p53 is correlated with low BMI negative progesterone receptor status and recurring disease in patients with endometrial cancer.

OBJECTIVE: P53 tumor suppressor gene plays a role in endometrial carcinogenesis. Former studies described correlations between p53 protein overexpression in endometrial cancer and prognostic factors, measured by immunohistochemistry. But data is still controversial. The aim of this study was to measure p53 and phospho-p53 overexpression by Western blot and evaluate correlations between overexpression and prognostic and clinical factors. Phospho-p53 seems to be the functional p53 protein and was examined for the first time in endometrial cancer. METHODS: 40 patients with endometrial cancer were included in the study. A control group of 20 patients with normal endometrial tissue samples was used. Western blot was performed for detection of p53 and phospho-p53. Clinical and pathological parameters were obtained from medical records. Statistical analysis was performed using the log-rank test, the Mann-Whitney test for two independent groups and the Fisher's exact test for dichotomous groupings. RESULTS: In 17.5% of the patients with endometrial cancer a p53 overexpression could be evaluated. There was a correlation between a p53 overexpression and recurring disease (p: 0.014), a negative progesterone receptor status (p: 0.021) and a low BMI (p: 0.022). Only one of 40 patients had a phospho-p53 expression. CONCLUSION: Western blot is a valid method for the detection of p53 overexpression. As other authors described before, p53 overexpression seems to correlate with negative prognostic factors. The correlation between p53 overexpression and a low BMI may underline the relationship between p53 alterations and biological aggressive endometrial carcinomas.

A prospective multicenter phase II study of oral and i.v. vinorelbine plus trastuzumab as first-line therapy in HER2-overexpressing metastatic breast cancer.

BACKGROUND: To evaluate the efficacy and safety of oral and i.v. vinorelbine plus trastuzumab as first-line regimen in a patient-convenient application for human epidermal growth factor receptor 2 (HER2)-overexpressing patients with metastatic breast cancer. PATIENTS AND METHODS: Forty-two women were enrolled in a multicenter study. The patients received i.v. vinorelbine at a dose of 25 mg/m(2) on day 1 followed by oral vinorelbine at a dose of 60 mg/m(2) on days 8 and 15 in a 3-week cycle. Standard dose trastuzumab was given at 3-week intervals. RESULTS: Complete response was observed in 7 patients (18.9%) and partial response in 19 patients (51.4%), for an overall response rate of 70.3% [95% confidence interval (CI) 53.0-84.1]. The disease control rate reached 91.9% (95% CI 78.1-98.3). The median time to progression was 9.3 months, while median overall survival reached 35.6 months. Hematological and non-hematological toxic effects were acceptable with grade 3-4 leukopenia of 14% and neutropenia of 38%; cardiac toxicity did not reach the level of clinical relevance. CONCLUSION: The combination of i.v. and oral vinorelbine plus trastuzumab demonstrates high activity and good tolerability in first-line treatment of HER2-overexpressing metastatic breast cancer. In addition, it offers convenience for the patients with only one i.v. treatment every 3 weeks.

[Clinical and economic challenges of moderate preterm babies born between 32+0 and 36+6 weeks of gestation]. / Klinische und ökonomische Herausforderung der moderaten Frühgeburt zwischen 32+0 und 36+6 SSW.

BACKGROUND: Preterm births show a worldwide increasing incidence. The majority of preterm births occur between 32+0 and 36+6 weeks of gestation and are associated with an increased rate of maternal and neonatal morbidity. The focus of our research is the clinical and economical analysis of all preterm births between 32+0 and 36+6 weeks of gestation in a German level 1 perinatal centre over a period of 3 years. MATERIALS AND METHODS: A retrospective analysis of all preterm births between 32+0 and 36+6 weeks of gestation in the University Hospital Mainz from 2007 to 2009 was undertaken. Data were collected using our electronic documentation system. Gestational age at delivery, mode of birth, indication for delivery, duration of the peripartum treatment, treatment of the newborn in the children's hospital, birth weight and therapy costs were evaluated. RESULTS: We recorded 407 moderate preterm births in total; this amounts to a rate of of 10% of all births. Major causes of prematurity were PPROM, preterm labour and preeclampsia/HELLP. Maternal and fetal systemic diseases were more uncommon. Rates of Caesarean sections (62%) and of neonatal inpatient treatment needs (58.5%) were high. Maternal treatment costs were 332 Euro/day. The mean duration of maternal inpatient treatment was 13.15 days. DISCUSSION: Moderate preterm birth is associated with maternal morbidity frequently due to a high rate of Caesarean sections. Neonatal morbidity is also increased. In comparison with previous research, we saw an increased rate of pregnancy complications. This could be typical for a level 1 perinatal centre. Moderate preterm birth is seen as the cause of considerable treatment costs.

