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Cancer risk in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are at increased risk for developing cancer of the gastrointestinal tract, particularly colorectal cancer. Because of the relative rarity of IBD in the general population, it has been difficult to quantify this risk. Efforts to reduce the risk have included both prophylactic surgery and endoscopic screening programs. Because of the potential impact on quality of life and life expectancy, the optimal strategy for reducing this risk has not been defined. This article reviews the current literature relating to the risk of cancer for patients with IBD and methods to reduce this risk.

Adenocarcinoma↗

Atypical ductal hyperplasia of the breast in young women: two case reports.

Atypical ductal hyperplasia of the breast is a benign proliferative condition that is associated with an increased risk of development of breast cancer in either the ipsilateral or contralateral breast. Following diagnosis at biopsy, respective management options range from observation to chemoprophylaxis to prophylactic surgery. We present two cases in young women, facing prolonged follow-up, one managed with observation only, and the other managed with ipsilateral mastectomy and reconstruction.

Adolescent↗

Symptomatic solitary right renal vein aneurysm: a case report.

Renal vein aneurysms are very uncommon. Those located in the right side are exceptional. A symptomatic, solitary, voluminous aneurysm of the right renal vein in a 33-year-old man is reported. The lesion was diagnosed preoperatively as a renal tumor. The pathologic study of the nephrectomy specimen disclosed a thrombosed saccular aneurysm measuring 5.5 cm with marked medial atrophy of its wall. Recognition that a mass like this reported is of vascular origin is very important to avoid percutaneous biopsy which could be potentially hazardous; and for undertaking conservative prophylactic surgery. Renal venography is indicated for the diagnosis of these lesions.

Adult↗

Deciding when to intervene: a Markov decision process approach.

The aim of this paper is to point out the difference between static and dynamic approaches to choosing the optimal time for intervention. The paper demonstrates that classical approaches, such as decision trees and influence diagrams, hardly cope with dynamic problems: they cannot simulate all the real-world strategies and consequently can only calculate suboptimal solutions. A dynamic formalism based on Markov decision processes (MPPs) is then proposed and applied to a medical problem: the prophylactic surgery in mild hereditary spherocytosis. The paper compares the proposed approach with a static approach on the same medical problem. The policy provided by the dynamic approach achieved significant gain over the static policy by delaying the intervention time in some categories of patients. The calculations are carried out with DT-Planner, a graphical decision aid specifically built for dealing with dynamic decision processes.

Cholecystectomy↗

BRCA1 mutation testing for Japanese patients with ovarian cancer in breast cancer screening.

From February 1996 to April 1998, 2967 women received screening for breast cancer in the gynecologic ambulatory practice of the Hokkaido University Hospital. In 116 Japanese women with epithelial ovarian cancer, mutation analysis of BRCA1 exon 11 in genomic DNA was performed by the stop codon (SC) assay and DNA sequence analysis. Clinicopathological factors were also investigated in these patients. The aim of this study was to examine the advantages of performing BRCA1 mutation testing for ovarian cancer patients during breast cancer screening. We achieved a high detection rate (6.0%) of patients with germline mutations in BRCA1. The high frequencies of breast ovarian cancer syndrome, serous adenocarcinoma, high histological grades, advanced FIGO stages, and breast cancer as double cancer were found to be characteristic of ovarian cancer with germline mutations in BRCA1. These characteristics may assist physicians in selecting BRCA1 mutation testing for ovarian cancer patients. The mean age at diagnosis of ovarian cancer was 51.0 and 51.2 years in the groups with and without mutation, respectively, and no difference was found in age at diagnosis. All of the nine living female mutation carriers were offered the options of increased surveillance or prophylactic surgery, and all chose the former. We have performed breast cancer screening and/or ovarian cancer screening every 6 months for these carriers. This may allow another advantage in establishing a relationship of mutual trust with a patient from a series of responsible follow-ups.

Adolescent↗

Management of familial breast cancer risk.

