To investigate the feasibility of a radiomics model for the detection of bladder invasion (BI) by colorectal cancer (CRC) on CT images. Ninety-six patients with CRC and a suspicion of BI who underwent tumor resection with partial or total cystectomy were reviewed. The 96 patients were randomly assigned to the training dataset (n = 68) or test dataset (n = 28) at a ratio of 7:3. The CT images were reviewed by two experienced radiologists, who provided a CT impression of the invasion of the bladder by CRC. A region of interest (ROI) on the CT images for each case was manually labeled by two radiologists. A radiomics model was constructed using a Categorical Boosting (CatBoost) classifier. The predicted probability by CatBoost was used to evaluate the efficacy of the radiomics model. The areas under the curve (AUCs) of the receiver operating characteristic were compared between the radiomics model and the CT impression. In the training dataset, the AUC of the radiomic model [0.864 (95% CI: 0.778, 0.951)] was significantly greater than that of CT impression [0.678 (95% CI: 0.569. 0.786), P = 0.007]. In the test dataset, the AUC of the radiomic model [0.883 (95% CI: 0.699, 1.000)] was also significantly greater than that of CT impression [0.570 (95% CI: 0.370, 0.770), P = 0.040]. It is feasible to use radiomics models for the prediction of BI by CRC, which might perform better than human radiologists.

Background There are different surgical strategies that can treat synchronous colorectal cancer (SCRC) involving separate segments, namely extensive resection (EXT) and left hemicolon-sparing resection (LHS). We aim to comparatively analyze short-term surgical results, bowel function, and long-term oncological outcomes between SCRC patients treated with the two different surgical strategies. Methods One hundred thirty-eight patients with SCRC lesions located in the right hemicolon and rectum or sigmoid colon were collected at the Cancer Hospital, Chinese Academy of Medical Sciences, and the Peking University First Hospital from January 2010 to August 2021 and divided into EXT group ( n = 35) and LHS group ( n = 103), depending on their surgical strategies. These two groups of patients were compared for postoperative complications, bowel function, the incidence of metachronous cancers, and prognosis. Results The operative time for the LHS group was markedly shorter compared with the EXT group (268.6 vs. 316.9 min, P = 0.015). The post-surgery incidences of total Clavien-Dindo grade ≥ II complications and anastomotic leakage (AL) were 8.7 vs. 11.4% ( P = 0.892) and 4.9 vs. 5.7% ( P = 1.000) for the LHS and EXT groups, respectively. The mean number of daily bowel movements was significantly lower for the LHS group than for the EXT group (1.3 vs. 3.8, P < 0.001). The proportions of no low anterior resection syndrome (LARS), minor LARS, and major LARS for the LHS and EXT groups were 86.5 vs. 80.0%, 9.6 vs. 0%, and 3.8 vs. 20.0%, respectively ( P = 0.037). No metachronous cancer was found in the residual left colon during the 51-month (median duration) follow-up period. The overall and disease-free survival rates at 5 years were 78.8% and 77.5% for the LHS group and 81.7% and 78.6% for the EXT group ( P = 0.565, P = 0.712), respectively. Multivariate analysis further confirmed N stage, but not surgical strategy, as the risk factor that independently affected the patients’ survival. Conclusions LHS appears to be a more appropriate surgical strategy for SCRC involving separate segments because it exhibited shorter operative time, no increase in the risk of AL and metachronous cancer, and no adverse long-term survival outcomes. More importantly, it could better retain bowel function and tended to reduce the severity of LARS and therefore improve the post-surgery life quality of SCRC patients.

Objective:To evaluate CT and or MRI imaging in the diagnosis of lateral lymph node metastasis in patients of middle and low rectal cancer.Methods:In this study, 112 lateral lymph nodes were harvested in 79 patients with middle and low rectal cancer. The relationship between the preoperative imaging features of the lateral lymph nodes and the postoperative pathology was evaluated.Result:Thirty-eight cases (48%) were pathologically confirmed to have lateral lymph node metastasis. The diameter of metastasis-positive lateral lymph nodes was significantly larger than that of metastasis-negative lateral lymph nodes ( P<0.01). Multivariate analysis of clinical features and imaging features found that, tumors poorly differentiated, mucinous adenocarcinoma, signet ring cell carcinoma ( P=0.006), and the largest short diameter of the lateral lymph node ≥7 mm ( P=0.024), uneven density or signal ( P=0.022) were independent risk factors for lateral lymph node metastasis. Conclusion:Poor tumor differentiation, lateral lymph node maximum short diameter ≥7 mm, density or signal unevenness are independent risk factors for lateral lymph node metastasis in middle and low rectal carcinoma.

