bluuebunny/crossref_metadata_2025 huggingface dataset:
The Changing Incidence of In situ and Invasive Ductal and Lobular Breast Carcinomas: United States, 1999-2004
Authors: Eheman Christie R. , Shaw Kate M. , Ryerson Aliza Blythe , Miller Jacqueline W. , Ajani Umed A. , White Mary C.
Published: June 2009

Background: National incidence rates for lobular and ductal breast cancers have not been available previously. Evidence suggests that the increased risk of breast cancer associated with combined hormone replacement therapy use is higher for invasive lobular cancers (ILC) than for invasive ductal cancers (IDC). This study provides U.S. incidence rates for these histologic types for both in situ and invasive cancers and assesses changes in the incidence of these cancers over time.

Methods: Data for this study included incident ductal and lobular breast cancer cases diagnosed from 1999 through 2004 in central cancer registries in 44 states and the District of Columbia from the National Program of Cancer Registries and the Surveillance, Epidemiology, and End Results program. We estimated incidence per 100,000 women by 10-year age groups, race, and ethnicity. We also assessed the percent change in invasive and in situ cancer incidence over time.

Results: We observed distinct differences in the change of incidence over time between in situ and invasive lobular and ductal breast cancers. The age-adjusted rates of ILC and IDC declined an average of 4.6% and 3.3% per year, respectively. Overall, ILC decreased 20.5% from 1999 to 2004. The patterns of ductal and lobular in situ cancer incidence were not consistent over time, and the total change was negligible.

Conclusion: The declines in ILC observed in our study are consistent with a decrease in cancer incidence related to a reduced use of combined hormone replacement therapy. However, other factors could also be responsible for these changes. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1763–9)
Dairy Consumption and Female Height Growth: Prospective Cohort Study
Authors: Berkey Catherine S. , Colditz Graham A. , Rockett Helaine R.H. , Frazier A. Lindsay , Willett Walter C.
Published: June 2009

Background: Because of its nutrients and anabolic hormones, cow's milk may promote height growth, which in turn has been related to breast cancer risk. We prospectively investigated associations between dairy intakes and height growth.

Methods: A cohort of 5,101 girls from throughout the United States completed annual surveys (1996-2001, 2003), providing height, weight, and past-year diet. At baseline, all were premenarchal, ages 9 years and above, with no serious medical conditions. We studied three outcomes: annual height growth, peak growth velocity, and adult height. Multivariate models estimated the effects of milk, cheese, yogurt, and energy on subsequent growth, adjusted for race/ethnicity, age, prior height, and body mass index. Other models studied fats and proteins.

Results: Premenarchal girls who drank >3 servings per day of milk grew 0.11 in. (P = 0.02) more the following year than girls consuming <1 serving per day. Yogurt (+0.13 in./cup; P = 0.02), but not cheese or total calories, predicted height growth. In a separate model, dairy protein (+0.034 in./10 g; P < 0.001) predicted height growth. Larger peak velocities were seen among girls reporting, at baseline, more milk (>3 glasses per day versus <1; +0.14 in., P = 0.01), more yogurt (+0.17 in./cup, P = 0.02), and, in a separate model, more dairy protein (+0.039 in./10 g; P = 0.003). Baseline milk and dairy protein predicted taller adults. Dairy protein was more important than dairy fat, for all outcomes. Nondairy animal protein and vegetable protein were never significant, nor were nondairy animal fat and vegetable fat.

Conclusion: Of the foods/nutrients studied, dairy protein had the strongest association with height growth. These findings suggest that a factor in the nonlipid phase of milk, but not protein itself, has growth-promoting action in girls. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1881–7)
Circulating Tumor Cells in Patients with Castration-Resistant Prostate Cancer Baseline Values and Correlation with Prognostic Factors
Authors: Goodman Oscar B. , Fink Louis M. , Symanowski James T. , Wong Bryan , Grobaski Beth , Pomerantz David , Ma Yupo , Ward David C. , Vogelzang Nicholas J.
Published: June 2009

Purpose: Circulating tumor cells (CTC) have been recently accepted by the Food and Drug Administration of the United States as a prognostic tool in advanced prostate cancer. However, a number of questions remain about the use of the test. The optimal clinical cut-off has never been determined. Also, the predictive value of CTCs in the setting of low-burden advanced prostate cancer has not been evaluated. Herein we describe our experience with the CellSearch method of CTC enumeration.

Experimental Design: CTCs enumerated from 100 patients with castration-resistant prostate cancer were correlated with clinicopathologic characteristics and conventional biomarkers, such as prostate-specific antigen and lactate dehydrogenase. Patients received ongoing medical oncologic follow-up for up to 26 months, and overall survival status was documented.

Results: Forty-nine of the patients (49%) were alive at the end of the study. CTC counts correlate well with overall survival (P < 0.001) but are also tightly interrelated to other biomarkers. Threshold analysis identified 4 CTC/7.5 cc (compared with the approved value of 5) as an optimal cut-off value with respect to correlation with survival outcomes as well as predictive of metastatic disease. Univariate analysis confirmed a tight interrelationship between cut-off CTC values and biomarkers. Multivariate analysis with bootstrap sampling validation identified lactate dehydrogenase (P = 0.002) and CTCs (P = 0.001) as independently prognostically significant.

