Short- and long-term results of open vs laparoscopic multisegmental resection and anastomosis for synchronous colorectal cancer located in separate segments

BACKGROUND It remains unclear whether laparoscopic multisegmental resection and ana-stomosis(LMRA)is safe and advantageous over traditional open multisegmental resection and anastomosis(OMRA)for treating synchronous colorectal cancer(SCRC)located in separate segments.AIM To compare the short-term efficacy and long-term prognosis of OMRA as well as LMRA for SCRC located in separate segments.METHODS Patients with SCRC who underwent surgery between January 2010 and December 2021 at the Cancer Hospital,Chinese Academy of Medical Sciences and the Peking University First Hospital were retrospectively recruited.In accordance with the RESULTS LMRA patients showed markedly less intraoperative blood loss than OMRA patients(100 vs 200 mL,P=0.006).Compared to OMRA patients,LMRA patients exhibited markedly shorter postoperative first exhaust time(2 vs 3 d,P=0.001),postoperative first fluid intake time(3 vs 4 d,P=0.012),and postoperative hospital stay(9 vs 12 d,P=0.002).The incidence of total postoperative complications(Clavien-Dindo grade:≥II)was 2.9%and 17.1%(P=0.025)in the LMRA and OMRA groups,respectively,while the incidence of anastomotic leakage was 2.9%and 7.3%(P=0.558)in the LMRA and OMRA groups,respectively.Furthermore,the LMRA group had a higher mean number of lymph nodes dissected than the OMRA group(45.2 vs 37.3,P=0.020).The 5-year overall survival(OS)and disease-free survival(DFS)rates in OMRA patients were 82.9%and 78.3%,respectively,while these rates in LMRA patients were 78.2%and 72.8%,respectively.Multivariate prognostic analysis revealed that N stage[OS:HR hazard ratio(HR)=10.161,P=0.026;DFS:HR=13.017,P=0.013],but not the surgical method(LMRA/OMRA)(OS:HR=0.834,P=0.749;DFS:HR=0.812,P=0.712),was the independent influencing factor in the OS and DFS of patients with SCRC.CONCLUSION LMRA is safe and feasible for patients with SCRC located in separate segments.Compared to OMRA,the LMRA approach has more advantages related to short-term efficacy.

Prognostic scoring system for synchronous brain metastasis at diagnosis of colorectal cancer: A population-based study

BACKGROUND Brain metastasis(BM)from colorectal cancer(CRC)is rarely encountered clinically,and its prognosis has not been fully evaluated.AIM To construct a scoring system and accurately predict the survival of patients with synchronous BM at diagnosis of CRC.METHODS A retrospective study of 371 patients with synchronous BM from CRC was performed,using the data from 2010 to 2014 from the Surveillance,Epidemiology,and End Results database.Survival time and prognostic factors were statistically analyzed by the Kaplan-Meier method and Cox proportional hazards models,respectively.A scoring system was developed using the independent prognostic factors,and was used to measure the survival difference among different patients.RESULTS For the 371 patients,the median overall survival was 5 mo,survival rates were 27%at 1 year and 11.2%at 2 years.Prognostic analysis showed that age,carcinoembryonic antigen level and extracranial metastasis to the liver,lung or bone were independent prognostic factors.A scoring system based on these three prognostic factors classified the patients into three prognostic subgroups(scores of 0-1,2-3,and 4).The median survival of patients with scores of 0-1,2-3 and 4 was 14,5 and 2 mo,respectively(P<0.001).Subgroup analysis showed that there were significant differences in prognosis among the groups.Score 2-3 vs 0-1:hazard ratio(HR)=2.050,95%CI:1.363-3.083;P=0.001;score 4 vs 0-1:HR=3.721,95%CI:2.225-6.225;P<0.001;score 2-3 vs 4:HR=0.551,95%CI:0.374-0.812;P=0.003.CONCLUSION The scoring system effectively distinguishes long-term and short-term survivors with synchronous BM from CRC.These results are helpful in providing a reference for guiding therapy.

