bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early colorectal cancer detection on routine CT to improve patient's 5-year survival.
Authors: Rodriguez Ricky , Perkins Bryce Daniel , Park Peter Yong Soo , Koo Phillip , Kundranda Madappa N. , Chang John 
Published: January 2019

593 Background: Prognosis of colorectal cancer (CRC) is greatly influenced by stage at diagnosis. Early colorectal cancer can be subtle on CT scans showing only mild wall thickening, small polyps, or subtle lymph nodes. Identifying these lesions on CT performed for nonspecific symptoms can help identify interval CRC and improve patient outcome. The purpose of the present study is to classify missed CRC on abdominal CT by their imaging features and whether early identification can downstage CRC patients. Methods: A retrospective analysis was conducted of patients (pts) diagnosed with CRC. Data collection included age, gender, ECOG, KRAS mutation status, overall survival (OS). CT obtained prior to and at diagnosis were evaluated. Images were reviewed for multiple CT features including appearance of mass, mesenteric infiltration, abnormal draining lymph nodes, contrast enhancement relative to adjacent mucosa, and intralesional calcifications. Staging was evaluated using available CT scan and based on the TNM staging system for CRC. Results: The 41 pts with 51 prediagnostic CTs from 1/1/2012 - 12/31/2015 had mean age of 68 years (range:44-90 ) Mean ECOG status for the population was 1.46. 41% of the prediagnostic CTs had missed findings. 52 and 43 % of the missed findings were in the rectosigmoid and ascending colon respectively. Of the 15 missed masses, 9 appeared as asymmetric wall thickening, 3 as concentric wall thickening, and 3 as polyps. Of the 14 missed lymph node groups, 2 were excluded due to stability or nonrelated condition. The remaining lymph nodes were found in the associated draining station and averaged 3±1.2 mm in size. On average, the stage at prediagnostic CT was 3A and the diagnostic CT was 3C (p = 0.0015). Average time lapse between prediagnostic and diagnostic CT was 21 months (3-64 months). Conclusions: High percentage of CRC findings are missed on abdominal CT due to their subtle feature, with most misses in the rectosigmoid and ascending colon. A dedicated search can improve detection by specifically looking for polyps, wall thickening, and small lymph nodes in the draining station. Early detection of CRC can improve survival by lowering the stage from 3C to 3A, thus providing 36% improvement in 5-year survival.
The expression of pAKT/survivin and their role in colorectal cancer.
Authors: Gu Junjie , Sun Zhao , Bai Chunmei , Luo Fei 
Published: January 2019

595 Background: Colorectal cancer(CRC) is the fourth most prevalent cancer and the leading cause of cancer mortality worldwide. Drug resistance remains the main obstacle to the success of cytotoxic therapies. It is reported that soluble factors released by carcinoma-associated fibroblasts(CAFs) can induce the translocation of AKT, Survivin, P38 to the nucleus of tumor cells, which might be the mechanism of microenvironment-mediated drug resistance to nonspecific conventional chemotherapeutic agents, such as platinum compounds or 5-FU. Methods: Clinicopathological data of colorectal cancer patients who underwent chemotherapy (XELOX or FOLFOX) were collected, followed up and evaluated. p-AKT and survivin expression were assessed by immunohistochemical (IHC) staining. The relationships between p-AKT and survivin expression and patients’ resistance to chemotherapy were analyzed by Chi square respectively. The expression between p-AKT and survivin expression and progression-free survival(PFS) of patients were analyzed by Kaplan-Meier. Results: 51 CRC patients were enrolled in our research. Among them, 21 patients were resistant to chemotherapy(PD), and 30 patients were sensitive to chemotherapy(PR). P-AKT and survivin were assessed by IHC in 47 patients. Among them, 17 patients were p-AKT positive, and 29 patients were survivin positive. Patients of progressive disease(resistant to chemotherapy) were significantly associated with p-AKT positive and survivin positive(p = 0.009, 0.000). Poorer progression-free survival(PFS) was observed in patients with survivin positive compared to those with survivin negative(6.323±0.9m, 13.857±2.664m, Breslow chi square = 4.885, p value = 0.027). There is no significant difference between p-AKT expression and PFS(Breslow chi square = 2.403, p value = 0.121). Conclusions: CRC patients with p-AKT positive or survivin positive were more likely to be resistant to chemotherapeutic agents. CRC patients with survivin positive had a shorter DFS.
Time to surgery in colon cancer: Predictors and association with survival—An analysis of the National Cancer Database (NCDB).
Authors: Satish Mohan , Aurit Sarah J , Zhang Yang , Walters Ryan W 
Published: January 2019

