WOMENS-HEALTH Messages for May, 1998: Re: Ovarian Cancer

Re: Ovarian Cancer

From: Judi (anonymous@obgyn.net)
Fri, 29 May 1998 21:47:04 -0500 (CDT)

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At Tue, 1 Jul 1997, Geffrey H. Klein, MD wrote: >
>>I am a 44 year old woman with three children. My one and only sibling
>>was diagnosed with Stage IV Ovarian Cancer 2 years ago at the age of 45.
>>My father was recently diagnosed with Penile Cancer. My mother died at
>>the age of 65 of lung cancer . She was a smoker.
>>I am very concerned of my risks for this disease. I have had one breast
>>biopsy 4 years ago which was benign. I have had regular checkups which
>>include mamograms and pap smears and since my sister was diagnosed I
>>have my CA125 level checked and trans-vaginal sonograms. My CA125 level
>>for the past two years has remained between 30 - 35. The trans-vaginal
>>sonogram was normal. I guess what I am asking is: Is there anything
>>else I should be doing?
>
>The major modalities of ovarian cancer screening include pelvic
>examination, tumor markers, and transvaginal ultrasonography. The problem
>with ovarian cancer screening is that it is not sensitive in picking up the
>disease and it is not specific for ovarian cancer when abnormalities are
>detected. Ovarian cancer, unfortunately, is usually diagnosed in the
>advanced stages when cure rates are poor.
>
>This is a stressful situation for women, especially for patients like
>yourself who see the disease process first hand and are at increased risk
>by virtue of genetics. You might consider phoning a medical center near
>you that conducts cancer research to see if they have an experimental
>protocol for ovarian cancer screening.
>
>More bad news.. there appears to be a link between ovarian cancer risk and
>risk of other malignancies, specifically, colon, breast, and endometrial
>(lining of the uterus). You should have mammograms and testing for occult
>blood in the stool. Any abnormal uterine bleeding should be aggressively
>evaluated..
>
>If you have access to a medical library, you might want to read some of the
>articles that I have included below..
>
>best of luck..
>
>--
>____________
>
>Unique Identifier
> 97201084
>Authors
> Boyd J. Rubin SC.
>Institution
> Department of Obstetrics and Gynecology, University of Pennsylvania Medical
> Center, Philadelphia 19104, USA.
>Title
> Hereditary ovarian cancer: molecular
> genetics and clinical implications. [Review] [152 refs]
>Source
> Gynecologic Oncology. 64(2):196-206, 1997 Feb.
>Abstract
> Epidemiologic data support the existence of two discrete manifestations of
> hereditary ovarian carcinoma: the breast and
> ovarian cancer syndrome and the hereditary
> nonpolyposis colorectal cancer (HNPCC) syndrome. Genetic
> linkage analyses reveal that the majority of breast and
> ovarian cancer families are linked to the
> BRCA1 gene, while some cases of hereditary ovarian
> cancer are also apparent in breast cancer
> families linked to the BRCA2 gene. The majority of HNPCC families are linked
> to one of four genes encoding a family of DNA mismatch repair proteins.
> Molecular analyses demonstrate that genetic screening for
> germline transmission of a defective allele of one or another of these genes
> is now possible for high-risk individuals. The ethical, legal, and social
> implications of this type of analysis are multiple and complex, and genetic
> counseling requires a thorough understanding of these issues and a cautious
> approach to most effectively meet the special needs of this patient
> population. Increased medical surveillance and prophylactic oophorectomy are
> among the management options that may be appropriate for some genetically
> predisposed, asymptomatic women. Further research is needed regarding the
> most effective use of this genetic information in formulating counseling and
> clinical management strategies. [References: 152]
>
>Unique Identifier
> 97071237
>Authors
> Guidozzi F.
>Institution
> Department of Obstetrics and Gynaecology, Johannesburg Hospital, Parktown,
> South Africa.
>Title
> Screening for ovarian
> cancer. [Review] [42 refs]
>Source
> Obstetrical & Gynecological Survey. 51(11):696-701, 1996 Nov.
