Expression of Estrogen Receptors (α, β), Cyclooxygenase-2 and Aromatase in normal endometrium and endometrioid cancer of uterus

PurposeEndometrial cancer (EC) is one of the most common malignancies of the female genital tract, but the etiology, especially its metabolism is still investigated. The aim of this study was to evaluate the presence and relative expression of Estrogen Receptors (α, β), Cyclooxygenase-2 and Aromatase in both endometrial cancer and normal mucosa.Material/MethodsTwo groups of women were selected for the study: 1) patients with endometrioid endometrial cancer (FIGO I; G1 - G3) (n=35) and 2) subjects with normal endometrial tissue (control group, n=29). The expression of Estrogen Receptors (ERα, β), Cyclooxygenase-2 (COX-2), Aromatase were estimated by Western blot analysis. Furthermore, the associations between FIGO classification (stage: Ia, Ib), tumor grade (G) and expression of ERα, β, COX-2, aromatase proteins were evaluated. Overall and disease-free survival curves were generated according to the Kaplan-Meier method. Median follow-up time of the patients examined in this study was 39 months.ResultsThe relative expression of each examined protein was markedly higher in the endometrial cancer tissue as compared to the healthy endometrium. The trends towards greater expression along with a tumor progression was noticed (FIGO stage: Ia vs. Ib). Analysis of endometrial cancer risk factors and their influence on survival curves showed only an inverse significant correlations between obesity (BMI: 36.2; n=21) and disease-free survival in EC group (p=0.00872), but there was no significant association between obesity and overall survival (p=0.358).ConclusionsEndometrioid endometrial cancer shows relatively higher expression of either ER, COX-2 and aromatase comparing to healthy mucosa, suggesting their involvement in tumor development and progression.     

Diabetes and life-long cognitive ability

Objectives

There is a widespread consensus that diabetes impairs cognitive functioning. However, some recent findings have shown that many health conditions generally thought to be detrimental to cognitive functioning are in fact linked to pre-morbid cognitive ability, suggesting reverse causation. To better understand the causality in diabetes–cognition relationship, this study investigates the association of older-age diabetes with concurrent and childhood cognitive functioning.

Methods

Lothian Birth Cohort 1936 participants (N = 1017) completed the same general cognitive ability test at ages 11 and 70 years. Scores were compared between those with and without diabetes at age 70. Diabetes status was based on self-reports and haemoglobin A1c levels.

Results

People with diabetes had lower mean cognitive ability scores at ages 11 and 70 when compared with those without diabetes. The effect size was roughly similar at both ages (Cohen's d ≈ 0.32). When adjusted for age-11 cognitive ability, diabetes status was not associated with cognitive ability at age 70. The association between childhood cognitive ability and older-age diabetes was partly accounted for by body mass index and cholesterol level in older-age.

Conclusion

In this sample, diabetes was associated with poorer cognitive ability in old age but this was because of life-long lower cognitive ability in people with diabetes instead of diabetes impairing cognitive functioning.     

Growing Up in the Bowels of Violence

Abstract

The author chronicles his struggle with violent behavior which stemmed from an abusive family life, both as a child in his parent's home and as a young man. Coupled with delusions brought on by mental illness, the author's violent tendencies led him to murder his own mother. This act led him into the criminal justice system and eventually to psychiatric therapy at a Midwestern state psychiatric facility. The author describes his growing ability to rein in his violent tendencies, and his gratitude to the mental health system for their support and guidance.     

Is Postexcision, Preradiation Mammogram Necessary in Patients After Breast-Conserving Surgery with Negative Margins

Background

In women with breast cancer and calcifications, controversy exists over the need for postexcision/lumpectomy, preradiation mammogram (PEM) after breast-conserving surgery (BCS). Further, the need for excision of remaining or suspicious calcifications after PEM when surgical margins are negative is unclear. We sought to characterize the utility of PEM hypothesizing that its value in directing the need for additional surgery is minimized after achieving negative surgical margins.

Methods

We identified 524 women with breast cancer and calcifications treated with BCS with negative margins between 1996 and 2011.

Results

PEM was performed in 112 of 524 (21 %) women, with residual calcifications identified in 10 of 112 (9 %); of these, 2 of 112 (1.8 %) had residual disease. Local recurrence occurred in 4 of 112 (4 %) patients, none of whom had residual calcifications identified on PEM. The remaining 412 of 524 (79 %) women did not have PEM but had a postradiation mammogram 6 to 12 months after treatment identifying calcifications in 19 (5 %) women. Tissue diagnosis was benign in 14 women and was not pursued in the remaining 5. Local recurrence occurred in 13 (3 %) patients, none of whom had calcifications on the new post radiation baseline mammogram.

