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Rectal cancer is mainly cured by radical resection with neoadjuvant chemoradiation or adjuvant chemotherapy. Pathological T1 lesions can be managed by local treatment and radiotherapy thereafter. Lower morbidity is the key benefit of these local treatments. Since nodal metastasis is important for staging, radical resection (RR) is suggested. Rectal cancer has higher surgical morbidity than colon cancer; local treatment has been the preferred choice by patients.We retrospectively enrolled data of 244 patients with pT1 rectal adenocarcinoma. A total of 202 patients (82.8%) underwent RR, including low anterior resection (LAR) and abdomino-perineal resection (APR), and 42 patients (17.2%) underwent LT, including transanal excision and colonoscopic polypectomy.In our study, seven patients (16.7%) had loco-regional recurrence and distant metastasis from the LT group while eight patients (4.0%) had distant metastasis without loco-regional recurrence from the RR group. The lymph node metastasis rate in RR group was 8.4%. Forty-seven patients (24.2%) underwent LAR with temporary stoma, and its reversal rate was 100%. In the RR group, postoperative complication rate was 10.4% with a mortality rate of 0.5%. Recurrence-free survival (RFS) was 95.7% for RR and 80.2% for LT (P = 0.001), and overall survival (OS) was 93.7% for RR and 70.0% for LT (P = 0.001).This study found that RFS and OS in patients of pT1 rectal adenocarcinoma that had received RR were better than receiving LT. Further adjuvant chemotherapy was possible for some RR patients. A higher recurrence rate after LT must be balanced against the morbidity and mortality associated with RR.

Supplementary Figure 2 from A Novel E1B-55kD-Deleted Oncolytic Adenovirus Carrying Mutant KRAS-Regulated hdm2 Transgene Exerts Specific Antitumor Efficacy on Colorectal Cancer Cells

Supplementary Figure 1 from A Novel E1B-55kD-Deleted Oncolytic Adenovirus Carrying Mutant KRAS-Regulated hdm2 Transgene Exerts Specific Antitumor Efficacy on Colorectal Cancer Cells

Lymph node skip metastasis is a subgroup of lymph node metastatic patterns with low incidence in node-positive colon cancer. Its clinical significance is still unclear.This study aimed to investigate the prognostic impact of lymph node skip metastasis in stage III colon cancer.Retrospective observational analysis.The study was conducted at Taipei Veterans General Hospital.Patients with stage III colon cancer who underwent D3 lymphadenectomy between 2006 and 2015.The patients were divided into a lymph node skip metastasis positive group and a negative group. Recurrence-free survival and overall survival were compared using Kaplan-Meier curves and log-rank test. Cox regression was applied to identify related risk factors influencing survival.A total of 461 patients were reviewed, and lymph node skip metastasis positive patients represented 13.2% of our sample. Patients with lymph node skip metastasis tended to present with a higher proportion of right sided cancer, lower positive lymph nodes, lower lymph node ratio and higher mean BMI. Liver recurrence was more prevalent in the lymph node skip metastasis group (p = 0.028) than in the negative group. The presence of lymph node skip metastasis was a negative prognostic factor for 5-year recurrence-free survival (51.4% vs. 68.7%, p = 0.002) and 5-year overall survival (66.4% vs. 80.4%, p = 0.024) in Kaplan-Meier curves and multivariate Cox regression. Subgroup analysis revealed the survival significance of recurrence-free survival (p = 0.001) and overall survival (p = 0.011) in lymph node skip metastasis with pN1 disease.Retrospective design, single center nature, and sampling error.Lymph node skip metastasis is an independent negative prognostic factor in stage III colon cancer with pN1 disease. More intensive surveillance may be necessary for patients of this subgroup. See Video Abstract at http://links.lww.com/DCR/C60.

