bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic effect of angiotensin-converting-enzyme inhibitors in HCC patients treated with sorafenib.
Authors: Abouelezz Khaled , Kaseb Ahmed Omar , Hassabo Hesham Mohamed , Garrett Chris R. , Vauthey Jean-Nicolas , Li Donghui , Hassan Manal 
Published: February 2017

328 Background: Experimental studies indicated that angiotensin-converting-enzyme inhibitors (ACEs) or angiotensin receptor blockers (ARBs) has a role in reducing malignant changes of the liver and may significantly improve the mortality in patients with other cancers. However it is not known whether ACE and ARB inhibitors may have prognostic impact on HCC survival outcome. We aimed at evaluating the role of ACE inhibitors and ARB blockers on the prognosis of HCC patients who have been treated by Nexavar (sorafenib). Methods: Using resources of our case-control study at MD Anderson, total of 187 (males, 76.5%; females, 23.5%) pathologically confirmed HCC had been treated by sorafenib. The overall mean age (±SD) was 62.5years ± 9.6. The majority of patients were Caucasians (62.6%) who were diagnosed at TNM stage III and IV (79.2%). Total of 89 (47.6%) patients had no evidence of hepatitis C virus (HCV) or hepatitis B virus (HBV). Median survival was calculated using Kaplan Meier product-limit method and survival rates were compared using the log rank test. Cox proportional hazards model was used to estimate the univariate and multivariate Hazard Risk Ratios (HRR) and 95% Confidence Interval (CI). Results: The overall median survival of HCC patients was 19.9 months (95% CI, 16.1-23.6). Intake of ACEs or ARBs inhibitors was reported in 94 patients (50.3%). We observed significant difference in overall median survival (months) between patients who had ACE/ARB inhibitors versus those who did not, median survival (95% CI) were 21.5 (17.1-25.8) and 14.6 (12.4-16.7), respectively, p=0.04. After adjustment for HCC prognostic factors and demographic factors, we observed 30% reduction in HCC mortality among those who received ACEs/ARBs inhibitors, the estimated HR was 0.7 (95% CI, 0.4-1), p=0.05. Conclusions: Our results may indicate that HCC patients under anti-angiogenic therapy (sorafenib) and have been under anti-hypertensive therapy like ACE/ARB may assist in depleting the collagen and may improve host matrix and tumor microenvironment to enhance drug delivery. Future analysis in a larger sample is warranted
Association of the establishment of multidisciplinary (MDC) hepatocellular carcinoma (HCC) clinic with clinical outcome.
Authors: Yopp Adam C. , Ostapoff Katherine T , Singal Amit G , Mansour John C. , Balch Glen C. , Marrero Jorge A. , Schwarz Roderich 
Published: February 2017

332 Background: Multidisciplinary clinics are prevalent in the management of cancer. However, there is a lack of data demonstrating improved outcomes. The variability of liver- and tumor-specific factors in HCC mandates multimodal therapy. The aim of this study was to evaluate the impact of establishing a MDC HCC clinic. Methods: A MDC HCC clinic consisting of surgeons, hepatologists, oncologists, and radiologists was established October 2010. After this date, any patient with HCC or suspected HCC (any liver mass on radiology or elevated AFP) was evaluated in the MDC clinic. We conducted a retrospective review of a prospective HCC database to identify patients diagnosed in the year following and three years prior to initiation of the MDC clinic. Demographics, tumor characteristics, treatment regimens, and survival were compared between the two groups of patients with one-way ANOVA and Chi-squared tests. Survival curves were generated using Kaplan-Meier with log rank test. Results: 105 patients were identified in the year prior to the MDC clinic and 209 patients in the 3 previous years. There was no difference in gender, race/ethnicity, etiology of cirrhosis, or Child-Pugh stage between the groups. Patients diagnosed after the MDC clinic were found at earlier tumor stages by AJCC and BCLC classification (p=0.001 and p=0.003, respectively). More post-clinic patients received treatment (56% vs. 44%, p=0.04), and time-to-treatment was shorter (2.2 vs. 4.6 months, p=0.001) than those diagnosed prior to the MDC clinic. Median survival of patients diagnosed after the MDC clinic was significantly longer than those seen during the 3 prior years (15.2 vs. 4.7 months, p=0.002). This difference in survival persisted when patients who were lost to follow-up or died within one month of HCC diagnosis were excluded (17.7 vs. 7.0 months, p=0.004). Survival after excluding BCLC D patients was also longer in the post-clinic period (one year survival, 64% vs. 47%, p=0.001). Conclusions: Formation of a MDC HCC clinic is associated with improved survival, most likely due to more streamlined care resulting in HCC diagnosis at earlier tumor stage and shorter time to treatment.
Temporal trends in colorectal cancer screening (CRCS).
Authors: Das Siddhartha , Chen Leo , Cheung Winson Y. 
Published: February 2017