Women who are members of breast cancer families are at increased risk for breast cancer. The cloning of BRCA1 and BRCA2 has made it possible to identify mutation carriers within some of these families. Management of breast cancer risk in these families, which presents enormous challenges to patients and clinicians, is addressed. Management should begin with a full evaluation of the patient, including construction of a three-generation pedigree, ascertainment of non-genetic factors that may impact on risk, information on previous and current breast health, practice of and attitudes toward screening, and the psychosocial impact of family history on the individual. Patient priorities in risk management should be explicitly reviewed; these may include survival, cancer prevention, breast preservation, optimization of quality of life or minimization of disruption of day-to-day activities. Approaches to risk management involve screening (usually considered the mainstay), anti-estrogens, prophylactic surgery and/or lifestyle modifications. Specific gene therapy may become available in the future. Management decisions should be individualized to reflect risk levels and patient priorities and goals, within bounds that are medically and scientifically reasonable. An explicit examination of different time-frames (1, 5, 10 years) is recommended given the rapid evolution of knowledge in this area.

Adult↗

Association of correlates of endogenous hormonal exposure with breast cancer risk in 426 families (United States).

OBJECTIVE: Women with a strong family history of breast cancer are at significantly increased risk of developing the disease. There is emerging evidence that certain reproductive factors may further elevate risk in these women. We examined whether a family history of breast cancer modifies the association between correlates of endogenous hormonal exposures and breast cancer in a study of 426 families ascertained through breast cancer probands. METHODS: Analyses of reproductive factors and breast cancer were performed on 395 sisters and daughters of probands, 3014 nieces and granddaughters. and 2768 marry-ins. RESULTS: Through 226,266 person-years of follow-up since 1952, 240 women developed breast cancer. No statistically significant interactions were observed between relationship to proband and age at menarche, age at menopause, other characteristics of the menstrual cycle, parity, age at first and last birth, infertility, and total ovulatory years. CONCLUSIONS: Our findings suggest that most reproductive factors influence breast cancer risk similarly in women with and without a family history of breast cancer. Further studies are needed on individuals who are more homogeneous with regard to hereditary background. However, other options for prevention, such as prophylactic surgery or chemoprevention, may be necessary to have a substantial impact on risk reduction in women at high genetic risk.

Adolescent↗

Short- and long-term impact of receiving genetic mutation results in women at increased risk for hereditary breast cancer.

Forty-seven unaffected women from high-risk breast cancer families who had received results for hereditary breast/ovarian predisposition genes between 1 month and 5 years ago were interviewed regarding their experiences. Women responded to open-ended questions. The initial emotional turmoil reported by most was generally short lived. However, the impact of genetic testing went beyond the individual to the extended family and social context, particularly in the short-term. A common theme was the difficulty associated with divulging a result to family members, who were also adjusting to their own result. The majority of carriers reported advantages that were both physical (options for surveillance programs and prophylactic surgery) and emotional (reduced uncertainty, increased awareness of options and knowledge about risk, preparation time). Most carriers reported no change in lifestyle although some reported discovering their mutation status as a positive life-changing experience. Implications for genetic counseling and further research are discussed.

Adaptation, Psychological↗

Analyzing the process and content of genetic counseling in familial breast cancer consultations.

A detailed examination of the process of genetic counseling has been identified as a priority area for research by previous authors. This multicenter longitudinal study examined the process and content of genetic counseling in initial consultations with women from high-risk breast cancer families. One hundred and fifty-eight consultations with women unaffected and affected with breast cancer were audio taped and transcribed verbatim. A detailed coding system was developed. Clinical geneticists and genetic counselors demonstrated consistently good practice in giving detailed information on essential aspects related to familial breast cancer such as screening and management, genetic testing, breast cancer genetics, and prophylactic surgery. Eliciting emotional concerns and facilitating communication were found to be inconsistently present. As clinical practice guidelines and the general communication literature emphasize the importance of these factors, this is an area where training in or self-monitoring of such behaviors may assist consultants to further develop these skills.