Background Clinically, metastatic rectal cancer has been considered a subset of left-sided colon cancer. However, heterogeneity has been proposed to exist between high and middle/low rectal cancers. We aimed to examine the efficacy of anti-epidermal growth factor receptor (EGFR) treatment for middle/low rectal and left-sided colon cancers. Methods This study enrolled 609 patients with metastatic colorectal cancer who were treated with anti-EGFR therapy. They were divided into groups based on primary tumour locations: the right-sided colon, the left-sided colon or the middle/low rectum. The efficacy of first-line and non-first-line anti-EGFR treatment was analysed. Genomic differences in colorectal cancer data from The Cancer Genome Atlas (TCGA) were investigated and visualised with OncoPrint and a clustered heatmap. Results On first-line anti-EGFR treatment, patients with middle/low rectal tumours had significantly lower progression-free survival, overall survival, and overall response rates (6.8 months, 27.8 months and 43%, respectively) than those with left-sided colon cancer (10.1 months, 38.3 months and 66%, respectively). Similar outcomes were also identified on non-first-line anti-EGFR treatment. In TCGA analysis, rectal tumours displayed genetic heterogeneity and shared features with both left- and right-sided colon cancer. Conclusions Anti-EGFR treatment has lower efficacy in metastatic middle/low rectal cancer than in left-sided colon cancer.

The effects of primary tumor location on colorectal liver metastasis (CRLM) and post-hepatic-metastasectomy overall survival (OS) are controversial. This study evaluated the difference in post-hepatic-metastasectomy OS among right-sided colon, left-sided colon, and rectal cancer groups. In total, 381 patients who underwent curative-intent CRLM resection were enrolled. Patients were grouped based on the primary tumor location (right-sided, left-sided, and rectum). The Kaplan–Meier analysis and log-rank test were performed for survival analysis. The univariate and multivariate analyses of clinical and pathological factors were performed using the Cox proportional hazards model. Significant OS difference was noted among the three groups (log-rank, p = 0.014). The multivariate analysis revealed a 32% lower death risk in left-sided colon cancer compared with right-sided colon cancer (hazard ratio [HR] 0.68, p = 0.042), whereas no OS difference was noted between the rectal cancer and right-sided colon cancer groups. The left- versus right-sided OS advantage was noted only in the KRAS wild-type subgroup (HR 0.46, p = 0.002), and a rectal versus right-sided OS disadvantage was noted in the KRAS mutant subgroup (HR 1.78, p = 0.03). The CRLM post-hepatic-metastasectomy OS was superior in left-sided colon cancer than in right-sided colon cancer and was similar in rectal and right-sided colon cancer. The OS difference in different primary tumor locations is dependent on KRAS mutation status, with a decreased left- versus right-sided death risk noted only in KRAS wild-type colon cancer and an increased rectal versus right-sided death risk noted only in KRAS mutant colon cancer.

BACKGROUND Both regorafenib and reduced-intensity FOLFOXIRI (riFOLFOXIRI) prolong survival in patients with metastatic colorectal cancer (mCRC). However, the sequence in which they should be administrated first in late-line treatment for refractory mCRC remains unclear. PATIENTS AND METHODS This study was a single-center retrospective cohort study that reviewed data from patients at Taipei Veterans General Hospital, Taiwan, with mCRC refractory to fluorouracil, irinotecan, oxaliplatin, cetuximab (wild-type RAS), and bevacizumab. Patients were divided into 2 groups: a regorafenib-first group and a riFOLFOXIRI-first group. The Kaplan-Meier method and log-rank test were used to analyze survival, and a Cox proportional hazards model was used for univariate, multivariate, and subgroup analyses. RESULTS A total of 136 and 55 patients followed a regorafenib-first or riFOLFOXIRI-first treatment strategy, respectively. At baseline, patient characteristics were similar between the groups, except for younger age in the riFOLFOXIRI-first group. The regorafenib-first group had better overall survival (13.8 vs. 10.7 mo, P=0.038), whereas patients in the riFOLFOXIRI-first group had a better partial response rate (P=0.005) but a higher rate of discontinuation due to adverse effects (P=0.004) and cross-over to regorafenib (P

