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.

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.

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.

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.

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.

Long-term outcome of laparoscopic-assisted right-hemicolectomy with D3 lymphadenectomy versus open surgery for colon carcinoma.

PURPOSE: To investigate the applicability, safety, short-term and long-term outcomes of laparoscopic surgery in the treatment of right-sided colon carcinomas with D3 lymphadenectomy. METHODS: Between June 2003 and September 2010, 324 patients with right-sided colon carcinoma underwent surgical treatment in the same hospital, 177 cases were treated by laparoscopic surgery (LRH group) and 147 cases by open surgery (ORH group). We performed a retrospective analysis of the differences between the two groups in terms of the clinical data. RESULTS: There were no significant differences between the two groups in the demographic data; however, the recovery time was significantly shorter in the LRH group, the number of overall lymph nodes harvested and principle lymph nodes harvested in the LRH group was significantly higher than in the ORH group, the incidence of postoperative complications was 12.99 % in the LRH group and 22.45 % in the ORH group (P < 0.05), and the recurrence rate in the LRH group was lower than that in the ORH group, although the difference was not significant (15.25 vs 19.73 %). The cumulative overall survival for all stages at 1, 3 and 5 years in the LRH group (97.18, 83.73 and 70.37 %) were not significantly different compared to those in the ORH group (94.56, 77.84 and 66.97 %). CONCLUSIONS: Laparoscopic-assisted right hemicolectomy with D3 lymphadenectomy for colon carcinomas is safe and effective, while it is also superior to open surgery regarding the short-term outcomes, and the long-term outcomes are similar to those of open surgery.

Long-term results of laparoscopy-assisted radical right hemicolectomy with D3 lymphadenectomy: clinical analysis with 177 cases.

PURPOSES: To study the feasibility, safety, and short-/long-term outcomes of laparoscopy-assisted right hemicolectomy with D3 lymphadenectomy for colon cancer. METHODS: The clinical data of 177 cases that underwent laparoscopy-assisted radical right hemicolectomy with D3 lymphadenectomy for colon cancer between Jun 2003 and Sep 2010 was collected; the safety of operation, status of recovery, complication, oncological outcomes, and results of short-/long-term follow-up were analyzed. RESULTS: No case died in this study; five cases (2.82 %) were converted to open surgery. Four cases (2.26 %) underwent hand-assisted laparoscopic right hemicolectomy. The average operation time was 133 ± 36 min, and the blood loss was 94 ± 34 ml. The average time for passage of flatus, liquid food eating, and hospitalization were 2.1 ± 0.7, 3.2 ± 0.5, and 10.4 ± 2.7 day, respectively. The total number of lymph nodes removed was 15.2 ± 10.1. Postoperative complications were observed in 23 of 177 patients (12.99 %). The median follow-up period was 54 months; port-site recurrence was observed in one patient; local recurrence was found in five cases (2.82 %); distant metastasis was found in 21 cases (11.86 %). The cumulative overall survival of all stages at 12, 36, 60, and 72 months was 97.18 %, 83.73 %, 70.37 %, and 68.99 %, respectively. The cancer-specific survival was 98.73 % (12 months), 87.81 % (36 months), and 80.17 % (60 months). CONCLUSIONS: Laparoscopy-assisted right hemicolectomy with D3 lymphadenectomy can be successfully performed for right colon cancer with the advantages of minimally invasive surgery. Moreover, the results implied appropriate short- and long-term outcomes.

FOXD1 promotes chemotherapy resistance by enhancing cell stemness in colorectal cancer through ß­catenin nuclear localization.

