Serum tetranectin as a preoperative indicator for postoperative complications in Danish ovarian cancer patients.

OBJECTIVE: The association between tetranectin (TN) and selected lifestyle factors (smoking and alcohol) and the postoperative complication rate for ovarian cancer (OC) patients undergoing primary cytoreductive surgery has not yet been characterized. The aim of the study was to examine the value of TN, smoking and alcohol as indicators of postoperative complications in OC patients. METHODS: Serum TN was measured for 374 OC patients undergoing primary cytoreductive surgery. In addition, they reported their smoking and alcohol status. The prognostic value of variables was found with univariate and multivariate analyses using logistic regression analysis. RESULTS: In univariate analysis TN was the only one out of 8 variables that significantly predicted postoperative complications (OR=0.55 (95% CI: 0.34-0.87), P=0.01). High preoperative serum TN was associated with a low risk of postoperative complications. Stepwise reduction of the multivariate model demonstrated that TN and histology were the only significant co-variables (TN, OR=0.51 (95% CI: 0.32-0.83), P=0.006; histology, OR=1.70 (95% CI: 1.02-2.82), P=0.041). TN was the only indicator, which was statistical significant in both univariate and multivariate analyses. CONCLUSION: Preoperative serum TN is a significant indicator of postoperative complications in Danish OC patients and deserves to be validated in larger future studies.

Three new potential ovarian cancer biomarkers detected in human urine with equalizer bead technology.

OBJECTIVE: To examine whether urine can be used to measure specific ovarian cancer proteomic profiles and whether one peak alone or in combination with other peaks or CA125 has the sensitivity and specificity to discriminate between ovarian cancer pelvic mass and benign pelvic mass. METHODS: A total of 209 women were admitted for surgery for pelvic mass at the Gynaecological Department at Rigshospitalet, Copenhagen. Of the women, 156 had benign gynaecological tumors, 13 had borderline tumors and 40 had malignant epithelial ovarian cancer. The prospectively and preoperatively collected urine samples were aliquotted and frozen at -80 degrees until the time of analysis. The urine was fractionated using equalizer bead technology and then analyzed with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Biomarkers were purified and identified using combinations of chromatographic techniques and tandem mass spectrometry. RESULTS: Benign and malignant ovarian cancer cases were compared; 21 significantly different peaks (p<0.001) were visualized using Mann-Whitney analysis, ranging in m/z values from 1,500 to 185,000. The three most significant peaks were purified and identified as fibrinogen alpha fragment (m/z=2570.21), collagen alpha 1 (III) fragment (m/z=2707.32) and fibrinogen beta NT fragment (m/z=4425.09). The area under the receiver operator characteristic curve (ROC AUC) value for these three peaks in combination was 0.88, and their ROC AUC value in combination with CA125 was 0.96. CONCLUSION: This result supports the feasibility of using urine as a clinical diagnostic medium, and the ROC AUC value for the three most significant peaks in combination with or without CA125 demonstrates the enhanced prediction performance of combined marker analysis.

Validation of epithelial ovarian cancer and fallopian tube cancer and ovarian borderline tumor data in the Danish Gynecological Cancer Database.

OBJECTIVE: To validate the data on epithelial ovarian cancer, fallopian tube cancer and borderline ovarian tumors registered in the nationwide Danish Gynecological Cancer Database (DGCD) in 2005 and 2006. The DGCD is a multidisciplinary database that contains data for research and quality improvement. DESIGN: Comparative registry-based study supplemented with data from medical records. SETTING: Six hospitals in Denmark. PARTICIPANTS: Women registered with epithelial ovarian cancer, fallopian tube cancer and borderline ovarian tumor. MAIN OUTCOME MEASURE: Data completeness and strength of agreement. RESULTS: The estimated completeness of reporting to the DGCD was 94.2% and the strength of agreement between the variables in the DGCD and the medical file varied from moderate to very good. The important quality indicator 'complication' had the lowest strength of agreement. CONCLUSION: The validity of ovarian cancer data in the DGCD is sufficient for quality monitoring in gynecological oncology.

