Citations

Purpose This study was undertaken to examine five possible prognostic factors in patients with recurrent stage II and III colon cancer: time from randomization on an adjuvant therapy clinical trial to tumor recurrence (< 1 year, 1 to 2 years, 2 to 3 years, 3 to 4 years, > 4 years), initial stage (II v III), initial adjuvant treatment (fluorouracil [FU]-based v surgery alone), the era in which the patient entered an adjuvant therapy clinical trial (1978 to 1985, 1986 to 1992, 1993 to 1999), and patient age at recurrence. Methods The Adjuvant Colon Cancer End Points (ACCENT) data set was analyzed using univariate and multivariate Cox proportional hazards models, stratified by study. Results 5,722 (32.9%) of 17,381 patients experienced recurrence. Median survival following recurrence was 13.3 months. Time from randomization to recurrence was highly prognostic of survival following recurrence (P < .0001). Longer survival following recurrence was seen in patients with initial stage II versus III disease (P < .0001; 14.3% 6-year overall survival after recurrence in initial stage II patients), patients entered more recently onto trials (P < .0001), and patients initially treated with surgery alone versus FU adjuvant treatment (P = .0005). All relationships were maintained in multivariate models. Conclusion Time from initial treatment to recurrence and initial stage are important prognostic factors in patients with recurrent colon cancer. Survival following recurrence increased modestly from 1978 to 1999. Patients who had a recurrence following adjuvant therapy had poorer prognosis than those who progressed after surgery alone. These prognostic factors may be useful for clinical trial design and treatment decisions in patients with recurrent colon cancer.

AbstractDiscriminant markers are required for accurate cancer screening. We evaluated genes frequently methylated in colorectal neoplasia to identify the most discriminant ones. Four genes specifically methylated in colorectal cancer [bone morphogenetic protein 3 (BMP3), EYA2, aristaless-like homeobox-4 (ALX4), and vimentin] were selected from 41 candidate genes and evaluated on 74 cancers, 62 adenomas, and 70 normal epithelia. Methylation status was analyzed qualitatively and quantitatively and confirmed by bisulfite genomic sequencing. Effect of methylation on gene expression was evaluated in five colon cancer cell lines. K-ras and BRAF mutations were detected by sequencing. Methylation of BMP3, EYA2, ALX4, or vimentin was detected respectively in 66%, 66%, 68%, and 72% of cancers; 74%, 48%, 89%, and 84% of adenomas; and 7%, 5%, 11%, and 11% of normal epithelia (P &lt; 0.01, cancer or adenoma versus normal). Based on area under the curve analyses, discrimination was not significantly improved by combining markers. Comethylation was frequent (two genes or more in 72% of cancers and 84% of adenomas), associated with proximal neoplasm site (P &lt; 0.001), and linked with both BRAF and K-ras mutations (P &lt; 0.01). Cell line experiments supported silencing of expression by methylation in all four study genes. This study shows BMP3, EYA2, ALX4, and vimentin genes are methylated in most colorectal neoplasms but rarely in normal epithelia. Comethylation of these genes is common, and pursuit of complementary markers for methylation-negative neoplasms is a rational strategy to optimize screening sensitivity. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2686–96)

ABSTRACT Mycobacterium peregrinum consists of two taxa: types I and II. We evaluated 43 clinical type II strains from throughout the United States. They were responsible for soft-tissue and bone infections, catheter-related infections, and possible pneumonitis. By carbohydrate utilization, they were indistinguishable from type I strains, being d -mannitol and trehalose positive. However, they had a distinct susceptibility pattern that included intermediate ciprofloxacin MICs but low clarithromycin and doxycycline MICs of ≤1 μg/ml. These features were also shared by reference isolates of Mycobacterium senegalense from African bovine cases of “farcy.” By 16S rRNA gene sequencing, the type II isolates shared 100% sequence identity with M. senegalense . Partial sequencing of the type II hsp65 gene (441 bp) revealed four sequevars showing ≥98.4% identity with each other and ≥98.6% identity with the sequence of five bovine strains of M. senegalense . There was ≤97.1% identity with M. peregrinum type I isolates and other Mycobacterium fortuitum group species. Sequencing of additional gene targets including the 16S-23S rDNA internal transcribed spacer region and the rpoB gene (partial sequence) revealed a similar phylogenetic grouping. DNA-DNA hybridization showed 76 to 99% relatedness between the bovine and human strains. These studies demonstrate that type II isolates are not isolates of M. peregrinum but represent human strains of M. senegalense . This study is the first to demonstrate this species as a human pathogen. Representative human M. senegalense strains include ATCC 35755 and newly submitted strains ATCC BAA-849, ATCC BAA-850, and ATCC BAA-851.

Hypnic headache syndrome is a rare, sleep-related, benign headache disorder. We report 19 new cases (84% females) with follow-up data. The mean age at headache onset was 60.5 ± 9 years (range 40–73 years). Headache awakened the patients from the night's sleep at a consistent time, usually between 1.00 and 3.00 a.m. (63%); three patients (16%) reported that identical headaches could occur also during daytime naps. Headache frequency was high, occurring more than 4 nights/week in 68% of the patients. Headache resolution occurred within 2 h in 68% of patients. Neurologic examination, laboratory studies, and brain imaging were unrevealing at the time of diagnosis. Headache severity largely remains unchanged or attenuates over time, but frequency may vary in either direction. Only one patient had spontaneous relief from headache. Four patients (24%) achieved permanent suppression of headache with medication, and two were able to abort individual headache attacks. Caffeine in a tablet or beverage was helpful in four patients. Lithium carbonate therapy caused side effects requiring cessation of treatment in four patients.