The influence on resection line during supracervical hysterectomy: physiological extension of endometrial cells in the cervix uteri

Objective: A straight resection of corpus uteri using the sacrouterine ligament as landmark is a common method during supracervical hysterectomy. Subsequent spotting rates of up to 25% suggest the existence of residual endometrial glands in the remaining cervical tissue, casting doubt on the landmark qualities of the sacrouterine ligament. Fifty-one females who underwent total laparoscopic hysterectomy for benign diseases were investigated. Material and Methods: Macroscopic uterine parameters were determined during operation. First appearance of endometrium cells, complete disappearance of endometrial cells in the cervix and others were measured microscopically with reference to the external cervical orifice. Associations were described using odds ratio with 95% confidence interval and p-value <0.05. Results: The region of the cervix, in which exclusively cervical glands are found, is relatively small but varies considerably around the mean (mean, 23.3 mm, range, 10 to 35 mm). In this cohort in a remnant cervical stump of 23 mm length, endometrial glands would be found in 51%. There was no correlation between full cervical length and uterine parameters but smaller uteri tended to be associated with deeper endometrial penetration. Conclusion: There is a discrepancy between common definition and histological findings concerning the cervix uteri. Our findings indicate that the sacral uterine ligament is not suitable as an anatomic landmark for the laparoscopic supracervical hysterectomy operation. Regarding the distribution pattern of endometrial glands in the isthmic zone, a deep conical excision seems to better prevent subsequent spotting than a straight resection with thermocoagulation of the remaining cervical canal.

Efficacy and Safety of Sequential Use of Everolimus in Patients With Metastatic Renal Cell Carcinoma Previously Treated With Bevacizumab With or Without Interferon Therapy: Results From the European AVATOR Study.

BACKGROUND: Everolimus is a mammalian target of rapamycin (mTOR) inhibitor. It gained approval based on the results of the RECORD-1 (Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism 1) trial, which included patients with metastatic renal cell carcinoma (mRCC) whose disease progressed after receiving vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). Bevacizumab is a monoclonal antibody targeting angiogenesis that is approved in patients with mRCC. The sequence of everolimus second-line therapy after failure of bevacizumab ± interferon (IFN) first-line therapy has not yet been studied. METHODS: AVAstin(®) followed by afiniTOR(®) (AVATOR) was a noninterventional retrospective multicenter European observational study of 42 unselected patients with mRCC who were previously or currently treated with everolimus after failure of bevacizumab ± IFN. The primary end point was everolimus progression-free survival (PFS). Secondary end points were related to the overall survival (OS) of patients receiving the drug sequence and everolimus treatment and safety. RESULTS: Exploring the duration of second-line everolimus treatment, 63.8% of patients received at least 3 months of everolimus and 28.8% received at least 8 months of treatment. At the time of data analysis, 15 patients (36%) were still receiving everolimus, 40% had stopped because of progressive disease, and 24% had discontinued treatment for other reasons. Patients receiving everolimus after bevacizumab experienced a median PFS of 17 months (95% confidence interval [CI], 5 [not reached]). Median OS was not reached with everolimus second-line therapy. At 32 months after the start of first-line therapy, 53.3% of patients were still alive. All grades of common adverse events (AEs) were consistent with the known safety profile of everolimus. CONCLUSION: The AVATOR-studied sequence displayed a longer than expected median PFS. Further prospective exploratory studies need to be performed to confirm these encouraging results in a larger cohort of patients.

Expression of AP-2γ in placentas of patients with preeclampsia and of smokers.

INTRODUCTION: There is evidence of a probable key role of the activator protein-2 γ (AP-2γ) in placental development. It is still an open question whether AP-2γ expression may be influenced by preeclampsia, which is a serious pregnancy complication, or by smoking, which has deleterious effects on trophoblastic development. MATERIAL AND METHODS: Thus, the expression of AP-2γ was studied in trophoblastic epithelium and endothelium of placentas from patients with preeclampsia (n = 43) and smokers (n = 45) as well as placentas of healthy pregnant women (control group, n = 26) between gestational ages 23 and 43 weeks. To allow differential expression in primary, secondary and tertiary villi, AP-2γ expression (arbitrary units) was determined immunohistologically. RESULTS: In preeclamptic placentas trophoblastic as well as endothelial cells AP-2γ expression was significantly higher compared to that in control placentas. Endothelial AP-2γ expression in placentas from smokers was similar to that of healthy women while trophoblastic AP-2γ expression in smokers' placenta was insignificantly higher compared to that of control placentas. In all three groups expression rates of AP-2γ did not differ between primary, secondary and tertiary villi. CONCLUSION: A correlation between increased trophoblastic and endothelial AP-2γ expression in patients with preeclampsia and reduced trophoblastic invasion and migration in preeclampsia has to be discussed. Furthermore, increased AP-2γ expression may play a protective role in preeclampsia, protecting from raised blood pressure. The tendency of an enhanced trophoblastic AP-2γ expression in smokers may indicate a compensatory response to the disturbed balance between proliferation and differentiation of villi induced by smoking.

