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Outcome of surveillance and prophylactic salpingo-oophorectomy in asymptomatic women at high risk for ovarian cancer.

OBJECTIVE: Women at high risk of ovarian cancer are currently offered two options: either surveillance or prophylactic bilateral salpingo-oophorectomy. The efficacy and outcome of surveillance remain unclear. METHODS: We performed a retrospective study. Between 1994 and 2000, we screened 383 high-risk women, of which 152 were BRCA1/2 mutation carriers. Surveillance consisted of annual gynecological examination, transvaginal ultrasound, and serum CA125 measurement. Exploratory or prophylactic surgery was performed in selected cases. RESULTS: There were no screen-detected primary ovarian cancers. Abnormal results at surveillance were observed in 74 (19.3%) of women; in 47 (63.5%), the abnormalities disappeared spontaneously. Exploratory surgery was performed in 20 (27.0%) women in whom one malignancy was found (metastatic breast cancer in the ovary). A rising CA125 value prompted further (non-surgical) evaluation in three women with a history of breast cancer: recurrent breast cancer was diagnosed in two women; in the third, a chondrosarcoma was found. 133 women opted for prophylactic bilateral salpingo-oophorectomy, whereby two unexpected malignancies were found (fallopian tube cancer and metastatic breast cancer). One interval primary ovarian cancer occurred, presenting as papillary serous carcinoma of the peritoneum 14 months after prophylactic bilateral salpingo-oophorectomy. Complications of prophylactic surgery were encountered in 15 (11.5%) women. CONCLUSIONS: Ovarian cancer surveillance has limited sensitivity, and a high number of false positive findings. This can lead to unnecessary surgical interventions, possibly resulting in surgery-related complications. It is important to inform high-risk women of these limitations. For now, prophylactic bilateral salpingo-oophorectomy remains the optimal risk-reducing strategy for women at high risk.

Adult↗

Behaviour of the fellow eye in acute angle-closure glaucoma.

A retrospective study of 245 fellow eyes of patients admitted in primary acute angle-closure glaucoma (ACG) is presented. Twenty-five (10.2%) had acute ACG in the fellow eye on presentation. Of the remaining 220, 33 (15%) subsequently developed acute ACG before prophylactic surgery was performed. Possible predisposing factors were analysed. The main findings were that acute ACG in the fellow eye occurred most frequently in hospital, or during the first month after discharge if prophylactic surgery was not performed. The instillation of mydriatics in the operated eye increased the risk to the fellow eye. Pilocarpine and carbonic anhydrase inhibitors confer the best protection on the fellow eye, but no medical regimen entirely prevented an attack of acute ACG in the fellow eye.

Acute Disease↗

An evaluation of needs of female BRCA1 and BRCA2 carriers undergoing genetic counselling.

BACKGROUND: The discovery of the breast and ovarian cancer susceptibility genes BRCA1 and BRCA2 has improved our ability to counsel women at increased risk of developing breast and ovarian cancer. The objective of our study was to identify the needs of women who have undergone genetic counselling and testing for BRCA1/2 and to determine the impact of receiving a positive BRCA1/2 result. This is the first study to report on a large group of women who have received positive BRCA1/2 mutation results. METHODS: Questionnaires were distributed to 105 women who had received pre- and post-test genetic counselling for a positive BRCA1/2 result at the University of Toronto or at McGill University in Montreal, Canada between the years of 1994 and 1998. The questionnaire items included patient motivation for seeking genetic services, information needs, screening and prophylactic surgery practices, satisfaction with access to services and support, the desire for a support group, and overall client satisfaction. RESULTS: Seventy nine female carriers were surveyed. The majority of the respondents (77%) were satisfied with the information they received during the genetic counselling process. Women with a previous diagnosis of cancer indicated that they needed more information relating to cancer treatment compared to women without cancer (p=0.05). Nineteen percent of the women felt they needed more support than was received. Fifty eight percent of the women reported that their screening practices had changed since they received their result. Young women (below the age of 50) and women with no previous diagnosis of cancer were most likely to have changed their screening practices. Nearly two thirds of the respondents said they had considered prophylactic surgery of the breasts or ovaries. Twenty eight percent of the women had prophylactic mastectomy and 54% had undergone prophylactic oophorectomy. Women with an educational level of high school or more were more likely to have undergone prophylactic bilateral mastectomy than those with less education (p=0.07) but were less likely to undergo prophylactic oophorectomy (p=0.0007). CONCLUSION: These findings have a direct impact on the counselling and risk management of female BRCA mutation carriers. Age, education, and a previous diagnosis of cancer are important determinants in a woman's decision making after receiving positive genetic test results.

