IGSF6 is a novel biomarker to evaluate immune infiltration in mismatch repair-proficient colorectal cancer.

Immunotherapy has dramatically changed the landscape of treatment for colorectal cancer (CRC), but currently lack of effective predictive biomarker, especially for tumors with mismatch repair (MMR) proficiency. The response of immunotherapy is associated with the cell-cell interactions in tumor microenvironment, encompassing processes such as cell-cell recognition, binding, and adhesion. However, the function of immunoglobulin superfamily (IGSF) genes in tumor immune microenvironment remains uncharacterized. This study quantified the immune landscape by leveraging a gene expression matrix from publicly accessible databases. The associations between IGSF6 gene expression and immune cell infiltration were assessed. The expression levels of IGSF6, CD8+ T cells, CD4+ T cells and CD68+ macrophage cells in cancer tissues from CRC patients and CRC cell lines were evaluated. IGSF6 was more highly expressed in CRC tumor tissues than adjacent normal tissues. And IGSF6 was significantly correlated with immune cell infiltration in MMR-proficient patients. Remarkably, MMR-proficient patients with high IGSF6 expression showed more sensitive to immunotherapy and chemotherapy than those with low IGSF6 expression. In summary, IGSF6 could be a novel biomarker to evaluate immune infiltration and predict therapeutic effect for MMR-proficient CRC.

Identification of an Autophagy-Related Gene Signature for the Prediction of Prognosis in Early-Stage Colorectal Cancer.

Purpose: A certain number of early-stage colorectal cancer (CRC) patients suffer tumor recurrence after initial curative resection. In this context, an effective prognostic biomarker model is constantly in need. Autophagy exhibits a dual role in tumorigenesis. Our study aims to develop an autophagy-related gene (ATG) signature-based on high-throughput data analysis for disease-free survival (DFS) prognosis of patients with stage I/II CRC. Methods: Gene expression profiles and clinical information of CRC patients extracted from four public datasets were distributed to discovery and training cohort (GSE39582), validation cohort (TCGA CRC, n = 624), and meta-validation cohort (GSE37892 and GSE14333, n = 420). Autophagy genes significantly associated with prognosis were identified. Results: Among 655 autophagy-related genes, a 10-gene ATG signature, which was significantly associated with DFS in the training cohort (HR, 2.76[1.56-4.82]; p = 2.06 × 10-4), was constructed. The ATG signature, stratifying patients into high and low autophagy risk groups, was validated in the validation (HR, 2.29[1.15-4.55]; p = 1.5 × 10-2) and meta-validation cohorts (HR, 2.5[1.03-6.06]; p = 3.63 × 10-2) and proved to be prognostic in a multivariate analysis. Functional analysis revealed enrichment of several immune/inflammatory pathways in the high autophagy risk group, where increased infiltration of T regulatory cells (Tregs) and decreased infiltration of M1 macrophages were observed. Conclusion: Our study established a prognostic ATG signature that effectively predicted DFS for early-stage CRC patients. Meanwhile, the study also revealed the possible relationship among autophagy process, immune/inflammatory response, and tumorigenesis.

An 11-gene signature for the prediction of systemic recurrences in colon adenocarcinoma.

BACKGROUND: Prognosis varies among patients within the same colon adenocarcinoma (COAD) stage, indicating the need for reliable molecular markers to enable individualized treatment. This study aimed to investigate gene signatures that can be used for better prognostic prediction of COAD. METHODS: Gene-expression profiles of COAD patients were obtained from the Gene Expression Omnibus database (n = 332) and The Cancer Genome Atlas database (n = 431). The relationship between gene signature and relapse-free survival was analysed in the training set (n = 93) and validated in the internal validation set (n = 94) and external validation sets (n = 145 and 431). RESULTS: Overall, 11 genes (N-myc downstream regulated gene 1 [NDRG1], fms-like tyrosine kinase 1 [FLT1], lipopolysaccharide binding protein [LBP], fatty acid binding protein 4 [FABP4], adiponectin gene [ADIPOQ], angiotensinogen gene [AGT], activin A receptor, type II-like kinase 1 [ACVRL1], CC chemokine ligand 11 [CCL11], cell division cycle 42 [CDC42], T-cell receptor alpha variable 9_2 [TRAV9_2], and proopiomelanocortin [POMC]) were identified by univariable and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. Based on the risk-score model, the patients were grouped into the high-risk or low-risk groups using the median risk score as the cut-off. The area under the curve (AUC) values for 1-, 3-, and 5-year recurrence were 0.970, 0.849, and 0.859, respectively. Patients in the high-risk group had significantly poorer relapse-free survival than did those in the low-risk group. The predictive accuracy of the 11-gene signature was proven in the validation sets. Our gene signature showed better predictive performance for 1-, 3-, and 5-year recurrence than did the other four models. CONCLUSIONS: The 11-gene signature showed good performance in predicting recurrence in COAD. The accuracy of the signature for prognostic classification requires further confirmation.