目的 探讨腹腔镜直肠癌根治术中行侧方淋巴结清扫(LLND)治疗局部进展期低位直肠癌的可行性、安全性及疗效.方法 回顾性分析2000年1月至2019年12月北京大学第一医院普通外科收治的行直肠癌根治术的200例进展期低位直肠癌病人的临床资料,术中均行LLND.根据手术方式分为腹腔镜组(77例)和开放组(123例),比较两组病人的近期疗效及中期肿瘤学结果.结果 与开放组比较,腹腔镜组病人手术时间缩短[240(110～550) min vs.310(140～780) min,Z=-8.714,P＜ 0.001],出血量减少[100(10～1200)mL vs.400(60～2500) mL,Z=-5.233,P＜ 0.001],术后尿潴留发生率降低(8.8％ vs.21.1％,x2=4.607,P=0.032),术后尿管拔除时间[4(1～12)d vs.5(2～24)d,Z=-2.722,P=0.006]和术后住院时间[11(6～59)d vs.16(7～64)d,Z=-2.274,P=0.023]均缩短.腹腔镜组单侧侧方淋巴结检出总数[5.5(1～17)枚vs.5.0(1～17)枚,Z=-2.134,P=0.033]和单侧髂内及闭孔动脉淋巴结检出数目[4(1～17)枚vs.3(1～11)枚,Z=-2.234,P=0.025]均增高.两组病人总生存率及无病生存率差异均无统计学意义(78.6％ vs.79.0％,69.8％ vs.71.3％,P＞0.05).结论 腹腔镜技术用于LLND有助于减少术中出血,更好地保护植物神经功能,病人术后恢复更快,可清扫更多的区域淋巴结,但中期肿瘤学结果与开放手术相当.

PURPOSE:The purpose of this study was to determine the risk factors for the development of a permanent stoma in laparoscopic intersphincteric resection (LS-ISR) for ultralow rectal adenocarcinoma and to develop and validate a prediction model to predict the probability of permanent stoma after surgery.METHODS:A primary cohort consisting of 301 consecutive patients who underwent LS-ISR was enrolled in this study. Multivariable logistic regression analysis was used to identify risk factors and develop the nomogram. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. An independent validation cohort contained 91 consecutive patients from January 2012 to January 2019.RESULTS:The permanent stoma rate was 11.3% (34/301) in the primary cohort and 18.7% (17/91) in the validation cohort. Multivariable analysis revealed that nCRT (OR, 3.195; 95% CI, 1.169-8.733; P=0.024), ASA score of 3 (OR, 5.062; 95% CI, 1.877-13.646; P=0.001), distant metastasis (OR, 14.645; 95% CI, 3.186-67.315; P=0.001), and anastomotic leakage (OR, 11.308; 95% CI, 3.650-35.035; P<0.001) were independent risk factors for permanent stoma, and a nomogram was established. The AUCs of the nomogram were 0.842 and 0.858 in the primary and validation cohorts, respectively. The calibration curves showed good calibration in both cohorts. Decision curve analysis demonstrated that the nomogram was clinically useful.CONCLUSION:We developed and validated a nomogram for ultralow rectal adenocarcinoma patients who underwent LS-ISR, and the nomogram could help surgeons identify which patients are at a higher risk of a permanent stoma after surgery.

Background Intracorporeal rectal transection at the anorectal junction for ultralow rectal cancer is technically difficult due to pelvic width and limited roticulation, which might require a transanal transection or an oblique transection with multiple firings. These procedures were reported to be associated with the increased risk of morbidity. To address these problems, we presented a novel technique Transanterior Obturator Nerve Gateway (TANG) to transect rectum for ultralow rectal cancer and evaluated its safety and feasibility in this study. Methods A total of 210 consecutive patients who underwent laparoscopic coloanal anastomosis with or without partial intersphincteric resection (CAA/pISR) for rectal cancers between January 2017 and January 2020 were included. Eighty of these patients were analyzed using propensity score matching (PSM). The perioperative characteristics, TANG-related variables, and genitourinary and anal function outcomes were analyzed. Results Among these enrolled patients, 170 patients underwent traditional transection, and 40 underwent TANG transection; the patients were matched to include 40 patients in each group by PSM. After PSM, there were no significant differences in the operating time ( p = 0.351) or bleeding volume ( p = 0.474) between the two groups. However, the TANG group had fewer cases of conversion to transanal transection (0 vs. 13, p < 0.001). Moreover, the patients in TANG group had a more desirable transection with longer distal resection margin (1.7 vs. 1.1 cm, p < 0.001), shorter stapling line (6.6 vs. 10.3 cm, p < 0.001) and fewer stapler firings ( p < 0.001). The overall postoperative complication rates and genitourinary and anal function outcomes were not significantly different between the two groups. Conclusions The TANG approach appears to be a safe, feasible and effective approach for intracorporeal ultralow rectal transection with more distal resection, more vertical transection and fewer stapler firings.

