Objective To develop a porcine model for laparoscopic intersphincteric resection (ISR) targeting ultra-low rectal cancer.Methods Six Bama mini-pigs underwent a standard laparoscopic ISR procedure: (1) Ligation and transection of the inferior mesenteric vessels; (2) Exposure and sparing of the pelvic autonomic nerves; (3) Dissection of the rectum; (4) Dissection and transection of hiatal ligament and rectourethralis muscle; (5) Transanal dissection of the anal canal; (6) Dissection of the intersphincteric space (ISS); (7) End-to-end handsewn coloanal anastomosis (CAA). Pathological evaluations were conducted to ascertain the precision of the ISR. Furthermore, postoperative fecal incontinence scores were systematically assessed on a weekly basis throughout a 12-week post-surgery follow-up period.Results All six pigs survived surgery without conversion to an open approach. There were no occurrences of incisional infection or any surgical complications, including anastomotic leakage, anastomotic bleeding, or ileus. Postoperatively, one pig manifested constipation and three exhibited anal redness, both conditions ameliorating within a week. No erosive ulcers were detected. Notably, all animals exhibited fecal staining on their tails within the first two weeks post-surgery, transitioning to formed feces by the third week. Improvement in defecation frequency was observed after 6 weeks, with a noticeable reduction in defecation areas after one month. Incontinence scores, evaluated three months post ISR surgery, revealed no significant abnormalities in anal function compared to preoperative assessments.Conclusions This study established a replicable porcine model for laparoscopic ISR, demonstrating its potential utility in clinical and fundamental research related to ultra-low rectal cancer treatment.

AIM:Sphincter-sparing surgery can be achieved in most cases of low rectal cancer with the development of intersphincteric resection. However, abdominoperineal resection is still inevitable for patients with tumours located below the dentate line. To address this, we have developed a procedure called conformal sphincteric resection (CSR) in which the corresponding part of the subcutaneous portion of the external anal sphincter and the perianal skin on the tumour side is removed to achieve a safe distal resection margin and lateral resection margin while the dentate line and the internal anal sphincter on the tumour-free side are preserved as much as possible, to achieve sphincter preservation without compromising oncological safety and functional acceptability, and to render tumour location no longer a contraindication for sphincter-sparing surgery. This is the first study to describe the concept, indication and surgical procedure of CSR and to report its preliminary surgical, oncological and functional results. METHODS:This is a retrospective, single-centre, single-arm pilot study conducted at Huashan Hospital, Fudan University. Demographic, clinicopathological, oncological and functional follow-up data were collected from 20 consecutive patients with rectal tumours located below the dentate line who underwent laparoscopic CSR by the same surgical team from June 2018 to March 2022. RESULTS:The mean distance of the tumour's lower edge from the anal verge was 13.1 ± 6.0 mm. The mean distal resection margin was 10.6 ± 4.3 mm. All circumferential resection margins were negative. There were no instances of perioperative mortality. The complication rate was 25% but all were Clavien-Dindo Grade I. Among the 20 cases, 17 were diagnosed with adenocarcinoma, one with squamous cell carcinoma and two with adenoma featuring high-grade intraepithelial neoplasia. Pathological TNM staging revealed two, seven, five, five and one case(s) in Stages 0, I, II, III and IV, respectively. The median follow-up period was 20 months (interquartile range 22 months), with no withdrawals. The overall and disease-free survival rates were both 95%. The mean Wexner incontinence score and low anterior resection syndrome score recorded 18 months following diverting ileostomy closure were 6.3 ± 3.8 and 27.3 ± 3.6, respectively. CONCLUSIONS:This study has proposed the CSR procedure for the first time, which is a technically feasible, oncologically safe and functionally acceptable procedure for carefully selected patients with rectal tumours located below the dentate line.

