Citations

Purpose To determine prognostic factors and impact of adjuvant chemotherapy (CT) and radiotherapy (RT) on overall survival (OS) after resection of pancreatic adenocarcinoma. Patients and Methods We performed a retrospective review 472 consecutive patients who underwent complete resection with negative margins (R0) for invasive carcinoma (T1-3N0-1M0) of the pancreas between 1975 and 2005 at the Mayo Clinic in Rochester, MN. Exclusion criteria included metastatic or unresectable disease at surgery, positive surgical margins, and indolent tumor types (islet cell tumors and mucinous cystadenocarcinoma). Median RT dose was 50.4 Gy in 28 fractions; 98% of RT patients also received concurrent fluorouracil-based CT. Results Six patients died within 30 days of surgery. For the 466 surviving patients, median follow-up was 32.4 months; median OS was 21.6 months. Median OS after adjuvant CT-RT was 25.2 versus 19.2 months after no adjuvant therapy (P = .001). Two-year OS was 50% versus 39%, and 5-year OS was 28% versus 17%. Adverse prognostic factors identified by univariate and multivariate analysis included positive lymph nodes (risk ratio [RR] = 1.3; P < .001), high histologic grade (RR = 1.2; P < .001), and no adjuvant therapy (RR = 1.3; P < .001). Tumor extension beyond the pancreas was an adverse prognostic factor by univariate analysis alone (P = .03). Patients receiving adjuvant therapy had more adverse prognostic factors than those not receiving adjuvant therapy (P = .001). Conclusion This study represents one of the largest, single-institution, retrospective reviews of adjuvant therapy in patients after R0 resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CT-RT.

Abstract Whole genome amplification (WGA) offers a means to enrich DNA quantities for epidemiologic studies. We used an ovarian cancer study of 1,536 single nucleotide polymorphisms (SNPs) and 2,368 samples to assess performance of multiple displacement amplification (MDA) WGA using an Illumina GoldenGate BeadArray. Initial screening revealed successful genotyping for 93.4% of WGA samples and 99.3% of genomic samples, and 93.2% of SNPs for WGA samples and 96.3% of SNPs for genomic samples. SNP failure was predicted by Illumina-provided designability rank, %GC (P ≤ 0.002), and for WGA only, distance to telomere and Illumina-provided SNP score (P ≤ 0.002). Distance to telomere and %GC were highly correlated; adjustment for %GC removed the association between distance to telomere and SNP failure. Although universally high, per-SNP call rates were related to designability rank, SNP score, %GC, minor allele frequency, distance to telomere (P ≤ 0.01), and, for WGA only, Illumina-provided validation class (P &lt; 0.001). We found excellent concordance generally (&gt;99.0%) among 124 WGA:genomic replicates, 15 WGA replicates, 88 replicate aliquots of the same WGA preparation, and 25 genomic replicates. Where there was discordance, it was across WGA:genomic replicates but limited to only a few samples among other replicates suggesting the introduction of error. Designability rank and SNP score correlated with WGA:genomic concordance (P &lt; 0.001). In summary, use of MDA WGA DNA is feasible; however, caution is warranted regarding SNP selection and analysis. We recommend that biological SNP characteristics, notably distance to telomere and GC content (&lt;50% GC recommended), as well as Illumina-provided metrics be considered in the creation of GoldenGate assays using MDA WGA DNA. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1781–9)

The American Heart Association’s (AHA’s) mission is “to build healthier lives, free of cardiovascular diseases and stroke.” This first article in a 2-part series will serve to present an overview of the work the AHA has undertaken to translate evidence into practice for healthcare professionals. It describes the extensive work of the AHA to support and further the delivery of evidence-based medicine, which includes the following: (1) supporting scientific discovery and the next generation of healthcare professionals and researchers; (2) disseminating scientific information; (3) developing evidence-based guidelines and statements; (4) creating and advocating for the implementation of performance indicators/measures; (5) developing clinical decision support and quality improvement tools; and (6) developing directed-cause campaigns, all of which can lead to improved patient care. This article also discusses the need for novel approaches and some of the AHA’s evolving strategies to help address gaps in care. The second article, which will be published shortly after this one, will examine the AHA’s efforts to engage and empower healthcare consumers to become more involved with their own health and health care.

