| 1. |
- Joneborg, Ulrika, et al.
(författare)
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Hydatidiform mole and subsequent pregnancy outcome : a population-based cohort study
- 2014
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 24:9, s. 1084-1084
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The objective of the study was to investigate whether a history of hydatidiform mole (HM) is associated with an increased risk of adverse outcomes in subsequent pregnancies. STUDY DESIGN: This was a nationwide cohort study with data from population-based registers. The study population consisted of all children registered in the Swedish Medical Birth Register 1973-2009 (n = 3,730,825). Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated for adverse maternal and offspring pregnancy outcomes by maternal history of HM prior to the delivery, with children to women with no maternal history of HM as the reference. Risk estimates were adjusted for maternal age at delivery and maternal country of birth. RESULTS: A history of HM was not associated with an increased risk of adverse maternal outcomes in subsequent pregnancies (n = 5186). Women exposed to a molar pregnancy prior to the index birth were at an almost 25% increased risk of preterm birth (OR, 1.23; 95% CI, 1.06-1.43), whereas women with at least 1 birth between the HM and the index birth were at an increased risk of a large-for-gestational-age birth and stillbirth (OR, 1.35; 95% CI, 1.10-1.67 and OR, 1.81; 95% CI, 1.11-2.96, respectively). The risk of repeat mole was 0.4%. CONCLUSION: Women with a history of HM are at no increased risk of adverse maternal outcomes in subsequent pregnancies but have an increased risk of large-for-gestational-age birth, stillbirth, and preterm birth. However, in absolute terms, the risk of subsequent adverse offspring outcomes is very low.
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| 2. |
- Joneborg, Ulrika
(författare)
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Hydatidiform mole : prevalence and outcome
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Hydatidiform mole (HM) is a genetically abnormal pregnancy with malignant potential, which exists in two forms, complete (CHM) and partial hydatidform mole (PHM). The incidence rates (IR) of HM show wide geographic variations, due to differences in registration practices and methods of estimating rates. With increasingly easy access to medical care, and introduction of better diagnostic techniques, pathological pregnancies are detected at an earlier gestational age (GA). As a result of earlier detection, the presenting symptoms and clinical features originally described for second trimester molar pregnancies, are becoming less frequent and the diagnostic criteria have changed. Women with a diagnosis of HM are of childbearing age, and many are eager for a new pregnancy. The aims of this thesis were to investigate the current epidemiology and diagnostic accuracy of HM, and to evaluate pregnancy outcomes subsequent to a HM. Methods: The study population in studies I, III and IV were all women with HM in Stockholm County 1991-2010 or subgroups thereof, and the cohort in study II was all births in Sweden 1973-2009. Study I compared the main presenting symptoms and clinical features of CHM and PHM, as well as of current CHM compared to a historic cohort. In study II, subsequent pregnancy outcomes of women with a history of HM were evaluated and compared to women with no history of HM. Incidence rates of HM, in relation to age groups and time periods, were investigated in study III. Finally, study IV examined the accuracy and the inter-rater agreement in the diagnosis of HM, by re-evaluating histological slides, and applying ancillary methods, including immunohistochemistry (IHC) and image cytometry. Results: The overall IR of HM was 2.08/1000 deliveries and 1.48/1000 viable conceptions. A temporal increase in the IR of HM was seen, while the proportion of malignant progression remained constant. The registered number and proportion of PHM increased, and a significant overdiagnosis of PHM was demonstrated. Women with HM were diagnosed 1-2 gestational weeks earlier than previously described in Stockholm County. Vaginal bleeding was the main presenting symptom for women with CHM (57%), but less common compared to a historic cohort (84%, p<0.01). The majority (53%) of women with PHM were asymptomatic at the time of diagnosis. A maternal history of HM was associated with a lower risk of preeclampsia (PE) (OR 0.75) and a slightly increased risk of preterm birth, stillbirth and large for gestational age birth (LGA), although the risk increases were inconsistent when stratified by the relationship between the molar exposure and the rankorder of subsequent births. Conclusion: The results indicate, that while the IR of HM is increasing, the rate of malignant progression remains constant. Women with HM are diagnosed at successively earlier gestational ages, with symptoms not differing from those of a normal miscarriage. The earlier detection also makes the histological diagnosis difficult, and ancillary diagnostic methods should be applied to avoid a misdiagnosis of HM, and potentially an undetected malignancy. Women with a history of HM can expect normal future reproductive outcomes.