Forkhead box D1 (FOXD1) serves a critical role in colorectal cancer (CRC). FOXD1 expression is an independent prognostic factor in patients with CRC; however, the molecular mechanism and signaling pathway of FOXD1 that regulates cell stemness and chemoresistance has not been fully characterized. The aim of the present study was to further validate the effect of FOXD1 on the proliferation and migration of CRC cells, and to delve into the possible potential of FOXD1 in the clinical treatment of CRC. The effect of FOXD1 on cell proliferation was assessed using Cell Counting Kit 8 (CCK­8) and colony formation assays. The effect of FOXD1 on cell migration was assessed by wound­healing and Transwell assays. The effect of FOXD1 on cell stemness was assessed by spheroid formation in vitro and limiting dilution assays in vivo. The expression of stemness associated proteins, leucine rich repeat containing G protein­coupled receptor 5 (LGR5), OCT4, Sox2 and Nanog, and epithelial­mesenchymal transition associated proteins, E­cadherin, N­cadherin and vimentin, were detected by western blotting. Proteins interrelationships were assessed by a co­immunoprecipitation assay. Oxaliplatin resistance was assessed using CCK­8 and apoptosis assays in vitro, and using a tumor xenograft model in vivo. By constructing FOXD1 overexpression and knockdown stably transfected strains of colon cancer cells, it was revealed that the overexpression of FOXD1 increased CRC cell stemness and chemoresistance. By contrast, knockdown of FOXD1 produced the opposite effects. These phenomena were caused by the direct interaction between FOXD1 and ß­catenin, thus promoting its nuclear translocation and the activation of downstream target genes, such as LGR5 and Sox2. Notably, inhibition of this pathway with a specific ß­catenin inhibitor (XAV­939) could impair the effects induced by the overexpression of FOXD1. In summary, these results indicated that FOXD1 may promote cell stemness and the chemoresistance of CRC by binding directly to ß­catenin and enhancing ß­catenin nuclear localization; therefore, it may be considered a potential clinical target.

Leveraging a KRAS-based signature to predict the prognosis and drug sensitivity of colon cancer and identifying SPINK4 as a new biomarker.

KRAS is one of the leading mutations reported in colon cancer. However, there are few studies on the application of KRAS related signature in predicting prognosis and drug sensitivity of colon cancer patient. We identified KRAS related differentially expressed genes (DEGs) using The Cancer Genome Atlas (TCGA) database. A signature closely related to overall survival was recognized with Kaplan-Meier survival analysis and univariate cox regression analysis. Then we validated this signature with overall expression score (OE score) algorithm using both scRNA-seq and bulk RNA-seq data. Based on this signature, we performed LASSO cox regression to establish a prognostic model, and corresponding scores were calculated. Differences in genomic alteration, immune microenvironment, drug sensitivity between high- and low-KRD score groups were investigated. A KRAS related signature composed of 80 DEGs in colon cancer were recognized, among which 19 genes were selected to construct a prognostic model. This KRAS related signature was significantly correlated with worse prognosis. Furthermore, patients who scored lower in the prognostic model presented a higher likelihood of responding to chemotherapy, targeted therapy and immunotherapy. Furthermore, among the 19 selected genes in the model, SPINK4 was identified as an independent prognostic biomarker. Further validation in vitro indicated the knockdown of SPINK4 promoted the proliferation and migration of SW48 cells. In conclusion, a novel KRAS related signature was identified and validated based on clinical and genomic information from TCGA and GEO databases. The signature was proved to regulate genomic alteration, immune microenvironment and drug sensitivity in colon cancer, and thus might serve as a predictor for individual prognosis and treatment.

Laparoscopic complete mesocolic excision (CME) with medial access for right-hemi colon cancer: feasibility and technical strategies.

OBJECTIVE: This study was designed to investigate the feasibility and technical strategies of laparoscopic complete mesocolic excision (CME) for right-hemi colon cancer. METHODS: The clinical and pathological findings of 64 patients with right-hemi colon cancer who underwent laparoscopic CME between March 2010 and September 2011 were collected retrospectively. Among them, 35 cases were eligible for the final analysis through various screening factors. The quality of surgery also was assessed by reviewing the recorded video obtained through the operations in terms of specimen anatomic planes and completeness of the excised mesocolon. RESULTS: Laparoscopic CME is focused on applying the concept of enveloped visceral and parietal planes during the operations. Laparoscopic approach proceeds with medial access where the dissection starts at ileocolic vessel before proceeds along with the superior mesenteric vessel. The access also emphasized en bloc resection of mesocolon without defections to the planes. Besides, lymph node resections at the root of ileocolic; right colic and middle colic vessels are necessary for ileocecum cancer. Cancers at the hepatic flexure requires further dissection of subpyloric lymph nodes and of greater omentum that is within 15 cm of the tumor and along the greater curvature. Thirty-five cases were evaluated as good plane. The median total number of central lymph nodes retrieved was 19 (range, 15-25) and central lymph node metastasis was found in 5 of all stage III cases. The median operation time was 2.6 h and the blood loss was 80 mL. The median time for passage of flatus and hospitalization were 2 and 12 days respectively. Complications were observed in three cases. CONCLUSIONS: CME is a novel concept for colon cancer surgery and might be a standard for the procedure. Laparoscopic CME with medial access is technically feasible and randomized trials are needed to evaluate its long-term outcomes.

