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Background: Human gut microbiome has complex relationships with the host, contributing to metabolism, immunity, and carcinogenesis. Methods: Summary-level data for gut microbiota and metabolites were obtained from MiBioGen, FINRISK and human metabolome consortia. Summary-level data for colorectal cancer were derived from a genome-wide association study meta-analysis. In forward Mendelian randomization (MR), we employed genetic instrumental variables (IV) for 24 gut microbiota taxa and six bacterial metabolites to examine their causal relationship with colorectal cancer. We also used a lenient threshold for nine apriori gut microbiota taxa as secondary analyses. In reverse MR, we explored association between genetic liability to colorectal neoplasia and abundance of microbiota studied above using 95, 19, and 7 IVs for colorectal cancer, adenoma, and polyps, respectively. Results: Forward MR did not find evidence indicating causal relationship between any of the gut microbiota taxa or six bacterial metabolites tested and colorectal cancer risk. However, reverse MR supported genetic liability to colorectal adenomas was causally related with increased abundance of two taxa: Gammaproteobacteria (β = 0.027, which represents a 0.027 increase in log-transformed relative abundance values of Gammaproteobacteria for per one-unit increase in log OR of adenoma risk; P = 7.06×10−8), Enterobacteriaceae (β = 0.023, P = 1.29×10−5). Conclusions: We find genetic liability to colorectal neoplasia may be associated with abundance of certain microbiota taxa. It is more likely that subset of colorectal cancer genetic liability variants changes gut biology by influencing both gut microbiota and colorectal cancer risk. Impact: This study highlights the need of future complementary studies to explore causal mechanisms linking both host genetic variation with gut microbiome and colorectal cancer susceptibility.

Table S4 shows the SNPs for colorectal cancer.

Supplementary Methods shows the formulas for calculating F-statistics.

Background:Human gut microbiome has complex relationships with the host, contributing to metabolism, immunity, and carcinogenesis.Methods:Summary-level data for gut microbiota and metabolites were obtained from MiBioGen, FINRISK and human metabolome consortia. Summary-level data for colorectal cancer were derived from a genome-wide association study meta-analysis. In forward Mendelian randomization (MR), we employed genetic instrumental variables (IV) for 24 gut microbiota taxa and six bacterial metabolites to examine their causal relationship with colorectal cancer. We also used a lenient threshold for nine apriori gut microbiota taxa as secondary analyses. In reverse MR, we explored association between genetic liability to colorectal neoplasia and abundance of microbiota studied above using 95, 19, and 7 IVs for colorectal cancer, adenoma, and polyps, respectively.Results:Forward MR did not find evidence indicating causal relationship between any of the gut microbiota taxa or six bacterial metabolites tested and colorectal cancer risk. However, reverse MR supported genetic liability to colorectal adenomas was causally related with increased abundance of two taxa: Gammaproteobacteria (β = 0.027, which represents a 0.027 increase in log-transformed relative abundance values of Gammaproteobacteria for per one-unit increase in log OR of adenoma risk; P = 7.06×10−8), Enterobacteriaceae (β = 0.023, P = 1.29×10−5).Conclusions:We find genetic liability to colorectal neoplasia may be associated with abundance of certain microbiota taxa. It is more likely that subset of colorectal cancer genetic liability variants changes gut biology by influencing both gut microbiota and colorectal cancer risk.Impact:This study highlights the need of future complementary studies to explore causal mechanisms linking both host genetic variation with gut microbiome and colorectal cancer susceptibility.

N6-methyladenosine (m6A) modification has been demonstrated to exhibit a crucial prognostic effect on colorectal cancer (CRC). Nonetheless, potential mechanism of m6A in survival rate and immunotherapeutic response remains unknown. Here we investigated the genes associated with m6A regulators and developed a risk score for predicting the overall survival (OS) of CRC patients. RNA-seq transcriptomic profiling data of COAD/READ samples were obtained from The Cancer Genome Atlas (TCGA) database. Absolute Shrinkage and Selection Operator (LASSO)- Cox regression analysis was conducted to identify the m6A-related gene expression signatures and the selected genes were inputted into stepwise regression to develop a prognostic risk score in TCGA, and its predictive performance of CRC survival was further validated in Gene Expression Omnibus (GEO) datasets. According to our results, the risk score comprising 18 m6A-related mRNAs was significantly associated with CRC survival in both TCGA and GEO datasets. And the stratified analysis also confirmed that high-risk score acted as a poor factor in different age, sex, T stage, and tumour, node, metastasis (TNM) stages. The m6A-related prognostic score in combination with clinical characteristics yielded time-dependent area under the receiver operating characteristic curve (AUCs) of 0.85 (95%CI: 0.79–0.91), 0.84 (95%CI: 0.79–0.90) and 0.80 (95%CI: 0.71–0.88) for the prediction of the 1-, 3-, 5-year OS of CRC in TCGA cohort. Furthermore, mutation of oncogenes occurred more frequently in the high-risk group and the composition of immune cells in tumour microenvironment (TME) was significantly distinct between the low- and high-risk groups. The low-risk group had a lower microsatellite instability (MSI) score, T-cell exclusion score and dysfunction score, implying that low-risk patients may have a better immunotherapy response than high-risk patients. In summary, a prognostic risk score derived from m6A-related gene expression signatures could serve as a potential prognostic predictor for CRC survival and indicator for predicting immunotherapy response in CRC patients.

Background Nearly 15% colorectal cancer (CRC) patients received ileostomy, while surgical site infection (SSI) is a common complication after ileostomy wound closure. Purse-string closure was reported to reduce SSI rate in ileostomy wound closure compared with conventional linear closure, but had never been systematically reported in CRC patients. The present study aimed to compare the short-term outcomes between purse-string and conventional closure in Chinese CRC patients. Patients and methods A total of 57 CRC patients underwent ileostomy wounds closure in the Second Affiliated Hospital of Zhejiang University during November, 2015 and October, 2017 were retrospectively reviewed. Twenty-nine received purse-string closure while the others received conventional closure. The short-term outcomes including SSI rate, scar length, pain score and hospital stay were reviewed and analyzed. Results There were no significant differences in the characteristics of the patients between two groups. The SSI rate was similar within two groups (10.3% vs 10.7%, p = 1.000). The purse-string closure group had a significantly short scar length (1.66 cm vs 5.30 cm, p Conclusion The present study did not find superiority of Purse-string closure in SSI rate control. It seemed only had a cosmetic effect according to its shorter scar length.

