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Genetic detection: the need for psychosocial support in modern cancer prevention.

During recent years the gap between the rapid implementation of new technologies in cancer prevention and the slow development of a complementary psychological framework to conceptualize the transmission of genetic informations to patients has been deplored. Such a framework should include all psychological aspects surrounding the genetic consultation, reaching from the information and education of the general public to the impact of prophylactic surgery. While some of the psychological consequences of modern cancer prevention can not be fully foreseen and have first to be documented and analysed, others can easily be anticipated. The authors will try to outline a psychological framework that could help in facing potential negative effects of these beneficial preventive possibilities.

Adaptation, Psychological↗

A risk-benefit analysis of elective bilateral oophorectomy: effect of changes in compliance with estrogen therapy on outcome.

A bilateral oophorectomy at the time of elective hysterectomy is often performed to prevent ovarian cancer. The assumption that endogenous estrogen can be easily replaced with supplemental medication fosters the decision for routine oophorectomy. Published reports on the use of postmenopausal estrogen indicate that compliance is less than perfect. This fact could affect the overall outcome. Decision analysis techniques with Markov cohort modeling were used to evaluate the policy of elective bilateral oophorectomy. Results from studies judged methodologically sound were combined to determine values representing the influence of estrogen on coronary heart disease, breast cancer, and osteoporotic fracture. The decision tree also explicitly incorporated patient compliance. When compliance with estrogen therapy is assumed to be perfect, oophorectomy yields longer life expectancy than retaining the ovaries. When actual drug-taking behavior is considered, retaining the ovaries results in longer survival. This analysis highlights the importance of including the effects of patient compliance with treatment recommendations when the impact of a health policy decision such as prophylactic surgery is assessed.

Adult↗

Natural history of fundic gland polyposis in patients with familial adenomatosis coli/Gardner's syndrome.

In order to study the natural history of fundic gland polyposis, 23 patients with familial adenomatosis coli/Gardner's syndrome were examined over a follow-up period ranging from 17 mo to 13 yr (average 6 yr). Examinations included gastric radiography and endoscopy with biopsy. Fundic gland polyps were found in 10 individuals. The size and number of polyps varied considerably. During the follow-up period, there was an increase in number or size of polyps, or both, in 5 patients (aged 8-27 yr), a decrease or disappearance in 2 patients (aged 36 and 41 yr), an initial decrease or disappearance followed by a late-occurring increase in 2 patients (aged 28 and 35 yr), In addition, malignant or adenomatous changes of fundic gland polyps were not observed in any patient. Therefore, fundic gland polyposis in patients with familial adenomatosis coli/Gardner's syndrome may appear as early as 8 yr of age. In some patients there is a gradual increase in number and size of polyps, whereas in others, polyp proliferation ceases and polyps may even decrease in number and size. Our findings indicate that the fundic gland polyposis does not require prophylactic surgery and that careful periodic follow-up should suffice.

Adolescent↗

Colonoscopic surveillance in long-standing total ulcerative colitis--a 15-year follow-up study.

In a 15-year surveillance program composed of 72 patients with total ulcerative colitis, 12 patients developed definite dysplasia. At endoscopy, low-grade dysplasia was detected in seven patients, high-grade in four, and a carcinoma (Dukes' stage A at operation) in one. One of the patients with high-grade dysplasia and macroscopical lesions at colonoscopy had a carcinoma (Dukes' A) detected at operation. A sequential development of dysplasia was found in seven patients. The cumulative risk of developing at least low-grade dysplasia was 14% after 25 years of disease duration. Using flow cytometric analyses, abnormal, aneuploid DNA content was detected in biopsies of 12 of 59 patients (20.3%); this correlated significantly with low-grade and high-grade dysplasia. Aneuploidy preceded dysplasia in two patients and was also detected in two dysplasia-free patients. The long-term use of colonoscopic surveillance in ulcerative colitis is a reliable way to select patients, in whom dysplasia is developing, for prophylactic surgery. Additionally, flow cytometric DNA analyses may help in the selection. The risk of missing a carcinoma until it becomes incurable appears to be low.

Adolescent↗

Rupture of an aneurysm of the splenic artery and pregnancy: a case report.

The mortality risk in rupture of an aneurysm of the splenic artery is 69.4% for pregnant women and 90.8% for the foetus. 95% of all patients are asymptomatic up to this stage. If the aneurysm is diagnosed earlier, the maternal mortality rate can be reduced to 0.5% by prophylactic surgery. 25% of patients with symptoms display prodromes which, with accurate knowledge of the syndrome, make it possible to make an early diagnosis. Characteristics of the disorder, its risk factors, signs for early diagnosis and therapeutic measures, as well as an up-to-date review of the literature are presented here, illustrated by one of our own case studies.

Adult↗

Vitreous base classification of retinal tears: clinical application.