>Abstract
> Ovarian cancer is the leading cause of
> death from gynecologic cancer. Despite aggressive
> cytoreductive surgery and platinum-based chemotherapy, the 5-year survival
> for patients with clinically advanced ovarian
> cancer is only 15 to 20 percent, although the cure rate for
> stage I disease is usually greater than 90 percent. These statistics provide
> the primary rationale for ovarian cancer
> screening. This overview of the current literature serves to
> show that mass screening for ovarian
> cancer is far from being established and fraught with
> management and procedural dilemmas. The reasonable assumption being that
> there is little evidence to support widespread screening of
> large populations of women who do not have familial or genetic risk factors
> for ovarian cancer. [References: 42]
>
>Unique Identifier
> 97088098
>Authors
> Bombard AT. Fields AL. Aufox S. Ben-Yishay M.
>Institution
> Albert Einstein College of Medicine, Bronx, New York, USA.
>Title
> The genetics of ovarian cancer: an
> assessment of current screening protocols and
> recommendations for counseling families at risk. [Review] [47 refs]
>Source
> Clinical Obstetrics & Gynecology. 39(4):860-72, 1996 Dec.
>Abstract
> Although the need for effective ovarian
> cancer screening is apparent, a highly
> sensitive and specific screening methodology has yet to be
> elucidated. 42-44 Given that there are more than 43 million women in the
> United States older than 45 years of age and that the average cost of a
> pelvic sonogram is $ 275 (and $ 45 for CA125 screening), the
> screening of this population is estimated to increase health
> care costs by $ 14 billion per year. 45 The additional cost of BRCA1
> screening varies according to the level of diagnostic effort
> required to establish BRCA1 gene mutations in a particular family and ranges
> from $ 295 to $ 1,200 per sample. Assuming an average cost of $ 600 per
> sample, initial screening of these same women would likely
> increased costs in excess of $ 25 billion. Current knowledge and technology
> in ovarian cancer
> screening has not yet proved beneficial for the general
> population or for women with fewer than two affected family members. For
> women with two or more affected family members, there is a 3% chance of that
> patient being a proband in a hereditary cancer syndrome
> family. 11,46 In this group, who may be at increased risk for developing a
> malignancy, heightened surveillance is warranted, although there are still no
> data to confirm that screening even these high-risk women
> will reduce mortality. Nevertheless, annual bimanual examination, serum
> CA125, and transvaginal sonography are recommended among this particular
> subgroup of women at risk, and are likely to be recommended for young,
> asymptomatic, at-risk women who screen positive for the 185delAG BRCA1
> deletion commonly found in persons of Ashkenazi Jewish ancestry. It is only
> through prospective, randomized trials that reliable data regarding the
> risk/benefit ratio of ovarian cancer
> screening among various populations at risk will be
> determined. The results of the prospective/randomized PLCO trial and the
> mature data from ongoing prospective, nonrandomized
> screening trials for women with a family history of
> cancer may provide this information and are eagerly awaited.
> [References: 47]
>
>Unique Identifier
> 96363299
>Authors
> Schwartz PE. Chambers JT. Taylor KJ.
>Institution
> Department of Obstetrics and Gynecology, Yale University School of Medicine,
> New Haven, CT 06520, USA.
>Title
> Early detection and screening for ovarian
> cancer. [Review] [20 refs]
>Source
> Journal of Cellular Biochemistry - Supplement. 23:233-7, 1995.
>Abstract
> Ovarian cancer is associated with
> postmenopausal women of North American or European descent, nulliparous
> women, and women with a first-degree relative with an epithelial
> ovarian cancer. Methods for early detection
> of ovarian cancer are the pelvic
> examination, ultrasound techniques, and CA-125 monitoring, none of which are
> highly sensitive or specific for the disease. At the Yale-New Haven Medical
> Center, first-degree relatives of women with epithelial
> ovarian cancer were invited to participate
> in an intense ovarian cancer
> screening program consisting of tumor markers, endovaginal
> ultrasound and color Doppler flow studies, and physical examinations
> performed in a serial fashion. The false-positive rate for the tumor markers
> varied from 2 to 9% at initial evaluation of the first 247 participants.
