BACKGROUND:Colorectal cancer (CRC) patients with stage pT4b are a complex group as they show differences in tumor-infiltrated organs. Patients with the same stage often exhibit differences in prognosis after multivisceral resection (MVR). Thus far, some important prognostic factors have not been thoroughly investigated. Here, we identified the prognostic factors influencing CRC patients at the pT4bN0M0 stage to stratify the prognostic differences among patients. MATERIALS AND METHODS:A retrospective analysis was conducted on patients diagnosed with locally advanced CRC and who underwent MVR at three medical institutions from January 2010 to December 2021. The prognostic factors affecting the survival of CRC patients at pT4bN0M0 stage were identified by multivariate Cox proportional hazard models. We then classified the prognosis into different grades on the basis of these independent prognostic factors. RESULTS:We enrolled 690 patients with locally advanced CRC who underwent MVR; of these, 172 patients with pT4bN0M0 were finally included. Patients with digestive system [overall survival (OS): hazard ratio (HR)=0.441; 95% confidence interval (CI)=0.217-0.900; P =0.024; disease-free survival (DFS): HR=0.416; 95% CI=0.218-0.796; P =0.008) or genitourinary system invasion (OS: HR=0.405; 95% CI=0.193-0.851; P =0.017; DFS: HR=0.505; 95% CI=0.267-0.954; P =0.035) exhibited significantly better OS and DFS as compared to those with gynecological system invasion, while the OS and DFS were similar between the digestive system and genitourinary system invasion groups (OS: HR=0.941; 95% CI=0.434-2.042; P =0.878; DFS: HR=1.211; 95% CI=0.611-2.403; P =0.583). Multivariate analysis showed that age (OS: HR=2.121; 95% CI=1.157-3.886; P =0.015; DFS: HR=1.869; 95% CI=1.116-3.131; P =0.017) and type of organs invaded by CRC (OS: HR=3.107; 95% CI=1.121-8.609; P =0.029; DFS: HR=2.827; 95% CI=1.142-6.997; P =0.025) were the independent prognostic factors that influenced the OS and DFS of CRC patients with pT4bN0M0 disease. The OS and DFS of patients showing invasion of the gynecological system group were significantly worse ( P =0.004 and P =0.003, respectively) than those of patients with invasion of the nongynecological system group. On the basis of the above-mentioned two independent prognostic factors, patients were assigned to high-risk, medium-risk, and low-risk groups. Subgroup analysis showed that the OS and DFS of the medium-risk and high-risk groups were significantly worse ( P =0.001 and P =0.001, respectively) than those of the low-risk group. CONCLUSION:Patients with pT4bN0M0 CRC show significant differences in their prognosis. The type of organs invaded by CRC is a valuable indicator for prognostic stratification of CRC patients with pT4bN0M0.

Background Fluorescence-guided lymphadenectomy (FLND) using indocyanine green (ICG) has emerged as a promising technique to enhance the accuracy of lymphadenectomy in rectal cancer surgery. Effective lymphadenectomy is crucial for improving prognosis in patients with advanced rectal cancer, but it remains technically challenging and controversial. Methods This prospective nonrandomized controlled study was conducted involving 129 patients underwent laparoscopic surgery, and 64 patients assisted by FLND. Patients received submucosal ICG injections before surgery to facilitate FLND. Lymph nodes were categorized as station 251, station 252, or station 253 based on their anatomical locations. The effectiveness of FLND was evaluated by comparing the number of harvested and metastatic lymph nodes between the FLND and control groups. Results The FLND group demonstrated a significantly higher median number of harvested station 253 lymph nodes compared to the control group (2.0 vs. 1.0, P = 0.007). The FLND cohort had a shorter postoperative hospital stay (6 days vs. 8 days, P < 0.001) and similar rates of postoperative complications compared to the control cohort. The study found no significant differences in the median number of harvested station 251 (10.0 vs. 11.0, P = 0.872) and station 252 (6.0 vs. 5.0, P = 0.369) lymph nodes between the groups. Univariate and multivariate analyses indicated that FLND significantly increased the harvested lymph node count. Conclusion Radical surgery assisted by FLND significantly improves the accuracy and yield of lymphadenectomy in mid-low rectal cancer, enhancing surgical outcomes and patient prognosis. Future advancements in fluorescence imaging and related technologies hold promise for further improving the clinical effectiveness of this technique.