The impact of insulin treatment on the expression of vascular endothelial cadherin and Beta-catenin in human fetoplacental vessels.

Vascular endothelial cadherin and ß-catenin play a key role in establishment and maintenance of the endothelial monolayer integrity, regulation of vascular barrier function, and initiation of angiogenesis. The cadherin-catenin complex has been shown to be reduced in type 1 diabetic placenta, but the exact relationship between histopathologic findings and clinical data is not known. Immunohistochemistry of placental tissue from type 1, type 2, and gestational diabetes showed that diabetes per se might be compatible with normal levels of vascular endothelial (VE)-cadherin and ß-catenin in fetoplacental vessels as long as the patient has not been treated with insulin. Immunoreactivity of VE-cadherin did correlate poorly with maternal glycemic control, as was investigated in this study, by birth weight, body mass index, and hemoglobin A1c (HbA1c). There was no correlation found between the immunoreactivity of ß-catenin and birth weight, body mass index, or HbA1c. However our data did show a strong correlation between immunoreactivity and whether or not the patient had been treated with insulin. Patients diagnosed with gestational diabetes who had not been treated with insulin had similar levels of VE-cadherin and ß-catenin to the control group, thus indicating that diabetes per se must not necessarily lead to a reduction. Our study suggests that therapeutic intervention using insulin in pregnancies complicated by diabetes might have potentially harmful effects on placental morphology. Future studies should further investigate these findings.

Development and evaluation of an open source Delphi-based software for morphometric quantification of liver fibrosis.

BACKGROUND: Computer-based morphometry can minimize subjectivity in the assessment of liver fibrosis. An image processing program was developed with Delphi for the quantification of fibrosis in liver tissue samples stained with Sirius Red. Bile duct ligated and sham operated wild type C57BL/6 mice served as a model of time-dependent induction of liver fibrosis. Formation of fibrosis was determined with the developed software at day 0, 3, 7, 10, 14, 20, 30 and 60. The results were compared to a semi-quantitative scoring system. RESULTS: Quantitative accumulation of collagen fibres was observed from day 3 to day 14, with a slight further increase thereafter. During ongoing fibrogenesis, there was a significant elevation of alanine aminotransferase (ALT), aspartate transaminase (AST) and bilirubin. The results from our computer-based morphometric analysis were highly correlated with the results that were obtained in a standardized pathology semi-quantitative scoring system (R 2 = 0.89, n = 38). CONCLUSIONS: Using our Delphi-based image analysing software, the morphometric assessment of fibrosis is as precise as semi-quantitative scoring by an experienced pathologist. This program can be a valuable tool in any kind of experimental or clinical setting for standardized quantitative assessment of fibrosis.

Determination of ploidy and steroid receptor status in breast cancer by laser scanning cytometry.

BACKGROUND: Measurements on DNA content and steroid receptor status in breast cancer are of great clinical interest. Objective determination of estrogen and progesterone receptor expression should help to define the lowest levels of positivity still responding to adjuvant antihormonal therapy. For this purpose, a simple protocol for laser scanning cytometry is presented. METHODS: Analysis of 54 routine breast cancer samples was performed by laser scanning cytometry (LSC). To obtain single cell preparations from fresh tumor tissue, slides were prepared using the Cervisoft cytological device. Exact determination of tumor cell DNA content was done by referring to the CD45-positive tissue leukocyte fraction as the internal diploid reference cell population. Steroid receptor-expressing cells were detected by indirect immunolabeling. RESULTS: Indirect immunofluorescence allowed the best quantification of both the estrogen and progesterone receptor-expressing cell fractions by LSC. The number of receptor-expressing cells could be given in percentage. For comparison, the 10% cutoff value was used to determine receptor positivity. CONCLUSION: LSC enabled a simple, reliable, and inexpensive determination of DNA index and steroid receptor expression in breast cancer specimens by objective criteria.