bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical features and outcome of sporadic colorectal carcinoma in young adults: A single center, cross sectional analysis.
Authors: Zahir Muhammad Nauman , Mahpara Eisha , Rafiq Sobia , Ghias Kulsoom , Shabbir-Moosajee Munira 
Published: March 2020

e14680 Background: Early onset colorectal carcinoma (CRC), defined as CRC at age below 45 years is rare. However, an increasing incidence has been noted in Southeast Asia. It is hypothesized to be a biologically and clinically distinct entity personifying aggressive disease and a worse survival. Data on this subject is scarce from this part of the world and hence our objective was to study the clinical presentation and outcome of early onset sporadic CRC in patients at a single tertiary care center in Pakistan. Methods: Data was collected by a retrospective chart review. 131 patients were found eligible for the period between January 1, 2004 and December 31, 2011. A pre-designed and coded questionnaire was used and analysis was done using SPSS. Cox proportional hazard model was used to compute prevalence ratios. Results: Early onset sporadic CRC accounted for 32% of all CRC treated in the specified time period. Colon and rectal cancers accounted for 55% and 45% of patients respectively. The median age was 35 years (range 16-45 years) and the male to female ratio was 2:1. 74% of patients presented with advanced stage disease [stages III (45%) and IV (29%)]. On comparison, bleeding per rectum, signet ring morphology, stage and grade of tumor were found to be statistically significant for the rectal cancer group on a univariate analysis. 93% of rectal carcinoma patients received appropriate surgery and/or neoadjuvant/adjuvant therapy as opposed to 69% of colon cancers. Median survival was 19 months (range 0-112.5 months). However, Kaplan-Meier analysis revealed a trend towards an inferior survival for rectal carcinoma 2 years after initial diagnosis (p=0.56). Conclusions: Higher incidence of early onset CRC is noted in our population as compared to the western literature. Rectal carcinoma accounts for almost half the patients in this young CRC population. This group was found to have a higher frequency of poor prognostic factors. However, we have noted a similar 2 year survival between the 2 groups, with a trend towards an inferior prognosis with longer followup. It is possible that a larger sample size may have elucidated a statistically significant difference between the two groups.
Comparison of predictors of survival in colon and rectal cancer patients.
Authors: Tang Ying Margie , Okoronkwo Nneoma Olivia , Patel Neal , Chang Victor Tsu-Shih , Wang Trent P , Barnes Tanganyika , Kasimis Basil , McPherson Monica , Crump Barbara , Zhong Fengming 
Published: March 2020

e14681 Background: We studied comorbidity and other predictors of survival for patients (pts) with colorectal cancer (CRC) and compared pts with colon (C) vs rectal (R) cancer (ca). Methods: In an IRB-approved protocol, we reviewed the records of pts diagnosed with CRC at a VA medical center from 01/01/2003 to 12/31/2011 for demographics, stage, grade, ECOG performance status (PS), CEA, Hemoglobin (HGB), and Albumin (ALB) at diagnosis (dx). Comorbidity was assessed with the Charlson Comorbidity Index (CCI), the Cumulative Illness Rating Scales (CIRS), and the Kaplan-Feinstein Index (KFI). Statistical analyses were performed with SAS 9.2/Stata 11.0. We compared the pts with C vs R ca. Results: There were 279 men. 191 pts (68.5%) had C ca and 88 pts (31.5%) had R Ca. The two groups were similar for stage, grade, age, HGB, CEA, ALB, and ECOG PS. For R ca pts, Median (M) CCI is 3.7 (0.4-13.9), M CIRS15 2.5 (0-5), M CIRS16 5 (0-13), M CIRS 17 2.0 (0-8), M CIRS18 0 (0-1), M CIRS19 0 (0-1), and M KFI 1 (0-3). For C ca pts, M CCI is 4.3 (0.9-19.6), M CIRS15 3.0 (0-6), M CIRS16 6.0 (0-13), M CIRS17 2.0 (0-9), M CIRS18 0 (0-1), M CIRS19 0 (0-2), and M KFI 2 (0-3). In univariate analysis, stage, ECOG PS, HGB, and ALB were significant survival predictors in R ca pts. Age, stage, grade, ECOG PS, HGB, CCI, CIRS16, CIRS17, CIRS19 and KFI were significant for C ca pts. Other significant multivariate predictors are summarized in the table. R ca pts are more likely to die (P=0.003, HR=0.51). Conclusions: In this larger population of pts with CRC, we confirmed our previous findings (ASCO 2012 e14125). Grade, stage, ECOG PS, and CIRS 19 are important independent survival predictors for veterans with CRC. Age, grade, stage, ECOG PS, CCI, CIRS 16 and CIRS 19 are independent predictors for colon ca pts. Only Stage and ECOG PS are independent predictors for rectal ca pts. Rectal ca pts are at increased risk of dying. More research is needed to confirm this. Supported by New Jersey Commission for Cancer Research. [Table: see text]
Association of the polymorphisms of the tandem repeat sequence in the thymidylate synthase gene with tumor stage in colon cancer.
Authors: Aguiar Samuel , Olivieri Eloisa , Carraro Dirce Maria , Mello Celso Lopes , Fanelli Marcelo , Lopes Ademar 
Published: March 2020

