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of colorectal adenocarcinoma at the major hospitals in metropolitan Columbus, Ohio, were eligible for the study. Genotyping of the tumor for microsatellite instability was the primary screening method. Among patients whose screening results were positive for microsatellite instability, we searched for germ-line mutations in the MLH1, MSH2, MSH6, and PMS2 genes with the use of immunohistochemical staining for mismatch-repair proteins, genomic sequencing, and deletion studies. Family members of carriers (...) Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). Germ-line mutations in the mismatch-repair genes MLH1, MSH2, MSH6, and PMS2 lead to the development of the Lynch syndrome (hereditary nonpolyposis colorectal cancer), conferring a strong susceptibility to cancer. We assessed the frequency of such mutations in patients with colorectal cancer and examined strategies for molecular screening to identify patients with the syndrome.Patients with a new diagnosis
therapy alone, stratified by age at diagnosis and histological findings.A retrospective population-based cohort study using Connecticut Tumor Registry data supplemented by hospital record and histology review of 767 men aged 55 to 74 years with clinically localized prostate cancer diagnosed between January 1, 1971, and December 31, 1984. Patients were treated with either observation or immediate or delayed androgen withdrawal therapy, with a median observation of 24 years.Probability of mortality from (...) prostate cancer or other competing medical conditions, given a patient's age at diagnosis and tumor grade.The prostate cancer mortality rate was 33 per 1000 person-years during the first 15 years of follow-up (95% confidence interval [CI], 28-38) and 18 per 1000 person-years after 15 years of follow-up (95% CI, 10-29). The mortality rates for these 2 follow-up periods were not statistically different, after adjusting for differences in tumor histology (rate ratio, 1.1; 95% CI, 0.6-1.9). Men with low
is unknown.To determine if cancer risks in AC-I families with no apparent deficiency in DNA MMR are different from cancer risks in AC-I families with DNA MMR abnormalities.Identification (1997-2001) of 161 AC-I pedigrees from multiple population- and clinic-based sources in North America and Germany, with families grouped into those with (group A) or without (group B) MMR deficiency by tumor testing. A total of 3422 relatives were included in the analyses.Cancer incidence in groups A and B (excluding the 3 (...) Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X. Approximately 60% of families that meet the Amsterdam-I criteria (AC-I) for hereditary nonpolyposis colorectal cancer (HNPCC) have a hereditary abnormality in a DNA mismatch repair (MMR) gene. Cancer incidence in AC-I families with MMR gene mutations is reported to be very high, but cancer incidence for individuals in AC-I families with no evidence of an MMR defect
instability.To establish the most effective and efficient strategy for the detection of MSH2/MLH1 gene carriers.A prospective, multicenter, nationwide study (the EPICOLON study) in 20 hospitals in the general community in Spain of 1222 patients with newly diagnosed colorectal cancer between November 1, 2000, and October 31, 2001.Microsatellite instability testing and MSH2/MLH1 immunostaining in all patients regardless of age, personal or family history, and tumor characteristics. Patients whose tumors (...) Accuracy of revised Bethesda guidelines, microsatellite instability, and immunohistochemistry for the identification of patients with hereditary nonpolyposis colorectal cancer. The selection of individuals for hereditary nonpolyposis colorectal cancer (HNPCC) genetic testing is challenging. Recently, the National Cancer Institute outlined a new set of recommendations, the revised Bethesda guidelines, for the identification of individuals with HNPCC who should be tested for microsatellite
Familial cancer associated with a polymorphism in ARLTS1. The finding of hemizygous or homozygous deletions at band 14 on chromosome 13 in a variety of neoplasms suggests the presence of a tumor-suppressor locus telomeric to the RB1 gene.We studied samples from 216 patients with various types of sporadic tumors or idiopathic pancytopenia, peripheral-blood samples from 109 patients with familial cancer or multiple cancers, and control blood samples from 475 healthy people or patients (...) with diseases other than cancer. We performed functional studies of cell lines lacking ARLTS1 expression with the use of both the full-length ARLTS1 gene and a truncated variant.We found a gene at 13q14, ARLTS1, a member of the ADP-ribosylation factor family, with properties of a tumor-suppressor gene. We analyzed 800 DNA samples from tumors and blood cells from patients with sporadic or familial cancer and controls and found that the frequency of a nonsense polymorphism, G446A (Trp149Stop), was similar
Randomised phase III study of intravenous vinorelbine plus hormone therapy versus hormone therapy alone in hormone-refractory prostate cancer. Vinorelbine (VRL) has been shown to be active in hormone-refractory prostate cancer (HRPC) in phase II studies, alone or in combination. Its moderate toxicity profile is well tolerated in elderly patients.Patients with metastatic prostate cancer, progressive after primary hormonal therapy, were randomised to receive intravenous VRL 30 mg/m2 on days 1 (...) and 8 every 3 weeks, and hydrocortisone 40 mg/day or hydrocortisone alone until disease progression. Centres could choose to add aminoglutethimide 1000 mg/day to hydrocortisone as second-line hormone therapy (HT) for all their patients. Randomisation was stratified by centre. Further chemotherapy was allowed after progression. The primary end point was progression-free survival (PFS). The final analysis was performed on a total of 414 patients. Reported results were all based on intention-to-treat
