bluuebunny/crossref_metadata_2025_split huggingface dataset:
Difference of colorectal cancer microbial community by metagenomics and culture-based methods.
Authors: Lee Dong Ho , Seol Mijin , Lee Yu Ra , Park Young Soo , Shin Cheol Min , Yoon Hyuk , Kim Nayoung , Cho Jae Ho , Song Dong Jin , Kim Kyung Mi 
Published: January 2019

489 Background: Dysbiosis of intestinal microbiota is promoting the development of colorectal cancer (CRC). We confirmed the intestinal microbiota composition from fecal sample of Korean CRC patients. Metagenomic analysis was performed and we isolated single microbes through culture-based method. Methods: CRC fecal samples were collected from 12 individuals. Metagenome Sequencing was based on the 16S rRNA gene amplicon on the Illumina MiSeq platform. The bacteria strains were subcultivated on the agar plate medium in aerobic and anaerobic and further identified by using the 16s rRNA gene sequencing. Results: Bacteria diversity by metagenome analysis was decreased in CRC group compared to control group. In CRC group, relative abundance of Firmicutes and Bacteroidetes were increased while the prevalence of Proteobacteria was decreased. The difference of microbial composition between control and CRC group was found at the genus level. Bacteroides, Parabacteroides of Bacteroidetes have increased and Acinetobacter, Pseudomonas of Proteobacteria have significantly decreased in CRC compared to control group. Using culture method, we isolated diverse bacteria of species level including five strains of Bacteroides; B. ovatus, B. uniformis, B. salyersiae, B. vulgatus and B. xylanisolvens and two strains of Fusobacterium; F. gonidiaformans and F. necrophorum from CRC patients. Conclusions: Metagenome analysis showed the genus Bacteroides, Parabacteroides of the phylum Bacteroidetes has increased and the genus Acinetobacter, Pseudomonas of Proteobacteria decreased in CRC group compared to control group. In addition to, we have isolated various strains associated with CRC by culture-based method.
Expression patterns of PD-L1 and other immune checkpoint molecules in gastric cancer.
Authors: Nakamura Kenichi , Hatakeyama Keiichi , Toriumi Tetsuro , Koseki Yusuke , Waki Yuhei , Fujiya Keiichi , Kamiya Satoshi , Makuuchi Rie , Tanizawa Yutaka , Bando Etsuro , Kawamura Taiichi , Yamaguchi Ken , Terashima Masanori 
Published: January 2019

49 Background: Immune checkpoint inhibitors (ICPIs) have provided clinical benefit for various malignancies. A new attempt was recently made to combine PD-1/PD-L1 inhibitors and other ICPIs. In order to establish a new strategy for ICPI combination therapy, we must first understand the expression patterns of PD-L1 and other ICP molecules. To identify possible candidate agents for application in combination therapy with PD-1/PD-L1, we analyzed the expression patterns of ICP molecules in gastric cancer. Methods: Tumor samples were obtained from 278 patients who underwent gastrectomy for gastric cancer from 2014 to 2016, and a comprehensive gene expression analysis using a DNA microarray. We analyzed the TCGA dataset to identify the candidate ICP molecules in relation to PD-L1. The immune landscape was evaluated according to the expression patterns of known immune cell markers reported by Bindea et al. Results: Seven ICP molecules ( PD-L2, IDO1, CD80, ICOS, CTLA4, LAG3 and TIM3) were coexpressed with PD-L1 in the TCGA dataset. In our cohort, all of these molecules were also coexpressed (R > 0.5, P < 0.0001). Using a cluster analysis based on these gene expression profiles, patients were divided into Group A, characterized by the co-overexpression of PD-L1 and other ICP molecules, and Group B, characterized by the underexpression of PD-L1. In Group A, PD-L2 (R = 0.67) and IDO1 (R = 0.61) were particularly strongly associated with the PD-L1 expression. In Group B, elevated expressions of CTLA4 and ICOS were predominantly observed, and these expressions were strongly correlated with each other (R = 0.90). The tumor stage was significantly more advanced in Group B than in Group A (P = 0.02). Accordingly, Group A exhibited a better survival outcome than Group B. The immune landscape of Group A was particularly enriched for Th1, NK CD56dim and activated dendritic cells. Conclusions: PD-L1 and several immune checkpoint molecules tend to be coexpressed in gastric cancer. The combination of PD-L1/-L2 and IDO1 target agents may be a new strategy for treating gastric cancer with PD-L1 overexpression. In contrast, the underexpression of PD-L1 might be an indication for the use of CTLA4- and/or ICOS-directed therapies.