BRCA1 Protein↗

[Prophylactic thyroid surgery].

Early diagnosis for thyroid carcinoma, potentially before neoplastic transformation has taken place, would allow preventive and thus curative surgical intervention. Identifying and characterizing the RET proto-oncogene as the disease-causing gene for hereditary medullary thyroid carcinoma and then establishing a genotype-phenotype correlation served as the prerequisite for the risk-adapted prophylactic surgical approach practised today. Carriers of RET mutations associated with very aggressive tumour behaviour should be subjected to prophylactic thyroidectomy within the 1st year of life. For individuals harbouring less virulent types of mutations, prophylactic intervention is recommended at 5-20 years. Although genetic research on hereditary nonmedullary thyroid cancer is still in progress, initial results indicate the need of prophylactic surgical treatment also for this subgroup of thyroid neoplasia.

Adolescent↗

Why do women attend familial breast cancer clinics?

The increasing demand for genetic assessment for familial breast cancer has necessitated the development of cancer genetics services. However, little is known about the factors motivating the client population likely to approach these services. A cross sectional questionnaire survey of 1000 women with a family history of breast cancer was conducted to identify self-reported reasons for attending a familial breast cancer clinic and possible differences in the characteristics of women who were attending for diverse reasons. Before attendance at clinic, 833 women completed a baseline questionnaire (83% response rate). Women who gave personal risk (n=188), awareness of a family history (n=120), risk to family members (n=84), reassurance (n=69), genetic testing (n=65), breast screening (n=46), or prevention (n=39) as their main reason for attending were compared on demographic and medical variables, and on psychological variables including general anxiety, cancer worry, perceived risk, and attitudes towards prophylactic surgery and genetic testing. Important differences in the psychological characteristics of these groups were found, which were unrelated to reported family history. In particular, women who primarily wanted genetic testing felt extremely vulnerable to developing breast cancer, were more likely to be considering prophylactic surgery, and perceived fewer limitations of testing. Those who primarily wanted reassurance were highly anxious about the disease. We recommend that cancer genetics services take into consideration the informational and psychological needs and concerns of their client group.

Ambulatory Care Facilities↗

Occult intracranial aneurysms in polycystic kidney disease. When is cerebral arteriography indicated?

Patients with polycystic kidney disease are at increased risk of subarachnoid hemorrhage from rupture of intracranial aneurysms. We used decision analysis to assess whether or not patients with polycystic kidney disease should undergo routine cerebral arteriography for intracranial aneurysms and prophylactic surgery, if an aneurysm is detected. We incorporated published data on the prevalence of intracranial aneurysms in patients with polycystic kidney disease, the annual rate of aneurysmal rupture, the risk of grave complications of rupture, and the likelihood of grave complications of arteriography and prophylactic surgery. Outcomes were assessed as years of survival, and benefit was calculated as the gain in survival. Our analysis shows that arteriography should not be carried out routinely because its benefit exceeds one year only if the prevalence of aneurysm exceeds 30 per cent, if the surgical complication rate is 1 per cent or less, and if the patient is under 25 years of age. If newer noninvasive tests, such as digital-subtraction angiography, prove to identify reliably patients who are highly likely to have a cerebral aneurysm, routine screening with these tests will be warranted in patients with polycystic kidney disease.

Adult↗

[Preventive therapy of HNPCC--a study concept].

Due to different pattern of penetrance and heterogeneity, the role of prophylactic surgery must be individually defined for every hereditary cancer predisposition. For HNPCC (hereditary nonpolyposis colorectal cancer) subtotal colectomy at the time of colorectal cancer diagnosis is being recommended by the Cancer Genetics Studies Consortium Recent Guidelines from the DGVS (Deutsche Gesellschaft für Verdauungs- und Stoffwechselkrankheiten) state that to date no general recommendation favouring this approach can be made. The open question is: how effective is segmental resection and endoscopic surveillance in given time intervals compared with the reduction of risk by performing extended (prophylactic) surgery. Also the issue of dealing with rectal cancer as the first primary in HNPCC patients must be addressed. In order to answer these questions and after the lessons learned from BRCA mutation carriers and prophylactic mastectomies, quality of life measurement is mandatory for this study.

