bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gender disparities in anal cancer incidence and mortality: A long-term US population-based analysis.
Authors: Baidoun Firas , Saad Anas M , Gad Mohamed , Asfari Mohammad Maysara , Sarmini Muhammad Talal , Elkeraie Yasmine , Alkehef Yazan , Al-Husseini Muneer J. , Alhaj Moustafa Muhamad 
Published: May 2020

e16059 Background: Anal cancer is an uncommon malignancy accounting for less than 3% of gastrointestinal malignancies in the US. In this large database study, we aimed to re-evaluate the difference in the incidence and mortality trend in both genders. Methods: We used SEER 18 database to study anal cancer cases in the US during 2000-2016. Incidence and mortality rates of anal cancer were calculated by gender and were expressed by 1,000,000 person-years. Annual percent change (APC) was calculated using join point regression software. Results: We reviewed 25,418 patients with anal cancer, of which 61.4% were females. Incidence of anal cancers was 14.375 and 19.427 per 1,000,000 person-years, in males and females, respectively. Incidence rates of anal cancer significantly increased over the study period, but this increase was sharper in females (APC = 2.220%, 95%CI [1.924-2.517], P < .001) when compared to males (APC = 0.915%, 95%CI [0.303-1.531], P = .006). Mortality rates from anal cancer over the study period were 7.425 and 7.532 per 1,000,000 person-years, in males and females, respectively. Overall anal cancer mortality rates did not change between 2000-2009 but started to decrease starting from 2010 and this decrease became sharpest between 2014-2016; APC = -44.905%, 95%CI [-57.572- -28.457], P = .001). Mortality rates followed the same trend in both genders. Conclusions: Anal cancer incidence is increasing with significant increase in the incidence trend is noticed in females compared to males which is a change from the previous trend that was seen from 1973-2000. On the other hand, anal cancer mortality has started to decrease for the first time starting from 2010 with no difference in the mortality trend between males and females. This improvement in mortality rate can be explained by the improvement in early detection rate and possibly improvement in the treatment approach for these high-risk patients.
Immune tolerance to colon cancer is mediated by colon dysbiosis: Human results and experimental In Vivo validation.
Authors: Bergsten Emma , Mestivier Denis , Amiot Aurelien , DeAngelis Nicola , Khazaie Khashayarsha , Sobhani Iradj 
Published: May 2020

e16062 Background: Lynch syndrome (Ly) but not Sporadic (Sp) CRC patients are responsive to immunotherapies. We have shown micorbiota from CRC patients induces precancerous colonic lesions in germ-free mice. The aim was to investigate microbiota linked compromised anti tumor immune response. Methods: We compared 1) Whole metagenomic fecal microbiotas of CRC patients [Sp, n = 53+Ly, n = 19] to controls (n = 90) or being first degree relatives of Ly patients (n = 14), respectively; 2) Tumoral to normal mucosa-adherent microbiota (16sRNA sequences); 3) Normal to tumoral tissues’ mRNA RT-PCRs of IL1b, IL4, IL6, IL8, IL17, TNFa, TGFb, FasL, Granzyme A&B, Thy1; 4) CD3, CD4, CD8, Granzym, KL1, FoxP3, RORgT, MastCell, cells in tumor tissues quantified by immunohistochemistry (IHC), between subgroups. Associations between bacteria, tissue immune cell infiltrates and clinical data (3-yrs follow up or death) were established by using unsupervised Systems Biology and Bioinformatics analyses (Institut Pasteur Shaman platform and Qlucor program). Anti tumoral immune response links with bacteria were based on differences between Ly and Sp CRC patients. Tumor tolerance links with bacteria were identified using germ-free mice (n = 185) who orally received microbiota (9 Sp CRC patients vs 9 controls) with colonic mucosa examined 3 months after human