Ekkehard Dreher

Three-dimensional laparoscopy. Gadget or progress? A randomized trial on the efficacy of three-dimensional laparoscopy.

AbstractBackground: This study was designed to compare conventional laparoscopy with three-dimensional (3-D) laparoscopy. Method: Thirty candidates, 20 inexperienced and 10 experienced in operative laparoscopy, executed standardized exercises on a pelvitrainer. The candidates were randomized to two groups. Group A executed the exercises first with the conventional and then with the three-dimensional system. Group B accomplished the exercises in the reverse sequence. At the end of the exercises, the candidates answered specific questions about the two systems. Results: A total of 21 h 6 min 6 sec of laparoscopic exercises were analyzed—10 h 8 min 1 sec with the conventional and 10 h 58 min 5 sec with the three-dimensional system (p= 0.38). Group A required 12 h 26 min 56 sec to perform all the exercises. There was no statistically significant difference from group B, where the candidates needed 8 h 39 min 10 sec (p= 0.14). Neither were there any differences in the number of failed attempts between the two groups. There were also no statistical difference when the results obtained from the candidates without experience in laparoscopy and the participants experienced in operative laparoscopy were analyzed separately. Both the inexperienced and the experienced candidates became tired earlier, had more headaches, and needed extra time to adapt to the 3-D system. Conclusion: When analyzed in a standardized fashion, 3-D laparoscopy does not have any significant advantages over conventional laparoscopy.

Progestins activate vascular endothelial growth factor gene transcription in endometrial adenocarcinoma cells

OBJECTIVE To determine whether progestins activate vascular endothelial growth factor (VEGF) gene transcription in endometrial adenocarcinoma cells. DESIGN In vitro study. SETTING University reproductive biology laboratories. PATIENT(S) None. INTERVENTION(S) Ishikawa cells were transfected with VEGF promoter-luciferase reporter constructs and expression vectors encoding human progesterone receptors (hPR) A or B. The cells were treated with different progestins and antiprogestins, and luciferase activity was compared with controls. MAIN OUTCOME MEASURE(S) Three functional progesterone response elements (PREs) in the VEGF promoter were identified by electrophoretic mobility-shift assay, and different constructs were created to assess each PRE. RESULT(S) In cells expressing hPRA or B, treatment with 10 nM R5020 or 100 nM medroxyprogesterone acetate statistically significantly increased luciferase activity (3.3- to 4.8-fold). Pretreatment with 100 nM RU486 blunted the effect of 10 nM R5020, resulting only in a slight, statistically nonsignificant increase in luciferase activity (1.3- to 1.7-fold). Although three different functional PREs could be identified, no single PRE accounted for the preponderance of the luciferase activity. Full VEGF promoter activation required all three PREs. CONCLUSION(S) Progestins have a direct effect on VEGF gene transcription. However, hPR-mediated transcriptional regulation of the VEGF promoter is complex and cannot be localized to confined PRE sequences. Other response element motifs are likely to play a contributory role.

Epithelial neutrophil-activating peptide 78 concentrations are elevated in the peritoneal fluid of women with endometriosis

OBJECTIVE To investigate the presence of epithelial neutrophil-activating peptide 78 (ENA-78) in peritoneal fluid of women with and without endometriosis and to identify the cells that produce this inflammatory protein. DESIGN Case-control study. SETTING University hospital. PATIENT(S) Eighteen women with and 9 women without endometriosis. MAIN OUTCOME MEASURE(S) ENA-78 protein and mRNA levels were compared among women with and without endometriosis in samples of peritoneal fluid, samples of endometriotic lesions obtained by biopsy during laparoscopy, and peritoneal macrophages. Enzyme-linked immunosorbent assay, reverse transcription polymerase chain reaction, and in situ hybridization methods were used. Secretion of ENA-78 protein by interleukin-1beta-stimulated endometriotic stromal cells and in the media of lipopolysaccharide-stimulated peritoneal macrophages were compared to that in unstimulated cell cultures. RESULT(S) Peritoneal fluid concentrations of ENA-78 were significantly higher in affected women than in controls. Ectopic epithelial and stromal cells and peritoneal macrophages express ENA-78 messenger RNA. Interleukin-1beta stimulation of stromal cell cultures resulted in a 23-fold increase in ENA-78 concentration, and lipopolysaccharide stimulation of peritoneal macrophages increased concentrations by 8-fold. CONCLUSION(S) Levels of ENA-78 are elevated in the peritoneal fluid of women with endometriosis. Ectopic glandular cells, ectopic stromal cells, and peritoneal macrophages express this inflammatory chemokine. Epithelial neutrophil-activating peptide 78 may play an important role in the pathogenesis of endometriosis.

