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PubMedDate not supplied

Understanding mathematical models for breast cancer risk assessment and counseling.

Chemoprevention and prophylactic surgery are effective interventions for lowering breast cancer incidence. However, these approaches are associated with risks of their own. Accurate individualized breast cancer risk assessment is an essential component of the risk/benefit analysis that must take place prior to implementing either of these strategies. Several mathematical models for estimating individual breast cancer risk have been proposed over the last decade. The Gail model is the most generally applicable model; however, it neglects family history information in second-degree relatives, treats pre- and postmenopausal breast cancer the same, and ignores personal histories of lobular neoplasia. The Claus model is a better family history model, but it does not assign any special relevance to histories of bilateral breast cancer or ovarian cancer, and neglects all of the nonfamily history information accounted for by the Gail model. BRCAPRO is a Bayesian family history model that calculates individual breast cancer probabilities based on the probability that a family carries a mutation in one of the BRCA genes. Though its treatment of family history information is more thorough than the other models, it neglects the nonfamily history risk factors accounted for by the Gail model and may not appreciate familial clustering unrelated to BRCA gene mutation. A thorough understanding of the principles of risk analysis and the available mathematical models is essential for anyone wishing to perform intervention counseling. This review describes the basic components of risk analysis, explains how the mathematical models work and compares the strengths and weaknesses of the various models. CancerGene is a software tool for running all of these models. It may be obtained without charge at http://www.swmed.edu/home_pages/cancergene.

Breast Neoplasms↗

PubMedDate not supplied

A unique BRCA1 mutation identified in Mongolia.

This is a case report of genetic assessment conducted on a family residing in the third world where two sisters have presented with early onset ovarian cancer. Protein truncation testing and DNA sequencing identified a unique mutation on exon 11 (3452delA) of the BRCA1 gene. Buccal swab testing of three siblings and three offspring showed that half of the family members carried the same mutation. Currently, genetic testing in third-world countries is conducted within research budgets, as testing is not affordable or locally available for such high-risk families. Unique mutations in the BRCA1 gene that are expressed in geographically isolated groups will be useful in genetic counseling and preventative maneuvers. The only preventive management strategy available in the third world is prophylactic surgery.

Adenocarcinoma↗

PubMed1996

Colorectal polyp counts and cancer risk in familial adenomatous polyposis.

BACKGROUND & AIMS: In familial adenomatous polyposis, colorectal cancer prevention is by prophylactic colectomy, but dietary or chemopreventative strategies have been recently proposed in low-risk individuals. The aim of this study was to define predictive risk factors for colorectal cancer in familial adenomatous polyposis. METHODS: Between 1918 and 1993, 317 patients underwent colectomy. A multivariate analysis was performed to assess the relationship between colorectal cancer risk and polyp count, sex, and age at colectomy. RESULTS: The median polyp count was 842 (range, 78-7500), and cancer was found in 22% of patients. Polyp count and age, but not sex, predicted cancer risk. Patients with >1000 polyps had 2.3 times greater risk of cancer than those with <1000 polyps (P=0.006). Synchronous cancers increased with poly count (P<0.05). Each 10-year age group had a 2.4-fold difference in cancer risk (95% confidence interval, 1.9-3.2; P<0.001). Four cases of cancer occurred in patients at low risk (younger than 30 years of age, <1000 polyps; 3.3%). CONCLUSIONS: More adenomas and older age are associated with a higher risk of colorectal cancer. However, cancer does occur in low-risk individuals and may be missed by surveillance, making alternatives to prophylactic surgery inadvisable.

Adenomatous Polyposis Coli↗

PubMed2003

The adolescent varicocele: the crucial role of hormonal tests in selecting patients with testicular dysfunction.