3533 Background: There is a lack of standardization in the comprehensive treatment strategies for rectal cancer with lateral lymph node metastasis (LLNM), which results in an unfavorable oncological outcome. We conducted the present phase II trial by performing neoadjuvant chemotherapy with 5-fluorouracil, irinotecan, and oxaliplatin (FOLFOXIRI) regimen plus lateral lymph node dissection (LLND) for resectable rectal cancer with LLNM to decrease the lateral recurrence and distant metastasis rates. Methods: This prospective, single-arm phase II trial was conducted from April 2018 to February 2023, and included patients with cT3-4aN+M0 resectable rectal cancer and clinical suspicion of LLNM based on preoperative MRI. Patients were treated with three cycles of FOLFOXIRI, and those with evidence of treatment response continued to receive two cycles of FOLFOXIRI. Total mesorectal excision plus LLND was performed at 3-4 weeks after completing the last cycle of preoperative chemotherapy, followed by 3 cycles of XELOX. Results: A total of 58 patients engaged in this research, and 53 were finally enrolled. The pathological examination detected microscopic LLNM in 12 (22.6%) patients. The pathologic complete response (pCR) rate was 11.3% (6/53), and the downstaging (ypstage 0 to 1) rate was 30.2% (16/53). DFS events were observed in 7 patients, and OS events were reported in 2 patients after a median follow-up of 30 months. The 3-year DFS rate was 88.3%, the 3-year local recurrence-free survival rate was 94.7%, and the 3-year OS rate was 91.3%. There were 14 (26.4%) cases with six grade 3/4 adverse events. Conclusions: Neoadjuvant chemotherapy with the FOLFOXIRI regimen plus LLND can significantly reduce the risk of local recurrence and distant metastasis in resectable rectal cancer with LLNM, which may be a new treatment option. Clinical trial information: NCT04850027 . Variable, n (%) Total pCR (ypT0N0), n (%) 6 (11.3%) Total LNs harvested Median (IQR) 30 (24~40) LLNs harvested Median (IQR) 12 (8~17) Pathological T category ypTis 1 (1.9%) ypT0 6 (11.3%) ypT1 2 (3.8%) ypT2 11 (20.8%) ypT3 31 (58.5%) ypT4 2 (3.8%) Pathological N category ypN0 30 (56.6%) ypN1 15 (28.3%) ypN2 8 (15.1%) Pathological stage 0 6 (11.3%) I 10 (18.9%) II 17 (32.1%) III 20 (37.7%) Tumor regression grade* 0 1 (1.9%) 1 21 (39.6%) 2 12 (22.6%) 3 12 (22.6%) 4 5 (9.4%) Pathological LLN status Positive 12 (22.6%) Negative 41 (77.4%) Histologic grade Moderate 42 (79.2%) Poor/Mucinous/signet 11 (20.8%) Blood vessel invasion Yes 11 (20.8%) No 42 (79.2%) Perinervous invasion Yes 12 (22.6%) No 41 (77.4%)

