ResearchPad - colorectal-cancer https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Decyl caffeic acid inhibits the proliferation of colorectal cancer cells in an autophagy-dependent manner <i>in vitro</i> and <i>in vivo</i>]]> https://www.researchpad.co/article/elastic_article_13874 The treatment of human colorectal cancer (CRC) cells through suppressing the abnormal survival signaling pathways has recently become a significant area of focus. In this study, our results demonstrated that decyl caffeic acid (DC), one of the novel caffeic acid derivatives, remarkedly suppressed the growth of CRC cells both in vitro and in vivo. The inhibitory effects of DC on CRC cells were investigated in an in vitro cell model and in vivo using a xenograft mouse model. CRC cells were treated with DC at various dosages (0, 10, 20 and 40 μM), and cell survival, the apoptotic index and the autophagy level were measured using an MTT assay and flow cytometry analysis, respectively. The signaling cascades in CRC were examined by Western blot assay. The anti-cancer effects of DC on tumor growth were examined by using CRC HCT-116 cells implanted in an animal model. Our results indicated that DC differentially suppressed the growth of CRC HT-29 and HCT-116 cells through an enhancement of cell-cycle arrest at the S phase. DC inhibited the expression of cell-cycle regulators, which include cyclin E and cyclin A proteins. The molecular mechanisms of action were correlated to the blockade of the STAT3 and Akt signaling cascades. Strikingly, a high dosage of DC prompted a self-protection action through inducing cell-dependent autophagy in HCT-116 cells. Suppression of autophagy induced cell death in the treatment of DC in HCT-116 cells. DC seemed to inhibit cell proliferation of CRC differentially, and the therapeutic advantage appeared to be autophagy dependent. Moreover, consumption of DC blocked the tumor growth of colorectal adenocarcinoma in an experimental animal model. In conclusion, our results suggested that DC could act as a therapeutic agent through the significant suppression of tumor growth of human CRC cells.

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<![CDATA[Risk of colorectal cancer in patients with alcoholism: A nationwide, population-based nested case-control study]]> https://www.researchpad.co/article/elastic_article_7832 Colorectal cancer (CRC) is regarded as a multifactorial disease and shares many risk factors with alcoholism. However, the association between alcoholism and CRC remains controversial.ObjectivesIn this study, we aimed to evaluate the association between alcoholism and risk of CRC.MethodsWe performed a large-scale, population-based nested case-control study using the Longitudinal Health Insurance Database 2013, derived from Taiwan’s National Health Insurance Research Database, and collected data from 2000 to 2013. There were 49,095 diagnosed cases of CRC defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification. Each case was matched with three controls by sex, age, index date of CRC, and annual medical visits; a total of 147,285 controls were identified. Multiple risk factors of CRC in alcoholism cases were investigated using unconditional multiple logistic regression analysis.ResultsAmong 49,095 cases of CRC, alcoholism was associated with a significantly higher risk of CRC (adjusted odds ratio (OR), 1.631; 95% CI, 1.565–1.699) in multivariate logistic regression, after adjusting other CRC risk factors, and in stratified analysis with multivariate logistic regression. In addition, there was a time-dependent relationship between alcoholism duration and CRC risk in >1 year, > 2 years, >5 years, and > 11 years groups (adjusted ORs, 1.875, 2.050, 2.662 and 2.670; 95% CI, 1.788–1.967, 1.948–2.158, 2.498–2.835, and 2.511–2.989 respectively).ConclusionAn association between alcoholism and risk of CRC was found in this study. Furthermore, patients with longer alcoholism history showed higher likelihood of developing CRC, which indicates a time-dependent relationship between alcoholism exposure and CRC. Further research on colorectal tumorigenesis is needed. ]]> <![CDATA[Role of intraoperative oliguria in risk stratification for postoperative acute kidney injury in patients undergoing colorectal surgery with an enhanced recovery protocol: A propensity score matching analysis]]> https://www.researchpad.co/article/N90678846-11a4-456d-84dc-7e3677d2f27e

Background

The enhanced recovery after surgery (ERAS) protocol for colorectal cancer resection recommends balanced perioperative fluid therapy. According to recent guidelines, zero-balance fluid therapy is recommended in low-risk patients, and immediate correction of low urine output during surgery is discouraged. However, several reports have indicated an association of intraoperative oliguria with postoperative acute kidney injury (AKI). We investigated the impact of intraoperative oliguria in the colorectal ERAS setting on the incidence of postoperative AKI.

