bluuebunny/crossref_metadata_2025 huggingface dataset:
Toona sinensisLeaf Aqueous Extract Improves the Functions of Sperm and Testes via Regulating Testicular Proteins in Rats under Oxidative Stress
Authors: Yu Bu-Chin , Yu Wen-Jen , Huang Chun-Yung , Chen Ying-Hsin , Tsai Yun-Ching , Chang Chen-Chin , Chang Sue-Joan
Published: October 2012

Toona sinensisleaf (TSL) is commonly used as a vegetable and in spice in Asia. In this study, feeding with aqueous extract of TSL (TSL-A) alleviated oxidative stress and recovered the motility and functions of sperm in rats under oxidative stress. Protein expressions in testes identified by proteomic analysis and verified by Western blot demonstrated that TSL-A not only downregulated the level of glutathione transferase mu6 (antioxidant system), heat shock protein 90 kDa-β(protein misfolding repairing system), cofilin 2 (spermatogenesis), and cyclophilin A (apoptosis) but also upregulated crease3-hydroxy-3-methylglutaryl-coenzyme A synthase 2 (steroidogenesis), heat shock glycoprotein 96, and pancreatic trypsin 1 (sperm-oocyte interaction). These results indicate that TSL-A promotes the functions of sperm and testes via regulating multiple testicular proteins in rats under oxidative stress, suggesting that TSL-A is a valuable functional food supplement to improve functions of sperm and testes for males under oxidative stress.
Combined Posterior and Anterior Ankle Arthroscopy
Authors: Scholten Peter E. , van Dijk C. Niek
Published: October 2012

Treatment of combined anterior and posterior ankle pathology usually consists of either combined anterior and posterior arthrotomies or anterior ankle arthroscopy with an additional posterolateral portal. The first technique bears the risk of complications associated with the extensive exposure, the latter technique provides limited access to the posterior ankle joint. A case is described of combined anterior and posterior arthroscopy, with the patient lying prone and then turned supine, addressing both anterior and posterior ankle pathologies in one tempo. This minimally invasive combined approach allows quick recovery and early return to work and sports activities.
Fulminant Hepatic Failure Attributed to Ackee Fruit Ingestion in a Patient with Sickle Cell Trait
Authors: Grunes Dianne E. , Scordi-Bello Irini , Suh Matthew , Florman Sander , Yao Jonathan , Fiel Maria Isabel , Thung Swan N.
Published: October 2012

We report a case of fulminant liver failure resulting in emergent liver transplantation following 3 weeks of nausea, vomiting, and malaise from Jamaican Vomiting Sickness. Jamaican Vomiting Sickness is caused by ingestion of the unripe arils of the Ackee fruit, its seeds and husks. It is characterized by acute gastrointestinal illness and hypoglycemia. In severe cases, central nervous system depression can occur. In previous studies, histologic sections taken from patients with Jamaican Vomiting Sickness have shown hepatotoxicity similar to that seen in Reye syndrome and/or acetaminophen toxicity. We highlight macroscopic and microscopic changes in the liver secondary to hepatoxicity of Ackee fruit versus those caused by a previously unknown sickle cell trait. We discuss the clinical variables and the synergistic hepatotoxic effect of Ackee fruit and ischemic injury from sickled red blood cells, causing massive hepatic necrosis in this patient.
Two-Layer Storage Scheme and Repair Method of Failure Data in Wireless Sensor Networks
Authors: Shen Yulong , Dang Xiaowei , Shu Min , Xi Ning , Ma Jianfeng
Published: October 2012

Distributed data storage is a key technology in the data collection in wireless sensor networks. The storage scheme based on network coding is applied to data collection in wireless sensor networks because of its high reliability and low overhead. However, it is an open problem to reduce data repair communication overhead caused by the failure of storage nodes. This paper focuses on this issue and presents a two-layer distributed data storage scheme. The lower-layer nodes store the encoded data blocks and the upper-layer nodes store the re-encoded blocks that are responsible for failure data recovery. Based on the two-layer data storage scheme, a data repair method is proposed to decrease the repair communication overhead with only sacrificing lower storage overhead. Compared with MSR, interference alignment-based scheme and group interference alignment scheme, the proposed method has lower repair communication overhead. We prove that the proposed method can reduce the repair communication overhead to [Formula: see text] times and it is suitable to resource-constrained distributed wireless sensor networks.
IgG4 Inflammatory Pseudotumor of the Kidney
Authors: Alkhasawneh Ahmed N. , Allan Robert W.
Published: October 2012

Hyper-IgG4 disease is a rare systemic disorder that usually affects middle age males. It is characterized by elevated serum IgG4 levels and infiltration of organs by IgG4 positive plasma cells associated with fibrosis. Patients usually present with mass or masses in the involved organ that mimic neoplasia. While initially described in the pancreas, IgG4-related inflammatory tumors have been now described in many organs. We describe an unusual case of an IgG4-related pseudotumor of the kidney.
Perceived and Objective Breast Cancer Risk Assessment in Chilean Women Living in an Underserved Area
Authors: Banegas Matthew P. , Püschel Klaus , Martínez-Gutiérrez Javiera , Anderson Jennifer C. , Thompson Beti
Published: October 2012

Background: Breast cancer is the most frequently diagnosed malignancy among Chilean women and an increasingly significant public health threat. This study assessed the accuracy of breast cancer risk perception among underserved, Chilean women.

Methods: Women aged 50 to 70 years, with no mammogram during the last 2 years, were randomly selected from a community clinic registry in Santiago, Chile (n = 500). Perceived risk was measured using three methods: absolute risk, comparative risk, and numerical risk. Risk comprehension was measured by comparing women's perceived and objective risk estimates. Multivariate logistic regression was used to assess overestimation of perceived risk.