356 Background: The rate of CRCS continues to be suboptimal. Our study objectives were to characterize temporal trends in CRCS in general and within specific subpopulations and identify clinical and system factors that pose barriers to CRCS. Methods: Data from respondents aged ≥50 years who were classified as average risk (no personal or family history of colorectal cancer) from the 2001 to 2009 California Health Interview Survey were analyzed. Up-to-date CRCS was defined as having had a sigmoidoscopy or colonoscopy within the past 10 years. Using multivariate regression analyses that adjusted for confounders, rates of CRCS over consecutive periods of 2 calendar years were determined. Stratified analyses that explored for effect modification based on gender, ethnicity, smoking history, educational attainment, income level, health insurance status, and urban vs. rural residence were conducted. Results: A total of 126,873 screening-eligible respondents was included: median age was 63 years (range 50-85); 50,303 (46%) were men, and 95,534 (63%) were white. In the entire cohort, only 73,589 (55%) reported up-to-date CRCS. Over time, there was a significant trend towards increased CRCS, ranging from 48% in 2001 to 61% in 2009 (p<0.01). After adjusting for confounding variables, this trend persisted with higher odds of up-to-date CRCS in more recent years (see Table). Specific characteristics were associated with decreased likelihood of CRCS: women (OR 0.63), low education (OR 0.72), poor income (OR 0.84), no insurance (OR 0.44), and rural residence (OR 0.93) (p<0.01 for all). Temporal increases in CRCS were most prominent in particular groups, such as women (OR 3.55 in 2009 vs. 2001) and the uninsured (OR 11.48 in 2009 vs. 2001) (p<0.01 for both). Conclusions: Although CRCS improved over time, there is still room for significant improvement. Temporal increases in CRCS were most substantial among women and the uninsured. Interventions used to improve CRCS in these groups should be harnessed and implemented within other minorities to enhance screening. [Table: see text]
Value of cardiophrenic angle lymph nodes for the diagnosis of colorectal peritoneal carcinomatosis.
Authors: Caramella Caroline , Malka David , Pottier Edwige , Goéré Diane , Boige Valerie , Honoré Charles , Ducreux Michel , Borget Isabelle , Dromain Clarisse , Elias Dominique 
Published: February 2017

372 Background: The radiological diagnosis of peritoneal carcinomatosis (PC) is challenging. Metastases in the cardiophrenic angle lymph nodes (CPALN) have been anecdotally reported in patients with abdominopelvic malignancies. We aimed to assess whether CPALN detected by computed tomography (CT)-scan are associated with PC in patients with colorectal cancer (CRC). Methods: Between 2007 and 2010, 550 patients with CRC, including 165 (30%) with PC, underwent surgery with complete exploration of the peritoneal cavity in our center. We retrospectively reviewed preoperative CT-scans for the presence of CPALN, and assessed the association of CPALN with surgically confirmed PC by univariate and multivariate analyses. Results: CPALN were present in 123 (75%) of the 165 patients with PC, but absent in 263 (68%) of the 385 patients without PC (sensitivity (Se), 0.72; specificity (Sp), 0.68; positive predictive value (PPV), 0.49; negative PV (NPV), 0.85; odds ratio [OR], 3.3; p<0.001). The presence of CPALN was not correlated with the extent of PC, the primary tumor and lymph node status , or the presence, number, size and location of liver metastases. Among the 165 patients with PC, 99 (60%) had visible signs of PC (other than CPALN) on CT-scan; among the remaining 66 patients, CPALN were the only potential sign of CP in 41 (62%), leading to Se, Sp, PPV, and NPV in patients with no signs of CP (other than CPALN) on CT of 0.62, 0.68, 0.24, and 0.92, respectively. Conclusions: The detection of CPALN on CT may be of valuable help for the diagnosis of PC in patients with CRC.
Pharmacogenetic biomarkers for predisposition to toxicity to adjuvant FOLFOX/XELOX in colorectal cancer.
Authors: Garcia Alfonso Pilar , Muñoz Andres J. , Blanco Codeisido Montse , Lopez-Trabada Ataz Daniel , Cortejoso-Fernandez Lucia , Garcia-Garcia Maria-Isabel , Gonzalez-Haba Eva , Sanjurjo-Saez Maria , Martin Miguel , Lopez-Fernandez Luis A. 
Published: February 2017