Conclusions: Baseline CTC values provide important prognostic information and specific prediction of metastatic disease. Their presence correlates with classic biomarkers. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1904–13)
Factors Associated with Awareness of Infection Status among Chronic Hepatitis B and C Carriers in Korea
Authors: Shin Aesun , Cho Eo Rin , Kim Jeongseon , Sung Joohon , Park Kyung Woo , Lim Min-Kyung , Shin Hai-Rim
Published: June 2009

Hepatitis B (HBV) and hepatitis C (HCV) viral infections are the most important risk factors for hepatocellular carcinoma (HCC), which is responsible for 17.5% of cancer deaths in Korea. The objectives of this study were to identify demographic characteristics that may affect hepatitis carriers' awareness of their infection status, and to assess whether health-related behaviors differed by awareness of the infection. Among 18,636 persons who were recruited from a cancer screenee cohort, 904 were HBV carriers and 146 were HCV carriers. Among the HBV carriers, 74.2% were aware of their infection status. Higher education (odds ratio, 1.8; college versus middle school or less), family history of liver cancer or disease, and marriage were associated with awareness of HBV infection status. Participants who were aware of their HBV carrier status were more likely to be former smokers or drinkers than those who were not aware of their status. Only 34.9% of HCV carriers were aware of their HCV infection status. No demographic characteristics were related to awareness of HCV infection status among HCV carriers. However, HCV carriers who were aware of their infection status were more likely to be former drinkers (odds ratio, 9.2; 95% confidence interval, 1.8-47.2). In conclusion, two thirds of HCV carriers and one fourth of HBV carriers in this study population were not aware of their infection status, and awareness of hepatitis infection status was significantly associated with other risk behaviors, such as alcohol consumption and cigarette smoking. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1894–8)
Apoptosis in the Colonic Crypt, Colorectal Adenomata, and Manipulation by Chemoprevention
Authors: West Nicholas J. , Courtney Edward D.J. , Poullis Andrew P. , Leicester Roger J.
Published: June 2009

This review discusses the biology and the methods of assessment of apoptosis, of which, the monoclonal antibody M30 would seem to be the most useful; the role of apoptosis in the etiology of colorectal cancer; and its use as a marker to monitor the beneficial effects of chemopreventative interventions to reduce the development of colorectal cancer within the context of clinical trials. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1680–7)
Bias Associated With Self-Report of Prior Screening Mammography
Authors: Cronin Kathleen A. , Miglioretti Diana L. , Krapcho Martin , Yu Binbing , Geller Berta M. , Carney Patricia A. , Onega Tracy , Feuer Eric J. , Breen Nancy , Ballard-Barbash Rachel
Published: June 2009

Background: Self-reported screening behaviors from national surveys often overestimate screening use, and the amount of overestimation may vary by demographic characteristics. We examine self-report bias in mammography screening rates overall, by age, and by race/ethnicity.

Methods: We use mammography registry data (1999-2000) from the Breast Cancer Surveillance Consortium to estimate the validity of self-reported mammography screening collected by two national surveys. First, we compare mammography use from 1999 to 2000 for a geographically defined population (Vermont) with self-reported rates in the prior two years from the 2000 Vermont Behavioral Risk Factor Surveillance System. We then use a screening dissemination simulation model to assess estimates of mammography screening from the 2000 National Health Interview Survey.

Results: Self-report estimates of mammography use in the prior 2 years from the Vermont Behavioral Risk Factor Surveillance System are 15 to 25 percentage points higher than actual screening rates across age groups. The differences in National Health Interview Survey screening estimates from models are similar for women 40 to 49 and 50 to 59 years and greater than for those 60 to 69, or 70 to 79 (27 and 26 percentage points versus 14, and 14, respectively). Overreporting is highest among African American women (24.4 percentage points) and lowest among Hispanic women (17.9) with non-Hispanic White women in between (19.3). Values of sensitivity and specificity consistent with our results are similar to previous validation studies of mammography.

Conclusion: Overestimation of self-reported mammography usage from national surveys varies by age and race/ethnicity. A more nuanced approach that accounts for demographic differences is needed when adjusting for overestimation or assessing disparities between populations. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1699–705)
Cancer Incidence in the U.S. Military Population: Comparison with Rates from the SEER Program
Authors: Zhu Kangmin , Devesa Susan S. , Wu Hongyu , Zahm Shelia Hoar , Jatoi Ismail , Anderson William F. , Peoples George E. , Maxwell Larry G. , Granger Elder , Potter John F. , McGlynn Katherine A.
Published: June 2009

The U.S. active-duty military population may differ from the U.S. general population in its exposure to cancer risk factors and access to medical care. Yet, it is not known if cancer incidence rates differ between these two populations. We therefore compared the incidence of four cancers common in U.S. adults (lung, colorectal, prostate, and breast cancers) and two cancers more common in U.S. young adults (testicular and cervical cancers) in the military and general populations. Data from the Automated Central Tumor Registry (ACTUR) of the Department of Defense and the nine cancer registries of the Surveillance, Epidemiology and End Results (SEER) of the National Cancer Institute for the years 1990 to 2004 for persons with ages 20 to 59 years were analyzed. Incidence rates were significantly lower in the military population for colorectal cancer in White men, lung cancer in White and Black men and White women, and cervical cancer in Black women. In contrast, incidence rates of breast and prostate cancers were significantly higher in the military among Whites and Blacks. Incidence rates of testicular cancer did not differ between ACTUR and SEER. Although the numbers of diagnoses among military personnel were relatively small for temporal trend analysis, we found a more prominent increase in prostate cancer in ACTUR than in SEER. Overall, these results suggest that cancer patterns may differ between military and nonmilitary populations. Further studies are needed to confirm these findings and explore contributing factors. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1740–5)
Sam-Pointed Domain Containing Ets Transcription Factor in Luminal Breast Cancer Pathogenesis
Authors: Sood Ashwani K. , Wang Jianmin , Mhawech-Fauceglia Paulette , Jana Bagirathan , Liang Ping , Geradts Joseph
Published: June 2009