The abundant data about retinal tears has shown that they are prevalent in the general population and that the vast majority of retinal tears do not lead to retinal detachment. What remains to be clarified are the criteria for identifying the few retinal breaks which require prophylactic surgery to prevent their progression to retinal detachment. Numerous reports have identified clinical features which correlate with the risk the retinal detachment. These correlative data offer at best only a suggestion about the need for treatment of any specific retinal break. This paper-demonstrates how the categorization of a retinal tear on the basis of vitreoretinal anatomic detail may be used clinically to make an objective and nonstatistical judgment about the prognosis of any specific retinal break. The application of this new categorization offers an advance in the care of patients with retinal tears.

Cataract Extraction↗

Rupture of a previously documented asymptomatic aneurysm enhances the argument for prophylactic surgical intervention.

A case is presented of an incidentally discovered 6-mm aneurysm that was left untreated and subsequently produced a subarachnoid hemorrhage. The patient had no previous history of intracranial hemorrhage from any other source. A case of this type has not been previously documented in the literature. This experience points out the potential for catastrophe in small unruptured aneurysms found in patients without previous subarachnoid hemorrhage. The extremely low operative morbidity for repair of these types of lesions in otherwise healthy individuals would argue strongly for prophylactic surgery in properly selected patients.

Female↗

Treatment of skeletal metastases from urologic malignancies.

Metastases from genitourinary tumors frequently involve the skeletal system and often produce the most disabling symptoms. Judicious early orthopedic management may prevent paralysis and maintain ambulation, thus significantly improving the quality of life. The role of prophylactic surgery for impending fractures and the symptomatic therapy of painful metastatic foci are discussed.

Adenocarcinoma↗

Prophylactic resection of a tricuspid valve vegetation in infective endocarditis.

A heroin addict who appeared to have recovered clinically from infective endocarditis of the tricuspid valve as judged by the usual criteria underwent prophylactic resection of a large vegetation on the tricuspid valve in order to prevent severe pulmonary embolism. Prophylactic surgery was justified by the size and as judged by cross-sectional echocardiography of the vegetation and its morphology.

Adult↗

Long-term outcome of surgically treated unruptured cerebral aneurysms.

We report the surgical morbidity and mortality and the results of statistical analysis based on the long-term outcome (average 50.1 months) of 69 patients with unruptured cerebral aneurysms. These patients harbored a total of 76 unruptured cerebral aneurysms, 72 larger than 3 mm in diameter. All the latter were surgically treated. There was no operative mortality. Operative morbidity occurred in 5 patients (7.2%), including hemiplegia in 2 from obliteration of perforator vessels, transient memory impairment in 2 due to brain retraction, and transient oculomotor nerve palsy in 1 patient resulting from an unknown etiology. During the observation period, 53 patients (76.8%) had a good or fair outcome, 11 (15.9%) had a poor outcome, and 5 (7.3%) died from causes unrelated to the aneurysms, such as pneumonia, gastrointestinal bleeding, and heart failure. The 5-year survival rate was 94%. Statistical analysis of the long-term outcome of all patients showed no significantly important factor influencing long-term morbidity. Prophylactic surgery of aneurysm is recommended for low-risk patients who may develop eventual rupture of an aneurysm, but perforator vessels around the aneurysm should be preserved, clips should be properly placed, and brain retraction should be minimized.

Adult↗

Personal health behaviors in women who have undergone risk-reducing mastectomy.

BACKGROUND: Risk-reducing mastectomy (RRM) remains an effective yet controversial modality for the primary prevention of breast cancer. Is the choice of RRM consistent with a generally proactive healthy lifestyle? METHODS: The National Prophylactic Mastectomy Registry is a volunteer database comprised of 460 women who have undergone bilateral RRM. Each patient received a questionnaire drawn from the Centers for Disease Control Behavioral Risk Factor Surveillance System. Their responses were compared with gender-specific national data from the Centers for Disease Control. RESULTS: Women in the RRM group were statistically more likely to engage in risk-reducing personal health behavior including not smoking, exercising, maintaining their health, and taking advantage of screening programs. CONCLUSIONS: Women in the registry who underwent RRM practiced a more "healthy" lifestyle than gender-matched controls. Therefore, the decision to have prophylactic surgery may have been part of a proactive approach toward their overall physical well-being.

Adult↗

RET oncogene mutations in 75 cases of familial medullary thyroid carcinoma in Japan.

The familial form of medullary thyroid carcinoma (MTC) is caused by mutations of the RET protooncogene. We registered 60 multiple endocrine neoplasia (MEN) 2A patients, 12 familial non-MEN medullary carcinoma (FMTC) patients, and three MEN2B patients with a confirmed RET germline mutation. All 60 MEN2A patients had RET mutations in a cysteine-rich domain. Seven of the FMTC patients had a mutation in cysteine-rich domain, and the other five had a mutation in codon 768, which encodes a tyrosine-kinase domain. Two of the MEN2B patients had a mutation in codon 918, and one patient had a double mutation, one in codon 804 and the other in codon 806, both of which are all encoded tyrosine-kinase domain. The genotype-phenotype correlations of our data will allow individualized recommendations for the optimal timing of prophylactic surgery.

Carcinoma, Medullary↗

Testing for ovarian cancer.

