Handheld vital microscopy for the identification of microcirculatory alterations in cervical intraepithelial neoplasia and cervical cancer.

BACKGROUND: Ninety percent of cervical cancer (CC) diagnoses and deaths occur in low and middle-income countries (LMICs). Especially in these countries, where human and material resources are limited, there is a need for real-time screening methods that enable immediate treatment decisions (i.e., 'see and treat'). OBJECTIVE: To evaluate whether handheld vital microscopy (HVM) enables real-time detection of microvascular alterations associated with cervical intraepithelial neoplasia (CIN) and CC. METHODS: A cross-sectional study was conducted in an oncologic hospital and outpatient clinic, and included ten healthy controls, ten women with CIN, and ten women with CC. The microvasculature was assessed in four quadrants of the uterine cervix using HVM. The primary outcome was the presence of abnormal angioarchitecture (AA). Secondary outcomes included capillary loop density (CD), total vessel density (TVD), functional capillary density (FCD), and the proportion of perfused vessels (PPV). RESULTS: 198 image sequences of the cervical microvasculature were recorded. Compared to healthy controls, significantly more abnormal image sequences were observed in women with high-grade CIN (11 % vs. 44 %, P < 0.001) and women with CC (11 % vs. 69 %, P < 0.001). TVD, FCD, and PPV were lower in women with CIN and CC. CONCLUSIONS: HVM enables easy, real-time, non-invasive assessment of cervical lesions through the detection of microvascular alterations. Thereby, HVM potentially provides an opportunity for point-of-care screening, which may enable immediate treatment decisions (see and treat) and reduce the number of unnecessary surgical interventions.

Vaginal Er:YAG laser application in the menopausal ewe model: a randomised estrogen and sham-controlled trial.

OBJECTIVE: To describe effects of non-ablative erbium-doped:yttrium-aluminium-garnet (Er:YAG) laser on vaginal atrophy induced by iatrogenic menopause in the ewe. DESIGN: Animal experimental, randomised, sham and estrogen-treatment controlled study with blinding for primary outcome. SETTING: KU Leuven, Belgium. SAMPLE: Twenty-four ewes. METHODS: Menopause was surgically induced, after which the ewes were randomised to three groups receiving vaginal Er:YAG laser application three times, with a 1-month interval; three sham manipulations with a 1-month interval; or estrogen replacement and sham manipulations. At given intervals, ewes were clinically examined and vaginal wall biopsies were taken. Vaginal compliance was determined by passive biomechanical testing from explants taken at autopsy. MAIN OUTCOME MEASURES: Vaginal epithelial thickness (primary), composition of the lamina propria (collagen, elastin, glycogen and vessel content), vaginal compliance, clinical signs. RESULTS: Animals exposed to Er:YAG laser application and sham manipulation, but not to estrogens, displayed a significant and comparable increase in vaginal epithelial thickness between baseline and 7 days after the third application (69% and 67%, respectively, both P < 0.0008). In laser-treated ewes, temporary vaginal discharge and limited thermal injury were observed. Estrogen-substituted ewes displayed a more prominent increase in epithelial thickness (202%; P < 0.0001) and higher vaginal compliance (P < 0.05). None of the interventions induced changes in the lamina propria. CONCLUSIONS: Vaginal Er:YAG laser has comparable effect to sham manipulation in menopausal ewes. TWEETABLE ABSTRACT: Vaginal Er:YAG laser has comparable effect to sham manipulation in menopausal ewes #LASER #GSM #RCT.

Follow-up ultrasound in second-trimester low-positioned anterior and posterior placentae: prospective cohort study.

OBJECTIVES: The majority of cases of placenta previa or a low-lying placenta in the second trimester will have a normal placental position in the third trimester. The aim of this study was to assess the accuracy of the distance between the placenta and the internal os of the cervix (IOD) in the second trimester for the prediction of third-trimester low-positioned placenta, and to define a cut-off value at which all cases of third-trimester low-positioned placenta are identified. METHODS: This was a prospective cohort study including women undergoing a transvaginal ultrasound examination between 18 and 24 weeks' gestation who had a low-positioned placenta, defined as an IOD of < 20 mm. Low-positioned placenta included placenta previa, defined as a placenta covering the internal os of the cervix, and a low-lying placenta, defined as a placenta lying near to (within 20 mm) but not overlying the internal os. All women were re-evaluated in the third trimester. Relative risks for a low-positioned placenta in the third trimester were calculated for women with placenta previa vs a low-lying placenta, posterior vs anterior placenta and positive vs negative history of Cesarean section. Multilevel likelihood ratios for ranges of IOD in the prediction of a low-positioned placenta in the third trimester were calculated separately for anteriorly and posteriorly located placentae. Corresponding receiver-operating-characteristics curves were constructed. RESULTS: In total, 958 women were included in the study. In the second trimester, placentae were more frequently located on the posterior side (62.0%) than on the anterior side (38.0%). In the third trimester, 48/958 (5.0%) placentae persisted as a low-positioned placenta. Women with placenta previa in the second trimester had a higher risk of a low-positioned placenta in the third trimester than did those with a low-lying placenta in the second trimester (37/181 (20.4%) vs 11/777 (1.4%); relative risk (RR), 17.9 (95% CI, 8.9-36.0)). Women with a posterior placenta had a higher risk of a low-positioned placenta in the third trimester than did those with an anterior placenta (38/594 (6.4%) vs 10/364 (2.7%); RR, 2.4 (95% CI, 1.2-4.9)), as did women with a history of Cesarean section compared with those without such a history (14/105 (13.3%) vs 34/853 (4.0%); RR, 3.7 (95% CI, 1.9-7.2)). The cut-off value of IOD in the second trimester to identify all cases of an abnormally located placenta in the third trimester was 15.5 mm for posteriorly located placentae, while for anteriorly located placentae the IOD cut-off was lower, namely -4.5 mm, representing a 4.5-mm overlap of the placental edge over the internal os of the cervix. CONCLUSIONS: With incorporation of a safety margin of 5 mm and ensuring that all women with placenta previa undergo a follow-up scan, we recommend lowering the IOD cut-off value for follow-up in cases of an anterior low-positioned placenta from 20 to 5 mm, which would decrease the number of unnecessary follow-up ultrasound examinations without missing any high-risk women. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.