PAPERS

Transabdominal ultrasound screening for early ovarian cancer

Stuart Campbell, Vijay Bhan, Patrick Royston, Malcolm I Whitehead, William P Collins

AbstractObjective-To assess the value of ultrasono-

graphy in a screening procedure for early ovariancancer.Design-Prospective study of at least 5000 self

referredwomen withoutsymptoms ofovarian cancer.Each woman was scheduled to undergo three annualscreenings (consisting of one or more scans) todetect grossly abnormal ovaries or non-regressingmasses.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 laparo-tomy, or both.Main outcome measures-Findings at surgery and

from histology of abnormal ovaries.Results-A total of 14594 screenings (15 977

scans) were performed. A positive result was ob-tained 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 screeningthree at second) were identified (prevalence 0.09%).An additional four patients had metastatic ovariancancer (three at first screening, one at second). Theapparent detection rate was 100%. It was not possibleto differentiate between the ultrasonic appearance ofearly malignant and benign tumours. The rate offalse positive results for primary ovarian cancer was3-5% at the first screening, 1-8% at the second, and1.2% at the third. Overall the rate of false positiveresults was 2.3%; the specificity was 97-7% and thepredictive value of a positive result on screening was1-5%. The odds that a positive result on screeningindicated the presence of an ovarian tumour,any ovarian cancer, or primary ovarian cancerwere about one to two, one to 37, and one to 67respectively.Conclusion-Ultrasonography can be used to

screen women without symptoms for persistentovarian masses that will include early ovarian cancer.

IntroductionOvarian cancer is an insidious and intractable

disease. The incidence in the United Kingdom in-creases with age to about 50 cases per 100 000 womenper year, and the cumulative risk up to 75 is 1-3%.' 2The disease is responsible for 4-5% of deaths in womenbelow 60. Currently less than 30% of primary cancersare confined to the ovaries at the time of diagnosis andthe overall five year survival rate is less than 25%.Consequently there is an urgent need for an effective,practical procedure to detect the disease at an earlystage when women are without symptoms and the fiveyear survival rate is greater than 80%.3The measurement of a tumour marker (CA-125) in

serum has been proposed as the initial stage of ascreening procedure for early ovarian cancer,5 butmore recent data suggest that the detection rate may beinadequate.6 For the past eight years we have investi-gated the use of real time pelvic ultrasonography as thefirst stage of a screening procedure for early ovarianneoplasms.7 Initially we showed that ovarian size andmorphology assessed by ultrasound examinationagreed well with results obtained by direct measure-ment and observation at laparotomy. Subsequently,the method of assessing ovarian morphology waspubished in more detail together with some preliminaryscreening results.8 Recently an encouraging reportfrom another group has shown the potential value ofultrasonography for the detection of ovarian cancer inwomen attending an outpatient clinic.9 We describethe results of a large prospective study of an ultrasono-graphy based screening procedure for early ovariancancer in relation to menopausal state in self referredwomen over 44 without symptoms.

Subjects and methodsThe plan was to screen at least 5000 self referred

women without symptoms annually for three years.Women were made aware of the study by advertise-ments placed within King's College Hospital or in thelocal or national press, and any woman aged 45 or morecould request a pelvic scan without the need for amedical referral. At each screening the women wereclassified as being either premenopausal (a menstrualperiod within the previous 12 months), artificiallypostmenopausal (due to hysterectomy with ovarianconservation or in one case to radiation treatment), ornaturally postmenopausal (age greater than 35 and atleast one elapsed year since the last menstrual period).Occasionally we recruited a woman who was under 44(about 4% of the total) because of a personal or familyhistory of cancer. One woman (aged 48) did not have auterus at birth and had only one ovary, which wasnormal. Before examination the women completed aquestionnaire designed to provide demographic dataand a relevant personal and family medical history. Ananalysis of the distribution of variates for social class,marital state, parity, and history of infertility indicatedthat the self referred group (between the ages of 45 and60) were similar to the general population of com-parable age according to data from the Office ofPopulation Censuses and Surveys over the period ofthe study.Each screening consisted of one or more ultrasound

examinations (scans). The women were instructed todrink a litre of fluid one hour before each scan. A fullbladder displaces intestinal loops and provides a sonicwindow that enhances inspection of the pelvic organs. "'The ovaries were scanned transabdominally in thetransverse and longitudinal planes with a Diasonics100 mechanical sector scanner (Sonotron, Bedford)using a 3 5 MHz transducer. Up to 30 women a day

