bluuebunny/crossref_metadata_2025_split huggingface dataset:
The correlation between mismatch repair status and clinicopathological characteristics in Chinese colorectal cancer patients.
Authors: Xiao Zhi-tao , Zhang Rong-xin , Zhao Yang , Peng Jian-Hong , Ding Pei-Rong , Wu Xiao Jun , LU Zhen-hai , LI Li-ren , Wan Desen , Pan Zhi-zhong , Zhang Hui-Zhong , Lu Shi-xun , Chen Gong 
Published: March 2017

544 Background: Our study aimed to explore the relationship between mismatch repair (MMR) status and clinicopathological characteristics in Chinese patients with colorectal cancer (CRC). Methods: A total of 2684 patients with histologically confirmed adenocarcinoma of CRC were consecutively recruited between May 2011 and May 2015 at Sun Yat-sen University cancer center. The exclusion criteria included multiple primary tumors, synchronous and metachronous CRC, and familial adenomatous polyposis. The CRC was defined as left colon with the tumor located below the splenic flexure or rectum, otherwise grouped as right colon. Correlations of MMR status and patient’s demographics, tumor characteristics and TNM staging (exclude 315 CRC patients receiving neoadjuvant therapy) were investigated. Results: We found that deficient MMR (dMMR) status was more likely detected in younger CRC patients compared to the the elderly (12.7% vs 7.5%, P < 0.001). The dMMR rate in right colon cancer was significantly higher than that in left colon cancer and rectal cancer (22.7% vs 7.2% vs 5.2%, P < 0.001).With respect to tumor differentiation, we found that the mucinous adenocarcinoma had the highest rate of dMMR(24.4%), followed by poorly differentiated adenocarcinoma(18.5%), signet-ring cell carcinoma(17.6%), well differentiated adenocarcinoma(9.5%), moderately differentiated adenocarcinoma(8.9%), and neuroendocrine carcinoma (0%) ( P < 0.001). In addition, the proportions in stage I, stage II, stage III and stage IV CRC were 9.7%, 16.5% , 8.5% and 3.9%, respectively ( P < 0.001). There was no significant difference in gender (P = 0.114). Conclusions: At the first time, our study demonstrated that dMMR status was most likely detected at younger age (less than 59 years) and stage II right colon mucinous adenocarcinoma in large volume Chinese patients, which was similar to the results in western countries.
Tracking emerging KRAS, BRAF and EGFR mutations through ccfDNA in colorectal cancers treated with EGFR blockade.
Authors: Yamada Takeshi , Takahashi Goro , Iwai Takuma , Takeda Kouki , Koizumi Michihiro , Shinji Seiichi , Matsuda Akihisa , Yokoyama Yasuyuki , Furuki Hiroyasu , Hara Keisuke , Matsumoto Satoshi , Ohta Keiichiro , Eiji Uchida 
Published: March 2017

547 Background: Epidermal growth factor receptor (EGFR) blockade can achieve considerable tumor shrinkage in patients with metastatic colorectal cancer (CRC). However, most patients who benefit from EGFR blockade acquire resistance within a year through emerging KRAS, BRAF or EGFR ( S492R) mutations. We have shown that patients with KRAS or BRAF mutations in circulating cell-free DNA (ccfDNA) do not respond favorably to EGFR blockade. In this study, we aimed to detect acquired resistance to EGFR blockade early by using ccfDNA to track emerging KRAS, BRAF and S492R mutations during chemotherapy. Methods: We enrolled 24 patients with metastatic CRC and no KRAS mutations in their primary tumors who were to be treated with systemic chemotherapy that included EGFR blockade. We purified ccfDNA from 1 mL of serum from each patient before they started chemotherapy. We also extracted ccfDNA from these patients every 2–3 months until disease progression. We detected nine KRAS, BRAF (V600E) and S492R mutations using digital polymerase chain reaction. Results: We detected KRAS mutations in ccfDNA of three patients before chemotherapy (12.5%; 3/24). The response rate was 83% (20/24); the four non-responders comprised the three with KRAS mutations and the other with BRAF mutations in their ccfDNA before chemotherapy. All patients with no KRAS or BRAF mutations in their ccfDNA before chemotherapy responded to the chemotherapy (20/20). Of these 20 initially responsive patients, 12 (60%) acquired resistance. We detected emerging KRAS mutations in the ccfDNA of eight of these 12 patients (67%) prior to relapse, six of them having multiple mutations. Five of these patients had mutations in codon 61 and one had solo codon 61 mutations. We also detected BRAF mutations in five patients; none had solo BRAF mutations. Four patients had S492R mutations; none had solo S492R mutations. Conclusions: If KRAS or BRAF mutation do not detected in primary tumor, EGFR blockade has no beneficial effect in patients with KRAS or BRAF mutations in their ccfDNA prior to commencing chemotherapy. Emerging KRAS, BRAF or S492R mutations that were undetectable before starting chemotherapy are associated with acquired resistance to EGFR blockade.
Demographic factors and rate of lymph node evaluation in colon cancer stage II using National Cancer Database (NCDB).
Authors: Tahseen Ahmed Ibrahim , Ahmed Aabra , Silberstein Peter T. 
Published: March 2017

