Inadequate maternal weight gain increases the risk of small-for-gestational age (SGA) infants. Women with hyperemesis gravidarum (HG) are at risk of significant early pregnancy weight loss and ...insufficient total pregnancy weight gain. Recent studies have implied that weight gain during the first half of pregnancy is more crucial to pregnancy outcome than total weight gain. The aim of this study was to investigate whether not regaining prepregnancy weight by 13-18 weeks of gestation contributed to not reaching minimum body mass index (BMI)-specific total pregnancy weight gain and influenced the risk of SGA outcome in HG pregnancies.
In this retrospective 15-year cohort (2002-2016) of women hospitalized due to hyperemesis gravidarum, we reviewed individual patient hospital files and corresponding outpatient maternity records to collect prepregnancy BMI and weight, pregnancy weight gain (spanning 3-week intervals), delivery weight and foetal outcomes. BMI and total pregnancy weight gain goals were categorized according to the Institute of Medicine (IOM) 2009 guidelines: BMI < 18,5 kg/m
: 12.5-18 kg, 18.5-24.9 kg/m
: 11.5-16 kg, 25-29.9 kg/m
: 7-11.5 kg and > 30 kg/m
: 5-9 kg. Birth weight was categorized as SGA if less than the 10th percentile of sex- and gestational length-specific Norwegian neonatal weight charts. Nonparametric tests were used to compare weight categories, and logistic regression was used to predict the odds ratio (OR) of inadequate total pregnancy weight gain or SGA delivery.
Out of 892 women hospitalized for HG during 2002-2016, 784 had a pregnancy lasting > 24 weeks, of which 746 were singleton pregnancies with follow-up until delivery. Among these women, 42 were classified as underweight, 514 as normal weight, 230 as overweight and 102 as obese before pregnancy. Not regaining prepregnancy weight by week 13-18 was an independent predictor of inadequate total gestational weight gain with an OR of 7.05 (95% CI 4.24-11.71) and an independent predictor for SGA outcome with an OR of 2.66 (95% CI 1.11-6.34), even when adjusted for total pregnancy weight gain, prepregnancy BMI, parity, age and smoking status.
Inadequate total maternal weight gain and not regaining prepregnancy weight by week 13-18 may be considered independent risk factors for delivering a baby that is small for gestational age in pregnancies with hyperemesis gravidarum. Achieving adequate weight gain during the first trimester in HG pregnancies is important for the foetal outcome, underscoring the importance of nutritional treatment during this period.
Summary Most endometrial carcinomas are diagnosed at an early stage. Still, 15–20% of these carcinomas recur with limited effect of systemic therapies in metastatic disease. Improved ability to ...target surgical and systemic therapies to well selected patient populations will increase the likelihood of benefits. Retrospective studies have identified several markers for lymph-node metastasis and poor prognosis. No new targeted treatments are available in the clinic, but recent comprehensive molecular characterisations of tumours have identified drugs targeting the PI3K/PTEN/AKT/mTOR pathway and fibroblast growth factor receptor (FGFR) 2 as promising for further studies, also reflected in current clinical trials investigating endometrial carcinoma. A more systematic approach to integration of biomarkers in surgical trials and clinical trials of therapeutics, earlier characterisation and standardisation of diagnostic imaging and biomarker assessment, and prospective implementation studies are needed for clinical implementation. We summarise the present knowledge regarding biomarkers in endometrial carcinoma, assessing how such markers could be applied to address key clinical challenges for the treatment of this disease.
Background
In endometrial cancer (EC), preoperative pelvic MRI is recommended for local staging, while final tumor stage and grade are established by surgery and pathology. MRI‐based radiomic tumor ...profiling may aid in preoperative risk‐stratification and support clinical treatment decisions in EC.
Purpose
To develop MRI‐based whole‐volume tumor radiomic signatures for prediction of aggressive EC disease.
Study Type
Retrospective.
Population
A total of 138 women with histologically confirmed EC, divided into training (nT = 108) and validation cohorts (nV = 30).
Field Strength/Sequence
Axial oblique T1‐weighted gradient echo volumetric interpolated breath‐hold examination (VIBE) at 1.5T (71/138 patients) and DIXON VIBE at 3T (67/138 patients) at 2 minutes postcontrast injection.
Assessment
Primary tumors were manually segmented by two radiologists with 4 and 8 years' of experience. Radiomic tumor features were computed and used for prediction of surgicopathologically‐verified deep (≥50%) myometrial invasion (DMI), lymph node metastases (LNM), advanced stage (FIGO III + IV), nonendometrioid (NE) histology, and high‐grade endometrioid tumors (E3). Corresponding analyses were also conducted using radiomics extracted from the axial oblique image slice depicting the largest tumor area.
Statistical Tests
Logistic least absolute shrinkage and selection operator (LASSO) was applied for radiomic modeling in the training cohort. The diagnostic performances of the radiomic signatures were evaluated by area under the receiver operating characteristic curve in the training (AUCT) and validation (AUCV) cohorts. Progression‐free survival was assessed using the Kaplan–Meier and Cox proportional hazard model.