Adult↗

Prospective study of 36 patients with 46 popliteal artery aneurysms with non-surgical treatment.

BACKGROUND: There is a lack of prospective studies with popliteal aneurysms (PAA) < 2 cm and the very few information about the natural cause of the disease. PATIENTS AND METHODS: Between 1995 and 2000 46 patients having 65 popliteal artery aneurysms have been examined. The mean diameter was 1.9 cm (0.8-4 cm). In 41% of the cases PAA were bilateral, additional extrapopliteal aneurysms were found in 37%. The PAA was occluded in 8 patients at the initial examination (mean diameter 2.4 cm: 1.4-4 cm). One of these patients had to be amputated (long-term diabetes, dialysis and severe generalized peripheral arteriosclerosis). Since no information could be obtained from two patients, it was possible to prospectively monitor 36 patients with 46 PAA (30 m, 6 f) over a period of 2.5 years. 19 patients were treated with platelet inhibitors, 16 with coumarin and one refused any thromboembolic prophylaxis. The patients were examined every year by telephone interview and duplexsonography. RESULTS: During the monitoring period there occurred two complete occlusions and one distal arterial progression, while 2 patients died, but no amputation. The total complication rate was 6.5% with a higher incidence in PAA > 2 cm of diameter (14.2 vs. 3.1%). All complications were found in PAA with mural thromboses. Coumarin seems to be superior platelet aggregation inhibitors with a complication rate of 0% vs. 14.3%. The mean increase in diameter during follow-up was dependent on PAA size, 1.5 mm/year for PAA > 2 cm vs. 0.7 mm/year for PAA < 2 cm. CONCLUSION: This prospective study emphasises the necessity of a prophylactical surgery in patients with an aneurysm diameter > 2 cm. In view of the low rate of complications of the natural course of PAA (6.5% of all PAA or 14.2% for PAA > 2 cm/2.5 years), the bypass surgery should be performed by an experienced vascular department. Patients with PAA < 2 cm or patients with contraindication for peripheral bypass should receive anticoagulation.

Adult↗

Decision making and decision support for hereditary breast-ovarian cancer susceptibility.

Genetic testing for disease susceptibility has the potential to revolutionize health care by allowing for individually tailored disease prevention strategies. To achieve this promise, patients and physicians must use the information obtained through genetic testing to make medical decisions that are consistent with patient preferences and that lead to reduced disease morbidity and mortality. However, decisions associated with genetic testing can be complex. In this article, the authors review decision making associated with genetic testing and the medical management of hereditary breast-ovarian cancer susceptibility. They focus on decisions regarding BRCA1/2 testing and prophylactic surgery among BRCA1 and BRCA2 mutation carriers. They highlight the role of patient preferences and decision support in this population. The studies reviewed indicate that although patients' preferences do predict genetic testing and management decisions, other factors also influence their decision making. In particular, the authors discuss the role of anxiety and worry in relation to testing and surgery decisions.

Breast Neoplasms↗

Clinical outcome of prophylactic oophorectomy in BRCA1/BRCA2 mutation carriers and events during follow-up.

A retrospective study was performed to assess the histopathologic findings in high-risk women undergoing bilateral prophylactic (salpingo)-oophorectomy. The medical files of BRCA1 or BRCA2 mutation carriers and members of a hereditary breast/ovarian cancer (HBOC) family, who had undergone prophylactic surgery, were reviewed. In all, 38 women underwent a bilateral oophorectomy (26 BRCA1, three BRCA2 and nine HBOC, respectively). A total of 90 women underwent bilateral salpingo-oophorectomy (58 BRCA1, six BRCA2, one BRCA1 and 2, 25 HBOC, respectively). At the time of salpingo-oophorectomy, five of 58 BRCA1 carriers (8.6%) were diagnosed with an occult carcinoma: two fallopian tube carcinomas, two ovarian carcinomas and one case was defined as a fallopian tube/ovarian carcinoma. No occult carcinomas were found in the other groups. Of the 38 patients, who underwent a bilateral oophorectomy (mean follow-up 45 months), three of 26 BRCA1 mutation carriers (3.4 in 100 women-years) developed peritoneal papillary serous carcinoma (PPSC) during follow-up. So far, no PPSC have occurred in the 90 women, who underwent a salpingo-oophorectomy (mean follow-up 12 months), including 58 BRCA1 carriers (0 in 60 in women-years). These results contribute to the thesis that BRCA1 germline mutation carriers are not only at risk for ovarian cancer, but also for fallopian tube carcinoma and peritoneal papillary serous carcinoma. Our data suggest that PPSC risk among BRCA2 carriers is lower than among BRCA1 carriers.