BMJ VOLUME 299 2 DECEMBER 1989

Department of Obstetricsand Gynaecology, King'sCollege School of Medicineand Dentistry, LondonSE5 8RXStuart Campbell, FRCOG,professorVijay Bhan, MRCOG, seniorresearch registrarMalcolm I Whitehead,FRCOG, senior lecturerWilliam P Collins, DSC,professor

Department ofEnvironmental andPreventive Medicine,Medical College of StBartholomew's Hospital,London ECIM 6BQPatrick Royston, MSC,statistician

Correspondence to:Professor Collins.

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were scanned. A morphologically normal ovary givesan image with a smooth ovoid outline and a uniform,low level echogenicity similar to that of the myome-trium.8The maximum transverse (D1), anteroposterior

(D2), and longitudinal (D3) diameters of both ovarieswere measured. Ovarian volumes were estimatedaccording to the formula: volume=(7r/6)xD1xD2 xD3. At each screening the result of a scan was regardedas positive if any of three criteria was considered to beabnormal: ovarian morphology (hyperechogenicity orhypoechogenicity), outline (irregular), or volume (>about 20 ml). Women with a normal (negative) resulton scanning were screened again about one year later.Those with an abnormal (positive) result were re-scanned after three to eight weeks to exclude transientchanges in ovarian morphology or size. If the result ofthe scan was still positive the woman was informedabout the nature and possible significance of thefindings. The information was sent to the appropriategeneral practitioner with a recommendation that thepatient should be referred for laparoscopy or laparo-tomy, or both. Ostensibly abnormal ovarian tissuesremoved at surgery were sent for histological examina-tion. The stage of the disease was estimated by thesurgeon, and the final diagnosis was based on thereport from the histologist. If the scan produced anequivocal result the woman was rescanned until thediagnosis was definitive or a decision had been made.All women who had at least one ovary received amaximum ofthree screens. The protocol was approvedby the ethics committee at King's College Hospital.

Histopatholog-Tissues from abnormal ovarieswere examined at the referral hospitals and histologyreports were sent to the ovarian screening clinic atKing's College Hospital. The masses were classifiedaccording to criteria recommended by the WorldHealth Organisation. " The groups were commonepithelial tumours, sex cord stromal tumours, germcell tumours, and tumour-like conditions. The mainsubdivisions of common epithelial tumours werelabelled as serous, mucinous, endometrioid, or clearcell. The tumours were also classified as benign,borderline, or malignant. The tumour-like conditionswere subclassified as simple cysts, solitary folliclecysts, corpus luteum cysts, surface epithelium in-clusion cysts, or parovarian cysts. We were unable(from the pathology reports) to differentiate betweenendometriosis (a tumour-like condition) and an endo-metrioid tumour. Accordingly, all such conditionswere classified as endometrioid tumours for thisanalysis. The stage of each primary ovarian cancer wasdetermined from the operation records according tothe revised recommendations of the InternationalFederation of Gynaecologists and Obstetricians.'2 Atstage Ia the tumour was limited to one ovary and thecapsule was intact. There was no tumour on theexternal surface of the ovary and no ascites waspresent. At stage lb the same criteria applied to bothovaries.

Database and statistical analysis-A database wasestablished using FoxBase running on an IBM PC/XTcompatible microcomputer with a hard disk. A tape

TABLE i-Age and menopausal state ofstudy population atfirst screening. Values are numbers (percentages)ofwomen

Age (years)

Menopausal state v44 45-49 50-54 55-59 -s60 All ages

Premenopausal 184 1457 740 78 5 2464 (45-1)Naturally postmenopausal 9 222 766 792 553 2342 (42-8)Artificially postmenopausal 31 218 217 130 65 661 (12-1)

Total 224(4-1) 1897(347) 1723(31-5) 1000(18-3) 623(11-4) 5467(100)*

*In all, 5479 women were studied: age was not recorded in 11 women and one woman did not have uterus at birth.

