Diagnostic accuracy of haptoglobin within ovarian cyst fluid as a potential point-of-care test for epithelial ovarian cancer: an observational study.

OBJECTIVE: To investigate haptoglobin within ovarian cyst fluid (OCF) as a diagnostic biomarker for epithelial ovarian cancer (EOC) and develop an in vitro diagnostic point-of-care device test (IVDPCT) for use in the operating theatre. DESIGN: Retrospective and prospective cohort study. SETTING: South-East Asia. POPULATION: Women with suspicious ovarian cysts. METHODS: Proteomic, immunohistochemical and ELISA methods measured haptoglobin in OCF to differentiate benign and EOCs. Diagnostic performance of haptoglobin was compared with CA125, risk malignancy indices (RMI) and frozen section. Blinded validation of the IVDPCT was performed. MAIN OUTCOME MEASURES: Prediction of malignancy. RESULTS: Haptoglobin concentration measured by ELISA was 0.70 ± 0.09 mg/ml in patients with benign cysts (n = 87), 6.22 ± 0.53 mg/ml in early stage-EOC (n = 17), and 6.57 ± 0.65 mg/ml in late stage-EOC (n = 20). Haptoglobin in EOCs was significantly higher than in benign cysts (P < 0.0001). Haptoglobin using rapid colorimetric assay (RCA) on a training set had a sensitivity of 97.3% and a specificity 92.0%, comparable to ELISA and frozen sections. The haptoglobin AUROC curve was 0.999 (95% CI 0.997-1.000) compared with 0.895 (95% CI 0.814-0.977, P < 0.05) for CA125. Haptoglobin performed significantly better than all the RMIs (P < 0.01). Blinded validation studies showed a minor drop in average diagnostic performance (sensitivity 85.2% and specificity 90.5%) compared with the training set. However, when compared with frozen section, haptoglobin was no worse in diagnostic accuracy for malignancy. CONCLUSION: Haptoglobin was identified as a biomarker for the detection of EOC with potential as a point-of-care diagnostic tool. TWEETABLE ABSTRACT: Haptoglobin within ovarian cyst fluid: a biomarker for epithelial ovarian cancer and point-of-care diagnostics.

Accuracy of frozen section in the diagnosis of ovarian tumours.

The purpose of our retrospective study was to assess the accuracy of intraoperative frozen section diagnosis compared to final paraffin diagnosis in ovarian tumours at a gynaecological oncology centre in the UK. We analysed 66 cases and observed that frozen section consultation agreed with final paraffin diagnosis in 59 cases, which provided an accuracy of 89.4%. The overall sensitivity and specificity for all tumours were 85.4% and 100%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) were 100% and 89.4%, respectively. Of the seven cases with discordant results, the majority were large, mucinous tumours, which is in line with previous studies. Our study demonstrated that despite its limitations, intraoperative frozen section has a high accuracy and sensitivity for assessing ovarian tumours; however, care needs to be taken with large, mucinous tumours.

The association with age, human tissue kallikreins 6 and 10 and hemostatic markers for survival outcome from epithelial ovarian cancer.

PURPOSE: To assess known cancer biomarkers CA-125, human tissue kallikreins KLK6 and KLK10, hemostatic markers and age with 5-year survival outcome from epithelial ovarian cancer. METHODS: Forty-one benign cyst cohorts and 83 patients diagnosed with ovarian cancer were recruited. The following assays were performed: fibrinogen, vWF antigen, D: -dimer, ATIII activity, tPA, PAI-1, uPAR, KLK6, KLK10 and CA-125. Follow-up visits of cancer patients of more than 60 months were noted. Data between those who survived past 60 months and mortality from cancer were analyzed. RESULTS: Only 24 patients lived past 60 months, and 31 died (advanced stage n = 27). Those living past 60 months were significantly older and associated with similar pre-operative levels seen in benign cyst cohorts especially for KLK6, fibrinogen, vWF, AT levels despite upregulation of D: -dimer, CA-125 and KLK10. Ovarian cancer cohorts living past 60 months were younger than those who died within 12 months (n = 12). Mortality within 12 months was associated with older age, upregulation of KLK6, fibrinogen, D: -dimer, vWF, tPA antigen and reduced ATIII levels. Similarly, mortality within 36 months of disease showed older age with upregulation of CA-125, KLK6 D: -dimer vWF antigen and tPA antigen levels. Late stage cancer (III/IV) showed upregulated CA-125, KLK6, KLK10, D: -dimer and reduced AT compared to early stage cancer (I/II). The 5-year survival rate for early cancer was 80%, advanced 22.9% and overall 5-year survival rate was 43.6%. CONCLUSION: Older age together with the novel biomarkers studied and their association with adverse outcome from epithelial ovarian cancer was seen especially within 12 and 36 months of disease. Those who lived past 60 months of disease showed similar pre-operative levels seen in benign cyst cohorts despite elevated D: -dimer, CA125 and KLK 10. An enlarged study is needed to confirm these findings.