BACKGROUND/PURPOSE: Early identification and treatment of varicocele during adolescence may reduce the risk of infertility. Prophylactic surgery on all adolescents with varicocele would be unnecessary surgery on a high percentage of them. Suggested guidelines for early intervention have included testicular volume loss and abnormality in the hormonal integrity of the hypothalamic-pituitary-testicular axes. Previous studies have documented no correlation between testicular volume loss and abnormal response to GnRH test. The role of these 2 prognostic factors in predicting semen abnormalities in this age group never has been investigated, so far. In the current study we correlated hormonal tests and orchidometry to semen analysis in a selected group of adolescents. METHODS: Adolescents with varicocele and Tanner stage V underwent semen analysis, Prader orchidometry, and hormonal tests (basal LH and FSH [bLH and bFSH], testosterone [T], LH and FSH after GnRH stimulation test [sLH and sFSH]). According to semen analysis (in relation to Oval Motility Index) patients were divided into 2 groups: group A, adolescents with pathologic semen and group B, adolescents with normal semen. Hormonal tests and testicular volumes (in those with left unilateral varicocele) were compared between the 2 groups. Statistical analysis was performed using Mann-Whitney U test and Student's t test. RESULTS: Of 76 patients, 20 (Group A) had a pathologic semen analysis. Levels of bLH, bFSH, sFSH were significantly higher in group A compared with group B (56 with normal semen). sLH was higher in group A, but the difference was not statistically significant. T levels were not different between the 2 groups. Of 68 patients who had left unilateral varicocele and no previous inguinal--scrotal surgery 14 had pathologic semen analysis. There was no statistically significant difference between the 2 groups for any of the orchidometric parameters investigated. CONCLUSIONS: The evaluation of testicular volumes during physical examination for varicocele in Tanner stage V adolescents is not predictive for testicular dysfunction. LH and FSH dosages with or without GnRH stimulation test can identify those subjects at risk for infertility, and their use should be encouraged for selecting patients who need surgical correction.

Adolescent↗

PubMed2003

[Hereditary medullary thyroid carcinoma--genotype-phenotype characterization].

BACKGROUND AND OBJECTIVE: Hereditary medullary thyroid carcinoma (MTC) is caused by germline mutations of the RET proto-oncogene. A genotype - phenotype correlation has been established, showing clustering of mutations in exons 10 and 11 in classical MEN 2 A syndrome, in exon 16 codon 918 in MEN 2 B syndrome and in exons 13-15 in familial MTC. A line of evidence suggested that the development and the aggressiveness of MTC in the different cancer syndromes is variable. Aim of this study was to compare the phenotype of exon 13-15 mutations with that of exon 11 mutation and possibly draw therapeutical consequences. PATIENTS AND METHODS: We compared the phenotype of 47 patients with mutations in exon 13-15 with 66 patients with exon 11, codon 634 mutation, the classical MEN2A. Patients were further subdivided as index and screening patients. RESULTS: Mean age of 19 index patients with codon 790, 791, 804 or 891 mutation was significant higher compared with 18 index patients with codon 634 mutation (mean age at diagnosis 50+/-12 years; range 30-69 y vs mean age 31+/-9 years; range 17-49 y), tumor stage at operation was favourable (C-cell hyperplasia n = 1; stage I n = 8; II n = 3; III n = 2; IV n = 2; no operation n = 1; no information n = 2 vs stage I n = 3; stage II n = 6; stage III n = 4, no information n =5), cure rate was better (56 % vs 38 %) and the death rate was lower (n = 2 vs n = 4). In screening patients no differences concerning the age, tumor stage, cure and death rate between patients with exons 13-15 and codon 634 mutations were seen. CONCLUSIONS: MTC in patients with exon 790, 791, 804, 891 mutations displayed a late onset and an indolent course compared to codon 634 mutation, this has to be taken into account when recommending timing and extent of prophylactic surgery.

Adolescent↗

PubMed2003

Urachal remnants: an enigma.

AIM: To determine what should be done with incidentally discovered urachal remnants. MATERIALS AND METHODS: A 10-year retrospective study revealed 24 patients with urachal remnants. The histology of the urachal remnants was reviewed. A review of the data on urachal carcinoma in adults diagnosed and treated during the same period in an adjacent adult hospital was carried out. A review of the literature was also performed. RESULTS: In the 23 patients where histology was available 17 had normal urothelial lining and 6 (25%) showed abnormal epithelium. This included colonic epithelium, small intestinal epithelium and squamous epithelium. Four of the patients with abnormal epithelium were in the group of "incidental removals". During the 10-year period, 4 cases of urachal carcinoma were managed at the adult urology centre. Three had extensive disease at presentation. Two died of the disease while the third died of myocardial infarction 5 months after resection. Only one was alive at one-year follow-up. The occurrence of such documented complications makes a strong case for "prophylactic" surgery when urachal remnants are diagnosed incidentally or recognised during other operative procedures. All paediatric patients who underwent excision of urachal remnants had an uncomplicated clinical course.