Colorectal cancer (CRC) is one of the most well-known malignancies with high prevalence and poor 5-year survival. Previous studies have demonstrated that a high-fat diet (HFD) is capable of increasing the odds of developing CRC. Acrolein, an IARC group 2A carcinogen, can be formed from carbohydrates, vegetable oils, animal fats, and amino acids through the Maillard reaction during the preparation of foods. Consequently, humans are at risk of acrolein exposure through the consumption of foods rich in fat. However, whether acrolein contributes to HFD-induced CRC has not been determined. In this study, we found that acrolein induced oncogenic transformation, including faster cell cycling, proliferation, soft agar formation, sphere formation and cell migration, in NIH/3T3 cells. Using xenograft tumorigenicity assays, the acrolein-transformed NIH/3T3 clone formed tumors. In addition, cDNA microarray and bioinformatics studies by Ingenuity Pathway Analysis pointed to the fact that RAS/MAPK pathway was activated in acrolein-transformed clones that contributed to colon tumorigenesis. Furthermore, acrolein-induced DNA damages (Acr-dG adducts) were higher in CRC tumor tissues than in normal epithelial cells in CRC patients. Notably, CRC patients with higher levels of Acr-dG adducts appeared to have better prognosis. The results of this study demonstrate for the first time that acrolein is important in oncogenic transformation through activation of the RAS/MAPK signaling pathway, contributing to colon tumorigenesis.

Given the unclear preference criteria for regorafenib in treating refractory metastatic colorectal cancer (mCRC), this study aimed to construct an algorithm in selecting right patients for regorafenib. This was a multicenter retrospective cohort study. Patients with pathology confirmed mCRC and administered with regorafenib for > 3 weeks were enrolled. Patients with good response were defined to have progression-free survival (PFS) of ≥ 4 months. The Kaplan–Meier plot was used to analyze survival. A Cox proportional hazards model was used to analyze univariate and multivariate prognostic factors and was visualized using forest plot. A clustering heatmap was used to classify patients according to responses. The decision tree and nomogram were used to construct the approaching algorithm. A total of 613 patients was analyzed. The median PFS and overall survival (OS) were 2.7 and 10.6 months, respectively. The partial response and stable disease rate are 2.4% and 36.4%. The interval between metastasis (M1) and regorafenib, metastatic status (number, liver, and brain), and CEA level were independent prognostics factors of PFS that classifies patients into three groups: good, bad and modest-1/modest-2 group with PFS > = 4 months rates of 51%, 20%, 39% and 30%, respectively. Results were used to develop the decision tree and nomogram for approaching patients indicated with regorafenib. The preference criteria for regorafenib in treating patients with refractory mCRC are small tumor burden (CEA), slow growth (interval between metastasis and regorafenib) and poor/scanty spread (metastatic status: number and sites of metastasis): The 3S rules. TRIAL registration ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT03829852","term_id":"NCT03829852"}}NCT03829852; Date of first registration (February 11, 2019).

Colorectal cancer (CRC) is one of the most well-known malignancies with high prevalence and poor 5-year survival. Previous studies have demonstrated that a high-fat diet (HFD) is capable of increasing the odds of developing CRC. Acrolein, an IARC group 2A carcinogen, can be formed from carbohydrates, vegetable oils, animal fats, and amino acids through the Maillard reaction during the preparation of foods. Consequently, humans are at risk of acrolein exposure through the consumption of foods rich in fat. However, whether acrolein contributes to HFD-induced CRC has not been determined. In this study, we found that acrolein induced oncogenic transformation, including faster cell cycling, proliferation, soft agar formation, sphere formation and cell migration, in NIH/3T3 cells. Using xenograft tumorigenicity assays, the acrolein-transformed NIH/3T3 clone formed tumors. In addition, cDNA microarray and bioinformatics studies by Ingenuity Pathway Analysis pointed to the fact that RAS/MAPK pathway was activated in acrolein-transformed clones that contributed to colon tumorigenesis. Furthermore, acrolein-induced DNA damages (Acr-dG adducts) were higher in CRC tumor tissues than in normal epithelial cells in CRC patients. Notably, CRC patients with higher levels of Acr-dG adducts appeared to have better prognosis. The results of this study demonstrate for the first time that acrolein is important in oncogenic transformation through activation of the RAS/MAPK signaling pathway, contributing to colon tumorigenesis.