We previously described frequent overexpression of Sam-pointed domain containing Ets transcription factor (SPDEF), also known as PDEF, in human breast cancer, and suggested a role for this transcription factor in breast tumor progression. To seek evidence in support of this hypothesis, the MCF-12A breast epithelial cell line was transfected with an SPDEF expression plasmid or with control vector plasmid and the transfected cells tested for their tumorigenic growth in vivo. The data showed that SPDEF expression in MCF-12A cells induced accelerated tumor growth in severe combined immune deficient mice compared with vector-transfected MCF-12A cells. Furthermore, Gene Expression Omnibus and Oncomine databases were mined to determine any correlation between SPDEF expression levels and clinical outcome. High SPDEF expression correlated with poor overall survival of patients with estrogen receptor+ breast cancer, in three independent data sets. In contrast, little correlation was observed between SPDEF expression and cancer relapse or remote metastases. SPDEF expression was further found to be restricted to tumors arising in the luminal epithelial lineage including estrogen receptor+ luminal subtype breast tumors, Her2/neu-positive tumors, and apocrine carcinomas. In contrast, little SPDEF expression was found in the basal subtype of breast tumors. Based on these results, we hypothesize that SPDEF has a function in the specification of the progenitor cells of the luminal epithelial lineage that become targets of oncogenesis in luminal breast cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1899–903)
Single and Multigenic Analysis of the Association between Variants in 12 Steroid Hormone Metabolism Genes and Risk of Prostate Cancer
Authors: Beuten Joke , Gelfond Jonathan A.L. , Franke Jennifer L. , Weldon Korri S. , Crandall AnaLisa C. , Johnson-Pais Teresa L. , Thompson Ian M. , Leach Robin J.
Published: June 2009

To estimate the prostate cancer risk conferred by individual single nucleotide polymorphisms (SNPs), SNP-SNP interactions, and/or cumulative SNP effects, we evaluated the association between prostate cancer risk and the genetic variants of 12 key genes within the steroid hormone pathway (CYP17, HSD17B3, ESR1, SRD5A2, HSD3B1, HSD3B2, CYP19, CYP1A1, CYP1B1, CYP3A4, CYP27B1, and CYP24A1). A total of 116 tagged SNPs covering the group of genes were analyzed in 2,452 samples (886 cases and 1,566 controls) in three ethnic/racial groups. Several SNPs within CYP19 were significantly associated with prostate cancer in all three ethnicities (P = 0.001-0.009). Genetic variants within HSD3B2 and CYP24A1 conferred increased risk of prostate cancer in non-Hispanic or Hispanic Caucasians. A significant gene-dosage effect for increasing numbers of potential high-risk genotypes was found in non-Hispanic and Hispanic Caucasians. Higher-order interactions showed a seven-SNP interaction involving HSD17B3, CYP19, and CYP24A1 in Hispanic Caucasians (P = 0.001). In African Americans, a 10-locus model, with SNPs located within SRD5A2, HSD17B3, CYP17, CYP27B1, CYP19, and CYP24A1, showed a significant interaction (P = 0.014). In non-Hispanic Caucasians, an interaction of four SNPs in HSD3B2, HSD17B3, and CYP19 was found (P < 0.001). These data are consistent with a polygenic model of prostate cancer, indicating that multiple interacting genes of the steroid hormone pathway confer increased risk of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1869–80)
Molecular Subtypes of Breast Cancer Emerging in Young Women in Taiwan: Evidence for More Than Just Westernization as a Reason for the Disease in Asia
Authors: Lin Ching-Hung , Liau Jau-Yu , Lu Yen-Shen , Huang Chiun-Sheng , Lee Wei-Chung , Kuo Kuan-Ting , Shen Ying-Chun , Kuo Sung-Hsin , Lan Chieh , Liu Jacqueline Ming , Kuo Wun-Hon , Chang King-Jen , Cheng Ann-Lii
Published: June 2009

Background: In the past two decades, the incidence of breast cancer in young Taiwanese females has been rapidly increasing, approaching the risk level of western countries. As a first step to investigate the possible etiology, we examined the molecular subtypes of female breast cancer in Taiwan.

Methods: This study included 1,028 consecutive patients with breast cancer diagnosed in National Taiwan University Hospital between 2004 and 2006. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2, cytokeratin 5/6, and epidermal growth factor receptor expression and/or gene amplification were analyzed.

Results: Younger (≤50 years) breast cancer patients had a higher prevalence of luminal A (67% versus 57%; P < 0.001) and a lower prevalence of basal-like subtype (9% versus 17%; P < 0.001) compared with older (>50 years) patients. The higher prevalence of luminal A subtype was mainly attributed to a higher ER (75% versus 63%; P < 0.001) and PR (47% versus 33%; P < 0.001) expression rate in younger patients than older patients. Tumors with histologic grade 3 were less prevalent in younger patients than in older patients (23% versus 30%; P = 0.01). For very young (<35 years) patients, the molecular subtype distribution, ER and/or PR expression rate, and histologic grade were not significantly different from those of less young (35-50 years) patients.