599 Background: Time-to-surgery (TTS) refers to the wait time from the diagnosis of cancer to surgical resection of the primary tumor. In breast and bladder cancers, longer TTS has been shown to be associated with lower long-term survival. Prior evidence in colon cancer, has shown that older age, urban residence, and comorbidity are independent predictors of TTS. However, evaluation of TTS with survival in colon cancer has been limited to mostly single-center studies. Using the NCDB, this study aimed to both evaluate patient and clinical factors associated with TTS, and determine if TTS was associated with overall survival in colon cancer. Methods: Patients with colon cancer who underwent partial or subtotal colectomy/hemicolectomy were included, excluding those receiving neoadjuvant therapy. With prior colon cancer studies showing a median TTS of 15-20 days, we dichotomized the number of days from diagnosis to definitive surgery (TTS) as ≤ 21 days or > 21 days. A modified Poisson regression model was utilized to evaluate relative risk of TTS > 21 days. Overall survival in association with TTS was estimated using both the Kaplan-Meier method and multivariable Cox regression model, adjusting for patient-, disease- and facility-level characteristics. All analyses were conducted with SAS version 9.4, p-values < 0.05 were considered significant. Results: We identified 26,999 colon cancer patients from 2006-2012 from the NCDB. Approximately 25.7% of patients had a TTS > 21 days. Patients with comorbidities, who were older, were African American, with lower disease stage, and treated in academic facilities located in the Northeast, had a significantly increased relative risk of a TTS > 21 days. Considering survival, a TTS > 21 days was associated with a 24.5% decreased adjusted risk of death (95% CI: 21.6% to 27.2%). Conclusions: A longer TTS with colon cancer is understandably associated with older age, greater comorbidity, and lower stage, but questionably so in African American patients. However, given that TTS > 21 days was associated with a lower adjusted risk of death, it may indicate that a reasonable delay could be pursued for more accurate preoperative evaluation and staging in colon cancer.
BRCA1 and BRCA2 gene mutations and colorectal cancer risk: Systematic review and meta-analysis.
Authors: Oh Mok , McBride Ali , Yun Seongseok , Bhattacharjee Sandipan , Slack Marion , Jeter Joanne M. , Abraham Ivo 
Published: January 2019

605 Background: The risks of breast and ovarian cancer associated with BRCA1 and BRCA2 mutations are well established. Investigations of the association of BRCA mutations and the risk of colorectal cancer(CRC) have yielded conflicting results. We performed a systematic review of published and unpublished studies evaluating BRCA and CRC risk, and meta-analyses to quantify overall CRC risk and in subgroups of BRCA mutation carriers. Methods: Eligible studies were retrieved from PubMed/MEDLINE, Embase, Cochrane, Scopus, and ProQuest Dissertation & Theses. Unadjusted odds ratios were used to derive pooled estimates of CRC risk overall (combined BRCA1/BRCA2) and in subgroups defined by mutation type, comparison group, and study design. Both fixed and random effects models were estimated with the latter having priority. We followed the guidelines summarized in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) as well as the Meta-analysis of Observational Studies in Epidemiology (MOOSE) statements. Results: A total of 18 studies were included in the systematic review: 7 cohort studies comparing to the general population, 5 case-control studies, 4 cohort studies involving pedigree analysis, and 2 kin-cohort studies. Fourteen studies included in the systematic review were used in the meta-analysis. The overall BRCA1/BRCA2 meta-analysis revealed an increased CRC risk in a fixed-effects (OR = 1.22, 95%CI = 1.01-1.48, p = 0.041, I2= 19.5%) but not in a random-effects model (OR = 1.20, 95%CI = 0.96-1.50, p = 0.111). In subgroup random-effects meta-analyses, BRCA1 was associated with increased CRC risk (OR = 1.48, 95%CI = 1.13-1.94, p = 0.005, I2= 3.7%) but BRCA2 was not. Analyses stratified by study design and comparator found no association between BRCA mutation and CRC risk (all 95%CIs crossing 1, all p > 0.05). Conclusions: Although studies differed in their findings about the association between BRCA mutations and CRC risk, meta-analyses revealed a potential 1.22-fold greater risk of CRC in BRCA mutation carriers. This elevated CRC risk was attributable largely to a 1.48-fold greater risk in BRCA1 mutation but not in BRCA2 carriers, regardless of age.
A proteomics analysis of cell signaling pathways in colon cancer.
Authors: Kit Oleg Ivanovich , Vodolazhsky Dmitriy I. , Kutilin Denis S. , Enin Yaroslav S. , Gevorkyan Yuri , Kharin Leonid V. , Panina Svetlana B. 
Published: January 2019

