Guenther Haeusler

Vascular endothelial growth factor serum concentrations in ovarian cancer

Objective To determine whether serum vascular endothelial growth factor is an independent prognostic factor in ovarian cancer patients. Methods We measured vascular endothelial growth factor in pretreatment serum samples of 60 women with International Federation of Gynecology and Obstetrics stages I to IV epithelial ovarian cancer, using an enzyme-linked immunosorbent assay. The results were correlated to clinical data. Results The median vascular endothelial growth factor serum level in ovarian cancer patients was 466.1 pg/mL (range 69.7-2835 pg/mL). The 75% quartile was defined as a cut-off level. Elevated vascular endothelial growth factor serum levels before therapy correlated significantly with a poorer disease-free (log-rank-test, P = .003) and overall survival (log-rank-test, P = .007). Multivariate analysis revealed serum vascular endothelial growth factor to be an independent prognostic factor of overall and disease-free survival. When median pretreatment levels of vascular endothelial growth factor were grouped by tumor stage, histologic grade of tumor cells, histologic type of the tumor, lymph node involvement, age of patient, and residual tumor mass, we found a statistically significant correlation between serum levels of vascular endothelial growth factor and histologic grade (Mann-Whitney U test, P = .03). Conclusion Vascular endothelial growth factor appears to be an additional factor for predicting the outcome of patients with epithelial ovarian cancer. Owing to its independence from established prognostic factors, vascular endothelial growth factor could be used for prognostic information in clinically relevant subsets such as early-stage or lymph node-negative ovarian cancers.

Transurethral injection of silicone microimplants for intrinsic urethral sphincter deficiency.

Objective To assess the short-term efficacy of transurethral injection of silicone microimplants in women with intrinsic sphincter deficiency. Methods During January 1995 and December 1996, 32 women (mean age 64.3 years, range 39-85 years) with type III stress incontinence (intrinsic sphincter deficiency) underwent transurethral injection of silicone microimplants under general anesthesia. Twenty-eight had undergone previous continence surgery. Subjective and urodynamic assessments were made at 6 and 12 months after injection to evaluate success and short-term effects. Results Objective and subjective success rates were 75% and 59% at 6 and 12 months, respectively. Injections of silicone microimplants significantly increased maximum urethral closure pressure (maximum urethral pressure at rest: 34.40 ± 16.46 cm H2O, 95% confidence interval [CI] 28.55, 40.25 versus 25.35 ± 10.78 cm H2O, 95% CI 21.52, 29.18; P = .027). There were no complications after surgery up to 1 year. Conclusion Transurethral silicone injections were effective in 60% of cases of intrinsic sphincter deficiency, although there was a time-dependent decrease.

Drug therapy of urinary urge incontinence: a systematic review

OBJECTIVE To review the efficacy of drug therapy for urinary urge incontinence by examining the published literature. METHODS OF STUDY SELECTION In October 1999, we searched the medical databases MEDLINE, EMBASE, and Cochrane Controlled Trials Register to identify prospective randomized, double‐blind, placebo‐controlled clinical trials in the English literature evaluating drug therapy (except hormonal therapy) of urinary urge incontinence. Trials were categorized by type of drug and outcome variables. TABULATION, INTEGRATION, AND RESULTS Forty‐seven trials were identified. Twenty‐four, 12, and 11 trials evaluated anticholinergic drugs, drugs with anticholinergic and calcium antagonistic properties, and alternative regimens, respectively. Data regarding treatment effects of anticholinergic drugs are consistent with a high therapeutic efficacy and characteristic side effects. Therapeutic efficacy and side effect patterns of terodiline, an agent with anticholinergic and calcium antagonistic properties, were comparable to those of anticholinergic agents. Terodiline, however, has been withdrawn from the market because of its association with cardiac arrhythmia. Of the investigated alternative drug regimens, the papaverine‐like smooth muscle relaxant flavoxate was reported to be ineffective. Studies investigating the dopamine agonist bromocryptine, the α‐adrenoceptor blocker prazosin, or the γ‐aminobutyric acid receptor agonist baclofen showed subjective and/or objective improvement of symptoms without reaching statistical significance, whereas the tricyclic anti‐depressant doxepin, the neurotoxin capsaicin, and the prostaglandin synthase inhibitor flurbiprofen led to statistically significant subjective and/or objective improvement of symptoms. No data for subjective and/or objective improvement of symptoms could be extracted from the studies using the anticholinergic and calcium antagonistic agent propiverine and the calcium antagonist thiphenamil. CONCLUSION Published trials support anticholinergic drugs as efficacious therapy for urinary urge incontinence, with predictable side effects. At present, these agents represent the pharmacological treatment of choice for this condition. The potential value of selected alternative drugs is underscored by the available data.