Cancer-associated fibroblasts impact the clinical outcome and treatment response in colorectal cancer via immune system modulation: a comprehensive genome-wide analysis.

BACKGROUND: Cancer-associated fibroblasts (CAFs) in the tumour microenvironment are associated with poor prognosis and chemoresistance in multiple solid tumours. However, there is a lack of universal measures of CAFs in colorectal cancer (CRC). The aim of this study was to assess the utility of a fibroblast-related gene signature (FRGS) for predicting patient outcomes and reveal its relevant mechanism. METHODS: The GSE39582 dataset, which includes 316 CRC patients who did not receive adjuvant chemotherapy was used as a discovery cohort to identify the prognostic fibroblast-related genes (FRGs). A total of 1352 CRC patients were divided into one training cohort (GSE39582, n = 461) and two validation cohorts (TCGA, n = 338; meta-validation, n = 553) for the construction of the FRGS and the verification of its prognostic value in stage II/III CRC patients. Functional annotation and analysis were performed to explore the underlying mechanism. The ability of the FRGS to predict immunotherapy response was further tested in a clear cell renal cell carcinoma (ccRCC) cohort. RESULTS: An 11-gene signature that had prognostic value for stage II/III CRC patients in both validation cohorts was developed (TCGA cohort: HR = 1.90, 95% CI 1.16-3.12, P < 0.01; meta-validation cohort: HR = 1.95, 95% CI 1.39-2.73, P < 0.001). A high level of CAFs was correlated with worse prognosis in CRC patients who did not receive adjuvant chemotherapy (HR = 3.63, 95% CI 2.24-5.88, P < 0.001). Importantly, patients in the low-risk group were found to be benefit from chemotherapy (P < 0.01), but not in the high CAF group (P > 0.05). Similar results were found in the TCGA cohort. Integrated with clinical characteristics, the FRGS was confirmed to be an independent prognostic factor in the multivariate analysis after adjustment for tumour TNM stage (GSE39582 cohort: HR = 3.19, 95% CI 1.88-5.41, P < 0.001; TCGA cohort: HR = 5.00, 95% CI 1.58-15.85, P = 0.007; meta-validation cohort: HR = 2.99, 95% CI 1.44-6.21, P = 0.003). Furthermore, the enrichment analysis found that the antitumour immune response was suppressed and the infiltration of CD4 T cells and M1 macrophages was depressed in the high CAF group. The FRGS was also found to have value in predicting for immunotherapy response in the ccRCC cohort. CONCLUSIONS: The 11-gene FRGS had independent prognostic value for CRC patients, as well as utility in the prediction of benefit from chemotherapy. CAFs in the tumour microenvironment might have an impact on the prognosis of CRC patients via inhibiting immune response.

Genome-Wide Analysis Reveals Hypoxic Microenvironment Is Associated With Immunosuppression in Poor Survival of Stage II/III Colorectal Cancer Patients.

