Diagnostic imaging of adnexal masses in pregnancy.

Adnexal masses detected during pregnancy require a prompt and accurate diagnosis to ensure fetal safety and good oncological outcomes. Computed tomography is the most common and useful diagnostic imaging modality for diagnosing adnexal masses; however, it is contraindicated in pregnant women because of the teratogenic effect of radiation on the fetus. Therefore, ultrasonography (US) is commonly used as the main alternative for the differential diagnosis of adnexal masses during pregnancy. Additionally, magnetic resonance imaging (MRI) can assist in the diagnosis when US findings are inconclusive. As each disease has characteristic US and MRI findings, understanding these features is important for the initial diagnosis and subsequent treatment. Thus, we thoroughly reviewed the literature and summarized the key findings of US and MRI to apply these in real-world clinical practice for various adnexal masses detected during pregnancy.

Preterm Labor and Preterm-PROM at a Lower Gestational Age Are Associated with a Longer Latency-to-Delivery Even in Patients with the Same Intensity of Intra-Amniotic Inflammation: "Carroll-Model" Revisited.

A previous study by Carroll et al. demonstrated that the time from preterm-PROM to delivery was longer at a lower gestational age (GA) when the membranes rupture, although the presence or absence of intra-amniotic inflammation (IAI) was not examined in that study. However, patients with either preterm labor (PTL) or preterm-PROM at a lower GA had more frequent IAI, which was associated with a shorter amniocentesis-to-delivery (ATD) interval as compared with inflammation-free amniotic fluid (AF). Up to now, there is no information about whether PTL and preterm-PROM at a lower GA are associated with a shorter or longer latency to delivery in cases with the same intensity of IAI. The objective of the study is to examine this issue. AF MMP-8 was measured in 476 singleton early preterm-gestations (21.5 < GA at amniocentesis < 34 wks) with PTL (n = 253) and preterm-PROM (n = 223). Patients were divided into three groups according to GA at amniocentesis (i.e., group-1: <26 wks; group-2: 26−30 wks; group-3: 30−34 wks). IAI was defined as an elevated AF MMP-8 (≥23 ng/mL), and IAI was classified into either mild IAI (AF MMP-8: 23−350 ng/mL) or severe IAI (AF MMP-8 ≥ 350 ng/mL). ATD interval was examined according to GA at amniocentesis in the context of the same intensity of IAI (i.e., inflammation-free AF, mild IAI, and severe IAI) among pregnant women with either PTL or preterm-PROM. IAI was more frequent at a lower GA in cases with PTL (group-1 vs. group-2 vs. group-3; 59.5% vs. 47.4% vs. 25.1%; X2test, p = 0.000034 and linear by linear association [LBLA], p = 0.000008) and in those with preterm-PROM (group-1 vs. group-2 vs. group-3; 69.2% vs. 50.0% vs. 32.0%; X2test, p = 0.000104, and LBLA, p = 0.000019). Of note, cases without IAI at a lower GA had a longer ATD interval in both PTL (Spearman's rank correlation test, γ = −0.360, p = 0.000003) and preterm-PROM (γ = −0.570, p = 0.000001) groups. Moreover, the lower the GA, the longer the ATD interval, even among patients with mild and severe IAI in both PTL (Spearman's rank correlation test; mild IAI, γ = −0.290, p = 0.039; severe IAI, γ = −0.299, p = 0.048) and preterm-PROM (mild IAI, γ = −0.565, p = 0.000013; severe IAI, γ = −0.363, p = 0.015) groups. In conclusion, PTL and preterm-PROM at a lower GA are associated with a longer latency to delivery, even in patients with the same intensity of IAI. This finding suggests that a more intense IAI may be needed for spontaneous preterm birth at a lower GA.

Inhibition of cyclic AMP response element-directed transcription by decoy oligonucleotides enhances tumor-specific radiosensitivity.

The radiation stress induces cytotoxic responses of cell death as well as cytoprotective responses of cell survival. Understanding exact cellular mechanism and signal transduction pathways is important in improving cancer radiotherapy. Increasing evidence suggests that cyclic AMP response element binding protein (CREB)/activating transcription factor (ATF) family proteins act as a survival factor and a signaling molecule in response to stress. We postulated that CREB inhibition via CRE decoy oligonucleotide increases tumor cell sensitization to γ-irradiation-induced cytotoxic stress. In the present study, we demonstrate that CREB phosphorylation and CREB DNA-protein complex formation increased in time- and radiation dose-dependent manners, while there was no significant change in total protein level of CREB. In addition, CREB was phosphorylated in response to γ-irradiation through p38 MAPK pathway. Further investigation revealed that CREB blockade by decoy oligonucleotides functionally inhibited transactivation of CREB, and significantly increased radiosensitivity of multiple human cancer cell lines including TP53- and/or RB-mutated cells with minimal effects on normal cells. We also demonstrate that tumor cells ectopically expressing dominant negative mutant CREB (KCREB) and the cells treated with p38 MAPK inhibitors were more sensitive to γ-irradiation than wild type parental cells or control-treated cells. Taken together, we conclude that CREB protects tumor cells from γ-irradiation, and combination of CREB inhibition plus ionizing radiation will be a promising radiotherapeutic approach.