Background Three-dimensional (3D) laparoscopy was developed to overcome the drawbacks of two-dimensional (2D) laparoscopy, namely lack of depth perception. However, the benefit of 3D laparoscopy in colorectal surgery is inconclusive. Here, we compare the 3-year follow-up outcomes of 3D and 2D laparoscopic colectomy. Patients and methods A total of 91 consecutive patients who underwent either 3D or 2D laparoscopy colectomy from October 2015 to November 2017 by a single surgical team for colon cancer were enrolled. Data were collected from a prospectively constructed database, including clinico-pathological features and operative parameters. The pathological results, recurrence, survival and systemic treatment were collected from the Taiwan Cancer Database. Results There were 47 patients in the 3D group and 44 in the 2D group. There were no significant differences in characteristics of patients, operation data, pathological results, complications, operative time, blood loss or the number of lymph node harvested between the two groups. In addition, disease-free survival and overall survival were equal between the two groups. Conclusions This is the first long-term result of a 3D laparoscopic colectomy. In our 3-year follow-up, there was no difference in long-term outcomes between 2D and 3D laparoscopy for colorectal surgery in an experienced centre.

To compare the cost-performance between planned short-course radiation and upfront concurrent chemoradiation on metastatic rectal cancer. A total of 75 patients with metastatic rectal cancer who underwent planned short-course radiation or upfront concurrent chemoradiation were enrolled. The Kaplan-Meier method was used to compute the survival rates. The χ2 test was used to compare baseline characteristics. The Cox proportional hazards model was applied to determine the prognostic influence of clinicopathological factors. The planned short-course radiation is superior to upfront concurrent chemoradiation in overall survival for the patients with metastatic rectal cancer (34.8 vs. 20.2 months, P = 0.010). The planned short-course radiation was an independent prognostic factor (P = 0.009, HR (95% CI) = 0.319(0.135–0.752)). The efficacy of radiation on downstaging was similar between planned short-course radiation and upfront concurrent chemoradiation. The total cost of concurrent chemoradiation is 4.52-fold more expensive than that of short-course radiation (340,142 vs. 75,106 NT dollars, respectively). Based on the impressive cost-performance of planned short-course radiation compared with upfront concurrent chemoradiation (better OS, modest downstaging and lower cost), planned short-course radiation should be the preferred radiation approach for managing metastatic rectal cancer.

Background Laparoscopic surgery has become a well-established technique for management of various surgical problems. A more efficient training methods are of upmost importance for current surgery residents. Methods This is a prospective, randomized, 3-arm trial to compare the training efficient of the naked-eye box trainer, training box games and conventional video-based box trainer in training laparoscopic suturing skill. Results The three training models were well acceptable and all could improve the acquisition of laparoscopic suturing and knotting skill in novices. The completion time was 604 ± 298 s in the box trainer games, 617 ± 335 s in the naked-eye training module, and 491 ± 334 s in the video-based box trainer (p = 0.322). Using the structured procedure-specific checklist, there was no significant difference in scores between these three groups (p = 0.977). Conclusions Naked-eye box trainer and training box games produce similar training effect as the conventional video-based box trainer. The naked-eye box trainer may serve as a convenient way for novice trainees to acquire laparoscopic suturing technique skills before video-based simulation.