Relation between the size of nonmetastatic and metastatic lymph nodes and outcomes in patients with stage III colon cancer.
Authors: Okada Kazutake , Sadahiro Sotaro , Kamei Yutaro , Ogimi Takashi , Miyakita Hiroshi , Saito Gota , Tanaka Akira , Suzuki Toshiyuki , Chan Lin Fung 
Published: January 2019

494 Background: In colon cancer, retrieval of less than 12 lymph nodes is a risk factor for recurrence. We previously reported that the long-axis diameter of the largest LNs (maximum LNs) is associated with a higher number of retrieved LNs and better outcomes in stage II disease (Int J Colorectal Dis 2015). Furthermore, the number of natural killer cells in the maximum LNs is associated with the number of retrieved LNs and lymph node size, and is an independent prognostic factor (Oncology 2018). We examined whether the long-axis diameter of maximum LNs with and without metastasis is a prognostic factor in stage III colon cancer. Methods: The study group comprised 190 patients with stage III colon cancer from 2005 to 2014. For each patient, one negative LN and one positive LN with the greatest long-axis diameter were selected, and the diameter was measured on H-E stained specimens. The endpoint of survival analysis was relapse free survival (RFS). The cut-off value (COV) was determined by using receiver operating characteristic curves. Results: The mean long-axis diameter of maximum negative and positive LNs were 8.5 ± 3.7 and 9.9 ± 4.9 mm, respectively. Factors related to the number of retrieved LNs were the tumor size (less than 4.3 cm, 13.5 ± 6.4; 4.3 cm or more, 16.6 ± 7.3; p = 0.004) and the long axis diameter of maximum negative LNs (< 8.1 mm, 13.4 ± 6.9; ≥ 8.1 mm, 17.6 ± 6.6; p < 0.001). Maximum negative LNs with a diameter of ≥ 8.1 mm was associated with significantly better RFS than maximum negative LNs with a diameter of < 8.1 mm (p = 0.020). The diameter of maximum positive LNs was not a prognostic factor. On multivariate analysis, the tumor size (≥ 4.3 cm/< 4.3 cm, HR 3.02; p < 0.001), venous invasion (absent/present, HR 0.41; p = 0.017), the number of LNs (≥ 12/< 12, HR 0.56; p = 0.043), and the diameter of maximum negative LNs (≥ 8.1 mm/< 8.1 mm, HR 0.45; p = 0.008) were independent prognostic factors. Conclusions: In stage III colon cancer, the long-axis diameter of negative maximum LNs was a prognostic factor. Enlarged negative LNs are caused by hyperplasia of cell components in LNs. The size of negative maximum LNs might reflect the tumor immunity of the host.
Utility of restaging patients with stage II/III rectal cancer following neoadjuvant chemo/XRT: A systematic review.