Background Radical surgery remains the primary option for locally recurrent rectal cancer (LRRC) as it has the potential to considerably extend the patient's lifespan. At present, the effectiveness of laparoscopic surgery for LRRC remains unclear. Methods The clinical data of LRRC patients who were admitted to the Cancer Hospital of the Chinese Academy of Medical Sciences between 2015 and 2021 were retrospectively analyzed in this study. Patients were categorized into two groups, namely the open group and the laparoscopic group, based on the surgical method used. The short-term outcomes and long-term survival between the two groups were compared. Results Curative surgery was performed on 111 patients who were diagnosed with LRRC. After propensity score matching, a total of 84 patients were included and divided into the laparoscopic group (42 patients) and the open group (42 patients). The laparoscopic group had less intraoperative bleeding (100 vs. 300, P = 0.023), a lower postoperative complication rate (19.0% vs. 42.9%, P = 0.018), and a lower incidence of wound infection (0 vs. 14.3%, P = 0.026). Additionally, the laparoscopic group had a higher R0 resection rate than the open group (92.9% vs. 83.3%, P = 0.313), as well as a shorter length of hospital stay (9.5 vs. 11.5 days, P = 0.304), although these differences were not statistically significant. The laparoscopic group had higher 3-year overall survival (86.3% vs. 58.9%, P = 0.022) and 3-year disease-free survival (60.6% vs 32.7%, P = 0.015). Conclusions In comparison to open surgery, laparoscopic surgery is linked to less bleeding during the operation, quicker recovery after the surgery, and a lower incidence of infections at the surgical site. Moreover, laparoscopic surgery for LRRC might yield superior long-term survival outcomes.

BACKGROUND:It remains unclear whether laparoscopic multisegmental resection and anastomosis (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 inclusion and exclusion criteria, 109 patients who received right hemicolectomy together with anterior resection of the rectum or right hemicolectomy and sigmoid colectomy were finally included in the study. Patients were divided into the LMRA and OMRA groups (n = 68 and 41, respectively) according to the surgical method used. The groups were compared regarding the surgical procedure's short-term efficacy and its effect on long-term patient survival.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.

Phosphofructokinase, platelet (PFKP) is a rate-limiting enzyme of glycolysis that plays a decisive role in various human physio-pathological processes. PFKP has been reported to have multiple functions in different cancer types, including lung cancer and breast cancer. However, no systematic pancancer analysis of PFKP has been performed; this type of analysis could elucidate the clinical value of PFKP in terms of diagnosis, prognosis, drug sensitivity, and immunological correlation. Systematic bioinformation analysis of PFKP was performed based on several public datasets, including The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), Genotype-Tissue Expression Project (GTEx), and Human Protein Atlas (HPA). Prospective carcinogenesis of PFKP across cancers was estimated by expression analysis, effect on patient prognosis, diagnosis significance evaluation, and immunity regulation estimation. Then, pancancer functional enrichment of PFKP was also assessed through its effect on the signaling score and gene expression profile. Finally, upstream expression regulation of PFKP was explored by promoter DNA methylation and transcription factor (TF) prediction. Our analysis revealed that high expression of PFKP was found in most cancer types. Additionally, a high level of PFKP displayed a significant correlation with poor prognosis in patients across cancers. The diagnostic value of PFKP was performed based on its positive correlation with programmed cell death-ligand 1 (PD-L1). We also found an obvious immune-regulating effect of PFKP in most cancer types. PFKP also had a strong negative correlation with several cancer drugs. Finally, ectopic expression of PFKP may depend on DNA methylation and several predicated transcription factors, including the KLF (KLF transcription factor) and Sp (Sp transcription factor) families. This pancancer analysis revealed that a high expression level of PFKP might be a useful biomarker and predictor in most cancer types. Additionally, the performance of PFKP across cancers also suggested its meaningful role in cancer immunity regulation, even in immunotherapy and drug resistance. Overall, PFKP might be explored as an auxiliary monitor for pancancer early prognosis and diagnosis.

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.