390 Background: 5-fluorouracil and capecitabine are the gold standards in colorectal cancer (CRC) treatment and are often combined with oxaliplatin (FOLFOX and XELOX chemotherapy, respectively). Our purpose was to analyze associations between severe adverse reactions to these regimes and polymorphisms in genes related to these drugs Methods: Retrospective study with 47 adult CRC patients treated with adjuvant FOLFOX/XELOX. 20 polymorphisms in 14 genes were selected: 6 genes [XRCC1 (rs25487), ERCC2 (rs131181), ERCC1 (rs11615), GSTP1 (rs1695), EGFR (rs4559542) and GSTT1 (copy number variation)] related to the pharmacokinetics and dynamics of oxaliplatin and 8 related to fluoropyrimidines [MTHFR (rs1801131 and rs1801133), DPYD (rs2297595 and rs3918290), TYMS (rs34743033 and rs34489327), ABCB1 (rs1128503, rs2032582 and rs1045642), ABCC4 (rs4148551 and rs3742106), ABCC5 (rs3805114), CYP2A6 (rs3742106 ) and CDA (rs2072671)]. Linear by linear association chi-square test (SPSS v.18.0.) was used to study associations. A multivariate analysis including sex and performance status was also conducted. p< 0.05 was considered significant. Results: Mean age was 62 (SD: 12) years and 78.7% male. Univariate analysis: statistically significant associations were obtained between rs11615 (ERCC1), neutropenia and hand-foot syndrome; rs3742106 (CYP2A6) and neutropenia; rs34743033 and rs34489327 (TYMS) and nausea/vomiting; and CNV of GSTT1 and neutropenia. Multivariate analysis: statistically significant associations were obtained between rs3742106 (CYP2A6) and neutropenia (GT vs. TT: OR, 0.042, 95% CI, 0004-0499, p = 0.012); rs2297595 (DPYD) and nausea/vomiting (GA vs AA: OR, 0.051, 95% CI, 0003-0772, p = 0.032); and rs11615 (ERCC1) and neutropenia (CC vs CT / TT: OR, 0.099, 95% CI, 0016-0615, p = 0.013) Conclusions: These results could help oncologists reduce adverse reactions associated to FOLFOX and XELOX chemotherapy by giving patients the best possible option, thus, improving their quality of life. Bigger cohorts are needed to verify the polymorphisms in ERCC1, CYP2A6, TYMS, DPYD and GSTT1 prior application in clinical practice.
Gender specific profiling in SCN1A polymorphisms and time to recurrence in patients with stage II/III colorectal cancer.
Authors: Benhaim Leonor , Gerger Armin , Bohanes Pierre Oliver , Paez David , Wakatsuki Takeru , Yang Dongyun , Labonte Melissa Janae , Zhang Wu , Ning Yan , Loupakis Fotios , El-Khoueiry Rita , Laurent-Puig Pierre , Lenz Heinz-Josef 
Published: February 2017

393 Background: Voltage-gated Na + channels (VGSCs) are involved in cells signalling and strongly contribute in the process of tumour progression. Two single nucleotide polymorphisms (SNPs) in the SCN1A gene encoding the α-subunit of VGSC recently showed an interesting gender-related association with survival in patients with metastatic colorectal cancer (CRC). The current study was designed to confirm the association between SCN1A and time to recurrence (TTR) in patients with stage II and III CRC and determine the influence of the gender on this association. Methods: The study enrolled patients with histologically confirmed CRC high risk stage II and stage III treated from 1987 to 2007 with adjuvant 5-FU-based chemotherapy at the University of Southern California/Norris Comprehensive Cancer Center (USC/NCCC) or in the Los Angeles County/USC Medical Center (LAC/USCMC). Peripheral blood samples were collected for each patient at the date of diagnosis. Genotypes were determined after DNA extraction and PCR amplification by direct sequencing. Results: A total of 127 males and 107 females were enrolled in this study. Baseline demographic and clinical characteristics according to the gender were similar. In univariate analysis female patients carrying the SCN1A rs3812718 TT genotype showed a significant shortened time to recurrence rate when compared to females with the alternate CT or CC genotype (HR: 2.26 [95%CI: 0.89, 5.70], p=0.039). This association remained significant in multivariate analysis. By contrast, in the male population, the shortened time to recurrence rate was oppositely associated with the CC genotype (HR: 0.49 [95%CI: 0.18, 1.38], p=0.048). For the SCN1A rs229877, in both female and male populations the CT genotype was associated with a trend for a shorter TTR. Conclusions: Our findings confirm that genomic SCN1A rs3812718 polymorphism is associated with TTR in patients with stage II and III CRC, supporting the hypothesis that this association is gender dependent. We furthermore verified the trend of a shorter recurrence rate for patients harboring the CT genotype in SCN1A rs229877 regardless of their gender.
Use of selective inhibition of nuclear export (SINE) using a CRM1/XPO1 antagonist to overcome resistance to CPT-11 in colon cancer in preclinical models.
Authors: Chung Hye Won , Salas Fragomeni Roberto A. , Shacham Sharon , Kauffman Michael , Cusack James C. 
Published: February 2017