Results: Women at high risk of breast cancer were more likely than average risk women to perceive themselves at high or higher risk, using absolute and comparative risk approaches (P < 0.001). The majority of participants (67%) overestimated their breast cancer risk, on the basis of risk comprehension; although, participants achieved higher accuracy with comparative risk (40%) and absolute risk (31.6%) methods. [Age, breast cancer knowledge and Breast Cancer Risk Assessment Tool (BCRAT) 5-year risk were significantly associated (P < 0.01) with accuracy of perceived risk].

Conclusion: Chilean women residing in an underserved community may not accurately assess their breast cancer risk, although risk perception and level of accuracy differed between perceived risk measures. Comparative and absolute risk methods may better reflect women's interpretation and accuracy of risk perception.

Impact: Improving our understanding of Chilean women's perceptions of developing breast cancer may lead to the development of culturally relevant efforts to reduce the breast cancer burden in this population. Cancer Epidemiol Biomarkers Prev; 21(10); 1716–21. ©2012 AACR.
A Multilevel Research Perspective on Cancer Care Delivery: The Example of Follow-Up to An Abnormal Mammogram
Authors: Taplin Stephen H. , Yabroff K. Robin , Zapka Jane
Published: October 2012

In 1999, researchers and policy makers recognized the challenge of creating an integrated patient-centered cancer care process across the many types of care from risk assessment through end of life. More than a decade later, there has been limited progress toward that goal even though the standard reductionist approach to health services and medical research has resulted in major advances in tests, procedures, and individualized patient approaches to care. In this commentary, we propose that considering an entire care process within its multilevel context may increase progress toward an integrated experience and improvements in the quality of care. As an illustrative case, we describe the multilevel context of care delivery for the process of follow-up to an abnormal screening mammogram. By taking a multilevel perspective on this process, we identify a rich set of options for intervening and improving follow-up to abnormalities and, therefore, outcomes of screening. We propose that taking this multilevel perspective when designing interventions may improve the quality of cancer care in an effective and sustainable way. Cancer Epidemiol Biomarkers Prev; 21(10); 1709–15. ©2012 AACR.
Global Gene Expression Analysis in Cord Blood Reveals Gender-Specific Differences in Response to Carcinogenic Exposure In Utero
Authors: Hochstenbach Kevin , van Leeuwen Danitsja M. , Gmuender Hans , Gottschalk Ralf W. , Løvik Martinus , Granum Berit , Nygaard Unni , Namork Ellen , Kirsch-Volders Micheline , Decordier Ilse , Vande Loock Kim , Besselink Harrie , Törnqvist Margareta , von Stedingk Hans , Rydberg Per , Kleinjans Jos C.S. , van Loveren Henk , van Delft Joost H.M.
Published: October 2012

Background: It has been suggested that fetal carcinogenic exposure might lead to predisposition to develop cancer during childhood or in later life possibly through modulation of the fetal transcriptome. Because gender effects in the incidence of childhood cancers have been described, we hypothesized differences at the transcriptomic level in cord blood between male and female newborns as a consequence of fetal carcinogenic exposure. The objective was to investigate whether transcriptomic responses to dietary genotoxic and nongenotoxic carcinogens show gender-specific mechanisms-of-action relevant for chemical carcinogenesis.

Methods: Global gene expression was applied in umbilical cord blood samples, the CALUX-assay was used for measuring dioxin(-like), androgen(-like), and estrogen(-like) internal exposure, and acrylamide–hemoglobin adduct levels were determined by mass spectrometry adduct-FIRE-procedureTM. To link gene expression to an established phenotypic biomarker of cancer risk, micronuclei frequencies were investigated.

Results: While exposure levels did not differ between sexes at birth, important gender-specific differences were observed in gene expressions associated with these exposures linked with cell cycle, the immune system and more general cellular processes such as posttranslation. Moreover, oppositely correlating leukemia/lymphoma genes between male and female newborns were identified in relation to the different biomarkers of exposure that might be relevant to male-specific predisposition to develop these cancers in childhood.

Conclusions/Impact: This study reveals different transcriptomic responses to environmental carcinogens between the sexes. In particular, male-specific TNF-alpha-NF-kB signaling upon dioxin exposure and activation of the Wnt-pathway in boys upon acrylamide exposure might represent possible mechanistic explanations for gender specificity in the incidence of childhood leukemia. Cancer Epidemiol Biomarkers Prev; 21(10); 1756–67. ©2012 AACR.
Associations of Lifestyle Factors and Anthropometric Measures with Repeat PSA Levels During Active Surveillance/Monitoring
Authors: Burton Anya J. , Martin Richard M. , Donovan Jenny L. , Lane J. Athene , Davis Michael , Hamdy Freddie C. , Neal David E. , Tilling Kate
Published: October 2012

Background: Assessment of prostate-specific antigen increase with time (PSA growth) is a fundamental component of active surveillance among men with localized prostate cancer. Factors that influence PSA growth, however, are unclear. We evaluated associations of anthropometric and lifestyle factors with age-related PSA growth.

Methods: Repeat PSA measures from 404 men, aged 50 to 69 years, with localized prostate cancer undergoing active monitoring were obtained. From log(PSA) measures, age-specific multilevel mixed effect linear models were developed to predict PSA at age 50 years and yearly increase in postdiagnosis PSA. Baseline anthropometric measures, alcohol consumption, occupational class, smoking status, and physical activity were added to the model as covariates.

