuksessa todettiin 2084 munanjohdinsyöpää aikavälillä 1943-2000. Näillä potilailla todettiin syövän hoidon jälkeisiä uusia syöpiä 36% enemmän kuin odotettiin (SIR 1.36, 95% CI 1.13-1.63). Riski oli erityisesti lisääntynyt non-lymfoidille leukemialle, rakko-, colorektaali-, rinta- sekä keuhkosyövälle. Yhteenvetona todetaan munanjohdinsyövän lisääntyneen Suomessa, etenkin ylemmissä sosiaaliluokissa ja tietyissä ammattiryhmissä. Koholla oleva seerumin hCGß on huonon ennusteen merkki. Synnyttäneisyys sekä aiempi sterilisaatio suojaavat munanjohdinsyövältä, mutta kohdunpoisto ei. Aiemmin sairastetun munanjohdinsyövän jälkeen todettiin kohonnut riski erityisesti rinta- sekä colorektaalisyövälle. Tämä saattaa kertoa aiempien hoitojen (säde- ja solunsalpaajahoidot) vaikutuksista, mutta myös syövän taustalla olevista yhteisistä geneettisistä, hormonaalisista, immunologisista tai ympäristötekijöistä

Cancer risk of Lichen planus : A cohort study of 13,100 women in Finland

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.Peer reviewe

Other Primary Malignancies Among Women With Adult-Type Ovarian Granulosa Cell Tumors

Objective: The aim of this study was to determine the incidence of new primary malignancies after adult-type granulosa cell tumor (AGCT) and the incidence of AGCT after breast and uterine cancer using nationwide population-based registry data. Methods: We used the Finnish Cancer Registry to identify all patients diagnosed with AGCT in 1968 to 2013 (n = 986). The number of subsequent primary malignancies among women with AGCT and the number of AGCTs in women with previous breast or uterine cancer were compared with the expected number of cases and expressed as standardized incidence ratios (SIRs). Results: There were 122 cases of subsequent cancers diagnosed at least 6 months after the primary diagnosis of AGCT (SIR, 1.09; 95% confidence interval [CI], 0.91-1.3). In particular, the observed number of cancers of the soft tissue (SIR, 4.13; 95% CI, 1.33-12.8), thyroid (SIR, 3.42; 95% CI, 1.54-7.62), and leukemia (SIR, 2.67; 95% CI, 0.98-5.82) exceeded the number of expected cases. The SIR for breast cancers after AGCT was 1.26 (95% CI, 0.92-1.73), and the SIR for AGCT after breast cancer was 1.59 (95% CI, 1.04-2.29). The risk for subsequent AGCT was more than 2-fold in breast cancer patients younger than 50 years, and over 15 years after primary diagnosis. Conclusions: There is an increased risk for thyroid and soft tissue cancer as well as leukemia after AGCT, which may be associated with late effects of carcinogenic treatments and possibly shared risk factors. After breast cancer, the risk for AGCT was higher, which may indicate a shared hormonal etiology.Peer reviewe

Characteristics and outcome of recurrence in molecularly defined adult-type ovarian granulosa cell tumors

Objective. Adult-type ovarian granulosa cell tumors (AGCTs) have an unpredictable tendency to relapse. In a carefully validated patient cohort, we evaluated the prognostic factors related to AGCT recurrence. Methods. We identified all patients diagnosed with AGCT during 1956-2014 in Helsinki University Hospital, with a minimum follow-up of one year (n = 240). After a histological review supplemented with FOXL2 (402C G) mutation status analysis, we analyzed the clinical data for association with relapse. Results. The final cohort included 164 (68%) molecularly defined AGCTs (MD-AGCTs). The majority of the women were postmenopausal (63%), and 92% of tumors were stage I. The median follow-up time was 15.5 years. Fifty-two (32%) patients developed tumor recurrence, of whom 55% had successive recurrences. Multiple-site recurrences were common, and nearly half of the recurrences were asymptomatic. The median time to the first relapse was 7.4 years, and 75% of relapses occurred within ten years after primary diagnosis. The median disease-free survival was 11.3 years. Premenopausal status at initial diagnosis, FIGO stage Ic versus la, and tumor rupture associated with relapse. However, tumor rupture was the only independent predictive factor. Of the relapsed patients, 48% died of AGO' in a median time of 153 years. Conclusion. Tumor rupture is the strongest predictive factor for recurrence, and these patients might benefit from a more aggressive initial treatment approach. AGCT requires active follow up for 10 to 15 years after primary diagnosis, since recurrences may develop late, asymptomatically and in multiple anatomical locations. (C) 2016 Elsevier Inc. All rights reserved.Peer reviewe