e14688 Background: Thymidylate synthase (TS) plays an important role in colorectal carcinogenesis and response to 5FU-based chemotherapy. TS expression can be modified due to polymorphisms in the 5'-untranslated region (5’-UTR) of the gene. The aim of this study is to investigate the association between TS polymorphisms with clinicopathological characteristics of colon carcinomas. Methods: we retrospectively studied 89 individuals with high risk stage II (obstruction, T4 stage, presence of lymphovascular invasion or preoperative CEA > 5.0) and stage III patients submitted to curative intent surgery. DNA was extracted from paraffin embedded tumor tissues and sequenced. The polymorphism studied was the variation of the number of the repeated 28-bp sequences (3 or 2 repeats) of the TS gene 5’-UTR. Results: The frequency of the polymorphisms was: 2R2R in 26 cases (29.2%), 2R3R in 36 cases (40.4%), and 3R3R in 27 cases (30.3%). We did not find associations between the frequencies of these polymorphisms and age, gender, presence of lymphovascular invasion, or level of preoperative CEA. We find a significantly higher proportion of T4 tumors between the 3R3R genotype compared with the 2R2R and 2R3R genotypes (OR=2.69; 95% CI: 1.05 – 6.94; p=0.04). By the other hand, a significantly lower proportion of positive lymph nodes were found among patients with tumors presenting the 3R3R genotype, by comparing with the 2R2R and 2R3R subgroup (OR: 0.28; 95%CI: 0.10 – 0.72; p=0.01). Five-year disease free survival and overall survival were, respectively, 81% and 85% among patients with tumors presenting the 3R3R genotype, and 62% and 67% among patients with tumors presenting 2R2R or 2R3R genotypes. These differences were not statistically significant. Conclusions: in this sample, the TS polymorphic tumor genotype 3R3R was associated with lower risk of lymph node metastases in colon carcinomas.
Role of clinical variables for predicting pathologic response to neoadjuvant chemoradiation in locally advanced rectal cancer.
Authors: Taglietti Paula Mendonca , Aguiar Samuel , Amor Divino Paulo Henrique , Begnami Maria D. , Batista Ranyell Spencer Sobreira , Mello Celso Lopes , Lopes Ademar 
Published: March 2020

e14691 Background: pathologic response to neoadjuvant chemoradiation is a strong prognostic factor for rectal cancer. Some studies have suggesting a wait and see approach for rectal cancer after clinical complete response to chemoradiation. In this study, we tried to identify clinical predictive factors of pathologic response to neoadjuvant chemoradiation. Methods: we retrospectively reviewed data of 129 patients from a prospective database, treated between January, 2008 and December, 2012. Patients with mid and low rectal adenocarcinoma, clinically staged (MRI) as T3,T4 any N or any T, N+, received pre-operative chemoradiation, which consists in 5040 cGy, concomitant to 5-FU-based chemotherapy. All patients were operated, by radical TME procedures. The clinical variables analyzed were: age, gender, distance from dentate line, cT stage, cN stage, pre-treatment CEA level, NIH toxicity during chemoradiation, endoscopic assessment of response, and interval between the end of radiation and surgery. We investigate associations between these variables with complete pathological response (cPR) and “good” pathological response (gPR), defined as ypT0orT1 N0. Results: the rate of cPR was 20.2%. The rate of gPR was 31.8%. For predicting cPR, only the endoscopic assessment of response showed significant association with cPR. Among 18 patients with complete endoscopic response, 8 (44.4%) confirmed cPR after resection. Among 93 patients with endoscopic findings suggesting residual disease, 14 (15.1%) presented cPR (p=0.008). 55.6% (10/18) of patients with complete endoscopic response still have microscopic residual disease in the resected specimen. For predicting gPR, only the cN staging was significantly associated with ypT0orT1 N0 (23.9% of gPR among cN+ patients against 41.3% among cN0 patients; p=0.038). Conclusions: clinical tools are very poor for predicting pathological response to neoadjuvant chemoradiation therapy in patients with locally advanced rectal carcinomas. Despite endoscopic assessment of response by retoscopy have showed significant association with cPR, the predictive value was weak.
Ovarian metastases in colorectal carcinoma.
Authors: Yucel Idris , Erdem Dilek , Yilmaz Bahiddin , Gonullu Guzin 
Published: March 2020

