Can serum human epididymis protein 4 (HE4) support the decision to refer a patient with an ovarian mass to an oncology hospital?

INTRODUCTION: The value of serum human epididymis protein 4 (HE4) in guiding referral decisions in patients with an ovarian mass remains unclear, because the majority of studies investigating HE4 were performed in oncology hospitals. However, the decision to refer is made at general hospitals with a low ovarian cancer prevalence. We assessed accuracies of HE4 in differentiating benign or borderline from malignant tumors in patients presenting with an ovarian mass at general hospitals. METHOD: Patients with an ovarian mass were prospectively included between 2017 and 2021 in nine general hospitals. HE4 and CA125 were preoperatively measured and the risk of malignancy index (RMI) was calculated. Histological diagnosis was the reference standard. RESULTS: We included 316 patients, of whom 195 had a benign, 39 had a borderline and 82 had a malignant ovarian mass. HE4 had the highest AUC of 0.80 (95%CI 0.74-0.86), followed by RMI (0.71, 95%CI 0.64-0.78) and CA125 (0.69, 95%CI 0.62-0.75). Clinical setting significantly influenced biomarker performances. Applying age-dependent cut-off values for HE4 resulted in a better performance than one cut-off. Addition of HE4 to RMI resulted in a 32% decrease of unnecessary referred patients, while the number of correctly referred patients remained the same. CONCLUSION: HE4 is superior to RMI in predicting malignancy in patients with an ovarian mass from general hospitals. The addition of HE4 to the RMI improved HE4 alone. Although, there is still room for improvement, HE4 can guide referral decisions in patients with an ovarian mass to an oncology hospital.

Single- versus double-layer closure of the caesarean (uterine) scar in the prevention of gynaecological symptoms in relation to niche development - the 2Close study: a multicentre randomised controlled trial.

BACKGROUND: Double-layer compared to single-layer closure of the uterus after a caesarean section (CS) leads to a thicker myometrial layer at the site of the CS scar, also called residual myometrium thickness (RMT). It possibly decreases the development of a niche, which is an interruption of the myometrium at the site of the uterine scar. Thin RMT and a niche are associated with gynaecological symptoms, obstetric complications in a subsequent pregnancy and delivery and possibly with subfertility. METHODS: Women undergoing a first CS regardless of the gestational age will be asked to participate in this multicentre, double blinded randomised controlled trial (RCT). They will be randomised to single-layer closure or double-layer closure of the uterine incision. Single-layer closure (control group) is performed with a continuous running, unlocked suture, with or without endometrial saving technique. Double-layer closure (intervention group) is performed with the first layer in a continuous unlocked suture including the endometrial layer and the second layer is also continuous unlocked and imbricates the first. The primary outcome is the reported number of days with postmenstrual spotting during one menstrual cycle nine months after CS. Secondary outcomes include surgical data, ultrasound evaluation at three months, menstrual pattern, dysmenorrhea, quality of life, and sexual function at nine months. Structured transvaginal ultrasound (TVUS) evaluation is performed to assess the uterine scar and if necessary saline infusion sonohysterography (SIS) or gel instillation sonohysterography (GIS) will be added to the examination. Women and ultrasound examiners will be blinded for allocation. Reproductive outcomes at three years follow-up including fertility, mode of delivery and complications in subsequent deliveries will be studied as well. Analyses will be performed by intention to treat. 2290 women have to be randomised to show a reduction of 15% in the mean number of spotting days. Additionally, a cost-effectiveness analysis will be performed from a societal perspective. DISCUSSION: This RCT will provide insight in the outcomes of single- compared to double-layer closure technique after CS, including postmenstrual spotting and subfertility in relation to niche development measured by ultrasound. TRIAL REGISTRATION: Dutch Trial Register ( NTR5480 ). Registered 29 October 2015.

Fertility and obstetric outcomes after curettage versus expectant management in randomised and non-randomised women with an incomplete evacuation of the uterus after misoprostol treatment for miscarriage.

