The gynecological surveillance of women with Lynch syndrome in Sweden.

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.

Familial cancer among consecutive uterine cancer patients in Sweden.

BACKGROUND: Uterine cancer (UC) represents 5.1% of all female malignancies in Sweden. Accumulation of UC in families occurs in around 5% of cases. We wanted to identify any familial association between UC and other selected cancers and to study the frequency of Lynch,Cowden and cancer syndromes among consecutive UC patients in Sweden. METHODS: 481 UC patients were included. Information on the cancer diagnoses of their relatives (first- (FDRs) and second-degree (SDRs) relatives and first cousins) was obtained. The relative frequencies of different cancers among relatives were compared to those in the Swedish general cancer population in 1970 and 2010. Families that fulfilled the criteria for hereditary cancer syndromes were tested for mutations in the causative genes. Families with at least one case of UC in addition to the index patient were compared to families with no additional cases to investigate possible characteristics of putative hereditary cancer syndromes. RESULTS: There was an increased prevalence of UC in our study population compared to the Swedish general cancer population in 1970 and 2010 (6% vs. 4% and 3%, respectively). Seven families had Lynch Syndrome according to the Amsterdam II criteria. No families fulfilled the criteria for Cowden syndrome. In total 13% of index patients had at least one relative with UC and these families tended to have more cases of early onset cancer among family members. In addition, 16% of index patients were diagnosed with at least one other cancer. No families fulfilled the criteria for Cowden syndrome. CONCLUSION: We showed a familial clustering of UC among relatives of our index patients. Of the seven families with mutation-verified Lynch Syndrome, only one had been previously diagnosed, highlighting the need to increase gynecologists' awareness of the importance of taking family history. Our data on multiple cancers and young age of onset in families with uterine cancer is compatible with the existence of additional hereditary uterine cancer syndromes.

Low molecular weight heparin stimulates myometrial contractility and cervical remodeling in vitro.

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.

Snake venom poisoning in Greece. Experiences with 147 cases.

BACKGROUND: Snake venom poisoning is a medical emergency requiring immediate attention. Bites from poisonous European snakes can lead to local tissue damage and systemic symptoms. Vipera ammodytes accounts for the most envenomation in Greece. METHODS: The demographic and epidemiological characteristics, clinical symptoms and signs, laboratory findings, treatment, and outcome of 147 consecutive victims of V. ammodytes admitted to our hospital from 1988 to 2003 were reviewed and analyzed. RESULTS: The most common symptoms and signs included fang marks (100%), pain (100%), swelling (98.64%), ecchymosis (60.54%), tachycardia (32.65%), fainting or dizziness (29.93%), fever (23.13%), enlargement of regional lymph nodes (17.69%), nausea (16.33%), hypotension (13.61%), and vomiting (12.93%). The main complications were reduced range of motion, thrombophlebitis, local hemorrhagic blister formation, skin bleeding, rhabdomyolysis, reduced sensation, acute renal failure, necrosis with tissue loss, carpal tunnel syndrome, compartment syndrome, Kounis syndrome, and digit amputation. CONCLUSIONS: A V. ammodytes bite is a potentially serious event that requires immediate hospital care. Yet, the majority of victims can be treated successfully with conservative methods. No deaths occurred in our series.

Screening for germline phosphatase and tensin homolog-mutations in suspected Cowden syndrome and Cowden syndrome-like families among uterine cancer patients.

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.

Successful pregnancy after treatment for ovarian malignant teratoma with growing teratoma syndrome.

OBJECTIVE: To report a case of successful IVF-pregnancy after treatment for ovarian growing teratoma syndrome. DESIGN: Case report. SETTING: Gynecologic department at a university hospital. PATIENT(S): A 20-year-old woman, gravida 0 para 0, was diagnosed with malignant teratoma of the ovary. She was treated by unilateral salpingo-oophorectomy and chemotherapy. A couple of years later she was diagnosed with growing teratoma syndrome. INTERVENTION(S): Fertility-preserving surgery with unilateral salpingo-oophorectomy and chemotherapy. In vitro fertilization. MAIN OUTCOME MEASURE(S): Disease free, successful pregnancy. RESULT(S): After treatment for ovarian immature teratoma and growing teratoma syndrome the patient was free of the disease. She underwent in vitro fertilization treatment with autologous embryo transfer and gave birth to a healthy child. CONCLUSION(S): Growing teratoma syndrome is an extremely rare metastatic complication of a malignant germ cell tumor after a combination treatment with surgery and adjuvant chemotherapy. This case shows that successful pregnancy outcome is possible after effective treatment for ovarian growing teratoma syndrome.