> Endovaginal ultrasound and color Doppler flow techniques were used to
> evaluate 326 ovaries in 169 women. Resistive indices < 0.5 were present in 26
> ovaries (8.4%), and peak systolic velocities > 30 cm/sec occurred in 7
> ovaries (2.3%). To date, four breast cancers have been
> detected, three cervical intraepithelial neoplasias have been identified, and
> three atypical adenomatous hyperplasias were diagnosed. No epithelial
> ovarian cancer was found. Isolated
> screening for ovarian
> cancer even in high-risk women is not cost effective. Women
> screened for ovarian cancer should also be
> evaluated for cancers of the breast, cervix, colon, rectum
> and endometrium. Isolated abnormal screening test values are
> not an indication for surgery. [References: 20]
>
>Unique Identifier
> 96363296
>Authors
> Bast RC Jr. Boyer CM. Xu FJ. Wiener J. Dabel R. Woolas R. Jacobs I.
> Berchuck A.
>Institution
> University of Texas M.D. Anderson Cancer Center, Houston
> 77030, USA.
>Title
> Molecular approaches to prevention and detection of epithelial
> ovarian cancer. [Review] [21 refs]
>Source
> Journal of Cellular Biochemistry - Supplement. 23:219-22, 1995.
>Abstract
> More than 90% of epithelial ovarian cancers
> arise from single cells. Malignant transformation can be associated with a
> number of molecular alterations including upregulation of tyrosine kinases
> and phosphatases, physiologic activation o ras, mutation of p53,
> amplification of myc, and increased activity of matrix metalloproteinases 2
> and 9. Proliferation of transformed epithelial cells can be enhanced through
> the persistence of autocrine growth stimulation by TGF-alpha, loss of
> autocrine growth inhibition by TGF-beta, as well as paracrine growth
> stimulation by macrophage derived cytokines and OCAF, a novel
> lyso-phospholipid. Ascites tumor cells retain responsiveness to growth
> inhibition by TGF-beta which induces apoptosis in malignant
> ovarian epithelial cells, but not in normal
> ovarian surface epithelium. Proliferation of surface
> epithelial cells following ovulation may contribute to the pathogenesis of
> ovarian cancer. Use of oral contraceptives
> that suppress ovulation has been associated with reduced risk of
> ovarian cancer in later life. Retinoids
> also deserve further evaluation for chemoprevention. Treatment with
> fenretinide was associated with decreased incidence of
> ovarian cancer. Additive or synergistic
> inhibition of ovarian tumor cell proliferation has been
> observed with TGF-beta in combination with all-trans-retinoic acid. Early
> detection of ovarian cancer could improve
> survival. Transvaginal sonography (TVS) and serum markers such as CA-125 have
> been evaluated in multiple clinical trials. The former lacks adequate
> specificity, whereas the latter is not sufficiently sensitive. Use of
> multiple serum markers can improve sensitivity. A combination of CA-125,
> M-CSF and OVX-1 has detected > 95% of Stage I ovarian
> cancers. If similar results are obtained with different data
> sets, multiple serum markers could be used to trigger the performance of TVS,
> providing a potentially cost effective screening strategy.
> Prospective trials will be required to demonstrate that
> screening for early stage ovarian actually
> impacts on survival. [References: 21]
>
>Unique Identifier
> 96229982
>Authors
> Berek JS. Bast RC Jr.
>Institution
> Gynecologic Oncology Service, UCLA School of Medicine 90024-1740, USA.
>Title
> Ovarian cancer screening.
> The use of serial complementary tumor markers to improve sensitivity and
> specificity for early detection. [Review] [25 refs]
>Source
> Cancer. 76(10 Suppl):2092-6, 1995 Nov 15.