Clinically, metastatic rectal cancer has been considered a subset of left-sided colon cancer. However, heterogeneity has been proposed to exist between high and middle/low rectal cancers. We aimed to examine the efficacy of anti-epidermal growth factor receptor (EGFR) treatment for middle/low rectal and left-sided colon cancers.This study enrolled 609 patients with metastatic colorectal cancer who were treated with anti-EGFR therapy. They were divided into groups based on primary tumour locations: the right-sided colon, the left-sided colon or the middle/low rectum. The efficacy of first-line and non-first-line anti-EGFR treatment was analysed. Genomic differences in colorectal cancer data from The Cancer Genome Atlas (TCGA) were investigated and visualised with OncoPrint and a clustered heatmap.On first-line anti-EGFR treatment, patients with middle/low rectal tumours had significantly lower progression-free survival, overall survival, and overall response rates (6.8 months, 27.8 months and 43%, respectively) than those with left-sided colon cancer (10.1 months, 38.3 months and 66%, respectively). Similar outcomes were also identified on non-first-line anti-EGFR treatment. In TCGA analysis, rectal tumours displayed genetic heterogeneity and shared features with both left- and right-sided colon cancer.Anti-EGFR treatment has lower efficacy in metastatic middle/low rectal cancer than in left-sided colon cancer.

Background. Colorectal cancer (CRC) is one of the most well-known malignancies with high prevalence and poor 5-year survival. Previous studies have demonstrated that intake of food rich in fat, and with low fiber content (as known as high-fat diet, HFD) is capable of increasing the odds of developing CRC. Acrolein, an IARC group 2A carcinogen, can be formed by thermal treatment of animal and vegetable fats, carbohydrates and amino acids through Maillard reaction. Also, acrolein has been shown to be produced from microbial glycerol metabolism in human gut. Consequently, humans are at risk of acrolein exposure through consumption of foods rich in fat. However, whether acrolein contributes to HFD-induced CRC tumorigenesis remains elusive.Methods. The effect of acrolein in oncogenic transformation was analyzed using NIH/3T3 cells with xenograft tumorigenesis mice models. Furthermore, cDNA microarray analysis with Ingenuity Pathway Analysis (IPA) was performed in acrolein-transformed NIH/3T3 cells. Finally, acrolein-induced DNA damages (Acr-dG) were analyzed in tumor tissues and normal epithelial of CRC patients using immunohistochemical analysis. The levels of Acr-dG adducts were associated with tumor characteristics and CRC patients’ survival using Chi-Square analysis and Kaplan Meier survival analysis, respectively.Results. In this present study, we found that acrolein induced oncogenic transformation including faster cell cycling, proliferation, soft agar formation, sphere formation, cell migration in NIH/3T3 cells. Using xenograft tumorigenicity assays, the acrolein-transformed NIH3T3 clone formed tumors whereas no tumors were observed in mice inoculated with NIH3T3 parental cells. In addition, RAS/MAPK pathway contributing to colon tumorigenesis was activated in NIH/3T3 Acr-clone using cDNA microarray analysis with IPA. Finally, Acr-dG adducts were higher in CRC tumor tissues compared to normal epithelial cells in CRC patients. Intriguingly, CRC patients with higher Acr-dG adducts have better prognosis. Conclusions. Taken together, this is the first study to demonstrate that acrolein is important in oncogenic transformation through activating RAS/MAPK signaling pathway contributing to colon tumorigenesis. Thus, acrolein might be a novel target for early detection, prevention and treatment of tumors in the future.

Background We present our initial single-centre experience with Senhance surgical robot-assisted colorectal surgery and examine its safety and feasibility. Methods From June 2019 to December 2019, patients who underwent Senhance surgical robot-assisted colorectal surgery in our hospital were retrospectively analysed. We focused on the short-term outcomes. Results In total, 46 patients were enrolled in the study. Colorectal cancer was the most common indication for surgery (39 patients). The median total operation time was 283 min, and the median blood loss was 50 cc. Meanwhile, the median number of harvested lymph nodes was 20. Elderly age, advanced American Society of Anaesthesiologists stage, and right-sided colon surgery were associated with the occurrence of complications greater than grade III. Conclusion Our findings demonstrate the feasibility and safety of the Senhance surgical robotic system in colorectal surgery. Care should be taken regarding the indications and patient selection.