FastFISH: technique for ultrarapid fluorescence in situ hybridization on uncultured amniocytes yielding results within 2 h of amniocentesis.

Rapid aneuploidy detection methods allow prenatal diagnosis results to be released within 48 h, but not on the same day as the invasive test. We aimed to develop a rapid fluorescence in situ hybridization (FISH) method (FastFISH) that releases accurate results on the same day as amniocentesis. FastFISH was optimized to be completed within 2 h of sample collection using CEP and LSI probes for chromosomes 13, 18, 21, X, Y and DiGeorge syndrome (DGS). The technique was tested on 100 consecutive amniotic fluid samples in a blinded study. It was also validated as a 1-day molecular genetic test on three representative fetal tissue samples: chorionic villus, amniotic fluid and fetal blood. In the blinded study, FastFISH results were ready within 2 h of sample collection. Of the 100 amniotic fluid samples, 49 male and 50 female fetuses were identified. One fetus was 47, XXY (Klinefelter syndrome). Three fetuses had trisomy 21. One fetus suspected of DGS by ultrasound was identified as normal. Results of FastFISH analyses in all 100 cases were concordant with their karyotypes (100% accuracy; lower 95% CI, 97.05%). In the 1-day test validation, all results were released on the same day and were concordant with their respective karyotypes. FastFISH allows results to be released on the same day as amniocentesis. It represents the necessary development for a 1-day prenatal diagnosis service.

Early enteral feeding following major abdominal surgery for recurrent gynaecological cancer.

We studied the safety of early postoperative enteral feeding in 22 patients with recurrent gynaecological cancer who underwent major abdominal surgery including extensive adhesiolysis, bowel resection and bowel anastomosis. A total of 19 patients (86.4%) had been treated by both radical surgery and radiation therapy with curative intent. In 18 cases (81.8%), the indication for surgery was bowel obstruction. Preoperative total parenteral nutrition (TPN) was not used. Enteral feeding was given through a gastrostomy tube or a jejunal feeding tube and was commenced within 72 h of completion of surgery. The age range was 30-78 years with a median of 52.8 years. A total of 13 patients (59.1%) had a bowel resection and 17 patients (77.3%) had a bowel anastomosis, all stapled. The median maximum tolerated full strength feeding was 50 ml/h for 18-20 h in a 24 h period and maintained for a median of 9 days. In six patients the feeding was interrupted but was re-commenced in five, in four of whom there was no further interruption of feeding. There were no anastomotic leaks and no cases of aspiration. Postoperative enteral feeding was safe in patients with recurrent gynaecological cancer who had undergone major abdominal surgery and should be considered as an alternative to TPN.

The "tamponade test" in the management of massive postpartum hemorrhage.

