Contribution of cervical cytology in the diagnostic work-up of patients with endometrial cancer.

INTRODUCTION: Abnormal cervical cytology in patients with endometrial cancer (EC) has been associated with poor outcome. The aim of this study was to evaluate whether cervical cytology could contribute to an improved preoperative identification of high-grade EC (serous, clear cell, carcinosarcoma, high-grade endometrioid EC) in final histology. METHODS: A retrospective cohort study was performed in five hospitals in the Netherlands. A total of 554 patients with EC that underwent primary surgical treatment between 2002 and 2010 were included. Primary outcome was defined as the contribution of abnormal cervical cytology in the preoperative identification of high-grade EC. As secondary outcome, recurrence-free survival (RFS) and disease-specific survival were determined based on preoperative cervical cytology, and compared to the currently established risk factors: myometrial invasion, high-grade and lymph vascular space invasion. RESULTS: Abnormal cervical cytology was present in 45.1%. For patients with preoperative inconclusive and high-grade histology, the presence of abnormal cervical cytology contributed to an improved identification of high-grade EC in final histology (odds ratio [OR] 6.40 [95% confidence interval {CI}: 1.92-21.26]; OR 2.86 [95% CI: 1.14-7.14]), respectively. Patients with abnormal cervical cytology had a significant worse 5-year median RFS. Abnormal cervical cytology was independently related to RFS (hazard ratio 1.67 [95% CI: 1.04-2.68]) and disease-specific survival (hazard ratio 3.15 [95% CI: 1.74-5.71]). CONCLUSIONS: Abnormal cytology contributes to the preoperative identification of patients with high-grade EC, and is associated with compromised outcome. Future studies are warranted to determine whether cervical cytology could be incorporated into preoperative prediction models for lymph node metastasis.

Levator hiatal area as a risk factor for cystocele recurrence after surgery: a prospective study.

OBJECTIVE: To investigate whether increased levator hiatal area, measured preoperatively, was independently associated with anatom-ical cystocele recurrence 12 months after anterior colporrhaphy. DESIGN: Multicentre prospective cohort study. SETTING: Nine teaching hospitals in the Netherlands. POPULATION: Women planned for conventional anterior colporrhaphy without mesh. METHODS: Women underwent physical examination, translabial three-dimensional (3D) ultrasound and magnetic resonance imaging (MRI) prior to surgery. At 12 months after surgery the physical examination was repeated. MAIN OUTCOME MEASURES: Women with and without anatomical cystocele recurrence were compared to assess the association with levator hiatal area on 3D ultrasound, levator hiatal area on MRI, and potential confounding factors. The receiver operating characteristic (ROC) curve was created to quantify the discriminative ability of using levator hiatal area to predict anatomical cystocele recurrence. RESULTS: Of 139 included women, 76 (54.7%) had anatomical cystocele recurrence. Preoperative stage 3 or 4 and increased levator hiatal area during Valsalva on ultrasound were significantly associated with cystocele recurrence, with odds ratios of 3.47 (95% confidence interval, 95% CI 1.66-7.28) and 1.06 (95% CI 1.01-1.11) respectively. The area under the ROC curve was 0.60 (95% CI 0.51-0.70) for levator hiatal area during Valsalva on ultrasound, and 0.65 (95% CI 0.55-0.71) for preoperative Pelvic Organ Prolapse Quantification (POP-Q) stage. CONCLUSIONS: Increased levator hiatal area during Valsalva on ultrasound prior to surgery and preoperative stage 3 or 4 are independent risk factors for anatomical cystocele recurrence after anterior colporrhaphy; however, increased levator hiatal area as the sole factor for predicting anatomical cystocele recurrence after surgery shows poor test characteristics.

The value of imaging of the lungs in the diagnostic workup of patients with endometrial cancer.

OBJECTIVE: Imaging of the lungs is part of the routine diagnostic workup of patients with endometrial cancer. The present study aimed to determine the incidence of lung metastases in patients with endometrial cancer and to evaluate the clinical relevance of preoperative chest imaging in this population. METHODS: A retrospective cross-sectional study was performed in four regional and one university hospital in the southeastern part of the Netherlands. A total of 784 patients with epithelial endometrial cancer diagnosed between 2002 and 2010 in five hospitals were included. Patients were followed up for at least 1 year. RESULTS: Of 784 patients, 541 (69.0%) underwent thoracic imaging and 11 showed findings suspicious for metastases perioperatively or during the 1-year follow-up period. In eight patients, the thoracic metastases were related to their endometrial cancer, resulting in an overall incidence of 1.0% (8/784, 95% CI=0.3-1.7%). These eight patients had high-risk subtypes of endometrial cancer (serous, clear cell or poorly differentiated endometrioid), and the incidence was 4.1% (8/193, 95% CI=1.9-8.3%) for these subtypes. Lung metastases were not detected in any of the patients with low-risk subtypes of endometrial cancer (n=566) at the time of diagnosis (95% CI=0-0.8%). CONCLUSIONS: The probability of detecting thoracic metastases during the diagnostic workup of patients with endometrial cancer is low. The present data suggest that thoracic imaging could be omitted from the diagnostic workup of patients with low-risk endometrial cancer.