3613 Background: Antiangiogenic therapy has shown benefit in metastatic colorectal cancer. However, the role of apatinib in adjuvant treatment of stage IIIB and IIIC colorectal cancer remains unclear. Methods: Patients received modified FOLFOX6 once every 2 weeks for a 6-month period (control group) or modified FOLFOX6 for 6 months plus apatinib (500mg) once a day for a 12-month period (experimental group). Progression free survival (PFS), overal survival (OS) and treatment-related adverse events were evaluated in two groups. Results: 63 patients have been enrolled in this study. This trial reported a 3-year PFS of 74.2% for modified FOLFOX6 plus apatinib vs. 61.5% for modified FOLFOX6 ( P< 0.05). 5-year OS was significantly improved in the experimental group compared with the control group (86.3% vs. 72.5%; P< 0.05). The most common grade 3 adverse events were hypertension and hand–foot syndrome. No treatment-related grade 4 adverse events or treatment-related deaths were observed. Conclusions: Apatinib can prolong PFS and OS when added to adjuvant chemotherapy in resected stage IIIB and IIIC colorectal cancer. The toxicities associated with apatinib were generally acceptable. Clinical trial information: NCT03365765 .

Introduction:Translocase of the inner mitochondrial membrane 50 (TIMM50) is universally considered to play a key role in several malignancies. However, its role in predicting colorectal cancer (CRC) patient prognosis remains unclear.Material and methods:A total of 192 CRC patients (123 men and 69 women) who underwent radical resection participated in this study. The patients were followed up every 3 months after surgery for 5 years. TIMM50 expression in tumour tissues was measured by quantitative real-time PCR, Western blotting and immunohistochemistry. TIMM50 expression was studied to assess correlations with clinicopathological factors and survival time.Results:TIMM50 expression increased significantly in CRC tumour tissues. Moreover, high TIMM50 expression was related to pathologic stage (p = 0.043), N stage (p = 0.048) and distant metastasis (p = 0.015), but TIMM50 expression was not related to other clinical factors. A Kaplan-Meier survival analysis indicated that patients with low TIMM50 expression had a longer overall survival than those with high TIMM50 expression (p = 0.002). Furthermore, distant metastasis and high TIMM50 expression were confirmed as independent prognostic factors for the overall survival of CRC patients in a multivariate analysis (p = 0.003).Conclusions:TIMM50 may be a key factor for monitoring CRC and a new prognosis indicator for CRC patients.

Background:Postoperative recurrence was a life-threatening condition for patients with rectal cancer. Due to the heterogeneity of locally recurrent rectal cancer (LRRC) and controversy of the optimal treatment for patients, it was difficult to predict the prognosis of LRRC. This study aimed to develop and validate a nomogram that could accurately predict the survival probability of LRRC.Methods:Patients diagnosed with LRRC between 2004 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database were included in the analysis. Multiple imputations with chained equations were used for missing values. These patients were further randomized into training set and testing set. Cox regression was used for univariate and multivariate analysis. Potential predictors were screened by the least absolute shrinkage and selection operator (LASSO). The Cox hazards regression model was constructed and it was visualized by nomogram. C-index, calibration curve, and decision curve were used to evaluate the model's predictive ability. Then X-tile was used to calculate the optimal cut-off values for all patients and the cohort was divided into three groups.Results:A total of 744 LRRC patients were enrolled and allocated to the training set (n=503) and the testing set (n=241). Cox regression analysis of the training set yielded meaningfully clinicopathological variables. A survival nomogram was created based on the identification of ten clinicopathological features in the LASSO regression analyses of the training set. The C-index of 3-, 5-year survival probabilities were 0.756, 0.747 in training set, and 0.719, 0.726 in testing set, respectively. The calibration curve and decision curve both demonstrated the satisfactory performance of the nomogram for prognosis prediction. Moreover, the prognosis of LRRC could be well distinguished according to the grouping of risk scores (P<0.001 in three groups).Conclusions:This nomogram was the first prediction model to preliminarily evaluate the survival of LRRC patients, which could provide more accurate and efficient treatment in clinical practice.