548 Background: Retrieving at least 12 lymph nodes (LN) is a quality indicator in colon cancer. Previous studies have shown about 38% of patients with stage II are estimated to have ≥12 LN checked. Methods: Community Programs (CCP) receive 100-500 newly diagnosed cancer cases per year. Hospitals receiving 500+ patients are either Academic Comprehensive Programs (ACP) or Comprehensive Community Programs (CCCP). Using NCDB (2003-2013), which includes >70% of newly diagnosed cancer patients, we utilized chi-square analysis, and compared frequencies of patients with and without having ≥12 LN examined. Results: In the NCDB database, the percent of patients with stage II colon cancer who have ≥12 LN checked is much lower than current estimates. Non-Hispanic and Hispanic patients have similar LN examination rate, as do Blacks and Whites. 4% less men have ≥12 LN examined than women. Large differences exist among patients with different insurance statuses. Uninsured and Medicaid patients have much lower LN examination with ~80% of having <12 LN examined. CCPs have a lower rate of LN examination, with 7.4% more patients having <12 LN checked than CCCPs and 9.1% more than ACPs. When comparing frequency of those with <12 and ≥12 LN examined in a demographic, p<.05 in all comparisons. Conclusions: This largest, and most recent analysis of frequencies in patients with stage II colon cancer reflects a low rate of ≥12 LN being examined in those with stage II colon cancer. Rates of ≥12 LN being examined is greater in stage III colon cancer, however, there is a significant difference in survival when ≥12 LN are checked in stage II colon cancer as well. From 2004-2008 rates of LN examination increased, but rates of LN examination have since stagnated. Only around a quarter of patients have ≥12 LN examined; thus, this quality measure is only achieved in a minority of patients. [Table: see text]
Association of ongoing systemic inflammatory response (SIR) at diagnosis with lymph node retrieval and node positivity in patients undergoing surgery for colonic cancer.
Authors: Dolan Ross , McSorley Stephen Thomas , McMillan Donald C , Horgan Paul G. 
Published: March 2017

550 Background: Prognosis in colonic cancer is largely based on pathological criteria such as TNM staging. However, there are deficiencies in this approach and the lymph node ratio (LNR) has been promoted as improving prediction of outcomes. In this context retrieval of lymph nodes and their examination is of considerable importance. Kennelly et al (World J Gastrointest Oncol 2016) in a recent study, in 331 patients undergoing surgery for colon cancer, reported an elevated LNR and lower lymph node retrieval in those patients with a SIR. In the present study these relationships were examined in a larger cohort of patients (n = 881). Methods: A prospectively maintained database of all patients undergoing elective curative colonic resection in our institution was examined. The SIR was measured by scores mGPS (C-reactive protein/ albumin), NLR (neutrophils/ lymphocytes), PLR (platelets/ lymphocytes) and LMR (lymphocytes/ monocytes) using standard thresholds mGPS (0,1,2), NLR ( ≥ 5), PLR ( ≥ 150) and LMR ( ≤ 2.4). Statistical analysis was carried out in SPSS using Independent Mann Whitney U and Kruskal-Wallis tests where appropriate. Results: Of the 881 patients included in the study, 467 (53%) were male, 414 (47%) female, the median lymph node count was 16 (0-48) and the median LNR in patients with positive nodal disease was 0.13 (0.02-1). There was a significant relationship between increased lymph node retrieval and laparoscopic surgery (p = 0.01), age < 70 (p = 0.021), lower BMI (p = 0.047), right sided tumours (p < 0.001), lymphatic invasion (p = 0.02) and neoadjuvant treatment (n = 0.001). There was a significant relationship between increased LNR and lower BMI (P = 0.022) and lymphatic invasion (p = 0.029). In contrast, lymph node retrieval was not associated with mGPS (p = 0.366), NLR (p = 0.523), PLR (P = 0.180) or LMR (p = 0.571). Similarly, LNR was not associated with mGPS (p = 0.313), NLR (p = 0.362), PLR (p = 0.592) or LMR (p = 0.263). Conclusions: The SIR as measured by a number of validated prognostic scores was not associated with either lymph node retrieval or positivity in patients undergoing elective surgery for colon cancer.
Demographic, clinical, and outcomes characteristics associated with screening colonoscopy in colorectal cancer patients.
Authors: Armstrong Samantha Ann , Shahda Safi , Sehdev Amikar 
Published: March 2017

