Changes in Micronutrient Intake and Status, Diet Quality and Glucose Tolerance from Preconception to the Second Trimester of Pregnancy.

Data on changes in dietary intake and related blood parameters throughout pregnancy are scarce; moreover, few studies have examined their association with glucose homeostasis. Therefore, we monitored intake of folate, vitamin B6, vitamin B12, vitamin D and iron, their status markers, and diet quality from preconception to the second trimester of pregnancy, and we examined whether these dietary factors were associated with glucose homeostasis during pregnancy. We included 105 women aged 18⁻40 years with a desire to get pregnancy or who were already <24 weeks pregnant. Women at increased gestational diabetes (GDM) risk were oversampled. Measurements were scheduled at preconception (n = 67), and 12 (n =53) and 24 weeks of pregnancy (n =66), including a fasting venipuncture, 75-grams oral glucose tolerance test, and completion of a validated food frequency questionnaire. Changes in micronutrient intake and status, and associations between dietary factors and glucose homeostasis, were examined using adjusted repeated measures mixed models. Micronutrient intake of folate, vitamin B6 and vitamin D and related status markers significantly changed throughout pregnancy, which was predominantly due to changes in the intake of supplements. Micronutrient intake or status levels were not associated with glucose homeostasis, except for iron intake (FE µg/day) with fasting glucose (ß = -0.069 mmol/L, p = 0.013) and HbA1c (ß = -0.4843 mmol, p = 0.002). Diet quality was inversely associated with fasting glucose (ß = -0.006 mmol/L for each DHD15-index point, p = 0.017). It was shown that micronutrient intakes and their status markers significantly changed during pregnancy. Only iron intake and diet quality were inversely associated with glucose homeostasis.

Supplement Use and Dietary Sources of Folate, Vitamin D, and n-3 Fatty Acids during Preconception: The GLIMP2 Study.

An adequate nutritional status during the preconception period is important, particularly for folate, vitamin D, and n-3 fatty acids (i.e., EPA+DHA). We aimed to determine supplement intake and the main dietary sources of folate, vitamin D, and EPA+DHA using the data of 66 Dutch women aged 18⁻40 years who wished to become pregnant. Additionally, associations of these intakes with their blood levels were examined. Dietary intake was assessed with a validated food frequency questionnaire, and supplement use with a structured questionnaire. 25-hydroxyvitamin D levels were determined in serum and folate and phospholipid EPA+DHA levels in plasma. Partial Spearman's correlations, restricted cubic splines and trend analyses over tertiles of nutrient intakes were performed to examine intake-status associations. A large proportion of women did not meet the Dutch recommended intakes of folate (50%), vitamin D (67%), and EPA+DHA (52%). Vegetables were the main contributor to dietary folate intake (25%), oils and fats to dietary vitamin D intake (39%), and fish to dietary EPA+DHA intake (69%). Fourteen percent of the women had an inadequate folate status and 23% an inadequate vitamin D status. Supplemental folate intake, supplemental and dietary vitamin D intake and dietary EPA+DHA intake were significantly associated with their blood levels. In conclusion, even in our highly educated population, a large proportion did not achieve recommended folate, vitamin D and n-3 fatty acid intakes. Promotion of folate and vitamin D supplement use and fish consumption is needed to improve intakes and blood levels of these nutrients in women who wish to become pregnant.

Use of risk of malignancy index to indicate frozen section analysis in the surgical care of women with ovarian tumors.

OBJECTIVE: To evaluate the importance of the risk of malignancy index (RMI) in the decision to perform frozen section analysis among women with ovarian tumors. METHODS: A retrospective study was conducted in 11 centers in the Netherlands. Women who underwent surgical treatment of an ovarian mass with unknown histology between January 2005 and September 2009 were included. The RMI was calculated retrospectively. Frozen section analysis and RMI values were assessed for patients with benign, borderline, and malignant ovarian tumors on final histopathology. RESULTS: Overall, 670 women were included. Frozen sections were performed in 323 (48.2%) patients, of whom 206 (63.8%) were diagnosed with benign ovarian tumors, 55 (17.0%) with borderline tumors, and 62 (19.2%) with malignant tumors. Overall, 109 (16.3%) women had an RMI below 20, 106 (97.2%) of whom had benign histology results. Among 235 patients with an RMI over 100, 3 (1.3%) postmenopausal women had malignancies that were missed because frozen sections were not performed. CONCLUSION: Women with an RMI below 20 have a low risk of malignancy and therefore do not require frozen section analysis. Postmenopausal women with an RMI greater than 100 should be referred to centers where frozen sections can be performed, and proper facilities and expertise are available to perform staging procedures if necessary.