BACKGROUND:Intersphincteric resection (ISR) has been proposed to offer sphincter-sparing solution for patients with ultra-low rectal cancer. However, complete and accurate concepts about the intersphincteric space (ISS) related anatomy are not demonstrated clearly. This study aimed to provide a comprehensive description about the anatomic structure of ISS related to ISR.METHODS:This was a descriptive morphological study. 28 pelvic specimens were obtained from body donors. Macroscopic and microscopic observation of ISS was performed via gross anatomy, plastinated sections and histologic staining. The anatomical parameters of the anal canal were measured. Images of laparoscopic ISS dissection procedures were real-timely captured during ISR.RESULTS:The hiatal ligament, microvessels on supra fascia of LAM and rectal longitudinal muscle at the level of anorectal ring, especially at 1, 5, 7, and 11o'clock, could be the preferred entrance of ISS. The conjoint longitudinal muscle (CLM), the major component of ISS, was the continuum of the rectal longitudinal muscle and got reinforcement from the elastic fibers from LAM and EAS. Microvessels and neuro tissues were also found in ISS. The ISS was split into two spaces by the CLM in the middle and might subjectively be divided into three segments according to its different compositions. The length and width of ISS varied from different segments and directions.CONCLUSIONS:We provided a systemic description of boundaries, contents and topographic structure of ISS, which may help proper determination of surgical approaches and dissection planes during ISR.

Locally recurrent rectal cancer (LRRC) leads to a poor prognosis and appears as a clinically predominant pattern of failure. In this research, whole-exome sequencing (WES) was performed on 21 samples from 8 patients to search for the molecular mechanisms of LRRC. The data was analyzed by bioinformatics. Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) were performed to validate the candidate genes. Immunohistochemistry was used to detect the protein expression of LEF1 and CyclinD1 in LRRC, primary rectal cancer (PRC), and non-recurrent rectal cancer (NRRC) specimens. The results showed that LRRC, PRC, and NRRC had 668, 794, and 190 specific genes, respectively. FGFR1 and MYC have copy number variants (CNVs) in PRC and LRRC, respectively. LRRC specific genes were mainly enriched in positive regulation of transcription from RNA polymerase II promoter, plasma membrane, and ATP binding. The specific signaling pathways of LRRC were Wnt signaling pathway, gap junction, and glucagon signaling pathway, etc. The transcriptional and translational expression levels of genes including NFATC1, PRICKLE1, SOX17, and WNT6 related to Wnt signaling pathway were higher in rectal cancer (READ) tissues than normal rectal tissues. The PRICKLE1 mutation (c.C875T) and WNT6 mutation (c.G629A) were predicted as “D (deleterious)”. Expression levels of LEF1 and cytokinin D1 proteins: LRRC > PRC > NRRC > normal rectal tissue. Gene variants in the Wnt signaling pathway may be critical for the development of LRRC. The present study may provide a basis for the prediction of LRRC and the development of new therapeutic drugs.