Patients and methods

From January 2017 to August 2019, a total of 453 patients underwent laparoscopic colorectal cancer resection with the ERAS protocol. Among them, 125 patients met the criteria for oliguria and were propensity score (PS) matched to 328 patients without intraoperative oliguria. After PS matching had been performed, 125 patients from each group were selected and the incidences of AKI were compared between the two groups. Postoperative kidney function and surgical outcomes were also evaluated.

Results

The incidence of AKI was significantly higher in the intraoperative oliguria group than in the non-intraoperative oliguria group (26.4% vs. 11.2%, respectively, P = 0.002). Also, the eGFR reduction on postoperative day 0 was significantly greater in the intraoperative oliguria than non-intraoperative oliguria group (−9.02 vs. −1.24 mL/min/1.73 m2 respectively, P < 0.001). In addition, the surgical complication rate was higher in the intraoperative oliguria group than in the non-intraoperative oliguria group (18.4% vs. 9.6%, respectively, P = 0.045).

Conclusions

Despite the proven benefits of perioperative care with the ERAS protocol, caution is required in patients with intraoperative oliguria to prevent postoperative AKI. Further studies regarding appropriate management of intraoperative oliguria in association with long-term prognosis are needed in the colorectal ERAS setting.

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<![CDATA[Ornithine decarboxylase antizyme inhibitor 2 (AZIN2) is a signature of secretory phenotype and independent predictor of adverse prognosis in colorectal cancer]]> https://www.researchpad.co/article/5c70673fd5eed0c4847c6c9d

Ornithine decarboxylase (ODC) is the rate-limiting enzyme of polyamine synthesis. The two ODC antizyme inhibitors (AZIN1) and (AZIN2) are regulators of the catalytic activity of ODC. While AZIN1 is a regulator of cell proliferation, AZIN2 is involved in intracellular vesicle transport and secretion. There are no previous reports on the impact of AZIN2 expression in human cancer. We applied immunohistochemistry with antibodies to human AZIN2 on tissue micro- arrays of colorectal cancers (CRC) from 840 patients with a median follow-up of 5.1 years (range 0–25.8). The 5-year disease-specific survival rate was 58.9% (95% Cl 55.0–62.8%). High AZIN2 expression was associated with mucinous histology (p = 0.002) and location in the right hemicolon (p = 0.021). We found no association with age, gender, stage, or histological tumor grade. High tumor expression of AZIN2 predicted an unfavorable prognosis (p<0.0001, log-rank test), compared to low AZIN2 expression. Cox multivariable analysis identified AZIN2 as an independent factor of an unfavorable prognosis in CRC. The strongest AZIN2 expression was seen in invasive tumor cells having morphological features of epithelial-mesenchymal transition (EMT). Induction of EMT in HT-29 CRC cells lead to upregulated expression of endogenous AZIN2. Given that AZIN2 is a regulator of vesicle transport and secretion, we overexpressed human AZIN2 cDNA in T84 CRC cells, and found strongly enhanced accumulation of CD63-positive exosomes in the culture medium. These findings indicate that AZIN2 expression is a signature of EMT-associated secretory phenotype that is linked to an adverse prognosis in CRC.

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<![CDATA[Complex harmonic regularization with differential evolution in a memetic framework for biomarker selection]]> https://www.researchpad.co/article/5c6f1534d5eed0c48467aebf

For studying cancer and genetic diseases, the issue of identifying high correlation genes from high-dimensional data is an important problem. It is a great challenge to select relevant biomarkers from gene expression data that contains some important correlation structures, and some of the genes can be divided into different groups with a common biological function, chromosomal location or regulation. In this paper, we propose a penalized accelerated failure time model CHR-DE using a non-convex regularization (local search) with differential evolution (global search) in a wrapper-embedded memetic framework. The complex harmonic regularization (CHR) can approximate to the combination p(12p<1) and q (1 ≤ q < 2) for selecting biomarkers in group. And differential evolution (DE) is utilized to globally optimize the CHR’s hyperparameters, which make CHR-DE achieve strong capability of selecting groups of genes in high-dimensional biological data. We also developed an efficient path seeking algorithm to optimize this penalized model. The proposed method is evaluated on synthetic and three gene expression datasets: breast cancer, hepatocellular carcinoma and colorectal cancer. The experimental results demonstrate that CHR-DE is a more effective tool for feature selection and learning prediction.