Diagnostic accuracy of 2 mm microlaparoscopy

Objective. To assess the diagnostic accuracy of a 2 mm microlaparoscope compared to the conventional 10 mm laparoscope.

The prognostic value of CD44 isoform expression in endometrial cancer.

Isoforms of the transmembrane glycoprotein CD44 have been implicated in tumour cell adhesion, tumour differentiation and metastatic spread in various human malignancies. We investigated the expression of CD44 isoforms containing variant exons v3, v5, v6 and v7-8 in 156 human endometrium cancer specimens by means of immunohistochemistry. CD44 isoforms CD44v3, CD44v5, CD44v6 and CD44v7-8 were detected in 26% (41 out of 156), 31% (48 out of 156), 22% (35 out of 156) and 15% (23 out of 156) of the tumour samples respectively. The expression of CD44 isoforms CD44v3, CD44v5 and CD44v7-8 showed no prognostic impact. In the univariate analysis, the expression of CD44v6 showed an association with shortened overall survival (log-rank test, P = 0.06). Multivariate analysis correcting for the confounding variable histological grading revealed CD44v6 not to be a prognostic factor in endometrial cancer (log-rank test, P = 0.06). Comparing the expression of CD44 isoforms CD44v3, CD44v5, CD44v6 and CD44v7-8 in 45 specimens of normal endometrial tissue, we found an up-regulation of all investigated CD44 isoforms in the secretory phase compared with the proliferative phase of the menstrual cycle. Our data indicate that the expression of CD44 isoforms, while obviously playing a role in the functional changes of normal endometrium, is not an adverse predictive factor in endometrial cancer.

Differential diagnosis of detrusor instability and stress‐incontinence by patient history: The Gaudenz‐Incontinence‐Questionnaire revisited

Objective. To evaluate the validity of the Gaudenz‐Incontinence‐Questionnaire in the differential diagnosis of genuine stress‐incontinence and detrusor instability.

Tissue polypeptide specific antigen in the follow-up of ovarian and cervical cancer patients

This retrospective study includes 425 serological examinations of 40 patients with epithelial ovarian cancer and 356 serological examinations of 33 patients with squamous cell cervical cancer. The serum levels of the tumor markers tissue polypeptide specific antigen (TPS), carbohydrate antigen 125 (CA 125) and squamous cell carcinoma antigen (SCC) were determined. Cutoff values of 93 U/l for TPS, 3 μg/l for SCC and 37 U/ml for CA 125 were selected according to the 95th percentile of serum concentrations measured in healthy control patients. For ovarian cancer sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of TPS were 67%, 84%, 59% and 90%, respectively. In 27 patients with recurrent ovarian cancer, CA 125 and TPS showed lead time effects in 8 and 11 cases, respectively. The combination of CA 125 and TPS provided lead time in 14 cases of recurrent disease with a time range from 1 to 23 months (median 3.9 months). In cervical cancer, TPS showed a sensitivity, specificity, PPV and NPV of 64%, 90%, 85% and 68%, respectively. In 16 patients with recurrent cervical cancer, SCC and TPS showed lead time effects in 7 and 8 cases, respectively. The combination of SCC and TPS provided lead time effects in 12 cases with a time range from 0.5 to 6 months (median 3.5 months). Our data indicate that TPS is a valuable tool in the follow‐up of patients with ovarian or cervical cancer. However, TPS does not appear to be adequate to replace tumor markers CA 125 and SCC. Int. J. Cancer (Pred. Oncol.) 79:241–244, 1998.© 1998 Wiley‐Liss, Inc.