Kohdunkaulan, emättimen ja ulkosynnytinten solumuutokset : KÄYPÄ HOITO -SUOSITUS (Päivitystiivistelmä)

Käypä hoito -suositus. Päivitystiivistelm

Systematic drug sensitivity testing reveals synergistic growth inhibition by dasatinib or mTOR inhibitors with paclitaxel in ovarian granulosa cell tumor cells

Objective. Resistance to standard chemotherapy poses a major clinical problem in the treatment of ovarian cancer patients. Adult-type granulosa cell tumor (AGCT) is a unique ovarian cancer subtype for which efficient treatment options are lacking in advanced disease. To this end, systematic drug response and transcriptomics profiling were performed to uncover new therapy options for AGCTs. Methods. The responses of three primary and four recurrent AGCTs to 230 anticancer compounds were screened in vitro using a systematic drug sensitivity and resistance testing (DSRT) platform, coupled with mRNA sequencing. The responses of the AGCTs were compared with those of human granulosa luteal cells and bone marrow mononuclear cells. Results. Patient-derived AGCT cells showed selective sensitivity to the Src family tyrosine kinase inhibitor dasatinib. A combination of either dasatinib or an mTOR-inhibitor everolimus with paclitaxel resulted in synergistic inhibition of AGCT cell viability. The key kinase targets of dasatinib and members of the mTOR pathway were constantly expressed at mRNA and protein levels, indicating multikinase signal addictions in the AGCT cells. Transcriptomic characterization of the tumors revealed no known oncogenic mutations, suggesting that the drug sensitivity of AGCTs was rather conveyed by selective target expression. Conclusions. We used a systematic functional approach to reveal novel treatment options for a unique gynecological cancer. The selective synergy found between taxanes and dasatinib or mTOR inhibitors warrants further clinical investigations of these combinations in relapsed or aggressive AGCTs and demonstrate that high throughput drug screening and molecular profiling can provide an effective approach to uncover new therapy options. (C) 2016 Elsevier Inc. All rights reserved.Peer reviewe

Nuorten uratoiveet korva-, nenä- ja kurkkutautien erikoisalalla

Lähtökohdat Erikoisalan ja sille hakeutuvien kannalta on hyödyllistä selvittää, mitkä tekijät ohjaavat ¬lääkäreitä erikoisalan valinnassa ja uralla eteenpäin. Menetelmät Haastattelimme 19 lääkäriä, jotka erikoistuivat tai olivat äskettäin erikoistuneet korva-, nenä- ja kurkkutauteihin. Tulokset Alan valintaan vaikutti sattuma. Sosiaaliset sekä käden taidot koettiin tärkeiksi, ja väitöskirjaa pidettiin oleellisena uralla etenemiselle. Johtotehtävissä toimivien epätasaisen sukupuolijakauman arvioitiin tasoittuvan, mutta yliopistoklinikoiden mukaan näin ei ole käynyt. Päätelmät Erikoisalan tulee profiloitua selvemmin. Erikoistumiskoulutuksessa tulee tukea sosiaalisia ja käden taitoja. Naisten urakehityksen esteiden tunnistaminen auttaa tasoittamaan sukupuolijakaumaa johtotehtävissä.Peer reviewe