Adolescent↗

PubMed1983

[Metipranolol in the prevention of intraocular pressure elevation after cataract extraction].

Elevated intraocular pressure during the first few days after routine intracapsular cataract extraction with and without alpha-chymotrypsin is a well-known symptom. A prospective, double-blind study was conducted to determine whether Metipranolol would prevent this increase in pressure. In 40 eyes which underwent routine, uncomplicated cataract extraction a drop of either Metipranolol 0,6% or placebo was administered before and during the first days after surgery. Prophylactic Metipranolol 0,6% can substantially reduce the incidence of severe early postoperative ocular hypertension.

Adrenergic beta-Antagonists↗

PubMed1992

A report of children with spinal dysraphism managed conservatively.

This investigation is a retrospective study of 12 patients with spinal dysraphism. There were 5 males and 7 females in the cohort. Their ages ranged from 4 to 13 years at the time of their last assessment. Initial presentation included one or more of the following--a blemish on the back in the midline (lump, hairy patch, sinus and/or angioma), abnormal neurological signs and symptoms in one or both legs, and in one case dribbling of urine. Investigations performed included plain X-rays of the spine, CT scans alone or in combination with a myelogram and MR scans. Findings included thickened filum terminale, low lying cord, lipoma, syringomyelia, diastematomyelia, spina bifida occulta and sacral agenesis. The children were followed up for between 2 and 10 years. During the period of observation, none developed new symptoms or signs, and there was no progression of existing neurological deficits. This preliminary report suggests that there is no justification for prophylactic surgery in this group of patients.

Adolescent↗

PubMed1988

[Extra- and intracranial Doppler ultrasound. Evaluation of patients with surgical anastomosis of the arteria temporalis superficialis superficialis and arteria cerebri media].

During a mean postoperative period of 16 months, 51 patients who had received an extracranial-intracranial (EC-IC) arterial bypass were examined by means of transcranial and extracranial Doppler ultrasound, with the following results: the flow velocities of the middle cerebral artery (MCA) are postoperatively significantly lower than in normal control subjects. No differences were seen if the MCA was supplied via the EC-IC bypass or via any "natural" collateral vessels. In 32 cases, blood supply of the MCA artery was provided via the EC-IC bypass. In another 13 cases the MCA was supplied via the contralateral carotid artery and in six further cases via other collateral vessels. In the extracranial area, an internalisation of the flow pattern of the superficial temporal artery was found if the bloodstream from the anastomosis passed through the MCA. Similar changes at the external carotid artery were mainly due to the changed haemodynamics resulting from the extracranial occlusion of the internal carotid artery. No correlation was found between the clinical neurological course and haemodynamic data. The only indication for the EC-IC bypass, as we see it at the moment, is prophylactic surgery, such as, for example, treatment of giant aneurysms and definitely insufficient crossflow. All other indications that have been suggested after the publication of the results of the EC-IC Bypass Study Group will have to be confirmed by further study.

Aged↗

PubMed1986

A randomized controlled trial of a low-molecular-weight heparin (enoxaparin) to prevent deep-vein thrombosis in patients undergoing elective hip surgery.