Authors: Hendrick Leah E. , Levesque Renee L , Shibata David , Hinkle Nathan M , Monroe Justin J , Glazer Evan Scott , Deneve Jeremiah Lee , Dickson Paxton Vandiver 
Published: January 2019

495 Background: In the US, patients with clinical stage II/III rectal cancer typically receive neoadjuvant chemoradiation (chemo/XRT) over 5-6 weeks followed by a 6-10 week break before proctectomy. As this chemotherapy is delivered at radio-sensitizing doses, there is essentially a 3-month window during which potential systemic disease is untreated. Evidence regarding the utility of restaging patients prior to proctectomy is limited. Methods: PubMed, Scopus, Web of Science, and the Cochrane Library were searched for studies evaluating the utility of restaging patients with locally advanced rectal cancer after completion of long course chemo/XRT, and reporting changes in management after restaging. Studies that were non-English, included < 50 patients, or examining the diagnostic accuracy of specific imaging modalities were excluded. Study quality was evaluated using the modified Newcastle Ottawa Scale. Results: Eight studies were identified including a total of 1251 patients restaged between completion of chemo/XRT and proctectomy. All studies were retrospective (6 single institution, 2 multi-institution). Restaging identified new metastatic disease in 72 (6.0%) patients, with 4 studies reporting specific sites: liver (n = 28), lung (n = 8), adrenal (n = 1), bone (n = 1), and multiple sites (n = 7). Overall, progression (distant or local) was detected in 85 (6.8%) patients and resulted in a reported change in management in 71 (5.7%) patients. One study identified an association of high-grade tumors with progression (p ≤ 0.05), however, this was not reported in any other study. Moreover, tumor-related prognostic characteristics were inconsistently reported among studies, precluding meta-analysis. Conclusions: Although restaging between completion of neoadjuvant chemo/XRT and proctectomy detects disease progression in only a small percentage of patients, findings may alter the treatment plan. A multi-institutional collaboration with analysis of well-defined prognostic variables may better identify a group of patients most likely to benefit from restaging.
Sidedness in metastatic colorectal carcinoma: Which are the factors which influence the prognosis?
Authors: Kogay Maria , Evesque Ludovic , Falcoz Antoine , Saint Angelique , Cavaglione Gerard , Schiappa Renaud , Baudin Guillaume , Milano Gerard A. , Chamorey Emmanuel , Francois Eric 
Published: January 2019

497 Background: Recent reports demonstrate prognostic and predictive impacts of the location of the primary tumor in metastatic colorectal cancer (mCRC). Our retrospective analysis aimed to determine the influence of primary site on metastatic distribution and disease evolution. Methods: From our database all patients (pts) with mCRC (except transverse carcinoma) treated from 1/12/2007 to 1/12/2016 in our institution were collected. Univariate and multivariate analyses were performed to identify predictors of overall survival (OS). Results: A total of 284 pts with available data were analyzed: 83 with Right-sided Colon Cancer (RCC) (29%), 123 with Left-sided Colon Cancer (LCC) (43%) and 78pts with Rectal Cancer (RC) (28%). Hepatic, lung, lymph nodes and peritoneal metastases were respectively found in 63%, 36%, 23% and 20% of the population. The incidence or number of liver metastases were not influenced by sidedness (p = 0.06), LCC presented more bilobar involvement compared to RCC and RC (p = 0.017). Peritoneal carcinomatosis was significantly correlated to colon cancer (p = 0.002), whereas lung metastases were more common in RC (p < 0.001). Patients with RCC more often presented distal lymph node involvement (p = 0.008). RAS mutation status was known for 241pts (80%), of those 110 (37%) were RAS mutated with no significant differences between RCC, LCC and RC (p = 0.4), BRAF mutation (p = 0.007) was more common in RCC. On a multivariable analysis, primary tumor resection (PTR) and complete response after first line therapy were associated with a better OS but only a trend was observed for LCC and RC. Lung, lymph and peritoneal metastasis were associated with worse OS (Table). Conclusions: These results suggests that mCRC had different clinical presentation at diagnosis, the association with molecular features may explain the independent prognostic factor for OS of the sidedness. [Table: see text]
Prognostic immune markers for recurrence and survival in locally advanced esophageal adenocarcinoma.