Overactive Bladder and Continence Guidelines: implementation, inaction or frustration?

Guidelines for the management of continence and overactive bladder are generally available across Europe. For a majority of countries, these have been adopted by professional societies in either urology or gynaecology for local use. There has, however, been little monitoring of formal implementation of these guidelines and seldom any attempt to audit their operation. The state of continence care therefore remains largely unknown. This article reviews current guidelines and their status across Europe and examines what might be relevant from other disease areas to promote successful implementation.

Gemcitabine and carboplatin in intensively pretreated patients with metastatic breast cancer.

BACKGROUND: Patients with metastatic breast cancer (MBC) are increasingly exposed to anthracyclines and taxanes either during treatment of primary breast cancer or during initial therapy of metastatic disease. The combination of gemcitabine and carboplatin was therefore investigated as an anthracycline- and taxane-free treatment option. PATIENTS AND METHODS: MBC patients previously treated with chemotherapy were enrolled in a multicenter phase II study. Treatment consisted of gemcitabine (1,000 mg/m(2) i.v. on days 1 and 8) and carboplatin (AUC 4 i.v. on day 1) applied every 3 weeks. RESULTS: Thirty-nine patients were recruited, and a total of 207 treatment cycles were applied with a median of 5 cycles per patient. One complete response and 11 partial responses were observed for an overall response rate of 31% (95% CI: 17-48%). Twelve patients (31%) had stable disease. Median time to progression was 5.3 months (95% CI: 2.6-6.7 months) and median overall survival from start of treatment was 13.2 months (95% CI: 8.7-16.7 months). Grade 3/4 hematological toxicity included leukopenia (59%/5%), thrombocytopenia (26%/23%) and anemia (10%/0%). Nonhematological toxicity was rarely severe. CONCLUSION: Combination chemotherapy with gemcitabine and carboplatin is an effective and generally well-tolerated treatment option for intensively pretreated patients with MBC. Due to a considerable incidence of severe thrombocytopenia it would be reasonable to consider starting gemcitabine at the lower dose level of 800 mg/m(2).

Combination therapy with pegylated liposomal doxorubicin and carboplatin in gynecologic malignancies: a prospective phase II study of the Arbeitsgemeinschaft Gynäekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and Kommission Uterus (AGO-K-Ut).

OBJECTIVE: A multicenter non-randomized phase II study was initiated to evaluate tolerability and efficacy of pegylated liposomal doxorubicin (PLD) in combination with carboplatin in gynecologic malignancies. METHODS: One hundred forty women with recurrent or advanced endometrial (n=31), cervical or vaginal cancer (n=31), uterine sarcomas (n=11), or recurrent platinum-sensitive ovarian cancer (n=67) received six courses of PLD 40 mg/m2 and carboplatin (AUC 6) every 28 days. RESULTS: Hematological toxicities with NCI-CTC grade 3/4 were anemia in 8%, thrombocytopenia in 14%, neutropenia in 24%, and febrile neutropenia in 2% of 652 cycles. Grade 3/4 non-hematological toxicities included fatigue (14% of patients), pain (10%), dyspnea (9%), palmar-plantar erythrodysesthesia (7%), and nausea/vomiting (7%). Dose intensity reached 87.2% for PLD and 88.2% for carboplatin. Seventy-four percent of all non-progressive patients received at least 5 cycles. Overall response rates were (116 patients evaluable for response): ovarian cancer (n=54) 68%, endometrial cancer (n=27) 44%, uterine sarcomas (n=9) 33%, and cervical/vaginal cancer (n=26) 12%. Median progression-free survival was 11.6 months (95%CI 9.6-14.1) for ovarian cancer and 9.5 months (95%CI 6.6-12.6) for endometrial cancer. Median overall survival was 23.8 months (95%CI 19.0-30.2) and 21.4 months (95%CI 11.9-), respectively. CONCLUSIONS: The combination of PLD and carboplatin was well tolerated and feasible in patients with gynecologic malignancies. Efficacy was low in cervical/vaginal cancer, but promising in patients with endometrial cancer. Efficacy was within the expected range in recurrent platinum-sensitive ovarian cancer and is currently under further investigation in a prospective randomized phase III trial comparing PLD/carboplatin with paclitaxel/carboplatin (CALYPSO-trial; AGO-OVAR 2.9).