Conclusions: Young breast cancer patients in Taiwan are characterized by a high prevalence of luminal A subtype and low prevalence of histologic grade 3 tumor and/or basal-like subtype. These features are distinct from young breast cancer patients in western countries. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1807–14)
Detection of Urothelial Bladder Cancer Cells in Voided Urine Can Be Improved by a Combination of Cytology and Standardized Microsatellite Analysis
Authors: Wild Peter J. , Fuchs Thomas , Stoehr Robert , Zimmermann Dieter , Frigerio Simona , Padberg Barbara , Steiner Inbal , Zwarthoff Ellen C. , Burger Maximilian , Denzinger Stefan , Hofstaedter Ferdinand , Kristiansen Glen , Hermanns Thomas , Seifert Hans-Helge , Provenzano Maurizio , Sulser Tullio , Roth Volker , Buhmann Joachim M. , Moch Holger , Hartmann Arndt
Published: June 2009

Purpose: To evaluate molecular and immunohistochemical markers to develop a molecular grading of urothelial bladder cancer and to test these markers in voided urine samples.

Experimental Design: 255 consecutive biopsies from primary bladder cancer patients were evaluated on a tissue microarray. The clinical parameters gender, age, adjacent carcinoma in situ, and multifocality were collected. UroVysion fluorescence in situ hybridization (FISH) was done. Expression of cytokeratin 20, MIB1, and TP53 was analyzed by immunohistochemistry. Fibroblast growth factor receptor 3 (FGFR3) status was studied by SNaPshot mutation detection. Results were correlated with clinical outcome by Cox regression analysis. To assess the predictive power of different predictor subsets to detect high grade and tumor invasion, logistic regression models were learned. Additionally, voided urine samples of 119 patients were investigated. After cytologic examination, urine samples were matched with their biopsies and analyzed for loss of heterozygosity (LOH), FGFR3 mutation, polysomy, and p16 deletion using UroVysion FISH. Receiver operator characteristic curves for various predictor subsets were plotted.

Results: In biopsies, high grade and solid growth pattern were independent prognostic factors for overall survival. A model consisting of UroVysion FISH and FGFR3 status (FISH + FGFR3) predicted high grade significantly better compared with a recently proposed molecular grade (MIB1 + FGFR3). In voided urine, the combination of cytology with LOH analysis (CYTO + LOH) reached the highest diagnostic accuracy for the detection of bladder cancer cells and performed better than cytology alone (sensitivity of 88.2% and specificity of 97.1%).

Conclusions: The combination of cytology with LOH analysis could reduce unpleasant cystoscopies for bladder cancer patients. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1798–806)
Effects of Nickel on Cyclin Expression, Cell Cycle Progression and Cell Proliferation in Human Pulmonary Cells
Authors: Ding Jin , He Guoping , Gong Wenfeng , Wen Wen , Sun Wen , Ning Beifang , Huang Shanna , Wu Kun , Huang Chuanshu , Wu Mengchao , Xie Weifen , Wang Hongyang
Published: June 2009

Frequent exposure to nickel compounds has been considered as one of the potential causes of human lung cancer. However, the molecular mechanism of nickel-induced lung carcinogenesis remains obscure. In the current study, slight S-phase increase, significant G2/M cell cycle arrest, and proliferation blockage were observed in human bronchial epithelial cells (Beas-2B) upon nickel exposure. Moreover, the induction of cyclin D1 and cyclin E by nickel was shown for the first time in human pulmonary cells, which may be involved in nickel-triggered G1/S transition and cell transformation. In addition, we verified that hypoxia-inducible factor-1α, an important transcription factor of nickel response, was not required for the cyclin D1 or cyclin E induction. The role of p53 in nickel-induced G2/M arrest was excluded, respecting that its protein level, ser15 phosphorylation, and transcriptional activity were not changed in nickel response. Further study revealed that cyclin A was not activated in nickel response, and cyclin B1, which not only promotes G2/M transition but also prevents M-phase exit of cells if not degraded in time, was up-regulated by nickel through a manner independent of hypoxia-inducible factor. More importantly, our results verified that overexpressed cyclin B1, veiling the effect of cyclin D1 or cyclin E, mediated nickel-caused M-phase blockage and cell growth inhibition, which may render pulmonary cells more sensitive to DNA damage and facilitates cancer initiation. These results will not only deepen our understanding of the molecular mechanism involved in nickel carcinogenecity, but also lead to the further study on chemoprevention of nickel-associated human cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1720–9)
Matrix Metalloproteinase-2Polymorphisms and Breast Cancer Susceptibility
Authors: Beeghly-Fadiel Alicia , Lu Wei , Long Ji-Rong , Shu Xiao-ou , Zheng Ying , Cai Qiuyin , Gao Yu-Tang , Zheng Wei
Published: June 2009

Matrix metalloproteinase-2 (MMP-2) is a well-known mediator of cancer metastasis but is also thought to be involved in several aspects of cancer development, including cell growth and inflammation. We comprehensively characterized genetic variation across the MMP-2 gene and evaluated associations with breast cancer risk using a two-phase (phase 1 and phase 2) study design. A total of 39 polymorphisms were genotyped among 6,066 Chinese women participating in the Shanghai Breast Cancer Study, a population-based case-control study. Two MMP-2 promoter polymorphisms were found to have consistent results between phase 1 and phase 2 participants, and to be significantly associated with breast cancer risk among all genotyped participants. Minor allele homozygotes for rs11644561 (G/A) were found to have a decreased risk of breast cancer [odds ratio (OR), 0.6; 95% confidence interval (CI), 0.3-1.0] compared with major allele homozygotes, as were minor allele homozygotes for rs11643630 (T/G) compared with major allele homozygotes (OR, 0.8; 95% CI, 0.7-1.0). When analyzed together, a rare haplotype (4.4%) with both rs11644561 A and rs11643630 G was found to have a significantly reduced risk of breast cancer (OR, 0.6; 95% CI, 0.4-0.8). In addition, rare allele homozygotes for rs243865 (−1306 C/T) tended to have an increased risk of breast cancer (OR, 1.4; 95% CI, 0.9-2.4). Together, these findings support a role for MMP-2 genetic variation in breast cancer susceptibility. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1770–6)
Increase in Incidence of Colorectal Cancer Among Young Men and Women in the United States
Authors: Siegel Rebecca L. , Jemal Ahmedin , Ward Elizabeth M.
Published: June 2009

