bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of hepatic fiblosis on the incidence of liver metastasis from colorectal cancer.
Authors: Kondo Takayuki , Okabayashi Koji , Hasegawa Hirotoshi , Tsuruta Masashi , Seishima Ryo , Matsui Shimpei , Yamada Toru , Takahashi Hidena , Shimada Takehiro , Matsuda Mutsuhito , Yahagi Masashi , Yoshikawa Yusuke , Asada Yusuke , Sugiura Kiyoaki , Suzuki Yoshiyuki , Tajima Yuki , Nakadai Junpei , Kitagawa Yuko 
Published: February 2017

529 Background: Non-alcoholic steatohepatitis (NASH) is closely associated with hepatic fibrosis (HF). The number of patients who have NASH is increasing by eating high-calorie diet. It remains unclear how much impact such NASH and HF on the development of liver metastasis by colorectal cancer (CRC). The objectives of this study is to clarify the influence of HF on metachronous liver-specific recurrence in colorectal cancer patients who underwent colorectal surgery with curative intent. Methods: Between 2000 and 2010, patients who underwent a curative surgical resection for CRC were included in this study. We evaluated the progression of HF by using non-alcoholic fatty liver disease fibrosis score (NFS) based on preoperative blood test result, age, BMI and DM. The patients with NFS higher than 0.676 were objectively defined as HF. The influence of HF on hepatic recurrence was assessed by survival analyses. Results: A total of 953 CRC patients were enrolled, comprised of 293 in stage I, 327 in stage II and 333 in stage III. The mean of NFS was 1.32±1.55, where the included patients were categorized into 77 HF and 876 non-HF. 5-year liver-specific disease-free survival rate in HF was significantly poorer than non-HF (HS 87.0% vs. non-HF 94.5%, log-rank p=0.009). Multivariate analysis demonstrated that HF significantly promoted liver-specific recurrence compared to non-HF (HR=2.16, 95% CI, 1.00 to 4.64; p=0.049). Conclusions: Hepatic fibrosis had a great impact on hepatic recurrence after curative surgical resection of CRCs. These findings indicated that HF might be a favorable microenvironment in developing colorectal liver metastasis. The evaluation of the degree of HF can be useful in selection of adjuvant chemotherapy and postoperative surveillance.
Effect of arecoline, the major alkaloid of areca nut, on the number of N-benzyl-N-methylnitrosamine (NMBA)-induced esophageal papilloma in F344 male rats.
Authors: Wu Ming-Tsang 
Published: February 2017

53 Background: Arecoline is the major alkaloid of areca nut which is one major risk of developing esophageal squamous cell carcinoma (ESCC) in the Asian population. This study aims to establish one rat model to study the relationship of areca nut exposure with the development of ESCC. Methods: Six-week-old Fischer 344 male rats were injected subcutaneously with 0.5 mg/kg NMBA thrice a week for the first 5 weeks and given water without or with arecoline (500 mg/ml) for 30 weeks. Results: With co-treatment of arecoline, NMBA-injected rats had significantly more esophageal papillomas (p = 0.02) and marginally significantly more tongue papillomas (p= 0.09) per rat, compared to those with NMBA only in the end of week 30. No papilloma was found in the lung, liver and/or stomach among all experimental groups. The histological features of esophageal papilloma showed the hyperplastic changes of squamous epithelium. Conclusions: This established animal model can be ideally used to study areca nut-associated esophageal carcinogenesis.
Burden of high-risk HPV infection in women in the United States and implications for anal cancer screening: NHANES (1999-2012).
Authors: Dunn Erin , Moore Kevin J. , Koru-Sengul Tulay 
Published: February 2017