Objective: The surgical indications, resection extent and management principle of lateral lymph node dissection (LLND) in lower rectal cancer have been controversial between Eastern and Western countries. This study aims to provide a theoretical basis for the rational implementation of LLND by reviewing the changes of LLND strategy over the past 30 years in a single-center, and analyzing prognostic factors for the survival outcomes of patients with lateral lymph node metastasis (LLNM). Methods: A retrospective observational study was performed. Clinical data of 289 patients with rectal cancer who received LLND at the Department of General Surgery of Peking University First Hospital from 1990 to 2019 were collected. Patients were divided into three groups based on decades. There were 89 cases in 1990-1999 group, 92 cases in the 2000-2009 group, and 108 cases in the 2010-2019 group. Data analyzed: (1) patient baseline data; (2) surgery and postoperative recovery; (3) lateral lymph node dissection; (4) postoperative survival and prognosis of patients with positive lateral lymph nodes. The surgical methods and pathological results of LLND were compared between groups, and the prognostic risk factors of patients with LLNM were analyzed. Results: A total of 289 patients underwent radical resection with LLND' accounting for 6.3% of the 4542 patients with rectal cancer during the same period in our hospital. Except decade-by-decade increase in tumors with distance from anal verge ≤ 7 cm, the proportion of ulcerated tumors, and the proportion of neoadjuvant radiochemotherapy, the differences in other baseline data were not statistically significant among 3 decade groups (all P>0.05). The proportion of LLND in the 3 groups decreased decade by decade [9.9% (89/898) vs. 8.0% (92/1154) vs. 4.3% (108/2490), χ(2)=40.159, P<0.001]. The proportion of laparoscopic surgery and unilateral LLND increased, while the mean operative time, intraoperative blood loss, surgical complications above grade III and postoperative hospital stay decreased decade by decade. These 289 patients completed a total of 483 lateral dissections, including 95 cases of the unilateral dissection and 194 cases of the bilateral dissection. The proportion of LLND in the 3 groups decreased decade by decade [9.9% (89/898) vs. 8.0% (92/1154) vs. 4.3% (108/2510), P<0.001]. The median number of dissected lymph nodes in the internal iliac artery and obturator regions increased (2 vs. 3 vs. 3, P<0.001), but those in the common iliac and external iliac regions decreased significantly (4 vs. 3 vs. 2, P=0.014). A total of 71 patients with LLNM were identified. The rate of LLNM in the 2010-2019 group was significantly higher than that in the previous two groups [37.0% (40/108) vs. 16.9% (15/89) vs. 17.4% (16/92), P=0.001]. The patients with LLNM showed a poorer overall survival (OS) and disease-free survival (DFS) compared with negative lateral lymph nodes (P<0.001). There were statistically significant differences in 5-year OS rate (30.9% vs. 27.2% vs. 0, P=0.028) and 5-year DFS rate (28.3% vs. 16.0% vs. 0, P=0.038) among patients with only internal iliac lymph node metastasis, patients with only obturator lymph node metastasis, and patients with external iliac or common iliac lymph node metastasis. Multivariate analysis of prognostic factors showed that external iliac or common iliac lymph node metastasis was an independent risk factor for OS (HR=1.649, 95%CI: 1.087-2.501) and DFS (HR=1.714, 95%CI: 1.173-2.504) in patients with LLNM (all P<0.05) . The OS and DFS were not significant different in patients with LLNM among 3 decade groups. Conclusions: In the past decade, the proportion of LLND in rectal cancer has decreased significantly. However, LLNM rate has been significantly increased due to preoperative imaging assessments focusing on suspicious LLNM without compromising the survival. Internal iliac artery and obturator lymph nodes can be regarded as regional lymph nodes with a satisfactory prognosis after LLND. For suspected external iliac or common iliac lymph node metastasis, the significance of LLND remains to be further evaluated.

目的 评价腹腔镜后盆腔脏器切除术治疗局部进展期直肠癌的安全性及近期疗效,分析腹腔镜后盆腔脏器切除术操作要点.方法 回顾性分析2014年4月至2019年10月由同一术者行腹腔镜后盆腔脏器切除术的15例局部进展期直肠癌患者临床资料,包括手术相关指标、病理指标和随访情况.结果 15例患者均顺利完成腹腔镜后盆腔脏器切除术(LPPE),无中转开腹病例.消化道重建方式中9例为结肠—直肠/肛管吻合,3例为乙状结肠造瘘,3例为远端直肠封闭近端乙状结肠造瘘;阴道处理方式中12例为阴道残端缝合,3例为阴道后壁切除.3例术前MRI检查提示侧方淋巴结肿大而行单侧侧方淋巴结清扫;1例联合膀胱部分切除,1例联合输尿管部分切除,1例联合右半结肠切除.平均手术时间(268.3±80.9)min,中位出血量150(100,200)mL,平均术后住院时间(15.2±7.2)d,2例患者出现术后并发症,1例为阴道残端瘘,保守治疗3周后痊愈出院,1例为直肠吻合口漏继发直肠阴道瘘,后期遗留吻合口狭窄,至今保护性回肠造口未能还纳.全组无术后膀胱功能恢复延迟.所有手术均为R0切除,11例为癌性侵犯,8例伴区域淋巴结转移.中位随访时间2年,随访期间4例患者因肿瘤术后复发转移死亡,11例患者实现无病生存,中位生存时间25个月.结论 腹腔镜后盆腔脏器切除术治疗局部进展期直肠癌安全可行,近期疗效尚可,远期肿瘤学效果仍需进一步扩大样本进行研究.