e14697 Background: 5-30 % of all ovarian tumors are metastatic and only 3-14 % of them derive from gastrointestinal tract. The aim of this study is to determine the rate of colorectal cancer patients with ovarian metastases and also to identify the features in the management of these patients. Methods: 972 colorectal cancer patients admitted to our clinic between 01/2001 and 12/2011 were included in the study. Among these patients, only 9 had ovarian metastases. Age, menopausal status, initial symptom, operation status, localisation of colorectal tumor, stage at diagnosis, tumor grade, histopathological type, colorectal tumor-ovarian metastases interval, having synchronous or metachronous metastases, the place of metastases and concurrent metastatic disease were evaluated. SPSS 16 is used. Results: Mean age of patients was 45 years (range between 21-72 years). 66.7 % had premenopausal state. 55 % of them had right colon tumor. 5 patients had stage IV disease. 5 patients had synchronous metastases (55 %). Colorectal cancer-ovarian metastases interval was 6-49 months in the patients with metachronous metastases. Among patients; 5 had right and 1 had left ovarian metastases and 3 had metastases to both ovaries. 2 of 3 bilateral ovarian metastases were derived from right-sided tumors (66.6 %). 7 patients also had metastases to other different parts and most of those had peritoneal involvement (85.7 %). PFS was between 2 and 27 months. At the time of ovarian metastases, 7 patients had high CA 125 levels and 3 had high CEA levels. All patients with high levels of CA 125 during diagnosis continued to have high levels of CA 125 with ovarian metastases. Conclusions: Premenopausal patients seem to have higher risk of ovarian metastases. This study support that examining CA 125 levels in colorectal cancer patients who have abnormal findings in the gynecological examination preoperatively may help not to miss synchronous ovarian metastases.The finding of ovarian metastases should make consideration that the disease is disseminated. Ovaries should be examined preoperatively and it should be kept in mind that CA 125 levels may be a valuable marker in this setting.
Clinical colorectal cancer (CRC) subsets in advanced disease: Patterns of metastatic spread to predict survival.
Authors: Bourlon María Teresa , Carpinteyro-Espin Paulina , Mora-Pineda Mauricio De Jesus , Gamboa-Dominguez Armando , Huitzil-Melendez Fidel David 
Published: March 2020

e14703 Background: Advanced CRC is a heterogeneous disease. Some patients exhibit diffuse metastatic spread while others show selective organ involvement. We aimed to investigate the frequency and survival implications of initial pattern of metastatic spread in a Mexican cohort. Methods: We retrospectively reviewed charts and radiologic images of patients with advanced CRC at our institution from 2004 to 2011. The initial pattern of spread was recorded. Categories depending on the predominant site of involvement were: 1) Locally advanced, 2) Hepatic, 3) Pulmonary, 4) Peritoneal or 5) Diffuse. Survival was estimated by the Kaplan Meier method and Log rank test used to determine survival differences among categories. Results: 179 patients with advanced CRC were identified. Median age was 60yo, 56% were male. Primary tumor location was 50.3% colon, 27.9% rectum, 17.9% recto-sigmoid and 3.4% had synchronous disease. 66% of patients had advanced disease at diagnosis and 34% were recurrent cases. Metastasis at diagnosis involved the liver in 105 (58.7%), peritoneum in 49 (27.4%), lung in 56 (31.3%) and non regional lymph nodes in 36 (20.1%) patients. Notably, 101 (56%) patients had a predominant site of metastatic involvement: locally advanced in 3 (1.7%), hepatic in 51 (28.5%), peritoneal in 21 (11.7%), pulmonary 21 (11.7%) while 78 patients (44%) had disseminated disease. Median overall survival was 15 months (n= 179) and differed according to predefined CRC subsets: 9, 13, 22, 23, and 52 months for peritoneal, disseminated, hepatic, locally advanced and pulmonary spread respectively p=.018 (significant after multivariate analysis). Other factors associated with better survival were female gender p=.040, absence of morbidity from primary tumor p=.27, resection of primary tumor p=.004, recurrent presentation p=.039, and access to 1stline chemotherapy p=.00. Conclusions: Over 50% of patients exhibited selective metastatic spread. Clinically defined subsets correlate with better (pulmonary) or worse (peritoneal/disseminated) survival. This finding might have implications in patient selection for regional therapies and encourage research to find the molecular determinants of this biologic behavior.
Defective mismatch repair proteins and microsatellite instability in young Mexican patients with colorectal cancer.
Authors: Quintanilla Guzman Arturo , Luevano Gonzalez Arturo , Rojas Martinez Augusto , Flores Gutierrez Juan Pablo , Gonzalez Guerrero Juan Francisco , Rios Ibarra Clara Patricia , Lopez Chuken Yamil Alonso , Rodriguez Silva Claudia , Ortiz Lopez Rocio 
Published: March 2020