OBJECTIVE: Massive postpartum hemorrhage is a major cause of pregnancy-related death in the United States. To date there is no diagnostic test to identify those women with intractable hemorrhage who will need surgery. Delay in making this decision can be catastrophic. The successful use of the inflated stomach balloon of a Sengstaken-Blakemore tube as a therapy for obstetric hemorrhage has been reported previously. Using the insertion of the Sengstaken-Blakemore tube as a diagnostic test has not been reported. An inflated Sengstaken-Blakemore balloon catheter creates tamponade and identifies those who will or will not need surgery. This is the basis for the "tamponade test." We evaluated the tamponade test in the management of women with massive postpartum hemorrhage. METHODS: In this prospective study, 16 cases of intractable postpartum hemorrhage were managed by the tamponade test. All 16 women had persistent bleeding despite the maximal and optimal application of conservative measures. Their condition deteriorated, such that surgical intervention was considered mandatory. It was at this predefined end point that the tamponade test was applied. RESULTS: Fourteen (87.5%) had a positive tamponade test result and therefore did not require surgery. Two (12.5%) had a negative test result and underwent laparotomy. CONCLUSION: This diagnostic test rapidly identifies those patients with postpartum hemorrhage who will require a laparotomy. Even when results are positive, life-threatening hemorrhage is arrested and time is also allowed to correct any consumptive coagulopathy.

Hemostatic and fibrinolytic status in patients with ovarian cancer and benign ovarian cysts: could D-dimer and antithrombin III levels be included as prognostic markers for survival outcome?

We determined the hemostatic and fibrinolytic status in 60 patients with ovarian cancer and benign ovarian cysts. Hypercoagulation, increased platelets, and enhanced fibrinolysis were seen in patients with preoperative ovarian cancer compared to patients with benign ovarian cysts. Enhanced thrombin generation, evidenced by increased F1+2 and decreased antithrombin III (ATIII) levels with further enhanced fibrinolysis by elevated D-dimer, was seen in advanced cancer. Ten ovarian cancer patients died within 13 months after diagnosis and another died at 24 months, all from advanced stage of cancer, except one from stage IC cancer who died at 11 months. The survival rates from the disease at 13 months and 24 months were 66.7% and 45%, respectively. Most of the patients had gone through the complete course of chemotherapy, and those patients still alive have been disease free between 13 and 42 months. No statistical relationships for the hemostatic parameters studied in ovarian cancer patients could be found between those who died and those still living 13 and 24 months after diagnosis, except for ATIII and D-dimer levels. Elevated D-dimer levels were associated with those who died within 13 and 24 months from the disease, and the decreased ATIII levels only reached statistical significance by 24 months. It could be suggested that these two parameters might be useful as systemic prognostic markers in survival outcome from the disease for the first 24 months in advanced ovarian cancer, in addition to the known correlation with the International Federation of Gynecology and Obstetrics stage.

A preliminary study of the immunohistochemical detection of a novel tumour marker, 22-1-1 antigen, in gynaecological cancer specimens.

A novel tumour associated antigen, 22-1-1, has been recently described in association with a cervical adenocarcinoma cell line. The aims of this paper were to study the tissue distribution of this antigen in sections of gynaecological cancer specimens and to compare it with negative controls. Six cases of cervical cancers, 5 cases of endometrial cancers, 4 cases of ovarian cancers and 5 cases each of normal endometrium and cervix were studied. Immunohistochemical staining using streptoavidin-biotin methodology was used for each tumour specimen. This revealed positive staining for the 22-1-1 antigen in 5 out of 6 cases of cervical cancer, 3 out of 5 cases of endometrial cancers, and all 4 cases of ovarian mucinous cystadenocarcinomas. Importantly, the antigen was expressed in the cytoplasm, cell membrane and glandular lumen of adenocarcinoma cells. The 22-1-1 antigen was not detected in normal uterine tissues except in uterine cervix, in which its expression was observed at low levels. This study shows that the 22-1-1 antigen was expressed in cancer cells derived from the uterus, cervix and the ovary and may be a potential tumour marker in the management of gynaecological cancer patients.

The clinical management of male infertility.