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<![CDATA[Early-stage serrated adenocarcinomas are divided into several molecularly distinct subtypes]]> https://www.researchpad.co/article/5c76fdead5eed0c484e5b080

Serrated adenocarcinoma (SAC) is considered the end stage of the serrated neoplasia pathway. Although SAC prognosis is not widely recognized, the serrated pathway-associated subtype consistently exhibits unfavorable prognosis in genetic studies. Herein, we classified molecularly distinct subtypes of serrated adenocarcinomas and clarified their associated clinicopathological characteristics and genetic changes. We examined 38 early-stage colorectal SACs. Of these, 24 were classified into three molecularly distinct groups by colon cancer subtyping (CCS). The clinicopathological characteristics, Ki 67 labeling index (LI), and SAC epithelial serration were assessed. The DNA from carcinomas and normal tissue/adenoma was extracted by laser microdissection and sequenced by next-generation sequencing, and mutation numbers and patterns of a 15-oncogene panel were determined. The CCS groups included CCS1 (CDX2+, HTR2B-, FRMD6-, ZEB1-, and microsatellite instable-low [MSI-L]/microsatellite stable [MSS]; 14 cases), CCS2 (microsatellite instable-high [MSI-H], 5 cases), and CCS3 (CDX2-, HTR2B+, FRMD6+, ZEB1+, and MSI-L/MSS; 5 cases). Invasive cancer was significantly more frequent in CCS3 than in CCS1 (5/5 versus 3/14, respectively). Ki67 LI and epithelial serration were higher in CCS3 than in CCS1 (83.0 ± 5.8 versus 65.4 ± 4.0 and 5/5 versus 3/14, respectively; p = 0.031 and 0.0048). CCS2 showed the highest mutation number, whereas KRAS and BRAF mutation numbers were higher in CCS3 than in CCS1. Early-stage SACs were classified into three molecularly distinct subtypes with different clinicopathological and genetic characteristics.

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<![CDATA[The Apparent Diffusion Coefficient (ADC) is a useful biomarker in predicting metastatic colon cancer using the ADC-value of the primary tumor]]> https://www.researchpad.co/article/5c633946d5eed0c484ae63d7

Purpose

To investigate the role of the apparent diffusion coefficient (ADC) as a potential imaging biomarker to predict metastasis (lymph node metastasis and distant metastasis) in colon cancer based on the ADC-value of the primary tumor.

Methods

Thirty patients (21M, 9F) were included retrospectively. All patients received a 1.5T MRI of the colon including T2 and DWI sequences. ADC maps were calculated for each patient. An expert reader manually delineated all colon tumors to measure mean ADC and histogram metrics (mean, min, max, median, standard deviation (SD), skewness, kurtosis, 5th-95th percentiles) were calculated. Advanced colon cancer was defined as lymph node mestastasis (N+) or distant metastasis (M+). The student Mann Whitney U-test was used to assess the differences between the ADC means of early and advanced colon cancer. To compare the accuracy of lymph node metastasis (N+) prediction based on morpholigical criteria versus ADC-value of the primary tumor, two blinded readers, determined the lymph node metastasis (N0 vs N+) based on morphological criteria. The sensitivity and specificity in predicting lymph node metastasis was calculated for both readers and for the ADC-value of the primary tumor, with histopathology results as the gold standard.

Results

There was a significant difference between the mean ADC-value of advanced versus early tumors (p = 0.002). The optimal cut off value was 1179 * 10−3 mm2/s with an area under the curve (AUC) of 0.83 and a sensitivity and specificity of 81% and 86% respectively to predict advanced tumors. Histogram analyses did not add any significant additional value.

The sensitivity and specificity for the prediction of lymph node metastasis based on morphological criteria were 40% and 63% for reader 1 and 30% and 88% for reader 2 respectively. The primary tumor ADC-value using 1.179 * 10−3 mm2/s as threshold had a 100% sensitivity and specificity in predicting lymph node metastasis.

Conclusion

The ADC-value of the primary tumor has the potential to predict advanced colon cancer, defined as lymph node metastasis or distant metastasis, with lower ADC values significantly associated with advanced tumors. Furthermore the ADC-value of the primary tumor increases the prediction accuracy of lymph node metastasis compared with morphological criteria.