TABLE II-Numbers ofscans undertaken at each screening

Screen No

Scan No 1 2 3 Total

1 5198 4576 3894 13 6682 203 230 217 6503 54 68 63 1854 13 23 14 505 5 5 9 196 3 5 1 9

7-12 3 7 3 13

Total 5479 4914 4201 14 594

streamer was used for back up of data. A suiteof programs was developed to facilitate data entry,checking, and retrieval. The detection rate (sensitivity)of the procedure was the proportion of women withprimary ovarian cancer who had a positive result onscreening. This criterion could only be ascertainedwithin the limitation of the study design-that is, wewere unable to ascertain independently whether everypatient who had a negative result on screening was freeof ovarian cancer. For some analyses the number ofwomen with primary or metastatic ovarian cancer wasused. The rate of false positive results for a particularscreen was the proportion of women with a positiveresult on screening who were free of ovarian cancer.Again, this value could only be determined within thelimitation of the study design -that is, we were unableto ascertain by another method the number of womenin the study who did not have ovarian cancer.

ResultsA total of 5479 women were recruited and under-

went the first screening; 4914 (90%) attended for thesecond screening and 4201 (77%) for the third. Table Ishows the age and menopausal state of each woman atthe first screening (first scan). Their mean age was 52(range 18-78). Initially about half of the women wereaged between 50 and 59 and similar proportions werepremenopausal (45%) and naturally postmenopausal(43%). Twelve per cent had undergone an artificialmenopause. The five women above 60 classified aspremenopausal all had menstrual cycles at the startof hormone replacement treatment. At the secondscreening roughly 36% (1644/4568) of the women werepremenopausal and 51% (2330) had had a naturalmenopause. At the third screening the proportionof premenopausal women had decreased to 28%(1099/3889) and the proportion of naturally postmeno-pausal women had increased to 58% (2256). Mostwomen who did not attend for the second and thirdscreenings were naturally postmenopausal and over 60.

Screening and scan variables-The median intervalbetween the first and second screenings was 614 days(range 289-1134 days). The corresponding intervalbetween the second and third screenings was 564 days(range 214-1019 days). Table II shows the number ofscans performed at each screening. Sixty six womenwith at least one abnormal ovary only had one scan at aparticular screen because the clinical ultrasonographerrecommended immediate surgical investigation. Themedian time interval between the first and final scans atthe first screening was 32 days (range 4-756 days). Thecorresponding value at the second screening was 65days (range 14-1099 days). At the third screening themedian time interval increased to 95 days (range6-1097 days).

Outcomes of screening-The proportion of womenwho had a negative result on screening (neither ovaryseemed to be abnormal), a positive and negative result(at least one ovary possibly abnormal at the first scanbut subsequently regarded as normal after one or morerepeat scans; positive, negative), and a positive and

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positive result (positive result on screening and recom-mended for surgical investigations; positive, positive)is shown for each screening in table III. The proportionof positive, positive results dropped from 3 6% at thefirst screening to 1-2% at the third and the ratio ofpositive, negative results for positive, positive resultsrose sevenfold from 0 7 to 5 2.

TABLE iii-Results at each screening. VIalues are numbers (percentages)ofwomen

Result

Screen No Negative Positive, negative* Positive, positivet

I (n=5479) 5145 (939) 139 (25) 195 (36)2 (n=4914) 4568(93-0) 254(5-2) 92 (1 9)3(n=4201) 3889(92-6) 261(6-2) 51(1 2)

Total 654 338

*Result initially positive but abnormality disappeared on rescanning.tOne or more rescans showed abnormality and patient referred for surgicalinvestigation.

Table IV shows for each screening the numbers ofwomen with different combinations of results and thenumbers not attending. Most women had negativeresults at all screenings or negative results followed bynon-attendance.

