IL-17A-mediated mitochondrial dysfunction induces pyroptosis in colorectal cancer cells and promotes CD8 + T-cell tumour infiltration.

BACKGROUND: Interleukin-17A (IL-17A), a proinflammatory cytokine primarily secreted by Th17 cells, γδT cells and natural killer T (NKT) cells, performs essential roles in the microenvironment of certain inflammation-related tumours by regulating cancer growth and tumour elimination proved in previous literature. In this study, the mechanism of IL-17A that induces mitochondrial dysfunction promoted pyroptosis has been explored in colorectal cancer cells. METHOD: The records of 78 patients diagnosed with CRC were reviewed via the public database to evaluate clinicopathological parameters and prognosis associations of IL-17A expression. The colorectal cancer cells were treated with IL-17A, and the morphological characteristics of those cells were indicated by scanning electron microscope and transmission electron microscope. After IL-17A treatment, mitochondrial dysfunction was tested by mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). The expression of pyroptosis associated proteins including cleaved caspase-4, cleaved gasdermin-D (GSDMD), IL-1ß, receptor activator of nuclear NOD-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck like protein containing a card (ASC), and factor-kappa B was measured through western blotting. RESULTS: Positive IL-17A protein expression was observed in CRC compared to the non-tumour tissue. IL-17A expression indicates a better differentiation, earlier stage, and better overall survival in CRC. IL-17A treatment could induce mitochondrial dysfunction and stimulate intracellular reactive oxygen species (ROS) production. Furthermore, IL-17A could promote pyroptosis of colorectal cancer cells and significantly increase the secretion of inflammatory factors. Nevertheless, the pyroptosis induced by IL-17A could be inhibited through the pre-treatment with Mito-TEMPO (a mitochondria-targeted superoxide dismutase mimetic with superoxide and alkyl radical scavenging properties) or Z-LEVD-FMK (caspase-4 inhibitor, fluoromethylketone). Additionally, after being treated with IL-17A, an increasing number of CD8 + T cells showed in mouse-derived allograft colon cancer models. CONCLUSION: IL-17A, as a cytokine mainly secreted by γδT cells in the colorectal tumour immune microenvironment, can regulate the tumour microenvironment in multiple ways. IL-17A could induce mitochondrial dysfunction and pyroptosis through the ROS/NLRP3/caspase-4/GSDMD pathway, and promote intracellular ROS accumulation. In addition, IL-17A can promote the secretion of inflammatory factors such as IL-1ß、IL-18 and immune antigens, and recruit CD8 + T cells to infiltrate tumours.

CCL7 and TGF-ß secreted by MSCs play opposite roles in regulating CRC metastasis in a KLF5/CXCL5-dependent manner.

CXCL5 is overexpressed in colorectal cancer (CRC) and promotes distant metastasis and angiogenesis of tumors; however, the underlying mechanism that mediates CXCL5 overexpression in CRC remains unclear. Here, we successfully extracted and identified primary mesenchymal stromal cells (MSCs) and verified the promoting effects of tumor-associated MSCs on CRC proliferation and metastasis in vivo and in vitro. We found that MSCs not only promoted the expression of CXCL5 by secreting CCL7 but also secreted TGF-ß to inhibit this process. After secretion, CCL7/CCR1 activated downstream CBP/P300 to acetylate KLF5 to promote CXCL5 transcription, while TGF-ß reversed the effect of KLF5 on transcription activation by regulating SMAD4. Taken together, our results indicate that MSCs in the tumor microenvironment promoted the progression and metastasis of CRC and regulated the expression of CXCL5 in CRC cells by secreting CCL7 and TGF-ß. KLF5 is the key site of these processes and plays a dual role in CXCL5 regulation. MSCs and their secreted factors may serve as potential therapeutic targets in the tumor environment.

High ligation versus low ligation of the inferior mesenteric artery in laparoscopic rectal cancer surgery: a retrospective study on surgical and long-term outcome.