Objective:To investigate clinical efficacy of conformal sphincter preservation operation (CSPO) versus intersphincteric resection (ISR) in the treatment of low rectal cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 183 patients with low rectal cancer who were admitted to two medical centers (117 in the Changhai Hospital of Naval Medical University and 66 in the Huashan Hospital of Fudan University) from August 2011 to April 2020 were collected. There were 110 males and 73 females, aged (57±11)years. Of 183 patients, 117 cases undergoing CSPO were allocated into CSPO group, and 66 cases undergoing ISR were allocated into ISR group, respectively. Observation indicators: (1) surgical situations of patients with low rectal cancer in the two groups; (2) postoperative complications of patients with low rectal cancer in the two groups; (3) follow-up; (4) influencing factors for prognosis of patients with low rectal cancer; (5) influencing factors for satisfaction with the anal function of patients with low rectal cancer. Follow-up was conducted using outpatient examination, questionnaire and telephone interview to determine local recurrence, distal metastasis, survival, stomal closure, satisfaction with the anal function of patients. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data was analyzed using the rank sum test.The Kaplan-Meier method was used to draw survival curves, and life table method was used to calculate survival rates. Log-rank test was used for survival analysis. Univariate analysis was performed using the linear regression. Variables with P<0.10 in the univariate linear regression analysis were included for multivariate analysis. Multivariate analysis was performed using the COX stepwise regression model and linear regression analysis. Results:(1) Surgical situations of patients with low rectal cancer in the two groups: cases with laparoscopic surgery, operation time, volume of intraoperative blood loss, distance from tumor to distal margin, cases with postoperative chemotherapy, duration of postoperative hospital stay were 44, (165±54)minutes, (142±101)mL, (0.6±0.4)cm, 76, (6.6±2.5)days for the CSPO group, respectively, versus 55, (268±101)minutes, (91±85)mL, (1.9±0.6)cm, 9, (7.9±4.7)days for the ISR group, showing significant differences between the two groups ( χ2=35.531, t=8.995, -3.437, -3.088, χ2=44.681, t=2.267, P<0.05). (2) Postoperative complications of patients with low rectal cancer in the two groups: 19 patients in the CSPO group had complications. There were 6 cases with grade Ⅰ complications, 12 cases with grade Ⅱ complications, 1 case with grade Ⅲb complication. Fourteen patients in the ISR group had complications. There were 4 cases with grade Ⅰ complications, 7 cases with grade Ⅱ complications, 1 case with grade Ⅲa complication, 2 cases with grade Ⅲb complications. There was no significant difference in the postoperative complications between the two groups ( χ2=0.706, P>0.05). Patients with complications in the two groups were improved after symptomatic and supportive treatment. There was no perioperative death in the postoperative 30 days of the two groups. (3) Follow-up: 183 patients received follow-up. Patients of the CSPO group and ISR group were followed up for (41±27)months and (37±19)months, respectively, showing no significant difference between the two groups ( t=-1.104, P>0.05). There were 2 cases with local recurrence and 9 cases with distal metastasis of the CSPO group, respectively, versus 3 cases and 4 cases of the ISR group, showing no significant difference between the two groups ( χ2=1.277, 0.170, P>0.05). The 3-year disease-free survival rate and 3-year total survival rate were 84.0% and 99.0% for the CSPO group, versus 88.6% and 92.8% for the ISR group, showing no significant difference between the two groups ( χ2=0.218, 0.002, P>0.05). The stomal closure rate was 92.16%(94/102) and 96.97%(64/66) for 102 patients of CSPO group and 66 patients of ISR group up to postoperative 12 months,respectively, showing no significant difference between the two groups ( χ2=1.658, P>0.05). Of the 8 cases without stomal closure in the CSPO group, 2 cases refused due to advanced age, 4 cases subjectively refused, and 2 cases were irreducible due to scar caused by radiotherapy. Two cases in the ISR group had no stomal closure including 1 case of postoperative liver metastasis and 1 case of subjective refusal. There were 92 and 61 patients followed up to 12 months after stomal closure, of which 75 cases and 38 cases completed questionnaires of satisfaction with the anal function. The satisfaction score with the anal function was 6.8±2.8 and 5.4±3.0 for CSPO group and ISR group, respectively, showing a significant difference between the two groups ( t=-2.542, P<0.05). Fifty-four cases in the CSPO group and 21 cases in the ISR group had satisfaction score with the anal function >5, showing no significant difference between the two groups ( χ2=3.165, P>0.05). (4) Influencing factors for prognosis of patients with low rectal cancer: results of COX stepwise regression analysis showed that gender and pT staging were independent influencing factors for disease-free survival rate of patients with low rectal cancer ( hazard ratio=2.883, 1.963, 95% confidence interval as 1.090 to 7.622, 1.129 to 3.413, P<0.05). Gender and pT staging were independent influencing factors for total survival rate of patients with low rectal cancer ( hazard ratio=10.963,3.187, 95% confidence interval as 1.292 to 93.063, 1.240 to 8.188, P<0.05). (5) Influencing factors for satisfaction with the anal function of patients with low rectal cancer: results of univariate analysis showed that surgical method and tumor differentiation degree were related factors for satisfaction with the anal function of patients with low rectal cancer (partial regression coefficient=1.464, -1.580, 95% confidence interval as 0.323 to 2.605, -2.950 to -0.209, P<0.05). Results of multivariate analysis showed that surgical method, tumor differentiation degree and preoperative radiotherapy were independent influencing factors for satisfaction with the anal function of patients with low rectal cancer (partial regression coefficient=1.637, -1.456, -1.668, 95% confidence interval as 0.485 to 2.788, -2.796 to -0.116, -2.888 to -0.447, P<0.05). Conclusion:Compared with ISR, CSPO can safely preserve the anus in the treatment of low rectal cancer, without increasing the incidence of postoperative complications, which can also guarantee the oncological safety and improve the postoperative anal function.

