Integrative analysis of the immunological significances of guanylate binding protein family genes in microsatellite stability colorectal cancer.

Background: Microsatellite stability (MSS) colorectal cancer (CRC) has poor sensitivity to immunotherapy and its underlying mechanisms are still unclear. Guanylate binding proteins (GBPs) are a family of GTPase involving innate immune responses by providing defense against invading microbes and pathogens. However, the immunological significances of GBPs in MSS CRC remain unknown. Methods: We utilized bioinformatic tools to comprehensively analysis the expression pattern, clinical relevance, prognostic value, biological function, and immunoregulation effect of distinct GBP members in MSS CRC. Results: The expression of all seven GBPs in MSS samples are remarkably decreased compared to microsatellite instability-high (MSI-H) samples. Among them, GBP1/2/4/5 are obviously correlated with distant metastasis status. High expression of GBP1/4/5/6 was remarkably related to favorable overall survival (OS) and progression-free survival (PFS) in CRC patients with MSS tumor. Subsequent enrichment analysis revealed that Interferon-gamma (IFN-γ) and NOD-like receptor signaling are the most relevant functions. Besides, the expression patterns of GBPs are remarkably associated with several tumor infiltrated immune cells (e.g. regulatory T cells, CD4+ T cells, and macrophages) and diverse immunoregulatory molecules (e.g. immune checkpoint biomarkers (ICBs) and major histocompatibility complex (MHC) molecules). Moreover, high GBP1/2/4/5 expression predicted better immunotherapy responsiveness in immunotherapy cohorts. Conclusion: These findings might provide novel insights for the identification of therapeutic targets and potential prognostic biomarkers of GBP family in CRC with MSS samples.

Identification of immunotherapy-related subtypes, characterization of tumor microenvironment infiltration, and development of a prognostic signature in gastric carcinoma.

BACKGROUND: Recent advances in immunotherapy have elicited a considerable amount of attention as viable therapeutic options for several cancer types, the present study aimed to explore the immunotherapy-related genes (IRGs) and develop a prognostic risk signature in gastric carcinoma (GC) based on these genes. METHODS: IRGs were identified by comparing immunotherapy responders and non-responders in GC. Then, GC patients were divided into distinct subtypes by unsupervised clustering method based on IRGs, and the differences in immune characteristics and prognostic stratification between these subtypes were analyzed. An immunotherapy-related risk score (IRRS) signature was developed and validated for risk classification and prognosis prediction based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts. Besides, the predictive ability of the IRRS in immunotherapy response was also determined. RESULTS: A total of 63 IRGs were identified, and 371 GC patients were stratified into two molecular subgroups with significantly different prognosis and immune characteristics. Then, an IRRS signature comprised of three IRGs (CENP8, NRP1, and SERPINE1) was constructed to predict the prognosis of GC patients in TCGA cohort. Importantly, external validation in multiple GEO cohorts further confirmed the universal applicability of the IRRS in distinct populations. Furthermore, we found that the IRRS was significantly correlated with patient's responsiveness to immunotherapy, GC patients with low IRRS are more likely to benefit from existing immunotherapy. CONCLUSIONS: The risk score could serve as a robust prognostic biomarker, provide therapeutic benefits for immunotherapy and may be helpful for clinical decision making in GC patients.

Development of a CD8+ T cell associated signature for predicting the prognosis and immunological characteristics of gastric cancer by integrating single-cell and bulk RNA-sequencing.

