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Metalloendocrinology is a new interdisciplinary field, which was established due to the importance of connections between inorganic chemicals and hormonal mechanisms. The role of cadmium in hormone-related tumors is an excellent example of this connection, as cadmium mimics estrogen in the human body. Since endometrial cancer (EC) is hormone-related, it is well-suited for assessing the estrogenic effects of cadmium. Therefore, the present study aims to explore the role of dietary cadmium intake in the progression-free survival (PFS) and overall survival (OS) in women with EC. Dietary cadmium intake was estimated based on a large cohort of Swedish women ( n  = 416) with EC. Median dietary cadmium intake was then analyzed in relation to different tumor characteristics and clinical outcomes. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Median daily dietary cadmium intake in the cohort was 13.1 μg (interquartile range 25%-75%=6.4). High dietary cadmium intake (μg/day) was associated with significantly decreased OS in the study cohort (HR = 0.956, 95% CI = 0.914-1.001, p  = 0.05). Dietary cadmium intake was not associated with PFS (HR = 0.975, 95% CI = 0.924-1.028, p  = 0.348). Therefore, our results indicate that high dietary cadmium intake could be associated with poor outcome in women with EC.

Background: The causal relation between high-risk human papillomavirus (HPV) and cervical cancer and its precursor lesions has led to the use of sensitive HPV molecular tests for screening. This study examined the impact of the baseline HPV status on the future risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) among women with cytology negative for intraepithelial lesions or malignancy (NILM)., Methods: This was a nested case-control study including women with NILM baseline cytology participating in the Swedish cervical screening program in 2005-2007. Ninety-six cases of CIN2+ and 5 age-matched controls per case were identified through the National Cervical Screening Registry by follow-up through 2014. Baseline liquid-based cytology samples were tested for HPV. Conditional logistic regression analysis was used to calculate odds ratios (ORs) with confidence intervals (CIs)., Results: The risk of future high-grade cervical intraepithelial neoplasia (CIN) was strongly associated with the baseline HPV status. For women younger than 30 years, HPV-16/18 showed a significant association with future risk for CIN2+ (OR, 9.44; 95% CI, 3.37-26.4). Other HPV types were not significantly associated with future CIN2+ in these younger women. For women 30 years old or older, both HPV-16/18 and other HPV subtypes conferred a significant risk., Conclusions: The presence of HPV-16/18 among women with NILM cytology is associated with an elevated future risk of high-grade CIN. HPV types other than HPV-16/18 seem to have a greater impact on women 30 years old or older than younger women. Women with NILM cytology and HPV-16/18 need specific follow-up management within screening., (© 2018 American Cancer Society.)

Individuals with a history of colorectal or endometrial cancer younger than 50 years of age or with relatives younger than 50 years of age with a history of any of these malignances should be referred to clinical genetics for further diagnostic examinations and genetic counseling. Lynch syndrome is caused by mutations in mismatch repair genes and implicates an increased risk for colorectal cancer as well as endometrial cancer. Routine surveillance for this group of individuals regarding colorectal cancer by means of colonoscopy and endometrial cancer by means of transvaginal ultrasound as well as endometrial biopsies is recommended annually or biennially. Several preventive measures are under development, such as chemoprevention and vaccination. During 2015 we investigated reasons for diagnosis among those registered at Karolinska University Hospital. We found that a substantial part of this group of individuals was diagnosed in conjunction with their diagnosis of cancer; a prerequisite in order to offer at-risk individuals preventive measures is to improve identification of these individuals and offer them presymptomatic genetic testing in order to identify predisposing mutations.

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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The aim of the present study was to assess predictive factors for occurrence of idiopathic menorrhagia (IM), a disease characterized by abnormal endometrial blood vessel morphology. It was hypothesized that IM exhibits familial clustering (suggesting inheritance) and is associated with other vascular abnormalities, primarily cutaneous hemangiomas. Women with IM (n=152) and healthy, regularly menstruating (n=56) women answered a questionnaire concerning menstrual pattern, susceptibility to bleeding and family history of abnormal gynecological bleeding. Factor analysis with principal component extraction was used to separate predictive factors that may be associated with IM. A total of 35 different items were analyzed. A strong association was found between IM and a family history of heavy menstrual bleeding (r=0.68), but not with cutaneous vascular abnormalities. Our results revealed that a family history of heavy menstrual bleeding may have the highest predictive value for the diagnosis of IM, indicating a hereditary trait.