Pleckstrin-2 (PLEK2) is a crucial mediator of cytoskeletal reorganization. However, the potential roles of PLEK2 in gastric cancer are still unknown. PLEK2 expression in gastric cancer was examined by western blotting and real-time PCR. Survival analysis was utilized to test the clinical impacts of the levels of PLEK2 in gastric cancer patients. In vitro and in vivo studies were used to estimate the potential roles played by PLEK2 in modulating gastric cancer proliferation, self-renewal, and tumourigenicity. Bioinformatics approaches were used to monitor the effect of PLEK2 on epithelial-mesenchymal transition (EMT) signalling pathways. PLEK2 expression was significantly upregulated in gastric cancer as compared with nontumour samples. Kaplan-Meier plotter analysis revealed that gastric cancer patients with higher PLEK2 levels had substantially poorer overall survival compared with gastric cancer patients with lower PLEK2 levels. The upregulation or downregulation of PLEK2 in gastric cancer cell lines effectively enhanced or inhibited cell proliferation and proinvasive behaviour, respectively. Additionally, we also found that PLEK2 enhanced EMT through downregulating E-cadherin expression and upregulating Vimentin expression. Our findings demonstrated that PLEK2 plays a potential role in gastric cancer and may be a novel therapeutic target for gastric cancer.

4111 Background: The aim of this study was to evaluate the comparative clinical and oncological outcomes of temporary ileostomy closure during or after adjuvant chemotherapy in patients with total mesorectal excision (TME) for rectal cancer. Methods: This randomized controlled trial investigated 87 patients (51 males, 36 females) with rectal cancer undergoing TME surgery with temporary ileostomy from January 2016 to December 2018. Patients were randomized divided into 2 groups: early group (43 patients, mean age: 60.35) who underwent stoma closure during adjuvant chemotherapy (3 months after primary surgery) and late group (44 patients, mean age 61.80) who underwent stoma closure after adjuvant chemotherapy (6 months after primary surgery). Both clinical and oncological outcomes were analyzed. Results: No significant differences were observed in operative time, blood loss, postoperative hospital stay, postoperative complications or hospital costs in ileostomy closure between the 2 groups. Stoma-quality of life (QOL) of patients in early group was significantly better than late group (52.02±5.68 vs 46.91±5.68, P <0.05). No significant difference in overall survival (P = 0.702) or progression-free survival (P = 0.638) was observed between the 2 groups. Conclusions: Ileostomy closure during adjuvant chemotherapy was clinically safe, and interruption of chemotherapy due to ileostomy closure did not change oncologic outcomes. Early ileostomy closure can improve QOL in those patients. Clinical trial information: NCT02665026 .

Aim: The T cell receptor-CD3 complex has shown great potential in tumor therapy. However, there is currently no research on CD3D in tumors. Materials & methods: Correlation between CD3D expression and clinical parameters and immune checkpoints of of colon adenocarcinoma (COAD) were analyzed. Results: CD3D decreased with increasing clinical stage and microsatellite status of COAD. Functional enrichment analysis revealed that CD3D is related to immune activation and regulation. Coexpression analysis indicated that CD3D is correlated with immune checkpoint and immune-infiltrated cells. Patients with higher expression of CD3D showed better clinical outcome. Conclusion: The findings suggest that the participation of CD3D may serve as a prognostic marker of COAD and may act as a guide in the development of immunotherapy.