Objective:To evaluate the factors affecting the degree of radical resection and the prognosis of patients with locally recurrent rectal cancer (LRRC).Methods:A retrospective case-control study was performed. Clinical data of 111 patients with LRRC undergoing operation at the General Surgery Department of Peking University First Hospital from January 2009 to August 2019 were analyzed retrospectively. The "Peking University First Hospital F typing" was performed according to the preoperative images of the pelvic involvement. The pelvis was assigned into four directions: the front wall, lateral sides of the pelvic wall and the sacrum. According to the degree of pelvic wall involvement, F typing included F0 type (no involvement of the pelvic wall, the cancer only involved the adjacent organs or invaded conteriorly the urinary tract, genital organs or small intestine), F1 type (cancer involved the pelvic wall in one direction, such as the sacrum, or one side of the pelvic wall), F2 type (cancer involved the pelvic wall in two directions) and F3 type (cancer involved the pelvic wall in three directions). Case inclusion criteria: (1) LRRC was confirmed by imaging and pathological examination of samples (puncture or endoscopic biopsy); (2) complete clinical and follow-up data; (3) informed consent of patient. Those with dysfunction of heart, lung, etc., intolerance of operation, F3 type indicated by image, and distant metastasis were excluded. The degree of radical resection was evaluated according to the postoperative pathological results. Patients were followed up every 12 months and related examinations were arranged. The univariate analysis of radical resection was performed by χ 2 test, and the multivariate analysis was performed by logistic methods. The survival rate was calculated by Kaplan-Meier method and the survival curve was drawn. The survival rate was compared by log-rank test. Cox proportional hazards model was used to analyze the factors affecting the prognosis of patients with LRRC. Results:A total of 111 patients were included in this study. Of 111 patients, 59 were male and 52 were female; recurrent age of 36 cases was ≥ 65 years old; CEA level of 48 cases was ≥15 μg/L. According to the "Peking University First Hospital F typing", 70 cases were F0 type, 38 F1 type and 3 F2 type. Surgical procedures were abdominoperineal resection ( n=28), posterior pelvic exenteration ( n=32), and total pelvic exenteration ( n=51, including 1 case of TPE combined with sacrectomy). According to the postoperative pathological results, R0, R1 and R2 resections were 83, 20 and 8 cases, respectively. Univariate analysis showed that the degree of radical resection was associated with the secondary surgical procedure, F typing and lymph node metastasis (all P<0.05). Multivariate analysis showed that F typing (F1-F2) was an independent risk factor for non- R0 resection (OR=37.256, 95%CI:8.572 to 161.912, P<0.001). The morbidity of operative complications was 22.5% (25/111); the perioperative mortality was 1.8% (2/111); the local recurrence rate after the second operation was 37.8% (42/111). The 3- and 5-year overall survival rates were 41.2% and 21.9% respectively. The 3-year survival rates of patients with and without postoperative chemotherapy were 52.7% and 32.4% respectively ( P=0.005). The 3-year survival rates of patients with lower (<15 μg/L) and higher CEA level (≥15 μg/L) were 52.9% and 24.3% respectively ( P<0.001). The 3-year survival rates of patients with R0, R1 and R2 resection were 49.8%, 21.3% and 8.5% respectively ( P=0.002). The 3-year survival rates of patients with F0, F1 and F2 type were 52.7%, 22.0% and 0 respectively ( P<0.001). Cox analysis confirmed that the degree of radical resection (HR=2.088, 95%CI:1.095 to 3.979, P=0.025), the CEA level before the secondary operation (HR=1.857, 95%CI:1.157 to 2.980, P=0.010) and postoperative chemotherapy (HR=1.826, 95%CI:1.137 to 2.934, P=0.013) were independent factors affecting the prognosis. Conclusions:The indication of LRRC surgical treatments must be strictly limited. Evaluation of the fixation site to the pelvic wall is helpful for improving the rate of R0 resection. Lower preoperative CEA level, radical resection and postoperative chemotherapy are protective factors of prolonged overall survival time of patients with LRRC.