Male infertility is a common cause of subfertility for which sperm disorders are the single most common cause. Genetic abnormalities, for example, microdeletions associated with the Y chromosome, defects in the androgen receptor gene and cystic fibrosis have gained recent prominence and it is envisaged that many of the 60% of men for which no cause is found may have a genetic basis for their subfertility. Although an abnormal semen analysis is commonly the first indicator of a male factor problem, further tests are usually required. Empirical treatment with hormones, varicocelectomy and immunological treatment have been proven to be disappointing whilst the treatment of infection and obstruction do not always translate into significantly higher fertility rates. Ejaculatory disorders and impotence can be effectively treated today whilst donor insemination can be offered to men with untreatable infertility. The advent of assisted reproduction and micromanipulation has greatly improved prospects for fertility of men with very poor semen quality. However, the genetic implications of these procedures have to be quickly addressed so that fertility is maximised without risk to the progeny.

Intrapartum fetal oxygen saturation monitoring in a busy labour ward.

OBJECTIVE: To measure the ease of use of a fetal pulse oximeter in a busy labour ward. DESIGN: Descriptive study in the Labour Ward, National University Hospital, Singapore, involving 145 labouring women with singleton pregnancies, and fetuses in cephalic presentation, with cervical dilatation >2 cm and amniotic membranes ruptured. RESULTS: Placement was comfortable. Oxygen saturation (SpO2) readings were obtained in 127 women (87.5%). Adequate readings were obtained a median of 69% of the time the transducer was in situ. SpO2 values in the last 10 min prior to delivery correlated poorly with parameters of neonatal outcome. CONCLUSION: The Nellcor N-400 fetal pulse oximeter and FS14 fetal sensor is a feasible method of intrapartum fetal monitoring in a busy labour ward and is acceptable to labouring women.

Necrotising fasciitis originating from a vulval abscess--a case report.

This article reports a rare case of necrotising fasciitis starting out as a vulval abscess with rapid progression to a potentially lethal condition. Elderly people with medical conditions such as diabetes are especially prone to it. A high index of suspicion and an early surgical consult are essential in improving outcome in this condition. Once diagnosed, aggressive surgical debridement with antibiotic cover is crucial. This is followed up with meticulous nursing care of the large wound till it heals. The various diagnostic points and treatment modalities are also discussed.

Evaluation of a new portable system for cord lactate determination.

To evaluate a new reflectance photometer (Accusport) for blood lactate determination, a prospective non-interventional study was performed on blood obtained from the umbilical cord artery immediately after delivery of the baby in 109 consecutive women. For each sample, the results of cord arterial blood lactate values measured with the reflectance photometer were compared with those obtained using a reference method in the laboratory. The values obtained using Accusport were comparable in accuracy with those obtained using a laboratory reference method (Ektachem 9501RC). The instrument provides a simple and reliable method for determining cord arterial blood lactate levels in a small blood sample.

Fetal oxygen saturation during labour.

OBJECTIVE: To derive oxygen saturation by pulse oximetry (SpO2) values at each cervical dilation in labour in fetuses with normal neonatal outcome. PARTICIPANTS: One hundred and forty-five women at term in established labour with ruptured membranes and cervical dilation at least 2 cm who had normal delivery outcome. The infants had 5 minute Apgar scores > or = 7, birthweight > or = 2500 g, umbilical cord artery pH > or = 7.15 and did not require assisted ventilation or admission to neonatal intensive care. METHODS: Women were monitored continuously with cardiotocography and fetal pulse oximetry using the Nellcor N-400 fetal pulse oximeter and FS-14 fetal oxisensor till delivery. Labour was managed according to established protocol without recourse to SpO2 readings. RESULTS: There was a wide range of SpO2 values during labour in fetuses with normal outcome. Mean values averaged 50% +/- 10% throughout the first stage of labour, with lower ranges of SpO2 values above 30%. There was no significant difference in SpO2 readings at different cervical dilatations in the first stage of labour. Mean SpO2 values in the last 10 minutes before delivery were also not significantly different from those in the first stage of labour. CONCLUSION: The range of SpO2 in 115 healthy fetuses during normal labour was wide, but always above 30%. There was no trend of SpO2 values in this study of 115 fetuses with normal neonatal outcome.

Is there a need to treat hypokalaemia associated with intravenous salbutamol infusion?