Background: Hypoxia is associated with a poorer clinical outcome and resistance to chemotherapy in solid tumors; identifying hypoxic-related colorectal cancer (CRC) and revealing its mechanism are important. The aim of this study was to assess hypoxia signature for predicting prognosis and analyze relevant mechanism. Methods: Patients without chemotherapy were selected for the identification of hypoxia-related genes (HRGs). A total of six independent datasets that included 1,877 CRC patients were divided into a training cohort and two validation cohorts. Functional annotation and analysis were performed to reveal relevant mechanism. Results: A 12-gene signature was derived, which was prognostic for stage II/III CRC patients in two validation cohorts [TCGA, n = 509, hazard ratio (HR) = 2.14, 95% confidence interval (CI) = 1.18 - 3.89, P = 0.01; metavalidation, n = 590, HR = 2.46, 95% CI = 1.59 - 3.81, P < 0.001]. High hypoxic risk was correlated with worse prognosis in CRC patients without adjuvant chemotherapy (HR = 5.1, 95% CI = 2.51 - 10.35, P < 0.001). After integration with clinical characteristics, hypoxia-related gene signature (HRGS) remained as an independent prognostic factor in multivariate analysis. Furthermore, enrichment analysis found that antitumor immune response was suppressed in the high hypoxic group. Conclusions: HRGS is a promising system for estimating disease-free survival of stage II/III CRC patients. Hypoxia tumor microenvironment may be via inhibiting immune response to promote chemoresistance in stage II/III CRC patients.

College of American Pathologists Tumor Regression Grading System for Long-Term Outcome in Patients with Locally Advanced Rectal Cancer.

BACKGROUND: The National Comprehensive Cancer Network's Rectal Cancer Guideline Panel recommends American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) system to evaluate pathologic response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC). Yet, the clinical significance of the AJCC/CAP TRG system has not been fully defined. MATERIALS AND METHODS: This was a multicenter, retrospectively recruited, and prospectively maintained cohort study. Patients with LARC from one institution formed the discovery set, and cases from external independent institutions formed a validation set to verify the findings from discovery set. Overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were assessed by Kaplan-Meier analysis, log-rank test, and Cox regression model. RESULTS: The discovery set (940 cases) found, and the validation set (2,156 cases) further confirmed, that inferior AJCC/CAP TRG categories were closely /ccorrelated with unfavorable survival (OS, DFS, LRFS, and DMFS) and higher risk of disease progression (death, accumulative relapse, local recurrence, and distant metastasis) (all p < .05). Significantly, pairwise comparison revealed that any two of four TRG categories had the distinguished survival and risk of disease progression. After propensity score matching, AJCC/CAP TRG0 category (pathological complete response) patients treated with or without adjuvant chemotherapy displayed similar survival of OS, DFS, LRFS, and DMFS (all p > .05). For AJCC/CAP TRG1-3 cases, adjuvant chemotherapy treatment significantly improved 3-year OS (90.2% vs. 84.6%, p < .001). Multivariate analysis demonstrated the AJCC/CAP TRG system was an independent prognostic surrogate. CONCLUSION: AJCC/CAP TRG system, an accurate prognostic surrogate, appears ideal for further strategizing adjuvant chemotherapy for LARC. IMPLICATIONS FOR PRACTICE: The National Comprehensive Cancer Network recommends the American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) four-category system to evaluate the pathologic response to neoadjuvant treatment for patients with locally advanced rectal cancer; however, the clinical significance of the AJCC/CAP TRG system has not yet been clearly addressed. This study found, for the first time, that any two of four AJCC/CAP TRG categories had the distinguished long-term survival outcome. Importantly, adjuvant chemotherapy may improve the 3-year overall survival for AJCC/CAP TRG1-3 category patients but not for AJCC/CAP TRG0 category patients. Thus, AJCC/CAP TRG system, an accurate surrogate of long-term survival outcome, is useful in guiding adjuvant chemotherapy management for rectal cancer.

Protein-protein interaction analysis reveals a novel cancer stem cell related target TMEM17 in colorectal cancer.