BACKGROUND: In laparoscopic low anterior resection for rectal cancer surgery, there has been controversy to whether the inferior mesenteric artery (IMA) should be ligated at the origin of its aorta (high ligation (HL)) or below the branches of the left colonic artery (LCA) (low ligation (LL)). This study was intended to clarify oncological outcome and long-term prognosis of retrospective analysis. METHODS: Analyzed the cases who underwent laparoscopic low anterior resection (LAR) in Shanghai Ruijin Hospital from January 2015 to December 2016, 357patients scheduled into 2 groups according to the level of IMA ligation: HL (n = 247) versus LL (n = 110). RESULTS: The primary endpoint is long-term outcomes, and the secondary endpoint is the incidence rate of major postoperative complications. There were no significant differences in 5-year overall survival (P = 0.92) and 5-year disease-free survival (P = 0.41). There were no differences between the clinical baseline levels in each group. The incidence of low anterior resection syndrome (LARS) in the two groups was statistically significant (P = 0.037). No significant differences were observed in operative time (P = 0.092) and intraoperative blood loss (P = 0.118). In the HL group, 6 cases (2.4%) had additional colonic excision due to poor anastomotic blood supply; none of the colonic anastomosis in the low ligation group had ischemic manifestations, and length from the proximal margin (P = 0.076), length from the distal margin (P = 0.184), the total number of lymph nodes excised (P = 0.065), and anastomotic leakage incidence (P = 0.33). CONCLUSION: Low ligation of the IMA which reserved LCA with vascular root lymph node dissection in laparoscopic low anterior resection for rectal cancer surgery may help protect the blood supply of the anastomosis, and will not increase postoperative complications while enhance recovery, without compromising radical excision and long-term prognosis.

Intracorporeal versus extracorporeal anastomosis in laparoscopic right colectomy: a retrospective study.

BACKGROUND: The surgical procedure for laparoscopic right colectomy (LRC) is not standardized. Some published studies show the superiority of ileocolic anastomosis (IIA), but the evidence so far is insufficient. This study aimed to investigate the potential advantages in postoperative recovery and safety of IIA in LRC. METHODS: A total of 114 patients who underwent LRC with IIA (n = 58) or extracorporeal ileocolic anastomosis (EIA, n = 56) between January 2019 and September 2021 were enrolled. We collected certain factors as clinical features, intraoperative characteristics, oncological outcomes, postoperative recovery, and short-term outcomes. Our primary outcome was time to gastrointestinal (GI) function recovery. Secondary outcomes were postoperative complications within 30 days, postoperative pain, and length of hospital stay. RESULTS: Faster GI recovery and less postoperative pain were observed in patients with IIA compared to EIA [time to first flatus: (2.4 ± 0.7) vs (2.8 ± 1.0) days, p < 0.01; time to liquid intake: (3.5 ± 0.7) vs (4.0 ± 1.1) days, p = 0.01; postoperative visual analogue scale score: (3.9 ± 1.0) vs (4.3 ± 0.6), p = 0.02]. No significant differences were detected in oncological outcomes or postoperative complications. IIA, rather than EIA, tended to be performed in patients with higher body mass index [(23.93 ± 3.52) vs (22.36 ± 2.87) kg/m2, p = 0.01]. CONCLUSIONS: IIA is associated with faster GI function recovery and less postoperative pain and may be more favorable for obese patients.

Combination of FOXD1 and Plk2: A novel biomarker for predicting unfavourable prognosis of colorectal cancer.

Colorectal cancer (CRC) is a worldwide disease with worse survival. Our objective is to identify previously unrecognized prognostic factors to better evaluate disease progression. Seven GEO datasets were collected and analysed using R software, followed by KEGG enrichment analysis and TFs network construction. LASSO-COX analysis was performed to select the most useful prognostic features. COX model was used to analyse prognostic factors associated with OS. The survival curve was constructed using Kaplan-Meier analysis. A Nomogram model was also constructed to predict prognosis. A total of 3559 differentially expressed genes (DEGs) and 66 differentially expressed transcription factors were identified. FOXD1 was identified as the most differentially expressed factor of TFs covering the most downstream DEGs and independent risk prognostic factor. Next, FOXD1 expression was detected using immunohistochemical staining in 131 CRC patients' tissue and the association between FOXD1 expression and clinicopathologic features was analysed. High expression of FOXD1 was correlated with TNM stage and pathological differentiation. Multivariate COX regression analyses confirmed that FOXD1 high-expression, TNM stage and tumour differentiation were independent prognostic risk factor of OS and DFS. Patients with high expression of FOXD1 were more likely to have poor overall survival and disease-free survival. The combination of FOXD1 and Plk2 which we have previously reported allowed us to predict the survival of post-surgical CRC patients more accurately, adding to the former prognostic model based on the TNM Stage. The results showed that patients with high expression of both FOXD1 and Plk2 have the worst survival. A combination of FOXD1 and Plk2 can better evaluate patients' survival.

