The effect of estrogen synthesis inhibition on hippocampal memory.

17-Beta-estradiol (E2) facilitates long term-potentiation (LTP) and increases spine synapse density in hippocampal neurons of ovariectomized rodents. Consistent with these beneficial effects on the cellular level, E2 improves hippocampus-dependent memory. A prominent approach to study E2 effects in rodents is the inhibition of its synthesis by letrozole, which reduces LTPs and spine synapse density. In the current longitudinal functional magnetic resonance imaging (fMRI) study, we translated this approach to humans and compared the impact of E2 synthesis inhibition on memory performance and hippocampal activity in post-menopausal women taking letrozole (n = 21) to controls (n = 24). In particular, we employed various behavioral memory paradigms that allow the disentanglement of hippocampus-dependent and -independent memory. Consistent with the literature on rodents, E2 synthesis inhibition specifically impaired hippocampus-dependent memory, however, this did not apply to the same degree to all of the employed paradigms. On the neuronal level, E2 depletion tended to decrease hippocampal activity during encoding, whereas it increased activity in the anterior cingulate and the dorsolateral prefrontal cortex. We thus infer that the inhibition of E2 synthesis specifically impairs hippocampal functioning in humans, whereas the increased prefrontal activity presumably reflects a compensatory mechanism, which is already known from studies on cognitive aging and Alzheimer's disease.

Are there changes in characteristics and therapy of young patients with early-onset breast cancer in Germany over the last decade?

PURPOSE: The objective of the study is to investigate recent changes in patient characteristics and treatment procedures of young breast cancer patients over the last 10 years in Germany. METHODS: The study describes the data of 518 patients who were treated adjuvantly between 2008 and 2011 and participated in a resident mother-child program for rehabilitation (cohort II). The data includes TNM-categories, biology of tumor and therapies. This population is compared to a cohort of 535 patients, who were treated between 2002 and 2006 (cohort I). Characteristics and treatment of cohort II are compared with a normally age distributed cohort. RESULTS: 51.5 % of the patients in cohort II were diagnosed with tumor category pT1, 36.9 % pT2, 4.4 % pT3 and 1.2 % pT4. 3.3 % had merely DCIS. 58.1 % of the patients were pN0, 28.4 % pN1 and 13.5 % had a more intense manifestation of lymph nodes. 45.8 % of the tumors showed a grading classified as G3, 69.3 % were estrogen and progesterone hormone receptor positive and 21.8 % Her2 positive. 24.5 % of the examined patients showed a triple negative carcinoma. 66.2 % of the patients with pT1 or pT2 underwent breast-conserving surgery. Overall 19.2 % of the women received mastectomy only and 17.4 % received mastectomy with subsequent reconstruction. 98.6 % of the patients received axillary surgery, 87.6 % chemotherapy. Overall, 21.0 % of the patients received their chemotherapy in connection with clinical studies. 88.0 % of the patients with hormone receptor positive tumors received endocrine therapy, 25.5 % of them with GnRH-analogs. In comparison with cohort I the tumors in cohort II were detected with a higher proportion of negative lymph nodes (48.8 %/58.1 %, p = 0.008) and G1 grading (4.9/5.6 %, p = 0.001). On the other hand the percentage of triple negative tumors increased from 21.0 % to 24.5 % (p = 0.018). Operative therapy has adjusted to a more moderate way. Breast-conserving therapy with pT1 and pT2 increases from 57.3 % to 66.2 % (p = 0.006), sentinel lymph node biopsy only from 24.5 % to 47.5 % (p[Symbol: see text]0.001) over the years. The percentages of chemotherapy, radiation, endocrine therapy and antibody therapy with positive receptor have stayed stable over the last decade. Comparing cohort II with a normally age distributed group (DMP II 2007-2009) the young patients have still a much lower portion of negative lymph nodes (58.1 %/67.9 %) and positive hormone receptor status (69.3 %/85.1 %). The percentage of a high grading G3 is 45.8 % in cohort II versus 24.7 % in DMP II. The portion of breast-conserving therapy with pT1 is with 68.9 versus 82.2 % still comparatively low. Young patients received more axillary surgery (98.6 %/81.5 %) but less endocrine therapy with hormone receptor positive tumors (93.3 %/94.7 %). CONCLUSION: Young breast cancer patients in Germany can still be regarded as a special group. Although tumors are now more often detected before reaching the lymph nodes than 10 years ago, an even bigger percentage is triple negative. Operative treatment has improved to a less aggressive way. Still operative and medical treatments have to be chosen after very careful evaluation.