Conclusions

Mammographically apparent calcifications representing residual disease occur infrequently after BCS with negative margins. The value of PEM may be to document the new radiographic baseline but should not be required to ensure adequate surgery. Radiation plays an integral role in sterilization of the remaining breast tissue after BCS.     

Long-Term Patient-Reported Satisfaction after Contralateral Prophylactic Mastectomy and Implant Reconstruction

Purpose

To determine whether satisfaction and health-related quality of life (HR-QoL) differ between women who do and do not undergo contralateral prophylactic mastectomy (CPM) in the setting of implant reconstruction using the BREAST-Q, a validated patient-reported outcome instrument.

Methods

From 2000 to 2007, a total of 3,874 patients with stage 0 to III unilateral breast cancer (BC) had mastectomy; 688 (18 %) pursued CPM within 1 year. Patients who completed the BREAST-Q reconstruction module as part of BREAST-Q validation studies or routine clinical care formed our study cohort. Comparisons were made between CPM and no-CPM patients using univariate analysis and multivariate models (MVA).

Results

Of 294 patients with BREAST-Q data, 112 (38 %) had CPM. Median time from mastectomy to BREAST-Q was 52 months. CPM patients were younger (mean 47 vs. 50 years), more likely to be White (98 vs. 86 %), married (84 vs. 71 %), have a family history of BC (60 vs. 44 %), and to choose silicone implants (67 vs. 48 %). There were no differences in tumor or treatment characteristics between groups at the time of BREAST-Q. Patients with CPM had a higher mean score for Satisfaction with Breasts (64.4 vs. 54.9; p < 0.001) and Satisfaction with Outcome (74.8 vs. 67.7; p = 0.007); other HR-QoL domains did not differ. On MVA, CPM and the absence of lymphedema were significant predictors of Satisfaction with Breasts (CPM p = 0.005, lymphedema p = 0.039). CPM was not associated with improved Satisfaction with Outcome.

Conclusions

This study suggests that in the setting of implant reconstruction, CPM has a positive correlation with patient satisfaction with their breasts, but not with improvements in other HR-QoL domains.     

A Phase I Trial of Isolated Hepatic Perfusion (IHP) Using 5-FU and Oxaliplatin in Patients with Unresectable Isolated Liver Metastases from Colorectal Cancer

Background

Isolated hepatic perfusion (IHP) with melphalan is an established approach for patients with unresectable metastatic liver lesions. This study determined the safety and maximum tolerated dose (MTD) of 5-FU with oxaliplatin via IHP.

Methods

Standard 3 × 3 Phase I design. Subjects with unresectable isolated CRC liver metastases scheduled for HAI pump were eligible. IHP used fixed-dose oxaliplatin with escalating 5-FU doses. Toxicity (CTCAE v 4.0) and response (RECIST), progression-free survival, and overall survival (OS) were assessed. Systemic and IHP plasma PK of 5-FU, anabolites, and platinum were determined.

Results

All 12 patients had received ≥1 line of pre-IHP chemotherapy. There were 4 grade 3 serious adverse events (33.3 %) and 1 grade 4 event (8.3 %). Also, 2 dose-limiting toxicities occurred at DL2 at 300 mg/m², resulting in expansion of DL1 at 200 mg/m² 5-FU, the eventual MTD. At 6-month follow-up, 9 patients (82 %) demonstrated partial response, while 2 (18 %) exhibited stable disease. Also, 64 % of patients demonstrated a >50 % decrease in CEA. The 1- and 2-year OS probabilities were 90.9 and 71.6 %, respectively, with median follow-up of 24 months. IHP exposures (AUC_0–60 min) were 10.9 ± 4.5 μgPt h/mL, 49.3 ± 30.7 μg h/mL 5-FU (DL1), and 70.5 ± 35.5 μg h/mL 5-FU (DL2). Systemic exposure (AUC_0–inf) relative to IHP exposure was negligible for both platinum (1.1 ± 1.5 %) and 5-FU (0.09 ± 0.10 %).

Conclusions

The MTD for IHP was 200 mg/m² 5-FU with 40 mg/m² oxaliplatin. Systemic exposure to the agents was minimal during IHP. The response and survival observed warrants assessment in a larger phase II trial.