Effects of 5-aminolaevulinic acid on human ovarian cancer cells and human vascular endothelial cells in vitro.

Results are reported on the cellular effects and the sensitivity of cultured tumor epithelial cells (TEC) derived from human ovarian cystadenocarcinoma and human umbilical vein-derived endothelial cells (HUVEC) to exogenous 5-aminolaevulinic acid (ALA) and ALA-induced photodynamic therapy (PDT). Cellular alterations and PDT efficiency were evaluated using colorimetric thiazolyl blue (MTT) assay, trypan blue exclusion assay, electron microscopy, and gel electrophoresis. ALA-induced protoporphyrin IX (PpIX) accumulation in TEC was associated with a concentration and time-dependent significant decrease in mitochondrial activity, increase in cell membrane permeability, and dark toxicity. Maximum PpIX loaded TEC demonstrated a high sensitivity to PDT. Neither cellular alterations nor PDT effects were observed in HUVEC under identical experimental conditions. These results indicate a potential clinical value for the use of ALA-mediated PDT to treat minimal residual disease in mucinous ovarian carcinoma. In addition, the ALA-induced PpIX cytotoxicity may be exported to a new chemotherapeutic regimen via a conventionally viewed photochemotherapeutic agent.

Detection of human papillomavirus in vulvar carcinoma A study by in situ hybridisation

SummaryFourty-four specimens of invasive cancers of the vulva, including 38 primary invasive squamous carcinomas, were analysed by in situ hybridisation with biotinylated HPV 6/11, 16 and 18 DNA probes. Four (9%) of the 44 carcinomas were positive for HPV DNA: three (7%) for HPV 16 DNA and one (2%) for HPV 6/11 DNA. HPV DNA was found only in squamous carcinomas. Of the 38 primary squamous carcinomas, 11% were positive (8% HPV 16, 3% HPV 6/11).The overall 5-year survival was 48.7%, 48.5% for the squamous carcinomas and 50.0% for the HPV DNA positive patients.

Creatine promotes the GABAergic phenotype in human fetal spinal cord cultures

In the present study, we investigated the expression pattern of cytosolic brain specific-BB-CK and ubiquitous mitochondrial-creatine kinases (uMt-CK) in developing human spinal cord. Consequently, we studied the effects of creatine treatment on cultured fetal human spinal cord tissue. We found that both CK isoforms were expressed in fetal spinal cord at all time points investigated (5 to 11.5 weeks post conception) and correspondingly specific CK activity was detected. Chronic creatine exposure resulted in significantly higher densities of GABA-immunoreactive neurons in the cultures, while total neuronal cell density was not altered, suggesting a differentiation inducing mechanism of creatine supplementation. Taken together, our observations favour the view that the creatine phosphocreatine system plays an important role in the developing CNS.

Ovarian cancer. an institutional review of patterns of care, health insurance and prognosis.