Results: The median number of repeat PSAs was 13 (range, 2–40), and the mean duration of follow-up was 4.8 years (SD, 2.3). The basic model of age-related PSA growth in men with localized prostate cancer estimated a mean PSA at age 50 of 3.95 ng/mL [95% confidence interval (CI): 3.55 to 4.39] and a yearly increase of 8.50% (95% CI: 7.90% to 9.10%). PSA at age 50 years was 2.1% lower per unit increase in weighted exercise score (95% CI: −3.3 to −0.8), 5.3% lower per 5 cm increase in height (95% CI: −9.4 to −1.1), and 24.5% higher (95% CI: 4.0 to 49.1) in current smokers than never smokers. Similar associations with PSA growth were seen.

Conclusion: Smoking and exercise are modifiable lifestyle factors that may be associated with PSA levels in men with localized prostate cancer undergoing active monitoring/surveillance.

Impact: These factors may be useful in understanding etiology of progression. Cancer Epidemiol Biomarkers Prev; 21(10); 1877–85. ©2012 AACR.
Age-Associated Gene Expression in Normal Breast Tissue Mirrors Qualitative Age-at-Incidence Patterns for Breast Cancer
Authors: Pirone Jason R. , D'Arcy Monica , Stewart Delisha A. , Hines William C. , Johnson Melissa , Gould Michael N. , Yaswen Paul , Jerry D. Joseph , Schneider Sallie Smith , Troester Melissa A.
Published: October 2012

Background: Age is the strongest breast cancer risk factor, with overall breast cancer risk increasing steadily beginning at approximately 30 years of age. However, while breast cancer risk is lower among younger women, young women's breast cancer may be more aggressive. Although, several genomic and epidemiologic studies have shown higher prevalence of aggressive, estrogen-receptor negative breast cancer in younger women, the age-related gene expression that predisposes to these tumors is poorly understood. Characterizing age-related patterns of gene expression in normal breast tissues may provide insights on etiology of distinct breast cancer subtypes that arise from these tissues.

Methods: To identify age-related changes in normal breast tissue, 96 tissue specimens from patients with reduction mammoplasty, ages 14 to 70 years, were assayed by gene expression microarray.

Results: Significant associations between gene expression levels and age were identified for 802 probes (481 increased, 321 decreased with increasing age). Enriched functions included “aging of cells,” “shape change,” and “chemotaxis,” and enriched pathways included Wnt/beta-catenin signaling, Ephrin receptor signaling, and JAK/Stat signaling. Applying the age-associated genes to publicly available tumor datasets, the age-associated pathways defined two groups of tumors with distinct survival.

Conclusion: The hazard rates of young-like tumors mirrored that of high-grade tumors in the Surveillance, Epidemiology, and End Results Program, providing a biologic link between normal aging and age-related tumor aggressiveness.

Impact: These data show that studies of normal tissue gene expression can yield important insights about the pathways and biologic pressures that are relevant during tumor etiology and progression. Cancer Epidemiol Biomarkers Prev; 21(10); 1735–44. ©2012 AACR.
Variation in IL10 and Other Genes Involved in the Immune Response and in Oxidation and Prostate Cancer Recurrence
Authors: Dluzniewski Paul J. , Wang Ming-Hsi , Zheng Siqun Lilly , De Marzo Angelo M. , Drake Charles G. , Fedor Helen L. , Partin Alan W. , Han Misop , Fallin M. Daniele , Xu Jianfeng , Isaacs William B. , Platz Elizabeth A.
Published: October 2012

Background: To evaluate the association of variation in genes involved in immune response, including IL10, production and detoxification of reactive oxygen species, and repair of oxidative DNA damage with risk of recurrence after surgery for localized prostate cancer.

Methods: We conducted a nested case-control study of men who had a radical prostatectomy in 1993 to 2001. A total of 484 recurrence cases and 484 controls were matched on age, race, and pathologic stage and grade. Germline DNA was extracted from paraffin-embedded unaffected lymph nodes. We genotyped candidate single-nucleotide polymorphisms (SNP) in IL10, CRP, GPX1, GSR, GSTP1, hOGG1, IL1B, IL1RN, IL6, IL8, MPO, NOS2, NOS3, SOD1, SOD2, SOD3, TLR4, and TNF and tagging SNPs in IL10, CRP, GSR, IL1RN, IL6, NOS2, and NOS3. We used conditional logistic regression to estimate OR and 95% confidence intervals (CI).

Results: The minor allele (A) in IL10 rs1800872, known to produce less interleukin-10 (IL-10), was associated with a higher risk of recurrence (OR = 1.76, 95% CI: 1.00–3.10), and the minor allele (G) in rs1800896, known to produce more IL-10, was associated with a lower risk of recurrence (OR = 0.66, 95% CI: 0.48–0.91). We also observed associations for candidate SNPs in CRP, GSTP1, and IL1B. A common IL10 haplotype and 2 common NOS2 haplotypes were associated with recurrence.

Conclusion: Variation in IL10, CRP, GSTP1, IL1B, and NOS2 was associated with prostate cancer recurrence independent of pathologic prognostic factors.

Impact: This study supports that genetic variation in immune response and oxidation influence prostate cancer recurrence risk and suggests genetic variation in these pathways may inform prognosis. Cancer Epidemiol Biomarkers Prev; 21(10); 1774–82. ©2012 AACR.
Do Breast Implants Adversely Affect Prognosis among Those Subsequently Diagnosed with Breast Cancer? Findings from an Extended Follow-Up of a Canadian Cohort
Authors: Lavigne Eric , Holowaty Eric J. , Pan Sai Yi , Xie Lin , Villeneuve Paul J. , Morrison Howard , Brisson Jacques
Published: October 2012

Background: Cosmetic breast implants may impair the ability to detect breast cancers. The aims of this study were to examine whether implants and implant characteristics are associated with more advanced breast tumors at diagnosis and poorer survival.