Authors: Babar Laila , Zaidi Ali Hussainy , Omstead Ashten N. , Zheng Ping , Kelly Ronan Joseph , Jobe Blair Anderson 
Published: January 2019

50 Background: Treatment options and risk stratification for esophageal adenocarcinomas (EAC) primarily rely on clinical and pathological criteria, such as tumor stage and pathological response (PR) evaluation. However, with immunotherapy showing hints of activity in EAC there is an emerging need to develop new predictive biomarkers that will not only identify high-risk patients but also unlock novel therapeutic strategies. The aim of this study was to evaluate if LAG3, TIM3, IDO and CXCL9 gene expression along with pathological classifiers correlate with recurrence and/or death in EAC. Methods: Clinical and histopathology data on 49 resectable EAC patients was captured. Mean age at diagnosis was 64.2 years with a median follow up of 21.2 months. Laser capture microdissection followed by qRT-PCR was performed on pretreatment FFPE samples to quantify LAG3, TIM3, IDO and CXCL9 gene levels. Statistical tools established individual biomarker cutoffs and these were correlated with clinical outcomes. Results: For disease free survival, a best fit Cox model was generated consisting of PR (HR=9.54, 95% CI = 2.13 ~ 42.62, p = .003), LAG3 (HR = 2.86, 95% CI = 1.03 ~ 7.94, p = .044), and CXCL9 (HR = 0.40, 95% CI = 0.16 ~ 0.99, p = .049). Moreover, the classification performance of the 3 predictor Cox model was deemed superior to PR alone; P = 0.0001 (Likelihood Ratio Test (LRT)) indicated strong significance in predictability with the recurrence model. For overall survival, a best fit Cox model was generated consisting of TIM3 (HR = 4.43, 95% CI= 1.70 ~ 11.5, p = .002) PR (HR = 3.09, 95% CI= 1.00 ~ 9.56, p = .051) and IDO (HR = 0.31, 95% CI = 0.11 ~ 0.82, p = .019). Likewise, the classification performance of the 3 predictor Cox model was deemed superior to PR alone; P = 0.0004 (LRT) indicated strong significance in predictability with the survival model. Conclusions: LAG3, TIM3, IDO and CXCL9 expression in conjunction with PR to neoadjuvant therapy provide superior tools to predict recurrence and death in locally advanced EAC patients. Additionally, given the paucity of treatment options for esophageal cancer we must check for these markers early on in the disease course to better risk stratify patients and provide newer targets for novel treatments.
Gene-specific features (MLH1, MSH2, MSH6, PMS2) of mismatch repair (MMR) protein expression and somatic mutations (muts), microsatellite instability (MSI) and tumor mutational burden (TMB) in MSI-H and MMR-mutated tumor genomic profiles (TGPs).
Authors: Hall Michael J. , Bodor Joseph Nicholas , Xiu Joanne , Feldman Rebecca , Grothey Axel , Goldberg Richard M. , Worrilow William Mills , Hwang Jimmy J. , Kim Edward S. , Lenz Heinz-Josef , Raghavan Derek , Shields Anthony Frank , Marshall John , Korn W. Michael , Salem Mohamed E. 