Object The cervical foraminotomy was pioneered in the 1940s to address radicular symptoms via a posterior approach, but the long-term outcome has not been adequately studied. Methods The authors retrospectively analyzed data obtained from 303 patients (188 male and 115 female, mean age 49.2 years) who had consecutively undergone a single-level posterior foraminotomy for cervical radiculopathy between 1972 and 1992. The median follow-up duration was 7.1 years. The major end point studied was the development of symptomatic adjacent- or same-segment disease. Incidence rates per 1000 person-years were calculated, and the natural history of the disease was predicted using Kaplan–Meier survivorship analysis. In 15 (4.9%) of 303 patients, symptomatic adjacent-segment disease developed, yielding a rate of 6.4/1000 person-years at risk. This included nine (2.9%) of 303 patients requiring reoperation, yielding a rate of 3.8/1000 person-years. Kaplan–Meier survivorship analysis suggested a relatively stable annual 0.7% rate for developing adjacent-segment disease, with a 10-year rate of 6.7%. Ten patients developed same-segment disease, yielding a risk rate of 3.9/1000 person-years. Kaplan–Meier survivorship analysis demonstrated a 5- and 10-year risk rate of developing same-segment disease of 3.2 and 5.0%, respectively. Conclusions Although additional study is needed, analysis of the present data suggests that posterior foraminotomy is associated with a low rate of same- and adjacent-segment disease.

Abstract The standard systemic treatment for prostate cancer (PCa) is androgen ablation, which causes tumor regression by inhibiting activity of the androgen receptor (AR). Invariably, PCa recurs with a fatal androgen-refractory phenotype. Importantly, the growth of androgen-refractory PCa remains dependent on the AR through various mechanisms of aberrant AR activation. Here, we studied the 22Rv1 PCa cell line, which was derived from a CWR22 xenograft that relapsed during androgen ablation. Three AR isoforms are expressed in 22Rv1 cells: a full-length version with duplicated exon 3 and two truncated versions lacking the COOH terminal domain (CTD). We found that CTD-truncated AR isoforms are encoded by mRNAs that have a novel exon 2b at their 3′ end. Functionally, these AR isoforms are constitutively active and promote the expression of endogenous AR-dependent genes, as well as the proliferation of 22Rv1 cells in a ligand-independent manner. AR mRNAs containing exon 2b and their protein products are expressed in commonly studied PCa cell lines. Moreover, exon 2b–derived species are enriched in xenograft-based models of therapy-resistant PCa. Together, our data describe a simple and effective mechanism by which PCa cells can synthesize a constitutively active AR and thus circumvent androgen ablation. [Cancer Res 2008;68(13):5469–77]

Objective: Mother-daughter communication may be a potential pathway between family history and cancer prevention behavior. We examined the degree to which mothers reported providing advice on breast cancer prevention to their daughters, the content of such advice, and correlates of providing such advice. Methods: Data were collected via a mailed questionnaire to 1773 women from 355 families in the Minnesota Breast Cancer Family Study. Women were asked whether or not they had provided advice to their daughters on what they should do to prevent breast cancer. An additional open-ended question asked them to describe the types of advice they had provided. Results: Nine hundred seventy-six (55%) of the women reported providing breast cancer prevention advice to their daughters. The most frequent types of advice were to have a mammogram (51%), perform breast self-examination (BSE) (39%), have a clinical breast examination (CBE) (30%), and maintain a healthy lifestyle (21%). From multivariate logistic regression, older age ( p < 0.001), having a personal history of breast cancer ( p < 0.001), higher degree of breast cancer worry/concern ( p < 0.001), engaging in a higher number of health-promoting behaviors ( p < 0.001), and ever performing a BSE ( p = 0.04) were factors independently associated with the provision of advice. Analyses accounting for sample nonindependence did not change our results. Conclusions: Breast cancer prevention behaviors were associated with providing advice. By better understanding the pathways through which breast cancer family history is associated with screening mammography and other prevention behaviors, researchers can develop more effective, tailored prevention interventions at the family level.