608 Background: Colorectal cancer is the second most common cancer in women and third most common cancer in men. Major signaling pathways are known to be deregulated in cancer, however, there are only a few studies addressing activation status of more than one or two pathways in colorectal cancer in comparison with the normal tissue. The present study aims to compare the expression pattern of proteins associated with cell signaling in paired tumor and non-tumor samples of patients with colon cancer, as well as to define the cluster of proteins to differentiate patients with non-metastatic (Dukes’ grade B) and metastatic (Dukes’ grade C&D) colon cancer. Methods: Frozen tumor and non-tumor samples were collected after tumor resection from 19 patients with colon cancer. The "Panorama" (Sigma-Aldrich) Antibody Microarray-Cell Signaling kits were used for the analyses. The expression ratios of paired tumor/non-tumor samples were calculated for the each protein. We employed R packages ‘samr’, ‘gplots’, ‘supclust’ ( pelora, wilma algorithms), ‘glmnet’ for the differential expression analysis, supervised clustering and penalized logistic regression, respectively. Results: Significance analysis of microarrays revealed 9 up-regulated proteins, including protein kinase C gamma, c-Myc, MDM2, bCOP, p14ARF, p57kip2, GRB2, APP, pan cytokeratin, and 1 down-regulated protein (GAP1) in tumoral mucosa. Pan cytokeratin and amyloid precursor protein were up-regulated in tumor vs. non-tumor tissue, and were selected in the predictive cluster to discriminate colon cancer type. Higher levels of S-100b and phospho-Tau-pSer199/202 were confirmed as the predictors of non-metastatic colon cancer by all of employed regression/clustering methods. Conclusions: Deregulated proteins in colon cancer are involved in oncogenic signal transduction, cell cycle control, and regulation of cytoskeleton formation/transport. Further studies are needed to validate potential protein markers of colon cancer development and metastatic progression.
Tumor-associated macrophages as predictive biomarkers for postoperative adjuvant chemotherapy in patients with stage II colon cancer.
Authors: Xu Jianmin , Feng Qingyang , Chang Wenju , Wei Ye , Ren Li , He Guodong , Zhong Yunshi , Zhu Dexiang , Chen Jingwen , Yi Tuo , Lin Qi , Zheng Peng , Ji Meiling 
Published: January 2019

620 Background: For stage II colon cancer, the effect of postoperative adjuvant chemotherapy is still controversial. It is well known that tumor-associated macrophages (TAMs) play an important role in tumor progression. The aim of this study is to determine the effect of TAMs as predictor for adjuvant chemotherapy for stage II colon cancer. Methods: From July 2009 to June 2012, 521 patients with pathological stage II colon cancer were included. TAMs were detected using tissue microarray and immunohistochemistry (all TAMs detected by CD68; M2 subtype detected by CD206). The density of CD68+ TAMs, CD206+ TAMs and the ratio of CD206+ TAMs / CD68+ TAMs (CD206 / CD68 ratio) were calculated. The cut-off values were defined using X-Tile software. Results: High CD206+ TAMs density and high CD206 / CD68 ratio were significantly associated with reduced disease-free survival (DFS, P < 0.001 and P < 0.001, respectively) and overall survival (OS, P < 0.001 and P < 0.001, respectively). And CD206 / CD68 ratio had a better prognostic power. Furthermore, for patients with low CD206 / CD68 ratio, adjuvant chemotherapy made no benefit. But for high CD206 / CD68 ratio, adjuvant chemotherapy significantly improved DFS and OS (as shown in Table 1). In subgroup analysis, for T3 with high-risk factors or T4 tumors, CD206 / CD68 ratio was also a significant predictor for adjuvant chemotherapy (interaction P = 0.024 in DFS). Conclusions: For stage II colon cancer, CD206 / CD68 ratio was a good prognostic and predictive biomarker for adjuvant chemotherapy. Together with clinicopathological high-risk factors, it might facilitate patient counselling and individualise management. [Table: see text]
Prognostic impact of PD-L1 and PD-1 expression by primary tumor location in colorectal cancer.
Authors: Berntsson Jonna , Larsson Anna , Nodin Bjorn , Eberhard Jakob , Jirstrom Karin 
Published: January 2019