e14708 Background: Colorectal carcinoma (CRC) is prevalent malignancy and a third of the cases affect young patients. 15% of CRC have microsatellite instability (MSI) due to disruptions in mismatch repair (MMR) genes, like germline mutations (3%) and hypermethylation of the MLH1 gene promoter associated to the BRAF V600E mutation (12%). The aim of this work was to assess MMR abnormalities in tumors of Mexican CRC patients under 50 years old. Methods: CRC paraffin-embedded tissues of 47 patients with available demographic/clinical data were studied by immunohistochemistry (IHC) for MLH1/MSH2, qPCR with specific probes/sequencing for the BRAF V600E mutation, and conventional PCR (5 markers) for MSI analysis. Results: Female:Male ratio was 0.81:1. Most of the cases were classified as TNM Stage II, were located in the cecum, invaded the serous coat, and showed intestinal-type histology. 20 samples showed alterations in MMR protein expression. MLH1, MSH2, and combined deficiency of both proteins were detected in 17, 4, and 4 tumors, respectively. No BRAF mutations were detected. MSI analysis restricted to the 20 altered IHC samples showed MSI in 10 tumors (3 MSI-low and 7 MSI-high tumors). The four cases with MLH1/MSH2 deficiency, showed MSI-high pattern. Conclusions: We found 42.6% cases with defective MMR expression. No epigenetic abnormalities associated to BRAF V600E mutation were registered. The lack of MSI in ten tumors with deficient MMR may be due to alternate DNA repair mechanisms. Acknowledgments. Work supported by the CHIBCHA Project (European Commission7FP grant #223678).
Diabetes as a predictor of colon cancer prognosis: A single institution based retrospective data analysis.
Authors: Ammannagari Nischala , Patel Anush V. , Bravin Eric N. , Scribani Melissa , Victory Jennifer 
Published: March 2020

e14709 Background: Prevalence of Diabetes mellitus (DM) has increased in dramatic proportions globally over last few decades. Several observational epidemiological studies have shown increased risk of colorectal malignancies in patients with DM. However, it is not yet clearly understood if DM can impact the prognosis of colon cancer. Methods: The hospital’s cancer registry was used to identify advanced (stage III or IV) colon cancer cases diagnosed from January 2007 to December 2009. To be included in the study, the patient must have been treated with a 5-Fluoro Uracil based chemotherapy regimen. Retrospective chart review of electronic medical records was used to collect patient characteristics, including diabetes mellitus (DM) status. Kaplan-Meier curves were constructed for disease free survival and overall survival time. These survival curves were compared between diabetics and non-diabetics using the log rank test. Results: A total of 40 subjects met inclusion criteria, with a mean age of 64.6 years. Compared to non-diabetic patients, patients with diabetes had significantly poorer disease free survival (p=0.03). There was no difference in overall survival when comparing diabetic patients to non-diabetics (p=0.47). Conclusions: While taking into consideration that the study was under powered due to the small sample size, this study does raise the possibility that diabetes mellitus might be an important prognostic indicator of colon cancer. Management of diabetes must be emphasized as an integral part of care of colon cancer.
Plasma TIMP-1 in patients with metastatic colorectal cancer treated with first-line oxaliplatin-based therapy with or without cetuximab: Results from the Nordic VII study.
Authors: Tarpgaard Line Schmidt , Guren Tormod Kyrre , Glimelius Bengt , Sorbye Halfdan , Ikdahl Tone , Christensen Ib Jarle , Qvortrup Camilla , Kure Elin , Pfeifer Per , Nielsen Hans J. , Brünner Nils 
Published: March 2020