>Abstract
> BACKGROUND. The use of serum tumor markers for the early detection of
> ovarian cancer has been limited because of
> their low sensitivity and low positive predictive value. CA 125 levels are
> elevated in only about one half of women with Stage I
> ovarian cancer, thus researchers have
> focused on using the serial measurement of complementary markers to improve
> the sensitivity, specificity, and positive predictive value of this approach
> for screening. METHODS. Multiple serum markers have been
> analyzed in women with early stage epithelial ovarian
> cancer. CA 125, CA 15-3, C19-9, CA 54-61, CA 72-4, CEA,
> HMFG2, IL-6, IL-10, LSA, M-CSF, NB70K, OVX1, PLAP, TAG72, TNF, TPA, and UGTF
> have been studied alone and in combination in this setting. Complementarity
> and logistic regression analyses have been performed to assess those markers
> with the highest likelihood of improving sensitivity and specificity for
> early detection. Serial analysis of a second-generation CA 125 measuring the
> intercept (initial level) and slope (change of levels over time) can be used
> to discriminate malignant cases from benign and normal cases. RESULTS.
> Analyses have shown that the serial measurement of the new, more sensitive CA
> 125 has a high sensitivity (83%), specificity (99.7%), and positive
> predictive value (16%) for the early detection of ovarian
> cancer. OVX1 used in combination with CA 125 provides the
> best complementarity. Serial measurements of the two markers have
> sensitivities in the range of that for transvaginal ultrasonography.
> CONCLUSION. The serial measurement of complementary serum markers can improve
> the use of marker screening for epithelial
> ovarian cancer. With the use of several
> different methods of analysis, it has been shown that this approach improves
> the sensitivity, specificity, and positive predictive value of serum markers
> CA 125 and OVX1. A procedure that measures complementary serum markers over
> time can be used as a primary screening technique followed
> by transvaginal ultrasonography. This could provide a cost-effective means of
> early detection and could significantly decrease the probability of surgical
> intervention for false-positive test results. [References: 25]
>
>Unique Identifier
> 96229981
>Authors
> van Nagell JR Jr. Gallion HH. Pavlik EJ. DePriest PD.
>Institution
> Department of Obstetrics and Gynecology, University of Kentucky Medical
> Center, Lexington 40536-0084, USA.
>Title
> Ovarian cancer screening.
> [Review] [27 refs]
>Source
> Cancer. 76(10 Suppl):2086-91, 1995 Nov 15.
>Abstract
> BACKGROUND. The three most extensively evaluated screening
> methods for ovarian cancer are pelvic
> examination, serum CA 125, and transvaginal sonography (TVS). The lack of
> sensitivity of pelvic examination and serum CA 125 has limited their use in
> ovarian cancer screening.
> Currently, the most effective screening method for
> ovarian cancer is TVS. METHODS.
> Transvaginal sonography was performed with a standard ultrasound unit and a
> 5.0 MHz vaginal transducer. Each ovary was measured in three dimensions and
> ovarian volume was calculated using the prolate ellipsoid
> formula (L x H x W x 0.523). An ovarian volume greater than
> or equal to 20 cm3 in premenopausal women and greater than or equal to 10 cm3
> in postmenopausal women was considered abnormal. Also, any internal papillary
> projection from the tumor wall was considered abnormal. A patient with an
> abnormal screen had a repeat TVS in 4-6 weeks. Women with a persisting
> abnormality on TVS underwent pelvic examination, serum CA 125 determination,
> Doppler flow sonography, and tumor morphologic indexing before operative
> tumor removal. RESULTS. Eighty-five hundred asymptomatic women underwent TVS
> screening. One hundred twenty-one of these women had a
> persisting abnormality and underwent tumor removal. Fifty-seven patients had
> serous cystadenomas and eight had primary ovarian
> cancers. Six patients had Stage IA ovarian
> cancer, one had Stage IIC ovarian
> cancer, and one had Stage IIIB ovarian
> cancer. Only one of these patients had palpable
> ovarian enlargement on clinical examination and one had an
> elevated serum CA 125. All patients are alive and well 4-61 months after
> conventional therapy. The direct cost of TVS screening was
> highest during the initial years of the program and fell progressively to
> $30/screen during the 4th year of the study. Worldwide, more than 14,000
> women have been screened using ultrasonography, and 19
> ovarian cancers have been detected. More
> than 20,000 patient-screening-years have been accrued, and
> there have been no deaths from primary ovarian
> cancer in the screened population. CONCLUSIONS. Transvaginal
> sonography screening causes a decrease in stage at detection
> and a decrease in case-specific mortality. Further study is needed to
> determine if annual TVS screening will significantly reduce
> ovarian cancer mortality. The cost for TVS
> screening is reasonable and is well within the range of that
> reported for other screening tests. [References: 27]
>
>Unique Identifier
> 96229969
>Authors
> Karlan BY. Platt LD.