628 Background: A plethora of studies report abundant expression of programmed death-ligand 1 (PD-L1) on tumors to be associated with poor outcome in several cancer forms, whereas immune cell-specific expression of PD-L1 has been associated with improved prognosis in colorectal cancer. However, none of these studies have investigated the association with prognosis according to primary tumor location. This study aimed to investigate the clinicopathological correlates and prognostic impact of PD-L1 and its receptor PD-1 in colorectal cancer, with particular reference to the anatomical subsite of the primary tumor. Methods: Immunohistochemical expression of PD-L1 and PD-1 was analysed in tissue microarrays with tumors from 557 incident cases of CRC from a prospective population-based cohort. Kaplan-Meier and Cox regression analyses were applied to determine the impact of biomarker expression on 5-year overall survival (OS), in the entire cohort and in subgroup analysis of right colon, left colon, and rectum. Results: High PD-L1 expression on tumor-infiltrating immune cells correlated significantly with an improved 5-year OS in univariable and multivariable analysis, adjusted for age, sex, TNM stage, differentiation grade, and vascular invasion, in the full cohort (HR = 0.49; 95 % CI 0.35-0.68), and in primary tumors of the right (HR = 0.43; 95 % CI 0.25-0.74) and the left colon (HR = 0.28; 95 % CI 0.13-0.61), but not in rectal cancer. High tumor-specific PD-L1-expression was not significantly associated with prognosis in neither the full cohort nor according to primary tumor location. High expression of PD-1 on tumor-infiltrating immune cells was significantly associated with an improved 5-year overall survival in the entire cohort (HR = 0.42; 95 % CI 0.21-0.87), but not in subsite analysis according to primary tumor location. Conclusions: This study is, to the best of our knowledge, the first to investigate the prognostic impact of PD-L1 and PD-1 expression according to primary tumor site in colorectal cancer. Dense infiltration of PD-L1+ immune cells was found to be an independent favorable prognostic factor in primary tumors of the right and left colon, but not in the rectum.
Association of increased neutrophil-lymphocyte ratio after curative surgery with prognosis in patients with locally advanced esophagogastric adenocarcinoma.
Authors: Suzuki Akihiro , Kubota Keisuke , Fujikawa Aoi , Taketa Takashi , Sunagawa Hiroki , Ohigashi Seiji , Kishida Akihiro 
Published: January 2019

63 Background: The neutrophil-lymphocyte ratio (NLR) is associated with the inflammatory status of patients with some cancers. We hypothesize that increased NLR was associated with prognosis in patients with stage II/III esophagogastric adenocarcinoma. Methods: We retrospectively analyzed 220 patients with stage II/III gastric cancer who underwent curative resection with suitable lymphadenectomy at our hospital, between 2000 and 2014. All patients underwent baseline staging, including blood tests, computed tomography, and endoscopic biopsy. The relationship between NLR and clinical outcomes was analyzed by univariate and multivariate analyses. Results: Average age was 67.9 [95% confidence interval (CI); 43.8, 92.1] years, and majority of the patients were male. After surgery, 111 (50.5%) patients underwent adjuvant chemotherapy, most of all patients received S-1 according to Japanese treatment guideline. Median follow-up time was 74.8 (95% CI; 69.9, 79.7) months. The preoperative NLR was 3.2 (95% CI; -4.2, 10.6), whereas the postoperative NLR was 3.0 (95% CI; -6.9, 12.8). In univariate analyses, age, stage, preoperative NLR, baseline CA19-9 levels, postoperative white blood cell (WBC) count, postoperative hemoglobin levels, postoperative NLR, increased NLR after surgery and adjuvant chemotherapy were associated with overall survival (OS). In multivariate analyses, age ( p < 0.001), stage ( p = 0.001), and increased NLR after surgery ( p = 0.048) were associated with OS. The prognosis of patients with increased NLR after surgery was observed to be worse than that of those with decreased NLR after surgery ( p = 0.001). Conclusions: Our findings indicated that increased NLR after curative resection was associated with poor OS in patients with locally advanced esophagogastric adenocarcinoma, suggesting that perioperative increased NLR was a potentially useful marker for individual therapy.
Phenotypic subtypes and risk of local recurrence after radical resection for rectal cancer.
Authors: Knight Katrina , Roseweir Antonia K. , Park James Hugh , Edwards Joanne , McMillan Donald C , Horgan Paul G. , Roxburgh Campbell SD 
Published: January 2019