Colectomy↗

Screening for familial ovarian cancer--management and outcome of women with moderate to high risk of developing ovarian cancer.

Five percent to ten percent of ovarian cancers are hereditary. Individual genetic risk of developing ovarian malignancy is discussed in women. Currently, prophylactic surgery is advised to women with a moderate to high risk of developing ovarian cancer. Workload and outcome of the multidisciplinary familial ovarian screening clinic in South Wales were assessed. This was an observational study of 145 women registered with the Familial Ovarian Screening Clinic between January 1998 and December 2003. The data were retrieved from the medical notes. Yearly follow-ups were investigated with a transvaginal scan and CA125 level. Post-surgery women were followed up with yearly CA125 estimations: 46.9% fell into moderate-risk and 50.3% into high-risk category. The median age was 42 (SD 10.4), 71.7% were pre menopausal, and 10.3% had a personal history of breast cancer and 1.4% colon cancer. Whereas 36.5% opted for surgery, the remaining women (but two) opted for annual follow-up. Histology of the women who had surgery showed three cases of malignancies (fallopian tube carcinoma, atypical ovarian epithelial cells, and metastatic breast cancer). Seven women developed breast cancer during the observation period. The follow-up period is too short to come to a final conclusion as to the benefits of yearly screening in this group of women. In our series, a significant number of patients developed malignancies, despite prophylactic surgery.

Adenocarcinoma↗

Prevention and genetic testing for breast cancer: variations in medical decisions.

The discovery linking the genes BRCA1&2 to familial breast cancer played an important role in the clinical practice of geneticists and physicians. The availability of genetic tests for BRCA gene mutations prompted cancer geneticists to give information about genetic risk and to assess many women with a personal or family history of breast or ovarian cancer to inform them of preventive measures. These consist mainly of breast self-examination, mammography screening, chemoprevention and prophylactic surgery (mastectomy, oophorectomy). This paper examines clinical practices related to hereditary breast cancer testing and introduces a number of results from a survey carried out, between 1996 and 1998, in three clinics located in Montreal (Quebec, Canada), Marseilles (France) and Manchester (Great Britain). Results show substantial differences in the way cancer geneticists deal with environmental risk factors, breast and ovarian cancer testing, and chemoprevention and prophylactic surgery. Differences across cities persist in the multivariate analysis, suggesting that attitudes towards preventive measures may be partially explained by cultural factors. Different dimensions of culture are discussed including the social representation of health and risk, the interpretation of scientific evidence and the role of innovation leadership.

Adolescent↗

Prophylactic portal nondecompression surgery in patients with esophageal varices. An interim report.

This is an interim report of a prospective controlled study to evaluate prophylactic surgery in 112 patients with portal hypertension and esophageal varices treated since 1980. Methods of operation were confined to those with the least influence on portal circulation, namely selective shunts and nonshunting direct interruption procedures. The bleeding rates were 19.2% in the medical group and none in the surgical group (p less than 0.01). The mortality in the medical group in case of first bleeding was 50%. Operative mortality was 3.3%. There was no difference in the survival rate between the two groups at the time of 2 years follow-up. Prophylactic surgery led to a prevention of esophageal bleeding without any increase in the mortality rates.

Adult↗

Risk factors and risk reduction of breast and ovarian cancer.

PURPOSE OF REVIEW: Breast and ovarian cancer remain a significant burden for women living in the Western world. This paper reviews the risk factors and current strategies to prevent these diseases. RECENT FINDINGS: Established factors associated with the risk of breast cancer include family history, reproductive factors and lactation, as well as age at menarche and menopause. Hormone replacement therapy increases the risk, whereas oral contraceptives probably confer no increased risk. Alcohol moderately increases the risk, whereas a diet rich in folate and carotenoids might be protective. The role of other dietary factors, smoking and physical exercise remain unclear. Important risk factors for ovarian cancer are reproductive factors and possibly the long-term use of hormone replacement therapy. The risk is decreased by oral contraceptives. In carriers of a BRCA1 or BRCA2 gene mutation, prophylactic surgery can significantly reduce the risk of breast as well as ovarian cancer. Tamoxifen may be considered as a chemopreventive agent in women with a high risk of breast cancer, including carriers of a BRCA2 mutation, but is probably not effective in BRCA1 carriers. SUMMARY: During the period of this review, the importance of several known risk factors was confirmed, whereas the effects of other factors became more clear. Chemoprevention and prophylactic surgery have emerged as preventative options that can reduce the risk of breast and ovarian cancer.