There is experimental evidence that low-molecular-weight fractions of heparin are as effective as the standard form but cause less bleeding. We therefore performed a double-blind, randomized trial comparing PK10169 low-molecular-weight heparin with placebo for the prevention of venous thrombosis in patients undergoing elective hip surgery. Prophylactic treatment with a fixed dose was begun postoperatively and continued for 14 days. Fifty patients in each treatment group underwent surveillance with [125I]fibrinogen leg scanning and impedance plethysmography. In the first 24 patients, venography was performed only if either surveillance test was positive. Because the rate of venous thrombosis detected in those patients was unexpectedly low, venography was requested in the remaining 76 patients, even if the screening tests were negative. In this latter group, venous thrombosis occurred in 4 patients (10.8 percent) given PK10169 heparin and 20 patients (51.3 percent) given placebo (P = 0.0002); the corresponding rates for proximal-vein thrombosis were 5.4 percent and 23.1 percent, respectively (P = 0.029). In the entire group of 100 patients, venous thrombosis occurred in 12 percent of those given PK10169 heparin and 42 percent of those given placebo (P = 0.0007), and the corresponding rates for proximalvein thrombi were 4 percent and 20 percent, respectively (P = 0.014). The observed hemorrhagic rate was 4 percent in each treatment group. We conclude that prophylaxis with fixed-dose PK10169 heparin is effective and safe for patients undergoing elective hip replacement.

Aged↗

PubMed2000

Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi)

BACKGROUND: Chinese-herb nephropathy is a progressive form of renal fibrosis that develops in some patients who take weight-reducing pills containing Chinese herbs. Because of a manufacturing error, one of the herbs in these pills (Stephania tetrandra) was inadvertently replaced by Aristolochia fangchi, which is nephrotoxic and carcinogenic. METHODS: The diagnosis of a neoplastic lesion in the native urinary tract of a renal-transplant recipient who had Chinese-herb nephropathy prompted us to propose regular cystoscopic examinations and the prophylactic removal of the native kidneys and ureters in all our patients with end-stage Chinese-herb nephropathy who were being treated with either transplantation or dialysis. Surgical specimens were examined histologically and analyzed for the presence of DNA adducts formed by aristolochic acid. All prescriptions written for Chinese-herb weight-reducing compounds during the period of exposure (1990 to 1992) in these patients were obtained, and the cumulative doses were calculated. RESULTS: Among 39 patients who agreed to undergo prophylactic surgery, there were 18 cases of urothelial carcinoma (prevalence, 46 percent; 95 percent confidence interval, 29 to 62 percent): 17 cases of carcinoma of the ureter, renal pelvis, or both and 1 papillary bladder tumor. Nineteen of the remaining patients had mild-to-moderate urothelial dysplasia, and two had normal urothelium. All tissue samples analyzed contained aristolochic acid-related DNA adducts. The cumulative dose of aristolochia was a significant risk factor for urothelial carcinoma, with total doses of more than 200 g associated with a higher risk of urothelial carcinoma. CONCLUSIONS: The prevalence of urothelial carcinoma among patients with end-stage Chinese-herb nephropathy (caused by aristolochia species) is a high.

Anti-Obesity Agents↗

PubMed2001

Prophylactic total gastrectomy for familial gastric cancer.

BACKGROUND: An autosomal dominant syndrome of diffuse gastric cancer has been reported with germline mutations in the E-cadherin (CDH1) gene and has been identified in approximately 14 families and 50 individuals worldwide. Penetrance of the gene is 70% to 80%, and the average age of onset of gastric cancer is 37 years. These characteristics have led to the consideration of prophylactic total gastrectomy in family members with CDH1 mutations. METHODS: We report here the first use of prophylactic gastrectomy in 6 asymptomatic members of 2 families (2 males, 4 females; ages 22, 27, 28, 35, 39, and 40) based on family pedigree and genetic analysis. Total gastrectomy was performed via an upper midline incision, and reconstruction of the gastrointestinal tract was done via a Roux-en-Y esophagojejunostomy. Complete removal of all gastric mucosa was documented intraoperatively, and confirmation was made that only esophageal mucosa remained at the proximal specimen margin. RESULTS: The gastric specimens appeared normal, and the results of routine pathologic examination were negative for cancer. All specimens from patients who tested positive for E-cadherin mutations were subjected to a research protocol of microscopic sectioning in which 150 to 250 tissue blocks were examined. All of these patients had microscopic foci of cancer, often at multiple sites, with overlying normal gastric mucosa. CONCLUSIONS: E-cadherin gene mutations in association with familial gastric cancer is a new disease for which prophylactic surgery must be considered. The morbidity of this operation is much higher than that for other genetic diseases, but the alternative is a mortality risk of more than 80% at a young age.