554 Background: Screening colonoscopy has well established role in CRC prevention. Factors associated with underutilization of screening colonoscopy, and how underutilization affects the CRC outcomes is unclear. We conducted a retrospective study with an aim to identify demographic, clinical and outcome characteristics associated with screening colonoscopy in patients with CRC. Methods: The Indiana Network for Patient Care (INPC) was used to identify patients diagnosed with CRC between 2001-2015. The INPC is the largest and longest tenured clinical data warehouse of the Indiana Health Information Exchange in the USA. Patient demographic (age, race, gender, median household income, insurance type, geographical location), clinical (BMI, year of diagnosis, stage, tumor location, CEA, surgery, chemotherapy, comorbidity) and outcome characteristics were obtained. Only patients who had colonoscopy prior to diagnosis were included, and divided those who received screening colonoscopy versus diagnostic colonoscopy. Chi-square was used for univariate analysis. Multivariate logistic regression was used to model the association of colonoscopy with overall mortality, and CRC-specific mortality. Results: A total of 1546 patients were identified, of which 361 (23.3%) and 1185 (76.6%) had screening and diagnostic colonoscopy, respectively. On univariate analyses, older age, female gender, Caucasian race, lower BMI and lack of insurance, were significantly associated with screening colonoscopy (P < 0.05). Additionally, patients receiving screening colonoscopy had higher likelihood to undergo surgery and receive chemotherapy (P < 0.05). Multivariate analyses adjusted for age, gender, race, surgery, chemotherapy and insurance status showed that screening colonoscopy (as compared with diagnostic colonoscopy) is associated with a 38% lower odds of overall mortality (adjusted OR = 0.62, 95% CI, 0.46-0.83, p < 0.001), and 68% lower odds of CRC-specific mortality (adjusted OR = 0.32, 95% CI, 0.19-0.51, p < 0.001). Conclusions: Screening colonoscopy is associated with decreased odds of overall and CRC-specific mortality and individuals with older age are more likely to receive it.
Correlation between total lesion glycolysis in 18F-FDG PET/CT and KRAS mutation and clinical features in patients with resectable colon cancer.
Authors: Hong Ji Hyung , Byun Jae Ho , Choi Eun Kyoung , Oh Jin Kyoung , Kim Ji-Hun , Lee YS 
Published: March 2017

555 Background: Recently, novel metabolic parameters in 18F-FDG PET/CT such as total lesion glycolysis (TLG) and metabolic tumor volume (MTV) as well as maximum standardized uptake value (SUVmax) have been reported to be prognostic and be related with genomic aberration. We evaluated the prognostic role of these metabolic parameters and the correlation with clinical features in resected colon cancer. Methods: This study included 212 colon cancer patients who underwent surgical resection of stage II and III disease and conducted pre-treatment 18F-FDG PET/CT between February 2009 and December 2013. TLG, MTV of the primary tumors as well as SUVmax were analyzed according to clinical features including KRAS mutation, pre-treatment carcinoembryonic antigen (CEA) and recurrence free survival (RFS). Results: TLG was significantly higher in patients with right colon cancer than those with left colon cancer ( P = 0.015) and in patients with elevated CEA than those with normal range of CEA ( P = 0.034), while MTV and SUVmax were not correlated with cancer location and CEA level. KRAS mutation analysis using peptide nucleic acid-mediated real-time polymerase chain reaction clamping was conducted in 94 patients and forty-one (43.6%) patients showed KRAS mutation in tumor tissues. TLG was significantly higher in patients with mutated KRAS compared with in those with wild KRAS ( P = 0.021). CEA was significantly higher in patients with mutated KRAS than those with wild KRAS ( P-value = 0.024). CEA and TLG could predict KRAS mutation showing odds ratio 1.07 and 1.02 in the multivariate logistic analysis ( P-value = 0.024, 0.048). There was no difference of RFS between in patients with high TLG and in those with low TLG. Conclusions: Based on the result that TLG had a predictive role for KRAS mutation and was related with tumor location and CEA value, we suggested that TLG might reflect genomic alteration and other clinical features as well as tumor burden. It could be useful for differentiating different population of colon cancer and further study is clinically warranted.
Associations between regorafenib-induced adverse events (AEs) and efficacy in metastatic colorectal cancer (mCRC).
Authors: Wakatsuki Takeru , Shinozaki Eiji , Suenaga Mitsukuni , Nakayama Izuma , Matsushima Tomohiro , Osumi Hiroki , Ichimura Takashi , Ogura Mariko , Takahari Daisuke , Ozaka Masato , Chin Keisho , Yamaguchi Kensei 
Published: March 2017