Adult↗

Estimating the survival benefits gained from providing national cancer genetic services to women with a family history of breast cancer.

The aim of this paper is to compare a service offering genetic testing and presymptomatic surveillance to women at increased risk of developing breast cancer with its predecessor of no service at all in terms of survival and quality-adjusted survival (QALYs) by means of a Markov cohort chain simulation model. Genetic assessment and presymptomatic care provided between 0.07-1.61 mean additional life years and 0.05-1.67 mean QALYs over no services. Prophylactic surgery and surveillance extended mean life expectancy by 0.41-1.61 and 0.32-0.99 years, respectively over no services for high-risk women. Model outcomes were sensitive to all the parameters varied in the sensitivity analysis. Providing cancer genetic services increase survival and as long as services do not induce adverse psychological effects they also provide more QALYs. The greatest survival and QALY benefits were found for women with identified mutations. As more cancer genes are identified, the survival and cost-effectiveness of genetic services will improve. Although mastectomy provided most additional life years, when quality of life was accounted for oophorectomy was the optimal strategy. Delayed entry into coordinated genetic services was found to diminish the average survival and QALY gains for a woman utilising these services.

Adult↗

DNA aneuploidy as a marker of premalignancy in surveillance of patients with ulcerative colitis.

BACKGROUND: Patients with ulcerative colitis have an increased risk of developing colorectal cancer. Specific and sensitive markers for premalignancy are needed. The present study evaluates the status of DNA aneuploidy (abnormal stemlines) as such a marker. METHODS: A prospective surveillance programme was conducted for all patients with ulcerative colitis from a defined area. Regular colonoscopy with mucosal sampling for histological evaluation and flow cytometric DNA analysis was performed. Some 147 patients were studied from 1984 to 1997. RESULTS: DNA aneuploidy was found in 20 patients. All but one had total colitis. The time from onset of disease to aneuploidy ranged from 5 to 31 years. Fourteen of the patients developed morphological alterations. In the same interval 127 patients, of whom 75 had total colitis, did not develop aneuploidy. Among patients with morphological alterations and aneuploidy, aneuploidy preceded these alterations in four patients and was present at the same examination in three; in seven patients the morphological alterations preceded the aneuploidy. Aneuploidy was diagnosed before the appearance of a dysplasia- associated lesion or mass in four of five cases. CONCLUSION: Flow cytometric DNA analysis has definite value as a complement to histological examinations in cancer surveillance of patients with ulcerative colitis. Aneuploidy indicates a high risk for developing severe premalignant changes. However, there is no evidence to support the use of DNA aneuploidy as a sole indication for prophylactic surgery against cancer.

Aneuploidy↗

Genetic predisposition to breast cancer: a surgical perspective.

BACKGROUND: Molecular alterations in proto-oncogenes, tumour suppressor genes, and genes that function in DNA damage recognition and repair are considered to be hallmarks of a carcinogenic process, including breast carcinogenesis. METHODS: A computer-assisted search of the English literature (Medline database, 1990-1999) was performed, followed by a manual search of the reference list of pertinent articles retrieved. RESULTS: Hereditary breast cancer accounts for 5-10 per cent of all breast cancer cases. About 90 per cent of hereditary breast cancers involve mutation of the BRCA1 and/or BRCA2 genes. Other cancer-related genes (including myc, c-erbB2, Tsg101 and Mdgi) are involved in breast carcinogenesis, but they do not give rise to familial breast cancer syndromes. Risk estimation is the most important clinical implication. Management options for the high-risk mutation carriers include cancer surveillance and preventive strategies (prophylactic surgery or chemoprevention). CONCLUSION: Despite inadequate knowledge about the genetic predisposition to breast cancer and its clinical implications, the demand for genetic testing is likely to expand rapidly. In addition to risk estimation, cancer surveillance and preventive strategies, gene therapy offers a new and theoretically attractive approach to breast cancer management.