Diabetes mellitus is a multivariate independent prognostic factor in endometrial carcinoma: a clinicopathologic study on 313 patients.

OBJECTIVE: The aim of this study was to analyse the influence of diabetes mellitus as a prognostic factor for overall survival in endometrial cancer. MATERIALS AND METHODS: Charts were reviewed from patients with endometrial carcinoma from 1985 to 2003. Data on clinicopathologic variables, adjuvant treatment, site of recurrence and survival were collected. The chi-square test was used to examine associations between variables. The Kaplan-Meier method was used for survival analysis and Cox's proportional hazards model for multiple regression analysis. RESULTS: Multivariate analysis revealed that diabetes mellitus, FIGO stage and depth of myometrial invasion were significantly associated with overall survival.

Guideline-Based Strategies in the Surgical Treatment of Female Urinary Incontinence: The New Gold Standard is Almost the Same as the Old One.

The modern sling procedures for treating female stress urinary incontinence encompass numerous methods, materials and manufacturers. On the basis of the current S2e guidelines, the methods used most frequently in the diagnosis of and therapy for stress urinary incontinence in women are critically illustrated. An individualised procedure is necessary for the choice of the surgical method, especially in the presence of accompanying pathologies. This article is intended to help the treating physician to carry out quality-assured diagnostics and therapy for the patient and to offer the best possible urogynaecological management. In addition to the complications and chances of success of the surgical options, the legal aspects of therapy planning are also taken into consideration.

Correlation of the volume of ectopic pregnancy and MTX therapy outcome: a retrospective cohort study.

OBJECTIVE: To investigate a possible correlation between the volume of the tubal ectopic pregnancy (EP) measured by vaginal-ultrasound (VUS) and methotrexate (MTX) therapy outcome. STUDY DESIGN: Data of EP volume measured by one expert-sonographer, viability, clinical symptoms, previous IVF/insemination, follow-up of ß-hCG and progesterone levels, and treatment of EP was collected of 100 patients with sonographically diagnosed EP, who attended the Department of Obstetrics and Gynecology of the Medical University Vienna between March 2008 and September 2011. RESULTS: The mean volume of EP (mVol.) in the group with successful MTX therapy (n = 38) was 5.11 ml, 95%CI [2.4; 7.8] with a median 3.2 ml, IQR [5.0], in the group with unsuccessful MTX treatment (n = 11) it was 15.24 ml, 95%CI [-2.6; 33.1], with a median 4.4 ml, IQR [11.4]. We could observe a trend towards a lower mVol. in the successful MTX group (5.11 ml vs. 15.24 ml). We could not show a significant correlation (u-test p = 0.208). CONCLUSION: A clear tendency was observed towards a lower mVol. in the successful MTX therapy group, but we could not verify a statistically significant correlation of volume of EP and MTX therapy outcome most likely due to the small sample size. This was the first study investigating the correlation of volume of EP and MTX therapy outcome as principal question.

Prognostic value of immunohistochemically detected CD44 isoforms CD44v5, CD44v6 and CD44v7-8 in human breast cancer.