Platelet infiltration predicts survival in postsurgical colorectal cancer patients.

Platelets promote tumor growth and metastasis in several tumor types. Recent research has found platelets can extravasate and infiltrate into the tumor stroma and interact with the tumor microenvironment. The prognostic role of platelet infiltration in colorectal cancer (CRC) remains controversial. A pan-cancer survival analysis was performed to find the potential prognostic value of platelet infiltration in patients with cancer. A survival analysis and a nomogram prognostic model were established to further confirm the results with data from our center. The correlations between patient outcomes and tumor-infiltrating platelets (TIPs) were identified by immunohistochemical staining for CD42b. The prognostic accuracy and discriminative ability of the nomogram were determined by the concordance index (C-index) and a calibration curve. The pan-cancer survival analysis showed platelet infiltration can lead to a poor prognosis in patients with several types of cancers, including CRC. Platelet infiltration was associated with overall survival (OS) and disease-free survival (DFS) in both primary and validation cohorts. The C-index values of the nomogram for predicting OS and DFS were 0.774 and 0.769, respectively, which were higher than that of the TNM staging system alone. Our study found platelet infiltration has a potential prognostic value regarding postsurgical survival in CRC patients. The proposed nomogram resulted in a more accurate prognostic prediction for postsurgical CRC patients.

The Medial Border of Laparoscopic D3 Lymphadenectomy for Right Colon Cancer: Results from an Exploratory Pilot Study.

BACKGROUND: Opinions vary on the medial border of D3 lymphadenectomy for right colon cancer. Most surgeons place the medial border along the left side of the superior mesenteric vein, but some consider the left side of the superior mesenteric artery as the medial border. OBJECTIVES: This study investigated the clinical outcomes of laparoscopic D3 lymphadenectomy for right colon cancer with the medial border along the left side of superior mesenteric artery. DESIGN: This was a retrospective study. SETTINGS: The study was conducted in specialized colorectal cancer department of 5 tertiary hospitals. PATIENTS: Patients receiving laparoscopic D3 lymphadenectomy for right colon cancer from January 2013 to December 2018 were included. MAIN OUTCOME MEASURES: After propensity score matching, 307 patients receiving laparoscopic D3 lymphadenectomy along the left side of the superior mesenteric artery were assigned to the superior mesenteric artery group and 614 patients were assigned to the superior mesenteric vein group. Univariate, multivariate, and Kaplan-Meier analyses were performed to assess the clinical data. RESULTS: The short-term outcomes were similar between the 2 groups; however, the superior mesenteric artery group had a higher rate of chylous leakage (p < 0.001). More lymph nodes were harvested from the superior mesenteric artery group than from the superior mesenteric vein group (p = 0.001). The number (p = 0.005) of metastatic lymph nodes and the lymph node ratio (p = 0.041) in main nodes were both higher in the superior mesenteric artery group. The 2 groups had similar long-term survival, but the superior mesenteric artery group tended to show better disease-free survival in patients with stage disease III (p = 0.056). LIMITATIONS: This was a retrospective, nonrandomized study. CONCLUSION: Laparoscopic D3 lymphadenectomy along the left side of the superior mesenteric artery, except for a higher rate of chylous leakage, had short-term outcomes comparable to the superior mesenteric vein group. The superior mesenteric artery group tended to achieve better disease-free survival in patients with stage III disease, but further study is required to better elucidate differences in these approaches because risks/benefits do exist.