The universally poor clinical outcome makes gastric cancer (GC) still a significant public health threat, the main goal of our research is to develop a prognostic signature that can forecast the outcomes and immunological characteristics of GC via integrating single-cell and bulk RNA-sequencing. The CD8+ T cell feature genes were screened out by exploring single-cell RNA-sequencing (scRNA-seq) profiles retrieved from the TISCH2 database. Then, Cox and LASSO regressions were exploited for constructing a prognostic model in TCGA cohort based on these CD8+ T cell feature genes. Survival analysis was conducted to investigate the predictive capability of the signature for the clinical outcome of GC patients in TCGA and GEO cohorts. Additionally, we further examined the correlations between the risk signature and tumor immunotherapeutic response from the perspectives of immune infiltration, tumor mutation burden (TMB), immune checkpoint biomarker (ICB) expression, tumor microenvironment (TME), microsatellite instability (MSI), TIDE, and TCIA scores. In total, 703 CD8+ T cell feature genes were identified, eight of which were selected for constructing a prognostic signature. GC patients who possess high-risk score had significantly poorer survival outcomes than those who possess low-risk score in TCGA and GEO cohorts. Immune infiltration analysis proved that the risk score was negatively connected with the infiltration abundance of CD8+ T cells. Then, our findings demonstrated that GC patients in the high-risk subgroup possess a higher proportion of MSI-L/MSS, lower immune checkpoint biomarker expression, lower TMB, higher TIDE scores and lower TCIA scores compared to those in the low-risk subgroup. What's more, immunotherapy cohort analysis confirmed that patients who possess high-risk score are not sensitive to anti-cancer immunotherapy. Our study developed a reliable prognostic signature for GC that was significantly correlated with the immune landscape and immunotherapeutic responsiveness. The risk signature may guide clinicians to adopt more accurate and personalized treatment strategies for GC patients.

Preserving the left colonic artery in radical sigmoid and rectal cancer surgery is feasible: A meta-analysis.

BACKGROUND: This study aims to investigate the safety and feasibility of preserving left colonic artery (LCA) in radical sigmoid and rectal cancer surgery. METHODS: Relevant articles were systematically searched on the PubMed, Embase, and Cochrane Library. The quality of included studies was evaluated using the Cochrane Handbook. A meta-analysis was conducted to assess the surgical outcomes and oncological outcomes by RevMan 5.4 software. RESULTS: Fifteen studies with a total of 5054 patients, including 2432 patients with LCA preservation and 2622 patients without LCA preservation, were included and analyzed in this study. The meta-analysis revealed that preserving LCA in radical surgery of sigmoid and rectal cancer has lower anastomotic leakage incidence (OR = 1.03, 95% confidence interval = 0.83-1.27, P < .0001). There were no significant differences in the operative time, intraoperative blood loss, number of dissected lymph nodes, postoperative complications as well as the oncological outcomes including systemic recurrence, local recurrence, 5-year overall survival rate, and 5-year disease-free survival rate. CONCLUSION SUBSECTIONS: This pooled analysis showed that preserving the LCA is safe and feasible in radical sigmoid and rectal cancer surgery.

Identification and validation of a novel prognostic model for gastric cancer based on m7G-related genes.

Background: The role of N7-methyladenosine (m7G)-related genes in the progression and prognosis of gastric cancer (GC) remains unclear. This study aimed to explore prognostic biomarkers for GC based on m7G methylation regulators and to construct a prognostic risk model. Methods: RNA sequencing profiles with corresponding clinicopathological information associated with GC of which the histological type was stomach adenocarcinoma (STAD) were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. A total of 29 m7G regulators were extracted from previous studies. According to the expression similarity of m7G regulators, the GC samples obtained from TCGA were further classified into 2 clusters demonstrating different overall survival (OS) rates and genetic heterogeneity, and the differentially expressed genes (DEGs) between these 2 clusters were defined as m7G-related genes. Univariate regression analysis and regression analysis were then used to obtain the prognostic m7G-related genes. The samples in TCGA and Genotype-Tissue Expression (GTEx) were used to verify the differential expression and prognostic value of these m7G-related genes contained in the prognostic model. Subsequently, the risk score was combined with other prognostic factors to develop a nomogram. The predictive ability of the nomogram was evaluated by the standard receiver operating characteristic (ROC) curve. Gene set enrichment analysis (GSEA) was used to identify activation pathways in both groups. Finally, the association between the prognostic model and the immune characteristics of GC were appraised. Results: A prognostic model consisting of 11 m7G-related genes was constructed. GC patients in the high-risk group were shown to have a poor prognosis and this result was further demonstrated in each group. The risk model can be applied for patients with different clinical features. The results of GSEA showed that cell adhesion, cell junction, and focal adhesion were highly enriched in the high-risk group. In addition, we found that the expression of programmed cell death ligand 1 (PD-L1) was significantly elevated in the low-risk group, whereas programmed cell death ligand 2 (PD-L2) and tumor necrosis factor receptor superfamily member 4 (TNFRSF4) were overexpressed in the high-risk group. Conclusions: We successfully built and verified a m7G relevant prognostic model for predicting prognosis and providing a new train of thought for improving the treatment of GC.