BACKGROUND: Cancer stem cells (CSCs) are a small subpopulation of cells within tumors with stem cell property. Increased evidence suggest that CSCs could be responsible for chemoresistance and recurrence in colorectal cancer (CRC). However, a reliable therapeutic target on CSCs is still lacking. METHODS: Here we describe a two-step strategy to generate CSC targets with high selectivity for colon stem cell markers, specific proteins that are interacted with CSC markers were selected and subsequently validated in a survival analysis. TMEM17 protein was found and its biological functions in CRC cells were further examined. Finally, we utilized the Gene Set Enrichment Analysis (GSEA) to investigate the potential mechanisms of TMEM17 in CRC. RESULTS: By combining protein-protein interaction (PPI) database and high-throughput gene profiles, network analysis revealed a cluster of colon CSCs related genes. In the cluster, TMEM17 was identified as a novel CSCs related gene. The results of in-vitro functional study demonstrated that TMEM17 depletion can suppress the proliferation of CRC cells and sensitize CRC cells to chemotherapy drugs. Enrichment analysis revealed that the expression of TMEM17 is associated with the magnitude of activation of the Wnt/ß-catenin pathway. Further validation in clinical samples demonstrated that the TMEM17 expression was much higher in tumor than normal tissue and was associated with poor survival in CRC patients. CONCLUSION: Collectively, our finding unveils the critical role of TMEM17 in CRC and TMEM17 could be a potential effective therapeutic target for tumor recurrence and chemoresistance in the colorectal cancer (CRC).

Impact of pelvic dimensions on anastomotic leak after anterior resection for patients with rectal cancer.

AIM: The impact of pelvis on the development of anastomotic leak (AL) in rectal cancer (RC) patients who underwent anterior resection (AR) remains unclear. The aim of this study was to evaluate the impact of pelvic dimensions on the risk of AL. METHODS: A total of 1058 RC patients undergoing AR from January 2013 to January 2016 were enrolled. Pelvimetric parameters were obtained using abdominopelvic computed tomography scans. RESULTS: Univariate analyses showed that pelvic inlet, pelvic outlet, interspinous distance, and intertuberous distance were significantly associated with the risk for AL (P < 0.05). Multivariate analysis confirmed that pelvic inlet and intertuberous distance were independent risk factors for AL (P < 0.05). Significant factors from multivariate analysis were assembled into the nomogram A (without pelvic dimensions) and nomogram B (with pelvic dimensions). The area under curve (AUC) of nomogram B was 0.72 (95% CI 0.67-0.77), which was better than the AUC of nomogram A (0.69, [95% CI 0.65-0.74]), but didn't reach a statistical significance (P = 0.199). Decision curve supported that nomogram B was better than nomogram A. CONCLUSION: Pelvic dimensions, specifically pelvic inlet and intertuberous distance, seemed to be independent predictors for postoperative AL in RC patients. Pelvic inlet and intertuberous distance incorporated with preoperative radiotherapy, preoperative albumin, conversion, and tumor diameter in the nomogram might provide a clinical tool for predicting AL.

Immune-related gene signature in predicting prognosis of early-stage colorectal cancer patients.

AIM: Immune-related genes are associated with the prognosis of colorectal cancer (CRC) patients. The aim of this study was to evaluate the impact of an immune-related gene signature (IRGS) in predicting the prognosis of early-stage CRC patients. METHODS: In total, 309 CRC patients were selected for the identification of prognostic IRGS using the CIT/GSE39582 microarray dataset. Five independent datasets including 1587 CRC patients were divided into a training cohort (n = 566) and two validation cohorts (n = 624 in validation-1 and n = 397 in meta-validation). Prognostic analyses were performed to test the predictive value of IRGS. RESULTS: A prognostic IRGS that included 23 immune-related genes was constructed and significantly stratified patients into immune low-vs. high-risk groups in terms of disease-free survival using patients with early-stage disease (I or II) in the training cohort. Similarly, a higher IRGS was correlated with significantly worse prognosis of early-stage patients in validation-1 and meta-validation cohorts. Compared with Oncotype DX colon, we found that IRGS exhibited an improved survival correlation in the training cohort. After integration with clinical characteristics, IRGS remained as an independent prognostic factor in multivariate analysis. Furthermore, IRGS-stratified immune low-risk group patients gained less benefit from adjuvant chemotherapy in the validation-1 cohort. Several biological processes, including inflammatory response, were enriched among genes in identified the immune high-risk group. Consistent with this finding, the IRGS-identified immune high-risk group exhibited significantly increased immune and stromal cell infiltration. CONCLUSION: The proposed prognostic IRGS is a promising system for estimating DFS of colorectal cancer patients, especially those with early-stage disease.