396 Background: Overcoming the resistance of topoisomerase I (TOP1) inhibitors has great clinical potential for treatment of advanced colon cancer. Previously, we showed a kind of novel CRM1-dependent SINEs leads to increase the anti-cancer effects of topoisomerase-1 (topo-1) inhibitor, CPT-11 (SN38), in colon cancer in vitro. However, its underlying mechanisms have not been fully understood. Here, we showed CRM1-dependent SINEs induced the sequestration of TOP1 into nucleus as well as other tumor suppressors or growth regulatory proteins. Methods: The synergism of KPT-251, a novel CRM1-dependent SINE, with SN38 were evaluated using Chou-Talalay method in both CPT-11/SN38-sensitive (SW480) and CPT-11/SN38-resistant colon cancers cells (WiDr) in vitro and animal experiments bearing CPT-sensitive and CPT-resistant cells in vivo. The expression change of TOP1, p-FOXO3a, p27, p53, p21, and IkBa in nucleus were evaluated by western blot. Nuclear trafficking of TOP1 was confirmed by immunofluorescence microscopy and measuring nuclear TOP1 catalytic activity. Increased apoptosis through TOP1 nuclear sequestration were evaluated by comet assay. Results: We found the dramatic synergism of KPT-251 with CPT-11 in both CPT-11/SN38-sensitive and CPT-11/SN38-resistant colon cancers cells in vitro and in vivo. We also found TOP1 was sequestrated into nucleus by KPT-251 through CRM1 inhibition, and this induced overcoming the resistance of CPT-11 in colon cancers, which were demonstrated by western blot, immunofluorescence microscopy, TOP1 catalytic activity, and comet assays. Conclusions: Our results suggest blocking TOP1 nuclear export by a novel CRM1-dependent SINE sensitizes colon cancer to TOP1 inhibitors. Our study supports the development of a novel treatment strategy to overcome the resistance of CPT-11 and other TOP1 inhibitors in colon and potentially other cancers.
Influence of KRAS mutation on recurrence patterns in patients undergoing hepatic resection of colorectal metastases.
Authors: Kemeny Nancy E. , Chou Joanne F. , Capanu Marinela , Gewirtz Alexandra N. , Cercek Andrea , Kingham T. Peter , Jarnagin William R. , Fong Yuman , DeMatteo Ronald P. , Allen Peter J. , Shia Jinru , Ang Celina , Vakiani Efsevia , D'Angelica Michael Ian 
Published: February 2017

398 Background: There have been conflicting results about whether KRAS mutation influences outcome in patients (pts) with colorectal cancer. In pts who underwent liver resection, Karagkounis reported a worse recurrence and survival in KRAS mutated (MUT) patients (ASCO 2012, abs 3616). Methods: In 105 pts who underwent liver resection and received adjuvant (adj) hepatic arterial infusion and systemic chemotherapy and in whom KRAS data was available, we evaluated recurrence patterns and survival. Correlation between KRAS and clinical factors such as prior chemotherapy, post operative CEA, clinical risk score, and stage at diagnosis was evaluated using Fisher’s exact test and the Wilcoxon rank sum test. Kaplan-Meier methods were used to estimate median overall recurrence free survival (RFS) and overall survival (OS) at 4 years. Log-rank test was used to determine whether survival functions differed by KRAS mutation status. Cumulative incidence function was used to estimate the probability of time from adj therapy to bone, brain, lung and liver metastases separately. Results: Of 105 patients, 76 were KRAS wildtype (WT), and 29 were KRAS MUT (26-G12 and 3-G13). The median RFS was 26 months for KRAS WT pts and 15 months for KRAS MUT pts (p=0.08). OS at 4 years was 88% [95% CI: 78%-94%] for KRAS WT and 78% [95% CI: 57%-90%] for KRAS MUT pts (p= 0.15). Cumulative incidence of developing bone, brain, lung, and liver metastases by 2 years is presented in the Table. The cumulative incidence of bone and brain metastases at 2 years was 0% and 0% in KRAS WT pts versus 16.4% [95% CI: 1.1%-31.7%] and 4.7% [95% CI: 0%-14.1%] in KRAS MUT pts (Table). There was no association between clinical factors and KRAS status. Conclusions: KRAS MUT pts appeared to have worse OS and RFS, although we were unable to show a significant difference between KRAS WT and MUT for OS and RFS. In addition, cumulative incidence of bone and brain metastases at 2 years appeared to be higher for KRAS MUT pts as compared to WT pts. Results are based on small sample size and further investigation is needed. [Table: see text]
A phase II, single arm clinical trial involving an alternative cancer treatment psorinum therapy in patients with unresectable metastatic colorectal carcinoma.
Authors: Chatterjee Aradeep , Bhattacharya Sudin , Chatterjee Ashim Kumar , Chakraborty Amitava , Biswas Jaydip 
Published: February 2017