目的通过应用术中盆腔自主神经监测（intraoperative monitoring of pelvic autonomic nerves，IMPAN）对中低位直肠癌腹腔镜手术中盆腔自主神经丛（pelvic autonomic nerve plexus，PANP）进行探查和保护，探讨术中盆腔神经保护的方法及神经监测的临床疗效。 方法回顾性分析2012年1月至2018年12月在复旦大学附属华山医院开展的腹腔镜中低位直肠癌根治术患者的临床资料，筛选其中79例术前肛门功能正常、性生活相对活跃的资料完整患者进入本研究，其中盆腔神经丛监测组包括双侧监测和单侧监测共43例，常规直肠全系膜切除术（total mesorectal excision，TME）肉眼判断者36例为对照组。比较两组手术时间、术中出血量、淋巴结阳性人数比例、术后平均住院时间及留置导尿管时间，通过标准化问卷随访比较两组患者术后生活质量、术后排尿功能、排便功能及性功能变化。 结果监测组与对照组平均手术时间、术中出血量、淋巴结阳性人数比例、术后平均住院时间及留置导尿管时间差异无统计学意义（P>0.05）。在79例患者中，双侧监测成功组（n=33）患者术后泌尿功能、生活质量相对较高，造口回纳后性功能障碍发生率较低。术后1年双侧监测组与对照组（n=36）相比，国际前列腺症状评分（international prostate symptom score，IPSS）分别为2.94±2.49 vs. 5.19±3.30，生活质量（quality of life，QoL）评分为1.73±0.67 vs. 2.56±0.84，差异有统计学意义（P 结论腹腔镜中低位直肠癌根治术中采用IMPAN技术有助于定位盆腔植物神经的走向、变异以及确认其功能完整性，降低医源性损伤的发生率，提高患者的生活质量，改善预后。

Robotic colorectal cancer surgery is widely accepted and applied. However, there is still no objective and comprehensive assessment on the data of nationwide multicenter series. A total of 28 medical centers in Mainland China participated in this nationwide retrospective observational study. From the first case performed in each center to the last until December 2017, patients with robotic resection for primary tumor and pathologically confirmed colorectal adenocarcinoma were consecutively enrolled. Clinical, pathological and follow-up data were collected and analyzed. A total of 5389 eligible patients were finally enrolled in this study, composing 72.2% of the total robotic colorectal surgery volume of Mainland China in the same period. For resections of one bowel segment of primary tumor, the postoperative mortality rate was 0.08% (4/5063 cases), and the postoperative complication rate (Clavien–Dindo grade II or higher) was 8.6% (434/5063 cases). For multiple resections, the postoperative mortality rate was 0.6% (2/326 cases), and the postoperative complication rate was 16.3% (53/326 cases). Out of 2956 patients receiving sphincter-preserving surgery in only primary resection, 130 (4.4%) patients had anastomotic leakage. Traditional low anterior resection (tumor at middle rectum) (OR 2.384, P < 0.001), traditional low anterior resection (tumor at low rectum) (OR 1.968, P = 0.017) and intersphincteric resection (OR 5.468, P = 0.006) were significant independent risk factors for anastomotic leakage. Female gender (OR 0.557, P = 0.005), age ≥ 60 years (OR 0.684, P = 0.040), and preventive stoma (OR 0.496, P = 0.043) were significant independent protective factors. Body mass index, preoperative chemotherapy/radiotherapy, tumor size, and TNM stage did not independently affect the occurrence of anastomotic leakage. Robotic colorectal cancer surgery was safe and reliable and might have advantages in patients at high risk of anastomotic leakage.