The recent, accelerated decline in colorectal cancer incidence rates has largely been attributed to an increase in screening rates among adults 50 years and older. We used data from 13 Surveillance, Epidemiology, and End Results cancer registries to report on colorectal cancer incidence trends from 1992 through 2005 among adults under age 50 years, for whom screening is not recommended for persons at average risk, by sex, race/ethnicity, age, stage at diagnosis, and anatomic subsite. Overall, incidence rates of colorectal cancer per 100,000 young individuals (ages 20-49 years) increased 1.5% per year in men and 1.6% per year in women from 1992 to 2005. Among non-Hispanic Whites, rates increased for both men and women in each 10-year age grouping (20-29, 30-39, and 40-49 years) and for every stage of diagnosis. The increase in incidence among non-Hispanic Whites was predominantly driven by rectal cancer, for which there was an average increase of 3.5% per year in men and 2.9% per year in women over the 13-year study interval. In contrast to the overall decreasing trend in colorectal cancer incidence in the United States, rates are increasing among men and women under age 50 years. Further studies are necessary to elucidate causes for this trend and identify potential prevention and early detection strategies. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1695–8)
Lead Exposure, Polymorphisms in Genes Related to Oxidative Stress, and Risk of Adult Brain Tumors
Authors: Bhatti Parveen , Stewart Patricia A. , Hutchinson Amy , Rothman Nathaniel , Linet Martha S. , Inskip Peter D. , Rajaraman Preetha
Published: June 2009

There is some evidence that oxidative stress plays a role in lead-induced toxicity. Mechanisms for dealing with oxidative stress may be of particular relevance in the brain given the high rate of oxygen metabolism. Using a hospital-based case-control study, we investigated the role of oxidative stress in the potential carcinogenicity of lead through examination of effect modification of the association between occupational lead exposure and brain tumors by single nucleotide polymorphisms in genes with functions related to oxidative stress. The study included 362 patients with glioma (176 of which had glioblastoma multiforme), 134 patients with meningioma, and 494 controls. Lead exposure was estimated by expert review of detailed job history data for each participant. We evaluated effect modification with 142 single nucleotide polymorphisms using likelihood ratio tests that compared nested unconditional logistic regression models that did and did not include a cross-product term for cumulative lead exposure and genotype. When the analyses were restricted to cases with glioblastoma multiforme, RAC2 rs2239774 and two highly correlated GPX1 polymorphisms (rs1050450 and rs18006688) were found to significantly modify the association with lead exposure (P ≤ 0.05) after adjustment for multiple comparisons. Furthermore, the same GPX1 polymorphisms and XDH rs7574920 were found to significantly modify the association between cumulative lead exposure and meningioma. Although the results of this study provide some evidence that lead may cause glioblastoma multiforme and meningioma through mechanisms related to oxidative damage, the results must be confirmed in other populations. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1841–8)
ProACT™ for Stress Urinary Incontinence after Radical Prostatectomy
Authors: Martens F.M.J. , Lampe M.I. , Heesakkers J.P.F.A.
Published: June 2009

Introduction: Stress urinary incontinence is a bothersome complication of radical prostatectomy. Surgical treatment consists of the artificial urinary sphincter (AUS), the male sling and bulk injections. This study presents the results of the first series of implantations of ProACTTM in the Netherlands. Materials and Methods: A non-validated questionnaire was sent to 29 male patients implanted with ProACT to determine Stamey score, pad count and questions about quality of life and satisfaction. Complications, revisions and explantations were registered. Results: Mean follow-up was 41 months. Based on Stamey score four patients are continent at the end and nine patients according to the pad count. The average pad count decreased significantly. Remarkable was the high rate of dislocations and revisions and patients’ satisfaction. Conclusions: ProACT is a less invasive treatment compared to the AUS. However, the procedure is associated with a substantial revision and explantation rate. ProACT can be part of a so-called step-up approach before opting for a more invasive treatment.
Robotic Repair of Complex Vesicouterine Fistula with and without Hysterectomy
Authors: Hemal Ashok K. , Sharma Nitin , Mukherjee Satyadip
Published: June 2009

Objective: To present robotic repair of vesicouterine fistulae (VUF) with and without hysterectomy in 3 cases and to discuss the technique with its outcome. Methods: Three patients were diagnosed with VUF, of whom 2 had a prior history of multiple cesarean sections and 1 had obstructed labor. Preoperative diagnosis of VUF was based on classic history, cystoscopy and imaging studies. All patients underwent pure robotic repair of VUF with hysterectomy in 1 case. The steps of the technique are cystoscopy, bilateral ureteral catheterization, port placement, adhesiolysis, separation of bladder and uterus and excision of the VUF with freshening of margins, closure of the uterus and bladder, hysterectomy in 1 case, and omental interposition. Results: Robotic repair of VUF was successful in all cases with mean operative time of 127.5 min and average blood loss of 120 ml. One patient underwent simultaneous robotic hysterectomy. All patients were ambulatory on day 1 and were discharged on day 3 with indwelling Foley’s catheter, which was removed on day 10. Conclusion: Robotic repair of VUF is safe and effective with successful outcome in all cases and has all the advantages of open and laparoscopic surgery. If required, concomitant robotic hysterectomy can also be performed. This is the first case series in the world.
Vacuum-Assisted Closure for the Treatment of Fournier’s Gangrene
Authors: Cuccia Giuseppe , Mucciardi Giuseppe , Morgia Giuseppe , Stagno d’Alcontres Francesco , Galì Alessandro , Cotrufo Stefano , Romeo Marco , Magno Carlo
Published: June 2009

