K. Hancke

Increased expression of matrix metalloproteinase 2 in uterosacral ligaments is associated with pelvic organ prolapse

The uterosacral ligaments are an important part of the pelvic support system and connective tissue alterations are thought to contribute to the development of pelvic organ prolapse (POP). The objective of this study was to compare the expression of matrix metalloproteinases (MMPs) 1 and 2 in these ligaments in women with and without POP. We analyzed the tissue samples obtained from left and/or right uterosacral ligaments of 17 women with POP and 18 controls by immunohistochemistry. There was no difference in MMP-1 expression between women with POP and those without. In contrast, the MMP-2 expression was significantly related to the presence of POP (p=0.004) rather than to age or parity. There was no difference in MMP-1 and MMP-2 expression between left and right uterosacral ligaments in women with POP compared to controls. Our findings strongly indicate that increased MMP-2 expression in uterosacral ligaments is associated with POP.

Standard treatment of female patients with breast cancer decreases substantially for women aged 70 years and older: a German clinical cohort study

BACKGROUND Standard treatment of patients with breast cancer decreases with age and older persons are mostly excluded from clinical trials. We hypothesized that non-adherence to treatment guidelines occurs for women aged > or =70 years and changes overall survival (OAS) and disease-free survival (DFS). PATIENTS AND METHODS We enrolled 1922 women aged > or =50 years with histologically confirmed invasive breast cancer treated at the University of Ulm from 1992 to 2005. Adherence to guidelines and effects on OAS and DFS for women aged > or =70 years was compared with that for younger women (50-69 years). RESULTS Women >70 years less often received recommended breast-conserving therapy (70-79 years: 74%-83%; >79 years: 54%) than women aged < or =69 years (93%). Non-adherence to the guidelines on radiotherapy (<70 years: 9%; 70-79 years: 14%-27%; >79 years: 60%) and chemotherapy (<70 years: 33%; 70-79 years: 54%-77%; > 79 years: 98%) increased with age. Omission of radiotherapy significantly decreased OAS [< or =69 years: hazard ratio (HR) = 3.29; P <0.0001; > or =70 years: HR = 1.89; P = 0.0005] and DFS (< or =69 years: HR = 3.45; P <0.0001; > or =70 years: HR = 2.14; P <0.0001). OAS and DFS did not differ significantly for adherence to surgery, chemotherapy, or endocrine therapy. CONCLUSION Our study confirms that substandard treatment increases considerably with age. Omission of radiotherapy had the greatest impact on OAS and DFS in the elderly population.

Pretreatment staging of cervical cancer: is imaging better than palpation?: Role of CT and MRI in preoperative staging of cervical cancer: single institution results for 255 patients.

BackgroundCervical carcinoma is clinically staged according to the criteria of the International Federation of Gynecology and Obstetrics (FIGO). Computed tomography (CT) and magnetic resonance imaging (MRI) can also be used in pretreatment evaluation of tumor extension and size; however, the diagnostic value and the impact on clinical decisions of cross-sectional imaging have been questioned.MethodsThe files of 255 patients with biopsy-proven cervical carcinoma receiving primary surgical treatment at the Department of Obstetrics and Gynaecology of Ulm University between 1992 and 2003 were analyzed retrospectively. All patients had a clinical pelvic examination; additionally, 164 underwent CT, 101 had an MRI, and 90 had both CT and MRI. Surgicopathologic findings were used as the standard of reference.ResultsTo evaluate detection of parametrial involvement, patients were divided into those with stage IIA or less disease (n = 171; 67%) and those with stage IIB or more disease (n = 84; 33%). The accuracy, sensitivity, and specificity were 75%, 66%, and 81% for clinical staging, 59%, 43%, and 71% for CT, and 58%, 52%, and 63% for MRI, respectively. After stratification for palpation, the results with CT and MRI were no better than with palpation (accuracy: CT 61% and 54%, MRI 61% and 56%, respectively). The sensitivity of CT and MRI for detecting lymph node metastasis was also poor (36% and 35%, respectively).ConclusionClinical examination was better than CT and MRI for pretreatment evaluation of early invasive cervical cancer.