556 Background: It is occasionally recognized that, in molecular targeted therapy, target-specific AEs can surrogate its efficacy, such as skin toxicities and anti-EGFR antibodies. Because of multikinase inhibitor, regorafenib is involved in various kinds of adverse events; however, the clinical associations between AEs and efficacy remain unclear. The aim of this study is to reveal what AEs could surrogate efficacy of regorafenib. Methods: AEs were graded according to CTCAE ver. 4.0. We defined as “CRP increased”, if CRP increased more than 5 mg/dl during treatment compared with the baseline level. Time to treatment failure (TTF) and overall survival (OS) were estimated using Kaplan-Meier methods and compared by the log-rank test. Covariates which were significant in univariate analysis were included in multivariate analysis. Results: One-hundred and two patients were enrolled in this study. Almost all patients were PS 0-1 and received 160mg of regorafenib as an initial dose. The median TTF and the median OS were 2.0 and 8.0 months, respectively. Major AEs were Hand-foot skin reaction (HFSR) in 82.4% (≥Gr3:38.2%), Hypertension (HT) in 39.2% (16.7%), Rash in 23.5% (8.8%), Blood bilirubin increased (BBI) in 58.8% (2.9%), Thrombocytopenia in 48.0% (3.9%), Neutropenia in 20.5% (0%), and CRP increased in 46.1%. Regarding TTF, in univariate analysis, BBI, AST increased Gr0-1, neutropenia, absence of CRP increased, Diarrhea, HFSR, and Rash Gr0-2 were associated with longer TTF. In multivariate analysis, HFSR (HR 0.34 95%CI 0.19-0.63, p = 0.001) and Rash ≥Gr3 (HR 2.43 95%CI 1.13-5.21, p = 0.023) retained to be significant. With respect to OS, in univariate analysis, AST increased Gr0-1, ALT increased Gr0-1, neutropenia, absence of CRP increased, HFSR, and Rash Gr0-2 were associated with longer OS. In multivariate analysis, HFSR (HR 0.47 95%CI 0.24-0.91, p = 0.026), neutropenia (HR 0.54 95%CI 0.30-0.95, p = 0.032) and AST ≥Gr2 (HR 5.72 95%CI 2.11-15.63, p = 0.023) retained to be significant. Conclusions: HFSR and neutropenia might surrogate regorafenib efficacy in mCRC. Elucidation of the mechanisms of these AEs may help to understand which the pathway is the key role of regorafenib treatment in mCRC.
Relationship between primary tumor location and prognosis in metastatic colorectal cancer patients treated with irinotecan/5-FU/leucovorin (FOLFIRI).
Authors: Yu Qianqian , Qiu Hong , Zhang Mingsheng , Yuan Xianglin 
Published: March 2017

557 Background: Clinical trials including CALGB/SWOG 80405 and FIRE-3 reveal differences in overall survival (OS) for metastatic colorectal cancer (mCRC) patients treated with targeted therapy based on primary tumor location. We assessed the impact of tumor location on prognosis in a prospective series of patients with mCRC received FOLFIRI in first-line therapy. Methods: Patients treated with FOLFIRI were consecutively recruited between November 2010 and December 2014. Follow-up information was updated in February 2016 when 77.3% of the patients were deceased. We defined the right-sided colon = cecum to transverse colon, left-sided colon = splenic flexure to sigmoid descending colon, rectum = rectosigmoid plus rectal cancer, respectively. We measured median survival using Kaplan-Meier plots and 2-year survival probability using life tables. Associations between tumor locations and treatment outcomes were estimated using a Cox proportional hazards model. Age and gender were included in adjusted Cox models to estimate the hazard ratio (HR) for death of rectal and left-sided tumors relative to right-sided tumors. Results: Right-sided cancer had a shorter median survival (13.5 vs. 20.4 months) and worse 2-year survival probability (28% vs. 39%) than left-sided and rectal cancers, however the difference was of no statistical significance no matter in unadjusted (HR = 1.002, 95% CI 0.635-1.581) or adjusted models (HR = 1.037, 95% CI 0.657-1.639). Conclusions: mCRC patients with right-sided colon got comparative survival benefit from FOLFIRI in first-line treatment to the left-sided colon and rectum. This result needs to be validated in studies with larger sample size. Clinical trial information: NCT01282658.
Evaluation of systemic inflammation-based prognostic scores in patients with advanced colorectal cancer receiving palliative pelvic radiotherapy (RT).
Authors: Dolan Ross , MacLeod Nicholas James , McSorley Stephen Thomas , Horgan Paul G. , Laird Barry , McMillan Donald C 
Published: March 2017