Methods: Study population includes all invasive breast cancer cases diagnosed during follow-up of the large Canadian Breast Implant Cohort. A total of 409 women with cosmetic breast implants and 444 women with other cosmetic surgery were diagnosed with breast cancer. These women were compared for stage at diagnosis using multinomial logistic regression models. Cox proportional hazards regression models were used for breast cancer-specific mortality analyses. Comparisons were also conducted according to implant characteristics.

Results: Compared with women with other cosmetic surgery, those with cosmetic breast implants had at later stage breast cancer diagnosis (OR of having stage III/IV vs. stage I at diagnosis: 3.04, 95% confidence interval (CI): 1.81–5.10; P < 0.001). A nonstatistically significant increase in breast cancer-specific mortality rate for women with breast implants relative to surgical controls was observed (HR = 1.32, 95% CI: 0.94–1.83, P = 0.11). No statistically significant differences in stage and breast cancer mortality were observed according to implant characteristics.

Conclusions: At diagnosis, breast cancers tended to be at more advanced stages among women with cosmetic breast implants. Breast cancer-specific survival was lower in these women although the reduction did not reach statistical significance.

Impact: Further investigations of the effect of breast implants on breast cancer prognosis are warranted. Cancer Epidemiol Biomarkers Prev; 21(10); 1868–76. ©2012 AACR.
The Ohio Patient Navigation Research Program: Does the American Cancer Society Patient Navigation Model Improve Time to Resolution in Patients with Abnormal Screening Tests?
Authors: Paskett Electra D. , Katz Mira L. , Post Douglas M. , Pennell Michael L. , Young Gregory S. , Seiber Eric E. , Harrop J. Phil , DeGraffinreid Cecilia R. , Tatum Cathy M. , Dean Julie A. , Murray David M.
Published: October 2012

Background: Patient navigation (PN) has been suggested as a way to reduce cancer health disparities; however, many models of PN exist and most have not been carefully evaluated. The goal of this study was to test the Ohio American Cancer Society model of PN as it relates to reducing time to diagnostic resolution among persons with abnormal breast, cervical, or colorectal cancer screening tests or symptoms.

Methods: A total of 862 patients from 18 clinics participated in this group-randomized trial. Chart review documented the date of the abnormality and the date of resolution. The primary analysis used shared frailty models to test for the effect of PN on time to resolution. Crude HR were reported as there was no evidence of confounding.

Results: HRs became significant at 6 months; conditional on the random clinic effect, the resolution rate at 15 months was 65% higher in the PN arm (P = 0.012 for difference in resolution rate across arms; P = 0.009 for an increase in the HR over time).

Conclusions: Participants with abnormal cancer screening tests or symptoms resolved faster if assigned to PN compared with those not assigned to PN. The effect of PN became apparent beginning six months after detection of the abnormality.

Impact: PN may help address health disparities by reducing time to resolution after an abnormal cancer screening test. Cancer Epidemiol Biomarkers Prev; 21(10); 1620–8. ©2012 AACR.
Boston Patient Navigation Research Program: The Impact of Navigation on Time to Diagnostic Resolution after Abnormal Cancer Screening
Authors: Battaglia Tracy A. , Bak Sharon M. , Heeren Timothy , Chen Clara A. , Kalish Richard , Tringale Stephen , Taylor James O. , Lottero Barbara , Egan A. Patrick , Thakrar Nisha , Freund Karen M.
Published: October 2012

Background: There is a need for controlled studies to assess the impact of patient navigation in vulnerable cancer populations.

Methods: Boston Patient Navigation Research Program conducted a quasi-experimental patient navigation intervention across six federally qualified inner-city community health centers, three assigned to a breast cancer navigation intervention and three assigned to a cervical cancer navigation intervention; each group then served as the control for the other. Eligible women had an abnormal breast or cervical cancer screening test conducted at one of the participating health centers during a baseline (2004–2005) or intervention period (2007–2008). Kaplan–Meier survival curves and proportional hazards regression examined the effect of patient navigation on time to definitive diagnosis, adjusting for covariates, clustering by clinic and differences between the baseline and intervention period.

Results: We enrolled 997 subjects in the baseline period and 3,041 subjects during the intervention period, of whom 1,497 were in the navigated arm, and 1,544 in the control arm. There was a significant decrease in time to diagnosis for subjects in the navigated group compared with controls among those with a cervical screening abnormality [aHR 1.46; 95% confidence interval (CI), 1.1–1.9]; and among those with a breast cancer screening abnormality that resolved after 60 days (aHR 1.40; 95% CI, 1.1–1.9), with no differences before 60 days.

Conclusions: This study documents a benefit of patient navigation on time to diagnosis among a racially/ethnically diverse inner city population.

Impact: Patient navigation may address cancer health disparities by reducing time to diagnosis following an abnormal cancer-screening event. Cancer Epidemiol Biomarkers Prev; 21(10); 1645–54. ©2012 AACR.
Beneficial Effects of a Combined Navigator/Promotora Approach for Hispanic Women Diagnosed with Breast Abnormalities
Authors: Dudley Donald J. , Drake Joan , Quinlan Jennifer , Holden Alan , Saegert Pam , Karnad Anand , Ramirez Amelie
Published: October 2012

Background: Patient navigation (PN) is an emerging strategy to overcome barriers to cancer care. We evaluated the efficacy of PN in improving time of key events in cancer care, including positive screening tests, definitive diagnosis, initiation of therapy, and completion of initial therapy.

Methods: We evaluated PN in a prospective observational study of predominantly poor Hispanic women with an abnormal breast cancer screening or untreated biopsy proven breast cancer (control = 200, intervention = 260). Controls were contemporary record-based patients with positive screening. Analyses were conducted for the entire cohort and separately by ethnic strata. We used χ2 tests to compare differences in proportions and Kaplan–Meier followed by Cox regression to compare time-to-event curves of the intervention and control groups.