Cytosol concentrations of CD44 isoforms in breast cancer tissue

The role of the adhesion molecule CD44 in the natural history of breast cancer is controversial. We investigated the CD44 isoform CD44v5 and CD44v6 concentrations in the cytosol of 90 breast cancer specimens, 9 fibroadenomas and 22 normal breast tissue specimens by means of ELISA. CD44v5 and CD44v6 cytosol concentrations were statistically significantly higher in breast cancer compared with fibroadenoma and normal breast tissue (Mann‐Whitney U‐test, p = 0.009 and p < 0.001, respectively). When CD44 isoforms were correlated with lymph node involvement, histological grading, histological type, tumor stage and age at diagnosis, we found no statistically significant correlation with any of the investigated clinico‐pathological parameters. In univariate and multivariate analyses, CD44v5 and CD44v6 were of no prognostic relevance regarding disease‐free survival in breast cancer patients (log‐rank test, p = 0.16 and p = 0.08, respectively). Our results indicate that CD44 isoforms are increased in samples from tumors relative to normal tissue. Our data show that CD44v5 and CD44v6 isoform expression, although up‐regulated by malignant transformation, is not required to acquire a metastatic phenotype in breast cancer. Furthermore, our data support the assumption that cytosolic CD44 isoforms are of no prognostic relevance for disease‐free survival of breast cancer patients. Int. J. Cancer (Pred. Oncol.) 79:541–545, 1998.© 1998 Wiley‐Liss, Inc.

Value of urethral pressure profilometry in the female incontinent patient: a prospective trial with an 8-channel urethral catheter

OBJECTIVES To measure the pressure profiles at different positions of the urethral circumference simultaneously. METHODS Twenty-two women with symptoms of genuine stress incontinence underwent urogynecologic assessment and multichannel urethral pressure profilometry (UPP) at rest with a specially designed 8-channel urethral catheter with radial openings. RESULTS The distribution pattern of maximum urethral closure pressure (MUCP) and functional urethral length (FUL) values were significantly different (P=0.004 and P=0.0004, respectively). Most of the highest MUCP values per patient were found between channels 2 and 4 (P=0.015); most of the greatest FUL values per patient were found between channels 3 and 4 (P=0.15). CONCLUSIONS The data of our study substantiate asymmetric radial pressure distribution within the urethra and underline the necessity of cautious interpretation of results of conventional single-channel UPP, which might vary because of transducer orientation.

M3/M21 serum levels in women with adnexal masses and inflammatory diseases

The aim of the present study was to evaluate the clinical usefulness of the cytokeratin tumor marker M3/M21 as a screening marker for ovarian cancer, as a predictive marker in patients with adnexal masses and as a prognostic factor in women with ovarian cancer. To determine the specificity of the M3/M21 test, we investigated M3/M21 serum levels in several benign conditions. This retrospective study comprises 37 patients with ovarian cancer FIGO stages Ia to III. Sera of patients with benign cysts, endometriosis, pelvic inflammatory disease, inflammatory bowel disease and liver cirrhosis were evaluated in 90, 10, 38, 10 and 20 cases, respectively. With a sensitivity of 57% and a specificity of 95%, M3/M21 is not suitable as a screening marker for ovarian cancer. Although M3/M21 is able to discriminate between ovarian cancer and benign adnexal tumors (univariate logistic regression, p = 0.0003), M3/M21 does not provide information additional to CA 125. M3/M21 serum levels are elevated in several benign conditions such as liver cirrhosis and inflammatory bowel disease. In ovarian cancer patients, elevated M3/M21 serum levels prior to therapy were associated with poor overall and disease‐free survival (log‐rank test, p = 0.03; log‐rank test, p = 0.01, respectively). M3/M21, while obviously not suitable for screening or differential diagnosis of adnexal masses, could be useful as an additional prognostic factor in ovarian cancer patients. Int. J. Cancer (Pred. Oncol.) 79:434–438, 1998.