We investigated the expression of CD44 isoforms containing variant exons v5, v6 and v7-8 in 115 human breast cancer specimens by means of immunohistochemistry. CD44 isoforms CD44v5, CD44v6 and CD44v7-8 were detected in 56% (n = 64), 24% (n = 28) and 15% (n = 17), respectively. In 36 specimens of axillary lymph node metastasis, expression of CD44v5, CD44v6 and CD44v7-8 was found in 94% (n = 34), 92% (n = 33) and 89% (n = 32), respectively. Five year survival rates with or without CD44v5 and CD44v6 expression were 71% versus 86% (log-rank test, P = 0.02) and 62% versus 81% (log-rank test, P = 0.001), respectively. For disease-free survival, expression of CD44v5, CD44v6 and CD44v7-8 showed a prognostic impact (log-rank test, P = 0.004, P = 0.0001 and P = 0.0001, respectively). However, multivariate analysis revealed that all investigated CD44 isoforms failed to be independent predictors of the patient's outcome.

Prognostic significance of tumor angiogenesis in epithelial ovarian cancer.

Since angiogenesis is considered essential for tumor growth and the development of metastasis, we assessed the correlation of microvessel density (MVD) with overall survival in patients with epithelial ovarian cancer. Histologic slides were immunostained for CD34-antigen. MVD was determined within each tumor by enumeration under a light microscope at 200x magnification and an examination area of 0.25 mm2. The Cox proportional-hazards model was used for multivariate analysis. In 63 patients with epithelial ovarian cancer the 5-year survival rate (OS-%) was as follows: 55.0% (+/-12.5) in 18 patients whose tumors had an MVD < 10/field, and 23.6% (+/-6.7) in 45 patients whose tumors had an MVD(10/field (log-rank P = 0.038). MVD showed a significant influence on survival in univariate analysis, but failed to attain a significant value after adjustment for established prognostic parameters such as patients' age at diagnosis, stage of disease, and histologic grading. High MVD was significantly associated with advanced patients' age at diagnosis. This and a considerable heterogenity in the vascular architecture of ovarian carcinoma tissue might be the reasons why MVD did not reveal prognostic significance in multivariate analysis. In contrast to a variety of solid neoplasms, MVD does not seem to be a useful predictor of survival in patients with epithelial ovarian cancer.

Hyperemesis gravidarum associated with Helicobacter pylori seropositivity.

OBJECTIVE: To test the hypothesis that infection with Helicobacter pylori is associated with hyperemesis gravidarum. METHODS: From January 1995 to November 1996 we enrolled 105 patients with hyperemesis gravidarum in a prospective study. The Helicobacter serum Immunoglobulin (Ig) G concentrations in these patients were compared with those in asymptomatic gravidas matched for week of gestation. RESULTS: Positive serum IgG concentrations were found in 95 of the 105 hyperemesis patients (90.5%) compared with 60 of 129 controls (46.5%). A chi2 test showed statistical significance (P < .001). The mean (+/-standard deviation) index percentages of the IgG titers were 74.2+/-23.6% in the hyperemesis group and 24.3+/-4.4% in the control group (P < .01, Student t test). CONCLUSION: Infection with H pylori may cause hyperemesis gravidarum.

Surgical therapy of radiation-induced small-bowel lesions. Report of 34 cases with a high share of patients with combined chemotherapy.

Operations on irradiation-injured bowel are rare, bear a high postoperative mortality, and the procedure of choice (resection vs bypass) is still controversial. Thirty-seven operations on small bowel for late effects of irradiation in 16 years were analyzed retrospectively. Fifty-one percent of the operations were performed in the last four years. Ovarian cancer treated by a combination of radiotherapy and chemotherapy was the most frequent underlying disease of 20 patients (58%) followed by carcinoma of the cervix (eight [24%] of the patients). The median latent period between irradiation and surgery was eight months after the combined radiotherapy/chemotherapy, and 12 months after radiotherapy alone. Thirty operations (81%) were done for small-bowel stricture, four for fistula, and three for perforation. Bypass was performed in 17 patients and resection in 16. Complications (fistula, peritonitis, perforation) occurred after 13 operations (35%). All three patients who developed peritonitis died (mortality, 8.1%): two after resection and one after bypass. Suture-associated complications occurred in three (23%) of 13 cases after single-layer and in three (35%) of 17 cases after two-layer anastomoses. Ten patients are still alive two to 76 months (median, 32 months) after operation, six of them free of tumor. All are underweight and suffer from diarrhea (four to 12 stools per day). Pernicious anemia developed in all six patients surviving more than two years.