OBJECTIVE: To assess fertility and obstetric outcomes in women treated with curettage or undergoing expectant management for an incomplete miscarriage after misoprostol treatment. STUDY DESIGN: Between June 2012 and July 2014, we conducted a multicentre randomised clinical trial (RCT) with a parallel cohort study for non-randomised women, treated according to their preference. In the RCT 30 women were allocated curettage and 29 expectant management. In the cohort 197 women participated; 65 underwent curettage and 132 women underwent expectant management. Primary outcome was curation, defined as either an empty uterus on sonography at six weeks or an uneventful clinical follow-up. We used questionnaires to assess fertility and obstetric outcome of the first new pregnancy subsequent to study enrolment. RESULTS: Curation was seen in 91/95 women treated with curettage (95.8%) versus 134/161 women managed expectantly (83.2%) (p=0.003). The response rate was 211/255 (82%). In 198 women pursuing a new pregnancy, conception rates were 92% (67/73) in the curettage group versus 96% (120/125) in the expectant management group (OR 0.96, 95% CI 0.89;1.03, p=0.34), with ongoing pregnancy rates of 87% (58/67) versus 78% (94/120), respectively (OR 1.12, 95% CI 0.99;1.28, p=0.226). Preterm birth rates were 1/46 in the curettage group versus 8/81 in the expectant management group (OR 0.22, 95% CI 0.03;1.71 P=0.15). Caesarean section rates were 23% and 24% for women in the curettage group and expectant management group respectively. CONCLUSION: In women with an incomplete evacuation of the uterus after misoprostol treatment, curettage and expectant management does not lead to different fertility and pregnancy outcomes, as compared to expectant management.

[Ascites, pleural effusion and a benign ovarian tumour; the triad of Meigs' syndrome]. / Ascites, pleuravocht en een benigne ovariumtumor.

BACKGROUND: Classical Meigs' syndrome consists of the triad of an ovarian fibroma, ascites and pleural effusion. A characteristic of the syndrome is that the excess fluid is resorbed after surgical resection of the tumour. CASE DESCRIPTION: A 49-year-old woman was admitted to accident and emergency department in a neglected, cachectic and hypothermic condition. A CT scan revealed an ovarian tumour, ascites and a right-sided pleural effusion. The level of the tumour marker CA-125 was also greatly elevated. Our initial working diagnosis was, therefore, 'high-grade ovarian carcinoma', but on repeated testing no malignant cells were found in the aspirated fluid. We suspected Meigs' syndrome. We first ensured that her general and nutritional condition improved; then she underwent a bilateral adnexectomy. A fibrothecoma was found in each ovary. The ascites and pleural effusion resolved following surgery and the patient recovered well. CONCLUSION: The clinical picture of Meigs' syndrome can resemble that of high-grade ovarian carcinoma. This syndrome should be included in the differential diagnosis in patients with an ovarian tumour, ascites and, possibly, pleural effusion.

No increase in C-reactive protein levels during intranasal compared to oral hormone therapy in healthy post-menopausal women.

BACKGROUND: Inflammation plays an important role in the development of atherosclerotic disease. Oral post-menopausal hormone therapy increases serum C-reactive protein (CRP) levels. This study compared the effects of intranasal and oral administration of 17beta-estradiol (E2) combined with norethisterone acetate (NETA) on markers of inflammation in healthy post-menopausal women. METHODS: Ninety healthy post-menopausal women (age 56.6 +/- 4.7 years) participated in this 1-year trial. After computerized block randomization, they daily received, in a double-blind fashion, either intranasal E2/NET [175 microg/275 microg (n = 47)] or oral E2/NETA [1 mg/0.5 mg (n = 43)]. Concentrations of high sensitivity CRP and adhesion molecules were measured at baseline and after 12, 24 and 52 weeks of treatment. RESULTS: CRP levels were increased (P = 0.001) in the oral but not in the intranasal group. The increase in the oral group was highest at week 12 (64.9%) and was larger (P < 0.01) compared with the non-significant increase (8.6%) found in the intranasal group. Both groups showed decreases (P < 0.001) in soluble vascular cell adhesion molecule (sVCAM), soluble intracellular adhesion molecule (sICAM) and sE-selectin. The decreases were larger (P < 0.01) in the oral than in the intranasal group. CONCLUSION: Intranasal E2/NET therapy did not significantly increase CRP levels, in contrast to the increase observed in the oral E2/NETA treatment group. Both intranasal and oral therapy lowered plasma concentrations of adhesion molecules, however, more so in the oral group.

Oral, more than transdermal, oestrogen therapy lowers asymmetric dimethylarginine in healthy postmenopausal women: a randomized, placebo-controlled study.