Background: Since 1989 large loop excision of the transformation zone (LLETZ) has become the treatment of choice for cervical intraepithelial neoplasia in many colposcopy clinics. This method has limitations however, in that the resection margins of the cone produced by LLETZ cannot give conclusive histological reassurance, because of thermal injury in 5 30% of the specimens. Furthermore, LLETZ are often taken in several sections, which makes the histopathological examination unnecessarily difficult. As a new and single treatment without these limitations, conization with the contoured loop excision of the transformation zone (C-LETZ) electrode was investigated in the present study. Material and methods. One hundred and seventy-four patients with CIN were treated with the C-LETZ electrode during 12 months at the Gynaecological Department, Karolinska University Hospital, Huddinge. The inclusion criteria were a histological diagnosis of CIN II-III, or persistent CIN I., Results: Eighty-six per cent of the patients had a complete excision according to histological findings, and 12% had an incomplete excision. The frequency of incomplete excisions increased with the severity of the CIN but were found in all groups of patients: 1 (3%) in CIN I, 5 (12%) in CIN II, and 12 (17%) in CIN III. The resection margins and histological diagnoses were certain in 98% of the cases. A cure rate of 90% was observed. Conclusions. Miniconization with the C-LETZ electrode makes it possible to individualize the size of the minicones and produce the minicones as one-piece specimens for histopathological assessment. Our findings confirm that this method is a reproducible, safe, and economical way to treat CIN with a low rate of morbidity in a hospital outpatient setting.

Background: Of the estimated one million Papanicolaou (pap) smears performed annually in Sweden, about 4% show any degree of abnormality. Approximately, 1% of these cases contain moderate or severe atypia (high-grade squamous intraepithelial lesions) and the rest contain low-grade atypia. Recommendations for the management of minor abnormalities vary in various parts of Sweden. Generally, a second Pap smear is obtained 4-6 months after the first one showing low-grade atypia. The aim of this study is to compare the sensitivity of human papilloma virus (HPV)-DNA testing for the detection of cervical intraepithelial neoplasia (CIN) 2-3 with that of a second Pap smear in women, who had low-grade atypia in their first Pap smear., Methods: Women with low-grade atypia in the Stockholm area, detected at a population-based cytology screening, were enrolled. A repeat Pap smear, HPV test, and colposcopically directed biopsies were obtained. For the detection of HPV, Hybrid Capture II (HC II) was used., Results: The HPV-DNA test was positive in 66% of the 177 participating women. The sensitivity of the second Pap smear and HPV-DNA test to detect CIN 2-3 was 61 (95% CI = 45-74) and 82% (95% CI = 67-91), respectively. The positive and negative predictive values of HPV testing were 27 (95% CI = 18-35) and 89% (95% CI = 80-97), respectively., Conclusions: In Sweden, a second Pap smear is often obtained for the follow-up of women with low-grade atypia. The results of our study show that compared to the second Pap smear, HPV testing with HC II is a more sensitive method for detecting high-grade lesions.

Objective: A retrospective study of short and long term results of transcervical endomyometrial resection for menorrhagia., Material and Methods: Patient data were collected from all 104 premenopausal women who had undergone a transcervical endomyometrial resection due to severe menorrhagia in 1990-95. Almost 40% had submucous fibromas that were resected together with the endometrium. A questionnaire about gynecological symptoms was mailed to all 104 women. Ninety-seven (93%) women answered the questionnaire., Results: The mean follow-up period was 29 months. The following short-term complications were encountered: fluid overload in four, one uterine perforation and one major bleeding. The long-term complications included: three hematometra and one pregnancy ending in a spontaneous abortion. Glandular hyperplasia of the endometrium without atypia was found in two cases, and adenomyosis in 31 (29%) cases. Twenty-one women (21%) became amenorrhoic after the treatment, whereas forty-nine (51%) had minimal menstrual bleeding. Eleven women (11%) suffered from dysmenorrhea. Due to dysmenorrhea and/or persistent menorrhagia thirteen (12.5%) underwent a hysterectomy, generally within one year after the resection. The histological examinations showed adenomyosis in three cases, fibromas in four and fibromas and adenomyosis in three cases., Conclusions: In our hands hysteroscopic transcervical endomyometrial resection was a safe and effective treatment for menorrhagia in spite of the fact that amenorrhea was not always achieved. However, dysmenorrhea appeared in 11% of the women. The reason for this remains to be studied. Correct selection criteria is important to get optimal results and reduce the treatment failure.