Alcoholism↗

Do physicians tailor their recommendations for breast cancer risk reduction based on patient's risk?

OBJECTIVE: To investigate how physicians tailor their recommendations for breast cancer prevention and risk reduction. DESIGN: Cross-sectional, mail survey. PARTICIPANTS: Random sample of primary care physicians in California (N = 822). MEASUREMENTS AND MAIN RESULTS: Six standardized patient scenarios were used to assess how women's breast cancer risk factors influence physicians' recommendations for screening mammography, counseling about lifestyle behaviors, genetic testing, the use of tamoxifen, prophylactic surgery, and referral to a breast specialist. Over 90% of physicians endorsed mammography for all of the scenarios. Similarly, approximately 80% of physicians endorsed counseling about lifestyle factors for all of the scenarios. Five-year risk of developing breast cancer and family history were both strongly associated with each of the 6 recommendations. Importantly, however, physicians were more likely to endorse the discussion of genetic testing, the use of tamoxifen, and prophylactic surgery for women with a family history of breast cancer compared with women at a higher risk of developing breast cancer but without a family history. Obstetrician-gynecologists were more likely to endorse most of these practices compared with internists. CONCLUSIONS: Mammography and counseling about lifestyle behaviors are widely endorsed by physicians for breast cancer prevention and risk reduction. Whereas physicians are generally able to tailor their recommendations for prevention and risk reduction based on risk, they may perhaps underutilize genetic evaluation and newer therapeutic options for primary prevention for women who are at high risk of developing breast cancer but do not have a family history.

Adult↗

BRCA-mutation-associated fallopian tube carcinoma: a distinct clinical phenotype?

OBJECTIVE: To compare clinical and histologic features between fallopian tube cancers in women with germline BRCA mutations and sporadic cases. METHODS: Twenty-eight patients with fallopian tube cancer had BRCA mutation testing using multiplex polymerase chain reaction and protein truncation testing. Histologic slides were reviewed by 2 pathologists, and immunohistochemical staining for p53, ki67, estrogen receptor, and progesterone receptor was performed on carcinomas and dysplastic and benign tubal epithelia. RESULTS: Twelve of 28 (43%) women had BRCA mutations: 11 BRCA1, 1 BRCA2. Excluding 4 cases found at prophylactic surgery, the median age of diagnosis of BRCA mutation carriers was 57 years compared with 65 years among sporadic cases (P = .09). Patients with BRCA-associated fallopian tube cancer had a median survival time of 68 months compared with 37 months when compared with sporadic cases (P = .14). Both groups had predominantly advanced stage, high grade, serous fallopian tube cancers. No patient had exclusively proximal disease. Occult fallopian tube cancer diagnosed at prophylactic surgery in BRCA mutation carriers was exclusively distal. "Skip" areas of high-grade dysplasia were only seen in 2 patients, both of whom were BRCA mutation carriers. There were no differences in the immunohistochemical staining for p53, ki67, estrogen receptor or progesterone receptor in carcinomas and dysplastic or benign epithelia of patients with or without BRCA mutations. Overexpression of p53 was commonly seen in fallopian tube cancers and dysplastic epithelium, but rarely noted in benign epithelium. CONCLUSION: Fallopian tube cancer is part of the BRCA mutation phenotype and seems to share many clinical features with sporadic fallopian tube cancers, including no exclusively proximal disease. The presentation of BRCA-associated fallopian tube cancers may, however, occur at a younger age and have an improved survival.

Adult↗

A perspective on the use of FVIII concentrates and cryoprecipitate prophylactically in surgery or therapeutically in severe bleeds in patients with von Willebrand disease unresponsive to DDAVP: results of an international survey. On behalf of the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the ISTH.