558 Background: The presence of a systemic inflammatory response (SIR) in patients with advanced cancer is an increasingly recognised prognostic domain and is commonly assessed by the Glasgow Prognostic Score (GPS) and the Neutrophil Lymphocyte Ratio (NLR). However, little work has been carried out to evaluate their role in the field of palliative RT. The aim of the present study was to compare the prognostic value of the GPS and NLR in patients with advanced colorectal cancer receiving palliative pelvic RT. Methods: From a database of all patients undergoing RT in the West of Scotland (2010-2015) patients receiving palliative pelvic RT for colorectal cancer were examined (n = 175). Patients were excluded if they died within 30 days of treatment (n = 15). Demographic data, time from treatment to death/last clinic visit, medical comorbidities, tumour and RT location/dose, CRP, albumin, and differential blood counts were all recorded. GPS, mGPS and NLR were calculated and Cox regression analysis conducted in SPSS. Results: Of the remaining 160 analysed 85 (53%) were male and the median age was 77 (Range: 34-98). The most common clinical indications for palliative radiotherapy were pain (n = 78), bleeding (n = 71) and obstruction/tenesmus (n = 29). Medical comorbidities varied with the most common being hypertension (n- = 75), IHD (n = 36) and diabetes (n = 19). At the time of analysis 130 (81%) of the patients were dead with median survival of 9 months (Range: 1-62 months). On univariate survival analysis Male sex (p = 0.021), GPS (p = 0.015), mGPS (p = 0.028) and NLR ≥ 5 (p = 0.045) but not age > 75 (p = 0.059), Tumour Site (p = 0.637), Performance Status (p = 0.747), ASA (p = 0.525), Delivered Fractions of Radiotherapy (p = 0.062), Dose of RT (p = 0.486) and low Haemoglobin (p = 0.383) were significantly associated with poor survival. On multivariate analysis of the significant variable only male sex (HR: 1.59, 95%CI 1.07-2.36, p = 0.021) and the GPS (HR: 1.47, 95%CI 1.09-1.98, p = 0.011) remained independently associated with survival. Conclusions: In the palliative RT setting systemic inflammation based scores (GPS, mGPS and NLR) had prognostic value and the GPS had independent prognostic value.
Meat and fish consumption and risk of colorectal adenomas in Korea.
Authors: Yang Sun Young , Doo Eun Young , Kim Young Sun , Lee Jung Eun , Youn Jiyoung , Song Ji Hyun , Yim Jeong Yoon , Lim Sun Hee 
Published: March 2017

559 Background: Consumption of red meat and alcohol are known risk factors for colorectal cancer. Colorectal adenomas are considered precursors to colorectal cancer through adenoma-carcinoma sequence. The identification of modifiable risk factors for colorectal adenoma contributes to prevent colorectal cancer from progressing. Many studies have suggested that high red meat or processed meat intake is associated with an increased risk of colorectal adenoma. However, the effect of high fish intake on colorectal adenoma has been insufficient in epidemiological studies. The aim of this study is examine the relationship between meat and fish intake and the risk of colorectal adenoma. Methods: The study enrolled participants who visited Seoul National University Hospital Healthcare System Gangnam Center from May to December, 2011. All participants underwent screening colonoscopy and completed validated food frequency questionnaire. The study sample included 414 adenoma patients, 142 advanced adenoma patients and 1160 polyp-free controls. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between meat and fish and colorectal adenoma using multivariate logistic regression. Results: The intake of total meat, red meat, poultry or processed meat showed no clear association with risk of colorectal adenoma or advanced adenoma. A significant negative association between fish intake and risk of advanced adenoma (OR = 0.51, 95% CI = 0.27 – 0.95, p for trend = 0.0281) after adjusting for confounders such as age, BMI, family history of colorectal cancer, alcohol consumption, smoking status, diabetes, total energy intake, fiber, vegetable/fruit and red meat intake. Conclusions: In conclusion, this study showed no clear relationship between the incidence of colorectal adenoma/advanced adenoma and meat intake. Although, high fish intake and incidence of advanced adenoma showed a significant inverse association in Korean.