Ovarian masses at operation-The median time

TABLE Iv-Numbers ofsubjects with different combinations of resultsand non-attendance at each screening

Screen No ofsubjects

1 2 3 (n=5479)

Negative Negative Negative 4061Negative Negative Non-attendance 639Negative Non-attendance Non-attendance 453Positive Non-attendance Non-attendance 112Positive Negative Negative 64Negative Positive Non-attendance 58Negative Negative Positive 45Negative Positive Negative 23Positive Negative Non-attendance 12Negative Positive Positive 5Positive Positive Non-attendance 4Positive Positive Negative 2Positive Negative Positive I

TABLE v-Characteristics ofpatients with ovarian cancer

Screen AgeCase No No (years) Menopausal state Histological diagnosis Stage

Primary cancer1 2 59 Naturally postmenopausal Mucinous cystadenocarcinoma borderline la2 1 53 Naturally postmenopausal Serous cystadenocarcinoma borderline lb3 2* 46 Premenopausal Endometrioid borderline Ia4 2 61 Naturally postmenopausal Serous papillary cystadenocarcinoma Ia5 1 60 Naturally postmenopausal Clear cell carcinoma Ia

Secondary cancer6 1 54 Premenopausal Breast7 2 58 Naturally postmenopausal Breast8 1 60 Artificially postmenopausal Colon9 1 49 Artificially postmenopausal Breast

*Contralateral ovary removed after benign endometrioid tumour detected on first screening.

TABLE VI-Relation between histological classification of 267 ovarian masses removed at laparotomy andovarian morphology observed by ultrasonography

Histological classification of tumours

Epithelial"Tumour Sex cord Germ

Ovarian morphology like"* stromal cell Benign Malignantt Total

Normal 17 1 1 12 31Unilocular cyst 79 4 3 49 5 140Unilocular cyst or solid 12 1 1 1 18 4 46Multilocular cyst 19 1 12 3 35Multilocular cyst or solid 6 1 7 14Solid 1 I

Total 133 8 16 98 12 267

*See World Health Organisation classification.'' tPrimary and secondary.

interval between the final scan at any screening andoperation was 48 days (range 12-191 days). A total of379 ovarian masses were found at operation in the 326women (from 338 screens) who had a positive result onscreening. There were six primary ovarian cancers(five patients, one having bilateral tumours) and sixmetastatic ovarian cancers (four patients, two havingbilateral tumours). Thus nine women had ovariancancer (the prevalence of all cancers was 0-16%; andthe prevalence of primary cancer was 0-09%). Table Vshows some details of the cases. All of the primarycancers were stage Ia or Ib. Most of the other classifiedovarian masses were either tumour-like conditions(50%) or benign epithelial tumours (37%). A further9% were either sex cord stromal or germ cell tumours.About 11% of all ovarian masses were unclassified butjudged to be non-malignant by the surgeon, and thepatient refused further investigation. A further 18% ofthe apparent masses (62 women) observed by ultra-sonography had either resolved spontaneously or werenot of ovarian origin at the time of operation. Twentytwo of these women were premenopausal and 28postmenopausal. Only 12 women (3 7% of those with apositive result on screening) were free of any pelvicdisease at the time of surgical investigation.

Table VI shows the relation between various charac-teristics of ovarian morphology as observed by ultra-sonography with the histological classification of tissuesremoved at operation. It was not possible to identifycharacteristics that were unique to the five earlymalignant tumours. An irregular outline was observedin 76% (101/133) of tumour-like conditions, 75% (6/8)of sex cord stromal tumours, 69% (11/16) of germ celltumours, 70% (69/98) of benign epithelial tumours,and 67% (8/12) of malignant tumours (primary andsecondary).

Evaluation of screening procedure-The screeningprocedure had a detection rate of 100% (within thelimitation of the study design) with an overall rate offalse positive results of 2-3%, as shown in table VII.

TABLE VII-False positive results of screening procedure for earlypriimary ovarian cancer expressed per screen* and overall according tomenopausal state

False positive rate (%) per screen

Menopausal state 1 2 3 Total

Premenopausal 3 5 1-6 1-3 2-4Naturally postmenopausal 3 1 1 8 1.0 1 9rotalt 3-5 1-8 1-2 2-3

*Twelve subjects had positive results at two screenings (see table IV).tIncludes subjects who had artificial menopause.

