To explore associations between specific treatments for intraepithelial or early invasive cervical lesions and adverse pregnancy outcomes.
We conducted a population-based cohort study in which ...treatment data from the Cancer Registry of Norway were linked to the Medical Birth Registry of Norway to identify adverse pregnancy outcomes. All women (n=545,243) with singleton births (N=943,321) in Norway during 1998-2014 were included; 9,554 of births were in women treated before delivery. Hazard ratios (HRs) with 95% confidence intervals (CIs) were derived from Cox regression models.
There was a significant association between preterm birth and previous treatment of cervical lesions overall (9.7 compared with 5.3%; HR 1.8, 95% CI 1.7-2.0). The strongest associations were seen for cold knife (13 compared with 5.3%; HR 2.6, 95% CI 1.3-5.3) and laser conization (12 compared with 5.3%; HR 2.3, 95% CI 2.0-2.5). The association was stronger for preterm birth at earlier gestational ages and increased with amount of tissue excised. Furthermore, the association weakened with calendar year of treatment. There was also an association with increased risks of spontaneous abortion (0.5 compared with 0.2%; HR 2.5, 95% CI 1.7-3.7), and the strongest associations were seen for laser conization (0.6 compared with 0.2%; HR 3.0, 95% CI 1.8-5.3) and a loop electrosurgical excision procedure (LEEP) (0.4 compared with 0.2%; HR 2.3, 95% CI 1.3-4.0).
Treatment with major excisional procedures, including LEEP, was associated with increased risks of preterm birth and spontaneous abortion. The risk of preterm birth was highest at early gestational ages and for those with the largest amount of tissue excised. Women should be informed about their future risk of adverse pregnancy outcomes, particularly preterm birth, after excisional treatment for cervical lesions.
The vast majority of epithelial ovarian cancer arises from tissues that are embryologically derived from the Müllerian Duct. Here, we demonstrate that a DNA methylation signature in easy-to-access ...Müllerian Duct-derived cervical cells from women with and without ovarian cancer (i.e. referred to as the Women's risk IDentification for Ovarian Cancer index or WID-OC-index) is capable of identifying women with an ovarian cancer in the absence of tumour DNA with an AUC of 0.76 and women with an endometrial cancer with an AUC of 0.81. This and the observation that the cervical cell WID-OC-index mimics the epigenetic program of those cells at risk of becoming cancerous in BRCA1/2 germline mutation carriers (i.e. mammary epithelium, fallopian tube fimbriae, prostate) further suggest that the epigenetic misprogramming of cervical cells is an indicator for cancer predisposition. This concept has the potential to advance the field of risk-stratified cancer screening and prevention.
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
Secondary cytoreductive surgery is a treatment option for relapsed platinum-sensitive epithelial ovarian cancer, but no clear indications are defined for the procedure. This systematic review aims to ...establish clear indications and compare outcomes versus standard-of-care chemotherapy. We conducted an electronic literature search across three databases and identified 2033 articles, including three phase 3 randomized controlled trials (RCT). The review adhered to PRISMA 2020 guidelines and was registered in PROSPERO (no. CRD42022379817). Despite varying patient selection methods, surgery plus chemotherapy demonstrated significantly prolonged progression-free survival compared to chemotherapy alone. However, overall survival outcomes were inconsistent: while GOG-0213 did not show extended overall survival, recent studies with stricter defined criteria for surgery (SOC-1 and DESKTOP-III) reported improved overall survival with the addition of surgery. Morbidity and mortality rates were low, with no difference in quality of life between the surgery and no-surgery groups. In conclusion, cytoreductive surgery presents a promising option for recurrent epithelial ovarian cancer treatment. Nonetheless, well-defined selection criteria appear crucial for achieving increased overall survival compared to conventional treatment.
Malignant melanoma is a prevalent and aggressive cancer, with globally increasing incidences. While immune checkpoint inhibitors (ICIs) have prolonged the survival of patients with advanced melanoma ...over the last decade, this improvement comes with the risk of severe immune-related adverse events (irAEs). This systematic review investigates patient baseline characteristics (BCs) as predictive factors for developing severe gastrointestinal, hepatic, and pulmonary irAEs in patients treated with ipilimumab (anti-CTLA-4) and/or nivolumab/pembrolizumab (anti-PD-1). A systematic literature search was conducted in the Ovid databases MEDLINE and EMBASE on 22 April 2022, following the PRISMA guidelines. Out of 1694 articles, 13 were included in the final analysis. We analyzed BCs and the occurrence of severe colitis, hepatitis, and pneumonitis in 22 treatment arms and 3 treatment groups: anti-CTLA-4 (
= 2904), anti-PD-1 (
= 1301), or combination therapy (
= 822). However, missing data preclude a direct comparison of individual BCs and the association to specific irAEs between studies. Descriptive analysis did not identify any significant association between median age, gender distribution, or performance status and severe colitis, hepatitis, or pneumonitis for any of the three treatment groups. We call for greater transparency and standardization in the reporting of patient-specific irAEs.
Utero-placental development in pregnancy depends on direct maternal-fetal interaction in the uterine wall decidua. Abnormal uterine vascular remodeling preceding placental oxidative stress and ...placental dysfunction are associated with preeclampsia and fetal growth restriction (FGR). Oxidative stress is counteracted by antioxidants and oxidative repair mechanisms regulated by the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2). We aimed to determine the decidual regulation of the oxidative-stress response by NRF2 and its negative regulator Kelch-like ECH-associated protein 1 (KEAP1) in normal pregnancies and preeclamptic pregnancies with and without FGR. Decidual tissue from 145 pregnancies at delivery was assessed for oxidative stress, non-enzymatic antioxidant capacity, cellular NRF2- and KEAP1-protein expression, and NRF2-regulated transcriptional activation. Preeclampsia combined with FGR was associated with an increased oxidative-stress level and NRF2-regulated gene expression in the decidua, while decidual NRF2- and KEAP1-protein expression was unaffected. Although preeclampsia with normal fetal growth also showed increased decidual oxidative stress, NRF2-regulated gene expression was reduced, and KEAP1-protein expression was increased in areas of high trophoblast density. The trophoblast-dependent KEAP1-protein expression in preeclampsia with normal fetal growth indicates control of decidual oxidative stress by maternal-fetal interaction and underscores the importance of discriminating between preeclampsia with and without FGR.