Identification of prognostic immune-related lncRNA signature predicting the overall survival for colorectal cancer.

Long non-coding RNA (lncRNA) is an important regulator of gene expression and serves a fundamental role in immune regulation. The present study aimed to develop a novel immune-related lncRNA signature to assess the prognosis of patients with colorectal cancer (CRC). Transcriptome data and clinical information of patients with CRC were downloaded from The Cancer Genome Atlas (TCGA) and UCSC Xena platforms. Immune-related mRNAs were extracted from the Molecular Signatures Database (MSigDB), and the immune-related lncRNAs were identified based on correlation analysis. Then, univariate, Lasso and multivariate Cox regression were applied to construct an immune-related lncRNA signature, and CRC patients were divided into high- and low-risk groups according to the median risk score. Finally, we evaluated the signature from the perspectives of clinical outcome, clinicopathological parameters, tumor-infiltrating immune cells (TIICs), immune status, tumor mutation burden (TMB) and immunotherapy responsiveness. In total, 272 immune-related lncRNAs were identified, five of which were applied to construct an immune-related lncRNA signature. The signature divided patients with CRC into low- and high-risk groups, the prognosis of patients in the high-risk group were significantly poorer than those in low-risk group, and the results were further confirmed in external validation cohort. Furthermore, the high-risk group showed aggressive clinicopathological characteristics, specific TIIC and immune function status, and low sensitivity to immunotherapy. The immune-related lncRNA signature could be exploited as a promising biomarker for predicting the prognosis and immune status of patients with CRC.

H19 may regulate the immune cell infiltration in carcinogenesis of gastric cancer through miR-378a-5p/SERPINH1 signaling.

BACKGROUND: Increasing studies have indicated that noncoding RNA (ncRNA)-mediated competing endogenous RNA (ceRNA) network serves as a significant role in cancer progression, but the underlying regulatory mechanisms of which in gastric cancer (GC) remain largely unclear. METHODS: Based on Gene Expression Omnibus and The Cancer Genome Atlas datasets, potential biomarkers for GC were screened and validated by machine learning. Then, upstream regulatory ncRNA of potential biomarkers was identified to construct a novel ceRNA network in GC through means of stepwise reverse prediction and validation. Ultimately, tumor immune cell infiltration analysis was performed based on the EPIC algorithm. RESULTS: A total of 188 differentially expressed genes (DEGs) were screened, and three candidate diagnostic biomarkers (FAP, PSAPL1, and SERPINH1) for GC were identified and validated. Subsequently, H19 and miR-378a-5p were identified as upstream regulatory ncRNAs that could potentially bind SERPINH1 in GC. Moreover, Immune infiltration analysis revealed that each component in the ceRNA network (H19/miR-378a-5p/SERPINH1) was significantly correlated with the infiltration abundances of diverse tumor-infiltrating immune cells. CONCLUSIONS: H19 may regulate the immune cell infiltration in carcinogenesis of GC through miR-378a-5p/SERPINH1 signaling.

Construction of a Novel Immune-Related mRNA Signature to Predict the Prognosis and Immune Characteristics of Human Colorectal Cancer.

Background: Anti-cancer immunotherapeutic approaches have gained significant efficacy in multiple cancer types. However, not all patients with colorectal cancer (CRC) could benefit from immunotherapy due to tumor heterogeneity. The purpose of this study was to construct an immune-related signature for predicting the immune characteristics and prognosis of CRC. Methods: RNA-sequencing data and corresponding clinical information of patients with CRC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and immune-related genes (IRGs) were downloaded from the Immunology Database and Analysis Portal (ImmPort). Then, we utilized univariate, lasso regression, and multivariate cox regression to identify prognostic IRGs and develop the immune-related signature. Subsequently, a nomogram was established based on the signature and other prognostic factors, and its predictive capacity was assessed by receiver operating characteristic (ROC) and decision curve analysis (DCA). Finally, associations between the signature and the immune characteristics of CRC were assessed. Results: In total, 472 samples downloaded from TCGA were divided into the training cohort (236 samples) and internal validation cohort (236 samples), and the GEO cohort was downloaded as an external validation cohort (122 samples). A total of 476 differently expressed IRGs were identified, 17 of which were significantly correlated to the prognosis of CRC patients. Finally, 10 IRGs were filtered out to construct the risk score signature, and patients were divided into low- and high-risk groups according to the median of risk scores in the training cohort. The high-risk score was significantly correlated with unfavorable survival outcomes and aggressive clinicopathological characteristics in CRC patients, and the results were further confirmed in the internal validation cohort, entire TCGA cohort, and external validation cohort. Immune infiltration analysis revealed that patients in the low-risk group infiltrated with high tumor-infiltrating immune cell (TIIC) abundances compared to the high-risk group. Moreover, we also found that the immune checkpoint biomarkers were significantly overexpressed in the low-risk group. Conclusion: The prognostic signature established by IRGs showed a promising clinical value for predicting the prognosis and immune characteristics of human CRC, which contribute to individualized treatment decisions.