The occurrence and development of colorectal cancer (CRC) and advanced adenoma (AA) are closely related to the gut microbiome, and AA has a high cancerization progression rate to CRC. Current studies have revealed that bacteriological analysis cannot identify CRC from AA. The objective was to explore microbial targets that could identify CRC and AA from a microecological perspective and to figure out the best way to identify CRC based on fecal microbes. The metagenomic sequencing data were used to describe the gut microbiome profile and analyze the differences between microbial abundance and microbial single nucleotide polymorphism (SNP) characteristics in AA and CRC patients. It was found that there were no significant differences in the diversity between the two groups. The abundance of bacteria (e.g.

The efficacy of laparoscopic vs open surgery for patients with low rectal cancer has not been established.To compare the short-term efficacy of laparoscopic surgery vs open surgery for treatment of low rectal cancer.This multicenter, noninferiority randomized clinical trial was conducted in 22 tertiary hospitals across China. Patients scheduled for curative-intent resection of low rectal cancer were randomized at a 2:1 ratio to undergo laparoscopic or open surgery. Between November 2013 and June 2018, 1070 patients were randomized to laparoscopic (n = 712) or open (n = 358) surgery. The planned follow-up was 5 years. Data analysis was performed from April 2021 to March 2022.Eligible patients were randomized to receive either laparoscopic or open surgery.The short-term outcomes included pathologic outcomes, surgical outcomes, postoperative recovery, and 30-day postoperative complications and mortality.A total of 1039 patients (685 in laparoscopic and 354 in open surgery) were included in the modified intention-to-treat analysis (median [range] age, 57 [20-75] years; 620 men [59.7%]; clinical TNM stage II/III disease in 659 patients). The rate of complete mesorectal excision was 85.3% (521 of 685) in the laparoscopic group vs 85.8% (266 of 354) in the open group (difference, -0.5%; 95% CI, -5.1% to 4.5%; P = .78). The rate of negative circumferential and distal resection margins was 98.2% (673 of 685) vs 99.7% (353 of 354) (difference, -1.5%; 95% CI, -2.8% to 0.0%; P = .09) and 99.4% (681 of 685) vs 100% (354 of 354) (difference, -0.6%; 95% CI, -1.5% to 0.5%; P = .36), respectively. The median number of retrieved lymph nodes was 13.0 vs 12.0 (difference, 1.0; 95% CI, 0.1-1.9; P = .39). The laparoscopic group had a higher rate of sphincter preservation (491 of 685 [71.7%] vs 230 of 354 [65.0%]; difference, 6.7%; 95% CI, 0.8%-12.8%; P = .03) and shorter duration of hospitalization (8.0 vs 9.0 days; difference, -1.0; 95% CI, -1.7 to -0.3; P = .008). There was no significant difference in postoperative complications rate between the 2 groups (89 of 685 [13.0%] vs 61 of 354 [17.2%]; difference, -4.2%; 95% CI, -9.1% to -0.3%; P = .07). No patient died within 30 days.In this randomized clinical trial of patients with low rectal cancer, laparoscopic surgery performed by experienced surgeons was shown to provide pathologic outcomes comparable to open surgery, with a higher sphincter preservation rate and favorable postoperative recovery.ClinicalTrials.gov Identifier: NCT01899547.

138 Background: Anlotinib is an oral multi-target tyrosine kinase inhibitor, mainly targeting VEGFR1-3, FGFR 1-4, PDGFR a/b and c-kit. Previous trial had demonstrated that anlotinib monotherapy was effective and safe in advanced colorectal cancer. ALTER-C002 trial is an open-label, single-arm, phase II study, aimed to evaluate the efficacy and safety of anlotinib plus CAPEOX as first-line therapy in patients with RAS/ BRAF wild-type unresectable metastatic colorectal cancer (mCRC). Preliminary results demonstrated significant antitumor activity and manageable toxicity. Here we reported the updated results at the data cutoff of August 19, 2022. Methods: RAS/BRAF wild-type unresectable mCRC patients with no prior systemic treatment received anlotinib (12 mg p.o. qd, d1-d14, q3w), capecitabine (850 mg/m2 p.o., bid, d1-d14, q3w) and oxaliplatin (130 mg/m2 i.v., d1, q3w) for 6 cycles followed by anlotinib and capecitabine as maintenance therapy until disease progression. Tumor response was assessed every 6 weeks according to RECIST v1.1 by investigator. The primary endpoint was ORR, and secondary endpoints included safety, DCR, DOR and PFS. Results: From Nov 2019 to February 2021, 30 eligible patients were enrolled, of whom, median age was 60y (range, 32-72y), 26 (86.7%) had left colon or rectal cancer, and 25 (83.3%) had liver metastases. The ORR was 76.7% (95% CI, 57.7-90.1%) with 2 patient achieved a complete response (CR); DCR was 93.3% (95% CI, 77.9-99.2%). At the data cutoff date, the median DOR was 7.9 months (95% CI, 4.3–11.4) and the median DOT was 8.38 months (95%CI, 5.9-10.9). The median OS has not reached yet, the 24-month OS rate was 72.8% (95%CI, 50.7-86.3%) and the 30-month OS rate was 58.3% (95%CI:25.5-80.8%). Grade 3-4 treatment-emergent adverse events (TEAEs) occurred in 25 (83.3%) patients; the most common grade 3 or 4 TEAEs ( > 10%) were hypertension (50%, 15/30 pts), neutropenia (26.7%, 8/30 pts) and diarrhea (13.3%, 4/30 pts). No grade 5 treatment-related events occurred. Conclusions: Anlotinib combined with CAPEOX exhibited promising ORR in the first-line treatment of mCRC compared to those of previous treatment. A longer follow-up is needed for a more complete assessment, and we launched a phase III, multicenter, open-label trial to assess the efficacy of this regimen comprehensively. Clinical trial information: NCT04080843 .