OBJECTIVE:To investigate the value of neoadjuvant chemoradiotherapy (nCRT) combined with total pelvic exenteration (TPE) in the treatment of primary T4b rectal cancer.METHODS:A retrospective cohort study was conducted to analyze the clinicopathological data of 31 patients with primary T4b rectal cancer who underwent TPE from January 2008 to December 2015 at Peking University First Hospital.INCLUSION CRITERIA:preoperative clinical stage (cTNM) was defined as cT4b primary rectal cancer with only front wall Invasion; the lower edge of tumor was within 10 cm from the anal margin; TPE was performed; R0 resection was confirmed by pathology. Patients with recurrent rectal cancer, distant metastasis, and undergoing TPE for non-rectal tumors were excluded. Patients were divided into nCRT group and non-nCRT group according to whether receiving nCRT before surgery. The nCRT group received long course radiotherapy (total dose 50 Gy in 25 daily fractions) with concomitant chemotherapy (Capecitabine), and the surgery was performed 6-8 weeks after the neoadjuvant chemoradiation, while the non-nCRT group received surgery directly. The intraoperative, postoperative and pathological conditions and local recurrence were compared between the two groups. The survival curves were drawn by Kaplan-Meier method and the survival of two groups were compared.RESULTS:A total of 31 patients were enrolled, including 13 patients in the nCRT group and 18 patients in the non-nCRT group. The baseline data, such as age, duration of disease, preoperative basic disease, body mass index, smoking rate, and tumor distance from the anal margin, were not significantly different between the two groups (all P>0.05). In the nCRT group and non-nCRT group respectively, the ratio of anal preservation was 30.8%(4/13) and 38.9%(7/18) (P=0.468), the median intraoperative blood loss was 1 000 ml and 800 ml (P=0.644), the operation time was (531.7±137.2) minutes and (498.0±90.1) minutes (P=0.703), the median hospital stay was 18 days and 14 days (P=0.400), the morbidity of complications within 30 days after surgery was 23.1%(3/13) and 38.9%(7/18)(P=0.452), the incidence of postoperative abdominal abscess was 15.4%(2/13) and 0 (P=0.168), the proportion of secondary surgery was 7.7%(1/13) and 11.1%(2/18)(P=1.000), whose differences were not significantly different. The proportion of postoperative pathological pT4b in whole group was 58.1%(18/31), including 53.8%(7/13) in nCRT group and 61.1%(11/18) in non-nCRT group, which was not significantly different between the two groups (P=0.691). The number of harvested lymph node in nCRT group was 13.5±5.9, which was significantly less than 23.0±11.8 in non-nCRT group (P=0.013). There was no pathological complete remission (ypCR) case in nCRT group, and among 13 patients, tumor regression grade (TRG) of 2, 3, 4, and 5 was in 1 case (7.7%), 6 cases (46.2%), 5 cases(38.5%), and 1 case (7.7%), respectively. The median follow-up time was 33 (2 to 115) months, and the follow-up rate was 93.5%(29/31). One case was lost in both the nCRT group and non-nCRT group. The 3-year disease-free survival rate was 43.5% in pooled data, and was 43.6% and 43.3% in nCRT group and non-CRT group respectively without significant difference (P=0.833). The 3-year overall survival rate was 51.1% in pooled data, and was 45.7% and 54.7% in nCRT group and non-nCRT group respectively without significant difference (P=0.653).The local recurrence rate of nCRT and non-nCRT groups was 8.3%(1/12) and 5.9%(1/17) respectively, and the distant metastasis rate was 50.0%(6/12) and 41.2%(7/17) respectively, whose differences were not statistically significant as well (P=1.000 and P=0.865, respectively).CONCLUSION:For primary T4b rectal cancer which can achieve R0 resection through total pelvic exenteration, neoadjuvant chemoradiotherapy has not been demonstrated any advantage in tumor regression, reducing local recurrence, or improving survival, and may increase postoperative complications.

TF/FVIIa (Tissue Factor/Active Coagulation factor VII) and EGFR (Epidermal Growth Factor Receptor) signaling both promote malignant progression of colorectal cancer. However, the crosstalk of these two signaling pathways in human colorectal cancer cells remains unclear. Here we detected the changes of mRNA profile in human colorectal cancer cell SW620 exposed to FVIIa. Microarray showed that mRNA levels of EGFR ligands were significantly upregulated. Western blot analysis confirmed the upregulation of EGFR ligands and the phosphorylation of EGFR at tyrosine-845 in colorectal cancer cells exposed to FVIIa. However, knockdown of TF by RNAi could block the upregulation of EGFR ligands induced by FVIIa stimulation. On the other hand, the expression of components of TF/FVIIa signaling was significantly upregulated in LoVo cells stimulated by EGF. However, the crosstalk between the two signaling pathways could not be detected in HT-29 colon cancer cells bearing wild-type KRAS. Taken together, our study suggest that the crosstalk between TF/FVIIa and EGFR signaling pathways in colon cancer cells depends on KRAS mutation.