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<![CDATA[BAP1 expression is prognostic in breast and uveal melanoma but not colon cancer and is highly positively correlated with RBM15B and USP19]]> https://www.researchpad.co/article/5c61e8c4d5eed0c48496f124

BAP1 is a tumor suppressor gene important to the development and prognosis of many cancers, especially uveal melanoma (UM). Its role in more common cancers such as breast and colon cancer is largely unknown. We collected the transcriptome profiling data sets from the TCGA uveal melanoma (TCGA-UVM), breast cancer (TCGA-BRCA), and colon cancer (TCGA-COAD) projects to analyze the expression of BAP1. We found that patients with UM and breast cancer, but not colon cancer, who died had a lower level of BAP1 gene expression compared to surviving patients. Importantly, in breast cancer patients, the lowest BAP1 expression levels corresponded to the dead young patients (age at diagnosis < 46). Since the number of cases in TCGA-BRCA was much higher than TCGA-UVM, we obtained highly correlated genes with BAP1 in invasive breast carcinomas. Then, we tested if these genes are also highly correlated with BAP1 in UM and colon cancer. We found that BAP1 is highly positively correlated with RBM15B and USP19 expression in invasive breast carcinoma, UM, and colon adenocarcinoma. All three genes are located in close proximity on the 3p21 tumor suppressor region that is commonly altered in many cancers.

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<![CDATA[Evaluation of the combined effect of factors influencing bowel preparation and adenoma detection rates in patients undergoing colonoscopy]]> https://www.researchpad.co/article/5c6db20dd5eed0c48450eadc

Background

Colonoscopy is a commonly used modality for screening and surveillance of colorectal cancer (CRC). Therefore, it is essential to have adequate bowel preparation (prep) for the procedure which depends on type of bowel regimens, diet before colonoscopy and timing of the procedure.

Aims

The purpose of this study is to analyse the effect of multiple factors on adenoma detection rate (ADR) and prep quality of colonoscopy. This is the also the first study determining outcomes based on various combinations of diet, timing of the procedure and bowel prep regimens.

Methods

This is a retrospective single-centre observational study. Data about diet before procedure, bowel prepprep regimen and timing of the procedure was collected for patients coming for screening colonoscopy.

Results

Patients with split prep had higher good prep rates (73.8% vs 56.2%) and higher ADRs (34.2 % vs 29.9%) as compared with non-split prep. The good prep quality (65.8% vs 62.1%) and ADRs (31.9% vs 31.5%) were comparable in patients who received clear liquid diet as compared with low residue diet. The good results of bowel prep were obtained with split prep with either clear liquids or low residue diet irrespective of the timing of procedure. The poor prep was noticed in patients who underwent procedure in afternoon, with a low restrictive diet and non-split bowel regimen.

Conclusions

The current study adds to our knowledge about the combined effect of multiple variables affecting the bowel prep quality and ADR. It is imperative to opt for the best combination required for colonoscopy, as this will influence the effectiveness of colonoscopies regarding timely cancer detection and prevention.

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<![CDATA[Clinical significance of cancer specific methylation of the CDO1 gene in small bowel cancer]]> https://www.researchpad.co/article/5c536ba8d5eed0c484a48f2d

Although small bowel cancer (SBC) is extremely rare, its prognosis is poor, and molecular mechanism of the SBC development remains unclear. The aim of our study is to elucidate whether DNA methylation of the promoter region of the cancer-specific methylation gene, cysteine dioxygenase 1 (CDO1), contributes to the carcinogenic process in SBC. The study group comprised patients with 53 patients with SBC, 107 colorectal cancer (CRC), and other rare tumors of the small intestine such as 4 malignant lymphomas, 2 leiomyosarcomas, and 9 gastrointestinal stromal tumors. We analyzed the extent of methylation in each tissue using quantitative TaqMan methylation-specific PCR for CDO1. Significantly higher CDO1 methylation was observed in cancer tissues compared with non-cancerous mucosa of the small intestine (ROC = 0.96). Among the various clinicopathological factors, positive correlation of CDO1 methylation with tumor diameter was observed (R = 0.31, p = 0.03), and the CDO1 methylation level was a possible prognostic factor for relapse-free survival (p = 0.09). Compared with CRC, SBC had a significantly poorer prognosis (p = 0.007) and displayed a significantly higher CDO1 methylation level (p < 0.0001). Intriguingly, especially in pStage I/II, there were robust prognostic difference between SBC and CRC (p = 0.08 / p < 0.0001), which may reflect CDO1 methylation status (p = 0.02 / p = 0.001). Among small bowel tumors, CDO1 methylation in SBC was higher in order of malignant lymphoma, cancer, and leiomyosarcoma/GIST (p = 0.002) by ANOVA. The CDO1 gene shows extremely cancer-specific hypermethylation, and it can be a prognostic marker in SBC.