High versus low ligation of the inferior mesenteric artery during laparoscopic rectal cancer surgery: A prospective study of surgical and oncological outcomes.

BACKGROUND AND OBJECTIVES: There is controversy regarding whether the inferior mesenteric artery (IMA) should be ligated at its origin from the aorta (high ligation, HL) or below the branch of the left colic artery (low ligation, LL) during surgery for rectal cancer. METHODS: This prospective study randomized 95 patients with histologically proven rectal cancer (clinical stages I-III based on the 8th American Joint Committee on Cancer guidelines) to undergo HL (n = 47) or LL with lymph node dissection at the root of the IMA (n = 48). RESULTS: Only two intraoperative adverse events were observed (two HL patients experienced anastomotic ischemia and underwent extended bowel excision and splenic flexure mobilization). The LL group had a significantly shorter time to first flatus (p < .0001). No significant differences were observed in operative time (p = .14), intraoperative blood loss (p = .21), distance from the upper margin (p = .77), distance from the lower margin (p = .35), harvested lymph nodes (p = .33), or anastomotic leakage (p = .44), 2-year overall survival (p = .97), or 2-year disease-free survival (p = .42). CONCLUSION: During laparoscopic low anterior resection, a combination of LL at the IMA and vascular root lymph node dissection may help protect the blood supply of the anastomosis, reduce postoperative complications, and enhance recovery, without compromising radical excision.

Staged laparoscopic management of locally advanced gastric cancer with outlet obstruction.

BACKGROUND: The prognosis of patients with locally advanced gastric cancer with outlet obstruction is poor. Gastrectomy with curative intent is often initially impossible or difficult. OBJECTIVE: We report our experience of curative distal gastrectomy after laparoscopic gastrojejunostomy and fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy to examine the feasibility and safety of this modified strategy for locally advanced gastric cancer with outlet obstruction, initially deemed unresectable. METHODS: Between October 2017 and June 2019, 15 patients diagnosed with locally advanced gastric cancer with outlet obstruction sequentially underwent gastrojejunostomy, received four cycles of FLOT chemotherapy, and underwent laparoscopic distal gastrectomy with curative intent (R0 resection + D2 lymphadenectomy). Clinical data were retrospectively collected and analyzed. RESULTS: R0 resection was possible in 12/15 patients, laparoscopically in 11, and one conversion to laparotomy was necessary. There was no perioperative mortality in the 12 patients. Pathologic evaluation of the resected specimens revealed that complete tumor grade regression 1a (TRG1a), TRG1b, TRG2, and TRG3 occurred in 3, 2, 4, and 3 patients, respectively. CONCLUSION: This case series showed that curative surgical resection was feasible as a staged approach for patients with locally advanced gastric cancer with outlet obstruction, after initial staged gastrojejunostomy and chemotherapy.

Comparative study of oncologic efficacy of cephalomedial to lateral dissection versus medial to lateral dissection in laparoscopic total mesorectal excision for rectal cancer: An RCT study.

BACKGROUND AND OBJECTIVES: We compared the 3-year overall survival between cephalomedial-to-lateral approach proctectomy (CEMP) and medial-to-lateral approach proctectomy (MAP) in patients undergoing laparoscopic total mesorectal excision for rectal cancer. The advantages of CEMP and the clinical value of No. 253 lymph nodes resection have not been objectively analyzed in literature. METHODS: This was a prospective, two-arm, multicenter, single-blinded, randomized trial. The primary endpoint was 3-year overall survival, and secondary endpoints included safety, feasibility, oncological radicality (including number of No. 253 lymph nodes harvested), short-term outcome, 3-year disease-free survival, rate of postoperative complications, mortality, and rate of recurrence. RESULTS: From May 2016 to July 2020, 506 patients were enrolled-256 in the CEMP group and 250 in the MAP group. Comparison of overall survival and disease-free survival showed that there was treatment benefit in the CEMP group (28.22 ± 12.12 vs. 27.44 ± 13.06, p = 0.485; 27.24 ± 12.01 vs. 26.42 ± 12.81; p = 0.457). More No. 253 lymph nodes were harvested in the CEMP group, and cases with positive No. 253 lymph nodes had worse prognosis in stage III. Surgical safety was equal for both approaches. CONCLUSIONS: Dissection of No. 253 lymph nodes may be important to improve clinical prognosis, but further studies with larger samples are needed to confirm this finding.