132 Background: Most recently, there were 3 reports of prospective randomized clinical trials comparing the effects of primary tumor resection (PTR) for multiorgan metastatic colorectal cancer followed by chemotherapy with chemotherapy alone, but the results differed and unconvincing due to the prematurely study termination and research protocol changes. PTR was preferably performed for patients with asymptomatic synchronous unresectable colorectal liver-limited metastases (CRLMs) with conversion therapy purpose, including the CELIM, OLIVIA and our study (J Clin Oncol 2013;31:1931-8). This randomized phase III study investigated the superiority of preoperative chemotherapy prior to PTR for patients with asymptomatic synchronous unresectable CRLMs. Methods: Patients with asymptomatic synchronous unresectable CRLMs were randomly assigned to receive pre-PTR chemotherapy (arm A) or upfront PTR (arm B). Chemotherapy regimens of mFOLFOX6 plus cetuximab, mFOLFOX6 plus bevacizumab or mFOLFOX6 alone were decided according to the RAS genotype. The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS), tumor response, disease control rate (DCR), liver metastases resection rate, surgical complications and chemotherapy toxicity. Results: Between June 2012 and June 2018, a total of 320 patients were randomly assigned to arm A (160 patients) or arm B (160 patients). The cutoff date for survival data was June 2021, the median follow-up time was 36.2 months. Patients were well balanced. For the intention-to-treat population, the median PFS, median OS, and 3-year OS rates were 9.9 months, 28.0 months, and 37.0%, respectively. The median PFS in arm A was significantly improved compared with arm B (10.5 v 9.1 months; hazard ratio [95% CI, 0.60 to 0.95], 0.76; P = 0.013). Patients in arm A also had a significantly better DCR (84.4% v 75.0%; P = 0.037). The median OS was not significantly different (29.4 v 27.2 months; hazard ratio [95% CI, 0.58 to 1.01], 0.77, P = 0.058), and the objective response rates were also not significantly different (53.1% v 45.0%; P = 0.146). The actual resection rate of liver metastases was not significantly different (21.9% v 18.1%; P = 0.402). There were mild morbidities and no 30-day postoperative mortalities in both arms. The rate of complications was not significantly different (37.7% v 30.8%, P = 0.201). The incidence of Clavien–Dindo 3-4 complications also did not reach statistical significance (4.5% v 3.8%, P = 0.759). Overall the observed toxicity was mostly mild. There was no significant difference in the overall incidence of predefined grade 3/4 events (42.2% v 40.4%, P = 0.744). There were no grade 5 events in either arm. Conclusions: For asymptomatic synchronous unresectable CRLMs, Pre-PTR chemotherapy improved the PFS compared with upfront PTR. Clinical trial information: NCT01307878 .

3563 Background: The prognosis of metastatic colorectal cancer (mCRC) patients with RAS gene mutation and microsatellite stable (MSS) is poor. MSS patients account for 95% of CRC and have a low response rate to immunotherapy. Previous studies have reported that chemotherapy and anti-angiogenesis therapy can promote immunotherapy response. This study aims to assess the safety and antitumor activity of sintilimab (IBI308) combined with CapeOx and bevacizumab in the first-line treatment of patients with RAS-mutant and MSS mCRC. Methods: This is an open-label, single-arm, phase II trial. Eligible patients were aged 18 to 75 years with histologically confirmed unresectable metastatic colorectal adenocarcinoma by multidisciplinary team, and had RAS gene mutation and confirmed MSS status. All patients received treatment with sintilimab (200 mg, day 1) plus bevacizumab (7.5mg/kg, day 1) and oxaliplatin (135 mg/m2, day 1) and capecitabine (1g/m2, bid, day 1-14) of each 21-day cycle. The primary endpoint included objective response rate (ORR) evaluated via RECIST 1.1 criteria and adverse events according to CTCAE 5.0. Secondary endpoint was progression-free survival (PFS). Results: 25 patients were enrolled and received at least two cycle treatment. At baseline, median age was 60 years (range 45-74), 72% of patients were male, ECOG PS 0/1 was 100%, 60% had liver metastases (mets), and the primary tumor site was right-sided colon in 36.0% and left-side colorectum in 64.0%. 25 patients completed at least one efficacy evaluation. 2 (8.0%) patients showed complete response (CR), 19 (76.0%) patients had a partial response (PR) and 4 (16.0%) had stable disease (SD). Patients with liver or lung mets had a higher ORR (93.3% and 100%, respectively) compared to the overall ORR (84.0%). Disease control rate (DCR) reached 100%. Median PFS has not yet reached. No grade 5 adverse events occurred. The most common treatment-related adverse events (TRAEs) in all grades were anemia (19/25, 76.0%), peripheral neurotoxicity (6/25, 24.0%) and neutropenia (17/25, 68.0%). The most frequent grade 3/4 TRAEs were neutropenia (3/25, 12.0%), elevated aspartate transaminase (1/25, 4.0%), elevated alanine transaminase (1/25, 4.0%) and elevated bilirubin (1/25, 4.0%). Conclusions: Combination treatment with sintilimab (IBI308) plus CapeOx and bevacizumab demonstrated a high ORR (84.0%; 93.3% in patients with liver mets, and 100% in patients with lung mets) and a manageable safety profile in RAS-mutant and MSS mCRC. Clinical trial information: NCT05171660. [Table: see text]

3515 Background: Neoadjuvant radiochemotherapy is the standard treatment for locally advanced rectal cancer. However, radiation therapy can lead to bowel, urinary and sexual dysfunction. The study aims to clarify whether locally advanced rectal cancer with a distance of 6 to 12 cm from the anus with negative circumferential margins (CRM) predicted by MRI can be exempted from preoperative radiotherapy. Methods: PSSR (NCT02121405), a multicentre, randomized, open-label, non-inferiority, phase 3 trial, was done across 10 hospitals in China. Patients aged from 18 to 75 years with locally advanced rectal cancer (including all cT3/4 and/or Nany) with negative MRI-predicted CRM and tumor distance of 6 to 12 cm from anus were randomly assigned (1:1), by central randomization, to intervention group (surgery directly, in which positive CRM was supplemented with chemoradiotherapy, negative CRM received adjuvant chemotherapy according to surgical pathologic staging), or control group (neoadjuvant chemoradiotherapy then underwent surgery and adjuvant chemotherapy). The primary endpoint is the rate of 3-year disease-free survival (DFS). A sample size of 350 was set according to the original non-inferiority margin of 15% for the difference of rates for 3-year DFS, which was changed to 5% under the Data Safety Monitoring Board (DSMB) suggestion after an interim analysis. The efficacy analysis followed the per-protocol (PP) principle. Results: From December 2015 to February 2021, 299 patients were recruited. DSMB stopped this trial due to the difference of 3-year DFS’s rate between two groups more than 5% at the interim analysis in July 2021. A total of 275 were included for the final analysis. Based on the PP dataset, 238 patients followed the original protocol (135 patients in the intervention group and 103 patients in the control group). Patients who had positive CRM were 2(1.5%) and 1(1.0%) in two groups, respectively ( P= 1.00). After a median follow-up of 34.6 (IQR: 18.2-45.7) months, a total of 42 patients had positive events (30 patients in the intervention group and 12 patients in the control group). There were 5 (3.7%) patients with local recurrence in the intervention group ( P= 0.062). Patients with pathological complete response (pCR) and near pCR were 19 (18.4%) and 21 (20.4%) in the control group. The rate of 3-year DFS was 81.1% (77.3%-84.9%) (HR = 2.02, 95%CI: 1.01-4.06, P= 0.048) in the intervention group and 86.6% (82.7%-90.5%) in the control group, with difference of 5.4% (5.3%-5.6%), which did not meet the criteria for non-inferiority. Conclusions: In terms of DFS, initial surgery was inferior to conventional preoperative radiochemotherapy for locally advanced middle rectal cancer with MRI negative circumferential margin. Clinical trial information: NCT02121405.