Association of mismatch repair status with survival and response to neoadjuvant chemo(radio)therapy in rectal cancer.

Prior reports have indicated that defective mismatch repair (MMR) has a favorable impact on outcome in colorectal cancer patients treated with surgery, immunotherapy, or adjuvant chemotherapy. However, the impact of MMR status on response to neoadjuvant radiotherapy in rectal cancer is not well understood. Here we report that dMMR was associated with improved disease-free survival (DFS) (P = 0.034) in patients receiving neoadjuvant chemotherapy (NCT). Patients with dMMR tumors who received neoadjuvant chemoradiotherapy (NCRT) achieved significantly worse DFS (P = 0.026) than those treated with NCT. Conversely, NCRT improved DFS (P = 0.043) in patients with pMMR tumors, especially for stage III disease with improved DFS (P = 0.02). The presence of dMMR was associated with better prognosis in rectal cancer patients treated with NCT. NCT benefited patients with dMMR tumors; while NCRT benefited patients with stage III disease and pMMR tumors. Patients stratified by MMR status may provide a more tailored approach to rectal cancer neoadjuvant therapy.

Effects of Huaier Extract on Ameliorating Colitis-Associated Colorectal Tumorigenesis in Mice.

BACKGROUND: Huaier extract has been a part of traditional Chinese medicine (TCM) for roughly 1600 years and may serve as a potential anti-cancer drug as it is associated with good efficacy and low toxicity. Individuals with inflammatory bowel disease (IBD) are at a higher chance of being diagnosed with colorectal cancer (CRC) and as Huaier extract may potentially influence tumorigenesis, we set out to determine the effect of Huaier extract on colitis-associated CRC. METHODS: The CRC mouse model, established through azoxymethane (AOM) and dextran sulfate sodium (DSS), was administered Huaier extract. Weight loss, colon length, tumor number and tumor size were evaluated macroscopically. Pro-inflammatory cytokine expression and STAT3 phosphorylation were assessed in the colon using ELISA, Western blot and/or immunohistochemistry. RESULTS: Huaier extract improved the severity of colitis-associated tumorigenesis compared with control group, with attenuated weight loss and longer colons. Tumor number, size and load were drastically decreased in mice treated with Huaier. Histological assessment suggested that Huaier could decrease histological injury of the colon tissue. Additionally, Huaier extract treatment led to reduced pro-inflammatory cytokine levels (TNF-α, IL-6, IFN-γ and IL-1ß) and a decrease of STAT3 phosphorylation in colon tissue. Additionally, present findings demonstrated that Huaier extract inhibited cell proliferation and induced apoptosis in CRC cells HCT116 and HCT8. The migration and invasion of CRC cells were markedly inhibited upon exposure to Huaier treatment. The apoptosis-associated protein levels (P53, Bax, Bcl-2, pro-caspase-3 and cleavage caspase-3) showed significant differences after the administration of Huaier extract in HCT116 and HCT8 cells. In vivo, the administration of Huaier extract to mice inhibited tumor growth and yielded a similar profile of apoptotic proteins expression p53, Bcl-2, pro-caspase-3 and cleaved caspase-3 while no significant differences in Bax were observed. Moreover, the ratio of TUNEL-positive/apoptotic cells was markedly increased in the Huaier-treated mice. CONCLUSION: Huaier extract may reduce the IBD-associated tumor development by suppressing pro-inflammatory cytokine levels and STAT3 stimulation.

Antitumor immunity of low-dose cyclophosphamide: changes in T cells and cytokines TGF-beta and IL-10 in mice with colon-cancer liver metastasis.