Efficacy of a regional network for ovarian cancer care.

OBJECTIVE: To study the influence of a regional collaboration in epithelial ovarian cancer care on staging procedures, debulking results, and survival. METHODS: In an effort to optimize epithelial ovarian cancer treatment, a regional collaboration was introduced in the Netherlands in 2000. Gynecologic oncologists from the university center conducted surgery in community hospitals when ovarian cancer was considered based on the risk of malignancy index or clinical suspicion. The National Cancer Registry registered 1,554 patients with epithelial ovarian cancer diagnosed in 11 participating Dutch hospitals between 1996 and 2010. Surgical procedures were compared during three periods (1996-1999, 2000-2004, and 2005-2009). Log-rank tests compared Kaplan-Meier survival curves of progression-free and overall survival before (1996-2000) and during the start of the collaboration (2001-2005). RESULTS: Staging was adequate for 139 patients (23.0%) before collaboration, and this proportion increased during the study periods to 32.1% and 62.1% (P<.01), when gynecologic oncologists more often staged cancer in patients (36.7% compared with 54.7% and 80.6%; P<.01). For 1,197 patients with advanced stage disease (stage IIb or greater), the proportion of debulking procedures with an optimal (residual volume less than1 cm) as well as a complete result (no residuals) increased during the 14-year study period from 57.4% to 76.5% (P<.01) and from 24.1% to 43.4% (P<.01), respectively. Survival rates were similar before and during the start of the collaboration. In multivariable analysis, the treatment variables completeness of debulking, chemotherapy, and gynecologic oncologist attendance were independent prognostic factors for overall survival, as were age, stage, and tumor grade. CONCLUSIONS: After regional collaboration, gynecologic oncologists attended more surgeries and surgical outcomes improved, but progress in survival could not be demonstrated. Regional collaboration improved care for ovarian cancer patients. LEVEL OF EVIDENCE: II.

Hybrid transvaginal cholecystectomy, clinical results and patient-reported outcomes of 50 consecutive cases.

OBJECTIVE: The aim of this study was to report the clinical and cosmetic results of transvaginal hybrid cholecystectomy (TVC). BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) has been developed as a minimal invasive alternative for conventional laparoscopic cholecystectomy. Although transvaginal NOTES procedures are becoming increasingly popular, data focussing on body image, cosmesis and sexual recovery are rare. METHODS: Our clinic started to perform the TVC in the beginning of 2011. Female patients with symptomatic gallstone disease that were treated between January 2011 and April 2012 with TVC were entered in a prospective database. All patients received a survey postoperative with questions about recovery, cosmesis and body image. RESULTS: Fifty consecutive patients were treated with a TVC. There were no major complications. Mean operative time was 61 min. In five patients (10 %), a conversion to another type of cholecystectomy was necessary. None of the sexually active women observed dyspareunia postoperative. The results for cosmesis and body image after the transvaginal approach were excellent. CONCLUSIONS: TVC is a safe and feasible procedure when performed on selected patients. The transvaginal route seems to result in excellent cosmetic outcomes without gynaecologic complications after short-term follow up. Randomised trials are needed to specify the role of TVC in the treatment of patients with symptomatic gallstone disease and to detect differences in cosmetic outcomes.

Preoperative CA-125 predicts extra-uterine disease and survival in uterine papillary serous carcinoma patients.

OBJECTIVE: We determined the clinical utility of preoperative serum CA-125 as predictor of extra-uterine disease and as prognosticator for survival in patients with uterine papillary serous carcinoma (UPSC). METHODS: Patients diagnosed with UPSC, identified between 1992 and 2009, and with preoperative CA-125 measurement were included. A receiver operator characteristic (ROC) curve was used to quantify marker performance. Overall and progression free survival were analyzed using the Kaplan-Meier method. Regression analyses were used to investigate the association of preoperative CA-125 levels and other clinicopathological variables with the presence of extra-uterine disease and the effects on survival. RESULTS: Sixty-six patients met the study criteria. Using ROC, the CA-125 concentration of 45 U/mL as cutoff level provided the best sensitivity (75%) and specificity (74%) for extra-uterine disease, with a positive predictive value of 86%. Survival was significantly longer in patients with preoperative CA-125 ≤ 45 U/mL (p<0.001). Only preoperative CA-125 >45 U/mL remained significantly associated with extra-uterine disease (OR=6.30, 95% CI 1.93-20.62). Furthermore, advanced FIGO stage (HR=4.53, 95% CI 1.50-13.62) and preoperative CA-125 >45 U/mL (HR=3.12, 95% CI 1.13-8.73) were associated with decreased survival. CONCLUSION: Preoperative elevated serum CA-125 is an independent predictor for the presence of extra-uterine disease and an independent risk factor for survival in UPSC patients.