Background: Establish patient-derived tumor xenograft (PDTX) from advanced GICs and assess the clinical value and applicability of PDTX for the treatment of advanced GICs. Method: Patients with advanced GICs were enrolled in a registered multi-center clinical study (ChiCTR-OOC-17012731). The performance of PDTX were evaluated includes: analyzing factors that affect the engraftment rate, comparing the histological consistency between primary tumors and tumorgrafts, examining the concordance between the drug effectiveness in PDTXs and clinical responses, and Identifying genetic variants and other factors associated with prognosis. Results: Thirty-three patients were enrolled in the study with the engraftment rate of 75.8% (25/33). The successfulness of engraftment was independent of age, cancer types, pathological stages of tumors, and particularly sampling methods. Tumorgrafts kept same histopathological characteristics as primary tumors. Forty-nine regimens involving twenty-eight drugs were tested in seventeen tumorgrafts. The median time for drug testing was 134.5 day. The follow up information of 10 regimens from 9 patients were obtained. The concordance of drug effectiveness in PDTXs and clinical responses was 100%. The tumor mutation burden (TMB) was correlated with the effectiveness of single drug regimens, while the outgrowth time of tumorgrafts was associated with the effectiveness of combined regimens. Conclusion: The engraftment rate in advanced GICs is higher than other cancers and meets the general acceptable standard of applying personalized therapeutic strategies. Tumorgrafts from PDTX kept attributes of primary tumor. Predictions from PDTX modeling highly agree with the clinical drug responses. PDTX may already be clinical applicable for the personalized medication in advanced GICs.

Objective: The present study aims to firstly describe the circulation immune landscape in the canonical pathogenesis of colorectal cancer (CRC) by detecting the peripheral white blood cell using mass cytometry by time-of-flight (CyTOF) technology. Methods: A total of 42 healthy controls (HC), 47 colorectal adenoma (CRA) patients, and 102 CRC patients were enrolled and their pathological information were also collected. A panel of 42 cell surface antigen markers were detected by mass spectrometry flow cytometry after peripheral blood mononuclear cells (PBMC) separated. The expression differences of various cell subsets among the three groups were further compared, and the cell subsets with different expressions were screened out for in-depth analysis. Results: We annotated the PBMC as T cells, B cells, NK cells and myeloid cells, and performed identification and component comparison of cell subgroups respectively. Compared with HC and CRA, NKT cell subsets were significantly reduced in CRC, while Naïve CD4+ T cells, effector CD8+ T cells and central memory CD8+ T cells were increased. Compared with HC, Treg cells increased in CRA, and central memory CD4+ T increased in CRC; but Naïve CD8+ T cells and Naïve double-negative T (DNT) cells decreased in both CRA and CRC. Compared with HC and CRA, Naïve B cells were significantly decreased in CRC; but switched memory B cells were increased. CD16- NK cells were significantly higher in CRC while CD16+ NK cells were decreased compared with HC. CD16- monocytes were increased, but CD16+ monocytes were decreased in CRC when compared to HC. Basophils and monocytes were significantly increased in CRC compared to CRA. Furthermore, we also found Effector CD4+ T cells and Naïve B cells increased during lymph node metastasis, while unswitched B cells, plasmablast and basophils decreased. Conclusion: We had successfully described the immune landscape of the canonical pathogenesis of CRC, and we further analyzed the changes in cell subsets related to the occurrence of lymphatic metastasis. Citation Format: Ke-Feng Ding, Xiang-Xing Kong, Jia-Sheng Xu, Yu-Rong Jiao, Ye-Ting Hu, Qian Xiao, Xu-Ran Hao, Zong-Bao Gao, Jun Li. Circulation immune landscape in canonical pathogenesis of colorectal cancer by CyTOF analysis [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr P016.

Background: Whether extended lymphadenectomy for right colon cancer leads to increased perioperative complications or improves survival is still controversial. This multicentre randomised controlled trial (RCT) aimed to compare the efficacy and safety of complete mesocolic excision (CME) versus D2 dissection in laparoscopic right hemicolectomy for patients with right colon cancer. Methods: This superiority phase III trial was undertaken at 17 hospitals in 9 provinces of China. Patients with adenocarcinoma located between the cecum and the right third of the transverse colon, without evidence of distant metastases, were randomly assigned (in a 1:1 ratio) to receive either CME or D2 dissection during laparoscopic right colectomy. Morbidity and mortality in the first 30 days after surgery were compared between the two groups using a modified intention-to-treat (mITT) analysis. Findings: A total of 1072 patients were enrolled between January 11, 2016, and December 26, 2019. Of these patients, 995 (495 CME patients, 500 D2 patients) were included in the mITT analysis. The 30-day postoperative morbidity rate was 19·6% in the CME group vs. 21·8% in the D2 group (difference, -2·2% [95%CI, -0·07, - 0·03]; P = 0·34); no deaths occurred in either group. The CME procedures harvested significantly more lymph nodes (26·0 vs 23·0, difference, 3·4 [95%CI, 2·0, 4·9]; P

Background Metastatic colorectal cancer (mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC. Methods Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), quality-of-life (QoL), and safety. Results Between July 18, 2012 and Jan 22, 2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib (n = 99) or placebo (n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups (hazard ratio = 0.60, 95% confidence interval = 0.41–0.86, P = 0.004). The DCR was 59.8% and 31.4% (P = 0.002) and the ORR was 2.2% and 0.0% (P = 0.540) in the famitinib and placebo groups, respectively. The most frequent grade 3–4 adverse events were hypertension (11.1%), hand-foot syndrome (10.1%), thrombocytopenia (10.1%), and neutropenia (9.1%). Serious adverse events occurred in 11 (11.1%) patients in the famitinib group and 5 (9.1%) in the placebo group (P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months (P = 0.657). Conclusion Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability. Trial registration This study was registered on ClinicalTrials.gov (NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal Symposium