Objective To detect the expression profile changes of human colon cancer cell SW620 when its tissue factor/active coagulation factor Ⅶ (TF/FⅦa) pathway is activated and discover new downstream effectors of TF/FⅦa pathway.Methods Total RNAs of two groups of SW620 cells (treated with 100 nmol/L FⅦa for 24 h in treament group and identical volume of phosphate-buffered saline in control group) were extracted and hybridization was performed on gene chips.Differentially expressed genes were screened and part of the gene expressions were verified using real-time reverse transcriptase-polymerase chain reaction (RT-qPCR),network of differentially expressed genes and pathways were analysed.Gene expressions of epidermal growth factor receptor (EGFR) ligands amphiregulin (AREG),epiregulin (EREG),Heparin-binding EGF-like growth factor (HB-EGF),transforming growth factor-α (TGF-α),β-cellulin (BTC),epidermal growth factor (EGF) and epigen (EPGN) were detected by RT-qPCR following activation of TF/FⅦa pathway of SW620,SW480,LoVo and HCT116 cells.Results There were 263 differentially expressed genes with a test/control fold change of ≥ 1.5 (150 upregulated,113 downregulated).Network analysis showed that genes of laminin-integrin system,pathways of glycometabolism and cancer related pathways were associated with TF/F Ⅶ a signalling's activation.Gene expressions of AREG,EREG,HB-EGF and TGF-α of SW620 were upregulated in a time-dependent manner and reached peaks at 12 h,relative gene expressions of control group vs treatment group were 0.92±0.13 vs.5.50 ±0.91(P=0.000),1.00±0.15 vs.2.17±0.44(P=0.002),1.11 ±0.08 vs.1.73 ±0.32(P =0.005),0.94 ±0.12 vs.1.49 ±0.09(P =0.002).When TF/FⅦa pathway was activated for 6 h,in SW480 cells,gene expressions of AREG and BTC were significantly upregulated,relative expressions were t.00 ±0.25 vs.2.19 ±0.60(P =0.033),1.00 ±0.23 vs.4.41 ±0.56 (P =0.001),expression of EPGN was not detected,in LoVo cells,AREG and BTC were significantly upregulated and EGF was significantly downregulated:1.00 ± 0.19 vs.1.87 ± 0.39 (P =0.025),1.00 ± 0.01 vs.1.86±0.06 (P=0.000),1.00±0.08 vs.0.68 ±0.16 (P=0.035),in HCT116 cells,AREG,EREG,HB-EGF,TGF-α,and EGF were significantly upregulated:1.00 ± 0.09 vs.1.38 ± 0.06 (P=0.004),1.00±0.02 vs.1.14±0.03 (P=0.003),1.00±0.03 vs.1.85 ±0.11 (P=0.000),1.00±0.05 vs.1.26±0.10 (P=0.015),1.00±0.26 vs.1.91 ±0.22 (P=0.010).Conclusion In SW620 cells,activation of TF/FⅦa pathway can induce expression changes of genes of laminin-integrin system,pathways of glycometabolism and cancer related pathways and EGFR pathway,these effectors and pathways may take critical roles in TF/FⅦa pathway-related bioeffect.

OBJECTIVE:To preliminarily verify the cross talk between tissue factor/active coagulation factor VII (TF/FVIIa) and epidermal growth factor receptor (EGFR) pathways in human colon cancer cells in culture.METHODS:FVIIa was treated to HT-29 (KRAS-wild type) and LoVo (KRAS-mutant) colon cancer cells to activate TF/FVIIa pathway, qRT-PCR and Western blot were used to detect the expressions of amphiregulin (AREG) and epiregulin (EREG), ligands of EGFR on mRNA and protein levels, respectively. After knocking down expression of TF by TF-targeted siRNA transfection, FVIIa was treated and mRNA expressions of AREG and EREG were detected to see whether the FVIIa-induced effects were dependent on TF. Expressions of mRNA of TF and FVII were detected by qRT-PCR following the activation of EGFR pathway by treatment with epidermal growth factor (EGF) to HT-29 and LoVo cells.RESULTS:After TF/FVIIa pathway was activated, for HT-29 cells, expressions of AREG (on mRNA level) and EREG (both on mRNA and protein level) were significantly down-regulated versus those of control group, gene expressions of AREG and EREG were 0.55±0.09 vs.0.99 ±0.09, 0.67±0.10 vs.1.02±0.02, protein expressions of EREG were 0.54±0.09 vs.1.04±0.13, all P<0.05. For LoVo cells, expressions of AREG (both on mRNA and protein level) and EREG (on protein level) were significantly up-regulated versus those of control group, gene expression of AREG were 1.87±0.39 vs. 0.93±0.23, protein expressions of AREG and EREG were 3.09±0.73 vs.1.11±0.21, 1.53±0.19 vs.0.97±0.23, all P<0.05. The regulating effect of AREG and EREG mRNA expression by FVIIa in HT-29 and LoVo cells could both be partly blocked by knocking down TF expression. For HT-29 cells, activation of EGFR pathway induced no significant TF mRNA expression, FVII mRNA expression was not detected. However,for LoVo cells, activation of EGFR pathway induced significantly higher mRNA expressions of both TF and FVII, expressions were 1.53±0.23 vs.1.00±0.23, 53.20±6.08 vs.1.00±0.15, all P<0.05.CONCLUSION:In colon cancer cell LoVo, when activated, TF/FVIIa pathway and EGFR pathway could interact through upregulating the other pathway's effectors, and mutant KRAS might play a critical role in the two pathways' cross talk.