The Effect and Mechanism of Duodenal-Jejunal Bypass to Treat Type 2 Diabetes Mellitus in a Rat Model.

OBJECTIVES: Bariatric surgery can treat obesity and T2DM, but the specific mechanism is unknown. This study investigated the effect and possible mechanism of duodenal-jejunal bypass (DJB) to treat T2DM. METHODS: A T2DM rat model was established using a high-fat, high-sugar diet and a low dose of streptozotocin. DJB surgery and a sham operation (SO) were performed to analyze the effects on glucose homeostasis, lipid metabolism, and inflammation changes. Furthermore, the glucagon-like peptide-1 (GLP-1) in the ileum and the markers of endoplasmic reticulum stress (ERS) in the pancreas were examined after the surgery. The insulinoma cells (INS-1) were divided into three groups; group A was cultured with a normal sugar content (11.1 mmol/L), group B was cultured with fluctuating high glucose (11.1 mmol/L alternating with 33.3 mmol/L), and group C was cultured with fluctuating high glucose and exendin-4 (100 nmol/L). The cells were continuously cultured for 7 days in complete culture medium. The viability of the INS-1 cells was then investigated using the MTT method, apoptosis was detected by flow cytometry, and the ERS markers were detected by Western blot. RESULTS: The blood glucose, lipids, insulin, and TNF-α were significantly elevated in the T2DM model. A gradual recovery was observed in the DJB group. GLP-1 expression in the distal ileum of the DJB group was significantly higher than that in the T2DM control group (DM) and the SO group (p < 0.05), and the markers of ERS expression in the pancreases of the DJB group decreased significantly more than those of groups DM and SO (p < 0.05). Compared with group A, the cell viability in group B was decreased, and the ERS and apoptosis were increased (p < 0.05). However, compared with group B, the cell viability in group C was improved, and the ERS and apoptosis declined (p < 0.05). CONCLUSIONS: DJB can be used to treat T2DM in T2DM rats. The mechanism may be that the DJB stimulates the increased expression of GLP-1 on the far side of the ileum, and then, GLP-1 inhibits ERS in the pancreas, reducing the apoptosis of ß cells to create a treatment effect in the T2DM rats.

Identification of novel survival-related lncRNA-miRNA-mRNA competing endogenous RNA network associated with immune infiltration in colorectal cancer.

Increasing studies have reported that long noncoding RNAs (lncRNAs) play critical roles in the initiation and progression of carcinogenesis. However, the underlying regulatory mechanisms of lncRNA-related competing endogenous RNA (ceRNA) network in colorectal cancer (CRC) are not fully understood. In the present study, we systematically analyzed the expression levels and prognostic values of dysregulated microRNAs (miRNAs) in human CRC to identify novel survival-related lncRNA-miRNA-mRNA ceRNA regulatory network. As a result, 28 dysregulated miRNAs were obtained, and hsa-miR-195-5p was identified as a key oncogene in human CRC based on analyses of expression levels and prognostic values. By means of stepwise prediction and validation, two upstream lncRNAs (NEAT1, XIST) and eight downstream mRNAs (ACOX1, CYP26B1, IRF4, ITPR1, LITAF, PHLPP2, RECK, and TPM2) were identified as key genes that interact with hsa-miR-195-5p. A ceRNA regulatory network consisted of these key genes was constructed, and Gene Set Enrichment Analysis (GSEA) indicated the possible association of key mRNAs with CRC onset and progression. Importantly, immune infiltration analysis revealed that the ceRNA network was remarkably associated with infiltration abundance of multiple immune cells and expression levels of immune checkpoints. These findings indicate that NEAT1 and XIST are potential prognostic factors that affect CRC onset and progression by targeting miR-195-5p.