Development of ovarian pathology after hysterectomy without oophorectomy.

This study was done to determine the occurrence of disease in retained ovaries after hysterectomy. A retrospective analysis of patient charts was performed, comparing the patient reports of women who had secondary ovarian lesions with those whose ovaries showed no pathologic findings during the ten year period of observation (1980 to 1990). The study included 1,265 women with at least one ovary saved after hysterectomy for benign indications. Main outcome measures were ovarian pathologic findings after hysterectomy requiring repeat operation. The overall incidence of lesions in retained ovaries was 3.95 percent. There was a 3 percent risk of having secondary ovarian pathologic findings within three years after hysterectomy, with a decreased risk for the following seven years (mean follow-up time of 60 months, range of three to 120 months). Histologic findings at reoperation included common benign conditions of the ovary. No instance of carcinoma of the ovary was found. The risk of having pathology in the retained ovaries after hysterectomy was significantly higher in women who had only one ovary saved, compared with those who had both ovaries saved (7.63 versus 3.47 percent; p < 0.05). The mean age at hysterectomy was significantly lower in women who had ovarian disorders subsequent to hysterectomy than in those who did not (39.3 versus 43.9 years; p < 0.001). In the group of women with secondary ovarian lesions, mean parity was significantly lower than in those without reoperation (1.22 versus 1.94; p < 0.0001). Women with unilateral oophorectomy at the time of hysterectomy had twice the risk of secondary ovarian lesions, compared with those without oophorectomy at hysterectomy. Determinants, such as age, parity and gravidity must be considered when deciding whether or not to perform oophorectomy at hysterectomy.

The diagnostic value of magnetic resonance imaging for the detection of tumor recurrence in patients with carcinoma of the ovaries.

Disease status during follow-up evaluation of patients with carcinoma of the ovaries is the main criterion for the selection of appropriate management. A cohort analysis was performed to investigate if magnetic resonance imaging (MRI) could improve noninvasive assessment of disease status in patients with carcinoma of the ovaries during follow-up examination. Twenty-four women with carcinoma of the ovaries after primary surgical treatment with subsequent platinum containing chemotherapy were entered into the study. MRI was performed in addition to sonography and computed tomography (CT). Patients without evidence of disease underwent restaging laparotomy. Sensitivity of sonography, CT and MRI was 50, 63 and 75 percent, respectively. Combination of CT and MRI revealed a 75 percent sensitivity rate. Specificity for sonography, CT and MRI was 100, 94 and 94 percent, respectively, and for the combination of CT and MRI, 88 percent. Positive and negative predictive value and accuracy of these methods were 100, 80 and 83 percent for sonography; 83, 83 and 83 percent for CT; 86, 88 and 88 percent for MRI, and 75, 88 and 83 percent for the combination of CT and MRI. In one instance of false-negative sonographic and CT results, MRI detected recurrence located in postoperative scar tissue. In one instance, MRI did not add essential information to the other imaging methods. Therefore, MRI as a time- and cost-intensive procedure should be reserved for instances in which there are doubtful findings arising with other diagnostic tools, rather than as an indispensable routine procedure in the follow-up evaluation of patients with carcinoma of the ovaries.

Significance of pretreatment serum hemoglobin and survival in epithelial ovarian cancer.