Results: The average days from definitive diagnosis to initiation of therapy was significantly reduced overall with PN (PN vs. control, 57 vs. 74 days, P = 0.04). This effect was more pronounced in the Hispanic strata (56 vs. 81 days, P = 0.02). More navigated Hispanic women were diagnosed within 60 days of abnormal screening (62.6% vs. 47.5%, P < 0.01) and more began treatment within 60 days of diagnosis (80% vs. 56.3%, P < 0.01). Navigated Hispanic and other ethnic minority women had a shorter time from positive screening test to definitive diagnosis (16 and 32 days, respectively).

Conclusions: Minority women may have benefited from navigation with shorter times from definitive diagnosis to initiation of therapy.

Impact: PN intervention may show promise in decreasing some delays that contribute to health disparities among minority women with breast cancer. Cancer Epidemiol Biomarkers Prev; 21(10); 1639–44. ©2012 AACR.
Lung Cancer Survival among Black and White Patients in an Equal Access Health System
Authors: Zheng Li , Enewold Lindsey , Zahm Shelia H. , Shriver Craig D. , Zhou Jing , Marrogi Aizen , McGlynn Katherine A. , Zhu Kangmin
Published: October 2012

Background: Racial disparities in lung cancer outcomes have been observed in the general population. However, it is unclear whether survival differences persist when patients have equal access to health care. Our objective was to determine if lung cancer survival differed among black and white patients in the U.S. Military Health System (MHS), an equal access health care system.

Methods: The study subjects were 10,181 black and white patients identified through the Department of Defense's Automated Central Tumor Registry, who were 20 years old or more and diagnosed with lung cancer between 1990 and 2003. Racial differences in all-cause survival were examined using the Kaplan–Meier method and Cox proportional hazards regression models stratified by histology. For comparison, survival rates in the general population were calculated using Surveillance Epidemiology and End Results-9 data.

Results: Analyses included 9,154 white and 1,027 black patients: 1,834 small cell lung cancers, 3,876 adenocarcinomas, 2,741 squamous cell carcinomas, and 1,730 large cell carcinomas. Although more favorable crude survival was observed among black patients than white patients with small cell lung cancer (P = 0.04), survival was similar between the two groups after covariate adjustment. Racial differences in survival were nonsignificant for adenocarcinomas, squamous cell carcinomas, and large cell carcinomas. Survival rates appeared to be better in the MHS than in the general population.

Conclusions and Impact: All-cause survival was similar among black and white lung cancer patients in the MHS. Providing equal access to health care may eliminate racial disparities in lung cancer survival while improving the outcome of all cases. Cancer Epidemiol Biomarkers Prev; 21(10); 1841–7. ©2012 AACR.
Estimated Mean Sojourn Time Associated with Hemoccult SENSA for Detection of Proximal and Distal Colorectal Cancer
Authors: Zheng Wenying , Rutter Carolyn M.
Published: October 2012

Background: Sojourn time is the length of the preclinical screen-detectable phase, a period when a test can detect asymptomatic disease. Mean sojourn time (MST) is an important factor in determining appropriate screening intervals. Available estimates of MST for colorectal cancer (CRC) are imprecise and are associated with the older Hemoccult II test. This article presents MST estimates associated with the newer Hemoccult SENSA test and describes differences in MST by the location of cancer in the colorectum and age at the time of screening.

Methods: MST was estimated from a cohort of 42,079 patients who underwent Hemoccult SENSA between January 1, 1997 and December 31, 2010. The precision of MST estimates was improved by incorporating information from a meta-analysis of the sensitivity of Hemoccult SENSA into the analytic model.

Results: Estimated MST for cancers in the proximal and distal colorectum, with 95% credible intervals (CrI) in years, were: 3.86 (1.55–6.91) and 3.35 (2.11–4.93) among 45- to 54-year olds; 3.78 (2.18–5.77) and 2.24 (1.48–3.17) among 55- to 64-year olds; and 2.70 (1.41–4.31) and 2.10 (1.34–3.04) among 65- to 74-year olds.

Conclusions: MST associated with Hemoccult SENSA was longer for CRC in the proximal versus distal colon. We found no evidence that MST increases with age and some evidence that it may decrease.

Impact: These results add new information about the natural history of CRC and information about the performance of Hemoccult SENSA. Cancer Epidemiol Biomarkers Prev; 21(10); 1722–30. ©2012 AACR.
A Prospective Study of Total and Ionized Serum Calcium and Time to Fatal Prostate Cancer
Authors: Schwartz Gary G. , Skinner Halcyon G.
Published: October 2012

Background: Higher levels of total and ionized serum calcium have been shown to predict fatal prostate cancer in prospective studies. Because the follow-up time in these studies was relatively short, these associations could reflect the effect of clinically significant but occult prostate tumors on serum calcium levels. If this were true, prostate cancer mortality rates among men with higher levels of serum calcium should be higher during the early follow-up period and should decline thereafter.

Methods: We tested this hypothesis by estimating the relative risk of death from prostate cancer in the National Health and Nutrition Examination Survey III for incremental increases in total and ionized serum calcium using Cox proportional hazards regression with time-dependent effects.

Results: Forty-nine (49) fatal prostate cancers occurred over 204 months of follow-up and 1,069,327 person–months of observation. Men with higher total serum calcium and higher serum ionized calcium had increased risks of fatal prostate cancer during the first 96 months of follow-up [Relative Hazard (RH) = 1.50 per 0.1 mmol/L total serum calcium, 95% confidence interval (CI) = 1.04–2.17; RH = 1.72 per 0.05 mmol/L ionized calcium, 95% CI = 1.11–2.66]. Evidence of an association between total and ionized serum calcium and prostate cancer deaths was not significant after 96 months.