Results
The whole‐tumor radiomic signatures yielded AUCT/AUCV of 0.84/0.76 for predicting DMI, 0.73/0.72 for LNM, 0.71/0.68 for FIGO III + IV, 0.68/0.74 for NE histology, and 0.79/0.63 for high‐grade (E3) tumor. Single‐slice radiomics yielded comparable AUCT but significantly lower AUCV for LNM and FIGO III + IV (both P < 0.05). Tumor volume yielded comparable AUCT to the whole‐tumor radiomic signatures for prediction of DMI, LNM, FIGO III + IV, and NE, but significantly lower AUCT for E3 tumors (P < 0.05). All of the whole‐tumor radiomic signatures significantly predicted poor progression‐free survival with hazard ratios of 4.6–9.8 (P < 0.05 for all).
Data Conclusion
MRI‐based whole‐tumor radiomic signatures yield medium‐to‐high diagnostic performance for predicting aggressive EC disease. The signatures may aid in preoperative risk assessment and hence guide personalized treatment strategies in EC.
Level of Evidence
4
Technical Efficacy Stage
2
Background
Improved methods for preoperative risk stratification in endometrial cancer are highly requested by gynecologists. Texture analysis is a method for quantification of heterogeneity in ...images, increasingly reported as a promising diagnostic tool in various cancer types, but largely unexplored in endometrial cancer.
Purpose
To explore whether tumor texture parameters from preoperative MRI are related to known prognostic features (deep myometrial invasion, cervical stroma invasion, lymph node metastases, and high‐risk histological subtype) and to outcome in endometrial cancer patients.
Study type
Prospective cohort study.
Population/Subjects
In all, 180 patients with endometrial carcinoma were included from April 2009 to November 2013 and studied until January 2017.
Field Strength/Sequences
Preoperative pelvic MRI including contrast‐enhanced T1‐weighted (T1c), T2‐weighted, and diffusion‐weighted imaging at 1.5T.
Assessment
Tumor regions of interest (ROIs) were manually drawn on the slice displaying the largest cross‐sectional tumor area, using the proprietary research software TexRAD for analysis. With a filtration‐histogram technique, the texture parameters standard deviation, entropy, mean of positive pixels (MPP), skewness, and kurtosis were calculated.
Statistical Tests
Associations between texture parameters and histological features were assessed by uni‐ and multivariable logistic regression, including models adjusting for preoperative biopsy status and conventional MRI findings. Multivariable Cox regression analysis was used for survival analysis.
Results
High tumor entropy in apparent diffusion coefficient (ADC) maps independently predicted deep myometrial invasion (odds ratio OR 3.2, P lt 0.001), and high MPP in T1c images independently predicted high‐risk histological subtype (OR 1.01, P = 0.004). High kurtosis in T1c images predicted reduced recurrence‐ and progression‐free survival (hazard ratio HR 1.5, P lt 0.001) after adjusting for MRI‐measured tumor volume and histological risk at biopsy.
Data Conclusion
MRI‐derived tumor texture parameters independently predicted deep myometrial invasion, high‐risk histological subtype, and reduced survival in endometrial carcinomas, and thus, represent promising imaging biomarkers providing a more refined preoperative risk assessment that may ultimately enable better tailored treatment strategies in endometrial cancer.
Level of Evidence: 2
Technical Efficacy: Stage 2
J. Magn. Reson. Imaging 2018;48:1637–1647
Women suffering from severe nausea and vomiting during pregnancy, hyperemesis gravidarum, have poor quality of life and increased risk of potentially fatal maternal and fetal complications. There is ...increasing and reassuring knowledge about safety of antiemetics in pregnancy. In 2013, the European Medical Agency (EMA) issued a warning on metoclopramide limiting treatment to maximum five days. Metoclopramide was the most used antiemetic in pregnancy at the time the warning was implemented in the Norwegian hyperemesis guidelines (2014). We aimed at describing changes in the treatment of hyperemesis over time, including changes associated with the EMA warning.
Retrospective chart review of all women hospitalized for hyperemesis gravidarum with metabolic disturbances between 01/Jan/2002 and 31/Dec/2019 at a university hospital serving nearly 10% of the pregnant population in Norway. Time-series analysis described changes over time and interrupted time series analysis quantified changes in treatment and clinical outcomes related to the EMA warning.
In total, 1,064 women (1.2% of the birthing population) were included. The use of meclizine, prochlorperazine, and ondansetron increased during 2002-2019. This led to a yearly increase in the percentage of women using any antiemetic of 1.5% (95%CI 0.6; 2.4) pre-hospital, 0.6% (95%CI 0.2; 1.1) during hospitalization, and 2.6% (95%CI 1.3; 3.8) at discharge. Overall, only 50% of the women received antiemetics pre-hospital. Following the EMA warning, prehospital use of metoclopramide dropped by 30% (95%CI 25; 36), while use of any antiemetic pre-hospital dropped by 20% (95%CI 5.7; 34). In timely association, we observed a decrease in gestational age (-3.8 days, 98.75%CI 0.6; 7.1) at first admission, as well as indication of increased rate of termination of pregnancy with an absolute increase of 4.8% (98.75%CI 0.9; 8.7) in 2014.