407 Background: We prospectively studied the clinical efficacy of an alternative cancer treatment “psorinum therapy” in treating unresectable metastatic colorectal carcinoma (UMCRC). Methods: Our study was phase-II, open level, single arm and single stage. Participants eligibility criteria included (1) histopathology confirmation of the malignancy (2) metastatic and unresectable disease status (3) no prior conventional cancer treatments (4) Karnofsky performance status between 40–70%. The primary outcome measures of the study were (1) to assess the radiological tumor response rate (using CT scanning procedure and following the RECIST criteria); (2) to assess how many participants survived at least 1 yr, 2 yrs, 3 yrs, 4 yrs and finally, after 5 yrs of the study. The secondary outcome measure was to assess the side effects of the investigational anti-cancer drug (psorinum) if any. Psorinum (an alcoholic extract of scabies slough and pus cells) was administered orally at a dose of 0.02ml/kg body weight/day as a single dose on an empty stomach for a complete course duration of 2 yrs to all the participants along with allopathic and homeopathic supportive cares. Results: 105 participants included in the final analysis at the end of the study. According to the RECIST criteria, complete response occurred in 12 (11.43%) cases and partial response occurred in 38 (36.19%) cases. 76 (72.38%) of them survived at least 1 yr, 58 (55.24%) survived at least 2 yrs, 51 (48.57%) survived at least 3 yrs, 43 (40.95%) survived at least 4 yrs and 37 (35.24%) of them survived at least 5 yrs. These participants didn’t receive conventional or any other investigational cancer treatments. Conclusions: The results of the study show clinical efficacy of psorinum therapy in treating patients with UMCRC. The investigational drug psorinum is non-toxic. Randomized controlled clinical trial should be conducted for further investigation of this alternative cancer treatment in treating unresectable metastatic colorectal carcinoma to integrate it into the mainstream of oncology treatments.
Clinical significance of tumor budding in colorectal cancer.
Authors: Lee Jae-Im , An Chang Hyeok , Kim Hyung Jin , Lee Sang Chul , Oh Seong-Taek 
Published: February 2017

422 Background: Tumor budding was defined as an isolated single cancer cell or a small cluster of cancer cells at the invasive margins. We assessed the clinical significance of tumor budding, as a predictor of outcomes in patients with non-metastatic colorectal cancer. Methods: We studied a total of 148 patients with colorectal cancer who underwent curative resection. Tumor budding was assessed on slides stained with hematoxylin and eosin (H&E). Tissue specimens including the entire invasive margin from largest cut sections of the whole tumor were examined. Tumor budding was not classified according to previously described classification. The actual number of tumor budding along the entire invasive margin was counted at a magnification of x200 with the use of light microscopy. We determined cut-off point of tumor budding, lymph node ratio and carcinoembryonic antigen (CEA) with receiver operating characteristic (ROC) curve. Results: Univariate analysis revealed that poorly differentiation (p=0.009), lymphatic invasion (p=0.035) venous invasion (p=0.007), CEA >6.3 (p=0.0007) and tumor budding >13 (p=0.0006) were significantly related to poor survival. Cumulative five survival rates differed significantly between patients with tumor budding ≤13 (92.3%) and those with tumor budding >13 (73.1 %). Multivariate analysis with Cox’s regression analysis demonstrated that tumor budding >13 (hazard ratio=4.925, p=0.003), poorly differentiation (hazard ratio=3.696, p=0.01) and CEA >6.3 (hazard ratio=3.085, p=0.024) were independent prognostic factors for overall survival. CEA >6.3 (hazard ratio=2.361, p=0.034) and tumor budding >20 (hazard ratio=3.293, p=0.008) were significant prognostic predictors for disease free survival Conclusions: Tumor budding is useful for prognosis and identifying patients with colorectal cancer who have a high-risk of disease recurrence after curative surgery. The proper cut-off level of tumor budding is 13.