Screening for early familial ovarian cancer with transvaginal ultrasonography and colour blood flow imaging.

OBJECTIVE--To assess the value of transvaginal ultrasonography with colour blood flow imaging in detecting early ovarian cancer in women with a family history of the disease. DESIGN--Study of self referred symptomless women with a close relative who had developed the disease. Each woman was screened to detect persistent lesions and defined changes in ovarian volume. Morphological score and pulsatility index were recorded. SETTING--Ovarian screening clinic. SUBJECTS--1601 self referred women. INTERVENTIONS--Women with a positive screening result were recommended to have further investigations. MAIN OUTCOME MEASURES--Findings at surgery and histology of abnormal ovaries. Morphological score > or = 5 and pulsatility index < 1.0 at last scan. RESULTS--Women were aged 17 to 79 (mean 47) years; 959 (60%) were premenopausal, 469 (29%) were naturally postmenopausal, and 173 (11%) had had a hysterectomy. 157 women had a pedigree suggestive of the site specific ovarian cancer syndrome and 288 of multiple site cancers. 61 women had a positive screening result (3.8%, 95% confidence interval 2.9 to 4.9%), six of whom had primary ovarian cancer detected at surgery (five stage Ia, one stage III). Use of a high morphological score or a low pulsatility index increased the odds of finding ovarian cancer from 1:9 to about 2:5 (1:1 in the highest risk groups). Five interval cancers were reported (three ovarian and two peritoneal). Eight of the 11 cancers developed in women with pedigrees suggestive of inherited cancer. CONCLUSIONS--Transvaginal ultrasonography with colour flow imaging can effectively detect early ovarian cancer in women with a family history of the disease. The screening interval should be less than two years.     

Transabdominal ultrasound screening for early ovarian cancer.

OBJECTIVE--To assess the value of ultrasonography in a screening procedure for early ovarian cancer. DESIGN--Prospective study of at least 5000 self referred women without symptoms of ovarian cancer. Each woman was scheduled to undergo three annual screenings (consisting of one or more scans) to detect grossly abnormal ovaries or non-regressing masses. SETTING--The ovarian screening clinic at King''s College Hospital, London. SUBJECTS--5479 Self referred women without symptoms (aged 18-78, mean age 52). INTERVENTIONS--Women with a positive result on screening were referred for laparoscopy or laparotomy, or both. MAIN OUTCOME MEASURES--Findings at surgery and from histology of abnormal ovaries. RESULTS--A total of 14,594 screenings (15,977 scans) were performed. A positive result was obtained at 338 screens (2.3%) comprising 326 subjects (5.9%). Five patients with primary ovarian cancer (four stage Ia, one stage Ib; two at first screening three at second) were identified (prevalence 0.09%). An additional four patients had metastatic ovarian cancer (three at first screening, one at second). The apparent detection rate was 100%. It was not possible to differentiate between the ultrasonic appearance of early malignant and benign tumours. The rate of false positive results for primary ovarian cancer was 3.5% at the first screening, 1.8% at the second, and 1.2% at the third. Overall the rate of false positive results was 2.3%; the specificity was 97.7% and the predictive value of a positive result on screening was 1.5%. The odds that a positive result on screening indicated the presence of an ovarian tumour, any ovarian cancer, or primary ovarian cancer were about one to two, one to 37, and one to 67 respectively. CONCLUSION--Ultrasonography can be used to screen women without symptoms for persistent ovarian masses that will include early ovarian cancer.     

Technetium-99m autologous phagocyte scanning: a new imaging technique for inflammatory bowel disease.

A method to determine the extent of active inflammatory bowel disease using selective labelling of autologous neutrophils and monocytes by phagocytosis of a technetium-99m (99mTc) stannous oxide colloid is described. Unlike leucocyte scanning techniques using Indium-III (IIIIn), the 99mTc colloid scan uses a cheap, readily available isotope, which specifically labels phagocytes. Scan results in 20 patients with inflammatory bowel disease were compared with barium examinations and colonoscopic appearances. There was close agreement in 15 of 20 patients as to the extent of mucosal disease. In four cases the scan showed more extensive disease than was suggested by barium examination. The scan showed terminal ileal Crohn''s disease in three patients in whom the barium studies of the ileum had been reported as normal. In four patients with inactive disease and normal barium examinations no activity was seen on the scans. The 99mTc phagocyte scan is a sensitive, reliable means of determining the extent of active inflammatory bowel disease and can be used to quantify disease activity.     

AFLP: a new technique for DNA fingerprinting.