Background: Fournier’s gangrene (FG) is a very aggressive necrotizing fasciitis involving subcutaneous fat and skin of scrotal and perineal regions. Vacuum-assisted closure (VAC) is a well-known method used to treat complex wounds. The authors for the first time enhance a multimodal strategy to treat the FG using VAC, reducing the number of surgical debridements, allowing a one-step surgical reconstruction with locoregional fasciocutaneous flap. Methods: Six patients with the diagnosis of FG were reviewed retrospectively at our institution. All patients were affected by very extensive FG. The FG Severity Index (FGSI) was used to evaluate the prognosis of the case at admission. Following the acute phase (24–48 h), VAC was used to achieve wound cleaning and prepare the area to a single-stage reconstruction with superomedial thigh flap. Hyperbaric oxygen therapy was also used before final reconstruction. Results: The average FGSI was 10.5, ranging from 8 to 12. All patients survived and were completely healed at the mean follow-up time of 9 months (range 3–30 months). Conclusions: VAC therapy is effective to clean and prepare the wounds, cutting off the fasciitis process and reducing the hospital stay and patient discomfort. Multidisciplinary treatment is mandatory during this devastating infection.
Influence of Body Mass Index on Operability, Morbidity and Disease Outcome following Radical Cystectomy
Authors: Maurer Tobias , Maurer Jean , Retz Margitta , Paul Roger , Zantl Niko , Gschwend Jürgen E. , Treiber Uwe
Published: June 2009

Introduction: Obesity may influence postoperative outcome after tumor surgery. We evaluated the impact of patients’ body mass index (BMI) on peri- and postoperative morbidity and outcome following radical cystectomy for bladder cancer. Patients and Methods: 390 consecutive patients who underwent radical cystectomy due to bladder cancer from January 1986 to December 2004 were reviewed. According to WHO criteria, patients were divided into normal weight (NW, 45.6%), overweight (OW, 44.4%) and obese (10.0%) subgroups. The BMI of patients was associated to the time of surgery, amount of intraoperative blood units, TNM stage, postoperative complication rate as well as overall survival. Results: The time of cystectomy increased with the degree of patients’ obesity (NW, 330 min; OW, 355 min; p = 0.007). Between NW and OW patients no significant differences were noted in respect to intraoperative blood transfusion rate (NW, 3.0; OW, 2.0; p = 0.47), postoperative TNM stage (pTis–pT2b: 42.6 vs. 48.6%; pT3a–4: 38.2 vs. 27.2%; pN+: 20.2 vs. 24.2%) and postoperative complications, except for postoperative bleeding, which was more common in OW patients (p = 0.02). Mean overall survival times showed no significant differences between NW and OW patients receiving ileal conduits (5-year survival rate: 34.0 vs. 41.1%; p = 0.140) or ileal neobladders (5-year survival rate: 65.1 vs. 70.8%; p = 0.127). Conclusions: Increased BMI poses a greater challenge for surgical interventions such as radical cystectomy in bladder cancer patients. However, in our series, intra- and postoperative morbidity was not significantly elevated in OW patients. Overall survival was not reduced in OW compared to NW patients. Therefore, elevated BMI is not an exclusion criterion for radical cystectomy in bladder cancer patients.
Tubeless and Stentless Percutaneous Nephrolithotomy in Patients Requiring Supracostal Access
Authors: Gonen Murat , Cicek Tufan , Ozkardes Hakan
Published: June 2009

Purpose: To evaluate the feasibility and safety of supracostal access in tubeless and stentless percutaneous nephrolithotomy (PCNL). Patients and Methods: From March 2005 to June 2007, 10 patients underwent tubeless and stentless PCNL via supracostal access. Patients requiring more than 2 percutaneous tracts, or those with significant intraoperative bleeding were excluded from the study. Perioperative and postoperative outcomes for these patients (the study group) were compared with those of a similar number of patients who underwent unilateral PCNL via an intercostal approach with routine placement of a nephrostomy tube before March 2005 (the control group). The 2 groups had a comparable demographic data. Results: Patients undergoing tubeless and stentless PCNL required less analgesia (p = 0.001) and were discharged earlier (p = 0.000) than were those in the control group. The difference in the mean decrease in hemoglobin concentration was not statistically significant. Conclusions: Supracostal access in tubeless and stentless PCNL appears to be safe and feasible, offering the advantages of a lower need for analgesia and a shorter hospital stay without increasing thoracic complications.
Role of Calcium in the Aggregation of Particles Coated by Urinary Macromolecules
Authors: Baumann J.M. , Affolter B. , Caprez U. , Clivaz C. , von Arx U.
Published: June 2009