Conclusions: Our analyses support the hypothesis that the elevated risk for fatal prostate cancer observed in men with high serum calcium is because of the presence of extant, but occult prostate cancer.

Impact: These findings have implications for the potential use of serum calcium in the detection of clinically significant prostate cancer. Cancer Epidemiol Biomarkers Prev; 21(10); 1768–73. ©2012 AACR.
BRAF Mutation Status and Survival after Colorectal Cancer Diagnosis According to Patient and Tumor Characteristics
Authors: Phipps Amanda I. , Buchanan Daniel D. , Makar Karen W. , Burnett-Hartman Andrea N. , Coghill Anna E. , Passarelli Michael N. , Baron John A. , Ahnen Dennis J. , Win Aung Ko , Potter John D. , Newcomb Polly A.
Published: October 2012

Background:BRAF mutations in colorectal cancer (CRC) are disproportionately observed in tumors exhibiting microsatellite instability (MSI) and are associated with other prognostic factors. The independent association between BRAF mutation status and CRC survival, however, remains unclear.

Methods: We evaluated the association between the BRAF c.1799T>A (p.V600E) mutation and survival in individuals with incident invasive CRC diagnosed between 1997 and 2007 in Western Washington State. Tumor specimens were tested for this BRAF mutation and MSI status. We used Cox regression to estimate HRs and 95% confidence intervals (CI) for the association between BRAF mutation status and disease-specific and overall survival. Stratified analyses were conducted by age, sex, tumor site, stage, and MSI status.

Results: Among 1,980 cases tested, 12% were BRAF c.1799T>A (p.V600E) mutation–positive (n = 247). BRAF-mutated CRC was associated with poorer disease-specific survival adjusting for age, sex, time from diagnosis to enrollment, stage, and MSI status (HR, 1.43; 95% CI, 1.05–1.95). This association was limited to cases diagnosed at ages <50 (HR, 3.06; 95% CI, 1.70–5.52) and was not evident in cases with MSI-high tumors (HR, 0.94; 95% CI, 0.44–2.03). Associations with overall survival were similar.

Conclusions: Our results show that the prevalence of BRAF mutations in CRC differs by patient and tumor characteristics and suggest that the association between BRAF status and CRC survival may differ by some of these factors.

Impact: The presence of a BRAF c.1799T>A (p.V600E) mutation is associated with significantly poorer prognosis after CRC diagnosis among subgroups of patients. Cancer Epidemiol Biomarkers Prev; 21(10); 1792–8. ©2012 AACR.
A Two-Stage Evaluation of Genetic Variation in Immune and Inflammation Genes with Risk of Non-Hodgkin Lymphoma Identifies New Susceptibility Locus in 6p21.3 Region
Authors: Cerhan James R. , Fredericksen Zachary S. , Novak Anne J. , Ansell Stephen M. , Kay Neil E. , Liebow Mark , Dogan Ahmet , Cunningham Julie M. , Wang Alice H. , Witzig Thomas E. , Habermann Thomas M. , Asmann Yan W. , Slager Susan L.
Published: October 2012

Background: Non-Hodgkin lymphoma (NHL) is a malignancy of lymphocytes, and there is growing evidence for a role of germline genetic variation in immune genes in NHL etiology.

Methods: To identify susceptibility immune genes, we conducted a 2-stage analysis of single-nucleotide polymorphisms (SNP) from 1,253 genes using the Immune and Inflammation Panel. In Stage 1, we genotyped 7,670 SNPs in 425 NHL cases and 465 controls, and in Stage 2 we genotyped the top 768 SNPs on an additional 584 cases and 768 controls. The association of individual SNPs with NHL risk from a log-additive model was assessed using the OR and 95% confidence intervals (CI).

Results: In the pooled analysis, only the TAP2 coding SNP rs241447 (minor allele frequency = 0.26; Thr655Ala) at 6p21.3 (OR = 1.34, 95% CI 1.17–1.53) achieved statistical significance after accounting for multiple testing (P = 3.1 × 10−5). The TAP2 SNP was strongly associated with follicular lymphoma (FL, OR = 1.82, 95%CI 1.46–2.26; p = 6.9 × 10−8), and was independent of other known loci (rs10484561 and rs2647012) from this region. The TAP2 SNP was also associated with diffuse large B-cell lymphoma (DLBCL, OR = 1.38, 95% CI 1.08–1.77; P = 0.011), but not chronic lymphocytic leukemia (OR = 1.08; 95% CI 0.88–1.32). Higher TAP2 expression was associated with the risk allele in both FL and DLBCL tumors.

Conclusion: Genetic variation in TAP2 was associated with NHL risk overall, and FL risk in particular, and this was independent of other established loci from 6p21.3.

Impact: Genetic variation in antigen presentation of HLA class I molecules may play a role in lymphomagenesis. Cancer Epidemiol Biomarkers Prev; 21(10); 1799–806. ©2012 AACR.
The Clinical Meaning of Intramammary Lymph Nodes
Authors: Lee Se Kyung , Kim Sangmin , Choi Min-Young , Kim Jiyoung , Lee Jeonghui , Jung Seung Pil , Choe Jun-Ho , Kim Jung-Han , Kim Jee Soo , Kil Won Ho , Lee Jeong Eon , Nam Seok Jin
Published: October 2012