532 Background: High-risk Human Papilloma Virus (HPV) infections put women at risk for cervical, anal, vaginal, and vulvar cancers. HPV can spread from the genital region to the anus even in absence of sexual intercourse. As anal cancer is more prevalent in women, it is important to consider HPV transmission from the vagina to the anus. National surveys provide estimates of population-specific prevalence to identify the burden of high-risk HPV infection in women. Appreciating high-risk HPV infection in women and the potential for HPV spread from the genitals to the anus is crucial for cancer screening efforts. Methods: We calculated prevalence of HPV infections in women in the United States from 1999-2012 National Health and Nutrition Examination Survey (NHANES) to obtain a representative sample of the U.S. non-institutionalized civilian population. NHANES performs in-person interviews and physical examinations and collects biological samples at homes and mobile examination centers. We provided epidemiology of HPV infection and its types for women. Analysis was performed by SAS v9.3. Results: DNA-measured HPV from vaginal swabs showed 42.9% of women were HPV positive. We calculated odds ratios across demographic groups for high-risk HPV types (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82). Non-Hispanic White (NHW) women had the highest prevalence of high-risk HPV (62.5%). Other Hispanic women had lower odds of having high-risk HPV compared to NHW (OR=0.65; 95% CI=0.49, 0.88). Never married women had greater odds of high-risk infection than married women (1.61; 1.26, 2.06). Current smokers had greater odds than never smokers of high-risk infection (1.26; 1.00, 1.59). Conclusions: Our results show the burden and demographic disparities of high-risk HPV infection in women. Understanding the burden of potentially oncogenic HPV infections in the female genital region is important for cervical cancer screening and highlights a potential importance for anal cancer screenings in HPV positive women. Recognizing demographic disparities could lead research into risk factors and risk conditions that guide the preponderance of HPV infection and anal cancer in specific female populations.
KRAS tests utilizations, biologics uptakes, and disparities in access by demographic groups among metastatic colon cancer patients.
Authors: Goto Daisuke , Mullins C. Daniel , Bikov Kaloyan A. , Seal Brian S. , Hanna Nader 
Published: February 2017

533 Background: Mutant KRAS oncogenes are observed in approximately 35%-45% of colorectal cancer patients. Cetuximab (CET) and panitumumab (PAN) are epidermal growth factor receptor (EGFR) inhibitors that are used in the treatment of metastatic colon cancer (mCC). KRAS mutations decrease the treatment response of these biologic agents. Reports of this decreased treatment response in CET and PAN surfaced in 2006. In 2009, the FDA changed the label on CET and PAN to state that these agents were “not recommended” for the treatment of colon cancer in patients with KRAS mutations. This label change encouraged prescribers to perform KRAS tests. The objective of this study is to examine the utilization of KRAS tests for mCC treatment in real-world practice. Methods: We examined 6,044 mCC patients in the SEER-Medicare database who were diagnosed between 2006 and 2009 (their median age at diagnosis was 78). Using recorded procedure codes, we identified whether each patient received a KRAS test or not and whether CET and/or PAN were given. We further identified demographic characteristics of patients. Results: Among the 6,044 patients, 15% patients were tested for KRAS mutations. This frequency increased from 7% for those diagnosed in 2006 to 24% for those diagnosed in 2009. Following KRAS testing, CET or PAN were administered to 29% of patients. On average for 2006-2009, 5% of patients who were not tested received CET or PAN (or 15% if patients who did not receive any treatment are excluded). This frequency dropped from 7% for those diagnosed in 2006 to 2% for those diagnosed in 2009 (19% and 7% respectively if patients without any treatment are excluded). We found disparities in receipt of KRAS testing: the test was administered to 12% of black patients, 16% of white patients, 17% of males, and 14% of females. These differences were found statistically significant (p < 0.05). Conclusions: KRAS testing rates increased over time. Moreover, as time passed fewer patients were administered CET and/or PAN without being tested for KRAS mutations. Black patients and women were less likely to receive a KRAS test, which could impact access to treatment.
Second primary malignancies in anal carcinoma.
Authors: Shah Binay Kumar , Budhathoki Nibash 
Published: February 2017

534 Background: Survival of cancer patients is increasing. Therefore, there is a need to evaluate long term complications in cancer survivors. There is no data on second primary malignancies in anal cancer. This study was conducted to evaluate second primary malignancies in patients with anal carcinoma. Methods: We selected adult patients diagnosed with anal cancer from National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) 13 database We calculated the risk of second primary malignancies in the anal cancer patients using multiple primary standardized incidence ratio (MP-SIR) session of SEER*stat software. Results: Among 7,661 patients with anal carcinoma, 3,196 were men and 4,465 were women. Median follow up duration was 87 months (range: 7-239 months). Median age at the time of diagnosis of SPM was 69.33 yrs (range: 34-103 yrs). Median latency for SPM was 52 months (range: 6-219 months). A total of 675 patients (9.07%) developed 747 second primary malignancies, with an observed/expected (O/E) ratio of 1.41 (95% confidence interval =1.32-1.52, p<0.001), and an absolute excess risk of 55.36 per 10,000 populations. Significant excess risks were observed for oral cavity and pharyngeal tumor, rectal and anal canal tumor, laryngeal tumor, lung and bronchial cancer, Kaposi sarcoma, hematologic malignancies, ovarian, vaginal, and vulval tumors. Conclusions: The risk of second primary malignancies in adult patients with anal cancer is significantly increased compared to general population.
Evaluation of two-dimensional response to predict overall survival in patients with metastatic colorectal cancer treated with the first-line bevacizumab-based chemotherapy.
Authors: Nakayama Goro , Takano Nao , Tanaka Chie , Kobayashi Daisuke , Koike Masahiko , Fujiwara Michitaka , Kodera Yasuhiro 
Published: February 2017