fecal transfer (whole exome sequencing, methylchips, IHC for CD3, CD11b, FoxP3, RORgT, ILC3). Results: Enrichment in Peptostreptococcus, Thermodesulfovibrio and diminution in Ruminococcus, Eubacterium, Coprococcus were linked with FoxP3 and IL-17 over expressions in tumor tissues. Enrichment in Escherichia, Enterobacter, Thioalkalimicrobium, and diminution in Eubacterium, Faecalibacterium and Butyrovibrio were associated with higher FoxP3, FasL, Granzyms A&B, Perforin, Thy1 mRNAs/mRNACD3. Diminution of Eubacterium, Dorea, Faecalibacterium genera and enrichment in Fusobacterium, E. Coli/Shigella were associated with higher CD3, FoxP3, GranzymA and B and FOXP3-RORgT cells in tumor tissues. Higher fecal enrichments in oral bacteria (parvimonas micra) and lack of Thermodesulfovibrio enrichment were associated with higher FoxP3-RORgt cells and short survival; in mice ILC3 and FoxP3-RORgT cells were linked with Sp CRC dysbiosis. Species linked with immunotolerance are identified. Conclusions: Fecal and tissue microbiota can impact failure of anti tumoral immune response in sporadic CRC patients by enhancing overexpression of IL-17 and reducing cytotoxic T-cell infiltration in tumors. Clinical trial information: NCT01270360 .
Mutation profile of colon cancer in hispanic population of central California.
Authors: Hinduja Sanjay , Ali Mir , Bukari Mohammed SANI , Chaudhary Uzair Bashir , Mortenson Tanner , Mahmood Omar , Lee Matthew , Chaudhary Fihr 
Published: May 2020

e16067 Background: The clinical and mutational profile of Hispanic patients with metastatic colon cancer is not well documented. In this retrospective study, we aim to describe the clinical and mutational profile of Hispanic patients with metastatic colon cancer in central California. Methods: We retrospectively evaluated the clinical and mutational profile of colon cancer at a single institution in Fresno, California from 2010-2019. We selected 136 patients out of which 70 patients self-identified as Hispanic and 66 self-identified as non-Hispanic. We studied clinical parameters and next-generation sequencing via Foundation one testing for these patients. Results: Among Hispanics, there were 43(61%) males and 27(38%) females. The median age at diagnosis was similar in both groups at 57. Right sided colon cancer accounted for 52% of Hispanic patients versus 40% in non-Hispanics. Fifty two percent of Hispanic patients presented with metastatic disease versus 45% in non-Hispanics. The frequency of commonly mutated genes in colon cancer in Hispanics versus non-Hispanics are as follows. KRAS (35.7% vs 37%), NRAS (11% vs 4%) BRAF (8% vs 7%), Her2/neu 0% in both groups. The frequency of other mutations such as TP53, APC, ATM, PTEN, CDKN2A, Myc amplification were also noted to be similar in both groups. PIK3CA mutation was seen in 18.6% of Hispanic patients versus 34% in non-Hispanic population which was statistically significant with a p value = 0.032. Microsatellite instability (MSI) was seen at 3.3% in Hispanics versus 10.6% in non-Hispanics. Tumor mutational burden was similar in both groups. Conclusions: The frequency of actionable mutations was similar in both Hispanic and non-Hispanic patients. Hispanics were noted to have lower PIK3CA and microsatellite instability. Metastatic disease and right sided colon cancer were seen at higher frequency in Hispanic population. Our results were similar to another population-based study which analyzed KRAS mutation with colon cancer patients in Puerto Rico[1]. Larger population based studies would be needed to further assess the differences in this patient population. Ruiz-Candelaria, Y., C. Miranda-Diaz, and R.F. Hunter-Mellado, K-RAS mutation profile in Puerto Rican patients with colorectal cancer: trends from April 2009 to January 2011. Int J Biol Markers, 2013. 28(4): p. e393-7.
Do differences in the microbiome explain early onset in colon cancer?