目的 探讨腹腔镜直肠癌经括约肌间切除术(Ls-ISR)后发生顽固性吻合口狭窄的影响因素及列线图预测模型构建.方法 采用回顾性病例对照研究方法.收集2012年6月至2021年12月2家医学中心收治的495例(北京大学第一医院448例、中国医学科学院肿瘤医院47例)行Ls-ISR患者的临床病理资料;男311例,女184例;年龄为61(20～84)岁.观察指标:(1)吻合口狭窄发生情况.(2)影响Ls-ISR后发生顽固性吻合口狭窄的因素分析.(3)Ls-ISR后发生顽固性吻合口狭窄列线图预测模型构建及评价.采用门诊、电话等方式进行随访,了解患者术后吻合口漏和吻合口狭窄情况.随访时间截至2022年8月.正态分布的计量资料以(x)±s表示,组间比较采用t检验;偏态分布的计量资料以M(范围)表示.计数资料以绝对数表示,组间比较采用x2检验.单因素和多因素分析均采用Logistic回归模型.将单因素分析中P＜0.10的因素纳入多因素分析.采用R软件(3.6.3)构建列线图预测模型.绘制受试者工作特征曲线,以曲线下面积评价效能.结果 (1)吻合口狭窄发生情况.495例患者均施行Ls-ISR,无中转开腹.495例患者术后均获得随访,随访时间为47(8～116)个月.495例患者随访期间,458例未发生吻合口狭窄、37例发生吻合口狭窄.37例发生吻合口狭窄患者中,A级15例、B级3例、C级19例;其中22例为顽固性狭窄.15例A级吻合口狭窄患者扩肛治疗后缓解;3例B级吻合口狭窄患者经球囊扩张及内镜治疗好转;19例C级吻合口狭窄患者行永久性肠造口术.495例 患者随访期间,发生吻合口漏42例(17例顽固性吻合口狭窄);未发生吻合口漏453例(5例顽固性吻合口狭窄),发生吻合口漏和未发生吻合口漏患者中顽固性吻合口狭窄比较,差异有统计学意义(x2=131.181,P＜0.05).(2)影响Ls-ISR后发生顽固性吻合口狭窄的因素分析.多因素分析结果显示:行新辅助治疗、肿瘤距肛缘距离≤4cm、临床N分期为N1～4期是影响Ls-ISR后发生顽固性吻合口狭窄的独立危险因素(风险比=7.297,3.898,2.672,95％可信区间为 2.870～18.550,1.050～14.465,1.064～6.712,P＜0.05).(3)Ls-ISR后发生顽固性吻合口狭窄列线图预测模型构建及评价.根据多因素分析结果,纳入新辅助治疗、肿瘤距肛缘距离、临床N分期,构建Ls-ISR后顽固性吻合口狭窄发生风险的列线图预测模型.受试者工作特征曲线结果显示:Ls-ISR后发生顽固性吻合口狭窄列线图预测模型的曲线下面积为0.739(95％可信区间为0.646～0.833).结论 行新辅助治疗、肿瘤距肛缘距离≤4cm、临床N分期为N1～4期是影响Ls-ISR后发生顽固性吻合口狭窄的独立危险因素,其列线图预测模型可预测患者术后顽固性吻合口狭窄发生率.

Background The diagnostic criteria and effect of persistent descending mesocolon (PDM) on sigmoid and rectal cancers (SRCs) remain controversial. This study aims to clarify PDM patients' radiological features and short-term surgical results. Method From January 2020 to December 2021, radiological imaging data from 845 consecutive patients were retrospectively analyzed using multiplanar reconstruction (MRP) and maximum intensity projection (MIP). PDM is defined as the condition wherein the right margin of the descending colon is located medially to the left renal hilum. Propensity score matching (PSM) was used to minimize database bias. The anatomical features and surgical results of PDM patients were compared with those of non-PDM patients. Results Thirty-two patients with PDM and 813 patients with non-PDM were enrolled into the study who underwent laparoscopic resection. After 1:4 matching, patients were stratified into PDM ( n = 27) and non-PDM ( n = 105) groups. The lengths from the inferior mesenteric artery (IMA) to the inferior mesenteric vein (1.6 cm vs. 2.5 cm, p = 0.001), IMA to marginal artery arch (2.7 cm vs. 8.4 cm, p = 0.001), and IMA to the colon (3.3 cm vs. 10.2 cm, p = 0.001) were significantly shorter in the PDM group than those in the non-PDM group. The conversion to open surgery (11.1% vs. 0.9%, p = 0.008), operative time (210 min vs. 163 min, p = 0.001), intraoperative blood loss (50 ml vs. 30 ml, p = 0.002), marginal arch injury (14.8% vs. 0.9%, p = 0.006), splenic flexure free (22.2% vs. 3.8%, p = 0.005), Hartmann procedure (18.5% vs. 0.0%, p < 0.001) and anastomosis failure (18.5% vs. 0.9%, p = 0.001) were significantly higher in the PDM group. Moreover, PDM was an independent risk factor for prolonged operative time (OR = 3.205, p = 0.004) and anastomotic failure (OR = 7.601, p = 0.003). Conclusion PDM was an independent risk factor for prolonged operative time and anastomotic failure in SRCs surgery. Preoperative radiological evaluation using MRP and MIP can help surgeons better handle this rare congenital variant.