BRCA2 Protein↗

Pathogenesis and clinical management of hereditary non-polyposis colorectal cancer.

BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is an inherited genetic condition associated with microsatellite instability; it accounts for around 5 per cent of all cases of colorectal cancer. This review examines recent data on management strategies for this condition. METHODS: A Medline-based literature search was performed using the keywords 'HNPCC' and 'microsatellite instability'. Additional original papers were obtained from citations in articles identified by the initial search. RESULTS AND CONCLUSION: The Amsterdam criteria identify patients in whom the presence of an inherited mutation should be investigated. Those with a mutation should be offered counselling and screening. The role of prophylactic surgery has been superseded by regular colonoscopy, which dramatically reduces the risk of colorectal cancer. Screening for extracolonic malignancy is also advocated, but the benefits are uncertain. Chemoprevention may be of value in lowering the incidence of bowel cancer in affected patients, but further studies are required.

Chemoprevention↗

Management of colorectal cancer patients in Australia: the National Colorectal Cancer Care Survey.

BACKGROUND: The National Colorectal Cancer Care Survey was undertaken to determine the management patterns for individuals newly diagnosed with colorectal cancer in Australia. METHODS: Between 1 February and 30 April 2000, all new cases of colorectal cancer registered at each Cancer Registry within Australia were entered into the survey. This generated a questionnaire that was sent to the treating surgeons. Chi-squared and logistic regression analyses were used to determine levels of statistical significance for the various comparisons of interest. RESULTS: Of 2383 surgical questionnaires generated, 2015 (85%) were completed. A total of 1911 patients (95% of those who responded to the questionnaire) had an operation. Of the 86 guidelines for the management of colorectal cancer published by the National Health and Medical Research Council, the survey allowed for comparison between 18 of these, which covered a spectrum of surgical management. Thromboembolic prophylaxis was given to 1843 patients (96.4%) undergoing surgery. Prophylactic antibiotics were commonly used, but there appear to be issues regarding the best regimen to use. Curative resections were carried out in 1563 patients (81.8%), with anterior resections being the most commonly performed procedure. Adjuvant therapy was regularly used, but not all eligible patients were offered such treatment. CONCLUSION: With the considerable resources required to develop clinical practice guidelines, studies like this are essential to monitor the impact of the guidelines. To ensure that the guidelines are in line with current evidence, regular reviews of the guideline recommendations are required.

Adolescent↗

Sebaceus naevi: a clinicopathologic study.

OBJECTIVE: To analyse sebaceus naevus (SN) incidence, associated malignancies, and developmental defects in a retrospective study. METHODS: We retrospectively analysed all cases of SN excised in our Department over a 20-year period. All cases of epidermal naevus syndrome (Schimmelpenning syndrome) associated with SN were recorded, as well as all patients with histological changes suggesting degeneration of the initial SN. RESULT: A total 226 patients with SN were included in the study. Stage II was the most common (65%), and the parietal area was the most common location of SN (42%), with only 7% located in non-scalp areas. Syringocystadenoma papilliferum and trichoblastoma were the most common tumours arising on SN. We only found five patients with basal cell carcinoma arising on previous SN. Epidermal naevus syndrome associated with SN was diagnosed in 16 patients, and this was the most common neurocutaneous association. CONCLUSION: The incidence of malignancy arising on SN was very low, indicating that prophylactic surgery of NS in children is not recommendable. Developmental defects should be investigated in order to evidence possible epidermal naevus syndrome associated with SN.

Adolescent↗