OBJECTIVES: To investigate the evolution of metabolic effects associated with intravenous salbutamol infusion given together with 2 doses of intramuscular steroids in the treatment of preterm labour. METHODS: Preterm labour was inhibited with an intravenous infusion of salbutamol in 8 women between 26 and 32(+6) weeks with normal singleton pregnancies. Serum glucose concentration, serum potassium, sodium and insulin concentrations, and total white cell count both during the infusion as well as post-therapy, were plotted against time. RESULTS: Intravenous salbutamol infusion administered at a rate required to inhibit uterine contractions in preterm labour causes a rise in serum glucose and plasma insulin concentrations. The serum glucose and plasma insulin levels peaked soon after cessation of therapy and took 2-3 hours to come to pre-infusion levels. The decline in serum potassium concentration was gradual and plateaued after 2 hours. Once the salbutamol infusion was stopped the potassium levels were back to normal by 2 hours. There is an increase in total white cell count within an hour of the initiation of therapy. CONCLUSION: There is no need to administer insulin for hyperglycaemia and/or potassium for hypokalaemia unless the patient is a known diabetic or when a patient needs immediate surgery.

Fetal breathing recorded by actocardiogram and real--time ultrasonography. A comparison.

BACKGROUND: The aim of the study is to evaluate the ability of fetal actocardiogram to assess fetal breathing movements. METHODS: A descriptive study. Evaluation of the agreement between real-time ultrasound and actocardiographic assessment of fetal breathing movements. Eleven unselected pregnancies admitted because of various pregnancy complications. RESULTS: In six cases the breathing pattern recorded by the actocardiogram correlated to the findings with real-time ultrasonography. In five cases where fetal breathing was observed on the ultrasound screen, the actocardiogram did not either indicate breathing or was of an indecisive appearance. Two cases where no breathing was observed on real-time ultrasound yielded actocardiograms without patterns typical of breathing, but with activity difficult to distinguish from breathing. CONCLUSIONS: With the paper speed set at 3 cm/min it is possible to detect some types of fetal breathing or the absence of breathing with accuracy on the actocardiogram. However, in cases without deep and regular diaphragmatic excursions it is not possible to evaluate breathing with certainty by the actocardiogram.

Mild cervical atypia: a management dilemma.

This study examined 117 patients with mild cervical atypia or atypical squamous cells of uncertain significance; it was found that 25% had histologically proven CIN lesions by colposcopically-directed punch biopsy or cone biopsy. 18% were found to have at least CIN 2 lesions and there was 1 case of invasive cancer. These data strongly support the recommendation of early colposcopic referral in patients with mild cervical atypia.

A comparison between visual estimation and laboratory determination of blood loss during the third stage of labour.

A prospective study was conducted to compare the accuracy of visual estimation of blood loss (EBL) at delivery with laboratory determination of measured blood loss (MBL). It showed that EBL tends to be clouded by the conventional teaching that blood loss at delivery is usually between 200 to 300 mL. Women with MBL up to 150 mL were overestimated and the best correlation was in women with MBL between 150 to 300 mL. There was a tendency to underestimate blood loss when the MBL was between 301 to 500 mL. Of the 9 women with a primary postpartum haemorrhage, only one was correctly diagnosed as such and 3 women were estimated to have blood losses of at least 500 mL but the measured blood losses were all lower. It was concluded that visual estimation of blood loss is inaccurate, especially at the extremes of MBL and that primary postpartum haemorrhage is not detected by visual estimation of blood loss, unless there are associated signs of haemodynamic instability.

Current approach to the management of urinary stress incontinence.

The plethora of treatment modalities available for the treatment of female urinary stress incontinence reflects the uncertainty in the pathophysiology of this condition and the mechanism of cure. No single treatment method is suitable for all patients. For best results, many factors must be considered before choosing the treatment method most suited to the particular patient. This review examines the various treatment options available and attempts to set out criteria for choice of treatment. The role of conservative treatment has been deliberately highlighted especially for young and well motivated women with mild to moderate urinary stress incontinence before surgical treatment is used. The role and limitations of well established surgical procedures like Burch colposuspension and urethroplasty and the more recently introduced procedures like collagen implants, laparoscopic colposuspension and the role of artificial urinary sphincter are also examined.