Authors: Keshinro Ajaratu , Vanderbilt Chad , Stadler Zsofia Kinga , Shia Jinru , Gonen Mithat , Chen Ching-Tung , Cercek Andrea , Mendelsohn Robin B , Yaeger Rona , Zehir Ahmet , Bowman Anita , Weiser Martin R. 
Published: May 2020

e16070 Background: Intestinal dysbiosis has been hypothesized as a possible etiology of the increasing incidence of early-onset colon cancer (EO-CC). Here, we compare the microbiome signature in nonmetastatic, microsatellite stable (MSS) EO-CC to average-onset colon cancer (AO-CC). Methods: Specimens from patients with resected stage I-III MSS colon cancer from 2014-2019 were sequenced by MSK-IMPACT, a large panel next generation sequencing (NGS) assay. A validated technique using non-human read sequences from NGS analysis was used to identify the microbial species in tumor tissue. The tumor microbial alpha diversity and differentially abundant microbiome were compared between patients younger than 40 years (EO-CC) with those older than 60 years (AO-CC). Results: Of 275 patients with MSS, 24 (mean 33.6, range 24-39) and 114 patients (mean 70, range 61-90) had EO-CC and AO-CC, respectively. There was no significant difference in clinicopathological features including gender, tumor stage and neoadjuvant treatment between the two groups. EO-CC was more likely to present with left sided disease compared to AO-CC (81% vs. 45%, p = 0.001). There was no significant difference in the tumor microbial diversity (alpha diversity) between the EO-CC and AO-CC (pShannon= 0.95). Although there was a relative abundance of microbial species from bacterial phylum such as Actinobacteria, Deinococcus-Thermus, α-proteobacteria, γ-proteobacteria and δ-proteobacteria in EO-CC compared to AO-CC, this difference was not significant after controlling for multiple comparisons (Table). Conclusions: Our analysis did not reveal a significant difference between EO-CC and AO-CC in both the abundance and diversity of tumor microbial species, suggesting intestinal dysbiosis may not be a major driver in early onset colorectal cancer pathogenesis. However, additional studies with a larger sample size are warranted for further analysis and subgroup comparison. [Table: see text]
A multi-institution analysis of molecular biomarkers in patients with metastatic colorectal cancer in ethnically diverse populations.
Authors: Choudhary Zunaira H , Advani Shailesh M , Ashai Nadia , Tariq Sara , Grothey Axel , Kopetz Scott , Rajdev Lakshmi 
Published: May 2020

e16074 Background: Differences in clinical outcomes for metastatic CRC (mCRC) have been reported across racial-ethnic groups, particularly between Hispanics (HA), non-Hispanic Blacks (NHB), and non-Hispanic Whites (NHW), with limited information available among Asian Americans (AA). We examined if there were differences in clinical outcomes by molecular drivers between these groups in a pooled analysis of two institutions serving ethnically diverse patient populations. Methods: We retrospectively examined 1927 mCRC patients from Montefiore Medical Center and the University of Texas MD Anderson Cancer Center. Mutations in KRAS, NRAS, and BRAF were determined by polymerase chain reaction or next generation sequencing. Mutations were then correlated with overall survival (OS). Results: Our patient population consisted of 1153 (61%) NHW, 314 (17%) HA, 320 (17%) NHB and 59 (3.1%) AA. Across subgroups, borderline significant difference in prevalence of BRAF mutation was observed (p = 0.04), with higher prevalence observed among NHW as compared to other groups. No differences were observed for KRAS and NRAS mutation prevalence. In univariate analysis, the median survival for BRAF MT tumors was 18.5 months vs 32 months for BRAF WT tumors (p < 0.0001). Similarly, median OS for KRAS WT, KRAS MT, NRAS WT and NRAS MT was 29.3, 27.4, 31 and 31.5 months respectively, with no differences between groups. In subgroup analysis by race/ethnicity, median OS in BRAF MT NHW was 19.98 months vs 33.48 in BRAF WT NHW (p < 0.0001). Similar trends were observed in HA and NHB. No differences in median OS were observed by KRAS or NRAS mutation status across racial-ethnic groups. Conclusions: This multi-institution study found no meaningful difference in the prevalence of molecular drivers across racial-ethnic groups. Additionally, in our subgroup analyses, OS based on the presence of a specific molecular driver mutation did not seem to vary by race. For example, RAS mutated and BRAF mutated patients showed similar OS across racial-ethnic groups. Our study demonstrates that reported differences in clinical outcomes by race and ethnicity in the literature are unlikely to be dependent on the difference in the presence of certain molecular drivers.
