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Sökning: WFRF:(Tzortzatos Gerasimos)

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  • Tzortzatos, G., et al. (författare)
  • The gynecological surveillance of women with Lynch Syndrome in Sweden
  • 2015
  • Ingår i: Gynecologic Oncology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0090-8258 .- 1095-6859. ; 138:3, s. 717-722
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. Women with Lynch syndrome (LS) have up to a 60% lifetime risk of endometrial cancer (EC) and up to a 24% risk of ovarian cancer (OC). Gynecological surveillance is recommended, but the benefit and how it should be performed remain unclear. The purpose of this study was to assess diagnostic modalities for gynecological screening of LS patients in Sweden and clinical outcome. Methods. A retrospective nationwide study of 170 women with molecularly confirmed LS. Data including gynecological LS screening history, biopsy results (if any), genetic records, number of screening visits, results from screening including transvaginal ultrasound (TVUS), endometrial biopsy (EB), blood test for tumor marker cancer antigen (CA) 125, prophylactic surgery including age at procedure, and setting from which screening data were obtained from medical records. Results. A total of 117 women were eligible for gynecological screening and of these, 86 patients attended screening visits. Of these, 41 underwent prophylactic hysterectomy and/or bilateral salpingo-oophorectomy. Two patients (4.9%) were diagnosed with EC and two (4.9%) with precancerous lesions in conjunction with prophylactic surgery. Total incidence of gynecological cancer in the surveillance group (45 women) was 20% EC, 4% OC. Five patients had endometrial cancer or complex hyperplasia with atypia (n = 2) detected by endometrial biopsy. Four additional cases were detected due to interval bleeding. Both cases of ovarian cancer were detected by transvaginal ultrasound in patients with ovarian cysts under surveillance. The youngest woman with endometrial cancer was diagnosed at 35 years of age, before she was aware of her diagnosis of Lynch syndrome. Conclusions. Gynecological surveillance of women with Lynch syndrome may lead to earlier detection of precancerous lesions, which might have some impact on the morbidity from endometrial cancer although further studies are needed to prove this. Prophylactic hysterectomy with or without bilateral salpingo-oophorectomy reduces the cancer incidence. A practical approach to surveillance in Lynch syndrome women would be to offer annual surveillance beginning at age 30 years including probably both TVUS and EB in order to increase diagnostic yield with prospective data registry for follow-up studies. Prophylactic surgery could be performed at a suitable age after childbearing to obtain a balance between reducing the risk of cancer and minimizing long-term complications from premature menopause.
  • Ekman-Ordeberg, G, et al. (författare)
  • Low molecular weight heparin stimulates myometrial contractility and cervical remodeling in vitro
  • 2009
  • Ingår i: Acta Obstet Gynecol Scand. - : Wiley-Blackwell. ; 88:9, s. 984-989
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: The low molecular weight heparin, Dalteparin, shortens human labor time. The aim of this study was to investigate if the mechanism behind this effect involves myometrial contractility and cervical ripening and if the anticoagulative activity is necessary for its effect. DESIGN: Experimental in vitro study. SETTING: Lund University and Karolinska Institute, Sweden. METHODS: The effect of low molecular weight heparins with or without anticoagulative properties on myometrial contractility was measured in vitro on smooth muscle strips from biopsies obtained at elective cesarean sections. The effects on cervical ripening were assessed in cervical fibroblasts cultured from explants of cervical biopsies obtained at delivery. MAIN OUTCOME MEASURES: Mean force and number of contractions in uterine smooth muscle strips and interleukin-8 (IL-8) secretion in cervical fibroblasts. RESULTS: Myometrial smooth muscle strips pretreated with low molecular weight heparins showed increased contractile activity compared to untreated smooth muscle strips. Secretion of IL-8 from cultured cervical fibroblasts was significantly increased after treatment with low molecular weight heparin. Both these effects were independent of anticoagulative activity of the low molecular weight heparin. CONCLUSIONS: A possible underlying mechanism for the shortened labor time after low molecular weight heparin treatment is enhanced myometrial contractility and an increased IL-8 secretion in cervical fibroblast, mimicking the final cervical ripening in vivo. Our data support the notion that anticoagulant activity is not required to promote labor.
