Functional estrogen receptor signal transduction pathway activity and antihormonal therapy response in low-grade ovarian carcinoma

Background

Advanced low-grade ovarian carcinoma (LGOC) is difficult to treat. In several studies, high estrogen receptor (ER) protein expression was observed in patients with LGOC, which suggests that antihormonal therapy (AHT) is a treatment option. However, only a subgroup of patients respond to AHT, and this response cannot be adequately predicted by currently used immunohistochemistry (IHC). A possible explanation is that IHC only takes the ligand, but not the activity, of the whole signal transduction pathway (STP) into account. Therefore, in this study, the authors assessed whether functional STP activity can be an alternative tool to predict response to AHT in LGOC.

Methods

Tumor tissue samples were obtained from patients with primary or recurrent LGOC who subsequently received AHT. Histoscores of ER and progesterone receptor (PR) were determined. In addition, STP activity of the ER STP and of six other STPs known to play a role in ovarian cancer was assessed and compared with the STP activity of healthy postmenopausal fallopian tube epithelium.

Results

Patients who had normal ER STP activity had a progression-free survival (PFS) of 16.1 months. This was significantly shorter in patients who had low and very high ER STP activity, with a median PFS of 6.0 and 2.1 months, respectively (p < .001). Unlike ER histoscores, PR histoscores were strongly correlated to the ER STP activity and thus to PFS.

Conclusions

Aberrant low and very high functional ER STP activity and low PR histoscores in patients with LGOC indicate decreased response to AHT. ER IHC is not representative of functional ER STP activity and is not related to PFS.     

WNT10A variants: following the pattern of inheritance in tooth agenesis and self-reported family history of cancer

Clinical Oral Investigations - The aim of this study was the analysis of WNT10A variants in seven families of probands with various forms of tooth agenesis and self-reported family history of...     

Sleep Research: A Primer for Media Scholars

ABSTRACT

The average amount of sleep people of all ages get has declined sharply in the past 50 years. The detrimental health effects of sleep deprivation are well documented and substantial. Even though electronic media use often takes place in the hours before sleep, the extent to which media use may interact with sleep is understudied and not well understood. Communication scholars are well positioned to contribute to this area, as a systematic, theoretical understanding of the relationship between media and sleep is still lacking. This primer charts the state of knowledge on electronic media and sleep and explores possible next steps. First, we introduce the problem of sleep deprivation and describe the basic science of sleep with relevant terminology. Then, we review the research on electronic media and sleep and offer an agenda for research.     

A retrospective alternative for active surveillance trials for ductal carcinoma in situ of the breast

Ductal carcinoma in situ (DCIS) of the breast is a nonobligate precursor of invasive breast cancer, accounting for 20 % of screen-detected breast cancers. Little is known about the natural progression of DCIS because most patients undergo surgery upon diagnosis. Many DCIS patients are likely being overtreated, as it is believed that only around 50 % of DCIS will progress to invasive carcinoma. Robust prognostic markers for progression to invasive carcinoma are lacking. In the past, studies have investigated women who developed a recurrence after breast-conserving surgery (BCS) and compared them with those who did not. However, where there is no recurrence, the patient has probably been adequately treated. The present narrative review advocates a new research strategy, wherein only those patients with a recurrence are studied. Approximately half of the recurrences are invasive cancers, and half are DCIS. So-called “recurrences” are probably most often the result of residual disease. The new approach allows us to ask: why did some residual DCIS evolve to invasive cancers and others not? This novel strategy compares the group of patients that developed in situ recurrence with the group of patients that developed invasive recurrence after BCS. The differences between these groups could then be used to develop a robust risk stratification tool. This tool should estimate the risk of synchronous and metachronous invasive carcinoma when DCIS is diagnosed in a biopsy. Identification of DCIS patients at low risk for developing invasive carcinoma will individualize future therapy and prevent overtreatment.     

Is repeat head CT necessary in patients with mild traumatic intracranial hemorrhage

BackgroundPatients with traumatic intracranial hemorrhage (TIH) frequently receive repeat head CT scans (RHCT) to assess for progression of TIH. The utility of this practice has been brought into question, with some studies suggesting that in the absence of progressive neurologic symptoms, the RHCT does not lead to clinical interventions.MethodsThis was a retrospective review of consecutive patients with CT-documented TIH and GCS ≥ 13 presenting to an academic emergency department from 2009 to 2013. Demographic, historical, and physical exam variables, number of CT scans during admission were collected with primary outcomes of: neurological decline, worsening findings on repeat CT scan, and the need for neurosurgical intervention.ResultsOf these 1126 patients with mild traumatic intracranial hemorrhage, 975 had RHCT. Of these, 54 (5.5% (4.2–7.2 95 CI) had neurological decline, 73 (7.5% 5.9–9.3 95 CI) had hemorrhage progression on repeat CT scan, and 58 (5.9% 4.5–7.6 95 CI) required neurosurgical intervention. Only 3 patients (0.3% 0.1–0.9% 95 CI) underwent neurosurgical intervention due to hemorrhage progression on repeat CT scan without neurological decline. In this scenario, the number of RHCT scans needed to be performed to identify this one patient is 305.ConclusionsRHCT after initial findings of TIH and GCS ≥ 13 leading to a change to operative management in the absence of neurologic progression is a rare event. A protocol that includes selective RHCT including larger subdural hematomas or patients with coagulopathy (vitamin K inhibitors and anti-platelet agents) may be a topic for further study.