There was a reduction in the rate of false positiveresults with each successive screening and the valueswere lower for women who were naturally postmeno-pausal. Table VIII summarises some of the criteria forevaluating the overall screening procedure-that is, allsubjects, three screens combined. The odds against apositive screen result being associated with any ovariantumour (by histological classification) were one totwo-that is, one tumour per three cases. The odds fell

TABLE VIII-Some criteria for evaluating screening procedure (allsubjects, three screens combined)

PositiveDetection False predictive

Ovarian rate positives Specificity valuepathology (%) (%) (%) (%) Odds*

All masses 80 8 4 2 to IAll tumours 36-3 1 to 1 8All cancers 100 2 3 97-7 2 7 1 to 37Primary cancer 100 2 3 97 7 1 5 1 to67

*Against positive result on screening indicating presence of each type ofpathology; odds=positive predictive value/(I -positive predictive value).

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to one to 37 for any ovarian cancer, and the values forprimary ovarian cancer were one to 67.

DiscussionTo our knowledge this is the first report of a

prospective study designed to assess the potential valueof pelvic ultrasonography as a technique for thedetection ofearly ovarian cancer in self referred womenwithout symptoms who are representative of thegeneral population between the ages of 45 and 60. Thelow prevalence of the disease necessitated the studyof at least 5000 women, and changes in ovarianmorphology and volume were monitored by repeatscans. In addition, all subjects were scheduled toundergo three screenings to obtain more informationabout the prevalence of the disease in the studypopulation and the most useful interval betweenscreenings. Eventually 5479 women were monitoredover eight years; 14 594 screenings (15 977 scans) wereundertaken and 29 140 ovaries were examined. Someof the potential screening indices of ovarian cancer hadnot been described or were ill defined at the start of thestudy and had to be analysed retrospectively. Thesevariates and new screening strategies will be thesubjects of an additional publication. Accordingly, thepersistence of abnormal ovarian morphology was themain criterion for the decision to refer women forfurther investigation. The results of the screeningprocedure are expressed either per screening or perpatient because 92 women had an initially positiveresult at more than one screening. Of these, 12 womenhad a finally positive result at the first and secondscreenings.

In practice many of the women had to travel longdistances to attend the scanning clinic and someunderwent unilateral or bilateral oophorectomy as aconsequence of the result on screening. For these andother reasons we were reassured that 90% of womenwho were screened initially attended for the secondscreening and 77% for the third-that is, compliancewas good. The progressive increase in the ratio ofinitially positive and finally negative results to initiallypositive and finally positive results at the second andthird screening probably reflects a change in the type ofovarian pathology because of previous interventions. Itmay also be due in part to the increased experience ofthe ultrasonographers or the changing menopausalstate of the study population. Five subjects withprimary ovarian cancer (all stage Ia or Ib) weredetected (a notable result for a screening procedure),giving an overall prevalence for the disease in the studypopulation of 0 09%, which is about the proportionexpected. Only one of the primary cancers could bedetected by manual examination after ultrasonography.Three of the primary cancers were classified as border-line. This finding, together with the prevalence of thedisease, may indicate the malignant potential of someborderline (or preinvasive) tumours. All of the womenwith primary ovarian cancer and three of the fourwomen with metastatic ovarian cancer were alive atleast two years after surgery. We currently have followup data on 86% (4705) of the other women showingthat they were free of any signs of ovarian cancer oneyear after the last screening or treatment. For thesereasons we believe that the overall detection rate of thescreening procedure and the predictive value of anegative test result were both probably 100% for thisparticular study, although the figure must of coursedecrease with time for both variables and will be thesubject of further publications. It is thus particularlyinteresting that three primary cancers were detected atthe second screening about 16, 18, and 22 months afterthe first. This finding suggests that screening every 12to 18 months is necessary. Only a few benign tumours

and no primary cancers were detected at the thirdscreening. The importance of this finding may becomeapparent from detailed follow up studies and may haveimportant implications for a screening programme.We have already published data on the size of ovaries