Published: January 2019

505 Background: MSI is a tumor biomarker for immunotherapy efficacy that is closely associated w/deficient MMR, and is also variably associated w/somatic muts of the MMR genes, loss of MMR protein expression by immunohistochemistry (IHC), and high TMB. Germ-line muts (Lynch syndrome/LS) in the 4 MMR genes are recognized to have distinct cancer spectrums/penetrance in LS, yet across all tumors, gene-specific variability in MMR IHC, MMR muts, and TMB is understudied. Methods: Results of TGPs performed by Caris Lifesciences (2015-17) were analyzed in colorectal (CRC), endometrial (EC) and all other cancers/tumors (OT) as: 1) all MSI-H tumors (n = 1057) and 2) all tumors w/ ≥1 mut in an MMR gene (n = 470). A subset of cases had IHC for MMR protein and PD-L1 expression. MSI and TMB were determined by NGS. Results: Characteristics of MSI-H tumors and tumors w/ ≥1 MMR mut are seen in the Table. A single MSH6 mut [F1088fs] in a coding microsatellite represented 31% of all MMR muts detected. F1088fs was found in 58% tumors w/MLH1/PMS2 loss (IHC) but only 25% w/MSH2/MSH6 loss (p < 0.001), was more commonly seen in EC vs CRC/OT (p < 0.001), and was negatively associated w/somatic POLE mut (p = 0.002). Distinct mut signatures in the MMR genes (e.g. GLUàSTOP) were seen in tumors w/POLE muts and DNA repair genes. Conclusions: MSI-H and MMR mutated tumors demonstrate marked gene-specific heterogeneity in IHC patterns, TMBs, and somatic muts that may be relevant to treatment selection, resistance, and response. [Table: see text]
Colorectal cancer (CRC) among very elderly ( > 80 yo) patients (pts): A Brazilian single institution cohort.
Authors: Crosara Alves Texeira Marcela , Moura Kelsen , Cabral Pedro , Silva Suelen Medeiros , Pereira Allan Andresson Lima , Costa Frederico , Sabagga Jorge , Hoff Paulo Marcelo , Fernandes Gustavo Dos Santos 
Published: January 2019

507 Background: Approximately 60% of all cancers and 70% of the mortality occurs in pts aged 65 years and over. Despite that, there is a significant lack of evidence regarding the safety and efficacy of treatments for this part of the population. Our goal is to profile very elderly (VE) pts with gastrintestinal malignancies to highlight research opportunities and improve cancer care among this growing population. Methods: We retrospectively analyzed very elderly pts that attended at Sírio Libanês Hospital in Brazil in a 3 year period and had colorrectal cancer (CRC) diagnosed. We collected information from electronic medical charts on age, gender, ECOG-PS, staging, and surgery. We also gathered information about the type of treatment and survival from diagnosis. Results: Of 88 consecutive VE GI cancer pts, 40 (45,4%) were found to have CRC being 29 colon and 11 rectum. 14 patients were considered to have right sided tumors and 26 left sided. Among CRC pts, the median age was 82, 5 yo and 21 (52.5%) were men. ECOG-PS at diagnosis was 0/1 in 29pts, 19 (47.5%) presented as stage IV disease and 27 pts had surgery of the primary site. As treatment 23(57.5%) received chemotherapy, being 4 adjuvant and 19 palliative. Single agent fluoropyrimidine was the first line therapy in 47%, chemotherapy doublet in 42%, 26% pts received anti-VEGF. Six patients with rectal cancer received chemoRT. The median survival among the stage IV CRC pts was 27.5ms. Conclusions: This cohort is one of the few reported data on VE population cancer, the incidence of cancer in this age group is high and deserve to be more characterized in both trials and retrospective data. Interestingly, those patients seem to benefit from treatments likewise historic data from average age patients. Treatment details, tumor location, pathology, and survival curves will be presented.
Retrospective multicenter study for assessment of association between imaging change and outcome after treatment of regorafenib: KSCC1603.