A multi-gene colorectal cancer liquid biopsy with >90% accuracy in diagnosis and assessment of disease status.
Authors: Modlin Irvin Mark , Kidd Mark S. , Kitz Alexandra , Drozdov Ignat A. , Malczewska Anna , Kusnierz Katarzyna , Aslanian Harry 
Published: May 2020

e16079 Background: There are few blood-based biomarkers for colorectal cancer (CRC). We report a 13-gene colon cancer circulating-free mRNA to diagnose CRC. Clinical utility was assessed in surgical and chemotherapy patients. Methods: Gene identification/validation: Publicly available colon cancer transcriptomes (E-MTAB-57) to identify candidate markers using gene co-expression network enrichment, differential expression and functional enrichment analyses. Cell line/tumor tissue gene expression: Candidate gene expression was evaluated in 3 CRC cell-lines (LOVO, LS-180 and COLO320DM) and surgical resection samples (CRC adenocarcinomas: n= 33) and biomarkers validated in the TCGA-COAD database ( n= 261 adenocarcinomas, 41 mucinous adenocarcinomas). Blood gene expression: CRC set (cancers: n= 312, controls n= 117) and a CRC artificial intelligence model constructed. Normalized gene expression algorithmically scored (0-100). Matched tumor/ blood samples were available in 33 patients. RECIST criteria Clinical score assessment: Score utility was assessed in surgical and treated cohorts: Surgical: n= 37, follow>7 days. Chemotherapy: n= 75; stable disease (SD): n= 20, progressive disease (PD): n= 55). The relationship to CEA and CA-19-9 were assessed. Statistics: Non-parametric (Mann-Whitney), Pearson-correlation, Fisher’s and AUROC analyses (Mean±SEM). Results: Transcriptomic analysis: Thirteen candidate CRC genes blood were identified. Cell lines and tumor tissue: Expression levels were significantly elevated ( p< 0.001, 20-100-fold) in cell lines and CRC tumors. All 13 markers were confirmed in TCGA-COAD samples (average TPM ranged from 692-4405). Blood gene expression: All 13 CRC marker genes were identified in CRC blood. Levels were 54.4±1.5 ( p< 0.0001) compared to controls (9.5±1.7); AUROC:0.91±0.02, accuracy 90.5% (sensitivity 93.1%, specificity 81.2%). The matched tissue/blood correlation was r = 0.80 ( p= 0.002). Clinical Utility: In the surgical cohort, accuracy was 100% vs CEA (35%) or CA-19-9 (17%) (both p< 0.0001). Resection (R0–92%) significantly decreased levels (47±2) at follow-up ( p< 0.006). In the treated cohort, levels were elevated in PD (63±4.1) vs SD (30±3.2, p< 0.0001). Conclusions: A CRC gene marker panel in blood identified colon cancer with a diagnostic accuracy of 91%. This was significantly greater than CEA or CA-19 in CRCs. Surgical resection decreased levels. CRC score was elevated in progressive vs stable disease. A colorectal cancer liquid biopsy will facilitate image-based management.
Patient characteristics and outcomes of colorectal cancer (CRC) at Butaro Cancer Center of Excellence (BCCOE): Results from a retrospective cohort.
Authors: Fadelu Temidayo , Sebahungu Fidel , Diasti Kevin , Nguyen Cam , Yeh Tiffany , Shyirambere Cyprien , Nkusi Eugene , Nsabimana Nicaise , Ruhangaza Deogratias , DeBoer Rebecca Jane , Chamberlin Mary D. , Mpunga Tharcisse , Shulman Lawrence N. 