in postmenopausal women" and ultrasound pictures ofthe primary cancers'4 and related all ovarian masses thatwere found at surgery to the number of the screeningand the menopausal state and age of the subjects." Asindicated in table VI, where the results are expressedper ovary, we were unable to identify any morpho-logical characteristics or patterns that could be used todifferentiate between ovarian tumour-like conditionsand tumours or between benign and early malignanttumours. The latter finding is disappointing in view ofthe more encouraging results reported by previousworkers,'6 7 who mainly studied later stages of thedisease in women with symptoms and excluded border-line tumours from their analyses. The finding ofvarious masses at surgery in ultrasonically normalovaries at the time of the last scan may be related to thetime interval between the two observations or to theoccasional use of an overtly enlarged ovary as acriterion for a positive result of screening.The screening procedure gave a rate of false positive

results for the detection of primary ovarian cancer of3 5% at the first screening and 1-2% at the third (2-3%overall). The reduction in the rate over successivescreenings is probably due to the treatment of womenwith one or more persistent ovarian masses. Theoverall specificity of the screening procedure was97 7%, and the predictive value for a positive test resultwas 1 5%-that is, odds of one to 67 that a positiveresult was indicative of primary ovarian cancer. Webelieve, however, that these values must be interpretedin the knowledge that the odds for a positive result onscreening indicating the presence of any ovariantumour were one to two (because some of thesetumours will constitute a health hazard); and for allovarian cancers the odds were one to 37. The rate offalse positive results for primary ovarian cancer waslower for women who were naturally menopausal andthe results from our more recent study suggest that thevalues for premenopausal women may be reduced by acareful consideration of the day of the menstrual cycleand the thickness of the endometrium in the presenceof an ovarian mass. The rate of false positive results forany ovarian abnormality was only 06% at the firstscreening and 04% overall, and these figures willundoubtedly be lower in future studies owing to theexperience gained and the technical developmentsin transvaginal ultrasonography (see accompanyingpaper'8). We believe that women will be attracted to ascreening programme if the chances of detecting thedisease at an early stage are high. Our results show thatultrasonography fulfils this criterion and future effortswill be directed toward reducing the rate of falsepositive results. There is still, however, the suggestionthat apparently benign epithelial tumours may have anincreased potential for malignancy compared withhealthy tissues. If this possibility were to be substan-tiated the removal of these tumours would mean thatultrasound screening would aid the prevention as wellas the detection of primary ovarian cancer.

We thank the Cancer Research Campaign for financialsupport, Dr R Goswamy for undertaking the initial ultra-sound scans, Sisters R Battersby, V Hall, J Foxton, andA Davies for their nursing skills, Messrs L Schiphorst andC Harris for establishing the database, and Mrs J Monk forsecretarial help. MIW was supported by the Imperial CancerResearch Fund.

I Cramer DW. Epidemiologic and statistical aspects of gynecologic oncology.In: Knapp RC, Berkowitz RS, eds. Gvnecologic oncology. New York:Macmillan, 1986:201-22.

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2 Beral V. The epidemiology of ovarian cancer. In: Sharp F, Soutter WP, eds.Ovarian cancer-the was ahead. Chichester: Wiley, 1987:21-31.

3 Longo DL, Young RC. The natural history and treatment of ovarian cancer.Annu RezvMed 1981;32:475-90.

4 Barker HRK. Ovarian cancer, diagnosis and management. Am J ObstetGvnecol 1984;150:910-6.

5 Jacobs I, Stabile I, Bridges J, et al. Multimodal approach to screening forovarian cancer. Lancet 1988;i:268-71.

6 Zurawski VR, Orjaseter H, Andersen A, Jellum E. Elevated serum CA-125levels prior to diagnosis of ovarian neoplasia: relevance for early detection ofovarian cancer. Int7 Cancer 1988;42:677-80.

7 Campbell S, Goessens L, Goswamy R, Whitehead MI. Real-time ultrasono-graphy for the determination of ovarian morphology and volume. A possibleearlv screening test for osarian cancer. Lancet 1982;i:425-6.

8 Goswamv RK, Campbell S, Whitehead MI. Screening for ovarian cancer. In:Campbell S, ed. Ultrasound in obstetrics and gmaecology: recent advances.London: Saunders, 1983:621-43. (Clinics in Obstetrics and Gynaecology1983;10:621-43.)