Adult↗

PubMed1988

Obstructive jaundice. Causes and surgical interventions.

Biliary obstruction can be caused by a number of conditions and can occur in persons of all ages. In every case, prompt diagnosis affords the best opportunity for surgical therapy. Accurate preoperative diagnosis can be difficult because benign and malignant causes may appear similar radiographically. Options in surgical management can be as simple as extraction of a solitary common duct stone or as extensive as pancreaticoduodenectomy or hepatectomy and liver transplantation. Because of the risk of infection with biliary surgery, prophylactic antibiotic treatment should be considered.

Adenoma, Bile Duct↗

PubMed2003

Is perioperative hypothermia a risk factor for post-Cesarean infection?

OBJECTIVE: To determine whether hypothermia during Cesarean delivery is a risk factor for postoperative infection. METHODS: An historical cohort investigation was conducted on all women delivered by Cesarean at our center during 2001. Initial recovery-room temperature, taken via the oral or axillary route, was used as a surrogate for intraoperative temperature. Adding 0.5 degrees C to axillary temperatures generated oral temperature equivalents. Women with chorioamnionitis were excluded, as were those with an initial recovery-room temperature that exceeded 37.9 degrees C or was recorded more than 20 minutes after the end of surgery. Prophylactic antibiotics (cefazolin, 1 g) were given during Cesarean delivery. RESULTS: A total of 42 women (7.6%) were diagnosed with postoperative infections. Infections included endometritis (n = 25), wound abscess (n = 7), wound cellulitis (n = 7) and urinary tract infection (UTI) (n = 4). No cases of septic pelvic thrombophlebitis or pelvic abscess occurred. One woman had both endometritis and a UTI. Mean temperatures were higher, rather than lower, for women who subsequently had postoperative infections compared with those who did not (36.4 +/- 0.8 degrees C vs. 35.9 +/- 0.7 degrees C; p < 0.001). Mean temperatures for the various postoperative infections were as follows: endometritis, 36.5 +/- 0.8 degrees C (p < 0.001 vs. uninfected group); wound abscess 36.0 +/- 0.8 degrees C (p = 0.63); wound cellulitis, 36.3 +/- 0.6 degrees C (p = 0.14); UTI, 36.7 +/- 0.9 degrees C (p = 0.04). CONCLUSIONS: Women who develop post-Cesarean infections have higher initial recovery-room temperatures than those who do not develop such infections. This suggests the presence of subclinical infection at the time of Cesarean. Evaluating whether intraoperative warming has any role during Cesarean delivery requires a randomized clinical trial.

Adult↗

PubMed2000

Evaluation of the needs of male carriers of mutations in BRCA1 or BRCA2 who have undergone genetic counseling.

To date, the concerns of men at risk of inheriting a BRCA1 mutation or a BRCA2 mutation have received little attention. It had been anticipated that few men would be interested in predictive testing when a BRCA mutation was identified in their family. However, these men are often affected emotionally by diagnoses of breast cancer in their relatives and may themselves harbor fears that cancer will develop. Male carriers of BRCA1/2 mutations are at increased risk of development of cancers of several types, including those of the breast and prostate. We conducted an evaluation of the needs and experiences of 59 male carriers of BRCA1/2 mutations followed at either the University of Toronto or Creighton University. We assessed their motivations for seeking genetic counseling and testing, involvement in family discussions of breast and ovarian cancer, risk perception, changes in cancer-screening practices, and overall satisfaction with the genetic-counseling process. The principal motivation for seeking genetic counseling was concern for their daughters. The majority (88%) of men participated in family conversations about breast and ovarian cancer, and 47% participated in conversations about prophylactic surgery. Most men believed that they were at increased risk of development of cancer (prostate, breast, colorectal, and skin cancers). However, fewer than one-half (43%) of the men with no previous diagnosis of cancer stated that their prostate cancer-surveillance practices had changed after they had received genetic test results. More than one-half (55%) had intrusive thoughts about their cancer risk. Although levels of satisfaction were high, practitioners should be aware of (a) potential pressures influencing men to request predictive testing, (b) the difficulties that men encounter in establishing surveillance regimens for breast and prostate cancer, and (c) the general lack of information about men's particular experiences in the medical community.