During 2002-2019, the overall use of antiemetics in treatment of hyperemesis increased. The EMA-warning on metoclopramide in 2013 temporarily limited pre-hospital antiemetic provision associated with hospitalization at lower gestational length and indication of an increase in termination of pregnancy.
Recent studies have detailed the genomic landscape of primary endometrial cancers, but the evolution of these cancers into metastases has not been characterized. We performed whole-exome sequencing ...of 98 tumor biopsies including complex atypical hyperplasias, primary tumors and paired abdominopelvic metastases to survey the evolutionary landscape of endometrial cancer. We expanded and reanalyzed The Cancer Genome Atlas (TCGA) data, identifying new recurrent alterations in primary tumors, including mutations in the estrogen receptor cofactor gene NRIP1 in 12% of patients. We found that likely driver events were present in both primary and metastatic tissue samples, with notable exceptions such as ARID1A mutations. Phylogenetic analyses indicated that the sampled metastases typically arose from a common ancestral subclone that was not detected in the primary tumor biopsy. These data demonstrate extensive genetic heterogeneity in endometrial cancers and relative homogeneity across metastatic sites.
Handheld point-of-care abdominal ultrasound (POCUS) may be used by primary care physicians while vaginal ultrasound is limited to use in specialist care. We aimed to compare abdominal handheld ...ultrasound to vaginal ultrasound in determining first trimester viable intrauterine pregnancy and estimate gestational length.
Prospective cohort study.
Gynaecologic outpatient clinic; women referred from GPs during early pregnancy. Handheld ultrasound using VscanExtend
®
was performed by fourth-year medical students with limited training. Transvaginal ultrasound using high-end devices was performed by ordinary hospital staff.
Women in the first trimester of pregnancy referred for termination of pregnancy or with symptoms of early pregnancy complications.
Rate of confirming vital intrauterine pregnancy (visualizing foetal heart beats) and measurement of crown-rump length (CRL) using handheld abdominal versus vaginal ultrasound.
In all 100 women were included; 86 confirmed as viable intrauterine pregnancies and 14 pathological pregnancies (miscarriages/extrauterine pregnancies). Handheld abdominal ultrasound detected fetal heartbeats in 63/86 (73% sensitivity) of healthy pregnancies and confirmed lack of fetal heartbeats in all pathological pregnancies, total positive predictive value (PPV) 100% and total negative predictive value (NPV) 38%. From gestational week 7, handheld abdominal ultrasound confirmed vitality in 51/54 patients: PPV 100% and NPV 79%. CRL (n = 62) was median 1 mm shorter (95% confidence interval 1-2 mm) measured by handheld abdominal versus vaginal ultrasound.
Handheld ultrasound has an excellent prediction confirming viable intrauterine pregnancy from gestational week 7. Validation studies are needed to confirm whether the method is suitable in primary care assessing early pregnancy complications.
KEY POINTS
When early pregnancy vitality needs to be confirmed, women will traditionally be referred to secondary care for transvaginal comprehensive ultrasonography performed with high-end devices by imaging specialists.
In this study personnel with limited former training (fourth-year medical students) performed transabdominal POCUS using a handheld device, investigating 100 first trimester pregnancies for confirmation of viability.
Using handheld ultrasound viable pregnancy was confirmed from gestational week 7 with 79% positive and 100% negative predictive value.
If handheld ultrasound used in primary care confirms vital intrauterine pregnancy, the need for specialist referral could be reduced.
Advanced cervical cancer carries a particularly poor prognosis, and few treatment options exist. Identification of effective molecular markers is vital to improve the individualisation of treatment. ...We investigated transcriptional data from cervical carcinomas related to patient survival and recurrence to identify potential molecular drivers for aggressive disease.
Primary tumour RNA-sequencing profiles from 20 patients with recurrence and 53 patients with cured disease were compared. Protein levels and prognostic impact for selected markers were identified by immunohistochemistry in a population-based patient cohort.
Comparison of tumours relative to recurrence status revealed 121 differentially expressed genes. From this gene set, a 10-gene signature with high prognostic significance (p = 0.001) was identified and validated in an independent patient cohort (p = 0.004). Protein levels of two signature genes, HLA-DQB1 (n = 389) and LIMCH1 (LIM and calponin homology domain 1) (n = 410), were independent predictors of survival (hazard ratio 2.50, p = 0.007 for HLA-DQB1 and 3.19, p = 0.007 for LIMCH1) when adjusting for established prognostic markers. HLA-DQB1 protein expression associated with programmed death ligand 1 positivity (p < 0.001). In gene set enrichment analyses, HLA-DQB1high tumours associated with immune activation and response to interferon-γ (IFN-γ).
This study revealed a 10-gene signature with high prognostic power in cervical cancer. HLA-DQB1 and LIMCH1 are potential biomarkers guiding cervical cancer treatment.
PDF