Preoperative CA125 as a prognostic factor in stage I epithelial ovarian cancer.

The purpose of the present study was to evaluate preoperative CA125 as a prognostic factor in stage I epithelial ovarian cancer (EOC). Preoperative serum CA125 levels from 118 women with FIGO (International Federation of Gynaecology and Obstetrics) stage I EOC were analysed and the prognostic value was evaluated and compared with other prognostic factors (age, grade, substages, histologic type). By the Kaplan-Meier estimate we demonstrated that patients with stage I EOC and preoperative serum CA125 levels <65 U/mL had a significantly longer survival compared to stage I EOC patients with preoperative serum CA125 > or = 65 U/mL (p=0.01). The results from the present study may be useful for decision making respecting postoperative chemotherapy in stage I EOC patients. Serum CA125 levels might therefore be included as a prognostic factor in future clinical trials of stage I EOC.

[Uterine rupture during second trimester abortion induced with misoprostol]. / Uterusruptur ved induktion af andettrimesterabort med misoprostol.

A 27-year-old woman with one prior cesarean section and one vaginal delivery was seen with a request for termination of pregnancy in her 17th week of pregnancy. Using vaginal misoprostol for two days the vaginal delivery failed. The fetus was giving way of previous scar resulting in rupture of the uterus, loss of blood and suture of uterus by laparotomy.

Prolonged length of hospital stay in Denmark after nephrectomy.

INTRODUCTION: Implementation of the principles of a fast-track surgical programme resulted in a decrease in the length of hospital stay after open nephrectomies. The aim of this study was to describe the regional distribution of nephrectomies, postoperative hospital stay and mortality. MATERIAL AND METHODS: This study was based on data extracted from the Danish National Patient Registry for the 2000-2009-period. RESULTS: A total of 6,790 nephrectomies were performed. The mean postoperative stay and mortality decreased from 10.1 days and 2.6% during the 2000-2004-period to 8.3 days (p > 0.05) and 1.7% (p < 0.05) during the 2005-2009-period. A significant decrease in length of postoperative stay (6.4 versus 9.0 days; p < 0.05) and mortality (0.9% versus 2.1%; p < 0.05) was found between laparoscopic and open nephrectomies, respectively, during the 2005-2009-period. Nephrectomies performed by laparoscopic technique rose from 7.6% to 30.8% (p < 0.05) and laparoscopic nephroureterectomies from 1.7% to 10.3% (p < 0.05) from the 2000-2004-period to the 2005-2009-period. CONCLUSION: We recommend the implementation of fast-track surgery programmes to further decrease postoperative stay and mortality. A further increase in the use of laparoscopy is warranted.

Proteomic biomarkers for overall and progression-free survival in ovarian cancer patients.

PURPOSE: To determine if the level of apolipoprotein A1, hepcidin, transferrin, inter-α trypsin IV internal fragment, transthyretin (TT), connective-tissue activating protein 3 (CTAP3), serum amyloid A1, ß-2 microglobulin (B2M) might have impact on overall and progression-free survival for ovarian cancer (OC) patients. EXPERIMENTAL DESIGN: Serum from 150 OC patients was tested using SELDI-TOF-MS. RESULTS: A proteomic prognostic index (xb-pro) was constructed using the regression coefficients based on inter-α trypsin IV internal fragment, B2M and TT. A multivariable Cox survival analysis including the xb-pro index showed that xb-pro (p<0.0001, HR=2.50, 95% CI: 1.65-3.79), residual tumor after primary surgery (p=0.0005), age (p=0.01) and chemotherapy (p=0.0002) are of independent prognostic value for overall survival. International Federation of Gynecology and Obstetrics stage, performance status, histological type of tumor and serum CA125 were found of no independent value. A proteomic index (xb-pfs) based on B2M and CTAP3 was found to predict progression-free survival (xb-pfs: p=0.008, HR=1.77, 95% CI: 1.17-2.70 together with type of surgery, age and chemotherapy. CONCLUSIONS AND CLINICAL RELEVANCE: We found an index with three proteomic biomarkers (xb-pro) to be of independent prognostic value for overall survival and an index with two proteomic biomarkers (xb-pfs) with evidence of independent prognostic value for progression-free survival.