Hepatitis B reactivation in patients with hepatocellular carcinoma undergoing systemic chemotherapy. Cancer patients who are hepatitis B virus (HBV) carriers and undergoing chemotherapy (CT) may be complicated by HBV reactivation. Over 80% of hepatocellular carcinoma (HCC) patients are HBV carriers; however, the incidence of HBV reactivation during CT has not been well-reported. A prospective study was conducted to determine the incidence of HBV reactivation, the associated morbidity
Hyperbaric oxygen as an adjuvant treatment for malignant otitis externa. Malignant, or necrotising, otitis externa is a potentially fatal infection of the external ear canal and surrounding soft tissue and bone. It may be complicated by involvement of cranial nerves, principally the facial nerves and the contents of the jugular foramen. It is an uncommon condition mainly found in the elderly or in diabetics.To assess the effectiveness of adjunctive hyperbaric oxygen treatment for malignant (...) otitis externa.We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2003), MEDLINE (January 1966 to April 2004) and EMBASE (January 1985 to April 2004) with pre-specified terms. The date of the last search was 5th April 2004.Randomised controlled trials, involving adults, undergoing hyperbaric oxygen therapy in malignant otitis externa.No identified articles described randomised controlled trials of hyperbaric oxygen therapy in the treatment
Prophylactic cranial irradiation for preventing brain metastases in patients undergoing radical treatment for non-small cell lung cancer. In non-small cell lung cancer (NSCLC), there is a relatively high incidence of brain metastases following radical treatment. At present, the role of prophylactic cranial irradiation (PCI) in this group of patients is not clear.To investigate whether PCI has a role in the management of patients with NSCLC treated with radical intent.The electronic databases
Racial differences in the use of BRCA1/2 testing among women with a family history of breast or ovarian cancer. Given the current context of racial disparities in health and health care and the historical context of eugenics, racial disparities in the use of genetic susceptibility testing have been widely anticipated. However, to our knowledge there are no published studies examining the magnitude and determinants of racial differences in the use of genetic susceptibility testing.To investigate (...) the relationship between race and the use of BRCA1/2 counseling among women with a family history of breast or ovarian cancer and to determine the contribution of socioeconomic characteristics, cancer risk perception and worry, attitudes about genetic testing, and interactions with primary care physicians to racial differences in utilization.Case-control study (December 1999-August 2003) of 408 women with a family history of breast or ovarian cancer, of whom 217 underwent genetic counseling for BRCA1/2 testing
confiding support also predicted more protracted episodes of depression and anxiety.Increased levels of depression, anxiety, or both in the first year after a diagnosis of early breast cancer highlight the need for dedicated service provision during this time. Psychological interventions for women with breast cancer who remain disease free should take account of the broader social context in which the cancer occurs, with a focus on improving social support. (...) Depression and anxiety in women with early breast cancer: five year observational cohort study. To examine the prevalence of, and risk factors for, depression and anxiety in women with early breast cancer in the five years after diagnosis.Observational cohort study.NHS breast clinic, London.222 women with early breast cancer: 170 (77%) provided complete interview data up to either five years after diagnosis or recurrence.Prevalence of clinically important depression and anxiety (structured
C-reactive protein levels are not associated with increased risk for colorectal cancer in women. Observations that risk for colorectal cancer is elevated in patients with inflammatory bowel disease and that long-term use of anti-inflammatory drugs may reduce colorectal cancer risk have raised the possibility that inflammation may play a role in the development of colorectal cancer. While a recent prospective study observed a positive association between C-reactive protein (CRP), a marker (...) colorectal adenocarcinoma confirmed by medical record review.169 women developed colorectal adenocarcinomas during follow-up. Baseline CRP levels were not significantly associated with colorectal cancer risk. The multivariate hazard ratios according to cutoff points for CRP proposed in clinical guidelines were 0.79 (95% CI, 0.53 to 1.17) for the category of 1 to 3 mg/L and 0.66 (CI, 0.43 to 1.03) for the category of greater than 3 mg/L (P for trend = 0.09), as compared with the category of less than 1 mg
Blue dye versus combined blue dye-radioactive tracer technique in detection of sentinel lymph node in breast cancer. Sentinel lymph node biopsy in breast cancer can be used to select patients in which axillary lymph node dissection could be avoided. In this study we compared the value of two methods for identification of sentinel node (SN) using either only blue dye or combination of blue dye and radioactive tracer.All patients were women with clinically T(1-2)N(0)M(0) breast cancer. They were (...) was significantly superior to blue-dye alone technique for negative-predictive value (p=0.033) and overall accuracy (p=0.048).The prediction of axillary lymph node status in breast cancer patients using combined technique has significantly higher accuracy than marking of SN with blue dye alone and therefore should be preferred.