BACKGROUND: The tumor immune microenvironment is one of the most important prognostic factors in liver metastasis from colorectal cancer. Low-dose cyclophosphamide (CTX) is widely believed to be involved in the modulation of the immune system. However, the underlying mechanism of low-dose CTX remains unknown. This study aimed to investigate the antitumor immunity of low-dose CTX in the treatment of colon-cancer liver metastasis. METHODS: Thirty mice were randomly divided into five groups. After liver metastasis was established in colon-cancer models, mice in the treatment groups were injected with low-dose CTX (20 mg/kg) at different time points. Liver and spleen tissues were examined for T-cell markers via flow cytometry. Interleukin (IL)-10 and transforming growth factor (TGF)-ß1 expression levels in liver tissues were analysed by immunohistochemistry. Serum interferon (IFN)-γ and IL-10 levels were detected by enzyme-linked immunosorbent assay. An additional 20 mice were randomly allocated into two groups and the survival times were recorded. RESULTS: The expression levels of CD4+ T cells, CD8+ T cells, and IFN-γ were down-regulated, whereas those of IL-10 and TGF-ß1 were up-regulated in liver metastasis from colon cancer in mice. Furthermore, the local and systemic microenvironments of the liver were altered, which led to reduced antitumor immune responses and subsequently liver metastasis. However, treatment with low-dose CTX reversed these effects. The survival times of mice treated with low-dose CTX were significantly longer than those of the other groups. CONCLUSIONS: Low-dose CTX exerts its antitumor activity by changing the systemic and local immune microenvironments and enhancing immune regulation in mice. CTX could be used as a drug to prevent and treat liver metastasis from colon cancer.

A signature of hypoxia-related factors reveals functional dysregulation and robustly predicts clinical outcomes in stage I/II colorectal cancer patients.

BACKGROUND: The hypoxic tumor microenvironment accelerates the invasion and migration of colorectal cancer (CRC) cells. The aim of this study was to develop and validate a hypoxia gene signature for predicting the outcome in stage I/II CRC patients that have limited therapeutic options. METHODS: The hypoxic gene signature (HGS) was constructed using transcriptomic data of 309 CRC patients with complete clinical information from the CIT microarray dataset. A total of 1877 CRC patients with complete prognostic information in six independent datasets were divided into a training cohort and two validation cohorts. Univariate and multivariate analyses were conducted to evaluate the prognostic value of HGS. RESULTS: The HGS consisted of 14 genes, and demarcated the CRC patients into the high- and low-risk groups. In all three cohorts, patients in the high-risk group had significantly worse disease free survival (DFS) compared with those in the low risk group (training cohort-HR = 4.35, 95% CI 2.30-8.23, P < 0.001; TCGA cohort-HR = 2.14, 95% CI 1.09-4.21, P = 0.024; meta-validation cohort-HR = 1.91, 95% CI 1.08-3.39, P = 0.024). Compared to Oncotype DX, HGS showed superior predictive outcome in the training cohort (C-index, 0.80 vs 0.65) and the validation cohort (C-index, 0.70 vs 0.61). Pathway analysis of the high- and low-HGS groups showed significant differences in the expression of genes involved in mTROC1, G2-M, mitosis, oxidative phosphorylation, MYC and PI3K-AKT-mTOR pathways (P < 0.005). CONCLUSION: Hypoxic gene signature is a satisfactory prognostic model for early stage CRC patients, and the exact biological mechanism needs to be validated further.

Transanal versus laparoscopic total mesorectal excision for mid and low rectal cancer: a meta-analysis of short-term outcomes.

INTRODUCTION: The benefit of transanal total mesorectal excision (TaTME) for mid and low rectal cancer is conflicting. AIM: To assess and compare the short-term outcomes of TaTME with conventional laparoscopic total mesorectal excision (LaTME) for middle and low rectal cancer. MATERIAL AND METHODS: We searched PubMed, Embase and Cochrane Library databases for studies addressing TaTME versus conventional LaTME for rectal cancer between 2008 and December 2018. Randomized controlled trials (RCTs) and retrospective studies which compared TaTME with LaTME were included. RESULTS: Twelve retrospective case-control studies were identified, including a total of 899 patients. We did not find significant differences in overall intraoperative complications, blood loss, conversion rate, operative time, overall postoperative complication, anastomotic leakage, ileus, or urinary morbidity. Also no significant differences in oncological outcomes including circumferential resection margin (CRM), positive CRM, distal margin distance (DRM), positive DRM, quality of mesorectum, number of harvested lymph nodes, temporary stoma or local recurrence were found. Although the TaTME group had better postoperative outcomes (readmission, reoperation, length of hospital stay) on average, the difference did not reach statistical significance. CONCLUSIONS: Transanal total mesorectal excision offers a safe and feasible alternative to LaTME although the clinicopathological features were not superior to LaTME in this study. Currently, with the lack of evidence on benefits of TaTME, further evaluation of TaTME requires large randomized control trials to be conducted.