9 Andolf E, Svalenius E, Astedt B. Ultrasonography for early detection ofovarian carcinoma. BrJ Obstet Gynaecol 1986;93:1286-9.

10 Donald I. Use of ultrasonics in the diagnoses of abdominal swellings. BrMedJ71963;ii: 1 154-5.

11 Serov SF, Scully RE, Sobin LH. International histological classification oftumours. No 9. Histological typing of ovarian tumours. Geneva: World HealthOrganisation, 1973.

12 Creasman WT. Changes in FIGO staging. Obstet Gynecol 1987;70:138.13 Goswamy RK, Campbell S, Royston JP, et al. Ovarian size in postmenopausal

women. Br7 Obstet Gynaecol 1988;95:795-801.14 Bhan V, Campbell S. Ultraschall als Screening-Vertahren zur Entdeckung von

Ovarialtumoren. Gvnakologe 1986;19:135-41.15 Bhan V, Amso N, Whitehead MI, Campbell S, Royston P, Collins WP.

Characteristics of persistent ovarian masses in asymptomatic women. BrJObstet Gynaecol (in press).

16 Meire HB, Farrant P, Guiha T. Distinction of benign from malignant ovariancysts by ultrasound. BrJ Obstet Gynaecol 1978;85:893-9.

17 Hermann UJ, Locker GW, Goldhirsh A. Sonographic patterns of ovariantumors: prediction of malignancy. Obstet Gynecol 1987;69:777-81.

18 Bourne T, Campbell S, Steer C, Whitehead MI, Collins WP. Transvaginalcolour flow imaging: a possible new screening technique for ovarian cancer.BrMhedJ 1989;299:1367-70.

(Accepted 10 October 1989)

Transvaginal colour flow imaging: a possible new screeningtechnique for ovarian cancer

Thomas Bourne, Stuart Campbell, Christopher Steer, Malcolm I Whitehead, William P Collins

Department of Obstetricsand Gynaecology, King'sCollege School ofMedicineand Dentistry, LondonSE5 8RXThomas Bourne, MB,research registrarStuart Campbell, FRCOG,professorMalcolm I Whitehead,FRCOG, senior lecturerWilliam P Collins, DSC,professor

Hallam Medical Centre,London WIN SLRChristopher Steer, MRCOG,research registrar

Correspondence to:Professor Collins.

BrMled_' 1989;299:1367-70.

AbstractObjective-To assess whether changes in

the intraovarian vasculature or blood flow impedancecan be used to identify potentially malignant masses.Design-Open, non-comparative prospective

study.Setting-Ovarian screening clinics at King's

College Hospital and the Hallam Medical Centre.Subjects-50 Women selected on the basis of

their medical history and the result of a previoustransvaginal ultrasound scan. Thirty women(10 premenopausal (scan taken on days 1 to 8 ofthe menstrual cycle) and 20 postmenopausal) hadnormal ovaries, and 20 had at least one ovary with anabnormal morphology or volume, or both.Interventions-Women with a positive result on

screening were referred for laparotomy.Main outcome measures-Presence or absence

of coloured areas (neovascularisation) and thepulsatility index within each ovary. The pulsatilityindex is a measure of the impedance to blood flow, alow value indicating decreased impedance and a highvalue increased impedance to blood flow.Results-Two women with a positive result on

screening had hydrosalpinges, 10 a benign tumour ora tumour-like condition, and eight primary ovariancancers. No areas ofneovascularisation were seen inthe 30 women with morphologically normal ovariesand the two patients with hydrosalpinges; thepulsatility index ranged from 3-1 to 9-4. Similarly,nine patients (10 affected ovaries) with a non-malignant mass had no signs of neovascularisationand the pulsatility index varied from 3.2 to 7 0. Onepatient with bilateral dermoid cysts containingnests of thyroid-like cells had vascular changes andpulsatility index values of 0 4 and 0 8. Seven patients(eight ovaries) with primary ovarian cancer (onestage IV, four stage III, and two stage Ia) showedclear evidence of neovascularisation and pulsatilityindex values were from 0-3 to 1-0. One patient withan intraepithelial serous cystadenocarcinoma in asmall ovary (