Characteristics and therapy of premenopausal patients with early-onset breast cancer in Germany.

PURPOSE: The objective of the study is to investigate what kind of tumors young, premenopausal breast cancer patients in Germany show at diagnosis and how they are treated adjuvantly in comparison with a normally distributed cohort. METHODS: The study describes the data of 535 patients who were treated adjuvantly between 2002 and 2006 and participated in a resident mother-child program for rehabilitation (Groemitz cohort). The data includes TNM categories, biology of tumor and therapies. This population is being compared to an age-heterogeneous cohort from the state of Schleswig-Holstein and the DMP-report of the state of North Rhine-Westphalia. RESULTS: 45.8 % of the patients were diagnosed with tumor category pT1, 37 % pT2, 7.3 % pT3 and 1.9 % pT4. 5 % had merely DCIS. 48.8 % of the patients were pN0, 31.4 % pN1 and 17.4 % had a more intense manifestation of lymph nodes. 43.5 % of the tumors showed a grading classified as G3, 64.3 % were estrogen and progesterone hormone receptor positive and 26.2 % Her2 positive. 21 % of the examined cohort members/patients showed a triple negative carcinoma. 59.1 % of the patients with pT1 underwent breast-conserving surgery, 56.1 % of those with pT2 and 25.6 % of those with pT3. Overall 31.0 % of the women received mastectomy and 14.8 % received mastectomy with subsequent reconstruction. 97.6 % of the patients received axillary surgery, 89.9 % chemotherapy. Overall 23.7 % of the patients received their treatment in connection with clinical studies. 95.3 % of the patients with hormone receptor positive tumor received endocrine therapy, 61.3 % of them with GnRH-analogs. In comparison with the OVIS and DMP cohorts patients of the Groemitz cohort were on average 20 years younger. Their tumors were of bigger size and had more often reached the axillary lymph nodes (pN0 48.8 % Groemitz/62.0 % OVIS/66.7 % DMP). The hormone receptor status was more often negative (35.7/16.6/16.5 %) and tumor grading higher (G3 43.5/29.0/28.5 %). Surgery was more extensive even with small tumors (breast conserving surgery with tumor stage pT1 59.1/81.2/77.6 %) and axillary surgery was performed more often in the young collective (97.6/89.3/62.5 %). More patients of the young collective received chemotherapy (89.9/58.4 %/unknown) and more patients of the young collective with hormone receptor positive tumor received endocrine therapy (95.3/77.4/90.6 %). CONCLUSION: Our study shows that young breast cancer patients in Germany can be regarded as a special group. At the time of diagnosis the tumor has frequently reached a more advanced stage, and carcinomas are more aggressive. Operative and medical treatment will often be more aggressive.

Total laparoscopic hysterectomy without uterine manipulator at big uterus weight (>280 g).

METHODS: The retrospective study included the total laparoscopic hysterectomy without uterus manipulator at big uterus >280 g (Group A), proceeding the same technique as known to show feasibility and safety of its technique, compared with a randomized patient group of a uterus weight below 280 g (Group B). Statistical measurement was proceeded in typical clinical parameters. RESULTS: No statistical differences in age, body mass index, further abdominal surgery, blood loss, and hospital stay were observed. Operating time was significantly different favouring the uterus below 280 g (111.74 min Group A/90.68 min Group B). No increase in intra- or postoperative complications in both groups was observed. CONCLUSION: Total hysterectomy at big uterus (>280 g) is safe and feasible. Statistical analysis shows a significant shorter operating time only in one parameter (Group B). The technique of hysterectomy without uterus manipulator offers a surgical advancement also at vaginal stenosis, early staged cervix, or endometrial cancer and exhibits an opportunity for laparoscopic advancement in these cases too.

The possible role of the Jak/STAT pathway in lymphocytes at the fetomaternal interface.

Pregnancy is accompanied by a Th2-prone immune modulation, which is a major puzzle piece among maternofetal tolerance-promoting factors. A large number of cytokines is physiologically or pathologically present in the decidua and is potentially able to act on lymphocytes and NK cells, which express a variety of respective receptors. Intracellular signals from these receptors are to a major part transduced via the Janus kinases (JAK) and signal transducers and activators of a transcription (STAT) system, which consists of at least 4 different kinases and 7 STATs plus several subtypes and splicing variants. A network of suppressors of cytokine signaling (SOCS) controls their balance. The interactions of all these intracellular factors and cross-linking with further signaling systems seem to be crucial for the maintenance of a maternal cytokine profile which promotes the tolerance of the fetus.