Polo-like kinase 1 is overexpressed in colorectal cancer and participates in the migration and invasion of colorectal cancer cells.

BACKGROUND: Polo-like kinase 1 (PLK1) is an important molecule in proliferation of many human cancers. The aim of study is to clarify the expression patterns and potential function of PLK1 in colorectal cancers. MATERIAL/METHODS: Fifty-six colorectal cancers samples were collected and arranged onto a tissue array and the expression of PLK1 were detected by immunohistochemistry and correlated with clinico-pathological characteristics and expression of PCNA. Expression of PLK1 in 9 colorectal cancer cells lines was investigated by RT-PCR and Western blot, then SW1116 cells lines were treated with PLK1 siRNA and the efficiency was examined by Western blot. Transwell test was applied to detect the migration and invasion capability of cancer cells by counting the number of cells passing through the membranes. Cell proliferation and apoptosis were examined by Cell Counting Kit-8 (CCK-8) and Annexin-V Kit. RESULTS: PLK1 was positively expressed in 73.2% (41/56) of colorectal cancers tissues, but in only 3.6% (2/56) of normal tissues, and was associated with Duke's stage (P<0.01), tumor size (P<0.01), invasion extent (P<0.05) and lymphatic metastasis (P<0.01). The expression of PLK1 was correlated with expression of PCNA (R=0.553, P<0.01). PLK1 was inhibited in SW1116 cells by treating with PLK1 siRNA oligos, which resulted in a decreased number of cells passing through the membrane as compared with control groups (P<0.01) at 24 hours after transfection. Cell proliferation was inhibited from 48 hours after transfection, while cells apoptosis was induced from 72 hours after transfection. CONCLUSIONS: PLK1 could be a progression marker for colorectal cancer patients and PLK1 depletion can inhibit migration and invasion capability of colorectal cancer cells SW1116, suggesting that PLK1 might be involved in metastasis and invasion of colorectal cancer. Therapeutic strategies targeting PLK1 may be a new approach to colorectal cancer.

Retrospective research of neoadjuvant therapy on tumor-downstaging, post-operative complications, and prognosis in locally advanced rectal cancer.

BACKGROUND: Neoadjuvant therapy (NAT) is becoming increasingly important in locally advanced rectal cancer. Hence, such research has become a problem. AIM: To evaluate the downstaging effect of NAT, its impact on postoperative complications and its prognosis with different medical regimens. METHODS: Seventy-seven cases from Shanghai Ruijin Hospital affiliated with Shanghai Jiaotong University School of Medicine were retrospectively collected and divided into the neoadjuvant radiochemotherapy (NRCT) group and the neoadjuvant chemotherapy (NCT) group. The differences between the two groups in tumor regression, postoperative complications, rectal function, disease-free survival, and overall survival were compared using the χ 2 test and Kaplan-Meier analysis. RESULTS: Baseline data showed no statistical differences between the two groups, whereas the NRCT group had a higher rate of T4 (30/55 vs 5/22, P < 0.05) than the NCT groups. Twelve cases were evaluated as complete responders, and 15 cases were evaluated as tumor regression grade 0. Except for the reduction rate of T stage (NRCT 37/55 vs NCT 9/22, P < 0.05), there was no difference in effectiveness between the two groups. Preoperative radiation was not a risk factor for poor reaction or anastomotic leakage. No significant difference in postoperative complications and disease-free survival between the two groups was observed, although the NRCT group might have better long-term overall survival. CONCLUSION: NAT can cause tumor downstaging preoperatively or even complete remission of the primary tumor. Radiochemotherapy could lead to better T downstaging and promising overall survival without more complications.

Direct and indirect costs and long-term survival of laparoscopic anterior resection for rectal cancer.

BACKGROUND: Few studies evaluate the cost-effectiveness issues of laparoscopic anterior resection (LAR) for rectal cancer. This study evaluates direct and indirect costs of LAR and its long-term survival rate in rectal cancer patients. MATERIAL/METHODS: This prospective nonrandomized controlled trial included 2 endpoints (direct and indirect costs, and disease-free survival). From January 2003 to May 2005, rectal cancer patients admitted to our center were assigned to 2 groups: 87 patients underwent LAR (LAP), while 86 cases received open anterior resection (OPEN). The direct costs were prospectively evaluated. Main indirect cost is productivity loss. The data of direct costs, indirect costs, and the total costs were collected for the minimal cost analysis. RESULTS: Disease-free survival at 65 months in the LAP group and the OPEN group was 78.2% and 74.7%; there was no significant difference between the groups. Median direct costs were not significantly different between the LAP and the OPEN groups. Indirect costs of the LAP group were significantly lower than those of the OPEN group, while total costs were not significantly different. Cost percentage for operations, medications, and hospitalization were 75.90%, 11.28%, and 2.18% in the LAP group; while in the operation group, they were 54.50%, 29.09%, and 3.35%. CONCLUSIONS: Total economic budget for a patient receiving LAR was not significantly increased compared with the conservative method owing to its technical predominance, oncologic safety, as well as frequent bed turnover.