When m-selection?

Caswell and Hastings (1980) introduced an explicit model for the relative merits, in terms of the growth rate λ, of developmental shifts vs. fecundity increases. Some aspects of their model are clarified by concentrating on the (fitness>1) half-plane rather than on the (accelerated reproduction) half-plane. There is no strict equivalence between Caswell and Hastings' key parameter [Formula: see text] and the dynamic behaviour of the population which is governed by λ. Thus in some stationary/declining populations time shifts of reproduction (forward or backward, according to the value of [Formula: see text]) are just as effective in promoting a high λ as they are in growing populations; therefore selection for higher m x may, but need not, prevail in stationary/declining populations.

Effect of Bellergal Retard on climacteric complaints: a double-blind, placebo-controlled study.

The effect of Bellergal Retard (BR) on climacteric complaints was evaluated versus a placebo in an 8-wk double-blind study, followed by a 4-wk open study in which only BR was used as medication. There was a marked decrease in complaints in both the BR and the placebo groups. Statistically significant differences were observed between the groups after 2 and 4 wk of treatment, indicating superior results with BR. After 8 wk of study however, these differences were no longer apparent. It was concluded that studies on medication for climacteric complaints should not only be placebo-controlled, but also be of at least 8 to 12 wk duration for proper evaluation.

Fetal and maternal transcutaneous PCO2 levels during labour and the influence of epidural analgesia.

The Departments of Obstetrics and Gynaecology of the Hvidovre University of Copenhagen and the Free University of Amsterdam collaborated in a study on the relationship of maternal and fetal acid-base state in the intrapartum period. Transcutaneous PCO2 levels of mother (tcPCO2m) and fetus (tcPCO2f) were continuously recorded in 52 patients during labour. TcPCO2f and tcPCO2m correlated significantly (r = 0.42, P < 0.002). During the first stage of labour, a rather stable level was found for tcPCO2f (7.7 +/- 1.6 kPa) and tcPCO2m (4.4 +/- 0.8 kPa). TcPCO2m decreased significantly to 3.8 +/- 0.7 kPa (P < 0.01) in the hour before full cervical dilatation, probably due to maternal hyperventilation as a reaction to painful uterine contractions. TcPCO2f likewise showed a tendency to a decrease to a mean value of 7.4 +/- 1.5 kPa. In eight cases epidural analgesia was applied because of painful uterine contractions. Prior to the epidural analgesia, tcPCO2m (3.8 +/- 0.8 kPa) and tcPCO2f (6.7 +/- 1.7 KPa) were significantly lower in this subgroup compared to the total population. After pain relief by application of epidural analgesia, tcPCO2m and tcPCO2f returned to the population mean.

Dysmenorrhea related to gallstone spilling after laparoscopic cholecystectomy.

A 28-year-old woman is presented with severe dysmenorrhea since a previous laparoscopic cholecystectomy for cholelithiasis. Spilled gallstones were embedded in the Douglas cavity and the visceral peritoneum of the genitalia interna. Dysmenorrhea was treated successfully by laparotomic hysterectomy and removal of all gallstones.

Fetal transcutaneous PCO2 measurements during labour.