539 Background: The evaluation of the quantitative analyses for tumor response, such as early tumor shrinkage (EST) or depth of response (DpR), could be useful to serve the surrogate for survival benefits in chemotherapies for patients with mCRC. However, these analyses might be insufficient to explain an individual-level surrogacy of long-term survival outcomes in anti-angiogenic agents, because patient tumor dynamics might be highly diverse. In this study, we defined ‘2-DR’ by both tumor shrinkage and time factors as a new efficacy outcome measure to explain the impact of chemotherapy with BEV on long-term survival outcome. Methods: All patients included in this analysis had participated in phase II clinical trial (CCOG-0801, UMIN000006818). Forty-seven patients with previously untreated mCRC were treated with mFOLFOX6 plus BEV, followed by FOLFIRI plus BEV. The median PFS and OS were 7.3 and 30.8 months, respectively. ETS and DpR are defined as the ratio of tumor shrinkage observed at 8 week after initiation of treatment and the nadir to baseline. 2-DR, that is the area enclosed by the coordinate points including ETS, DpR and 20% increase over nadir at progression disease, is calculated as follows: 2-DR (week×%) = (0.5 TR+1.1 TP-4)×DpR+0.5 TR×ETS–10 TP, where TR is the time duration from the date of initiation of therapy to maximum tumor shrinkage and TP is the time duration from the date of observation of maximum tumor shrinkage to 20% increase over nadir. Results: Median ETS, DpR and 2-DR were 23% (range, -33 to 72), 31% (range, -33 to 100) and 10.3 (week×%) (range, -4.4 to 92.6), respectively. The Spearman rank correlation coefficients were 0.27 between ETS and OS, 0.28 between DpR and OS, and 0.46 between 2-DR and OS, respectively. There was strong relationship between 2-DR and OS (p<0.01). Median OS in the higher and lower 2-DR groups was 21.5 months (95% CI, 20.4 to 29.8) and 32.9 months (95% CI, 24.5 to 41.3), respectively (p<0.01). A Cox regression model revealed that 2-DR was the only independent prognostic factors for OS (HR 0.26, p<0.01). Conclusions: 2-DR could be a new surrogate marker of OS in the BEV-based first-line chemotherapy for mCRC.
Delay to colectomy and survival for patients diagnosed with colon cancer.
Authors: Bagaria Sanjay Prakash , Heckman Michael , Diehl Nancy N. , Parker Alexander S. , Wasif Nabil 
Published: February 2017

541 Background: A long wait-time for colectomy for colon cancer should theoretically affect survival but, to date, the association between delay to colectomy and survival remains unresolved. Methods: We studied 4,692 patients who underwent colectomy for colon cancer between 1990 and 2012. Wait-time was defined as the number of days between diagnosis and colectomy. Cox regression models were used to estimate all-cause mortality across wait-time categories. Multivariable analyses were controlled for clinicopathologic variables and Charlson comorbidity index. Results: The number of patients in the wait-time group of 1-28 days was 3,950 (84.2%), 29-84 days was 681 (22.7%), and >84 days was 61 (1.3%). A wait-time of 29-84 days was not associated with an increased risk of death (HR=1.13; p=0.056) when compared to a wait-time of 1-28 days. Though a wait-time >84 days represented a small group, it was associated with an increased risk of death (HR=1.60; p=0.013). For patients with stage I and II disease, wait-times of 29-84 days (HR =1.44; p=0.0001) and >84 days (adjusted HR=2.24; p=0.0007) were associated with an increased risk of mortality. Conclusions: A wait-time for colon cancer surgery of up to 12 weeks is likely safe for most patients. However, those suspected to have early-stage colon cancer may benefit from less of delay. These data provide a framework to address concerns over prolonged wait-times and can direct efforts for timely surgical intervention in patients with colon cancer. [Table: see text]
A prospective study to evaluate the usefulness of the clanging tuning fork test and the nerve conduction velocity test for oxaliplatin-induced peripheral neuropathy.
Authors: Hirashima Yoshinori , Hanaoka Takuya , Watanabe Koichiro , Nagashina Kengo , Inagaki Takashi , Nishikawa Kazuo , Hisamatsu Yasushi , Morinaga Ryotaro , Otsu Satoshi , Kumamoto Toshihide , Shirao Kuniaki 
Published: February 2017