Evaluation of clinical significance of claudin 7 and construction of prognostic grading system for stage Ⅱ colorectal cancer

BACKGROUND Claudin 7 is often abnormally expressed in cancers and promotes the progression of some malignancies. However, the role of claudin 7 in stage Ⅱ colorectal cancer(CRC) has not been studied.AIM To assess the expression and prognostic value of claudin 7 in stage Ⅱ CRC.METHODS We retrospectively studied 231 stage Ⅱ CRC patients who underwent radical surgery at our hospital from 2013 to 2014. The protein expression level of claudin7 was assessed and its relationship with clinicopathological features and prognosis was statistically analyzed. The independent prognostic factors were identified by Cox proportional hazards models. A prognostic grading system was constructed to stratify the survival of CRC patients.RESULTS The expression of claudin 7 was significantly reduced in cancer tissues compared with normal tissues(P < 0.001), and its low expression was closely related to recurrence of the disease(P = 0.017). Multivariate analysis confirmed that claudin7 low expression(claudin 7-low)(P = 0.028) and perineural invasion positivity(PNI+)(P = 0.026) were independent predictors of poor disease-free survival(DFS). A prognostic grading system based on the status of claudin 7 and PNI classified the patients into three prognostic grades: grade A(claudin 7-high and PNI-), grade B(claudin 7-low and PNI-, claudin 7-high and PNI+), and grade C(claudin 7-low and PNI+). The DFS was significantly different among the three grades(grade B vs grade A, P = 0.032;grade C vs grade A, P < 0.001;grade C vs grade B, P = 0.040).CONCLUSION Claudin 7 can be used as a new prognostic marker to predict the DFS of patients with stage Ⅱ CRC. The prognostic grading system with the addition of claudin 7 can further improve prognosis stratification of patients.

lncRNA-PACER upregulates COX-2 and PGE2 through the NF-κB pathway to promote the proliferation and invasion of colorectal-cancer cells

Background p50-associated cyclooxygenase-2 extragenic RNA(PACER)is a recently identified antisense long non-coding RNA(lncRNA)located on the upstream of the promoter region of cyclooxygenase-2(COX-2).Preliminary studies have suggested that PACER is involved in the regulation of COX-2 expression in macrophagocyte and osteosarcoma cells.However,the role of this lncRNA in colorectal cancer(CRC)remains elusive.Here,we investigated the expression of PACER and its effect on cell proliferation and invasion to explore the role of PACER in CRC.Methods Real-time quantitative PCR(RT-qPCR)analysis was used to evaluate the expression of PACER in CRC tissues and cells.Methyl thiazolyl tetrazolium(MTT)analysis was then used to investigate the inhibition effect of PACER knock-down in cell proliferation.The promoting role of this lncRNA on invasion by CRC cells was analysed by wound-healing assays,colony-formation assay,and transwell assays.We then used fluorescence in situ hybridization(FISH)to establish the subcellular localization of PACER.COX-2 protein levels were quantified by Western blot analysis and grayscale scanning analysis following the knock-down of PACER.Luciferase assay was carried out to monitor the modulation of the COX-2 promoter region by PACER.Tumor xenografts models were used to investigate the impact of PACER on the tumorigenesis of CRC cells in vivo.Enzyme-linked immunosorbent assay(ELISA)was then used to quantify prostaglandin E2(PGE2)production upon knock-down of PACER.Results RT-qPCR analysis revealed that PACER was highly expressed in CRC tissues and cells,and a high PACER-expression level was associated with poor prognosis.MTT assay,wound-healing assay,colony-formation assay,and transwell assay revealed that PACER enhanced CRC-cell proliferation,invasion,and metastasis in vitro.Analysis of lncRNA localization by FISH showed that it mainly resided in the nucleus.RT-qPCR showed that PACER increased mRNA levels of COX-2.Western blot analysis demonstrated,under normal circumstances,that knock-down of PACER decreased the COX-2 protein level.In the case of p50 absence,COX-2 protein increased rapidly and remained highly expressed after knocking down PACER.Luciferase assay revealed that PACER modulated the COX-2 promoter region.Mouse xenograft models of CRC revealed that PACER promoted colorectal tumorigenesis in vivo.ELISA revealed that PACER knock-down inhibited PGE2 production.Conclusions PACER modulates COX-2 expression through the nuclear factor kappa B(NF-jB)pathway in CRC.An increased level of PACER enhances proliferation,migration,and invasion of tumor cells by increasing COX-2 and PGE2 synthesis.