Purpose
Fluorescence imaging (FLI) using targeted near-infrared (NIR) conjugates aids the detection of tumour lesions pre- and intraoperatively. The optimisation of tumour visualisation and contrast ...is essential and can be achieved through high tumour-specificity and low background signal. However, the choice of fluorophore is recognised to alter biodistribution and clearance of conjugates and is therefore a determining factor in the specificity of target binding. Although ZW800-1, IRDye® 800CW and ICG are the most commonly employed NIR fluorophores in clinical settings, the fluorophore with optimal
in vivo
characteristics has yet to be determined. Therefore, we aimed to characterise the impact the choice of fluorophore has on the biodistribution, specificity and contrast, by comparing five different NIR fluorophores conjugated to folate, in an ovarian cancer model.
Procedures
ZW800-1, ZW800-1 Forte, IRDye® 800CW, ICG-OSu and an in-house synthesised Cy7 derivative were conjugated to folate through an ethylenediamine linker resulting in conjugates
1
–
5
, respectively. The optical properties of all conjugates were determined by spectroscopy, the specificity was assessed
in vitro
by flow cytometry and FLI, and the biodistribution was studied
in vivo
and
ex vivo
in a subcutaneous Skov-3 ovarian cancer model.
Results
We demonstrated time- and receptor-dependent binding of folate conjugates
in vitro
and
in vivo
. Healthy tissue clearance characteristics and tumour-specific signal varied between conjugates
1
–
5
. ZW800-1 Forte (
2
) revealed the highest contrast in folate receptor alpha (FRα)-positive xenografts and showed statistically significant target specificity. While conjugates
1
,
2
and
3
are renally cleared, hepatobiliary excretion and no or very low accumulation in tumours was observed for
4
and
5
.
Conclusions
The choice of fluorophore has a significant impact on the biodistribution and tumour contrast. ZW800-1 Forte (
2
) exhibited the best properties of those tested, with significant specific fluorescence signal.
Objectives
To evaluate both incidence and prevalence of drugs used for chronic diseases in survivors of adult‐onset gynaecological cancer.
Design
A prospective study.
Setting
Population‐based ...registries.
Population
1.76 million women, including 17 500 women with gynaecological cancers.
Methods
Data from the Cancer Registry of Norway was linked to the Norwegian Prescription Database and other national databases.
Main Outcome Measures
Prevalence ratios (PRs) and hazard ratios (HRs), with 95% confidence intervals (CIs), of dispensed drugs in gynaecological cancer patients (up to 15 years after diagnosis) were estimated by log‐binomial and Cox regression, respectively, with cancer‐free women as reference.
Results
For gynaecological cancer patients, the incidence of drugs used for pain control was higher than in cancer‐free women, especially the first 5 years after diagnosis, and the prevalence was high at least 10 years after. The prevalence of sex hormones was high in women with gynaecological cancer at least 10 years after diagnosis (cervical and ovarian cancer PR = 23, 95% CI 18–30 and PR = 29, 95% CI 15–38, respectively), but low in cancer‐free women (0.3%). Patients with uterine corpus cancer had a higher prevalence of antidiabetics before and at least 10 years after diagnosis, most pronounced in women diagnosed before age 50 (PR = 10, 95% CI 5.0–21). The prevalence of antidepressants was moderately elevated in women with gynaecological cancers.
Conclusions
Gynaecological cancer survivors, particularly cervical and ovarian cancer survivors, had an increased long‐term use of drugs for pain control and sex hormones. Survivors of uterine corpus cancer used antidiabetics more often, both before and after diagnosis.
Abstract Introduction Preeclampsia is a heterogeneous gestational disease characterized by maternal hypertension and proteinuria, affecting 2–7% of pregnancies. The disorder is initiated by ...insufficient placental development, but studies characterizing the placental disease components are lacking. Methods Our aim was to phenotype the preeclamptic placenta using high-resolution magic angle spinning nuclear magnetic resonance spectroscopy (HR-MAS MRS). Placental samples collected after delivery from women with preeclampsia (n = 19) and normotensive pregnancies (n = 15) were analyzed for metabolic biomarkers including amino acids, osmolytes, and components of the energy and phospholipid metabolism. The metabolic biomarkers were correlated to clinical characteristics and inflammatory biomarkers in the maternal sera. Results Principal component analysis showed inherent differences in placental metabolic profiles between preeclamptic and normotensive pregnancies. Significant differences in metabolic profiles were found between placentas from severe and non-severe preeclampsia, but not between preeclamptic pregnancies with fetal growth restricted versus normal weight neonates. The placental metabolites correlated with the placental stress marker sFlt-1 and triglycerides in maternal serum, suggesting variation in placental stress signaling between different placental phenotypes. Discussion HR-MAS MRS is a sensitive method for defining the placental disease component of preeclampsia, identifying several altered metabolic pathways. Placental HR-MAS MRS analysis may improve insight into processes affected in the preeclamptic placenta, and represents a novel long-required tool for a sensitive placental phenotyping of this heterogeneous disease.
PDF