目的 探讨盆腔增强CT和MRI在局部复发直肠癌(LRRC)多器官联合切除中的价值.方法 回顾性分析2012年1月至2018年12月复旦大学附属华山医院外科收治的行手术治疗的48例LRRC病人的临床资料,病理组织保存完整.LRRC根据纪念斯隆-凯特琳癌症中心(MSKCC)标准分为中央型、前向型、后向型和侧向型.术前均行腹部增强CT和盆腔平扫+增强MRI检查.比较CT和MRI对LRRC术前诊断准确率、对邻近器官侵犯的预测价值,并分析二者融合图像对手术的指导作用.结果 48例病人中41例(85.4％)经术后病理学检查确诊直肠癌术后复发.MRI和CT对LRRC检出率分别为95.1％(39/41)和87.8％(36/41),差异无统计学意义(x2=1.406,P=0.236),MRI诊断LRRC的准确率高于CT[91.7％(44/48) vs.77.1％(37/48),x2=3.872,P=0.049].盆腔增强CT及MRI鉴别LRRC累及邻近器官的准确率分别为70.8％ (34/48)和68.7％(33/48),差异无统计学意义(x2=0.049,P=0.824).各LRRC亚型分析提示,增强CT的鉴别准确率:后向型100％(7/7)、侧向型71.4％(5/7)、中央型69.6％(16/23)、前向型54.6％ (6/11);盆腔增强MRI的鉴别准确率:中央型78.3％(18/23)、前向型63.6％ (7/11)、后向型57.1％(4/7)和侧向型57.1％(4/7).所有病人均顺利完成手术,R0切除率为85.4％(41/48).结论 推荐增强MRI检查作为LRRC诊断辅助手段;增强CT对后向型LRRC骶尾骨侵犯检出率高,而增强MRI判断中央型LRRC准确率较高;多模态融合图像有助于确定LRRC手术切除范围并制定策略.

Purpose Colorectal cancer (CRC) stem cells are tumorigenic, capable of self-renewal, and resistant to therapy. Although the expression pattern and functions of micro RNA (miR)-194 in CRC cells have been widely investigated, little is known about its role in CRC stem cells. Therefore, the aim of this study was to investigate the potential role of miR-194 in CRC stem cells. Materials and methods CRC stem cells were isolated from the SW620 colon cancer cell line using microbeads. The expression levels of miR-194 and slingshot 2 (SSH2) in CRC stem cells were detected by RT-PCR and Western blot. A luciferase reporter assay was performed to confirm that miR-194 directly targets SSH2. Proliferation of CRC stem cells was examined by colony formation and MTT assays. Apoptosis in CRC stem cells was detected by cell cycle and apoptosis assays. The role of miR-194 in tumor growth was determined in vivo. Results Cells positive for CD44 and CD133 accounted for approximately 88.7% of the isolated population after microbead isolation. We reveal for the first time that miR-194 expression is decreased in CRC stem cells. Specifically, miR-194 is involved in inhibiting the proliferation of CRC stem cells and promoting CRC stem cell apoptosis by directly targeting SSH2. Furthermore, overexpression of miR-194 resulted in blocking the G1/S transition, the induction of cellular apoptotic process, thereby suppressing the malignant behaviors of CRC stem cells. Conclusion This study represents a novel characterization of miR-194 function in CRC stem cells, which may aid in the development of promising therapeutic strategies targeting CRC.

Colon cancer is one of the most malignant cancers worldwide. Nearly 20% of all colon cancer patients are diagnosed at stage IV (metastasis). However, further study of colon cancer is difficult due to a lack of understanding of its pathogenesis. In this study, we acquired high-throughput sequence data from TCGA datasets and performed integrated bioinformatic analysis including differential gene expression analysis, gene ontology and KEGG pathways analysis, protein-protein analysis, survival analysis, and multivariate Cox proportional hazards regression analysis in order to identify a panel of key candidate genes involved in the metastasis of colon cancer. We then constructed a prognostic signature based on the expression of REG1B, TGM6, NTF4, PNMA5, and HOXC13 which could provide significant prognostic value for colon cancer.