The departments of Obstetrics and Gynaecology of the Universities of Bonn and Copenhagen and the Free University of Amsterdam cooperated in the European Community Concerted Action Project 'New methods for Perinatal Surveillance'. In 95 patients fetal transcutaneous PCO2 (tcPCO2) recording (measuring temperature 41 degrees C) during labour was evaluated regarding its clinical applicability. During the first stage of labour fetal tcPCO2 was rather stable at a level of 7.3 +/- 1.4 kPa. In the second stage there were marked differences between the three subpopulations. In the first stage of labour the correlation between tcPCO2 and PCO2 in fetal blood samples was 0.38 (P = 0.02) and in the second stage -0.20 (P = 0.36). The correlation of fetal tcPCO2 with umbilical artery PCO2 was 0.30 (P = 0.01) and with pH -0.30 (P = 0.01). Using a fetal tcPCO2 level of 8.0 kPa as a cut-off point to predict an umbilical artery pH less then 7.20, sensitivity was 88%, specificity 65%, positive predictive value 29% and negative predictive value 97%. The likelihood ratio of a positive test was 2.47 and of a negative test 0.13. It is concluded that fetal tcPCO2 possibly can be an additional tool to exclude fetal acidosis. In case of values above 8.0 kPa further evaluation of the fetal acid-base balance is indicated.

Study on causes and prevention of electrostatic charge build-up during extracorporeal circulation.

For many years it has been known that roller pumps interfere regularly with the electrocardiogram (ECG) signal. This electrical activity is also considered responsible for the electrostatic charge build-up in some oxygenators with a plastic heat exchanger. During use of such an oxygenator, an electrical shock can be felt when touching the device. In the absence of a provoked discharge, a spontaneous discharge may occur. The construction of the heat exchanger and the use of nonconductive materials enable some devices to function as a capacitor. If the voltage difference across the fibre wall is too high, an electrostatic discharge may occur. In 1997, four blood-to-water leaks in Maxima Forté oxygenators were reported on a worldwide basis. After thorough research by Medtronic Cardiac Surgery (Cardiopulmonary Division), the cause of the leaks was found to be an electrothermal event across the fibre wall of one single fibre. No patient injuries were reported in any of the events. Medtronic patented a number of US Food and Drug Administration-approved and patient-safe solutions to prevent this electrostatic charge build-up. We studied the electrostatic phenomenon in order to clarify the clinical aspects. The in vitro part of the study is related to the behaviour of the Medtronic Biopump and the Stockert Shiley roller pump--in combination with the use of a PVC or silicone pumpheader. Subsequently, we have investigated the influence of the rotation or flow of both types of blood pumps and occlusion settings on the roller pump. Furthermore, we tried to capture the electrical charge generated by the roller pumps in a capacitor and in some oxygenators with different types of heat exchanger. Finally, we tested the external CEL (Charge Equalization Line) and the internal 'Gold Wire' charge equalization systems, both patented by Medtronic. In the in vivo part of the study, 15 patients were divided into three groups of five patients each. In the first group a roller pump with a PVC pumpheader was evaluated and, in the second group, a roller pump with a silicone pumpheader. The third group consisted of the Medtronic Biopump. In all the groups, a Maxima Forté oxygenator with the external CEL protection was used. Owing to the fact that, at the time, the Maxima Forté 'Gold Wire' oxygenator was not available for clinical use, only the external CEL could be evaluated.

Obstetrical and neonatological aspects of a child with atresia of the small bowel.

A patient was admitted to the hospital in the 31st week of gestation because of reduced sensation of fetal movements and a pathologic fetal heart rate tracing (Fig. 1). At first no underlying pathology could be found. After a week she developed a polyhydramnios. After repeated ultrasonographic examinations an atresia of the fetal small bowel was suspected (Fig. 2). The diagnosis could be confirmed after birth and on the same day the child was operated on. An atresia of the ileum was found. After liberal resection of the atretic part, recovery was complete. The malformation has an incidence of 1: 12,500-20,000. The etiology is thought to be a temporary or definite obstruction of a mesenterial artery branch, supplying the small bowel of the fetus. It develops after organogenesis and could be caused by kinking of an artery during rotation, an embolus, amniocentesis, volvulus, intussusception or snaring at the umbilical ring. Polyhydramnios is the first symptom in about one third of the cases. Diagnosis can be confirmed by fetography or ultrasonography. The latter is preferred because of its non-invasivity. In amniotic fluid, high levels of bile salts (up to thirty times the normal level) have been described in combination with atresia of the small bowel. A diminished disacharidase activity is also ascribed to it. Most of the time the diagnosis is suspected after birth on the basis symptoms such as a gastric aspirate of more than 25 cc, bile vomiting within a few hours, absence of meconium stool or distension of the abdomen. It can be confirmed by X-ray examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Transcutaneous and arterial carbon dioxide tension at various conditions of fetal stress in lambs.