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| 3. |
- Moyano-Galceran, Lidia, et al.
(författare)
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Adaptive RSK-EphA2-GPRC5A signaling switch triggers chemotherapy resistance in ovarian cancer.
- 2020
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Ingår i: EMBO Molecular Medicine. - : EMBO. - 1757-4676 .- 1757-4684. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- Metastatic cancers commonly activate adaptive chemotherapy resistance, attributed to both microenvironment-dependent phenotypic plasticity and genetic characteristics of cancer cells. However, the contribution of chemotherapy itself to the non-genetic resistance mechanisms was long neglected. Using high-grade serous ovarian cancer (HGSC) patient material and cell lines, we describe here an unexpectedly robust cisplatin and carboplatin chemotherapy-induced ERK1/2-RSK1/2-EphA2-GPRC5A signaling switch associated with cancer cell intrinsic and acquired chemoresistance. Mechanistically, pharmacological inhibition or knockdown of RSK1/2 prevented oncogenic EphA2-S897 phosphorylation and EphA2-GPRC5A co-regulation, thereby facilitating a signaling shift to the canonical tumor-suppressive tyrosine phosphorylation and consequent downregulation of EphA2. In combination with platinum, RSK inhibitors effectively sensitized even the most platinum-resistant EphA2high , GPRC5Ahigh cells to the therapy-induced apoptosis. In HGSC patient tumors, this orphan receptor GPRC5A was expressed exclusively in cancer cells and associated with chemotherapy resistance and poor survival. Our results reveal a kinase signaling pathway uniquely activated by platinum to elicit adaptive resistance. They further identify GPRC5A as a marker for abysmal HGSC outcome and putative vulnerability of the chemo-resistant cells to RSK1/2-EphA2-pS897 pathway inhibition.
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| 4. |
- Salehi, Sahar, et al.
(författare)
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Cardiophrenic lymph node resection in advanced ovarian cancer : surgical outcomes, pre- and postoperative imaging
- 2018
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Ingår i: Acta Oncologica. - 0284-186X. ; 57:6, s. 820-824
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the accuracy of preoperative imaging in the diagnosis of cardiophrenic lymph node (CPLN) metastases and to report perioperative outcomes after resection of CPLN at the time of cytoreductive surgery for advanced epithelial ovarian cancer (EOC). Furthermore, to assess clearance of CPLN by postoperative imaging. Methods: All women with stage IIIC/IV EOC subjected to surgery at our institution from January 2014 to October 2016 were retrospectively identified from a database. Among these, women subjected to CPLN resection during surgery were identified. Pre- and postoperative computed tomography (CT) scans, pathology reports, surgical approach and outcomes were reviewed. Results: One hundred and eighty women with stage IIIC/IV EOC subjected to surgery with curative intent were identified. Twenty-four (13%) of these women underwent CPLN resection. All had CT imaging suggestive of CPLN metastases. 20/24 (83%) had confirmed metastases upon final pathology. CPLN resection was associated with longer operation time, more often advanced upper abdominal surgery and more postoperative complications but there was no difference in days from surgery to initiation of chemotherapy. Postoperative CT was still indicative of CPLN metastases in 13/22 (59%) women despite resection with confirmative pathology. Conclusions: Resection of CPLN metastases is highly feasible without considerable added morbidity. Concern regarding surgical clearance is raised since postoperative imaging was indicative of metastases in the majority of women. The prognostic significance of stage IV disease based exclusively on CPLN metastases is unclear and any survival benefit from the procedure is yet to be determined.
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