Comparison of In Vitro- and Chorioallantoic Membrane (CAM)-Culture Systems for Cryopreserved Medulla-Contained Human Ovarian Tissue

At present, there are three ways to determine effectively the quality of the cryopreservation procedure using ovarian tissue before the re-implantation treatment: evaluation of follicles after post-thawing xenotransplantation to SCID mouse, in-vitro culture in a large volume of culture medium under constant agitation and culture on embryonic chorio-allantoic membrane within a hens eggs. The aim of this study was to compare the two methods, culture in vitro and culture on embryonic chorioallantoic membrane (CAM) of cryopreserved human ovarian medulla-contained and medulla-free cortex. Ovarian fragments were divided into small pieces (1.5–2.0×1.0–1.2×0.8–1.5) of two types, cortex with medulla and medulla-free cortex, frozen, thawed and randomly divided into the following four groups. Group 1: medulla-free cortex cultured in vitro for 8 days in large volume of medium with mechanical agitation, Group 2: medulla-containing cortex cultured in vitro, Group 3: medulla-free cortex cultured in CAM-system for 5 days, Group 4: medulla-containing cortex cultured in CAM-system. The efficacy of the tissue culture was evaluated by the development of follicles and by intensiveness of angiogenesis in the tissue (von Willebrand factor and Desmin). For Group 1, 2, 3 and 4, respectively 85%, 85%, 87% and 84% of the follicles were morphologically normal (P>0.1). The immunohistochemical analysis showed that angiogenesis detected by von Willebrand factor was lower in groups 1 and 3 (medulla-free cortex). Neo-vascularisation (by Desmin) was observed only in ovarian tissue of Group 4 (medulla-contained cortex after CAM-culture). It appears that the presence of medulla in ovarian pieces is beneficial for post-thaw development of cryopreserved human ovarian tissue. For medical practice it is recommended for evaluation of post-warming ovarian tissue to use the CAM-system as a valuable alternative to xenotransplantation and for cryopreservation of these tissues to prepare ovarian medulla-contained strips.

In-vitro culture of human embryos with mechanical micro-vibration increases implantation rates

The in-vitro culture of human embryos in a medium subjected to regular short intervals of mechanical agitation leads to increased development rates. This type of treatment tries to mimic conditions in nature whereby oviductal fluid is mechanically agitated by the epithelial cilia. This phenomenon can be explained by the fact that an embryo developing in vivo is naturally exposed to constant vibrations of around 6Hz with the periodically repeating increase to 20Hz. This review covers the history of this question and in this light offers an explanation through biological concept for one of the most recent developments in this area: in-vitro culture of human embryos with mechanical micro-vibration. The effect of mechanical micro-vibration on embryos during their in-vitro culture was examined. Pregnancy rates after the transfer of embryos in the group with in-vitro culture under mechanical vibration were increased.

Patients undergoing frozen-thawed embryo transfer have similar live birth rates in spontaneous and artificial cycles

PurposeTo evaluate the outcome of frozen-thawed embryo transfer (FET) when freezing takes place at the pronuclear stage, a retrospective analysis was performed comparing spontaneous and artificial cycles.Methods148 women received FET in a spontaneous cycle (Group A) and 55 women received FET in an artificial cycle (Group B) induced by administering estrogen (E2) and progesterone (P). Pregnancy rates, endometrial thickness and serum levels of E2, P and luteinizing hormone (LH) were measured. Statistical analysis included the mean, the standard deviation, the Chi-squared test and the T-test.ResultsThe clinical pregnancy rate was 34.5% for Group A and 21.8% for Group B (p = 0.084), with a live birth rate of 20.9% and 12.7% respectively (p = 0.15). There was no difference in endometrial thickness or the P levels, while LH and E2 levels were significantly higher in group B (p < 0.0001).ConclusionOur retrospective study shows a trend towards higher pregnancy rates and live birth rates with the administration of FET during a spontaneous cycle compared to FET during an artificial cycle. Large randomized controlled trials are needed to confirm this trend.