Laparoscopic Surgery for Complex Crohn's Disease: A Meta-Analysis.

Aim: There is still no consensus on whether laparoscopic surgery can be routinely recommended as a safe approach for complex Crohn's disease (CD). Methods: PubMed, Embase, and Cochrane library databases were searched (up to February 2019). Comparative studies reporting laparoscopic surgery for complex CD (LC group) comparing with simple CD (LS group) were included. The outcomes were blood loss, operative time, conversion rate, length of hospital stay, postoperative complications, and reoperation rate within 30 days after surgery. Results: Thirteen retrospective studies with 1120 participants were included. The LC group has significantly more blood loss (weighted mean difference [WMD] 43.64 mL; 95% confidence interval (CI) 8.37-78.91; P = .020), longer operative time (WMD 17.59 minutes; 95% CI 6.38-28.81; P = .002), higher conversion rate (WMD 2.04%; 95% CI 1.43-2.91; P < .001), and longer length of hospital stay (WMD 0.86 day; 95% CI 0.53-1.19; P < .001). Overall postoperative complication rates (WMD 0.98; 95% CI 0.71-1.34; P = .90) did not differ significantly between the 2 groups. Conclusions: LC is safe and feasible with comparable postoperative complications, although there is a more blood loss, longer operative time, higher conversion rate, and longer length of hospital stay.

Overexpression of G protein-coupled receptor 31 as a poor prognosticator in human colorectal cancer.

AIM: To investigate the expression of G protein-coupled receptor 31 (GPR31) and its clinical significance in human colorectal cancer (CRC). METHODS: To determine the association between the GPR31 expression and the prognosis of patients, we obtained paraffin-embedded pathological specimens from 466 CRC patients who underwent initial resection. A total of 321 patients from the First Affiliated Hospital of Sun Yat-sen University from January 1996 to December 2008 were included as a training cohort, whereas 145 patients from the Sixth Affiliated Hospital of Sun Yat-sen University from January 2007 to November 2008 were included as a validation cohort. We examined GPR31 expression levels in CRC tissues from two independent cohorts via immunohistochemical staining. All patients were categorized into either a GPR31 low expression group or a GPR31 high expression group. The clinicopathological factors and the prognosis of patients in the GPR31 low expression group and GPR31 high expression group were compared. RESULTS: We compared the clinicopathological factors and the prognosis of patients in the GPR31 low expression group and GPR31 high expression group. Significant differences were observed in the number of patients in pM classification between patients in the GPR31 low expression group and GPR31 high expression group (P = 0.007). The five-year survival and tumor-free survival rates of patients were 84.3% and 82.2% in the GPR31 low expression group, respectively, and both rates were 59.7% in the GPR31 high expression group (P < 0.05). Results of the Cox proportional hazard regression model revealed that GPR31 upregulation was associated with shorter overall survival and tumor-free survival of patients with CRC (P < 0.05). Multivariate analysis identified GPR31 expression in colorectal cancer as an independent predictive factor of CRC patient survival (P < 0.05). CONCLUSION: High GPR31 expression levels were found to be correlated with pM classification of CRC and to serve as an independent predictive factor of poor survival of CRC patients.

Male gender is associated with an increased risk of anastomotic leak in rectal cancer patients after total mesorectal excision.