In an acute fetal lamb model the relation between arterial PCO2 (PaCO2), transcutaneous PCO2 (tcPCO2) and pH was studied at different conditions of stress. Occlusion of the maternal common iliac artery for 8 min, umbilical cord obstruction for 5 min and placental embolization were performed subsequently, every time with an interval of 1 h for fetal recuperation. During the first 2 experiments arterial values changed rapidly after occlusion and returned nearly to normal within 30-60 min after the end of occlusion. TcPCO2 started to increase several minutes after occlusion and reached its maximum about 5 min after the end of occlusion. Afterwards a gradual decrease towards the onset value was observed. During placental embolization tcPCO2 did not increase until 15 min before fetal death. It is concluded that tcPCO2 can follow a gradual trend, but not quick changes in PaCO2.

Transcutaneous and arterial carbon dioxide tension during intermittent umbilical cord occlusion in fetal sheep.

To study the relationship between arterial PCO2 (PaCO2) and transcutaneous PCO2 (tcPCO2) intermittent 2-min total umbilical cord occlusions were performed with a 3-min interval (n = 12) in 5 fetal sheep, tcPCO2 was measured continuously. Arterial acid-base balance was analyzed at the end of occlusion periods and at the end of occlusion intervals. During each occlusion, PaCO2 increased 1.9 kPa (p < 0.001) and pH decreased 0.07 units (p < 0.001). Partial recovery occurred between occlusion intervals resulting in development of mild fetal acidemia. The quick fluctuations in PaCO2 during occlusions were not followed by tcPCO2, but tcPCO2 was capable following the trend in PaCO2. Measurement of tcPCO2 may therefore be an additional tool in the detection of the development of fetal acidemia.

Measurement and processing of fetal transcutaneous Pco2 levels.

Because asphyxia is not the only factor influencing fetal heart rhythm, a non-optimal cardiotachogram is not necessarily a sign of fetal distress. It makes further evaluation of the fetal condition advisable, especially determination of the acid-base equilibrium. The method of fetal blood sampling, introduced by Saling, has a number of disadvantages for mother and fetus, because of the invasiveness for both. Further, the measured acid-base equilibrium is only representative for a very short period of time and often repeated micro-blood sampling is necessary. A major problem with regard to determination of the acid-base equilibrium in intermittently obtained fetal blood samples is the inclusion of air bubbles in the sample. When they are introduced into the electrode cuvettes, the measured values cannot be considered reliable. The problem was solved in the Department of Obstetrics and Gynecology of the Vrije Universiteit of Amsterdam with a "pipe" shaped special collecting vessel. Similar measuring results were obtained with the formerly used glass capillary method and the special collecting vessel method. Continuous, non-invasive methods have been pursued to avoid the above mentioned problems. Fetal transcutaneous Po2 measurement has been possible for years, but does not provide adequate information during the important second stage of labor because of methodological problems. Continuous fetal tissue pH surveillance is possible, but it also has an invasive character and is technically difficult to perform, leading to many methodological failures. Recently, continuous transcutaneous Pco2 measurement tcPco2 became available. A good correlation was found with simultaneously measured Pco2 levels in fetal blood samples and with those of umbilical artery blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclophosphamide, epirubicin and cisplatin (CEP) versus epirubicin plus cisplatin (EP) in stage Ic-IV ovarian cancer: a randomized phase III trial of the Gynecologic Oncology Group of the Comprehensive Cancer Center Limburg.

Cisplatin is the most important drug in the treatment of advanced ovarian cancer. The role of anthracyclines is controversial. We compared a combination of epirubicin plus cisplatin (EP) with a regimen of cyclophosphamide, epirubicin and cisplatin (CEP). Patients with stage Ic-IV ovarian cancer were randomized to receive either epirubicin 100 mg/m2 plus cisplatin 75 mg/m2 q 4 weeks or cyclophosphamide 500 mg/m2 plus epirubicin 75 mg/m2 plus cisplatin 50 mg/m2 q 4 weeks, which we considered the reference treatment based on our previous experience. Patients were initially debulked, followed by six cycles of chemotherapy, or in case primary debulking was insufficient or considered inappropriate, secondary debulking was attempted in selected cases after sufficient chemotherapy-induced regression. Optimal debulking was defined as residual lesions < or = 2 cm. A total of 210 patients (191 eligible) were randomized. Results did not show significant differences in all major endpoints (pathologically documented complete response and survival). The median survival for all patients was 34 months, for patients with stage III 26 months, for patients with stage IV 20 months and it has not been reached for patients with stage Ic-II. As no significant differences between an equitoxic regimen of EP and CEP were detected, it might be more useful to look again at the anthracyclines as part of combination chemotherapy instead of the alkylating agents.