BackgroundThe prognosis of mucinous adenocarcinoma (MAC) and non-mucinous adenocarcinoma (NMAC) in colorectal cancer (CRC) is controversial, and the molecular differences between them are unclear.MethodsBetween 2000 and 2010, a total of 1,483 CRC patients were included. Among them, 73 patients (4.9%) were diagnosed with MAC. The clinicopathological features and genetic alterations were compared between MAC and NMAC.ResultsAfter propensity score matching to balance age and sex between MAC and NMAC patients, 292 CRC patients (73 MAC and 219 NMAC) were enrolled in the analysis at a 1:3 ratio. In right-sided colon cancer, patients with MAC were more likely to have Borrmann types 3 and 4 tumors, poor differentiation, and advanced T category and tumor, node, metastasis (TNM) stage, chemotherapy, and a similar 5-year overall survival (OS) rate compared with patients with NMAC. In left-sided colon cancer and rectal cancer, patients with MAC were more likely to have Borrmann types 3 and 4 tumors, poor differentiation, lymphovascular invasion, advanced T and N categories and TNM stages, chemotherapy, and a worse 5-year OS rate than patients with NMAC. Regarding genetic alterations, for NMAC, right-sided colon cancer had more BRAF mutations than left-sided colon cancer and rectal cancer. For MAC, right-sided colon cancer was associated with more microsatellite instability-high tumors and more AKT1 mutations than left-sided colon cancer and rectal cancer.ConclusionThe genetic alterations are distinct between MAC and NMAC in CRC. Tumor location may have an impact on genetic alterations and patient prognosis in MAC and NMAC.

The molecular difference between synchronous and metachronous metastases in colorectal cancer (CRC) remains unclear. Between 2000 and 2010, a total of 492 CRC patients were enrolled, including 280 with synchronous metastasis and 212 with metachronous metastasis. Clinicopathological and molecular features were compared between the two groups. Patients with synchronous metastasis were more likely to have right-sided CRC, poorly differentiated tumors, lymphovascular invasion, advanced pathological tumor (T) and node (N) categories, and liver metastases than those with metachronous metastasis. For right-sided CRC, patients with synchronous metastasis had more lymphovascular invasion and liver metastases than those with metachronous metastasis. For left-sided CRC, patients with synchronous metastasis were more likely to have poorly differentiated tumors, lymphovascular invasion, advanced pathological T and N categories, and liver metastases than those with metachronous metastasis. Regarding the genetic mutations, patients with metachronous metastasis had more mutations in TP53, NRAS, and HRAS and fewer mutations in APC than those with synchronous metastasis; for right-sided CRC, synchronous metastasis was associated with more APC mutations than metachronous metastasis, while for left-sided CRC, metachronous metastasis was associated with more TP53 and NRAS mutations than synchronous metastasis. The 5-year overall survival (OS) rates were significantly higher in metachronous metastasis patients than in synchronous metastasis patients, especially those with left-sided CRC. Multivariate analysis showed that age, sex, lymphovascular invasion, pathological N category, metachronous metastasis, and BRAF and NRAS mutations were independent prognostic factors affecting OS. CRC patients with synchronous metastasis had a worse OS than those with metachronous metastasis and exhibited distinct genetic mutations.