An international registry was established by the Subcommittee on von Willebrand Factor of the SSC/ISTH on the treatment of patients with types of von Willebrand disease (vWD) unresponsive to DDAVP infusion. Data was collected on 76 surgical events in 64 patients from 19 treatment centers. Thirty-three non-mucosal, 12 mucosal, 10 orthopedic and 21 dental procedures were reported. In the 76 surgical events, 14 cases prophylactically received cryoprecipitate while 62 received factor VIII (FVIII) concentrate. Surgical hemostasis was reported as satisfactory, good, or excellent in 75 of the 76 cases. Post-infusion bleeding times were measured in only three of 14 surgical events treated with cryoprecipitate. All three cases had a reduction but not correction of the bleeding time. The post-infusion bleeding time was measured in 27 of 62 cases in which FVIII concentrates were used. The bleeding time time was normalized in 15, reduced but not normalized in eight, and not changed from baseline in four. Data was also collected from 16 treatment centers on 50 serious bleeding events in 35 patients. These included 19 gastrointestinal, 15 other mucosal, four central nervous system, seven orthopedic, and five other mucosal, four central nervous system, seven orthopedic, and five other bleeds. Eleven cases received cryoprecipitate and 39 received FVIII concentrate as primary therapy. The efficacy of treatment was considered good or excellent in 49 of 50 cases. Post-infusion bleeding times were measured in only 15 of the 50 reported bleeding events. The post-infusion bleeding time was normalized in six, decreased but not normalized in eight, and not changed from baseline in one. In this retrospective survey, FVIII concentrates were subjectively as efficacious as cryoprecipitate in both the surgical setting and for the treatment of severe bleeds in patients with types of vWd unresponsive to DDAVP. Since the bleeding time was monitored during therapy in only a minority of these cases, a definitive relationship between the efficacy of therapy and normalization or reduction of the bleeding time in these two clinical settings cannot be established from this study. A prospective study on the use of FVIII and/or vWf concentrates in these clinical settings is necessary to address this issue.

Cryoglobulins↗

Risk reduction behaviors and provider communication following genetic counseling and BRCA1 mutation testing in an African American kindred.

Little is known about the impact of cancer genetic counseling and testing on health behaviors in racial and ethnic subgroups. This prospective observational study examined use of risk reduction strategies following BRCA1 counseling and testing. Participants were female members of an African American kindred who received genetic education, counseling and testing (n = 40) and completed a 1-year follow-up interview. Mutation carriers were more likely to opt for breast (100%, 7/7) and ovarian (25%; 1 of 4) cancer surveillance than prophylactic surgery. Following genetic counseling, 71% (5/7) of the BRCA1 carriers who opted for surveillance reported having a mammogram within the year following receipt of their genetic test results. Ovarian cancer screening among mutation carriers increased from 0% at baseline to 25% (one of four) at 1 year. Compared to noncarriers (23%, 7/30), carriers (70%, 7/10) were more likely to discuss their BRCA1 test results with their primary health care providers. Surveillance for breast cancer was preferred to prophylactic surgery and chemoprevention as a way to reduce risk for these cancers. Our data indicate that patient-provider communication about BRCA1 test results is suboptimal.

Adult↗

Referral and experience with genetic testing among women with early onset breast cancer.

The purpose of this study was to determine whether physicians refer women with early onset breast cancer for genetic testing for BRCA1 and BRCA2, and how women respond to being offered testing and use the results. A web-based survey was distributed to 1221 women with early onset breast cancer. The survey included 158 questions divided into the following sections: demographics, family history of cancer, medical history, treatment history, and experience with genetic testing. Of 551 women diagnosed since 1993 who responded to the survey (45.1%), less than half (45%, n = 246) had ever discussed genetic testing with their physician and/or been referred to see a genetic counselor. Women with a family history of cancer (53%) and Ashkenazi Jewish women (81%) were more likely to have been referred. Of those who had discussed testing, 60% had undergone or were interested in testing. Overall 92 women were tested and 19 (20.6%) of these tested positive for a deleterious BRCA1 or BRCA2 mutation. Fourteen (74%) who tested positive subsequently underwent prophylactic surgery. Satisfaction with counseling and the decision to be tested was high. Among women who were not offered testing, the fact that the test had not been offered by their physician (89%), and fear of discrimination (83%) were the two most frequently cited factors for lack of interest in testing. A substantial number of women are not being referred to genetic counseling and/or testing after a diagnosis of early onset breast cancer. Among those who were tested, there was high interest in prophylactic surgery after confirmation of a BRCA1/2 mutation.

Adult↗