A novel DNA fingerprinting technique called AFLP is described. The AFLP technique is based on the selective PCR amplification of restriction fragments from a total digest of genomic DNA. The technique involves three steps: (i) restriction of the DNA and ligation of oligonucleotide adapters, (ii) selective amplification of sets of restriction fragments, and (iii) gel analysis of the amplified fragments. PCR amplification of restriction fragments is achieved by using the adapter and restriction site sequence as target sites for primer annealing. The selective amplification is achieved by the use of primers that extend into the restriction fragments, amplifying only those fragments in which the primer extensions match the nucleotides flanking the restriction sites. Using this method, sets of restriction fragments may be visualized by PCR without knowledge of nucleotide sequence. The method allows the specific co-amplification of high numbers of restriction fragments. The number of fragments that can be analyzed simultaneously, however, is dependent on the resolution of the detection system. Typically 50-100 restriction fragments are amplified and detected on denaturing polyacrylamide gels. The AFLP technique provides a novel and very powerful DNA fingerprinting technique for DNAs of any origin or complexity.     

Cells on microspheres: a new technique for flow cytometric analysis of adherent cells

Technical problems have previously prevented the application of fluorescence activated cell sorting to the study of adherent cell populations. We have developed a procedure for attachment of human monocyte-macrophages to 14-20 micrometer microspheres. These adherent cells on microspheres retained phagocytic capacity, could be stained for cell surface antigens using indirect immunofluorescence, and could be maintained in long-term culture. They could be examined and sorted on a fluorescence activated cell sorter while still in the adherent state. This technique facilitates the flow cytometric study of adherent cells and permits the isolation of subpopulations of these cells.     

Contact x-ray microscopy. A new technique for imaging cellular fine structure.

Contact x-ray microscopy potentially allows living, wet cells to be visualized at a resolution of up to 100 A. Furthermore, differential absorption by specific elements permits the study of the distribution of those elements in biological specimens. In contact x-ray microscopy, soft x-rays (10 A to 100 A) pass through a biological sample and expose an underlying x-ray sensitive polymer (resist), producing an image that reflects the photon absorbance within the specimen. The high penetrating power of soft x-ray enables images to be obtained from specimens up to several microns thick. In this paper, the technique is described, some of the areas currently under study are considered, and biological examples of the use of contact x-ray microscopy are given.     

Promise of new imaging technologies for assessing ovarian function

Advancements in imaging technologies over the last two decades have ushered a quiet revolution in research approaches to the study of ovarian structure and function. The most significant changes in our understanding of the ovary have resulted from the use of ultrasonography which has enabled sequential analyses in live animals. Computer-assisted image analysis and mathematical modeling of the dynamic changes within the ovary has permitted exciting new avenues of research with readily quantifiable endpoints. Spectral, color-flow and power Doppler imaging now facilitate physiologic interpretations of vascular dynamics over time. Similarly, magnetic resonance imaging (MRI) is emerging as a research tool in ovarian imaging. New technologies, such as three-dimensional ultrasonography and MRI, ultrasound-based biomicroscopy and synchrotron-based techniques each have the potential to enhance our real-time picture of ovarian function to the near-cellular level. Collectively, information available in ultrasonography, MRI, computer-assisted image analysis and mathematical modeling heralds a new era in our understanding of the basic processes of female and male reproduction.     

The role of CA 125 in screening for ovarian cancer

Ovarian cancer has the worst prognosis of any gynaecological malignancy, primarily because it tends to present at an advanced stage. The excellent survival rates of early stage disease have provided the rationale for efforts to detect ovarian cancer early by screening, in the hope that survival rates will be improved. Available data suggests that CA 125 is elevated in the majority of epithelial ovarian malignancies prior to clinical presentation. Large trials of screening for ovarian cancer indicate that using a CA 125 cutoff value of 30 U/mL has good sensitivity, but inadequate specificity for detecting preclinical disease. Use of transvaginal ultrasonography as a second-line test in women with elevated CA 125 levels improves specificity to acceptable levels, as does use of a mathematical algorithm which analyses rates of change of CA 125. Two major randomised controlled trials, investigating the effect of screening strategies incorporating CA 125 on mortality, are currently underway.     

Colorectal cancer screening: a new strategy for the demonstration of occult intestinal bleeding

The topic of colorectal cancer screening is discussed with special emphasis on its history and improvement of its methodology. The author's own results are evaluated in terms of international data published in literature in order to put forward his proposals for a new strategy. The devastating power and endemic character of colorectal cancers is stressed and the development of screening activities is recommended to accomplish within the frame of the complex health service.     

The HOME microscope workstation. A new tool for cervical cancer screening.

The Highly Optimized Microscope Environment (HOME) is a computerized microscope design for assisting pathologists and cytotechnologists in routine clinical tasks. The prototype system consists of an IBM PC-compatible computer and a light microscope in which a built-in high-resolution computer display image is super-imposed on the optical image of the specimen. Also, an encoding stage and objective turret encoder are used to provide continuous monitoring of the stage coordinates and microscope magnification to the computer. This allows any position on the stage to be uniquely defined. Software, written in C language and running under the MS-DOS/MS-Windows environment, is controlled by means of a mouse-driven cursor. A specific application has been developed for cervical cancer screening, taking into account the needs and constraints of microscopists performing this task. Informatics tools offered by the HOME system provide them with precise flagging and relocation of objects on the slide, control of the scanning pathway, and ability to write and print the report directly through the microscope. The computer files generated by microscopic examination are stored and contain information available for quality control assessment and laboratory management.