Objective: The clinical meaning of intramammary lymph nodes (iMLNs) is uncertain. We wanted to describe the clinical characteristics and understand the implications of iMLNs detected by sentinel LN biopsy (SLNB). Methods: We reviewed the clinical, radiological and pathological records of women diagnosed with invasive carcinoma of the breast at the Samsung Medical Center between January 2001 and January 2011. A total of 69 patients were identified, and SLNB was performed in 31 patients. Results: Of the 69 patients included in the study, 22 (31.9%) had metastases in iMLNs. The presence of lymphovascular invasion and the number of axillary LN metastases were associated with iMLN metastasis. Of the 31 patients who underwent SLNB, there were no cases with axillary LN metastasis when axillary SLNB was negative, even in cases of iMLN-positive patients. Of the 10 patients in whom intramammary SLNs (iMSLNs) were detected during SLNB, 8 patients without iMLN metastases were also negative for axillary LNs. Conclusion: Patients with metastatic iMLNs had more aggressive cancers with lymphovascular invasion and increased axillary LN metastases. When iMSLN was detected by SLNB, performing of axillary dissection could be determined by the status of the iMSLN itself.
Oral Administration of Lactoferrin Attenuates Intestinal Ischemia-Reperfusion Injury in Rats
Authors: Zhang T. , Wang Y. , Ban R. , Tong L. , Qiao H. , Lao H. , Zhao H. , Jiang X. , Sun X. , Zhang F.
Published: October 2012

Background: Intestinal ischemia-reperfusion (I/R) is a common and serious clinical condition. Lactoferrin (Lf) has displayed antioxidative and anti-inflammatory activities in protecting the intestinal mucosa. The objective of this study was to investigate whether oral administration of Lf could attenuate I/R-induced intestinal injury. Methods: The experimental design consisted of three groups of Wistar rats (24 per group): sham operation, control (I/R, saline), Lf (I/R, Lf). Intestinal I/R was produced by occlusion of the superior mesenteric artery for 45 min. Eight rats from each group were randomly sacrificed 3, 12 or 36 h after reperfusion, and blood and intestinal samples were collected. Results: Intestinal I/R resulted in gut damage evidenced by morphological alteration, reduction of γ-glutamyl transpeptidase (γ-GGT) activity and increased cell apoptosis. Daily administration of Lf (200 mg/kg) for 14 days before surgery significantly attenuated gut damage by reducing the histologic score and apoptosis index, and restoring intestinal γ-GGT activity. Lf reduced intestinal malondialdehyde and myeloperoxidase, restored glutathione and decreased serum levels of tumor necrosis factor-α, interleukin (IL)-1β and IL-6 compared with saline control in I/R rats. In addition, oral administration of Lf did not produce any significant effects in healthy rats; Lf at doses of 50 or 100 mg/kg also attenuated I/R-induced gut damage, but administration of Lf for 7 days did not exert a significant protective effect against I/R-induced gut damage. Conclusions: These results indicate that Lf may serve as a potent supplement in protecting the gut from intestinal I/R-induced injury by its antioxidative, anti-inflammatory and antiapoptotic activities.
A Family with an Inverted Tandem Duplication 5q22.1q23.2
Authors: Schmidt T. , Bartels I. , Liehr T. , Burfeind P. , Zoll B. , Shoukier M.
Published: October 2012

Here, we report a 3-year-old boy with short stature, developmental delay and mild facial dysmorphic signs. Karyotype analysis and array-CGH revealed a pure duplication 5q22.1q23.2 with a length of 14.25 Mb. As demonstrated by multicolor-fluorescence in situ hybridization, the duplicated segment was orientated in an inverted tandem manner. One of the 2 older half-brothers of the index patient was intellectually disabled and showed short stature as well. The mother of the siblings was only 149 cm in height. The affected half-brother as well as the mother of the siblings were tested positive for the same duplication. Duplications of the long arm of chromosome 5 are rare. There are 16 reported cases of different 5q segments with a pure duplication and no additional chromosomal imbalance. In order to refine the 5q-duplication phenotype, reported cases were recently classified in 3 groups on the basis of clinical findings and the involved chromosome segments. However, our case does not fit in any of these groups but is placed in the interjacent chromosomal area between 2 of these groups. Overall, this is the second reported family with a duplication of 5q22.1q23.2 and both families share phenotypic features like short stature, facial dysmorphic signs and speech delay. The reported family provides further information for delineating phenotype-genotype correlations of pure duplications of the 5q region.
Current Size Criteria for the Management of Neuroendocrine Tumors of the Appendix: Are They Valid? Clinical Experience and Review of the Literature
Authors: Grozinsky-Glasberg S. , Alexandraki K.I. , Barak D. , Doviner V. , Reissman P. , Kaltsas G.A. , Gross D.J.
Published: October 2012

We evaluated the latest pathological criteria for completion right hemicolectomy (RHC) in patients with appendiceal neuroendocrine tumors (ANETs) with emphasis on the size of the primary tumor. Data of 28 consecutive patients who underwent RHC for ANETs in three tertiary hospitals were reviewed retrospectively to assess the indications for completion RHC. 10/28 patients were found to have residual disease (36%). In 8/28 patients (29%), the tumor diameter was <1 cm (mean 0.7 ± 0.2 cm, range 0.5-0.9 cm); the indications for RHC included: tumor presence in surgical margins (1 patient), extensive mesoappendiceal invasion (EMI) (1 patient), vascular invasion (VI) (3 patients), Ki-67 ≥2% (3 patients); residual disease was present in 1 patient (3.5%). In 13/28 patients (46%), the tumor diameter was ≥1 and <2 cm (mean 1.30 ± 0.2 cm, range 1.0-1.8 cm); the indications for RHC were: EMI (2 patients), VI (2 patients), Ki-67 ≥2% (2 patients); residual disease was present in 5 patients (18%). In 7/28 patients (25%), the tumor diameter was ≥2 cm (mean 2.5 ± 0.7 cm, range 2.0-4.0 cm). In this final subgroup, RHC was an accepted practice irrespective of other pathologic findings: the tumor was present in surgical margins in 2 patients, in 5 patients VI was demonstrated, and Ki-67 ≥2% was found in 5 patients; residual disease was present in 4 patients (14%). Using the latest European Neuroendocrine Tumor Society criteria for RHC, residual disease may be missed in 18% of ANET patients.
Neonatal Testosterone Exposure Protects Adult Male Rats from Stroke
Authors: Persky Rebecca W. , Liu Fudong , Xu Yan , Weston Gillian , Levy Stephanie , Roselli Charles E. , McCullough Louise D.
Published: October 2012