Pelvic peritoneum closure reduces postoperative complications of laparoscopic abdominoperineal resection: 6-year experience in single center.

BACKGROUND: To investigate feasibility of laparoscopic abdominoperineal resection with pelvic peritoneum closure (LAPR-PPC) for lower rectal cancer. METHODS: LAPR-PPC has been used for lower rectal cancer in our institution since 2014. In this study, we retrospectively analyzed the data from 86 patients who underwent LAPR-PPC and compared with the data from 96 patients who underwent laparoscopic APR without PPC (LAPR) from January 2013 to December 2018. RESULTS: The rate of perineal surgical site infection (SSI) (18.75% (18/96) vs. 5.81% (5/86), p < 0.01), delayed (> 4 weeks) perineal healing (12.50% (12/96) vs. 3.49% (3/86), p = 0.027), ileus (7.29% (7/96) vs 1.16% (1/86), p = 0.044), and postoperative perineal hernia (PPH, 5.21% (5/96) vs. 0% (0/86), p = 0.032) were significantly lower in LAPR-PPC group than LAPR group. The patients in LAPR-PPC group had shorter hospitalization time (21.32 ± 11.95 days vs. 13.93 ± 11.51 days, p < 0.01). CONCLUSIONS: PPC procedure enabled the reduction in perineal wound complications, ileus, PPH, and consequently shortened hospitalization time. LAPR-PPC is beneficial for the patients with lower rectal cancer.

Completely medial access by page-turning approach for laparoscopic right hemi-colectomy: 6-year-experience in single center.

BACKGROUND: To investigate the safety and feasibility of the completely medial access by page-turning approach (CMAP) for laparoscopic right hemi-colectomy. METHODS: In this retrospective study, the data from 72 patients who underwent laparoscopic right hemi-colectomy with CMAP were analyzed and compared with data from 124 patients who underwent the conventional medial approach performed by the same surgical team from September 2011 to March 2017. RESULT: Complete mesocolic excision (CME) was achieved in 67 of 72 patients (93.1%) with laparoscopic CMAP. The average operation time, blood loss, and specimen length was 135.9 ± 28.3 min, 63.2 ± 32.2 ml, and 23.9 ± 4.7 cm, respectively. The number of lymph nodes harvested was 20.6 ± 7.7, the time-to-flatus was 2.5 ± 0.8 days, the time-to-fluid intake was 3.2 ± 0.8 days, and the average hospital stay was 8.9 ± 4.7 days. No intra-operative complications occurred in this study. The vessel-related complication and total post-operative complication rate was 2.78% (2/72) and 6.94% (5/72), respectively. CONCLUSIONS: Laparoscopic CMAP was an alternative approach for CME in laparoscopic right hemi-colectomy, which was proved safe and feasible for right colon cancer.

Bone marrow-derived mesenchymal stromal cells promote colorectal cancer cell death under low-dose irradiation.