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<![CDATA[Distinct shed microvesicle and exosome microRNA signatures reveal diagnostic markers for colorectal cancer]]> https://www.researchpad.co/article/5c390bcfd5eed0c48491e776

Extracellular vesicle (EV) microRNAs are of major interest as potential diagnostic biomarkers in all cancer types. This study aims to identify miRNA profiles of shed microvesicles (sMVs) and exosomes (Exos) secreted from the isogenic colorectal cancer (CRC) cell lines SW480 and SW620 and evaluate their ability to predict CRC. Deep sequencing of miRNAs in parental cell lysates (CLs) and highly-purified sMVs and Exos was performed. We focused on miRNAs enriched in EVs and dysregulated miRNAs in metastatic cells (SW620) relative to primary cancer cells (SW480). We investigated the ability of EV miRNA signatures to predict CRC tumours using 594 tumours (representing different pathological stages) and 11 normal samples obtained from TCGA. In SW480 and SW620 cells we identified 345 miRNAs, of which 61 and 73 were upregulated and downregulated in SW620-CLs compared to SW480-CLs, respectively. Selective distribution of cellular miRNAs into EVs results in distinct miRNA signatures for sMVs and Exos in each cell line. Cross cell line comparisons of EV miRNA profiles reveal a subset of miRNAs critical in CRC progression from primary carcinoma to metastasis. Many miRNAs non-detectable (<5 TPM) in CLs were significantly enriched (>1000 TPM) in secreted EVs. Strikingly, miR-7641 which is non-detectable in SW480-CL but upregulated in SW620-CL is highly enriched in EVs secreted from both cell lines. Pearson correlation analysis demonstrated that EV miRNA profiles can be used to predict CRC tumours with ~96% accuracy. Our findings suggest that EV miRNA profiles from CRC cell lines may allow prediction of CRC tumours, and that miR-7641 may serve as an attractive candidate for the specific, non-invasive diagnosis and prognosis of CRC.

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<![CDATA[Risk interval analysis of emergency room visits following colonoscopy in patients with inflammatory bowel disease]]> https://www.researchpad.co/article/5c3fa587d5eed0c484ca5700

Background and aims

Prior studies suggest that colonoscopy may exacerbate inflammatory bowel disease (IBD) symptoms. Thus, our study aimed to determine risk of emergency room (ER) visits associated with colonoscopy among IBD patients and evaluate potential modifiers of this risk.

Methods

The study population included IBD patients in the Multi-Payer Claims Database who were >20 years old and had a colonoscopy from 2007–2010. We used a self-controlled risk interval design and mixed-effects Poisson regression models to calculate risk ratios (RR) and 95% confidence intervals (CI) comparing the incidence of ER visits in the 1–4 weeks following colonoscopy (risk interval) to the incidence of ER visits in the 7–10 weeks after colonoscopy (control interval). We also conducted stratified analyses by patient characteristics, bowel preparation type, and medication.

Results

There were 212,205 IBD patients with at least 1 colonoscopy from 2007–2010, and 3,699 had an ER visit during the risk and/or control interval. The risk of an ER visit was higher in the 4-week risk interval following colonoscopy compared to the control interval (RR = 1.24; 95% CI: 1.17–1.32). The effect was strongest in those <41 years old (RR = 1.60; 95% CI: 1.21–2.11), in women (RR = 1.32; 95% CI: 1.21–1.44), and in those with sodium phosphate bowel preparation (RR = 2.09; 95% CI: 1.02–4.29). Patients using immunomodulators had no increased risk of ER visits (RR = 0.75; 95% CI: 0.35–1.59).

Conclusions

Our results suggest that there is an increased risk of ER visits following colonoscopy among IBD patients, but that immunomodulators and mild bowel preparation agents may mitigate this risk.

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<![CDATA[Cost-effectiveness of mini-laparotomy in patients with colorectal cancers: A propensity scoring matching approach]]> https://www.researchpad.co/article/5c3fa59cd5eed0c484ca6752

Objective

Surgical technique process innovations are expected to generally incur no additional cost but gain better quality. Whether a mini-laparotomy surgery (MLS) in the treatment of colorectal cancer (CRC) is more cost effective than conventional open surgery had not been well examined. The objective of this study was to apply cost-effectiveness approaches to investigate the cost effectiveness of adopting MLS compared with open surgery 1 year following resection in CRC patients.

Research design

A prospective non-randomized cohort study design

Setting

An academic medical center

Participants

A total of 224 patients who received elective MLS and 339 who received conventional surgery; after propensity score matching, 212 pairs were included for analysis.