BACKGROUND: The impact of a patient's gender on the development of anastomotic leak (AL) in rectal cancer patients following total mesorectal excision (TME) remains controversial. The aim of this study was to evaluate the association between patients' gender and the risk of AL. METHODS: All rectal cancer patients following TME with a primary anastomosis during the study period from 2010 to 2014 were examined. Comparisons of the post-operative AL incidence rate between male and female patients were performed. RESULTS: Of all patients examined (n = 956), 587 (61.4%) were males and 369 (38.6%) were females. Male patients were more likely to have a history of smoking and drinking alcohol, but less likely to have a history of abdominal surgery compared to female patients. A higher incidence rate of pre-operative bowel obstruction and larger tumor volume in male patients was observed in our study. Of all the patients, 81 (8.5%) developed post-operative AL. More male patients (n = 62, 10.6%) suffered from AL than females (n = 19, 5.1%) (P = 0.003). Multivariate logistic regression analyses confirmed the association between male gender and AL [odds ratio (OR): 2.41, 95% confidence interval (CI): 1.37-4.23, P = 0.002]. Similar results were also obtained in patients who underwent laparoscopic TME (OR: 2.11, 95% CI: 1.15-3.89, P = 0.016). CONCLUSIONS: Male patents were found to have an increased risk for AL following TME with a primary anastomosis. A temporary protecting stoma may help to protect the anastomosis and lessen the risk for AL especially in male patients.

Conversion is a risk factor for postoperative anastomotic leak in rectal cancer patients - A retrospective cohort study.

AIM: The impact of conversion from laparoscopic surgery to laparotomy on the development of anastomotic leak (AL) in rectal cancer patients following laparoscopic low anterior resection (LAR) with total mesorectal excision (TME) has not been evaluated. The aim of this study was to evaluate the impact of conversion on the risk of AL and develop a prediction nomogram for postoperative AL. METHODS: All rectal cancer patients following laparoscopic LAR with TME from January 2010 to October 2014 were enrolled in the primary cohort. Comparisons of the postoperative anastomotic leak incidence rate between converted patients and non-converted patients were performed using both univariate and multivariate logistic regression analyses. The result of multivariable analysis was used to develop the predicting model and the performance of nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. An independent validation cohort containing 200 patients from November 2014 to October 2015 was assessed. RESULTS: Of all patients enrolled (n=646), 592 (91.6%) patients underwent totally laparoscopic surgery, and 54 (8.4%) were converted from laparoscopic surgery to laparotomy. Converted group patients were more likely to have a higher body mass index (BMI), prolonged length of stay (LOS), increased overall postoperative complication rates and advanced clinical T stage (T3 or T4), pathological N stage (N1 or N2) and pathological TNM stage (III or IV). The percentage of patients who had preoperative radiotherapy for rectal cancer was higher in non-converted patients. Patients who underwent conversion to laparotomy (n=10, 18.5%) were more likely to suffer from postoperative AL than those undergoing totally laparoscopic surgery (n=38, 6.4%) (P=0.004). Multivariate logistic regression analyses confirmed the association between conversion and postoperative AL (Odds ratio [OR], 95% confidence interval [CI]: 2.71 [1.31-5.63], P=0.007). Conversion, gender, and clinical N stage incorporated in the individualized prediction nomogram showed good discrimination, with a C-index of 0.697 (C-index, 0.621 and 0.772 through internal validation), and good calibration. In the validation cohort, the main results were consistent with the findings of the primary cohort, with a C-index of 0.670 (C-index, 0.562 and 0.777 through internal validation). Decision curve analysis demonstrated that the prediction nomogram was clinically useful. CONCLUSION: Conversion during laparoscopic LAR was found to be associated with an increased risk for the postoperative AL in RC patients. A nomogram model incorporating conversion, gender and patient's clinical N stage seems to offers a useful tool for predicting postoperative AL in these patients.

Graphene-ß-Ga2 O3 Heterojunction for Highly Sensitive Deep UV Photodetector Application.

A deep UV light photodetector is assembled by coating multilayer graphene on beta-gallium oxide (ß-Ga2 O3 ) wafer. Optoelectronic analysis reveals that the heterojunction device is virtually blind to light illumination with wavelength longer than 280 nm, but is highly sensitive to 254 nm light with very good stability and reproducibility.