e14710 Background: Plasma Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) is a biomarker in patients with metastatic colorectal cancer (mCRC). TIMP-1 inhibits matrix metalloproteinases and has tumor promoting functions. High levels of TIMP-1 associate with reduced sensitivity to irinotecan-based but not oxaliplatin-based treatment in patients with mCRC. Based on our prior studies, we here tested the hypothesis that high pretreatment plasma TIMP-1 correlate with short overall survival (OS) and short progression-free survival (PFS) but not response rate (RR) in patients with mCRC included in the NORDIC VII Study in which patients received oxaliplatin-based therapy. Methods: In the NORDIC VII Study patients were randomized to: A) Nordic FLOX; B) Nordic FLOX + cetuximab or C) Nordic FLOX intermittently + cetuximab continuously. Plasma samples for TIMP-1 analysis were available from 426 patients. Plasma TIMP-1 was determined using the MAC15 antibody in-house validated kinetic ELISA. Results: The three study populations were comparable and not different from the total intention to treat population. The median pretreatment plasma TIMP-1 was 269 ng/mL (58-1318 ng/mL). KRAS mutated in 149 patients (35%). There was no interaction between treatment arms and pretreatment plasma TIMP-1 either for PFS (p = 0.16) or OS (p = 0.64). High pretreatment plasma TIMP-1 was associated with shorter PFS (HR=1.22, 1.07-1.39, p=0.003) and shorter OS (HR=1.55, 1.36-1.80, p<0.0001). RR did not correlate significantly to pretreatment plasma TIMP-1 (OR=1.16, 0.91-1.49, p=0.22). Multivariate analysis (TIMP-1, Köhne index, KRAS and BRAF status, CRP, CEA, age, gender) demonstrated that high pretreatment plasma TIMP-1 was not an independent biomarker of PFS (HR=1.06, 0.88-1.28, p=0.52) or OS (HR=1.19, 0.96-1.47, p=0.11). Conclusions: Plasma TIMP-1 is a prognostic biomarker in patients with mCRC treated with 1st line oxaliplatin-based therapy +/- cetuximab. A predictive effect of plasma TIMP-1 could only be estimated for cetuximab treatment, and no significant treatment by marker interaction was observed.
Prediction of tumor recurrence by tumor location in stage II and III colon cancer patients through common germ-line variants of genes involved in wnt signaling pathway.
Authors: Zhang Wu , Ning Yan , Yang Dongyun , Wakatsuki Takeru , Stintzing Sebastian , Volz Nico Benjamin , Li Joseph Ethan , Labonte Melissa Janae , El-Khoueiry Rita Elie , Barzi Afsaneh , El-Khoueiry Anthony B. , Kahn Michael , Lenz Heinz-Josef 
Published: March 2020

e14714 Background: Wnt signaling is essential for embryonic development, stem cells and tissue regeneration. The Wnt signaling pathway was found to be deregulated in 93% of colorectal cancer (CRC). Tumor recurrence after curative resection is still a major problem in the management of adjuvant CRC, with recurrence rate approximately 30-40%. Identifying molecular markers for tumor recurrence is critical for successfully selecting patients who are more likely to benefit from adjuvant chemotherapy. In this study, our group tested whether gene polymorphisms [TCF7L2 rs7903146, AXIN2 (rs2240308, rs3923087) and P300 (rs7286979, rs220551 and rs5782022)] involved in Wnt signaling pathway could predict the risk of tumor recurrence in stage II and III CRC patients. Methods: Either blood or FFPE tissue specimens were obtained from 234 patients (107 females and 127 males; median age 59 years (range 22–78 years)) with stage II (105 patients) or III (129 patients) colon cancer at the University of Southern California/Norris Comprehensive Cancer Center. The median follow-up was 4.4 years. TCF7L2, AXIN2 and p300 SNPs were determined by PCR-RFLP or PCR-based direct sequence. The primary endpoint of the study was time to tumor recurrence (TTR). Results: In univariate analysis, patients with TCF7L2 rs7903146 TT genotype had significantly longer TTR (median=10.7 months, 95%CI 4.9,10.7 +) compared with those harboring CT (median=3.9months, 95% CI 2.4, 10.7) or CC genotype (median=5.9months, 95% CI 2.8, 11.4+) patients (p=0.042, log-rank test). In multivariate analysis, left-side tumor patients with p300 rs7286979 AA genotype had highest risk of TTR (HR=2.85, 95% CI 1.03,7.89) compared to those carring GA (HR=0.81, 95% CI 0.35,1.84) or AA genotype (p=0.048, Wald test). Conclusions: Our results show that germline polymorphisms profiling of Wnt signaling pathway TCF7L2 rs7903146, p300 rs7286979 may predict tumor recurrence risk in adjuvant colon cancer patients, and may dependent on tumor location. Our exploratory data warrants further validation.