Comparison of proteomic biomarker panels in urine and serum for ovarian cancer diagnosis.

PURPOSE: The purposes of this study were to confirm previously found candidate epithelial ovarian cancer biomarkers in urine and to compare a paired serum biomarker panel and a urine biomarker panel from the same study cohort with regard to the receiver operating characteristic curve (ROC) area under the ROC curve (AUC) values. EXPERIMENTAL DESIGN: Four significant urine biomarkers were confirmed among 130 pelvic mass patients in the present study. The four biomarkers form a potential urine biomarker panel. From the same study cohort, the potential urine biomarker panel was compared to a serum biomarker panel, consisting of seven proteins/peptides, OvaRI. RESULTS: Multivariate analysis of the urine panel demonstrated a significant differentiation (p<0.0001) between epithelial ovarian cancer patients and patients with benign ovarian pelvic masses. The ROC AUC of the urine panel was 0.84 and the ROC AUC of OvaRI was 0.83. Combining the urine panel with OvaRI demonstrated a significant contribution from both, for urine peaks, OR=2.12 and for OvaRI, OR=1.39; the ROC AUC of this model was 0.88. CONCLUSIONS AND CLINICAL RELEVANCE: We demonstrated that both urine and serum can be used individually or in combination to potentially aid in ovarian cancer diagnostics. Urine proteomic profiling could provide biomarkers for the non-invasive test required in clinical practice.

[Registration of primary ovarian cancer in Denmark]. / Diagnoseregistrering af primaer ovariecancer i Danmark.

The purpose of this status article was to summarise the registration of ovarian cancer in Denmark up to 2007. In Denmark ovarian cancer is registered in four different registers/databases: The Danish Cancer Registry (CR), The Pathology Data Bank (PDB), The National Registry of Patients (LPR) and The Danish Gynaecology Cancer Database (DGCD). All four registers are obligatory, but none are 100% complete. In the future a faithful electronic registration by an electronic patient record will probably complete the variable profit ratio and data completeness.

[Analysis of quality data based on national clinical databases]. / Analyse af kvalitetsdata baseret på landsdaekkende kliniske databaser.

There is little agreement on the philosophy of measuring clinical quality in health care. How data should be analyzed and transformed to healthcare information is an ongoing discussion. To accept a difference in quality between health departments as a real difference, one should consider to which extent the selection of patients, random variation, confounding and inconsistency may have influenced results. The aim of this article is to summarize aspects of clinical healthcare data analyses provided from the national clinical quality databases and to show how data may be presented in a way which is understandable to readers without specialised knowledge of statistics.

Sample handling for mass spectrometric proteomic investigations of human urine.

Because of its non-invasive sample collection method, human urine is an attractive biological material both for discovering biomarkers and for use in future screening trials for different diseases. Before urine can be used for these applications, standardized protocols for sample handling that optimize protein stability are required. In this explorative study, we examine the influence of different urine collection methods, storage temperatures, storage times, and repetitive freeze-thaw procedures on the protein profiles obtained by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Prospectively collected urine samples from 11 women were collected as either morning or midday specimens. The effects of storage temperature, time to freezing, and freeze-thaw cycles were assessed by calculating the number, intensity, and reproducibility of peaks visualized by SELDI-TOF-MS. On the CM10 array, 122 peaks were detected and 28 peaks were found to be significantly different between urine types, storage temperature and time to freezing. On the IMAC-Cu array, 65 peaks were detected and 1 peak was found to be significantly different according to time to freezing. No significant differences were demonstrated for freeze-thaw cycles. Optimal handling and storage conditions are necessary in clinical urine proteomic investigations. Collection of urine with a single and consistently performed protocol is needed to reduce analytical bias. Collecting only one urine type, which is stored for a limited period at 4°C until freezing at -80°C prior to analysis will provide the most stable profiles.