Authors: Esaki Taito , Kawahira Masahiro , Kusumoto Tetsuya , Yuki Satoshi , Hatanaka Kazuteru , Kobayashi Yoshimitsu , Nishie Akihiro , Kawanami Satoshi , Makiyama Akitaka , Saeki Hiroshi , Shimokawa Mototsugu , Oki Eiji , Maehara Yoshihiko 
Published: January 2019

509 Background: Molecular-targeted drugs are known to have angiogenesis-inhibiting properties, and thus can inhibit angiogenesis inside the tumor tissue to cause necrosis, even if the tumor diameter is unchanged. We retrospectively investigated relationship between imaging change associated with regorafenib (REGO) treatment and the treatment outcome in Japanese mCRC. Methods: Eligibility included ECOG-PS 0 or 1, treated with REGO with lung or liver metastasis, started dose with 120 or 160mg/day of regorafenib and duration of treatment (DOT) must be 35 days or more (excluding interruption). Patients (Pts) were performed baseline CT within 28 days before and first CT assessment were between eight and 12 weeks after start of regorafenib. The main objective of this analysis is to investigate the correlation between the imaging change and outcome. As imaging change, onset or increase of Cavitation of lung lesion (CLL), morphologic response of liver lesion (MRL), Change of liver metastasis density (CLD) were evaluated. In all cases, independent two radiologists are evaluating radiological change after regorafenib treatment. Results: We finally screened 671 cases and 231 cases were eligible. The pts background was male/female 147/84, median age　64.0 (range: 32-83), median DOT of REGO　86 days (range: 35-818). The pts with lung metastasis were 153, and with liver metastasis were 166. CLL were positive in 69 (40.0%) pts. The median progression free survival (PFS) of the pts with/without CLL were 3.2/2.4 months (HR 0.794; 95% CI 0.584-1.080). Median overall survival (OS) of the pts with/without CLL were 10.5/9.0 months (HR 1.058; 95% CI 0.751-1.489). Median OS of pts with/without CLL in female were 11.4/7.9 months (HR 0.630; 95% CI 0.352-1.127). The MRL and CLD of liver metastasis were analyzed in 147 / 91 pt. Median OS of pts with/without MRL were 9.9/8.2 months (HR 1.015; 95% CI 0.581-1.774) and Median OS with/ without CLD were 11.6/7.0 months (HR 0.604; 95% CI 0.353-1.031). Conclusions: Cavitation of lung metastasis may predict PFS of the pts but not OS. Change of Liver metastasis density were predictor of favorable outcome to regorafenib. (UMIN000023329).
Early detection of lower GI tract tumors by dedicated assessment of the colon on routine computed tomography (CT) imaging: An observational study.
Authors: Chang John , Pluhm Russell , Lutrick Ashley , Guerra Jessica , Koo Phillip , Kundranda Madappa N. 
Published: January 2019

510 Background: We have previously reported that up to 48% of the early features of colorectal cancer (subtle wall thickening, pericolonic stranding, and small lymph nodes in the draining nodal station) were not identified on the original CT abdomen and pelvis (CTAP) reports. This resulted in a 36% decrease in five-year survival based on historical data. In this report, we assessed whether dedicated assessment of the colon on routine CT scans could lead to early detection of colorectal cancer. Methods: 210 CTAPs over a three-month period were screened from the emergency room records at a tertiary care hospital. 194 scans met eligibility. Exclusion criteria included: cases known to the evaluating radiologist and age ≤ 19 or > 89 years. No study was excluded for suboptimal image quality. The original report was reviewed for abnormalities involving the colon, mesentery and bowel and was recorded. A blinded evaluation of the eligible case was then performed by a board-certified radiologist with attention specifically to the colon and the mesentery for the suspicious early features of CRC. The concordance and discordance was then tabulated. Discordant findings were re-evaluated to determine if the discordance was true. Results: 72/194 patients were male, median age 44.5 years (range 20 - 89). 55/194 patients (29.1%) included in the study were noted to have suspicious features. 26 had abnormal lymph nodes, 24 had abnormal colonic wall thickening and 16 had pericolonic stranding and/or wall edema. 45/55 studies were truly discordant from the original interpretation. These included one missed colorectal cancer (confirmed), one likely small bowel neuroendocrine tumor (no follow up), and one likely transitional cell carcinoma of the right renal pelvis (no follow up). Conclusions: Dedicated search of the colon and mesentery on CTAP can identify subtle findings, although their true relevance is being evaluated in a larger future study. Our observational data does indicate that there maybe a potential role for a focused evaluation of the colon and mesentery on routine CTAP in an attempt to potentially increase the rate of cancer detection especially in younger low-average risk patients.