637 Background: Phenotypic subtypes for CRC are reported to stratify outcomes. The four subtypes are based on features within the consensus molecular subtypes (CMS): immune, canonical, latent and stromal. In 81 pts, we recently reported concordance between CMS and phenotypic subtypes. Of note, the stromal subtype matched the CMS4 subtype in 84%. Local recurrence (LR) after rectal cancer surgery remains a problem. Identifying those at risk determines who should receive neoadjuvant therapy (NT) and guides surgery. We evaluated whether phenotypic subtypes are associated with LR after radical treatment of rectal cancer. Methods: From a CRC database, pts with rectal cancer and phenotypic subtyping available were identified. Subtyping was performed based on immune cell infiltrate, stromal volume and tumor proliferation. LR was considered pelvic or peritoneal. Results: Between 1997-2007, 260 pts had surgery for rectal cancer. Most were > 65yrs (63%), male (58%) and TNM stage II (39%) or III (37%). 32 (13%) received NT. For phenotypic subtypes, 88 (35%) were Immune, 47 (19%) Canonical, 48 (19%) Latent and 67 (27%) Stromal. Median FU was 138 months (min 88). 70 pts (27%) developed recurrence: LR in 23 (8.8%) and systemic in 44 (16.9%). LR was associated with higher T stage (pT1-3 7% vs pT4 17%, p = 0.024), presence of vascular invasion (15% vs 6%, p = 0.018), serosal involvement (21% vs 6%, p = 0.001), margin involvement (22% vs 7%, p = 0.010), > 50% tumor stroma (18% vs 3%, p = 0.002) and phenotypic subtype (immune 5%, canonical 6%, latent 4% and stromal = 21%, p = 0.002). Similar LR rates were obtained after excluding pts who had NT: Immune (4%), canonical (4%), latent (5%) and stromal (23%). Of the 23 LRs, most were Stromal subtype (n = 14) vs Immune (n = 4), Canonical (n = 3) and Latent (n = 2). Apart from increased node positivity (50% vs 30-44% p < 0.05), there were no differences in rates of pT4 disease, tumor grade, vascular invasion, serosal involvement and margin positivity between stromal subtype and other groups. Conclusions: LR after rectal cancer surgery was associated with the stromal subtype. Validation is needed but pre-treatment tumor subtyping may identify subsets at risk of LR and have implications for patient selection for neoadjuvant therapy.
Clinical implications of muscle mass and quality in early-stage colorectal cancer (CRC).
Authors: Hopkins Jessica , Baracos Vickie E , Bigam David , Eurich Dean , Sawyer Michael B. 
Published: January 2019

648 Background: Body composition has emerged as a potential prognostic factor for outcomes in early-stage CRC. Specifically, muscle mass and quality and visceral fat have been shown to be related to overall survival (OS) and disease-free survival (DFS). The objective of this study was to determine associations of sarcopenia, reduced skeletal muscle radiodensity (SMR) and visceral obesity (VO) with 5-year OS and DFS. Methods: Muscle and visceral fat at the time of diagnosis were quantified in a retrospective cohort of consecutive, early-stage CRC patients (pts), identified from a prospectively collected cancer database. Skeletal muscle area on computed tomography (CT) was measured and normalized by height (m2) in order to compare skeletal muscle index (SMI) between pts. Mean SMR and visceral fat area were measured. All parameters were analyzed using Kaplan-Meier curves and univariate Cox regression. Sarcopenia was defined as SMI < 41 cm2/m2 in females and < 43 cm2/m2 in males with BMI < 25 kg/m2 and < 53 cm2/m2 with BMI > 25 kg/m2. Reduced SMR was defined as < 41 HU if BMI < 25 kg/m2 and < 33 HU if BMI > 25 kg/m2. VO was defined as VAT > 160cm2 in males and > 80cm2 in females. Results: We identified 968 pts with available CTs and anthropometric data. Prevalence of sarcopenia was 44.5% in males and 59.6% in females. Myosteatosis was present in 60.9% of pts. The mean length of follow up was 5.0 years, with 254 patients developing recurrent disease and 351 deaths. Males with sarcopenia and myosteatosis had worse overall survival (HR, 0.69, p = 0.005; HR 0.49, p < 0.001) but no difference in DFS. Presence of VO was not associated with worse OS or DFS. There was no difference in OS for females with sarcopenia or VO, but myosteatosis predicted reduced OS (HR 0.53, p = 0.004). There was no difference in DFS for females by presence of sarcopenia, myosteatosis or VO. Conclusions: Body composition, specifically sarcopenia and myosteatosis, are highly prevalent in CRC pts treated with curative intent, and their presence is associated with reduced OS. Therefore, skeletal muscle mass and radiodensity are important prognostic factors in CRC outcomes, which are easily attained in a clinical setting.