Thymol is a phenolic compound with various pharmacological activities such as anti-inflammatory, anti-bacterial and anti-tumor effects. However, the effect of thymol on bladder cancer cell growth is still elusive. The purpose of this study is to investigate the efficacy of thymol in bladder cancer cells and its underlying mechanism. Thymol inhibited bladder cancer cell proliferation in a dose and time-dependent manner. We also observed cell cycle arrest at the G2/M phase after the treatment of thymol. Moreover, thymol could induce apoptosis in bladder cancer cells via the intrinsic pathway along with caspase-3/9 activation, release of cytochrome c and down-regulation of anti-apoptotic Bcl-2 family proteins. The activation of JNK and p38 was also critical for thymol-induced apoptosis since it was abrogated by the treatment of JNK inhibitor (SP600125), and p38 inhibitor (SB203580) but not ERK inhibitor (SCH772984). Furthermore, the generation of ROS (reactive oxygen species) was detected after the treatment of thymol. ROS scavenger NAC (N-acetyl cysteine) could block the thymol-triggered apoptosis and activation of MAPKs. These findings offer a novel therapeutic approach for bladder cancer.

Gastrointestinal stromal tumors (GISTs) are rare in the rectum. Radical surgery, such as an abdominoperineal resection, is necessary for large rectal GISTs, which can result in the loss of function of involved organs. Imatinib mesylate can be used as perioperative therapy and may reduce tumor size, and it is now approved for use in the adjuvant therapy of locally resected anorectal GISTs. The present study describes two cases of large rectal GISTs, for which abdominoperineal resections were initially planned. The two patients received pre-operative imatinib mesylate treatment, and the therapeutic response was assessed by magnetic resonance imaging. Finally, transsacral local resection was successfully performed for these two GISTs. A macroscopically complete resection was achieved, and microscopically, the resection margin was negative. One patient experienced the complication of rectal leakage, which was successfully managed by drainage. No recurrence occurred in the two patients after more than two years. Pre-operative imatinib mesylate therapy with subsequent transsacral local resection for selected rectal GISTs is a feasible treatment modality and can prevent extended surgery.

To investigate the impact of a laparoscopic resection on the quality of life in rectal cancer patients.This study included 135 patients (laparoscopic resection [LR] 65 cases and open resection [OR] 70 cases). The European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR38 questionnaires were used to measure the quality of life before the operation, then 1 week, 3 months, and 1 year after the operation.Eleven (16.9%) patients underwent a conversion from laparoscopic to open surgery. The incision length and blood loss both decreased significantly in the LR group in comparison to the OR group (P0.05). Recovery of the gastrointestinal function, bladder function, and ambulation was more rapid in the LR group (P0.05). The patients in the LR group reported better global health status (33.3 vs 25.0, P0.001), body image (77.8 vs 66.7, P = 0.008), and less pain (33.3 vs 50. 0, P = 0.009) 1 week after operation. Better body image was reported in the LR group even 1 year after the operation (P0.05). Fewer financial difficulties were reported by patients in the LR group (P0.001). No significant differences were found between two groups on other scales.This study showed that the quality of life benefits due to minimally invasive laparoscopic surgery were evident only in the immediate postoperative period. A laparoscopic rectal resection therefore provided only better cosmetic benefit over the longer term.

ST14 (suppression of tumorigenicity 14) is a transmembrane serine protease that contains a serine protease catalytic (SP) domain, an SEA domain, two complement subcomponent C1r/s (CUB) domains, and four low density lipoprotein receptor class A domains. Glutathione S-transferase fusion proteins with SP, CUB, and low density lipoprotein receptor domains and their corresponding mutants were generated to analyze protein interactions with these domains. Modified glutathione S-transferase pull-down assays demonstrated the interaction between the SP domain and hepatocyte growth factor activator inhibitor-1. With the same method, a CUB domain-interacting protein was isolated and turned out to be the transmembrane protein with epidermal growth factor-like and two follistatin-like domains 1 (TMEFF1). Quantitative real time PCR revealed that the expression of the TMEFF1 gene was dependent on the transfection of the ST14 gene in the RKO cell line. Our results also suggested that ST14 and TMEFF1 were co-expressed in the human breast cancer cell line MCF7, human placenta, kidney, and liver tissues. Interestingly, these two genes were co-up-regulated in kidney tumors versus normal tissues, consistent with our results that showed the dependence of TMEFF1 expression on ST14 in RKO cells. Finally, homology modeling studies suggested that TMEFF1 might form a complex with ST14 by an interaction between epidermal growth factor and CUB domains.

α-fetoprotein (AFP)-producing colorectal adenocarcinoma is rare and typically not well recognized. In the present study, 3 cases of AFP-producing colorectal cancer are described. All 3 of these cases demonstrated increased levels of blood AFP associated with disease progression. Only case 2 exhibited classical histological hepatoid features. Following immunohistochemical tissue staining, all 3 cases were observed to be positive for AFP expression. In addition, the expression of hepatocyte growth factor (HGF), c-Met receptor and the transcription factor c-Myc were identified to be associated with the expression of AFP. The 3 cases demonstrated resistance to multiple drugs, including epidermal growth factor receptor inhibitors, despite the presence of wild-type Kirsten rat sarcoma viral oncogene homolog (K-RAS; codons 12 and 13), neuroblastoma-RAS (codons 12 and 13) and B-Raf proto-oncogene, serine/threonine kinase (V600E). We propose that hepatoid histological features or a positive AFP finding by immunohistochemistry are sufficient for a diagnosis of AFP-producing colorectal adenocarcinoma. Furthermore, we speculates that autocrine HGF/c-Met activation may be capable of inducing the dedifferentiation of common adenocarcinoma cells, reverting them to a cancer stem cell state and producing AFP or hepatoid differentiation. Consequently, therapy targeted to the HGF/c-Met signaling pathway may potentially be effective for the treatment of AFP-producing colorectal adenocarcinoma.