544 Background: Neurotoxicity is the most frequent dose-limiting toxicity of oxaliplatin. Cumulative sensory peripheral neurotoxicity results in discontinuation of chemotherapy for cancer and impairs neurological function irreversibly. To develop new strategies to continue chemotherapy according to the treatment plan without more severe neurotoxicity, objective assessment tools for oxaliplatin-induced peripheral neuropathy (OIPN) are needed. The clanging tuning fork test (CTFT) and the nerve conduction velocity test (NCVT) are widely used forbenign neuropathies. However, little is known about their clinical usefulness for OIPN. Methods: Colorectal cancer patients were prospectively monitored at baseline and during chemotherapy with modified FOLFOX6. The incidence and severity of OIPN were recorded using NCI-CTC grading (ver. 4.0). CTFT was conducted every 2 weeks and NCVT every 8 weeks. A generalized estimating equation model was used to examine the correlations between NCI-CTC grade and CTFT/NCVT. The accuracy of the assessment was evaluated using receiver operating characteristic (ROC) curve analysis. Results: Twenty-one patients without peripheral sensory neuropathy (PSN) were enrolled. Mean CTFT values were 13.4 ± 0.7 sec at baseline, 14.1 ± 0.4 sec with grade 0 PSN, 14.0 ± 0.4 sec with grade 1 PSN, 12.5 ± 0.7 sec with grade 2 PSN, and 7.5 ± 0.9 sec with grade 3 PSN. The mean CTFT value with grade 3 PSN was significantly shorter than with the other grades (p<.001, all). ROC curve analysis showed that variation in CTFT provides a high-accuracy assessment of grade 3 PSN (AUC=0.898, 95% CI: 0.764-1.000, p=.004), and its optimal cut-off value was -3.5 sec (sensitivity and specificity for grade 3 PSN were 86% and 79%, respectively). Unlike CTFT, NCVT showed little association with OIPN. Conclusions: CTFT was found to be very effective for assessing grade 3 OIPN. The present results suggest that CTFT, a simple, quick, and non-invasive examination, is a promising assessment tool for OIPN. Clinical trial information: 000004305.
Awareness of KRAS testing by oncologists and panitumumab use in colorectal cancer patients: A European survey.
Authors: Trojan Jorg , Taylor Aliki , Terwey Jan-Henrik , Downey Gerry , Kafatos George , Garcia Alfonso Pilar , Tomasek Jiri , Mineur Laurent , van Krieken Han , Aprile Giuseppe 
Published: February 2017

547 Background: Panitumumab (Pmab) is licensed for treatment in metastatic colorectal cancer (mCRC) patients with wild type KRAS mutation status (US) and wild type RAS (KRAS and NRAS) mutation status (most other countries). To resolve uncertainties about KRAS testing, a survey and medical records review (MRR) are being carried out in Europe in three rounds: the first two rounds (2012-2013) evaluated KRAS testing and round 3 is evaluating RAS testing. These studies are specific obligations in Europe for the conditional marketing authorization for Pmab. Here we present results of rounds 1 and 2. Methods: Eligible oncologists were contacted by telephone in nine European countries (France, Germany, Italy, Spain, Czech Republic, Netherlands, Belgium, Denmark, and Sweden). To be eligible, the physician was required to be a practicing oncologist and have prescribed Pmab to mCRC patients. Results: 299 of 301 (99.3%) oncologists participating in the survey were aware of the need to perform KRAS testing prior to first dose of Pmab and 294 (97.7%) were aware of patients’ KRAS mutation status prior to first dose. 283 of 301 (94.0%) did not prescribe Pmab to mCRC patients with mutant or unknown KRAS status. 164 physicians administered Pmab simultaneously with oxaliplatin-containing chemotherapy to patients and 10 (6.1%) to patients with mutant or unknown KRAS status. 306 patients from 79 participating oncologists were included in the MRR. 302 of 306 mCRC patients (98.7%) were tested for KRAS tumor status, known by the oncologist before first dose of Pmab. 299 of 302 patients (99.0%) had wild-type KRAS tumor status. 83 of 85 patients (97.6%) treated with Pmab and oxaliplatin-containing chemotherapy had wild-type KRAS tumor status. 55 of 56 linked pathology laboratories (98.2%) participated in a Quality Assurance scheme; all used a CE marked or otherwise validated KRAS detection method. Conclusions: Results from both studies show a high level of knowledge among oncologists of the need for KRAS testing in mCRC patients prior to treatment with Pmab and the contraindication with oxaliplatin-containing chemotherapy with mutant or unknown KRAS tumour status. The final round of this study evaluating RAS testing in Europe is currently underway.
Improving the prediction of colon cancer survival after curative resection.
Authors: Pabani Aliyah , Cheung Winson Y. , Mazurek Matthew , Spratlin Jennifer L. , Mulder Karen E. , Ghosh Sunita , Price Hiller Julie A. , Standeven Leah Jean , Ho Maria Yi 
Published: February 2017