A Novel Technique for Extracorporeal Anastomosis: The Bronchus Forceps Is Applied to Reinforce the Esophageal Ring.

Background: For laparoscopic gastrectomy, it is significant to reduce the incidence of anastomotic leakage. The authors develop a novel technique for safe extracorporeal anastomosis that employs the bronchus forceps to reinforce the esophageal ring. Methods: From January 2017 to July 2020, 173 consecutive patients with gastric cancer received laparoscopic total gastrectomy or laparoscopic proximal gastrectomy. One hundred thirty-one patients only underwent extracorporeal anastomosis with a purse-string suture instrument (PSI) and a 25 mm circular stapler (Ethicon Intraluminal Circular Staplers CDH25A, Ethicon) (Conventional Surgery Group). In addition to these tools for extracorporeal anastomosis, the surgeon creatively used bronchus forceps to reinforce the esophageal ring on the anvil of circular stapler in 42 patients (Bronchus Forceps Ligation Group). The condition and the mean diameter of the narrowest part of the esophageal rings, postoperative outcomes, and complications were compared between the two groups. Results: Under direct vision, the esophageal rings were more complete in the Bronchus Forceps Ligation Group. Furthermore, the mean diameter of the narrowest part of the esophageal rings in the Bronchus Forceps Ligation Group was wider than that in the Conventional Surgery Group (4.34 ± 0.84 versus 2.68 ± 0.74 mm; P < .001). Meanwhile, the incidence of anastomotic leakage was lower in the Bronchus Forceps Ligation Group. Although reinforcing the anvil with the bronchus forceps will add additional surgery time, almost all can be done in less than 5 minutes. Conclusions: With applying the bronchus forceps to reinforce the esophageal ring on the anvil of the circular stapler, the extracorporeal anastomosis can be performed more safely.

[Retracted] H19 promotes the migration and invasion of colon cancer by sponging miR­138 to upregulate the expression of HMGA1.

Following the publication of this paper, it was drawn to our attention by an interested reader that a row of tumour images featured in Fig. 5A of the above paper were strikingly similar to those featured in Fig. 7A of an article appearing in Oncology Research [Zhang X, Gao F, Zhou L, Wang H, Shi G and Tan X: UCA1 regulates the growth and metastasis of pancreatic cancer by sponging miR­135a. Oncol Res 25: 1529­1541, 2017]. Furthermore, similarities in the data were also identified comparing Fig. 4A in the above paper with Fig. 6A in the same paper published in Oncology Research by Zhang et al. Finally, immunohistochemistry data featured in Fig. 5G were strikingly similar to data featured in Fig. 7G in the following article [Li Y, Luo H, Xiao N, Duan J Wang Z and Wang S: Long noncoding RNA SChLAP1 accelerates the proliferation and metastasis of prostate cancer via targeting miR­198 and promoting the MAPK1 pathway. Oncol Res 26: 131­143, 2018]. The Editor asked the authors for an explanation to account for the appearance of strikingly similar data in their paper independently, although the authors never responded within a reasonable time to confirm that the paper should be retracted. The Editor has therefore made the executive decision to retract this paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in International Journal of Oncology 50: 1801­1809, 2017; DOI: 10.3892/ijo.2017.3941].

H19 promotes the gastric carcinogenesis by sponging miR-29a-3p: evidence from lncRNA-miRNA-mRNA network analysis.

Aim: To identify novel competing endogenous RNA (ceRNA) network correlated with the prognosis of gastric cancer (GC) patients. Materials & methods: We systematically analyzed the aberrantly expressed genes in human GC to construct a ceRNA network by using multiple bioinformatic tools. Results: Aberrantly expressed mRNAs in GC were identified. By means of stepwise reverse prediction and validation from mRNA to lncRNA, a ceRNA network comprised of H19, miR-29a-3p, COL3A1, COL5A2, COL1A2 and COL4A1 was constructed, and all genes in the network are significantly correlated with the prognosis of GC patients. Conclusion: The present study successfully constructed a GC related ceRNA network, and provided potential targets for GC clinical treatment.