Screening for breast cancer. Breast cancer screening in community practices may be different from that in randomized controlled trials. New screening modalities are becoming available.To review breast cancer screening, especially in the community and to examine evidence about new screening modalities.English-language articles of randomized controlled trials assessing effectiveness of breast cancer screening were reviewed, as well as meta-analyses, systematic reviews, studies of breast cancer (...) screening in the community, and guidelines. Also, studies of newer screening modalities were assessed.All major US medical organizations recommend screening mammography for women aged 40 years and older. Screening mammography reduces breast cancer mortality by about 20% to 35% in women aged 50 to 69 years and slightly less in women aged 40 to 49 years at 14 years of follow-up. Approximately 95% of women with abnormalities on screening mammograms do not have breast cancer with variability based
%) patients were 65 years or older and 159 (2%) were 70 years or older.Comparison of disease-free survival, overall survival, and treatment-related mortality among different age groups.Multivariate analysis showed that smaller tumor size, fewer positive lymph nodes, more chemotherapy, and tamoxifen use were all significantly (P<.001) related to longer disease-free and overall survival. There was no association between age and disease-free survival. Overall survival was significantly (P<.001) worse (...) Adjuvant chemotherapy in older and younger women with lymph node-positive breast cancer. Adjuvant chemotherapy improves survival for patients with local-regional breast cancer, but healthy older patients at high risk of recurrence are frequently not offered adjuvant chemotherapy, and the benefit of adjuvant chemotherapy in older patients is uncertain.To compare the benefits and toxic effects of adjuvant chemotherapy among breast cancer patients in age groups of 50 years or younger, 51 to 64
, advanced non-small-cell lung cancer who had a relapse after two years of complete remission during treatment with gefitinib. The DNA sequence of the EGFR gene in his tumor biopsy specimen at relapse revealed the presence of a second point mutation, resulting in threonine-to-methionine amino acid change at position 790 of EGFR. Structural modeling and biochemical studies showed that this second mutation led to gefitinib resistance.Copyright 2005 Massachusetts Medical Society. (...) EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. Mutations of the epidermal growth factor receptor (EGFR) gene have been identified in specimens from patients with non-small-cell lung cancer who have a response to anilinoquinazoline EGFR inhibitors. Despite the dramatic responses to such inhibitors, most patients ultimately have a relapse. The mechanism of the drug resistance is unknown. Here we report the case of a patient with EGFR-mutant, gefitinib-responsive
14, 1998. These women were participants in a large population-based case-control study of breast carcinoma in situ. Telephone interviews were used to collect risk factor information and blood or buccal specimens were collected for BRCA1 and BRCA2 mutation testing.Prevalence of disease-associated mutations of BRCA1 and BRCA2 in women diagnosed with DCIS.Three (0.8%) and 9 (2.4%) of 369 DCIS cases had disease-associated mutations in BRCA1 or BRCA2, respectively. One woman had a mutation in both (...) cancer before 50 years (OR, 10.6; 95% CI, 3.0-37.0).Ductal carcinoma in situ is a part of the breast/ovarian cancer syndromes defined by BRCA1 and BRCA2, with mutation rates similar to those found for invasive breast cancer. These findings suggest that patients with breast cancer with an appropriate personal or family history of breast and/or ovarian cancer should be screened and followed according to high-risk protocols, regardless of whether they are diagnosed with in situ or invasive breast cancer.
Conversion analysis for mutation detection in MLH1 and MSH2 in patients with colorectal cancer. The accurate identification and interpretation of germline mutations in mismatch repair genes in colorectal cancer cases is critical for clinical management. Current data suggest that mismatch repair mutations are highly heterogeneous and that many mutations are not detected when conventional DNA sequencing alone is used.To evaluate the potential of conversion analysis compared with DNA sequencing (...) alone to detect heterogeneous germline mutations in MLH1, MSH2, and MSH6 in colorectal cancer patients.Multicenter study with patients who participate in the Colon Cancer Family Registry. Mutation analyses were performed in participant samples determined to have a high probability of carrying mismatch repair germline mutations. Samples from a total of 64 hereditary nonpolyposis colorectal cancer cases, 8 hereditary nonpolyposis colorectal cancer-like cases, and 17 cases diagnosed prior to age 50
Detection of bladder cancer using a point-of-care proteomic assay. A combination of methods is used for diagnosis of bladder cancer because no single procedure detects all malignancies. Urine tests are frequently part of an evaluation, but have either been nonspecific for cancer or required specialized analysis at a laboratory.To investigate whether a point-of-care proteomic test that measures the nuclear matrix protein NMP22 in voided urine could enhance detection of malignancy in patients (...) with risk factors or symptoms of bladder cancer.Twenty-three academic, private practice, and veterans' facilities in 10 states prospectively enrolled consecutive patients from September 2001 to May 2002. Participants included 1331 patients at elevated risk for bladder cancer due to factors such as history of smoking or symptoms including hematuria and dysuria. Patients at risk for malignancy of the urinary tract provided a voided urine sample for analysis of NMP22 protein and cytology prior