Colorectal carcinoma (CRC) is one of the most prevalent cancers worldwide and has a high mortality rate. Long noncoding RNAs (lncRNAs) have been noted to play critical roles in cell growth, cell apoptosis, and metastasis in CRC. This study determined that LOC441461 expression was significantly higher in CRC tissues than in adjacent normal mucosa. Pathway enrichment analysis of LOC441461-coexpressed genes revealed that LOC441461 was involved in biological functions related to cancer cell growth and motility. Knockdown of the LOC441461 expression significantly suppressed colon cancer cell growth by impairing cell cycle progression and inducing cell apoptosis. Furthermore, significantly higher LOC441461 expression was discovered in primary colon tumors and metastatic liver tumors than in the corresponding normal mucosa, and LOC441461 knockdown was noted to suppress colon cancer cell motility. Knockdown of LOC441461 expression suppressed the phosphorylation of MLC and LIMK1 through the inhibition of RhoA/ROCK signaling. Overall, LOC441461 was discovered to play an oncogenic role in CRC cell growth and motility through RhoA/ROCK signaling. Our findings provide new insights into the regulation of lncRNAs and their application in the treatment of colon cancer

Background Perineal wound complications are a long-lasting issue for abdominoperineal resection (APR) patients. Complication rates as high as 60% have been reported, with the most common complication being delayed perineal wound healing. The aim of this study was to identify risk factors for delayed perineal wound healing and its impact on prolonged hospital stay. Methods We included low rectal tumor patients who underwent APR at a referral medical center from April 2002 to December 2017; a total of 229 patients were included. The basic characteristics and surgical outcomes of the patients were analyzed to identify risk factors for delayed perineal wound healing (> 30 days after APR) and prolonged hospital stay (post-APR hospital stay > 14 days). Results All patients received primary closure for their perineal wound. The majority of patients were diagnosed with adenocarcinoma (N = 213, 93.1%). In the univariate analysis, patients with hypoalbuminemia (albumin P = 0.001), which was an independent risk factor in the multivariable analysis (OR 2.962, 95% CI 1.437–6.102, P = 0.003). Patients with delayed wound healing also had a significantly increased risk of prolonged hospital stay (OR 6.404, 95% CI 3.508–11.694, P < 0.001). Conclusions Hypoalbuminemia was an independent risk factor for delayed wound healing, which consequently led to a prolonged hospital stay. Further clinical trials are needed to reduce the incidence of delayed perineal wound healing by correcting albumin levels or nutritional status before APR.

Objective: Mutation spectra in colorectal cancer with metastasis and its response to chemotherapy. Summary of Background Data: No molecular markers are available for selecting the optimal chemotherapeutic regimen (irinotecan or oxaliplatin) for metastatic colorectal cancer (mCRC). Methods: We enrolled 161 mCRC patients who underwent surgery for their primary tumors at Taipei Veterans General Hospital from 2004 to 2010. The prevalence of gene mutations was measured and correlated with responses to different cytotoxic agents. Results: We detected 1,836 mutations in 12 genes. KRAS mutants affected 44.3% of the tumors. The rate of good response was insignificantly higher for patients with KRAS mutant tumors who received oxaliplatin-based chemotherapy compared with patients with KRAS wild-type tumors (65.6% versus 47.0%; P = 0.15). For patients who received irinotecan-based chemotherapy, the rate of good response was similar in patients with wild-type (55.0%; n = 11) and those with KRAS mutant tumors (54.5%; n = 12; P = 1). In patients with KRAS mutant tumors treated with an oxaliplatin-based regimen, the overall survival was 38.5 months (95% CI: 26.6–50.5 months), which was insignificantly better than that for patients treated with an irinotecan-based regimen (30.4 months; 95% CI: 15.8–45.1 months; P = 0.206). Conclusions: Our data could not come to the conclusion that patient with KRAS mutation mCRC may have better response with oxaliplatin-based first-line chemotherapy. Further study is needed to confirm the relationship between gene mutation and chemotherapy response.