BACKGROUND: Radiotherapy remains one of the cornerstones to improve the outcome of colorectal cancer (CRC) patients. Radiotherapy of the CRC not only help to destroy cancer cells but also remodel the tumour microenvironment by enhancing tumour-specific tropism of bone marrow-derived mesenchymal stromal cell (BM-MSC) from the peripheral circulation. However, the role of local MSCs and recruited BM-MSC under radiation were not well defined. Indeed, the functions of BM-MSC without irradiation intervention remained controversial in tumour progression: BM-MSC was previously shown to modulate the immune function of major immune cells, resulting in an impaired immunological sensitivity and to induce an increased risk of tumour recurrence. In contrast, it could also secrete various cytokines and possess anticancer effect. METHODS: Three co-cultivation modules, 3D culture modules, and cancer organoids were established. The induction of cytokines secretion in hBM-MSCs after irradiation was analysed by ELISA array and flow cytometry. AutoMac separator was used to separate hBM-MSC and CRC automatically. Cells from the co-cultured group and the control group were then irradiated by UV-C lamp and X-ray. Proliferation assay and viability assay were performed. RESULTS: In this study, we show that BM-MSCs can induce the EMT progression of CRC cells in vitro. When irradiated with low doses of ultraviolet radiation and X-rays, BM-MSCs show an anti-tumour effect by secreting certain cytokine (TNF-α, IFN-γ) that lead to the inhibition of proliferation and induction of apoptosis of CRC cells. This was further verified in a 3D culture model of a CRC cell in vitro. Furthermore, irradiation on the co-culture system induced the cleavage of caspase3, and attenuated the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/AKT and extracellular signal-regulated kinase in cancer cells. The signal pathways above might contribute to the cancer cell death. CONCLUSIONS: Taken together, we show that BM-MSC can potentially promote the effect of radiotherapy in CRC.

CCR6 promotes tumor angiogenesis via the AKT/NF-κB/VEGF pathway in colorectal cancer.

Chemokines and chemokine receptors play an important role in tumorigenesis. Angiogenesis is a vital part of the occurrence, development and metastasis of cancer. CCR6 is an important factor during tumor progression; however, its function in tumor angiogenesis is not fully understood. In our study, we found that CCR6 was significantly overexpressed in colorectal cancer (CRC) tissues and predicted a poor prognosis in CRC patients. We then verified the function of CCR6 on tumor angiogenesis in vivo and in vitro. We observed that silencing CCR6 could decrease angiogenesis by inhibiting the proliferation and migration of human umbilical vein endothelial cells (HUVECs), whereas overexpression of CCR6 can promote angiogenesis. Additionally, we investigated the molecular mechanisms and demonstrated that activation of the AKT/NF-κB pathway maybe involved in CCR6-mediated tumor angiogenesis, which was able to promote the secretion of vascular endothelial growth factor A (VEGF-A). In conclusion, CCR6 facilitates tumor angiogenesis via the AKT/NF-κB/VEGF pathway in colorectal cancer. CCR6 inhibition may be a novel option for anti-vascular treatment in CRC.

Tumor-derived CXCL5 promotes human colorectal cancer metastasis through activation of the ERK/Elk-1/Snail and AKT/GSK3ß/ß-catenin pathways.

BACKGROUND: Metastasis is a major cause of death in human colorectal cancer patients. However, the contribution of chemokines in the tumor microenvironment to tumor metastasis is not fully understood. METHODS: Herein, we examinined several chemokines in colorectal cancer patients using chemokine ELISA array. Immunohistochemistry was used to detect expression of CXCL5 in colorectal cancer patients tissues. Human HCT116 and SW480 cell lines stably transfected with CXCL5, shCXCL5 and shCXCR2 lentivirus plasmids were used in our in vitro study. Immunoblot, immunofluorescence and transwell assay were used to examine the molecular biology and morphological changes in these cells. In addition, we used nude mice to detect the influence of CXCL5 on tumor metastasis in vivo. RESULTS: We found that CXCL5 was overexpressed in tumor tissues and associated with advanced tumor stage as well as poor prognosis in colorectal cancer patients. We also demonstrated that CXCL5 was primarily expressed in the tumor cell cytoplasm and cell membranes, which may indicate that the CXCL5 was predominantly produced by cancer epithelial cells instead of fibroblasts in the tumor mesenchyme. Additionally, overexpression of CXCL5 enhanced the migration and invasion of colorectal cancer cells by inducing the epithelial-mesenchymal transition (EMT) through activation of the ERK/Elk-1/Snail pathway and the AKT/GSK3ß/ß-catenin pathway in a CXCR2-dependent manner. The silencing of Snail and ß-catenin attenuated CXCL5/CXCR2-enhanced cell migration and invasion in vitro. The elevated expression of CXCL5 can also potentiate the metastasis of colorectal cancer cells to the liver in vivo in nude mice intrasplenic injection model. CONCLUSION: In conclusion, our findings support CXCL5 as a promoter of colorectal cancer metastasis and a predictor of poor clinical outcomes in colorectal cancer patients.