Intervention

None

Main outcome measures

Cost measures were hospital-index cost and outpatient and inpatient costs within 1 year after discharge. Effectiveness measures were life-years (LYs) gained and quality-adjusted life-year (QALYs) gained.

Statistical methods

We calculated incremental costs and effectiveness by differences in these values between MLS and conventional surgery using adjusted predicted estimates.

Results

MLS patients had lower rates of blood transfusions, less complication, and shorter post-surgical lengths of stay and more medical cost savings. One-year overall medical costs for MLS patients were TWD 748,269 (USD 24,942) per QALY gained, significant lower than for the comparison group (p-value = 0.045).

Conclusion

Our findings supported that the less invasive surgical process through MLS not only saved medical costs, but also increased QALYs for surgical treatment in CRC patients.

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<![CDATA[Metabolomics and 16S rRNA sequencing of human colorectal cancers and adjacent mucosa]]> https://www.researchpad.co/article/5c269780d5eed0c48470fb79

Colorectal cancer (CRC) is ranked the third most common cancer in human worldwide. However, the exact mechanisms of CRC are not well established. Furthermore, there may be differences between mechanisms of CRC in the Asian and in the Western populations. In the present study, we utilized a liquid chromatography-mass spectrometry (LC-MS) metabolomic approach supported by the 16S rRNA next-generation sequencing to investigate the functional and taxonomical differences between paired tumor and unaffected (normal) surgical biopsy tissues from 17 Malaysian patients. Metabolomic differences associated with steroid biosynthesis, terpenoid biosynthesis and bile metabolism could be attributed to microbiome differences between normal and tumor sites. The relative abundances of Anaerotruncus, Intestinimonas and Oscillibacter displayed significant relationships with both steroid biosynthesis and terpenoid and triterpenoid biosynthesis pathways. Metabolites involved in serotonergic synapse/ tryptophan metabolism (Serotonin and 5-Hydroxy-3-indoleacetic acid [5-HIAA]) were only detected in normal tissue samples. On the other hand, S-Adenosyl-L-homocysteine (SAH), a metabolite involves in methionine metabolism and methylation, was frequently increased in tumor relative to normal tissues. In conclusion, this study suggests that local microbiome dysbiosis may contribute to functional changes at the cancer sites. Results from the current study also contributed to the list of metabolites that are found to differ between normal and tumor sites in CRC and supported our quest for understanding the mechanisms of carcinogenesis.

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<![CDATA[Colorectal cancer survival rates in Ghana: A retrospective hospital-based study]]> https://www.researchpad.co/article/5c23f27cd5eed0c484046ef3

Background

Colorectal cancer (CRC) is one of the commonest cancers associated with diverse prognosis times in different parts of the world. Despite medical interventions, the overall clinical outcomes and survival remains very poor for most patients in developing countries. This study therefore investigated the survival rate of colorectal cancer and its prognostic factors among patients at Komfo Anokye Teaching Hospital, Ghana.

Methodology

In this retrospective cohort study, a total of 221 patients diagnosed with CRC from 2009 to 2015 at the Surgical and Oncological units of Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana were employed. The survival graphs were obtained using the Kaplan–Meier method and compared by the Log-rank test. Cox regression analysis was used to assess prognostic factors. All analyses were performed by SPSS version 22.

Results

The median survival time was 15 months 95% CI (11.79–18.21). The overall survival rate for CRC over the 5 years period was 16.0%. The survival rates at the 1st, 2nd, 3rd, 4th and 5th years were 64% 95% CI (56.2–71.1), 40% 95% CI (32.2–50.1), 21% 95% CI (11.4–30.6) 16% 95% CI (8.9–26.9) and 16% 95% CI (7.3–24.9). There was a significant difference in the survival rate of colorectal cancer according to the different stages (p = 0.0001). Family history [HR = (3.44), p = 0.029)], Chemotherapy [HR = (0.23), p = <0.0001)], BMI [HR = (1.78), p = 0.017)] and both chemo/radiotherapy (HR = (3.63), p = 0.042)] were the significant social and clinical factors influencing the overall survival. Pathological factors such as TNM tumour stage (p = 0.012), depth of tumour invasion (p = 0.036), lymph node metastasis (p = 0.0001), and distance metastasis (p = 0.001) were significantly associated with overall survival.

Conclusion

The study has clearly demonstrated that survival rate for CRC patients at KATH, Ghana is very low in a 5 years period. This is influenced by significant number of clinical and pathological prognostic factors. Identification of prognostic factors would be a primary basis for early prediction and treatment of patients with colorectal cancer.