Tumor anemia is common in patients with malignant tumors and it was repeatedly demonstrated to be associated with impaired prognosis in patients with malignant tumors. We conducted a retrospective analysis based on 553 patients with histologically proven epithelial ovarian cancer. Blood hemoglobin levels were determined before surgery and patients with values <12 g/dl were considered anemic. Data analysis included univariate and multiple Cox models. Tumor anemia was present in 143 (25.9%) patients before surgery. Tumor anemia was present in 143 (25.9%) patients before surgery. In a multivariate Cox model, pretreatment hemoglobin values proved to be an independent prognostic factor for patients with stage I-II epithelial ovarian cancer (n=203), but failed to attain significance in patients with stage III-IV disease (n=350). Tumor anemia defined as pretreatment hemoglobin values <12 g/dl may indicate patients with stage I and II epithelial ovarian cancer, who are at increased risk of relapse.

Ovarian tumors of low malignant potential (borderline tumors): immune morphology and current status.

CA 125, CA 19-9 and CEA were demonstrated in tissue samples of 30 ovarian borderline tumors by immunohistochemistry. Of the 21 serous and 9 mucinous borderline tumors, 23 were in stage I and 7 stage III. None of the patients died of disease. All mucinous borderline tumors were CA 125 negative, 89% CA 19-9 positive and 44% CEA positive. 62% of the serous borderline tumors were CA 125 positive, 52% CA 19-9 and 19% CEA positive. Tumors of low malignant potential responded to CA 19-9 like invasive carcinomas. The incidence of positive responses to CA 125 ands CEA fell between that of benign and malignant tumors. The marker pattern did not correlate with tumor stage and cytological grading. The biological behavior of ovarian borderline tumors ranges between that of benign tumors and invasive carcinomas and cannot be classified as definitely belonging to either group. It is plausible that they are primarily of the borderline type, and not benign tumors that undergo malignant degeneration.

Basaloid carcinoma and keratinizing squamous cell carcinoma of the vulva: a case of two primary carcinomas.

Basaloid carcinomas of the vulva have been reported to occur mostly in young women and are often associated with Human Papillomavirus (HPV) infection, whereas older women mostly suffer from keratinizing squamous cell carcinomas unassociated with HPV. The rare case of a 75 year old woman coincidentally suffering from a basaloid carcinoma and a keratinizing squamous cell carcinoma of the vulva is reported. With in situ hybridisation, hybrid capture and immunohistochemical methods we searched for HPV and expression of cytokeratin AE1/AE3, cytokeratin HMW and cytokeratin 8, 18, 19. HPV was not found in either of the carcinomas. Cytokeratin HMW showed a focal staining reaction in the keratinizing squamous cell carcinoma and no expression in the basaloid carcinoma. Immunohistochemical staining reaction for cytokeratin AE1/AE3 was found in both tumors with the same staining pattern. Cytokeratin 8, 18, 19 was not detected in either of the two carcinomas.

Argifin, a new chitinase inhibitor, produced by Gliocladium sp. FTD-0668. I. Taxonomy, fermentation, and biological activities.

A new chitinase inhibitor, named argifin, was isolated from the cultured broth of a fungal strain FTD-0668. The strain was identified as Gliocladium sp. from morphological characteristics. The IC50 value of argifin against Lucilia cuprina chitinase was 3.7 microM. Argifin arrested the moult of cockroach larvae upon injection into the ventral abdominal part.

[Value of anamnesis and the clinical stress test in the diagnosis of incontinence before gynecologic operations]. / Die Aussagekraft von Anamnese und klinischem Stresstest in der Inkontinenzdiagnostik vor gynäkologischen Operationen.

In a study comprising 471 patients the clinical value of a standardized questionnaire (Gaudenz questionnaire) and the standing clinical stress test were determined in the diagnosis of urinary incontinence. The sensitivity, specificity and predictive value of the positive and negative test of both methods were ascertained. As opposed to the final urodynamic result the clinical stress test alone showed a sensitivity of 48% (specificity 70%) in the diagnosis of genuine stress incontinence. 82% of all patients with stress incontinence were ascertained by the questionnaire, but only 54% were classified correctly as negative. The specificity of both methods combined was 94% and the predictive value 89%. On the other hand the questionnaire's predictive value in the diagnosis of urge incontinence was 9% (specificity 58%). However, the predictive value of both questionnaire and standing clinical stress test, combined, rose to 15%. Our results statistically demonstrate that the use of both methods together provides more significant information than the use of either separately.