Published: May 2020

e16081 Background: There are few studies on CRC in sub-Saharan Africa. BCCOE in Rwanda provides patients with CRC access to chemotherapy, surgery and radiotherapy referrals. Here, we describe patient characteristics, treatments delivered and outcomes. Methods: This retrospective observational study included 136 patients with CRC who presented between July 2012 and June 2018. We abstracted patient characteristics, diagnostic and treatment data, and outcomes from electronic and paper records. We compared baseline and treatment characteristics for colon cancer (CC) versus (vs.) rectal cancer (RC) patients. For patients treated with curative intent, we plotted Kaplan Meier estimation of disease free survival (DFS), defined as time from presentation to cancer recurrence, progression or death. Log-rank test was used to examine subgroup differences. Results: The mean age was 52.5, and 71 (52.2%) were female. 101 (74.2%) patients had RC. Compared to CC, patients with RC were older 54.5 vs. 46.9 (p = 0.0084), and more likely female 59.4 vs. 31.4 (p = 0.0043). All provinces in Rwanda were represented including 14 (10.3%) from outside Rwanda; 79 (58.1%) patients lived in rural areas. Median duration of symptoms prior to presentation was 12 months, and 57 (41.9%) had used traditional medicine prior to presentation. 72 (52.9%) patients were non-metastatic, 46 (33.8%) de novo metastatic, 4 (2.9%) recurrent, and 14 (10.2%) had indeterminate stage. Of the patients treated with curative intent, 54 (65.1%) had neoadjuvant and/or adjuvant chemotherapy, while only 34 (41.0%) had curative surgery. 40 (48.2%) patients received a permanent colostomy. 18 (27.7%) patients with RC received concurrent chemoradiation. Over the follow up period, 49 (36%) patients died or were referred for end of life care, 13 (9.3%) remain in surveillance, while 65 (47.8%) were lost to follow up. Median DFS for patients with non-metastatic disease was 22.2 months. On exploratory analyses, there were no statistically significant differences in DFS by cancer type, gender, or performance status, though these analyses were underpowered and follow-up short. Conclusions: CRC treatment requires multidisciplinary care, which is a challenge in low-resource settings. Our results highlight gaps in CRC care delivery and suboptimal patient outcomes; most striking gaps were the low rates of surgery and radiation, and high loss to follow up rates. Rigorous research is needed to understand the underlying causes, and to develop interventions to address these gaps.
Exosomal marker CD63 expression pattern using immunohistochemistry (IHC) in patients with rectal adenocarcinoma in comparison with left-sided colon cancer.
Authors: Prodduturvar Pranitha , McCormick Ben , Mneimneh Wadad , Dal Zotto Valeria , Escobar Daisy E , Manne Ashish , Grimm Leander , Rider Paul , Hunter John , Iliff Greire , Singh Ajay Pratap , Patel Girijesh Kumar , Alkharabsheh Omar , Khushman Moh'd M. 