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<![CDATA[Bayesian adjustment for trend of colorectal cancer incidence in misclassified registering across Iranian provinces]]> https://www.researchpad.co/article/5c1c0a86d5eed0c4844262c1

Misclassification error is a common problem of cancer registries in developing countries that leads to biased cancer rates. The purpose of this research is to use Bayesian method for correcting misclassification in registered cancer incidence of eighteen provinces in Iran. Incidence data of patients with colorectal cancer were extracted from Iranian annual of national cancer registration reports from 2005 to 2008. A province with proper medical facilities can always be compared to its neighbors. Almost 28% of the misclassification was estimated between the province of East Azarbaijan and West Azarbaijan, 56% between Fars and Hormozgan, 43% between Isfahan and Charmahal and Bakhtyari, 46% between Isfahan and Lorestan, 58% between Razavi Khorasan and North Khorasan, 50% between Razavi Khorasan and South Khorasan, 74% between Razavi Khorasan and Sistan and Balochestan, 43% between Mazandaran and Golestan, 37% between Tehran and Qazvin, 45% between Tehran and Markazi, 42% between Tehran and Qom, 47% between Tehran and Zanjan. Correcting the regional misclassification and obtaining the correct rates of cancer incidence in different regions is necessary for making cancer control and prevention programs and in healthcare resource allocation.

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<![CDATA[Genome wide association study to identify predictors for severe skin toxicity in colorectal cancer patients treated with cetuximab]]> https://www.researchpad.co/article/5c21513cd5eed0c4843f9470

EGFR-antibodies are associated with significant skin toxicity, including acneiform rash and folliculitis. It remains impossible to predict the occurrence of severe skin toxicity due to the lack of predictive markers. Here, we present the first genome-wide association study (GWAS) to find single nucleotide polymorphisms (SNPs) associated with EGFR inhibitor-induced skin toxicity using data of the multicentre randomized phase III CAIRO2 trial (clinicaltrials.gov NCT00208546). In this study, advanced or metastatic colorectal cancer patients were treated with capecitabine, oxaliplatin and bevacizumab with or without cetuximab. Germline DNA was available in 282 of the 368 patients in the cetuximab arm. Mild skin toxicity occurred in 195 patients (i.e. CTC grade 1 or 2, respectively 91 and 104 patients) and severe skin toxicity (i.e. grade 3) in 36 patients. Grade 4 skin toxicity did not occur. None of the SNPs reached the formal genome wide threshold for significance of 5x10-8, though SNPs of at least 8 loci did show moderate association (p-value between 5x10-7 and 5x10-5) with the occurrence of grade 3 (severe) skin toxicity. These SNPs did not overlap with SNPs associated with cetuximab efficacy as found in a previous GWAS in the same CAIRO2 cohort. If formally proven by replication, the SNPs associated with severe EGFR induced skin toxicity may be helpful to predict the occurrence and severity of skin toxicity in patients that will receive cetuximab and allow for adequate information on the risk of skin toxicity and prophylactic measurements.

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<![CDATA[Value of preoperative spirometry test in predicting postoperative pulmonary complications in high-risk patients after laparoscopic abdominal surgery]]> https://www.researchpad.co/article/5c23f277d5eed0c484046d45

Whether preoperative spirometry in non-thoracic surgery can predict postoperative pulmonary complications (PPCs) is controversial. We investigated whether preoperative spirometry results can predict the occurrence of PPCs in patients who had undergone laparoscopic abdominal surgery. This retrospective observational study analyzed the records of patients who underwent inpatient laparoscopic gastric or colorectal cancer surgery at Seoul National University Bundang Hospital between January 2010 and June 2017. Preoperative spirometry was performed for patients at a high risk of PPCs, such as elderly patients (age >60 years), patients aged <60 years with chronic pulmonary disease, and current smokers. The main outcome was the association between the results of spirometry tests performed within 1 month prior to surgery and the occurrence of PPCs, as determined by multivariable logistic regression analysis. Of the 898 included patients who underwent laparoscopic gastric (372 patients) or colorectal cancer surgery (526 patients), PPC occurred in 117 patients (gastric cancer: 74, colorectal cancer: 43). A 1% greater preoperative forced vital capacity (FVC) was associated with a 2% lower incidence of PPCs after laparoscopic gastric or colorectal cancer surgery (odds ratio: 0.98, 95% confidence interval: 0.97–0.99, P = 0.018). However, the preoperative forced expiratory volume in 1 second (FEV1) (%) and FEV1/FVC (%) were not significantly associated with PPCs (P = 0.059 and P = 0.147, respectively). In conclusion, lower preoperative spirometry FVC, but not FEV1 or FEV1/FVC, may predict PPCs in high-risk patients undergoing laparoscopic abdominal surgery.