To evaluate the clinical value of radial endorectal ultrasound (ERUS) in the assessment of preoperative staging of rectal carcinoma.One hundred and ten patients with rectal cancer underwent preoperative endorectal ultrasound (ERUS) examination in our hospital from February 2010 to September 2011. ERUS was performed using a Hitachi 900, Hitachi HI Vision Preirus US scanner, with a 5 - 10 MHz rigid rotating radial transducer and a focal length of 2 - 5 cm. The size, shape, echo pattern, infiltration depth, degree of circumferential involvement, extra-rectal invasion of the lesions and lymph node involvement were observed. The results of ERUS staging were compared with histopathological findings of the surgical specimens.The accuracy of ERUS for T staging was 91.4%. The accuracy of ERUS in diagnosing stage T1, T2, T3, T4 cancers was 92.7%, 88.2%, 88.2% and 96.4%, respectively. The sensitivity of ERUS in diagnosing stage T1, T2, T3, T4 cancers was 92.3%, 72.7%, 85.4% and 71.4%, respectively. The specificity of ERUS in diagnosing stage T1, T2, T3, T4 cancer was 92.9%, 92.0%, 90.3% and 100.0%, respectively. Comparing the consistency of preoperative T-staging and postoperative pathological results, the Kappa value was 0.75, with a considerable consistency. The sensitivity, specificity, and accuracy of ERUS in the assessment of lymph node metastasis were 74.2%, 89.9% and 85.5%, respectively. Comparing the consistency of preoperative N-staging and postoperative pathological results, the Kappa value was 0.64, with a considerable consistency.ERUS is a practical and accurate tool in assessment of preoperative staging of rectal tumors in regard to tumor invasion depth (T) and regional lymph node status (N), with advantages of simple operation, less pain, and high accuracy.

Supplemental Digital Content is available in the text, The gradient monotonicity of existing tumor, node, metastases staging systems for colorectal cancer is unsatisfactory. Our proposed T-plus staging system strengthens weighting of the T stage. In this study, applicability of the T-plus staging system was verified with data of a Chinese colorectal cancer center. Records of 2080 nonmetastatic, advanced cancer patients undergoing colorectal cancer surgery from 1985 to 2011 were reviewed for T, N stage pathology and follow-up information. Using overall and disease-specific survival data, the 7th edition tumor, node, metastases staging system and the T-plus staging system were compared for stage homogeneity and discrimination and gradient monotonicity. For gradient monotonicity, the T-plus staging system was superior for both colon and rectal cancer. With Kaplan–Meier survival curves, the T-plus staging system discriminated among different stages, and the corresponding survival was inversely associated with the stage. However, for the 7th edition tumor, node, metastases staging system, stage IIIa had a better prognosis than stage II for rectal cancer and stage I for colon cancer. For homogeneity within the same stage and discrimination between different stages, the 2 staging systems were similar for colorectal cancer, but the T-plus system was clearly better for colon cancer. The T-plus staging system provides good gradient monotonicity. For future colorectal cancer staging systems, we propose replacement of lymph node status as the criterion to discriminate colorectal cancer stage II and stage III with greater weighting of the T stage.

Recently, the coexistence of gastrointestinal stromal tumors (GISTs) with other neoplasms has been studied with increasing frequency. Coexistence of pancreatic cancer with GISTs remains a rarity; however, here, we report a very rare case of adenosquamous carcinoma (ASC) of the uncinate process of the pancreas with synchronous GISTs of the stomach in a 62-year-old female. The patient presented with epigastric discomfort and vomiting. Radiographic imaging revealed two masses; one located at the body of the stomach and the other located at the uncinate process of the pancreas. Intraoperatively, a fine needle aspiration biopsy was conducted in the uncinate process of the pancreas, which revealed the malignancy of the masses. A pancreaticoduodenectomy and partial gastrectomy were then conducted, and subsequent pathological examinations identified an ASC of the pancreas and a GIST of the stomach. In our case, contrary to the majority of previous cases of synchronous GISTs and other malignancies, GIST was not an incidental finding. The initial suspicion on the GIST as the underlying cause of clinical symptoms led to the discovery of the ASC of the uncinate process of the pancreas.

Objective: Cancer-associated fibroblasts (CAFs) are one of the hallmarks of the cancer microenvironment. Recent evidence has indicated that CAFs are more competent in enhancing cancer cell growth and migration than normal fibroblasts. However, the unique protein expression of CAFs has not been fully elucidated. This study aims to investigate the characterizations of colon CAFs by comparing the differential protein expression between CAFs and normal fibroblasts. Methods: Primary fibroblasts were isolated from surgical specimen of human colon cancer and matched normal colonic tissue. Purity of the cell population was verified through immunostain analysis. Total cell lysates and conditioned media from each group of cells were extracted, and protein expression analysis was conducted using the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) ProteinChip platform. Results: Most primary cells showed typical fibroblast-like features after two weeks. Increased proportion of α-smooth muscle actin-positive myofibroblasts was detected within the CAFs in four of the six pairs of primary cells. Fibroblast activation protein was weakly expressed in most cells without differences. Using SELDI-TOF-MS ProteinChip platform, four protein peaks mass over charge ratio (m/z) 1142, 3011, 4035, and 4945 were detected in the total cell lysates, and two protein peaks m/z 1368 and 1389 were detected in the conditioned media. The potential candidate proteins found in the Swiss-Prot database include morphogenetic neuropeptides, FMRFamide-related peptides, insulin-like growth factor II, thymosin β-4-like protein 3, and tight junction-associated protein 1. Conclusions: Using the SELDI-ProteinChip platform, differential protein expressions were identified in colon CAFs compared with normal colonic stromal fibroblasts. The complex proteomic alternations in colon CAFs may play important roles related to the colon cancer microenvironment.

BACKGROUND/AIMS To comprehensively understand the influence of laparoscopic resection on expressions of metastasis related genes in colorectal cancer by microarray. METHODOLOGY Adjacent cancer tissues were obtained from the same patient with rectal cancer pre and post laparoscopic resection. The mRNA expressions of metastasis related genes were detected by GEArray Q Series human tumor metastasis gene array HS-007. The microarray results were verified by real-time PCR. Preclinical studies focusing on the effect of CO2 pneumoperitoneum on colorectal cancer metastasis over the last ten years were reviewed. RESULTS Microarray analysis revealed that the expression of many metastasis related genes changed significantly post laparoscopic operation. Several metastatic mechanisms were activated including extracellular matrix degradation, cell adhesion, inflammation and angiogenesis. Meanwhile, some well known metastasis inhibition pathways were also activated, including NM23, PTEN and Thrombospondin. In the literature review there were inconsistent findings among reported experimental studies in terms of the effect of CO2 pneumoperitoneum on colorectal cancer metastasis. CONCLUSIONS This microarray finding implies that laparoscopic resection produced no overwhelming adverse effect on the expressions of metastasis related genes in colorectal cancer. In view of the increasing follow-up results from a number of clinical trials, laparoscopic surgery with CO2 pneumoperitoneum appears to be safe.