OBJECTIVE: To compare the effects of oral and transdermal hormone therapy (HT) on asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in postmenopausal women. DESIGN: In a multicentre, placebo-controlled, double-blind study, 152 hysterectomized healthy women were randomized to receive daily transdermal 17beta-oestradiol (tE2, n = 33), or oral micronized 17beta-oestradiol either unopposed (oE2, n = 37), or continuous combined with gestodene (oE2 + G, n = 33), or placebo (n = 49) for 13, 28-day treatment cycles. Plasma concentrations of ADMA, arginine and symmetric dimethylarginine (SDMA) were measured at baseline and in treatment cycles 4 and 13 with a high-performance liquid chromatography method. RESULTS: After 13 cycles all active treatment groups showed a significant reduction in ADMA compared with placebo: tE2, -4.0% (95% CI: -7.5 to -0.6%); oE2, -7.7% (95% CI: -10.9 to -4.4%) and oE2 + G, -7.5% (95% CI: -10.8 to -4.3%). ancova showed a significantly larger reduction in the oral groups compared with the transdermal group (tE2 vs. oE2 and tE2 vs. oE2 + G, both P < 0.01). Oral, but not transdermal treatment, significantly reduced arginine compared with placebo. All active treatments reduced SDMA; however, this was only statistically significant in the oE2 group. CONCLUSION: Reduction of ADMA was more pronounced after oral than after tE2 administration. Adding gestodene to oral 17beta-oestradiol did not alter the reduction of ADMA. The clinical implications of these findings remain uncertain; however, the decrease of ADMA by 17beta-oestradiol could be a key phenomenon in the modulation of nitric oxide synthesis by postmenopausal HT.

Reproducibility of antroduodenal motility during prolonged ambulatory recording.

Ambulatory recording of antroduodenal manometry is a novel technique with several advantages over standard stationary manometry recording. Although the feasibility of this technique in clinical practice has been demonstrated, reproducibility of antroduodenal motility recorded by means of ambulatory manometry has not been investigated. To test whether antroduodenal motility recorded by ambulatory manometry is reproducible, we performed two 24-h ambulatory antroduodenal manometry recordings in 18 healthy subjects according to an identical protocol with a 1-week interval. Motility was recorded with a five-channel solid-state catheter. Postprandial motility was recorded after consumption of two test meals and interdigestive motility was recorded nocturnally. Postprandial antroduodenal motor characteristics were identical between the separate recordings. The number and duration of nocturnal cycles of the interdigestive migrating motor complex were also in the same range. Phase III characteristics in general were not different between the two recordings. Only minor alterations were observed in the duration of phase III motor fronts with duodenal onset and in the number of interdigestive cycles concluded by duodenal onset phase III. Parameters obtained by qualitative analysis were comparable between the two recordings. The antroduodenal motility pattern, when measured by ambulatory recording with solid state catheters under standardized conditions, is very reproducible.

Prolonged ambulatory recording of antroduodenal motility in slow-transit constipation.

BACKGROUND: Slow-transit constipation may be part of a pan-enteric motor disorder. To test this hypothesis 24-h ambulatory antroduodenal manometry was performed and orocaecal transit time determined in patients with slow-transit constipation and in healthy controls. METHODS: Antroduodenal motility was recorded with a five-channel solid-state catheter. Postprandial motility was recorded after consumption of two standardized test meals and interdigestive motility was recorded nocturnally. Manometry tracings were analysed for quantitative and qualitative abnormalities. Orocaecal transit time was determined by means of the lactulose hydrogen breath test. RESULTS: Postprandial motility was no different between patients and controls. However, some minor changes of interdigestive motility were observed. The proportion of phase II activity of the nocturnal cycles of the interdigestive migrating motor complex was increased in patients while phase I activity was decreased. The total number of observed phase III fronts was no different in patients and controls, although the number of phase III fronts with antral onset was decreased. Furthermore, the amplitude of phase III activity of duodenal onset was also decreased. Specific motor abnormalities such as retrograde propagation of phase III fronts were more frequent in patients. Orocaecal transit time was delayed in patients. CONCLUSION: In patients with slow-transit constipation, orocaecal transit time is delayed but antro- duodenal motility is generally well preserved with only minor alterations. Presented as a poster to the Digestive Disease Week meeting in New Orleans, Louisiana, USA, May 1998, and published in abstract form as Gastroenterology 1998; 114: A820