Long-term outcome of laparoscopic total mesorectal excision for middle and low rectal cancer.

This study aimed to assess the feasibility and long-term outcome of laparoscopic total mesorectal excision for middle and lower rectal cancer. Retrospective assessment was performed on 612 patients with middle and low rectal cancer in the surgery department of our hospital. Three-hundred and three patients underwent laparoscopic total mesorectal excision (LTME), and 309 patients underwent open TME (OTME). All the data regarding patient details, operative variables and the short- and long-term outcomes were collected and compared. The sphincter-preserving rates of the two groups were similar. The conversion rate in LTME was 2.31% (seven cases). Fourteen cases (6.67%) of protective diverting stoma were fashioned in the LTME group compared with 57 cases (26.64%) in the OTME group. The postoperative morbidity was the same in these two groups, while the postoperative period until bowel movement and hospital discharge was shorter in the LTME group (P < 0.01). The median follow-up period was 34 (6-81) months for the LTME group and 36 (6-81) months for the OTME group. Local recurrence rates, the five-year disease-free survival rate and the five-year overall survival rate showed no difference between the two groups. Laparoscopic surgery is feasible and safe in patients with middle and lower rectal cancer and can provide favorable short-term and long-term outcomes.

[Impact of previous abdominal operations on the outcome of laparoscopic colorectal cancer surgery: a non-randomized cohort study].

OBJECTIVES: To investigate the impact of previous abdominal operations on the outcome of laparoscopic colorectal cancer surgery and to evaluate the feasibility and safety of laparoscopic reoperation in treatment for colorectal cancer. METHODS: According to the statistical standards, 653 consecutive patients treated from March 2002 and March 2009 were enrolled in this study. The patients were divided into three groups: upper abdominal surgery group (n = 48), middle-lower abdominal surgery group (n = 110) and non-previous abdominal surgery group (n = 495). Demographic, pathoanatomical and surgical data were compared among the three groups. RESULTS: There was no significant differences in demographic, pathoanatomical data and post-operative complications among the three groups. Compared with the other two groups, middle-lower abdominal surgery subgroup had a higher intra-operative conversion rate due to intra-abdominal adhesion (4.2%, 11.8% and 3.8% in upper abdominal surgery group, middle-lower abdominal surgery group and non-previous abdominal surgery group, respectively). And no significant differences was found in operating time [(132 ± 36), (141 ± 42), (132 ± 36) min], intra-operation blood loss [(58 ± 50), (81 ± 99), (57 ± 57) ml], blood transfusion rate (6.3%, 10.9%, 7.9%), low sphincter-preserving surgery rate (47.1%, 44.7%, 55.2%), time of first flatus passage [(2.5 ± 1.4), (2.9 +/- 1.7), (2.5 ± 2.1) d], fasting time [(5 ± 4), (5 ± 4), (4 ± 3) d], hospital stay [(17 ± 9), (15 ± 8), (16 ± 10) d] between the three groups. CONCLUSIONS: The history of previous abdominal operations should not be regarded as a contraindication for laparoscopic colorectal cancer reoperation. The laparoscopic reoperation for colorectal cancer is safe and feasible.

Intraoperative cholangiography in combination with laparoscopic ultrasonography for the detection of occult choledocholithiasis.