Transverse colon cancer accounts for about 10% of all colonic cancers. The resection of cancers in the transverse colon is technically more challenging, compared with other cancer locations in the colon because the variable anatomy of the middle colic vessels demands excellent surgical skills and the anatomical location of the transverse colon is related to major organs. We report a novel laparoscopic technique for the first time used in surgery of transverse colon cancer which combines a total intracorporeal anastomosis with natural orifice specimen extraction to solve the problems of traditional laparoscopic surgery. A 48-year-old male patient, whose diagnosis was transverse colon adenocarcinoma, was admitted to the hospital. The surgery was performed in accordance with the procedure of totally laparoscopic right hemicolectomy and the specimen was extracted by opening the rectum. Natural orifice specimen extraction surgery has many advantages, including less pain, better cosmesis and minimising risks of complications and also has comparable long-term outcomes compared to conventional laparoscopic surgery.

Abstract Background PFKP (phosphofructokinase, platelet), a rate-limiting enzyme of glycolysis, plays a decisive role in various human physio pathological processes. Multiple function of PFKP in different cancer types was reported, including lung cancer, breast cancer et al. However, systematic pan-cancer analysis of PFKP has not been performed now, which could reflect its clinically value about diagnosis, prognosis, drug sensitivity, and immunological correlation. Methods Systematic bioinformation analysis of PFKP was performed based on several public datasets including TCGA (The Cancer Genome Atlas), CCLE (Cancer Cell Line Encyclopedia), GTEx (Genotype-Tissue Expression Project), and HPA (Human Protein Atlas). Prospective carcinogenesis of PFKP in pan-cancer was estimated by expression analysis, effect on patients’ prognosis, diagnosis significant evaluation, and immunity regulation estimation. Then, pan-cancer function enrichment of PFKP was also accessed through its effect on signaling score and gene expression profile. Finally, upstream expressing regulation of PFKP was explored by promoter DNA methylation and transcription factors (TFs) prediction. Results Our analysis revealed that highly expression of PFKP was found in most cancer types. Meanwhile, high level of PFKP displayed a significant correlation with poor prognosis of patients across pan-cancer. And a fine diagnosis value of PFKP was summarized, especially in its positive correlation with PD-L1 (programmed cell death-Ligand 1). Then, we also found an obvious immunity regulating effect of PFKP in most cancer types. PFKP also had a remarkably negative correlation with several cancer drugs. Finally, ectopic expression of PFKP may depend on DNA methylation and several predicated transcription factors, including KLF (KLF transcription factor) and Sp (Sp transcription factor) family. Conclusion This pan-cancer analysis revealed that high expression level of PFKP might be a fine biomarker and predictor in most cancer types. Meanwhile, performance of PFKP across pan-cancer also implied its meaningful role in cancer immunity regulation even in immunotherapy and drug resistance. All in all, PFKP might be explored as an aux monitor for pan-cancer early prognosis and diagnosis.