Pre-pregnancy obesity compromises obstetric and neonatal outcomes

Abstract Objective: Obesity is an important issue among fertile women as it may affect obstetric and neonatal outcomes. Methods: Obstetric and neonatal outcomes of primiparous women were retrospectively analyzed in non-obese (n=11387) and obese (n=943) women. A subgroup analysis was performed in obese women divided into three groups: Grade I obesity (Group A, n=654), Grade II obesity (Group B, n=192), and Grade III obesity (Group C, n=97). Odds ratios (OR) were expressed with the corresponding 95% confidence intervals (CI). Results: The incidence of gestational diabetes (non-obese, 1.9%; obese, 7.6%; Group C, 19.6%) and preeclampsia (non-obese, 3.3%; obese, 13.5%; Group C, 17.5%) increased with rising weight. The risk of non-elective cesarean section was significantly higher in obese women than in non-obese women (21.7% vs. 13.2%). The risk of extreme preterm birth (before 28 weeks of gestation) doubled in the Grade I obesity group (OR, 2.1; 95% CI, 1.4–3.2) and nearly tripled in women with body mass index ≥35 kg/m2 (OR, 2.9; 95% CI, 1.7–4.9). Conclusion: Pre-pregnancy obesity is associated with higher incidences of gestational diabetes and preeclampsia. Our study shows that obese women have a higher risk of non-elective cesarean section and preterm birth.

Prevention of ovarian damage and infertility in young female cancer patients awaiting chemotherapy—clinical approach and unsolved issues

Great advances in the oncological therapy of childhood and adolescent cancer patients lead to an increase of young cancer survivors with a normal expectancy of life. The aggressive chemotherapy and/or radiation often compromises endocrine function with consecutive menopausal symptoms and sterility. Recently, new approaches were developed to preserve fertility with different methods to restore the ovarian function. The present review gives an overview of the current possibilities, which may be offered to these young cancer patients, as well as the chances of success and risks and the unsolved issues in special situations.

Identifying the impact of inflammatory breast cancer on survival: a retrospective multi-center cohort study

PurposeInflammatory breast cancer (IBC) represents a rare and aggressive form of cancer with negative prognosis and high rate of recurrence. The purpose of this retrospective multi-center study was to evaluate the effect of IBC on overall and disease-free survival. Furthermore we analyzed the influence of hormone and Her2 receptor expression on inflammatory breast cancer cells on the clinical outcome of patients.MethodsThis retrospective German multi-center study included 11,780 patients with primary breast cancer recruited from 1992 to 2008. In this sub-group analysis we focused on 70 patients with IBC.ResultsDespite the relatively small sample size, we could confirm the aggressiveness of inflammatory breast cancer and the different clinical behavior of IBC subtypes. It could be demonstrated that the lack of expression of hormone receptors on tumor cells is associated with a more aggressive clinical course and decreased overall and disease-free survival. Higher incidence of Her2 overexpression, that is typically associated with poor prognostic outcome among women with non-IBC tumors, seems however to have no prognostic significance.ConclusionsThis BRENDA sub-group analysis, on a German cohort of breast cancer patients confirmed the negative outcome of IBC and the different clinical behavior of IBC subtypes. The best management of IBC requires intensive coordination and cooperation between various clinical disciplines involved in the treatment of IBC patients. Moreover there is a need to identify IBC-specific targeted therapies to improve the curing prospects of this subtype of cancer.

Recurrent Miscarriage: Diagnostic and Therapeutic Procedures. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry Number 015/050)

Purpose Official guideline of the German Society of Gynecology and Obstetrics (DGGG), the Austrian Society of Gynecology and Obstetrics (ÖGGG) and the Swiss Society of Gynecology and Obstetrics (SGGG). The aim of this guideline was to standardize the diagnosis and treatment of couples with recurrent miscarriage (RM). Recommendations were based on the current literature and the views of the involved committee members. Methods Based on the current literature, the committee members developed the statements and recommendations of this guideline in a formalized process which included DELPHI rounds and a formal consensus meeting. Recommendations Recommendations for the diagnosis and treatment of patients with RM were compiled based on the international literature. Specific established risk factors such as chromosomal, anatomical, endocrine, hemostatic, psychological, infectious and immunological disorders were taken into consideration.