Ovarian cancer is responsible for more deaths per annum than cervical and endometrial cancer combined. Patients are often diagnosed at a late stage because of the non-specific symptoms of this disease. It can be difficult to differentiate between benign and malignant ovarian pathology, and a malignancy risk index has been developed to guide clinicians. The accuracy of CA125 and ultrasound scans as screening tests is being assessed in randomised controlled trials and proteomic technology shows promise for the early detection of cancers. At present, without accurate screening and early diagnostic techniques, high-risk patients often chose to have prophylactic surgery.

Carcinoma↗

Patient responses to the disclosure of BRCA mutation tests in hereditary breast-ovarian cancer families.

Limited attention has been given to the impact of BRCA mutation disclosure on participants' psychological reaction and cancer control compliance. We asked women (290 mutation-positive, 370 mutation-negative) from 84 hereditary breast-ovarian cancer (HBOC) families with known deleterious BRCA mutations to participate in an evaluation regarding cancer prevention recommendations before and after BRCA mutation disclosure. Both men and women (n = 780) were invited to complete a questionnaire to evaluate their psychological response to BRCA mutation disclosure. Before BRCA testing, 23.0% (152 of 660) of these women underwent prophylactic bilateral mastectomy, oophorectomy, or both; of these, 53% (80 of 152) were subsequently found to be mutation negative. After mutation disclosure, 52.9% (110 of 208) of mutation carriers and 0% (0 of 203) of noncarriers underwent prophylactic surgeries. These changes were statistically significant compared with before disclosure (P < 0.0001). The rate of transvaginal ovarian ultrasound screening was significantly increased in mutation carriers (P < 0.015) and marginally decreased in noncarriers (P = 0.063) post disclosure. Psychologically, compared with noncarriers without cancer, a significantly higher percentage of carriers, regardless of their cancer status, felt guilt about passing a mutation to their children, worried about developing additional cancer or their children developing cancer, and were concerned about health insurance discrimination. Despite these psychological consequences, carriers and noncarriers reported a positive attitude toward genetic testing.

Breast Neoplasms↗

Preoperative atrial histological changes are not associated with postoperative atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) remains the most common complication of cardiac surgery. Prophylactic therapies have been studied, but their utility has been limited by the inability to accurately identify patients who will develop this complication. Recent studies have suggested that atrial myolysis and lipofuscin pigmentation are associated with post-coronary artery bypass grafting (CABG) AF. We sought to determine whether there is an association between preoperative atrial histology and subsequent post-CABG AF. METHODS: Samples of right atrial appendage were obtained from 94 patients undergoing CABG. Tissue was formalin fixed and paraffin embedded. Sections 4 mum thick were cut, stained with hematoxylin and eosin, and examined for the following parameters: fibrosis, myolysis, inflammation, nuclear size, pericardial exudates, lipofuscin pigment, arteriolar hypertrophy, contraction banding, mesothelial hyperplasia, and atrial diverticula. Results were graded as absent, mild, moderate, or severe by two independent observers who were blinded to the clinical outcomes. Univariate and multivariate analyses were carried out. RESULTS: Thirty-six (38%) patients developed AF. No correlation was found between the 10 features assessed, including myolysis and lipofuscin pigmentation, and the development of AF. CONCLUSION: Simple morphology of right atrial appendages does not predict the development of postoperative AF.

Aged↗

[Hereditary predispositions to gynaecological cancers].

The breast, ovary and endometrial cancers are hereditary in 5 to 10% of the cases. These genetic predisposition syndromes can be classified into two major classes: ovarian cancer and breast cancer predisposition family cases (genes BRCA1 and BRCA2) and family cases of colon cancer, endometrial cancer and ovarian cancer (Lynch syndrome or HNPCC) (genes hMLH1, hMSH2, hMLH6). The estimate of the family and individual risk can contribute in a determining manner to the management of these patients, by the practice of screening or an adapted prevention. Indeed, the risk of cancer of an individual having a positive test for a gene of predisposition to breast cancer (BRCA1, BRCA2) or to the colon cancer (hMLH1, hMSH2, hMLH6) lies between 50 and 70% at the age of 70 years. The indication of a genetic test must be discussed within the framework of an oncogenetic consultation. An individual and family medical management ranging from simple monitoring to prophylactic surgery is proposed to these predisposed people.

Adaptor Proteins, Signal Transducing↗

[Identification and management of hereditary breast-ovarian cancers (2004 update)].

BACKGROUND: Since the last recommendations, up to 2500 new references had been published on that topic. METHODOLOGY: On the behalf of the health Minister, the Ad Hoc Committee consisted of 13 experts carried out a first version revisited by five additional experts who critically analyzed the first version of the report. MAIN UPDATING: Breast and ovarian cancer seem to be associated with fewer deleterious mutations of BRCA1 and BRCA2 than previously thought. The screening of ovarian cancer is still not an attractive option while in contrast MRI may be soon for these young women with dense breast, the recommended option for breast cancer screening. The effectiveness of prophylactic surgeries is now well established. French position is to favor such surgeries with regard to a quality of life in line with the expected benefit, and providing precise and standardized process described in the recommendation. CONCLUSIONS: Due to methodological flaws, the low power and a short follow-up of the surveys, this statement cannot however aspire to a high stability.

Breast Neoplasms↗