  • Tzortzatos, Gerasimos, et al. (författare)
  • Screening for germline phosphatase and tensin homolog-mutations in suspected Cowden syndrome and Cowden syndrome-like families among uterine cancer patients
  • 2015
  • Ingår i: Oncology Letters. - 1792-1074 .- 1792-1082. ; 9:4, s. 1782-1786
  • Tidskriftsartikel (refereegranskat)abstract
    • Cowden syndrome (CS) is an autosomal dominant disorder characterized by multiple hamartomas in the breast, thyroid and endometrium, with a prevalence of 1 per 250,000. Females with CS have a 21-28% lifetime risk of developing uterine cancer. Germline mutations in the phosphatase and tensin homolog (PTEN) gene, a tumor suppressor gene, are responsible for 30-80% of CS cases. PTEN is a nine-exon gene, located on chromosome 10q23.3, which encodes the 403 amino acid PTEN protein. It negatively regulates the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathway, affecting various cellular processes and signaling pathways. The present study examined whether PTEN mutations are present in CS-like families with uterine cancer (UC). UC patients underwent surgery at Karolinska University Hospital, Stockholm, Sweden (2008-2012). Pedigrees were analyzed and 54 unrelated CS-like families were identified. CS-like families were defined as having at least one occurrence of uterine cancer and one of breast cancer, as well as at least one additional Cowden-associated tumor (uterine, breast, thyroid, colon or kidney cancer) in the same individual or in first-degree relatives. Genomic DNA was amplified using polymerase chain reaction, and DNA sequencing analysis of all nine exons of the PTEN gene was conducted. No germline PTEN mutations or polymorphisms were identified. Germline PTEN mutations are rare in CS-like families with uterine cancer, therefore, genetic screening must be restricted to patients that meet the strict National Comprehensive Cancer Network criteria. Gynecologists must be aware of the CS criteria and identify potential cases of CS in females where uterine cancer is the sentinel cancer.
  • Tzortzatos, Gerasimos (författare)
  • Hereditary factors in endometrial cancer
  • 2015
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Endometrial carcinoma (EC) is the most common gynecological malignancy in Sweden and accounts for about 6 % of all female malignancies. The risk of EC increases with age and the majority of cases are diagnosed between age 50 and 60. Ninety percent of cases occur in women older than age 50. About 2% of EC may have a familial association related to Lynch syndrome (LS). About 80% of women with Cowden syndrome have the PTEN mutation, which increases their lifetime risk of developing EC. The benefit of EC surveillance among LS patients remains undetermined. Available studies are controversial concerning optimal age at which to initiate screening and screening modalities. Our first study explored the prevalence of LS, Cowden syndrome (CS) and hereditary breast ovarian cancer syndrome in consecutively diagnosed women with EC. In addition, we explored the possibility of a familial association between uterine cancer and other specific malignancies. In all, we included 481 consecutively diagnosed cases of endometrial cancer. We used the Swedish Cancer Registry to confirm all diagnoses, as well as for a reference population for the years 1970 and 2010. We conducted mutation analyses on all families who met criteria for the syndromes referred to above to identify potential causal genes. Our study demonstrated familial clustering among relatives of our index EC cases; EC prevalence was twice as high in our study population as in the cancer population in Sweden at large (6% vs 4% and 3%). In addition, we identified LS in 1.5% of all women. No BRCA1 and BRCA2 mutations were identified. No families fulfilled the CS criteria. Among all the LS families in which mutation could be verified, only one had previously been diagnosed. Moreover, we found that onset of cancer at a young age in family members of EC patients and diagnosis of multiple malignancies in the same patient lend support to the concept of hereditary uterine cancer syndromes. In study II, 54 Cowden syndrome-like families were identified from consecutively diagnosed EC patients. PCR and DNA sequencing analysis were carried out on genomic DNA to amplify all nine PTEN gene exons. Since we identified no germline mutations or polymorphisms, the implication is that these must be rare among CS-like families. Therefore strict Cowden syndrome criteria should be applied to identify CS patients. Our third study involved a retrospective nationwide study of 170 women with Lynch syndrome. We gathered data on all diagnostic methodology employed for gynecological screening of LS and prophylactic surgery, including age at surgery. In all, 86 of the 117 women who were eligible for screening complied with the screening program. Gynecological surgery was carried out on 43 women prior to diagnosis with LS, for which reason they were inappropriate for screening. A lower incidence of cancer was found in the screened group than in the non-screened group. EC was diagnosed by endometrial biopsy in a large number of cases. In addition, the incidence of cancer was significantly reduced by prophylactic surgery. In conclusion, the results from our studies will improve both characterization of EC and family screening while expanding genetic counseling, and thereby help to prevent endometrial cancer in high-risk patients by enrolling them in EC prevention programs before endometrial cancer develops. Our results will improve routine procedures used to investigate families and surveillance programs for patients at high risk. Such patients can then be offered a choice between participation in screening programs or surgery for prophylactic purposes. According to our results, LS patients should be screened for gynecological cancer with transvaginal ultrasound (TVUS) and endometrial biopsy (EB) by age 30-35. Once high-risk women have completed childbearing, prophylactic surgery should be made available.
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