目的 探讨miR-34a和CTHRC1在结直肠癌中的生物学功能,miR-34a参与结直肠癌发生的可能机制.方法 采用qRT-PCR检测miR-34a在结肠癌患者及五株不同结肠癌细胞中的表达;采用双荧光素酶法分析miR-34a与CTHRC1之间的靶向关系;通过将miR-34a过表达或敲除质粒转染入HT-29细胞,采用流式细胞术、MTT法和Transwell法分别观察细胞的凋亡、细胞周期、增殖、侵袭及迁移情况.结果 qRT-PCR结果显示miR-34a在结肠癌组织中表达下调,且在结直肠癌细胞株HT-29中的表达最低.双荧光素酶测定法也确定miR-34a可直接靶向调控CTHRC1.此外,上调miR-34a的表达后可诱导细胞周期停滞、促进细胞凋亡、抑制细胞增殖,但下调miR-34a的表达则可抑制细胞凋亡并促进细胞周期和细胞增殖.最后,Transwell实验也发现过表达miR-34a,可显著性地降低HT-29细胞的侵袭和迁移,但抑制miR-34a则可显著性地增加HT-29细胞的侵袭和迁移.结论 miR-34a可通过调控CTHRC1的表达而在体外阻止结直肠癌的进展和转移,因此,miR-34a可能为后续开发结直肠癌的新型抗癌分子提供了新的方向.

PURPOSE:Colorectal cancer (CRC) is the most common malignancy in the gastrointestinal tract. The liver is the most common location of CRC metastases, which are the main causes of CRC-related death. However, the mechanisms underlying metastasis of CRC to the liver have not been characterized, resulting in therapeutic challenges.METHODS:The effects of hepatic stellate cells (HSCs) on T cells were evaluated using in vitro mixed lymphocyte reactions (MLRs) and cytokine production assays. HSC-induced CT26 cell migration and proliferation were evaluated in vitro and in vivo.RESULTS:HSCs induced T cell hypo-responsiveness, promoted T cell apoptosis, and induced regulatory T cell expansion in vitro. IL-2 and IL-4 were significantly lower in MLRs incubated with HSCs. Supernatants of MLRs with HSCs promoted CT26 cell proliferation and migration. Furthermore, the presence of HSCs increased the number of liver metastases and promoted proliferation of liver metastatic tumor cells in vivo.CONCLUSION:HSCs may contribute to an immunosuppressive liver microenvironment, resulting in a favorable environment for the colonization of CRC cells in the liver. These findings highlight a potential strategy for treatment of CRC liver metastases.

Colorectal cancer is one of the most common malignancies. Aberrant expressed microRNAs (miRNAs) have been demonstrated to have strong associations with colorectal cancer by repressing their targets. Therefore, miRNAs are thought to have significant promise in the diagnosis and prognosis of colorectal cancer. Previous studies indicated that miR-155 and collagen triple helix repeat containing 1 (CTHRC1) were both involved in pathogenesis of colorectal cancer, but the underlying mechanisms of miR-155 and CTHRC1 are still unknown. The present study aimed to investigate the biological functions of miR-155 and CTHRC1 in colorectal cancer. Reverse transcription-quantitative polymerase chain reaction was used to examine miR-155 and CTHRC1 expression levels. A dual-luciferase reporter assay was applied to verify the target interaction between miR-155 and CTHRC1. Proliferation, cell cycle, apoptosis, cell migration and invasion were measured using the MTT assay, flow cytometry and Transwell assays, respectively. Results showed that miR-155 expression was decreased, but CTHRC1 expression was increased in colorectal cancer tissue and cell lines. Furthermore, it was demonstrated that miR-155 negatively regulated CTHRC1. Additionally, miR-155 overexpression suppressed cell proliferation, induced cell cycle arrest and promoted cell apoptosis, while an inhibitor of miR-155 facilitated cell proliferation and cell cycle and repressed apoptosis. Transwell experiments indicated that miR-155 inhibited the cell migratory and invasive abilities of HT-29 cells, but miR-155 inhibitor enhanced these abilities of HT-29 cells. These results suggested that miR-155 prevented colorectal cancer progression and metastasis via silencing CTHRC1 in vitro, which provides evidence for miR-155 and CTHRC1 as a novel anti-onco molecular target for the treatment of colorectal cancer in the future.