The purpose of this study was to investigate the prognostic importance of the health insurance status in 145 consecutive patients with ovarian cancer diagnosed between 1984 and 1996. All patients had basic (Type III) insurance to cover outpatient treatment and hospital expenses for a per diem flat fee; some patients had one of two types of supplemental private insurance (Type I and Type II) to cover the treatment by physicians of their choice and fee-for-service hospital treatment. The prognostic impact of health insurance was evaluated by multivariate statistical methods. The median follow-up was 81.9 months (range: 21-181); the 5-year probability of survival was 72% (standard error of the mean (SEM) 9.8%) for stage I, 53% (SEM 16.2%) for stage II, 17% (SEM 5. 9%) for stage III and 11% (SEM 5.5%) for stage IV cancer. Age, stage, histological grade and debulking surgery were independent predictors of survival in multivariate proportional hazards regression analysis. Patients with private insurance were younger and received more chemotherapy than patients with basic insurance. In multivariate analysis, insurance was an independent predictor of survival: patients with Type II insurance had a hazard ratio of 2.31 (95% confidence interval (CI): 1.05-5.04), and patients with Type III insurance had a hazard ratio of 3.30 (95% CI 1.52-7.17) compared with the reference group of Type I insured patients. Health insurance status was an independent predictor of survival in ovarian cancer. Research is needed to devise strategies to improve the medical care of patients with basic insurance.

Tubal sterilization by means of endoluminal coagulation: an in vivo study in rabbits.

This study was conducted to investigate the effectiveness and safety of endoluminal tubal coagulation in obliterating the tubal lumen in rabbits. Forty female rabbits were subjected to laparotomy and hysterotomy. Endoluminal tubal coagulation was induced over a length of 3 cm in the proximal, extramural fallopian tube by using a heated stainless steel cannula or a cylindrical diffusing tip emitting argon laser radiation for one to 5 minutes. Tubal patency was evaluated by observing patterns of injected methylene blue and/or breeding success rates. Postoperative recovery was uneventful in all animals. A negative methylene blue test indicated occlusion in 51 of 52 tubes (tubal occlusion rate 98.1%), and a contraception rate of 100% in all 17 uteri in which the tube had been treated. The described endoluminal tubal coagulation method proved suitable for safe and effective sterilization in rabbits and has potential as a new transcervical tubal sterilization method for humans.

Is laparoscopic oophorectomy rational in patients with breast cancer

AbstractBackground: Unsuspected malignancy remains a problem for the laparoscopic surgeon. The aim of this study was to evaluate the risk of ovarian micrometastasis in patients with breast cancer who undergo laparoscopic oophorectomy. Methods: We analyzed 25 premenopausal women with breast cancer who underwent therapeutic laparoscopic oophorectomy. The patients were subdivided into the following two groups according to ovarian pathology: group A with and group B without breast carcinoma micrometastasis. We then reviewed the follow-up data for both groups, with special attention to metastasis of the abdominal wall. Results: Twelve of 44 ovaries removed by laparoscopy showed ovarian breast carcinoma micrometastasis. There were no predictive factors of micrometastasis. After a mean follow-up of 38.1 months (95% CI: 29.2–46.9 months), none of the patients with proven micrometastasis developed metastasis of the abdominal wall, and the 21 puncture sites were inconspicuous. Conclusions: Although 32% of patients may have unexpected ovarian micrometastasis, laparoscopic oophorectomy in patients with breast cancer remains a safe procedure.

Hormone-dependent nuclear localization of the tyrosine kinase iyk in the normal human breast epithelium and loss of expression during carcinogenesis

iyk, a member of the frk family of non‐receptor tyrosine kinases, was originally isolated from normal mouse mammary glands and is characterized by a nuclear localizing signal within the SH2 domain. We have investigated the expression and subcellular localization of iyk in the normal human breast and in malignant breast diseases. Immuno‐histochemical analyses revealed that in normal tissue iyk localizes to both cytoplasmic and nuclear compartments of breast epithelial cells. The subcellular distribution was dependent on the hormonal state, being mostly cytoplasmic during the follicular, proliferative phase of the menstrual cycle, whereas frequent nuclear staining was observed in the resting stages during the luteal phase and, most prominently, after menopause. Strikingly, invasive carcinomas, irrespective of tumor type or hormonal status of the patient, exhibited almost complete loss of iyk expression in both the cytoplasm and the nucleus. In contrast, in situ breast carcinomas from post‐menopausal patients showed a clear reduction of the nuclear iyk localization while retaining cytoplasmic staining. Our results indicate that iyk expression is gradually lost during carcinogenesis; thus, iyk may be classified as a tumor‐suppressor gene. Int. J. Cancer 85:889–894, 2000.