Published: May 2020

e16096 Background: Adenocarcinomas arising from the distal one third of the transverse colon, splenic flexure, descending colon, sigmoid colon and rectum are often grouped together due to their hindgut embryologic origin and referred to as left-sided colorectal cancer (CRC). Rectal cancer represents a subset of CRC that has distinct differences in anatomical location, clinical behavior, prognosis and molecular background. In patients with left sided colon cancer (LSCC), the expression of exosomal marker CD63 was reported to be higher in the adjacent normal mucosa (ANM) compared to the tumor (224 vs 154, p = 0.0001). Here, we explored the pattern of CD63 expression using immunohistochemistry in patients with rectal cancer in comparison with patients with LSCC. Methods: Between 2015 and 2018, 53 patients underwent rectal cancer biopsy/resection and had available tissues for CD63 IHC staining. Two pathologists independently scored CD63 expression in the tumor and ANM. Staining intensity was graded from 1-3. Staining percentage was estimated in 10% increments. Mean quick-score (Q-score) was calculated (intensity x percentage). Paired t test was used for statistical analysis. Results: Median age was 60 (range 34-80). Females represented 26%. Caucasians and African Americans represented 74% and 26%, respectively. In patients with rectal cancer, the mean CD63 expression was higher in ANM compared to their expression in the tumor (147 vs 113, p = 0.0012). Compared to patients with LSCC (N = 30), the mean CD63 expression in patients with rectal cancer was lower in the ANM (224 vs 147, p < 0.0001) and in the tumor (154 vs 113, p = 0.01). Conclusions: In our cohort of patients with rectal cancer, exosomal marker CD63 expression was lower in tumor compared to ANM. This observation was similar to our previously reported findings in patients with LSCC. Compared to patients with LSCC, patients with rectal cancer had lower expression of CD63 in the tumor and ANM. To our knowledge, this is the first study to explore exosomal marker CD63 expression using IHC in patients with rectal cancer.
Treatment of colorectal cancer in Armenia: A retrospective hospital-based study from a developing world.
Authors: Bardakhchyan Samvel , Mkhitaryan Sergo , Zohrabyan Davit , Safaryan Liana , Avagyan Armen , Harutyunyan Lilit , Arakelyan Jemma , Tamamyan Gevorg , Tananyan Armen 
Published: May 2020

e16099 Background: In Armenia colorectal cancer (CRC) is on the third place by incidence. Every year around 700 new cases are diagnosed with 60% diagnosed in 3rd and 4th stages. Methods: For this retrospective hospital-based study we have collected data from two main oncology centers in Armenia: National Oncology Center and Muratsan Hospital Complex of Yerevan state medical university. The information about patients with CRC who were treated at these two centers during 01/01/2010 - 07/01/2018 period was collected from the medical records. Results: 602 patients with CRC treated during mentioned period in these two hospitals were involved in final analysis. From them 51.8% were female. Median age at diagnosis was 58. Median follow up time was 37 months (range 3-207). 26.1% had right sided, 30.9% left sided and 43.0% rectum cancer. 8.6% of patients had stage 1, 32.9% stage 2, 38.0% stage 3, 17.6% stage 4 CRC and for 2.7% patients stage was unknown. The median survival was not reached for the entire cohort ( > 37 months). Median survival was > 66.5 months for 1st, > 48.5 months for 2nd, > 35 months for 3rd and 19 months for 4th stages. Tumor stage, grade and histology were the main independent prognostic factors by univariate and multivariate Cox regression analysis. For stage 2 CRC patients (198) we found significant difference regarding overall survival (OS) (p = 0.024) and disease free survival (DFS) (p = 0.006) for those who received adjuvant chemotherapy after surgery compared to those who didn’t receive adjuvant chemotherapy. For stage 2 and 3 rectum cancer patients, our study failed to show OS (2nd stage: p = 0.961; 3rd stage: p = 0.348) or DFS (2nd stage: p = 0.719; 3rd stage: p = 0.983) advantage for those who received radiotherapy (RT) compared with those who didn’t receive RT. In our study population 28.3% of stage 4 patients received chemotherapy combined with Bevacizumab while 70% were treated with chemotherapy only. Median OS between these two groups wasn’t significantly different (21 months in Chemo+Bevacizumab group and 18.5 months in chemo only group (p = 0.382)). 3 and 5-year survival rates were 62.9% and 51.8% for all stages combined and 79.7% and 68.5% for stages 1-2, 62.5% and 48.4% for stage 3, 24.4% and 17% for stage 4 respectively. Conclusions: As seen from our results our survival rates are inferior compared to that of developed world. The reasons for that could be compromise in surgery and RT, poor pathological assessment, unavailability of some molecular markers, poor availability of new targeted drugs and absence of national treatment guidelines.