552 Background: Cancer staging systems convey valuable prognostic information to both clinicians and patients. Currently, colon cancer is staged according to the American Joint Committee on Cancer (AJCC) TNM classification system. However, survival estimates for patients with the same stage of colon cancer may vary considerably due to other factors including age, sex, grade, and number of lymph nodes sampled. The objectives of this study are to 1) assess the accuracy of the seventh edition of the TNM classification system in predicting survival of patients with primary colon cancer after curative-intent surgery, and 2) evaluate the utility of incorporating additional demographic and tumor variables beyond TNM staging in improving prognostic accuracy. Methods: Patients with curative-intent resection of a first primary adenocarcinoma of the colon at the time of referral to the Cross Cancer Institute between 2004 and 2007 were identified from the Alberta Cancer Registry. We constructed three multivariate Cox’s proportional hazard models to explore the effect of supplementing TNM staging with additional demographic and tumor variables in predicting overall survival (OS). Results: 559 consecutive patients with complete chart records were identified. 52 % (n=290) were male; median age was 74. In the first model based only on T and N elements, N2 disease was correlated with increased mortality (hazard ratio [HR], 2.546; p<0.0001). When the number of lymph nodes examined (HR, 0.980; p=0.034) and number of metastatic lymph nodes detected (HR, 1.094; p<0.0001) were substituted for the N-staging element, both variables correlated positively and negatively with outcome, respectively. Finally, when tumor grade, sex and age were incorporated into the model, number of examined lymph nodes (HR, 0.980; p=0.029) and those containing tumor (HR, 1.093; p<0.0001) remained independent predictors of OS. Conclusions: Incorporating readily available demographic and tumor variables, such as age, sex and number of lymph nodes examined, can enhance the current TNM staging system and improve prognostication in early stage colon cancer.
RacGAP1 expression, increasing tumor malignant potential, as a predictive biomarker for lymph node metastasis and poor prognosis in colorectal cancer.
Authors: Imaoka Hiroki , Toiyama Yuji , Saigusa Susumu , Mori Koichiro , Noguchi Tomofumi , Ide Shozo , Uratani Ryo , Oki Satoshi , Fujikawa Hiroyuki , Hiro Junichiro , Kobayashi Minako , Tanaka Koji , Ohi Masaki , Araki Toshimitsu , Inoue Yasuhiro , Mohri Yasuhiko , Kusunoki Masato 
Published: February 2017

555 Background: Rac GTPase activating protein (RacGAP) 1 plays a key role in controlling various cellular phenomena including cytokinesis, transformation and migration. Recently, the clinical significance of RacGAP1 expression has been reported in several malignancies. However, direct association between the RacGAP1 expression and colorectal cancer (CRC) has not been fully investigated. The aim of this study is to elucidate the function and clinical significance of RacGAP1 expression in CRC. Methods: The intrinsic functions of RacGAP1 in CRC cells were analyzed using small interfering RNA (siRNA). We analyzed RacGAP1 mRNA expression in surgical specimens from 193 CRC patients (Cohort 1) by real-time polymerase chain reaction. Then, we validated RacGAP1 protein expression using formalin-fixed paraffin-embedded samples from 298 CRC patients (Cohort 2) by immunohistochemistry. Finally, we evaluated the association between RacGAP1 mRNA and protein expression and clinicopathological data. Results: Reduced RacGAP1 expression by siRNA in CRC cell lines showed significantly decreased cellular proliferation, migration, and invasion. In Cohort 1, RacGAP1 expression in CRC was significantly higher than in adjacent normal mucosa, and increased according to TNM stage progression. High RacGAP1 expression in tumors was significantly associated with progression and prognosis. In Cohort 2, RacGAP1 protein was overexpressed mainly in the nuclei of CRC cells; however, its expression was scarcely observed in normal colorectal mucosa. RacGAP1 protein expression was significantly higher in CRC patients with higher T stage, vessel invasion, and lymph node and distant metastasis. Increased expression of RacGAP1 protein was significantly associated with poor disease-free and overall survival. Multivariate analyses revealed that high RacGAP1 expression was an independent predictive marker for lymph node metastasis, recurrence, and poor prognosis in CRC. Conclusions: Our data provide novel evidence for the biological and clinical significance of RacGAP1 as a potential biomarker for identifying patients with lymph node metastasis and poor prognosis in CRC.