CDK1 and CDC20 overexpression in patients with colorectal cancer are associated with poor prognosis: evidence from integrated bioinformatics analysis.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies of the digestive system, which causes severe financial burden worldwide. However, the specific mechanisms involved in CRC are still unclear. METHODS: To identify the significant genes and pathways involved in the initiation and progression of CRC, the microarray dataset GSE126092 was downloaded from Gene Expression Omnibus (GEO) database, and then, the data was analyzed to identify differentially expressed genes (DEGs). Subsequently, the Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on these DEGs using the DAVID database, and the protein-protein interaction (PPI) network was constructed using the STRING database and analyzed using the Cytoscape software. Finally, hub genes were screened, and the survival analysis was performed on these hub genes using the Kaplan-Meier curves in the cBioPortal database. RESULTS: In total, 937 DEGs were obtained, including 316 upregulated genes and 621 downregulated genes. GO analysis revealed that the DEGs were mostly enriched in terms of nuclear division, organelle fission, cell division, and cell cycle process. KEGG pathway analysis showed that the DEGs were mostly enriched in cell cycle, oocyte meiosis, cytokine-cytokine receptor interaction, and cGMP-PKG signaling pathway. The PPI network comprised 608 nodes and 3100 edges, and 4 significant modules and 10 hub genes with the highest degree were identified using the Cytoscape software. Finally, survival analysis showed that overexpression of CDK1 and CDC20 in patients with CRC were statistically associated with worse overall survival. CONCLUSIONS: This bioinformatics analysis revealed that CDK1 and CDC20 might be candidate targets for diagnosis and treatment of CRC, which provided valuable clues for CRC.

Stenting as a bridge to resection versus emergency surgery for left-sided colorectal cancer with malignant obstruction: A systematic review and meta-analysis.

PURPOSE: This study aims to discuss the safety and feasibility of a combined treatment consisting of stent insertion and elective surgery for left-sided colorectal cancer with malignant obstruction. METHODS: Randomized clinical trials (RCTs) that discussed the safety and feasibility of stenting as a bridge to surgery in malignant colorectal cancer were identified in a search of medical databases, including PubMed, Embase, Cochrane Library, and SCIENCE. Each paper's quality was assessed using the Jadad scale. A meta-analysis was conducted using RevMan 5.3, and statistical heterogeneity between RCTs was defined as I2>50%. RESULTS: Nine RCTs included 594 patients were selected and analyzed. Of the included patients, 281 underwent stent insertion followed by elective surgery (SG group), and 313 underwent emergency surgery (EG group). The meta-analysis revealed that the patients in the SG group had a higher one-stage anastomosis rate. Patients in the SG had lower mortality rates and minor complications. There was no significant difference in anastomotic leakage between the two groups. The funnel plot showed that there was no publication bias in these outcomes. CONCLUSION: Stenting as a bridge to surgery was safe and feasible in left-sided colorectal cancer with malignant obstruction. Compared with the patients in the EG group, the SG patients had an improved primary anastomosis rate and experienced no increase in the risk of other complications.

H19 promotes the migration and invasion of colon cancer by sponging miR-138 to upregulate the expression of HMGA1.

Colon cancer is the most common digestive system malignancy, along with high mortality rate, familial transmissibility and hepatic metastasis. Our study investigated the role of long non-coding RNA H19 in colon cancer. We found that H19 was overexpressed in colon cancer tissues and cell lines, the interference of H19 by short hairpin RNA (shRNA) effectively decreased the migration and invasion of colon cancer cells (HT-29 and RKO). Besides, miR-138 was predicted a target of H19, and low expression of miR-138 was found in colon cancer tissues and cells. The silence of H19 strongly increased the expression of miR-138. The decreased level of miR-138 was elevated adding miR-138 mimic in RKO cells transfected with lncRNA-H19. Similarly, the upregulated level of miR-138 was downregulated adding miR-138 inhibitor in RKO cells transfected with H19 shRNA. The luciferase reporter confirmed the targeting reaction between H19 and miR-138. Moreover, the high-mobility group A (HMGA1) protein was predicted as a target of miR-138. HMGA1 was suppressed by H19 shRNA and could be up-regulated by miR-138 inhibitor. The migration and invasion ability of colon cancer was restrained by H19 shRNA and promoted by miR-138 inhibitor. Finally, the in vivo experiment revealed that H19 shRNA strongly reduced the tumor growth and tumor volume. H19 shRNA also inhibited metastasis via suppressing hepatic metastases and the expression of metastasis-related proteins. Taken together, our research indicated an H19-miR138-HMGA1 pathway in regulating the migration and invasion of colon cancer, providing new insight for treatment of colon cancer.