BACKGROUND: There is still a debate about the utility of intraoperative cholangiography (IOC) or laparoscopic ultrasonography (LUS) for detection of occult choledocholithiasis during laparoscopic cholecystectomy (LC). The aim of this study was to assess the value of IOC combined with LUS for detection of occult common bile duct (CBD) stones at LC. MATERIAL/METHODS: From Dec 2002 to Aug 2006, 103 patients with moderate risk of CBD stones underwent IOC and LUS simultaneously during LC. The physician teams for the two different procedures were blinded by each other. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio were calculated by several contingency tables that cross-tabulated the results of each technique with those of the gold standard. RESULTS: The success rate of IOC and LUS were 91.3% and 100% respectively and the time required for LUS was significantly shorter (P<0.01). The visualization of intrapancreatic part of CBD by IOC (97.3%) was significantly higher than LUS (73.8%). The sensitivities, specificities, accuracies, positive and negative predictive values, positive and negative likelihood rations identifying occult CBD stones were 75.0%, 98.7%, 92.2%, 95.5%, 91.4%, 57.7 and 0.253 by IOC, and 82.1%, 98.7%, 94.2%, 95.8%, 93.7%, 63.2 and 0.181 by IUS respectively. The McNemar test showed no significant difference between two methods. The sensitivity of IOC combined with LUS was 92.9%, which was greater than that of IOC and LUS taken separately. CONCLUSIONS: LUS is usually performed in case where IOC has failed or is contraindicated. The combination of both methods maximizes intraoperative detection of occult CBD stones and should at least be recommended as two complementary methods.

[Galectin-9 isoforms influence the adhesion between colon carcinoma LoVo cells and human umbilical vein endothelial cells in vitro by regulating the expression of E-selectin in LoVo cells].

OBJECTIVE: To study the regulatory effect of galectin-9 isoforms on some molecules involved in cell adhesion/invasion, and the influence of this regulation action on the adhesion between colon carcinoma LoVo cells and human umbilical vein endothelial cells (HUVECs) in vitro. METHODS: Various expression vectors of galectin-9 isoforms were transfected into LoVo cells. 24 h after transfection, the expression of integrin-beta1, E-cadherin, E-selectin, ICAM-1, CD44 and MMP-9 was detected by RT-PCR and Western blot analysis. LoVo cell-HUVEC adhesion assay was performed under conditions of galectin-9 transfection, galectin-9 transfection + galectin-9 antibody, galectin-9 transfection + E-selectin antibody and galectin-9 transfection + beta-lactose, respectively. RESULTS: Galectin-9L down-regulates the mRNA and protein levels of E-selectin while galectin-9M and galectin-9S up-regulate the expression of E-selectin. In LoVo cell-HUVEC adhesion assay, the average fluorescence intensity of vector transfection group, galectin-9L transfection group, galectin-9M transfection group and galectin-9S transfection group was 0.90 +/- 0.20, 0.94 +/- 0.24, 1.60 +/- 0.11 and 1.45 +/- 0.13, respectively, indicating that galectin-9M and galectin-9S facilitated the adherence of LoVo cells to HUVECs (P < 0.05). E-selectin antibody, galectin-9 antibody or beta-lactose inhibited that effect. CONCLUSION: Galectin-9 isoforms regulate the E-selectin expression in LoVo cells differently and thus influence the adhesion between LoVo cells and HUVECs in vitro in different modes. The mechanisms through which galectin-9 isoforms participate in the metastasis process of colon cancer may not be the same.

CXCL5 induces tumor angiogenesis via enhancing the expression of FOXD1 mediated by the AKT/NF-κB pathway in colorectal cancer.

The mechanisms underlying the role of CXCL5 in tumor angiogenesis have not been fully defined. Here, we examined the effect of CXCL5 on tumor angiogenesis in colorectal cancer (CRC). Immunohistochemistry was used to monitor the expression of CXCL5 and CD31 in CRC patients' tissues. HUVEC cell lines stably transfected with shCXCR2 and shFOXD1 lentivirus plasmids were used in an in vitro study. Based on some molecular biological experiments in vitro and in vivo, we found that CXCL5 was upregulated in tumor tissues and that its level positively correlated with the expression of CD31. Next, we used recombinant human CXCL5 (rhCXCL5) to stimulate HUVECs and found that their tube formation ability, proliferation, and migration were enhanced by the activation of the AKT/NF-κB/FOXD1/VEGF-A pathway in a CXCR2-dependent manner. However, silencing of CXCR2 and FOXD1 or inhibition of the AKT and NF-κB pathways could attenuate the tube formation ability, proliferation, and migration of rhCXCL5-stimulated HUVECs in vitro. rhCXCL5 can promote angiogenesis in vivo in Matrigel plugs, and the overexpression of CXCL5 can also increase microvessel density in vivo in a subcutaneous xenotransplanted tumor model in nude mice. Taken together, our findings support CXCL5 as an angiogenic factor that can promote cell metastasis through tumor angiogenesis in CRC. Furthermore, we propose that FOXD1 is a novel regulator of VEGF-A. These observations open new avenues for therapeutic application of CXCL5 in tumor anti-angiogenesis.