BACKGROUND:Laparoscopic surgery is controversial for patients with clinical T4b colorectal cancer (CRC) who require multivisceral resection (MVR). This study aims to explore and compare the safety and long-term oncological outcomes of laparoscopic surgery and open surgery for patients with clinical T4b CRC. MATERIALS AND METHODS:This study was a retrospective cohort study based on a multicentre database. According to the operation method, the patients were divided into a laparoscopic MVR group and an open MVR group. The short-term and long-term outcomes were compared. RESULTS:From January 2010 to December 2021, a total of 289 patients in the laparoscopic MVR group and 349 patients in the open MVR group were included. After propensity score matching, patients were stratified into a laparoscopic MVR group (n = 163) and an open MVR group (n = 163). Compared with the open MVR group, the laparoscopic MVR group had less blood loss (100 vs. 200, p < 0.001), a shorter time to first flatus (3 vs. 4, P < 0.001), a shorter postoperative hospital stay (10 vs. 12, P < 0.001), and a lower incidence of surgical site infection (2.5 % vs. 8.0 %, P = 0.043). The Kaplan-Meier curves showed that the two groups had similar overall survival (P = 0.283) and disease-free survival (P = 0.152). CONCLUSION:Compared with open MVR, laparoscopic MVR had less blood loss, fewer surgical site infection complications, faster recovery and a shorter hospital stay. The long-term survival outcome of laparoscopic MVR was not inferior to that of open MVR.

目的 分析腹腔镜直肠癌超低位前切除术吻合口漏的危险因素.方法 回顾性分析2012年6月至2021年2月由同一手术团队收治的381例行直肠癌超低位前切除术患者的临床资料,分析影响术后吻合口漏发生的危险因素.结果 直肠癌超低位前切除术后吻合口漏的总体发生率为9.19％.单因素分析结果显示吻合口漏在性别、新辅助同步放化疗、是否保留左结肠动脉(LCA)、侧方淋巴结清扫、吻合口距肛缘距离及肿瘤N分期的分组中存在差异.进一步行多因素logistic回归分析结果显示,术后吻合口漏发生的独立危险因素包括新辅助同步放化疗[OR(95％CI):5.213(2.214～12.272);P=0.000]、未保留LCA[OR(95％CI):2.725(1.186～6.261);P=0.018]、吻合口距肛缘距离≤2 cm[OR(95％CI):3.104(1.126～8.559);P=0.029].结论 新辅助同步放化疗、未保留LCA及吻合口距肛缘距离≤2 cm是腹腔镜直肠癌超低位前切除术后吻合口漏发生的独立危险因素.

Abstract 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-κB) pathway in CRC. An increased level of PACER enhances proliferation, migration, and invasion of tumor cells by increasing COX-2 and PGE2 synthesis.

Background: Our understanding in prognosis of bone metastasis (BM) from colorectal cancer (CRC) is limited. We aimed to establish a clinical risk stratification for individually predicting the survival of CRC patients with BM. Methods: A total of 200 CRC patients with BM were included in this study. Survival time from BM diagnosis was estimated using the Kaplan-Meier method. The multivariable COX regression model identified the risk factors on cancer specific survival (CSS). Based on weighted scoring system, the stratification model was constructed to classify patients with BM according to prognostic risk. Discrimination power and calibration ability of risk stratification were measured. Results: The median CSS time was 11 months after BM diagnosis. Lymph node metastasis, Carbohydrate antigen 199 (CA199) levels, bone involvement, Karnofsky Performance Status (KPS) scores, primary tumor resection, bisphosphonates therapy and radiotherapy were identified as predictors of CSS. Four risk groups were stratified according to weighted scoring system, including low risk, medium risk, medium-high risk and high risk group, with 35, 16, 9 and 5 months of median CSS, respectively (P=0.000). The risk stratification displayed good accuracy in predicting CSS, with acceptable discrimination and calibration. Conclusions: This novel risk stratification predicts CSS in CRC patient with BM using easily accessible clinicopathologic factors, which is recommended for use in individualized clinical decision making in patient with BM.