Adult↗

PubMed2002

Adverse events in surgical patients in Australia.

OBJECTIVE: To determine the adverse event (AE) rate for surgical patients in Australia. DESIGN: A two-stage retrospective medical record review was conducted to determine the occurrence of AEs in hospital admissions. Medical records were screened for 18 criteria and positive records were reviewed by two medical officers using a structured questionnaire. SETTING: Admissions in 1992 to 28 randomly selected hospitals in Australia. STUDY PARTICIPANTS: Five hundred and twenty eligible admissions were randomly selected from in-patient database in each hospital. A total of 14,179 medical records were reviewed, with 8747 medical and 5432 surgical admissions. MAIN OUTCOME MEASURES: Measures included the rate of AEs in surgical and medical admissions, the proportion resulting in permanent disability and death, the proportion determined to be highly preventable, and the identification of risk factors associated with AEs. RESULTS: The AE rate for surgical admissions was 21.9%. Disability that was resolved within 12 months occurred in 83%, 13% had permanent disability, and 4% resulted in death. Reviewers found that 48% of AEs were highly preventable. The risk of an AE depended on the procedure and increased with age and length of stay. CONCLUSION: The high AE rate for surgical procedures supports the need for monitoring and intervention strategies. The 18 screening criteria provide a tool to identify admissions with a greater risk of a surgical AE. Risk factors for an AE were age and procedure, and these should be assessed prior to surgery. Prophylactic interventions for infection and deep vein thrombosis could reduce the occurrence of AEs in hospitals.

Adolescent↗

PubMed1988

Ulcerative colitis. Colorectal cancer risk in an unselected population.

One hundred twenty-seven patients were studied, representing the unselected population of patients with ulcerative colitis from a defined catchment area of about 70,000 inhabitants during 1961-1983. Seventy-seven patients had total colitis, and 50 patients had left-sided colitis. No prophylactic colectomy was performed. Despite this and a comprehensive follow-up of patients with long-standing, extensive colitis, primary colorectal carcinomas were diagnosed in only three patients, all of whom had total colitis. This was significantly (p less than 0.001) more than the expected number of patients with colorectal cancer in this subgroup, namely, 0.13. There were no deaths in colorectal carcinoma. Factors determining completeness of inclusion are discussed, and it is concluded that, in an unselected series of patients with ulcerative colitis, close cancer surveillance is indicated, although prophylactic surgery does not seem to be generally warranted.

Adolescent↗

PubMed2004

Evidence-based diagnosis and management of tubal factor infertility.

PURPOSE OF REVIEW: The investigation for potential tubal disease is an essential step in the work-up of infertility. This review article provides an evidence-based overview of the diagnosis and management of tubal factor infertility. RECENT FINDINGS: While laparoscopic chromopertubation remains the gold standard in the diagnosis of tubal disease and hysterosalpingography is still widely used, newer modalities offer some advantages. Sonohysterography with the use of contrast medium is superior to hysterosalpingography and comparable to laparoscopic chromotubation in diagnosing tubal blockage. Chlamydia serology is the most cost-effective and least invasive diagnostic test for tubal disease, and it is comparable to, if not better than, hysterosalpingography. Depending on the nature and degree of tubal dysfunction as well as the age and ovarian reserve of the patient, various treatments for tubal infertility are available. For proximal tubal obstruction, transcervical tubal cannulation with tubal flushing is a reasonable first approach. Surgical techniques for tubal repair, such as salpingostomy or fimbrioplasty for distal tubal obstruction, can provide good results. Still, tubal factor remains a major indication for in-vitro fertilization and embryo transfer, which bypasses the tubal problem altogether. In certain situations, such as the presence of hydrosalpinx, prophylactic surgery can be used in conjunction with in-vitro fertilization and embryo transfer. SUMMARY: As with infertility in general, the diagnosis and management of tubal infertility should be tailored to the individual patient. Future studies should help to further clarify the role of the various diagnostic tests and therapeutic approaches for tubal infertility.

Evidence-Based Medicine↗