Mitigating the Consequences of Anastomotic Leakage After Laparoscopic Rectal Cancer Resection: Is It Achievable by a Simple Method?

BACKGROUND: With regard to laparoscopic low anterior resection, anastomotic leakage still remains a challenge and continues to account for approximately 30% of postoperative deaths. This study was designed to evaluate whether the intracolonic and perineal drainage is associated with a decreased risk for anastomotic leakage after laparoscopic rectal cancer surgery without stool diversion. PATIENTS AND METHODS: Prospective data were collected from 337 patients with rectal cancer who underwent laparoscopic resection without defunctioning stoma. RESULTS: A total of 157 patients underwent laparoscopic rectal resection, followed by the placement of intracolonic and perineal drainage, while 180 underwent laparoscopic surgery routinely. No difference in clinically significant leakage was observed between the intracolonic and perineal drainage and the control groups (3.8% vs 8.3%, P = .0874). However, reoperation was underwent at a significantly lower rate after the placement of intracolonic and perineal drainage (intracolonic and perineal drainage: 1 of 6 [16.7%] vs control: 14 of 15 [93.3%]; P < .01). In multivariate analysis, extraperitoneal tumor location and operation duration ≥180 minutes were independently associated with anastomotic leakage. CONCLUSIONS: Significant risk factors of anastomotic leakage include extraperitoneal tumor location and operation duration ≥180 minutes. The placement of intracolonic and perineal drainage was not found to be significantly associated with anastomotic leakage, but this method could mitigate the clinical consequences of leakage and decrease the rate of reoperation and transverse colostomy after laparoscopic anterior resection for rectal cancer.

Surgical margins and short-term results of laparoscopic total mesorectal excision for low rectal cancer.

BACKGROUND AND OBJECTIVES: The confines of the narrow bony pelvis make laparoscopic surgery more challenging in the treatment of low rectal cancer. Macroscopic evaluation of the completeness of the mesorectum provides detailed information about the quality of surgery. This study was performed to observe the short-term outcomes and evaluate the macroscopic quality of specimens acquired from laparoscopic total mesorectal excision versus open total mesorectal excision in patients with low rectal cancer. METHODS: A total of 177 patients with low rectal cancer underwent total mesorectal excision by either a laparoscopic (n = 87) or open (n = 90) approach. In all cases the surgical time, blood loss, intraoperative and postoperative complications, postoperative bowel opening, and hospital stay were assessed. Special attention was given to the macroscopic judgment concerning the cut edge of peritoneal reflection, Denonvilliers fascia, completeness of the mesorectum, and bowel wall below the mesorectum. RESULTS: The surgical time was 160 ± 40 minutes in the laparoscopic group. It was not significantly different from that in the open group (P = .782). The operative blood loss was 28 ± 5 mL in the group undergoing laparoscopic surgery and 80 ± 20 mL in the group undergoing open surgery (P < .01). Intraoperative injuries to the pelvic autonomic nervous system were recorded in 4 cases in the laparoscopic group compared with 12 cases in the open group (P < .05). The incidences of chest infection and anastomotic leakage were similar between the 2 approaches. The postoperative bowel opening time was 2.1 ± 1.5 days in the laparoscopic group and 3.5 ± 1.6 days in the open group (P < .01), whereas the hospital stay was 5.2 ± 1.8 days and 7.0 ± 2.1 days, respectively (P < .01). Intact Denonvilliers fascia and complete total mesorectal excision were more likely to be achieved by the laparoscopic approach than the open approach (P < .01). Colorectal anastomoses were located significantly lower in the laparoscopic group than in the open group (P < .01). CONCLUSION: Laparoscopic total mesorectal excision has consistent advantages over open total mesorectal excision, including similar surgical time, less blood loss, reduced hospital stay, and shorter disability period. A complete macroscopic specimen is more likely to be acquired by laparoscopy because of the better pelvic view offered by the approach.