Background: Cancer stem cells (CSCs), which are characterized by self-renewal and plasticity, are highly correlated with tumor metastasis and drug resistance. To fully understand the role of CSCs in colorectal cancer (CRC), we evaluated the stemness traits and prognostic value of stemness-related genes in CRC.Methods: In this study, the data from 616 CRC patients from The Cancer Genome Atlas (TCGA) were assessed and subtyped based on the mRNA expression-based stemness index (mRNAsi). The correlations of cancer stemness with the immune microenvironment, tumor mutational burden (TMB), and N6-methyladenosine (m6A) RNA methylation regulators were analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to identify the crucial stemness-related genes and modules. Furthermore, a prognostic expression signature was constructed using the Lasso-penalized Cox regression analysis. The signature was validated via multiplex immunofluorescence staining of tissue samples in an independent cohort of 48 CRC patients.Results: This study suggests that high-mRNAsi scores are associated with poor overall survival in stage IV CRC patients. Moreover, the levels of TMB and m6A RNA methylation regulators were positively correlated with mRNAsi scores, and low-mRNAsi scores were characterized by increased immune activity in CRC. The analysis identified 34 key genes as candidate prognosis biomarkers. Finally, a three-gene prognostic signature (PARPBP, KNSTRN, and KIF2C) was explored together with specific clinical features to construct a nomogram, which was successfully validated in an external cohort.Conclusion: There is a unique correlation between CSCs and the prognosis of CRC patients, and the novel biomarkers related to cell stemness could accurately predict the clinical outcomes of these patients.

Objective:To explore the effect of mesentery prior, pulling and pushing method for NOSESⅠ in lower rectal cancer patients with obesity or fat mesentery.Methods:This is a retrospective analysis of 55 patients with rectal cancer admitted to Department of Colorectal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, between January 2017 and December 2020. All patients received NOSESⅠ. The following were recorded: duration of surgery, intraoperative blood loss, the number of lymph nodes harvested, the maximum diameter of the tumor, the distance of the inferior resection margin, the length of the excised bowel, duration of hospitalization and complication. And the safety and effectiveness of the operation was explored.Results:Surgery was successfully finished in all 55 patients with mesentery prior, pulling and pushing method. There are 41 patients with BMI between 24 and 28 kg/m2, and 14 patients with BMI between 28 and 33 kg/m2.The median duration of surgery was 180 min (84 min, 339 min), the median intraoperative blood loss was 30 mL (10 mL, 200 mL),the median number of lymph nodes harvested was 18 (9, 45), the median maximum diameter of the tumor was 3 cm (1 cm, 7 cm), the median distance of the inferior resection margin was 2 cm (1 cm, 3 cm), the median length of the excised bowel was 11 cm (7.5 cm, 29 cm), the median exhaust time was 2 d (1 d, 5 d), the median duration of hospitalization was 7 d (4 d, 22 d) and complication rate was 5.5% (3/55).Conclusion:Mesentery prior, pulling and pushing method for NOSES in rectal cancer patients with obesity or fat mesentery was safe and effective.

Background: Colon cancer (CC) remains one of the most common malignancies with a poor prognosis. Pyroptosis, referred to as cellular inflammatory necrosis, is thought to influence tumor development. However, the potential effects of pyroptosis-related regulators (PRRs) on the CC immune microenvironment remain unknown. Methods: In this study, 27 PRRs reported in the previous study were used to cluster the 1,334 CC samples into three pyroptosis-related molecular patterns. Through subtype pattern differential analysis and structure network mining using Weighted Gene Co-expression Network Analysis (WGCNA), 854 signature genes associated with the PRRs were discovered. Further LASSO-penalized Cox regression of these genes established an eight-gene assessment model for predicting prognosis. Results: The CC patients were subtyped based on three distinct pyroptosis-related molecular patterns. These pyroptosis-related patterns were correlated with different clinical outcomes and immune cell infiltration characteristics in the tumor microenvironment. The pyroptosis-related eight-signature model was established and used to assess the prognosis of CC patients with medium-to-high accuracy by employing the risk scores, which was named “PRM-scores.” Greater inflammatory cell infiltration was observed in tumors with low PRM-scores, indicating a potential benefit of immunotherapy in these patients. Conclusions: This study suggests that PRRs have a significant effect on the tumor immune microenvironment and tumor development. Evaluating the pyroptosis-related patterns and related models will promote our understanding of immune cell infiltration characteristics in the tumor microenvironment and provide a theoretical basis for future research targeting pyroptosis in cancer.