Background Colorectal carcinoma is one of the most common malignant tumors. Despite advances in therapy, mortality is still very high. The aim of this study was to evaluate the expression of paxillin in the human colon adenocarcinoma cell line SW480 and its role in cell cycle and apoptosis. We also investigated the expression of paxillin in colorectal carcinoma tissues and its relationship to clinicopathological features and survival. Methods Paxillin short hairpin RNA (shRNA) was constructed and transfected into the colon adenocarcinoma cell line SW480. The influence of paxillin shRNA on the cell cycle and cell apoptosis was analyzed by flow cytometry. Immunohistochemistry staining was used to assess the expression of paxillin and its association with the expression of carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, p53 and Bcl-2 in 102 patients with primary colorectal carcinoma. Western blotting was also used to investigate the expression of paxillin. Medical records were reviewed and a clinicopathological analysis was performed. Results In vitro, the percentage of cells in S phase was (45.23±1.05)%, (43.53±1.23)%, and (36.13±0.57)% in the blank control group, negative control group, and paxillin shRNA group respectively. It was significantly decreased in the paxillin shRNA group ( P =0.000). The early apoptosis index of the paxillin shRNA group (17.2±1.18%) was significantly increased compared to the control shRNA group ((13.17±1.15)%, P =0.013). Paxillin was positive in 71 (69.6%) patients, and it was found to be overexpressed in tumor tissues compared with normal adjacent tissues. Paxillin positive rate was higher in patients who are less than 50-years old (100.0% vs. 65.6%, P =0.016). Paxillin expression was associated with a high histologic grade of carcinoma (81.4% vs. 61.0%, P =0.031), a high rate of regional lymph node metastasis (22.5% vs. 13.0%, P =0.031), mesenteric artery lymph node metastasis (100.0% vs. 64.8%, P =0.008), distant metastasis (94.1% vs. 64.7%, P =0.016) and a high Tumor Node Metastasis (TNM) stage (94.1%, 73.2%, 60.0%, and 50%, P =0.030). Multivariate analyses revealed that recurrence was associated with the rate of regional lymph node metastasis ( P =0.001) and paxillin expression ( P =0.024). Multivariate analysis indicated that the overall survival is related to the TNM stage ( P =0.000). Conclusions In vitro, paxillin may promote cell proliferation and inhibit apoptosis in SW480 cells. Paxillin may be a potential metastasis predictor, and an independent prognosis factor of recurrence. It may also be related to poor patient outcomes, but was not an independent predictor of survival.

Objective To investigate the relationship between the expression level of deleted in liver cancer-1 (DLC-1) gene and colon cancer staging or lymph nodes metastatic ratio.Methods Total 60 resection specimens were collected from colon cancer patients between September 2009 and September 2011,and 10 resection specimens from patients with trauma,colonic diverticulitis and colitis were used as the control.The DLC-1 mRNA level was measured with real time quantitative RT-PCR in colon cancer patients and the control group.TNM system was used for colon cancer staging.The linear correlation analysis was performed to determine the relationship between DLC-1 expression level and colon cancer staging or lymph nodes metastatic ratio.Results The mRNA level of DLC-1 was significantly reduced in colon cancer tissues in comparison to that in adjacent normal tissues,while adjacent tissues showed significantly lower DLC-1 level than normal clone tissues.The expression of DLC-1 was negatively correlated with both colon cancer stage and the lymph nodes metastatic ratio (r =0.46,P ＜ 0.05).Conclusions DLC-1 expression was negatively correlated with pathological stage and lymph node metastasis ratio,indicating a critical role of DLC-1 gene in colon cancer genesis,which provide a possible new direction for colon cancer research.

Objective To investigate the effects of exogenous secreted protein acidic and rich in cysteine (SPARC) on proliferation,migration and invasion ability of human pancreatic cancer cell lines.Methods The cuhured Mia PaCa-2 and PANC-1 pancreatic cancer cells were established in the presence of different concentrations (0,0.5,1.0,3.0,5.0,10.0 mg/L) or absence of exogenous SPARC as experimental and control groups.The change of proliferation was measured by methyl thiazol tetrazolium (MTT) assay.The 24 h cultured Mia PaCa-2 and PANC-1 pancreatic cancer cells were established in the presence (5 mg/L) or absence of exogenous SPARC as experimental and control groups,and the change of migration ability was detected by single cell migration assay and the change of invasion ability by Matrigel invasion assay respectively.Results Exogenous SPARC could inhibit the proliferation of cells in a concentration-dependent manner.Cell proliferation was inhibited in the presence of 10.0 mg/L exogenous SPARC by (32.8 ± 7.4) ％ and (32.5 ± 1.8) ％ in Mia PaCa-2 and PANC-1,respectively.5.0 mg/L SPARC reduced the distance covered within 24 h by 26％ and 39％,and in the presence of 5.0 mg/L SPARC the number of invasive cells was inhibited by 30％ and 56％ in 24 h,respectively.Conclusion Exogenous SPARC could inhibit the proliferation,migration and invasion ability in pancreatic cancer cells,suggesting extracelluar matrix may affect biological functions of malignant tumors.

Secreted protein acidic and rich in cysteine (SPARC) gene has been shown to be epigenetically silenced in several cancers. We investigated the loss of expression and promoter methylation of this tumor suppressor gene in gastric cancers and correlated the data with clinicopathological features. We observed the loss of SPARC mRNA and SPARC protein expression in 7 of 10 (70%) gastric cancer cell lines. Upon treatment of expression-negative cell lines with a demethylating agent, expression of mRNA and protein was restored in all cells. Methylation rate of SPARC gene was 80% in ten gastric cancer cell lines and 74% (163 of 220) in primary tumors, while it was 5% in normal gastric mucosa (n = 40). In intestinal gastric cancer, SPARC methylation correlated with a negative prognosis (P < 0.001; relative risk 2.754, 95% confidence interval 1.780–4.261). Immunostaining revealed that SPARC protein was overexpressed in stromal fibroblasts adjacent to neoplastic epithelium but rarely expressed in the primary gastric cancer cells. These results implicate SPARC promoter methylation as an important factor in the tumorigenesis of gastric carcinomas and provide new insights into the potential use of SPARC as a novel biomarker and the potential clinical importance in human gastric cancers.