Osteopontin (OPN) is a multi-functional phospho-glycoprotein that can stimulate angiogenesis through acting on endothelial cells. As angiogenic sprouting involves endothelial-to-mesenchymal transition (EndoMT), we are intrigued to know whether OPN exerts an effect on EndoMT. Clinically, we indeed detected EndoMT-derived cells next to OPN-expressing cells in colorectal cancer tissues. Furthermore, we treated OPN to primary cultures of endothelial cells to investigate the EndoMT-inducing activity and the underlying mechanisms. Integrin αVβ3 rather than CD44 is involved in OPN-induced EndoMT. OPN-integrin αVβ3 engagement induces HIF-1α expression through a PI3K/Akt/TSC2-mediated and mTORC1-dependent protein synthesis pathway, which in turn trans-activates TCF12 gene expression. TCF12 further interacts with EZH2 and histone deacetylases to transcriptionally repress VE-cadherin gene and thus facilitates EndoMT. Like cancer-associated fibroblasts, EndoMT-derived cells promote tumor growth and metastasis by secreting certain proteins. Secreted HSP90α is a candidate suggested by microwestern array assay, and is herein verified to induce stemness properties in colorectal cancer cells. As OPN is overexpressed in human cancers, OPN-induced EndoMT and EndoMT-derived cells can be potentially taken as cancer therapeutic targets.

Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is an RNA-binding protein and serves as a post-transcriptional fine-tuner regulating the expression of mRNA targets. However, the clinicopathological roles of IGF2BP1 in colorectal cancer (CRC) remains limited. Thus, we aimed to elucidate the clinical significance and biomarker potentials of IGF2BP1 in CRC. A total of 266 specimens from two sets of CRC patients were collected. IGF2BP1 expression was studied by immunohistochemical (IHC) staining. The Kaplan-Meier survival plot and a log-rank test were used for survival analysis. The Cox proportional hazards model was applied to determine the survival impact of IGF2BP1. Public datasets sets from The Cancer Genome Atlas (TCGA) and Human Cancer Metastasis Database (HCMDB), receiver operating characteristic (ROC) plotter, and two CRC cell lines, HCT-116 and DLD-1, were used for validating our findings. We showed that IGF2BP1 was overexpressed in tumor specimens compared to 13 paired normal parts by examining the immunoreactivity of IGF2BP1 (p = 0.045). The increased expression of IGF2BP1 in primary tumor parts was observed regardless of metastatic status (p &lt, 0.001) in HCMDB analysis. IGF2BP1 expression was significantly associated with young age (59.6% vs. 46.7%, p-value = 0.043) and advanced stage (61.3% vs. 40.0%, p-value = 0.001). After controlling for confounding factors, IGF2BP1 remained an independent prognostic factor (HR = 1.705, p-value = 0.005). TCGA datasets analysis indicated that high IGF2BP1 expression showed a lower 5-year survival rate (58% vs. 65%) in CRC patients. The increased expression of IGF2BP1 in chemotherapy non-responder rectal cancer patients was observed using a ROC plotter. Overexpression of IGF2BP1 promoted the colony-forming capacity and 5-fluorouracil and etoposide resistance in CRC cells. Here, IGF2BP1 was an independent poor prognostic marker in CRC patients and contributed to aggressive phenotypes in CRC cell lines.

Objectives Patients with systemic lupus erythematosus are considered vulnerable to infective endocarditis and prophylactic antibiotics are recommended before an invasive dental procedure. However, the evidence is insufficient. This nationwide population-based study evaluated the risk and related factors of infective endocarditis in systemic lupus erythematosus. Methods We identified 12,102 systemic lupus erythematosus patients from the National Health Insurance research-oriented database, and compared the incidence rate of infective endocarditis with that among 48,408 non-systemic lupus erythematosus controls. A Cox multivariable proportional hazards model was employed to evaluate the risk of infective endocarditis in the systemic lupus erythematosus cohort. Results After a mean follow-up of more than six years, the systemic lupus erythematosus cohort had a significantly higher incidence rate of infective endocarditis (42.58 vs 4.32 per 100,000 person-years, incidence rate ratio = 9.86, p Conclusions A higher risk of infective endocarditis was observed in systemic lupus erythematosus patients. Risk factors for infective endocarditis in the systemic lupus erythematosus cohort included heart disease, chronic kidney disease, steroid pulse therapy within 30 days, and a recent invasive dental procedure within 30 days.