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<![CDATA[Prevalence of elevated microsatellite alterations at selected tetranucleotide repeats in pancreatic ductal adenocarcinoma]]> https://www.researchpad.co/article/5c141e95d5eed0c484d274a5

Pancreatic ductal adenocarcinoma (PDAC) prognosis remains poor even after complete resection owing to no valuable biomarkers for recurrence and chemosensitivity. Tumors not expressing MSH3 show elevated microsatellite alterations at selected tetranucleotide repeats (EMAST). EMAST reportedly occurs in several tumors. In colorectal cancer (CRC), EMAST was reportedly correlated with 5-fluorouracil (5-FU) sensitivity. However, EMAST prevalence in PDAC and its significance as a prognostic biomarker are unknown. This study aimed to investigate EMAST prevalence in PDAC and the associations between EMAST and pathological factors, EMAST and prognosis, and EMAST and MSH3 expression via immunohistochemistry (IHC). We assessed 40 PDAC patients undergoing surgery. Genomic DNA was extracted from tumors and normal tissues. EMAST and microsatellite instability-high (MSI-H) were analyzed using five polymorphic tetranucleotide markers and five mononucleotide markers, respectively. Tumor sections were stained for MSH3, and staining intensity was evaluated via the Histoscore (H-score). Eighteen of 40 (45%) PDAC patients were EMAST-positive; however, none were MSI-H-positive. Clinicopathological characteristics including overall survival (OS) and recurrence-free survival (RFS) were not significantly different between EMAST-positive and EMAST-negative patients (P = 0.45, 0.98 respectively). IHC was performed to evaluate MSH3 protein expression levels for the PDAC tissue specimens. H-scores of EMAST-positive patients ranged from 0 to 300 (median, 40) and those of EMAST-negative patients ranged from 0 to 300 (median, 170). MSH3 protein was not significantly downregulated in EMAST-positive patients (P = 0.07). This study is a preliminary study and the number of cases investigated was small, and thus, study of a larger cohort will reveal the clinical implication of EMAST.

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<![CDATA[Establishment of inflammation biomarkers-based nomograms to predict prognosis of advanced colorectal cancer patients based on real world data]]> https://www.researchpad.co/article/5c10288bd5eed0c48424776c

Purpose

To establish three novel prognostic nomograms with inflammatory factors for advanced colorectal cancer (ACRC), right-sided colon cancer (RSCC) and left-sided colorectal cancer (LSCRC) according to real world data.

Materials and methods

ACRC patients receiving medicine therapy from January 1st, 2005 to September 31th, 2015 in Sun Yat-sen University Cancer Center were enrolled. Inflammatory indicators such as the neutrophil-to-lymphocyte ratio (NLR), the platelet-lymphocyte ratio (PLR), carcinoembryonic antigen (CEA), carbohydrate antigen 19–9 (CA 19–9), lactate dehydrogenase (LDH) and C-reactive protein (CRP) were analyzed for establishing nomograms predicting overall survival (OS). Concordance index (C-index) determined predictive accuracy and discriminative ability.

Results

Our study selected 807 ACRC patients, 29.6% RSCC and 70.4% LSCRC. Median OS was 23.36 months. Patients at lower level of NLR, PLR, CEA, CA 19–9, LDH and CRP showed longer OS (P < 0.001). For all patients, pathological grade (P = 0.018), treatments (P = 0.042), sidedness (P = 0.003), NLR (P < 0.001), CA 19–9 (P < 0.001), LDH (P < 0.001) and CRP (P = 0.0012) contributed to OS independently. For RSCC, pathological grade (P = 0.022), CA 19–9 (P < 0.001), LDH (P < 0.001) and CRP (P = 0.001) were significantly related with OS. For LSCRC patients, treatments (cetuximab vs chemotherapy: P = 0.008; bevacizumab vs chemotherapy: P = 0.166), NLR (P < 0.001), CA 19–9 (P = 0.030) and LDH (P < 0.001) were independent factors for OS. Final models showed acceptable internal validity with C-indexes of 0.687, 0.697 and 0.667 in all, RSCC and LSCRC patients.

Conclusions

Inflammatory factors enrolled in the proposed nomograms showed accurately individualized prognostic prediction, and prognostic factors for RSCC and LSCRC were different.

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