A modified uncut Roux-en-Y anastomosis in totally laparoscopic distal gastrectomy: preliminary results and initial experience.

OBJECTIVE: To investigate the safety and feasibility of totally laparoscopic uncut Roux-en-Y anastomosis in the distal gastrectomy with D2 dissection for gastric cancer. We also summarized the preliminary experience of totally laparoscopic uncut Roux-en-Y anastomosis. METHODS: A retrospective analysis was done in 51 cases of total laparoscopic uncut Roux-en-Y anastomosis in the distant gastrectomy with D2 dissection for gastric cancer in our hospital from September 2014 to December 2015. RESULTS: All of 51 cases underwent total laparoscopic uncut Roux-en-Y anastomosis. All the procedures were performed successfully. There were neither conversions to open surgery nor intraoperative complications in all 51 cases. In this study, the median operative time was 170 (135-210) min and the median time of anastomosis was 27 (24-41) min. The blood loss was 60 (30-110) ml. The time to flatus and length of postoperative hospital stay were 2 (1-3) days, and 8 (7-12) days, respectively. The mean lymph node harvest was 34 (18-49). One anastomotic bleeding occurred postoperatively which was cured by conservative treatment. No major postoperative complication occurred, such as anastomotic leak, anastomotic stenosis, and Roux stasis syndrome. After a short-term follow-up, no recanalization or reflux gastritis was encountered by endoscopy. CONCLUSION: The totally laparoscopic uncut Roux-en-Y anastomosis in distal gastrectomy with lymph node dissection for gastric cancer is safe and feasible, with a very low rate of recanalization and reflux gastritis.

Cadherin-12 enhances proliferation in colorectal cancer cells and increases progression by promoting EMT.

Cadherin-12 (CDH12) is a subtype of N-cadherin family. In this study, we investigated the expression of CDH12 and the role of CDH12 in prognosis of colorectal cancer (CRC) patients. In addition, we observed the influence of CDH12 on proliferation and progression of CRC cell lines. By using immunohistochemical staining, we analyzed CRC samples and adjacent non-tumor tissues collected from 78 patients who underwent laparoscopic surgery in Shanghai Minimally Invasive Center, China. Statistical analyses were used to analyze relationship between CDH12 and tumor features. Kaplan-Meier method was used to analyze patients' survival. Proliferation ability of CRC cells was tested by CCK-8 assay, and transwell assays were performed to detect migration and invasion ability. Western blot assay was performed to investigate epithelial-mesenchymal transition (EMT) variants. We found that expression of CDH12 in tumor tissue was higher than in adjacent normal tissue. High expression of CDH12 was associated with tumor invasion depth and predicts poor prognosis of CRC patients. Ectopic/repressing expression of CDH12 increased/decreased the proliferation and migration ability of CRC cells. CDH12 is able to increase cancer cell migration and invasion via promoting EMT by targeting transcriptional factor Snail. These findings may conclude that CDH12 may act as a predictor in CRC patients' prognosis and an oncogene in CRC cell proliferation and migration. CDH12 may influence CRC cell progression through promoting EMT by targeting Snail. In addition, CDH12 is promoted by MCP1 through induction of MCPIP.

Survival of Colorectal Cancer in Patients With or Without Inflammatory Bowel Disease: A Meta-Analysis.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of colorectal cancer (CRC), but little is known about the influence of IBD on CRC prognosis. AIMS: The aim of this study was to perform a meta-analysis to compare survival in CRC patients with IBD (IBD-CRC) and without IBD. METHODS: An electronic search was conducted via PubMed, Embase, and the Cochrane Library to identify eligible trials until July 2015. We pooled the hazard ratios (HRs) and their 95% confidence intervals (CIs) to quantitatively assess the survival of CRC in patients with or without IBD. In addition, clinicopathological parameters of IBD-CRC versus non-IBD CRC were evaluated. RESULTS: Twelve studies containing a total of 3472 IBD-CRC patients were eligible according to our selection criteria. Our analysis indicated that CRC patients with IBD had shorter overall survival than those without IBD (HR 1.24, 95% CI 1.19-1.29). IBD-CRC showed a propensity to develop in proximal colon [odds ratio (OR) 2.52, 95% CI 1.35-4.72] and correlated with worse differentiation of tumor (OR 1.59, 95% CI 1.26-1.99) compared to non-IBD CRC. Meta-regression analysis showed that sample size (P = 0.002) could explain 99.01% inter-study heterogeneity. CONCLUSION: This meta-analysis found poorer overall survival in CRC patients with IBD than CRC patients without IBD, and further prospective research to confirm these findings is warranted.