[Basic registration of risk factors in medical records. Malnutrition, overweight, physical inactivity, smoking and alcohol]. / Basale journaloplysninger om risikofaktorer. Underernaering, overvaegt, fysisk inaktivitet, rygning og alkohol.

INTRODUCTION: Lifestyle factors are important for clinical outcome. Systematic and early identification of these factors is important in order to offer relevant lifestyle intervention programmes. The objective was to evaluate whether basic registration of risk factors was understandable, applicable and sufficient in the clinical workday. MATERIALS AND METHODS: Eleven clinical specialists participated from a broad range of departments. They performed identification and registration of malnutrition, overweight, physical inactivity, smoking and harmful alcohol consumption based on medical records from own departments (in total 2420 times). The specialists then evaluated the understanding, applicability and sufficiency (363 times). Their comments were noted. RESULTS: Identification and registration was accomplished for 85% (0-100%) of the records. Except for two fields--"measurements of waist" and "other training programs"--the specialists found the basic registration understandable, applicable and sufficient. They lacked more details regarding stress-response in the information material and pointed out inconsistencies in the wording. Ten specialists found that the recommended clinical approach was possible to implement in the present routines. CONCLUSION: Basic registration of lifestyle factors for adult patients is possible and clinical relevant. It is recommended that the Danish National Board of Health uses the results in future.

[Identification of new ovarian cancer biomarkers with proteomic analyses--the diagnostic tool of the future?]. / Identificering af nye ovariecancerbiomarkører med massespektrometriske proteomanalyser--fremtidens diagnostiske redskab?

New non-invasive diagnostic tests for detection of ovarian cancer in early stages can improve survival. One approach is the proteomic analysis of serum or urine, which may be the technology needed. Preliminary proteomic analyses of serum and urine have shown a higher positive predictive value than that of the combination of serum CA125 and ultrasound examination, which actually is used preoperatively for the ovarian cancer diagnosis (RMI index). Identification of new ovarian cancer biomarkers will optimally be usable as an ovarian cancer-screening tool.

Alcohol intake, type of beverage, and risk of breast cancer in pre- and postmenopausal women.

BACKGROUND: Most studies of the relation between alcohol consumption and breast cancer have shown a modestly increased risk, although the results are still conflicting. METHODS: The aim of this prospective population-based cohort study was to assess the influence of alcohol intake and type of beverage (beer, wine, or spirits) on breast cancer risk in relation to menopausal status. Among 13,074 women aged 20 to 91 years, we examined the relationship between breast cancer risk, total alcohol intake, and type of alcohol in relation to menopausal status. The women were classified as premenopausal or as postmenopausal at younger than 70 years or 70 years or more. RESULTS: During follow-up, 76 premenopausal and 397 postmenopausal women developed breast cancer. Premenopausal women who had an intake of more than 27 drinks per week had a relative risk of breast cancer of 3.49 (95% confidence limits, 1.36-8.99) compared with light drinkers (p = 0.011), whereas there were no differences in risk in the lower-intake categories. The increased risk of breast cancer among premenopausal women was independent of the type of alcohol. Postmenopausal women older than 70 years of age who had an intake of more than six drinks per week of spirits had a relative risk of breast cancer of 2.43 (95% confidence limits, 1.41-4.20) compared with women who consumed less than one drink of spirits per week (p = 0.0014). CONCLUSIONS: Total alcohol intake of more than 27 drinks per week increases breast cancer risk in premenopausal women independently of the type of alcohol. Among postmenopausal women, an intake of spirits of more than six drinks per week increases breast cancer risk.