Background: Men have a higher stroke incidence compared to women until advanced age. The contribution of hormones to these sex differences has been extensively debated. In experimental stroke, estradiol is neuroprotective, whereas androgens are detrimental. However, prior studies have only examined the effects of acute treatment paradigms; therefore, the timing and mechanism by which ischemic sexual dimorphism arises are unknown. Methods: The effects of exogenous neonatal androgen exposure on subsequent injury induced by middle cerebral artery occlusion in adulthood in male rats were examined. Rats were administered vehicle (oil), testosterone propionate (TP) or the non-aromatizable androgen dihydrotestosterone (DHT) for 5 days after birth. At 3 months of age, a focal stroke was induced. Results: Testosterone-treated rats (but not DHT-treated animals) had decreased infarct volumes (20 vs. 33%, p < 0.05) as well as increased estradiol levels (39.4 vs. 18.6 pg/ml, p < 0.0001) compared to oil-treated animals. TP-injected males had increased testicular aromatase (P450arom) levels (3.6 vs. 0.2 ng/ml, p < 0.0001) compared to oil-treated males. The level of X-linked inhibitor of apoptosis, the primary endogenous inhibitor of caspase-induced apoptosis, was increased in TP-treated rats compared with the oil-treated males. Conclusions: Neonatal exposure to exogenous testosterone upregulates testicular aromatase expression in male rats and leads to adult neuroprotection secondary to changes in serum estradiol levels and cell death proteins. This study suggests that early exposure to gonadal hormones can have dramatic effects on the response to adult cerebrovascular injury.
Diurnal Variation of Hypothalamic Function and Chronic Subthalamic Nucleus Stimulation in Parkinson's Disease
Authors: Seifried Carola , Boehncke Sandra , Heinzmann Jannika , Baudrexel Simon , Weise Lutz , Gasser Thomas , Eggert Karla , Fogel Wolfgang , Baas Horst , Badenhoop Klaus , Steinmetz Helmuth , Hilker Rüdiger
Published: October 2012

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) improves quality of life in patients with advanced Parkinson's disease (PD), but is associated with neuropsychiatric side effects and weight gain in some individuals. The pathomechanisms of these phenomena are still unknown. Considering anatomical and functional connections of the STN with the hypothalamic-pituitary (HP) system, we prospectively investigated whether chronic STN-DBS alters HP functioning in 11 PD patients. Methods: Basal hormone levels of the HP-adrenal (HPA), HP-gonadal and HP-somatotropic axis were determined before surgery as well as 3 and 6 months after electrode implantation. In addition, 24-hour cortisol profiles and dexamethasone suppression tests were obtained. Postoperative hormone changes were correlated with individual neuropsychological test performance, psychiatric status and anthropometric measures. Results: While PD patients experienced weight gain (p = 0.025) at follow-up, most neuropsychological data and basal HP hormone levels did not change over time. HPA regulation and diurnal rhythmicity of cortisol remained intact in all patients. The 24-hour mean cortisol levels decreased 6 months after surgery (p = 0.002) correlating with improved postoperative depression (p = 0.02). Conclusions: Chronic application of high-frequency electrical stimuli in the STN was not associated with HP dysfunction in patients with advanced PD. The diurnal variability of peripheral cortisol secretion as one important element of the endogenous biological clock remained intact. Evening cortisol levels decreased after surgery reflecting a favorable regulation of the cortisol setpoint. STN-DBS can be considered safe from a neuroendocrine perspective, but the origin of unwanted side effects warrants further elucidation.
Secondary Eyewall Formation and Eyewall Replacement Cycles in a Simulated Hurricane: Effect of the Net Radial Force in the Hurricane Boundary Layer
Authors: Wang Xingbao , Ma Yimin , Davidson Noel E.
Published: October 2012

Multiple secondary eyewall formations (SEFs) and eyewall replacement cycles (ERCs) are simulated with the fifth-generation Pennsylvania State University (PSU)–National Center for Atmospheric Research (NCAR) Mesoscale Model (MM5) at horizontal grid spacing of 0.67 km. The simulated hurricane is initialized from a weak, synthetic vortex in a quiescent environment on an f plane. After spinup and rapid intensification, the hurricane enters a mature phase during which the intensity change is relatively slow. Convective clouds then organize into a ring with a secondary tangential wind maximum at radii beyond the hurricane’s primary eyewall. This secondary eyewall (SE) then contracts and strengthens. The primary eyewall weakens and is eventually replaced by the SE. The hurricane grows in size and the radius of maximum wind (RMW) increases as similar ERCs repeat 5 times during the simulation.

Two existing hypotheses on SEF are evaluated using the simulation output. Then, model diagnostics are used to reveal that crucial linked components of SEF are (i) a broadening of the swirling flow, (ii) the structure of the evolving secondary circulation, and (iii) the structure of the net radial force (NRF) in the boundary layer (with largest contributions from the agradient and frictional forces). During SEF, there exists strong positive NRF in the region of the primary eyewall, a secondary positive maximum over the SEF region, and a minimum between the two. As a response of the boundary layer depth–integrated radial flow to the NRF, a secondary maximum convergence zone (SMCZ) in the boundary layer develops at the SEF radii. Eventually moist convection in the SMCZ becomes active as the SEF develops.