Objectives: In urine, aggregation (AGN) of crystal occurs although they are coated by negatively charged urinary macromolecules (UM) and isolated at a distance from each other, where attraction forces become extremely weak. Calcium (Ca) bridges or viscous binding by UM could explain this AGN. Methods: Suspensions of Ca oxalate monohydrate (COM) and carboxylated latex (CL) were prepared in buffered water and UM solutions which were obtained from the urine of 6 healthy men. Surface potential or zetapotential (ZP) of the particles was measured at various concentrations of Ca and UM. AGN of CL was monitored determining particle size and optical density. Results: The ZP of COM was neutralized by Ca and stabilized around –15 mV by UM. In CL, a stable ZP of about –20 mV was achieved at >3 mM Ca. However, to induce AGN further addition of Ca was necessary. AGN then increased independently of ZP with increasing Ca and decreased with increasing UM concentration. Conclusions: In CL, two different Ca effects could be distinguished, one on ZP and another on AGN. The latter is probably based on the formation of Ca bridges between particles and is inhibited by a steric barrier of adsorbed UM. A similar mechanism is postulated for crystal aggregation.
Prophylaxis of Experimentally Induced Calcium Oxalate Nephrolithiasis in Rats by Zhulingtang, a Traditional Chinese Herbal Formula
Authors: Tsai Chou-Huang , Pan Tien-Chien , Lai Ming-Tsong , Lee Shih-Chang , Chen Ming-Lun , Jheng Jhih-Ren , Chen Wen-Chi
Published: June 2009

Background: Zhulingtang (ZLT), a traditional Chinese medicine formula, was used to evaluate the antilithic effects of experimentally induced calcium oxalate (CaOx) nephrolithiasis in ethylene glycol (EG)-fed rats. Materials and Methods: A total of 35 male Sprague-Dawley rats were randomly divided into 4 groups. Rats in group 1 (n = 8) served as the normal control. Rats in group 2 (n = 11) were treated with gastric gavages of starch as placebo and 0.75% EG as a stone inducer. Rats in group 3 (n = 8) were given 0.75% EG and a low dose (305 mg/kg) of ZLT. Rats in group 4 (n = 8) were treated with EG and a high dose (915 mg/kg) of ZLT. Twenty-four-hour urine and blood samples were collected at the beginning and at the end of the experiment for biochemical analysis. The histological appearances of the kidneys were observed under a polarized light microscope, and the crystal deposits were evaluated by a semiquantitative scoring method, computer assisted with ImageScoring software. Results: Our results revealed that rats fed with 0.75% EG for 4 weeks successfully produced renal deposition of CaOx. The severities of crystal deposition were significantly reduced in the 2 ZLT-fed groups compared with the placebo group (p = 0.025 and 0.047, respectively). Rats in the low-dose ZLT and placebo groups exhibited significantly lower serum phosphorus in comparison with the control rats (p = 0.005 and 0.03, respectively). Rats of the placebo group (EG + starch) encountered growth retardation, with their body weights slowly increasing, expressed as 160.63 ± 23.06 g, compared with 179.63 ± 13.41 g in normal rats (p < 0.001). Conclusion: ZLT reduced the severity of CaOx crystallization and slowed down the body weight loss effects. Therefore, the traditional Chinese medicine herbal formula ZLT may be an effective reagent for renal stone prophylaxis. Although the mechanism of ZLT in crystal inhibition remains unclear, macromolecules may be involved.
Epididymo-Orchitis due to Brucellosis: Not Only to Be Considered in Endemic Areas
Authors: Moens A.A. , Vlaspolder F. , Verlind J. , Sepers J.M. , Stam F.
Published: June 2009

We report 2 patients with epididymo-orchitis, caused by Brucella melitensis, accompanied by severe delay of diagnosis. In 1 patient the correct diagnosis was only suspected after his wife had been diagnosed with brucellosis. Our cases illustrate that diagnosing brucellosis can be difficult in nonendemic areas, especially when physicians are unfamiliar with it. Important clues pointing to brucellosis as cause of epididymo-orchitis are a travel history to endemic areas, unresponsiveness to empiric antibiotic treatment, and a preceding period of episodic subfebrile temperature, night sweats and fatigue. Serology is the diagnostic test of choice because it is faster and more sensitive than blood cultures. Delay of diagnosis may lead to serious complications. Therefore, alertness for brucellosis is warranted, also, if not especially, in nonendemic areas.
Soluble HLA-G Molecule in Patients with Perennial Allergic Rhinitis
Authors: Ciprandi Giorgio , Contini Paola , Murdaca Giuseppe , Gallina Anna Maria , Puppo Francesco
Published: June 2009

Background: Allergic rhinitis (AR) is characterized by T helper 2 polarized immune response. The soluble HLA-G (sHLA-G) molecule has an immunomodulatory activity. However, so far, no study has investigated this activity in perennial AR (PAR). Objective: The aim of this study was to evaluate serum sHLA-G levels in PAR patients and in a group of healthy controls. Methods: Twenty-five PAR patients were enrolled. A group of 50 healthy non-allergic subjects was considered as control. sHLA-G serum levels were determined by immunoenzymatic method. Results:Allergic patients had significantly higher levels of the sHLA-G (p < 0.001) molecule than normal controls. Moreover, there was a very strong correlation between sHLA-G and symptom severity and drug use (r = 0.85 and 0.793, respectively). Conclusion: The present study provides first evidence that serum sHLA-G levels are significantly increased in PAR patients. Moreover, sHLA-G might be considered as a biomarker for assessing clinical severity.
Long-Term Follow-Up of GH-Treated Girls with Turner Syndrome: Metabolic Consequences
Authors: Bannink Ellen M.N. , van der Palen Roel L.F. , Mulder Paul G.H. , de Muinck Keizer-Schrama Sabine M.P.F.
Published: June 2009