Completely medial versus hybrid medial approach for laparoscopic complete mesocolic excision in right hemicolon cancer.

OBJECTIVE: To explore the feasibilities between operational approaches for laparoscopic complete mesocolic excision (CME) to right hemicolon cancer. METHODS: This prospective randomized controlled trial included patients admitted to a Shanghai minimally invasive surgical center to receive laparoscopic CME from September 2011 to January 2013 randomized into two groups: hybrid medial approach (HMA) and completely medial approach (CMA). The feasibilities and strategies of the two techniques were studied and compared. Furthermore, the operation time and vessel-related complications were designed to be the primary end points, and other operational findings, including the classification of the surgical plane and postoperative recovery, were designed to be the secondary end points for this study. RESULTS: After screening, 50 cases were allocated to the HMA group and 49 to the CMA group. Within the HMA group, there were 48 cases graded with mesocolic plane and 2 with intramesocolic plane. For the CMA group, there were 42 cases graded with mesocolic plane and seven with intramesocolic plane. The differences between the two were insignificant, as were the number of lymph nodes retrieved. The mean±standard deviation total operation time for the CMA group was 128.3 ± 36.4 min, which was significantly shorter than that for the HMA group, 142.6 ± 34.8 min. For the CMA group, the time involved in central vessel ligations and laparoscopic procedures was 58.5 %, 14.1 and 81.2 ± 23.5 min, respectively, which were shorter than the HMA group. The vessel-related complication rate was significantly higher in the HMA group. CONCLUSIONS: Laparoscopic CME via the total medial approach is technically feasible after the precise identification of the surgical planes and spaces for the right hemicolon. The procedure has a shorter operation time and fewer vessel-related complications.

Antitumor efficacy of CC motif chemokine ligand 19 in colorectal cancer.

OBJECTIVES: To investigate the function of CC motif chemokine ligand 19 (CCL19) in colorectal cancer (CRC). METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry were performed separately to detect the expression of CCL19 in colorectal carcinoma tissues. The expression of CCL19 and its receptor (CCR7) in CRC cell lines were screened by Western blot. SW620, SW1116 and LoVo cell lines were screened and processed with recombinant human CCL19 (rhCCL19) or si-CCL19 RNA. Cell proliferation assay and transwell assay were performed to evaluate the proliferation, migration and invasion of CRC cells, respectively. And the role of proangiogenesis was checked by endothelial tube formation assay. RESULTS: qRT-PCR, Western blot and immunohistochemistry revealed that both CCL19 mRNA and protein were obviously expressed in a lower degree in CRC tissues than normal tissues (P < 0.01). The CCL19 expression correlated with tumor size (P = 0.03) and invasion depth (P = 0.04) in a negative manner and CCL19-positive patients had longer lifespans (P < 0.05). SW620 and SW1116 cells were screened as CCL19/CCR7 high-expression cells, while LoVo was selected as CCL19/CCR7 low-expression cell among seven CRC cell lines by Western blot. The proliferation, migration, invasion and proangiogenesis of SW620 and SW1116 cells were distinctly suppressed after they were stimulated by rhCCL19 (P < 0.05), and the data presented dose-dependency. Oppositely, these abilities were significantly enhanced after CCL19 gene was silenced (P < 0.05). However, the effects of rhCCL19 and si-CCL19 RNA on LoVo were not significant (P > 0.05). CONCLUSION: Our research findings indicate that CCL19 may play a suppressive role in colorectal tumorigenesis.