To evaluate the safety of simultaneous and staged resection for synchronous liver metastasis from colorectal cancer.PubMed/Medline, ISI Web of Knowledge, Springer link, ebscohost, Elsevier Wiley Interscience, Google Scholar were searched for case-control studies concerning simultaneous versus staged resection of synchronous liver metastasis from colorectal cancer between January 1989 and March 2009. A meta-analysis was performed to analyze the morbidity and perioperative mortality.Seven case-control studies, with a total of 1390 patients of liver metastasis from colorectal cancer undergone curative hepatic resection, were reviewed. There were 495 simultaneous and 895 staged resections. Perioperative mortality was 1.1% in the staged resection group and 2.4% in the the simultaneous group, the difference was statistically significant[Peto OR 3.39, 95% CI 1.29-8.93, P=0.01]. No significant difference was found in morbidity between two groups[OR(random)0.88, 95% CI 0.51-1.51, P=0.64].Selective staged resection is safe for synchronous liver metastasis from colorectal cancer.

This study aimed to assess the efficacy and safety of laparoscopic resection (LR) for rectal cancer.A case-control study involving three Chinese medical centers was conducted. Rectal cancer patients undergoing LR were compared with open resection (OR) cases simultaneously from January 2004 to December 2005. Data were collected, and basic characteristics, conversion rate, recovery, complications, adjuvant therapy, and recurrence rate were compared. Analysis was by intention to treat.A total of 335 rectal cancer procedures (115 LR and 220 OR) met the inclusion criteria. The patients' basic characteristics were similar in the two groups (p0.05). Total mesorectal excision was performed for 85.59% of the patients (201/235), who received anal sphincter preservation. Compared with OR, LR had a shorter incision length, less blood loss, and less need for transfusion, but the operation time was longer (p0.05). No significant differences were observed between the two groups in positive rates of longitudinal resection margins, numbers of harvested lymph nodes, complication rates during operation and postoperation, and perioperative reoperation and morbidity rates (p0.05). Postoperative parenteral narcotics were used less in LR than in OR (47.8% vs 62.7%; chi(2)=6.867; p=0.009). The median time until first flatus; resumption of diet, defecation, micturition, and ambulation; and discharge were reduced in LR (p0.05). Conversion from LR to OR was required by 11.3% of the patients (13/115). The intraoperative complication rate was 30.8% for the patients who underwent conversion. The operation time and postoperative complication rate were the same as for LR alone (p0.05). The local recurrence rate was 3.7% for the LR group and 4.9% for the OR group (chi (2)=0.209; p=0.647) during the 20-month median follow-up period.The findings showed that LR for rectal cancer was safe and effective, resulting in faster recovery and a similar complication rate compared with OR. Conversion did not alter the patients' outcomes.

To assess the quality of life in patients with rectal cancer after laparoscopic colectomy.From Sep.2004 to Dec. 2005, 51 patients with rectal cancer were recruited in this prospective, non-randomized study.Twenty-three patients underwent laparoscopic colectomy (LC), 28 patients had open colectomy (OC). EORTC QLQ-C30 and QLQ-CR38 questionnaire were applied to evaluate quality of life baseline, discharging and 3 months after operation.Before operation,the median score of role functioning in LC group was lower. However, LC group patients complained less financial difficulties. The differences were of statistical significance (P0.05), but not of clinical significance. The median scores of other function domains and symptom domains were similar between two groups (P0.05). Postoperatively, the most median scores of function domains and symptom domains between two groups were similar (P0.05). The only score with statistically significant difference was the pain when patients left hospital (U=218.5, P=0.042). However, the difference was not of clinical significance, too.Only minimal benefits in short-term postoperative quality of life are found with laparoscopic colectomy in patients with rectal cancer compared with open colectomy.

To evaluate the short-term curative effects and safety of laparoscopic resection (LR) in treatment of colorectal cancer.The databases PubMed, Embase, CCTR, and CBMdisc were retrieved and 15 medical journals published in different countries were retrieved manually to search the literatures related to randomized controlled trials (RCTs) on the comparison between the effects and safety of LR and open resection (OR) in treatment of colorectal cancer that were published before the end of 2005. After selected based on the inclusion and exclusion standards, the valid literature were appraised by 2 reviewers independently.Nine articles, with a mean quality score of 7.6 +/- 0.6 were included into the meta-analysis. The baseline characteristics of the LR group were similar to those of the OR group. In comparison with the OR group, the incision length of the LR group was shorter by 12 cm [95% CI (-13.51, -10.49), P0.01], blood loss was less by 75 ml [95% CI (-86.06, -62.99), P0.01], intensity of pain in the first day after operation was lower [weight mean deviation = -0.80, 95% CI (-1.26, -0.34), P0.01], parenteral narcotic requirement was lower [standard mean deviation = -0.31, 95% CI (-0.42, -0.21), P0.01], and average times before the post-operative first flatus, first bowel movement, and diet resumption, and discharge were all shorter (all P0.05); however, the operation time was longer by 42 min [95% CI (32.18, 52.50), P0.01]. There were no significant differences in the length of resected specimen, positive rate of resection margin, number of retrieved lymph nodes, and morbidity rates of intra-operative and post-operative complications.With faster recovery and less pain compared with OR, LR is safe and effective in the treatment of colorectal cancer.

To evaluate the efficacy and safety of postoperative adjuvant chemotherapy with imatinib in gastrointestinal stromal tumor(GIST) patients who had high risk of recurrence.A prospective, open-label, multi-center trial conducted in sixteen teaching hospitals in China was carried out. The criteria of the enrolled patients included age more than 18 years old, CD117 positive GIST, tumor size more than 5 cm, pathological mitosis counts more than 5/50 HPF, and treatment beginning within 4 weeks after complete resection and with imatinib (400 mg, once a day) for at least 12 months. The 1, 3 year recurrence rates, disease free survival, overall survival rate and quality of life were evaluated.From Aug. 16th 2004 to Sep. 13th 2005, there were totally 74 patients screened and 57 patients (34 men, 23 women) enrolled in the imatinib treatment group. The primary tumors were located in the stomach in 50.9%, the small intestine in 38.6% and the colorectum in 10.5% of the cases. All the patients received radical resection. Until the cut-off date of interim analysis, there was no evidence of tumor relapse or metastasis in all patients and no death was reported either. Among the 57 enrolled patients with intention to treat(ITT), twelve patients finished the protocol (per protocol, PP). The disease free survival was (268.3 +/-120.2) d in ITT analysis, and (396.7+/-38.2) d in the PP analysis. The incidence of adverse effect was 44.4% . The score in quality of life showed no statistically significant difference between the baseline visit and the follow-up visits.Imatinib is a promising postoperative adjuvant chemotherapy in GISTs patients with high risk of recurrence, and the adverse effects are receivable.