Objective: Stage II colorectal cancer (CRC) manifests various treatment responses and outcomes. To assess the recurrence risk, we established a molecular subtype classification for stage II CRC. Methods: We developed a novel molecular subtyping clustering algorithm CRC-MSC for determining molecular subtypes in stage II CRC using only whole exome sequencing (WES). It utilized a specified distance estimate, calculated according to the shared alterations among samples. CRC-MSC was qualified for classification and risk stratification on samples from National Cancer Center (NCC) and The Cancer Genome Atlas (TCGA). To facilitate application to individual management decision, this algorithm was simplified by a decision tree classifier (CRC-MDTC). Phylogenetic analysis was conducted to clarify the mutated genes constituting the decision tree. Results: Using CRC-MSC successfully subtyped 60 stage II CRC samples from NCC into three groups, favorable prognosis (S-I), unfavorable prognosis (S-II) and intermediate (S-III) groups, which was verified in TCGA dataset. These subtypes feature unique molecular, clinicopathological phenotypes and clinical outcomes, especially immune traits.A simplified version of decision tree classifier (CRC-MDTC), TMB, PRKDA and KRAS alterations are three top classification indications, could also reliably categorize samples into three groups. It was validated in an independent cohort with an accuracy of 74.7%. CRC-MSC and CRC-MDTC were available at https://bioinfo.org/crcmsc. Conclusions: In addition to the initial risk evaluation, we developed a framework for the classification of stage II CRC subtypes based on genome profiling, which may shed new light on the management of patients with stage II CRC, especially with regarded to individualized chemotherapy and immunotherapy. Funding: This work was supported by National Program Project for Precision Medicine in National Research and Development Plan of China (2016YFC0905300), and CAMS Innovation Fund for Medical Sciences (CIFMS) (2019-I2M-2-002). Declaration of Interest: None to declare. Ethical Approval: The ethical approval of this study was granted by the Institutional Review Board of Chinese Academy of Medical Sciences (CHCAMS, Beijing, China)/National Cancer Center (NCC, Beijing, China).

Background: The impact of the timing of bone metastasis (BM) diagnosis on colorectal cancer (CRC) patients is unclear. Our study aimed to explore the differences in clinicopathological characteristics, treatments and prognosis between synchronous BM (SBM) and metachronous BM (MBM) from CRC. Methods: We retrospectively investigated clinical data of CRC patients with SBM or MBM from 2008 to 2017 at Chinese National Cancer Center. Cancer specific survival (CSS) after BM diagnosis was estimated using the Kaplan-Meier method. The multivariable COX regression model identified the prognostic factors of CSS. Results: Finally, 63 CRC patients with SBM and 138 CRC patients with MBM were identified. Compared to SBM from CRC, MBM significantly was more involving multiple bone lesions (63.0 vs. 7.9%; p < 0.001), and more frequently originated from rectal cancer (60.9 vs. 41.3%; p = 0.033). The therapeutic strategies in SBM and MBM group were contrasted including systemic treatment, bisphosphonates, radiotherapy and metastasectomy for BM. 85.5% of patients in MBM group and 25.4% of patients in SBM group underwent primary tumor resection at initial diagnosis (p < 0.001). The median CSS was 11 months in both SBM and MBM group (p = 0.556), yet MBM patients developed from CRC in early AJCC stage presented obviously longer survival than those from advanced stage. Furthermore, patients could have improved CSS from primary tumor resection while there might be no survival benefit from targeted therapy in both SBM and MBM groups. Bisphosphonates was associated with a better CSS for patients with SBM, while radiotherapy for BM was related to a better CSS for patients with MBM. Conclusion: The CRC patients in SBM and MBM group represented different clinicopathological characteristics and treatment modalities, which affected the prognosis in different ways. Distinct consideration for CRC patients with SBM and MBM in clinical decision making is required.