Aims: To investigate the metabolic consequences of long-term GH treatment in young women with Turner syndrome (TS), several years after GH discontinuation. Methods: Follow-up study of a randomized GH dose-response trial, with 3 GH dosages (1.3, 2.0, and 2.7 mg/m2/day). Thirty-nine TS patients (20.0 ± 2.1 years) participated 4.8 ± 1.9 years after GH discontinuation. Mean GH treatment duration was 8.7 ± 2.0 years. Fasting glucose, insulin, and serum lipids were measured. Results: Several years after GH discontinuation, insulin sensitivity remained lower, while β-cell function and fasting insulin levels remained higher than before treatment. Only BMI influenced β-cell function. Serum total cholesterol (TC), low-density lipoprotein and high-density lipoprotein (HDL) had further increased compared to 6 months after GH, resulting in higher TC, but also higher HDL levels compared to controls. The atherogenic index remained constant, but lower than controls. Conclusions: Besides height, GH therapy in girls with TS has additional beneficial effects on serum lipids. Nearly 5 years after discontinuation of GH therapy the favorable effect of GH was still noticeable. The GH-induced decrease in insulin sensitivity, however, remained unchanged, possibly due to having TS.
Testicular Growth and Tubular Function in Prepubertal Boys Conceived by Intracytoplasmic Sperm Injection
Authors: De Schepper Jean , Belva Florence , Schiettecatte Johan , Anckaert Ellen , Tournaye Herman , Bonduelle Maryse
Published: June 2009

Objective: Little is known about the gonadal function of boys conceived by intracytoplasmic sperm injection (ICSI) from fathers with compromised spermatogenesis. To evaluate the potential risk of tubular dysfunction in these boys, we assessed morphological and functional gonadal parameters and their correlation with paternal sperm characteristics. Study Design: In a group of 88 eight-year-old ICSI boys, we measured testicular and penile size. Serum concentrations of anti-mullerian hormone (AMH) and inhibin B were analyzed in 59 of them. Results: Except for two boys with micropenis, penis length and mean testicular length were normal in all boys. In 7 boys inhibin B concentrations were below the lower limit for age, while all AMH results were within normal limits. Serum Sertoli cell markers correlated significantly with each other (p < 0.005), but were independent of paternal sperm parameters. Conclusion: Our data suggest that penile and testicular growth as well as Sertoli cell function are normal in the majority of prepubertal ICSI boys. Serum AMH and inhibin B levels were found to be independent of sperm quality of the father. Further follow-up of these prepubertal children is needed to examine whether normal Sertoli cell markers will be followed by a normal spermatogenesis in puberty.
Acute Pancreatitis in a Girl with Panhypopituitarism Due to Craniopharyngioma on Growth Hormone Treatment. A Combination of Risk Factors
Authors: Faienza Maria Felicia , Delvecchio Maurizio , Indrio Flavia , Francavilla Ruggiero , Acquafredda Angelo , Cavallo Luciano
Published: June 2009

Craniopharyngioma is a rare, benign, suprasellar brain tumor associated with a significant number of endocrine and metabolic impairments. Growth hormone deficiency, caused by the tumor itself or by its subsequent surgical treatment, is the most common hormone deficiency in these patients and replacement is frequently necessary. Hypothalamic obesity observed after surgery treatment, whether combined with radiotherapy or not, presents with increased abdominal fat and altered lipid profiles and is likely caused by both disruption of the mechanisms controlling satiety, hunger and energy balance and impairment of sensitivity to leptin, insulin and ghrelin axis. It is well known that hyperlipemia is associated with acute pancreatitis, both as a precipitant and as an epiphenomenon. Moreover, the increased incidence of acute pancreatitis during growth hormone therapy is possibly due to increased enzyme production (e.g., amylase, lipase and elastase). We report the case of a 13-year-old girl affected by craniopharyngioma on growth hormone replacement treatment who developed acute pancreatitis. We suggest including routine evaluation of lipid profile during follow-up of all children on growth hormone treatment, especially those affected by hypopituitarism secondary to craniopharyngioma, given pancreatic adverse effects of growth hormone replacement therapy and associated metabolic impairment due to hypothalamic obesity.
Prognostic Value of Tiam1 and Rac1 Overexpression in Nasopharyngeal Carcinoma
Authors: Qi Yan , Huang Bo , Yu Linlin , Wang Qi , Lan Guiping , Zhang Qiuhang
Published: June 2009

Purpose: This study is designed to investigate the roles of Tiam1 and Rac1 in nasopharyngeal carcinoma (NPC). Methods: NPC samples (n = 102) were analyzed with immunohistochemistry for Tiam1 and Rac1 proteins, 28 of which were also analyzed with quantitative RT-PCR and Western blots for Tiam1 and Rac1 mRNA and protein expression. The expression of Tiam1 and Rac1 in noncancerous nasopharyngeal tissue (n = 26) acted as a control. The expression was gauged regarding stage, grade and survival. Results: Tiam1 and Rac1 were overexpressed in NPC cells and their protein upregulation was significantly associated with stage and grading (p < 0.05 for all). Cox regression analysis revealed Tiam1 and Rac1 protein upregulation was correlated with lower disease-free and overall survival rates (p < 0.001). Conclusions: Upregulation of Tiam1 and Rac1 proteins may play a critical role in tumor progression of NPC, and work as a prognostic factor for NPC patients.
International and Intranational Technological Spillovers and Productivity Growth in China
Authors: Fu Xiaolan , Gong Yundan
Published: June 2009

Technological spillovers from foreign direct investment (FDI) have been regarded as a major source of technical progress and productivity growth. This paper explores the role of international and intranational technological spillovers from FDI in technical change, efficiency improvement, and total factor productivity growth in Chinese manufacturing firms using a recent Chinese manufacturing firm-level panel data set over the 2001–05 period. International industry-specific research and development (R&D) stock is linked to the Chinese firm-level data, international R&D spillovers from FDI and intranational technological spillovers of R&D activities by foreign invested firms in China are examined as well. Policy implications are discussed.