To evaluate the efficacy of Dexon continuous intracutaneous sewing (DCIS) and Redon negative pressure absorbing drainage (RNPAD) in modified radical mastectomy of breast cancer.The clinical data of 128 patients treated with DCIS and RNPAD, and 123 cases treated with traditional sewing and negative pressure absorbing ball were analyzed retrospectively.There were 16 cases (12.5%) of seroma formation,1 (0.8%) of skin flay necrosis among 128 cases treated by DCIS and RNPAD, and 47 cases (38%) of seroma formation, 16 (13%) of skin flay necrosis among 123 cases treated by traditional method. The statistically significant difference was found (P0.001). The average length of post-operation hospital stay in DCIS and RNPAD group was 8.8 days compared with 14.7 days in traditional treatment group.The use of DCIS and TNPAD could decrease the complication rate of breast cancer operation.

To assess the significance of expression of sialylated carbohydrate antigens and nm23-H1 gene in metastasis and prognosis of breast cancer.Tissue specimens from 102 cases of primary breast cancer were stained with antibodies against sialyl Lewis A (SleA) and salyl Lewis X (SleX), and nm23-H1 proteins by immunohistochemical methods.Of the 102 cases, the positive cases of SleA and SleX were 24.5% (25/102) and 59.89% (61/102),respectively; the reduced expression of nm23-H1 was showed in 37.3% (38/102) of the cases. The positive expression of SleX and the reduced expression of nm23-H1 gene were significantly associated with lymph node involvement. Among the 100 patients who underwent curative surgery, the disease-free survival rate was significantly correlated with nm23-H1 and SleX expression, respectively,but not with SleA expression. In multivariate analysis using Cox regression model, combination assay of nm23 H1 and SleX expression emerged as independent prognostic factors.These results suggest that nm23-H1 gene and SleX may be involved in the metastatic process in human breast cancer, and immunohistochemical detection of SleX and nm23-H1 may be used as a biologic marker of prognosis.

To study the effect of SNC19/ST14 gene transfection and expression into colorectal cancer cells on biological behavior.The recombination vector pSecTag2a-SNC19/ST14 was constructed, and transfected into the RKO colorectal cancer cell line by liposome. The transfected cell was screened by real time PCR, Western Blot and Immunohistochemical technique. The population doubling time (T(D)) and cell cycle of the transfected cell were analyzed by MTT assay and flow cytometer. Rhodamine-labeled Phallodin was used to label the cell cytoskeletal protein-F-actin, and the F-actin distribution was observed by confocal scanning microscope. The adhesion ability of the transfected cell to extracellular matrix (ECM) was measured by MTT assay.The full length Open Reading Frame (ORF) of SNC19/ST14 gene was inserted into the vector pSecTag2a, and transfected into RKO cells, and expressed successfully. The changes of F-actin organization took place in transfected cell. The Adherence ability of the transfected cell to ECM was decreased, but the proliferation ability was not significantly changed except highly expressing of the SNC19/ST14, and not the cell cycle and the apoptosis.SNC19/ST14 gene was successfully expressed into the RKO cell line, and could influence on the cell cytoskeletal protein (F-actin) organization and on cell adherence ability to ECM, but could not make the cell cycle, apoptosis and proliferation ability change significantly.

To assess the association of five types of fucosyltransferase gene (Fuc-T), the important biosynthesis gene of sialylated carbohydrate antigens (Sialyl Lewis A, Sialyl Lewis X), with metastasis and prognosis of breast cancer.The real-time quantitative PCR of five-type Fuc-T III, IV, V, VI, VII genes was performed in 80 patients with breast cancer.The result showed that Fuc-TVII gene had higher gene copy compared to other type of Fuc-T in breast cancer. The grading of Fuc-TVII gene was related to lymph node metastasis and poor disease-free survival. Statistically difference was significant (P0.01). Fuc-T III, IV, V, VI gene were not significant relation to the metastasis and prognosis in 80 cases.These findings suggest that Fuc-TVII gene is a prognostic indicator of breast cancer, and it may be play an important role in the biosynthesis of sialylated carbohydrate antigens in breast cancer.

Objective To study the detailed effect of laparoscopy or open surgery with fast track or conventional treatment on patient's postoperative nutrition and immune recovery and stress response. Methods Patients with resectable colon cancer and high rectal cancer were randomized to 4 groups: (1) Laparoscopy with fast track treatment (LAFT); (2) Open surgery with fast track treatment (OSFT); (3) Laparoscopy with conventional treatment (LAC); (4) Open surgery with conventional treatment (OSC). Blood samples were collected preoperatively (baseline), and 12, 96 hours after surgery. Peripheral blood levels of albumin, prealbumin, Ig G, Ig A, Ig M and C-reactive protein (CRP) were analyzed. Results 19 patients were randomized for LAFT group, 18 for OSFT, 17 for LAC, and 19 for OSC. The four groups were balanced with respect to patients' characteristics. Mean albumin level (in percentage from baseline) was 94.35 in the LAFT group, 88.16 in the LAC group, 79.05 in the OSFT group, and 76.50 in the OSC group. Only in LAFT and LAC groups, the albumin level of 96 hours was higher than that of 12 hours, indicating the better potency of postoperative recovery of nutrition status. Similarly, postoperative Ig G levels were also highest in the LAFT group and showed the same rank with albumin levels in the 4 groups. Repeated-measures (2-way ANOVA) indicated the difference of albumin and Ig G can be attributed to surgery type and not perioperative treatment (P Conclusions Our FTMDT randomized trial indicats: 1. laparoscopic surgery shortens the period of postoperative nutrition and immune recovery while fast track treatment retards the decrease of postoperative nutrition and immune levels; 2. Combined laparoscopic surgery with fast track treatment provides best postoperative recovery of nutrition and immune status and lowest stress response. This study was registered under NCT01080547 (ClinicalTrials.gov). Disclosure All authors have declared no conflicts of interest.