>Institution
> Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, UCLA
> School of Medicine, USA.
>Title
> Ovarian cancer screening.
> The role of ultrasound in early detection. [Review] [35 refs]
>Source
> Cancer. 76(10 Suppl):2011-5, 1995 Nov 15.
>Abstract
> BACKGROUND. Because of the urgent need for effective techniques with which to
> detect organ-confined curable ovarian
> cancers, efforts have been focused on early detection.
> Current ovarian cancer
> screening trials have been hampered by deficiencies in our
> knowledge of the molecular and biologic events leading to
> ovarian tumorigenesis. The lack of early
> ovarian cancer symptoms and the
> intraperitoneal location of the ovaries contribute to the dilemma of early
> diagnosis. METHODS. Real-time ultrasound screening is aimed
> at detecting the earliest possible architectural alterations in the ovary
> indicative of neoplastic growth. Color Doppler imaging detects early
> alterations in ovarian blood flow that accompany
> tumorigenesis. RESULTS. To be effective, these modalities must diagnose
> asymptomatic curable Stage I ovarian
> cancers and improve ovarian
> disease-specific survival. Because of the relatively low prevalence of
> ovarian cancer in the general population,
> investigators have targeted women at increased risk of
> ovarian cancer either based on their
> increasing age or their family histories of cancer. Some of
> these studies have been underway since the late 1980s and have already
> demonstrated the potential usefulness and limitations of current sonographic
> techniques used for screening. CONCLUSIONS. Ultrasound
> screening for ovarian
> cancer has not demonstrated adequate sensitivity and
> specificity, thus it is not used widely outside of the clinical trial
> setting. Current clinical guidelines for ovarian
> cancer screening as well as exploratory
> methods for use in early ovarian cancer
> detection are presented. [References: 35]
>
>Unique Identifier
> 96229967
>Authors
> Claus EB. Schwartz PE.
>Institution
> Department of Epidemiology and Public Health, Yale University School of
> Medicine, New Haven, Connecticut, USA.
>Title
> Familial ovarian cancer. Update and
> clinical applications. [Review] [62 refs]
>Source
> Cancer. 76(10 Suppl):1998-2003, 1995 Nov 15.
>Abstract
> BACKGROUND. Genetics plays a role in all cancers. Evidence
> exists for the presence of inherited genes associated with the development of
> ovarian cancer in three familial
> ovarian cancer syndromes: a site-specific
> ovarian cancer syndrome, a
> breast/ovarian cancer syndrome, and an
> ovarian cancer syndrome associated with
> hereditary nonpolyposis colorectal cancer. METHODS AND
> RESULTS. The authors present an updated summary of recent advances within the
> field of ovarian cancer genetics and
> examine the extent to which this genetic information, at both an
> epidemiologic and molecular level, may be used to identify a subset of women
> who are likely to be at increased risk of developing ovarian
> cancer. In addition, the extent to which these data may be
> used to define methods of prevention or treatment for women at risk is
> discussed. CONCLUSION. Women who are members of high risk
> ovarian cancer families should receive
> genetic screening and medical follow-up in an effort to
> reduce their overall chances of morbidity and death associated with the
> development of ovarian and other cancers.
> The construction of cancer family registries will help to
> identify women at risk and facilitate their entry into clinical trials and
> screening programs for ovarian
> cancer. [References: 62]
>
>Geffrey H. Klein, MD
>listowner: OB-GYN-L
>Advisory Board Chairman, OBGYN.net < http://www.obgyn.net >
>Co-moderator: sci.med.obgyn
>gklein@bcm.tmc.edu gklein@icsi.net
>
>*Note: Opinions expressed here are for educational purpose only.
>This information is not intended to supplant the need for you to
>consult with your physician prior to choosing therapeutic options.
>

--
What would the normal treatment be for serous cystadenomas in a 27 yr. old female, having never been pregnant and having a history of female problems?

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