Secreted protein acidic and rich in cysteine (SPARC) is a glycoprotein which plays multiple roles in different types of cancer. Our previous study showed that SPARC overexpression inhibited the growth and angiogenesis of tumors, and reduced expression of vascular endothelial growth factor (VEGF). However, the relationship between SPARC expression and clinicopathological factors of gastric cancer (GC) is controversial, and the role of SPARC in GC remains unclear. We evaluated expression of SPARC in 65 human GC tissues using immunohistochemistry (IHC). The results indicated that SPARC expression was negatively correlated with clinicopathological factors of GC. In vitro assay showed that SPARC overexpression decreased proliferation and clonogenicity by suppressing CD44 expression. In addition, SPARC overexpression inhibited VEGF induced proliferation and arrested cell cycle of GC cells by reducing the activation of VEGFR2, ERK1/2 and AKT signaling pathways. SPARC suppressed the invasion and migration of GC by reducing MMP-7, MMP-9, N-cadherin, Sp1 and p-ERK1/2 expression. In the in vivo assay, cancer metastasis mouse models were established by tail vein injection. The results revealed that the lung metastases of SPARC-overexpressing GC cells in the mice were much fewer than those of control cells.

Colon cancer may invade the adjacent organ in the absence of distant metastasis, which is called stage T4bM0 colon cancer according to the 7th edition of TNM staging system. It is not rare in clinical setting, and usually recognized intraoperatively. How to deal with this situation is a big challenge for the surgeons. It is difficult to distinguish between dense adhesion and cancerous invasion. Intraoperative biopsy should be avoided because of the risk of tumor cell dissemination and frozen often gives false-negative results. After evaluating the resectability of the tumor sufficiently, the surgeon should make every effort to do an en bloc multivisceral resection and to achieve a margin-free (R0) resection if there is no absolute contraindication. This effort will bring long-term prognosis benefit for the patients with stage cT4bM0 colon cancer.

Objective To investigate the surgical treatment strategies and prognostic factors of cT4bM0 primary rectal cancer.Methods The clinical data of 53 patients with cT4bM0 primary rectal cancer who were admitted to the First Hospital of Peking University from January 2000 to December 2010 were retrospectively analyzed.All the patients received en-bloc multivisceral resection and postoperative chemotherapy.The survival and prognostic factors were analyzed.The patients were followed up via out-patient examination,phone call or mail,and the follow-up was ended till December 2012.The survival curve was drawn using the Kaplan-Meier method,and the survival was analyzed using the Log-rank test.Uni-and multivariate analysis were done using chisquare test and COX's proportional hazard model.Results Of all the 53 patients,20 received posterior pelvic exenteration (PPE),20 received total pelvic exenteration (TPE),3 received low anterior resection (LAR) +local resection of ballder,2 received LAR + ovariectomy,2 received LAR + local resection of ureter,1 received LAR + local resection of posterior vaginal wall,1 received LAR + vesiculectomy and vesectomy,3 received abdominoperineal resection (APR) + local resection of posterior vaginal wall,1 received APR + sacrectomy.R0 resection was achieved in all the patients.No intraoperative death was observed,and the incidence of postoperative complication was 9.4％ (5/53).The results of postoperative pathological examination showed that 2 patients were with well-differentiated adenocarcinoma,41 with moderate-differentiated adenocarcinoma,and 10 with poorly differentiated adenocarcinoma.Twenty-four patients were with lymph node metastasis.Four patients were in TNM stage Ⅰ,25 in TNM stage Ⅱ and 24 in TNM stage Ⅲ.Fifty-three patients were followed up postoperatively,and the median time for follow-up was 33 months (range,4-116 months).The overall 5-year survival rates was 57.3％.The 5-year survival rate for patients with or without lymph node metastasis were 77.1％ and 30.4％,respectively,with significant difference between the 2 groups (x2 =7.374,P ＜ 0.05).The 5-year survival rates of patients with malignant infiltration and inflammatory adhesion mere 51.0％ and 68.5％,with no significant difference (x2=1.148,P ＞0.05).The 5-year survival rates of patients with malignant infiltration and inflammatory adhesion in stage Ⅱ were 74.6％ and 85.7％,with no significant difference between the 2 groups (x2=0.118,P ＞ 0.05).The 5-year survival rates of patients with malignant infiltration and inflammatory adhesion in stage Ⅲ were 28.8％ and 37.5％,with no significant difference between the 2 groups (x2 =0.959,P ＞ 0.05).The results of univariate analysis showed that lymph node metastasis and TNM stage were the risk factors influencing the prognosis of patients with cT4bM0 primary rectal cancer (x2=6.468,6.596,P ＜ 0.05).The results of multivariate analysis showed that lymph node metastasis was the independent risk factor (RR =3.797,P ＜ 0.05).Conclusions En-bloc multivisceral resection should be the first surgical treatment choice for patients with cT4bM0 primary rectal cancer,and lymph node metastasis is the independent risk factor.Under the same N stage,the prognosis of patients with malignant infiltration or inflammatory adhesion is similar if R0 resection is achieved.