External validation of the adapted Risk of Malignancy Index incorporating tumor size in the preoperative evaluation of adnexal masses.

OBJECTIVE: The Risk of Malignancy Index (RMI) is a simple scoring system to standardize and improve the preoperative evaluation of adnexal masses. Since 1990, three versions of the RMI have been validated in different clinical studies. Recently, a fourth version of the RMI (RMI-4) was introduced that includes tumor size as an additional parameter. The aim of this study was to validate the ability of RMI-4 to discriminate between non-invasive lesions and invasive malignant adnexal masses, and to compare its performance with RMI-3. STUDY DESIGN: Women scheduled for surgery for an adnexal mass between 2005 and 2009 in 11 hospitals were included. Ultrasonographic characteristics, menopausal status and serum CA 125 level were registered preoperatively, and combined into the RMI. The performances of RMI-3 and RMI-4 were assessed and statistically tested for differences. RESULTS: A total of 643 patients were included: 469 benign, 73 borderline and 101 malignant tumors. The RMI-3 had a sensitivity of 76%, specificity of 82%, positive and negative predictive values (PPV and NPV) of 45% and 95%, and an accuracy of 81%. The RMI-4 had a sensitivity of 74%, specificity of 79%, PPV of 40%, NPV of 94%, and an accuracy of 78%. The accuracy of RMI-3 was significantly higher than the accuracy of RMI-4 (p=.001). Both models had an area under the curve of 0.86. CONCLUSION: Both RMI-3 and RMI-4 were able to discriminate between non-invasive lesions and invasive malignant adnexal masses, with similar performances. Including tumor size in the RMI does not improve its performance.

Factors influencing the use of frozen section analysis in adnexal masses.

OBJECTIVE: To determine the factors that influence the use of frozen section analysis in adnexal masses and the factors that predict malignancy. METHODS: The study participants were women scheduled for adnexal mass surgery in 11 hospitals between 2005 and 2009. Factors that potentially influenced the use of frozen section analysis and potentially predicted malignancy were studied, such as menopausal status, CA 125 level, ultrasound characteristics, presence of adhesions, and tumor size. We used univariable and multivariable analyses to assess the factors. RESULTS: A total of 670 patients were included in the study. The frozen section analyses for 323 patients (48%) showed 206 benign, 55 borderline, and 62 malignant adnexal masses. The CA 125 level, locularity of the tumor, and presence of solid areas predicted both the use of frozen section analysis and the presence of malignancy. The presence of adhesions predicted malignancy, but not the use of frozen section analysis. Menopausal status and tumor size predicted the use of frozen section analysis, but not malignancy. CONCLUSION: Menopausal status and tumor size are associated with more use of frozen section analysis, but they have not been identified as factors associated with malignancy. Frozen section analysis is useful when the CA 125 levels are greater than 35 units/mL and when there are multilocular tumors, solid areas on ultrasonography, and adhesions revealed during surgery.

Evaluation of the Risk of Malignancy Index in daily clinical management of adnexal masses.

OBJECTIVE: To verify the effectiveness of the Risk of Malignancy Index in the discrimination between non-invasive (benign and borderline) lesions and invasive malignant adnexal masses in daily clinical practice. METHODS: This prospective observational study was conducted in a multicentre cooperation of 11 hospitals. A total of 548 women with adnexal masses were included. Ultrasound characteristics, menopausal status and serum CA 125 level were registered preoperatively, and combined into the RMI afterwards. Final diagnosis was based on routine histopathologic examination. The decision to have patients operated by or with a gynecologic oncologist was based on the clinical impression of the gynecologist in the local hospital, based on physical examination, testing of serum samples, and ultrasound examination. This was compared with the hypothetical situation in which the RMI would have been applied as method of selection. RESULTS: An RMI of 200 achieved a sensitivity of 81% and specificity of 85% in the detection of ovarian cancer. Positive and negative predictive values were 48% and 96% respectively. In current practice, 64% of ovarian cancer patients were operated by a gynecologic oncologist. This percentage would have increased to 80% if the RMI with a cutoff value of 200 would have been used as method of selection. CONCLUSIONS: In our study population, introduction of the RMI would improve the management of adnexal masses, with a higher percentage of ovarian cancer patients that are operated by a gynecologic oncologist. At the same time, referral of patients with non-invasive (benign and borderline) lesions would be reduced.