Sushi domain-containing protein 4 (SUSD4) is a complement regulatory protein whose primary function is to inhibit the complement system, and it is involved in immune regulation. The role of SUSD4 in cancer progression has largely remained elusive. SUSD4 was studied across a variety of cancer types in this study. According to the results, there is an association between the expression level of SUSD4 and prognosis in multiple types of cancer. Further analysis demonstrated that SUSD4 expression level was related to immune cell infiltration, immune-related genes, tumor heterogeneity, and multiple cancer pathways. Additionally, we validated the function of SUSD4 in colorectal cancer cell lines and found that knockdown of SUSD4 inhibited cell growth and impacted the JAK/STAT pathway. By characterizing drug sensitivity in organoids, we found that the expression of SUSD4 showed a positive correlation trend with IC50 of Selumetinib, YK-4-279, and Piperlongumine. In conclusion, SUSD4 is a valuable prognostic indicator for diverse types of cancer, and it has the potential to be a target for cancer therapy.

This study investigated the role of C-X-C motif chemokine receptor 6 (CXCR6) in colorectal cancer (CRC). It was found that lower CXCR6 expression is correlates with poorer prognostic outcomes, suggesting that CXCR6 may inhibit tumor progression and thus improve patient outcomes. Silencing CXCR6 in CRC cell lines SW620 and CT-26 resulted in significantly enhanced migration and invasion, as demonstrated by wound healing and transwell assays. Further analysis revealed that CXCR6 activity is associated with activation of the VEGFA/PI3K/AKT/mTOR signaling pathway. Inhibition of this pathway through VEGFA siRNA and pathway-specific inhibitors reversed the effects of CXCR6 silencing on cell migration and invasion. Moreover, xenograft experiments showed that silencing CXCR6 led to increased tumor growth and upregulated proteins associated with the extracellular matrix and epithelial-mesenchymal transition. These findings were validated through immunohistochemical, immunofluorescence, and Western blot analyses. This study highlights CXCR6's critical role in CRC and its potential as a therapeutic target to manage cancer progression.

PURPOSE:The aim of this work was to determine whether locally advanced rectal cancer (LARC) with negative mesorectal fascia (MRF) predicted by magnetic resonance imaging (MRI) can be excluded from preoperative radiation therapy treatment. METHODS AND MATERIALS:This multicenter, open-label, non-inferiority, randomized clinical trial enrolled patients with LARC within 6 to 12 cm from the anal verge and with negative MRI-predicted MRF. Participants were randomized to the intervention group (primary surgery, in which the patients with positive pathologic [CRM] circumferential margins were subjected to chemoradiotherapy [CRT] and those with negative CRM underwent adjuvant chemotherapy according to pathologic staging) or the control group (preoperative CRT, in which all patients underwent subsequent surgery and adjuvant chemotherapy). The primary endpoint was 3-year disease-free survival (DFS). RESULTS:A total of 275 patients were randomly assigned to the intervention (n = 140) and control (n = 135) groups, in which 33.57% and 28.15% patients were at clinical T4 stage and 85.92% and 80.45% patients were at "bad" or "ugly" risk in the intervention and control groups, respectively. There were 2 patients (1.52%) and 1 patient (0.77%) with positive CRM in the intervention and control groups, respectively (P > .05). The non-adherence rates for the intervention and control groups were 3.6% and 23.7%, respectively. After a median follow-up of 34.6 months (IQR, 18.2-45.7), 43 patients had positive events (28 patients and 15 patients in the intervention and control groups, respectively). There were 6 patients (4.4%) with local recurrence in the intervention group and none in the control group, which led to the termination of the trial. The 3-year DFS rate was 81.82% in the intervention group (95% CI, 78.18%-85.46%) and 85.37% in the control group (95% CI, 81.75%-88.99%), with a difference of -3.55% (95% CI, -3.71% to -3.39%; hazard ratio, 1.76; 95% CI, 0.94-3.30). In the per-protocol data set, the difference between 3-year DFS rates was -5.44% (95% CI, -5.63% to -5.25%; hazard ratio, 2.02; 95% CI, 1.01-4.06). CONCLUSIONS:Based on the outcomes of this trial, in patients with LARC and MRI-negative MRF, primary surgery could negatively influence their DFS rates. Therefore, primary surgery was an inferior strategy compared with preoperative CRT followed by surgery and cannot be recommended for patients with LARC.

Objective: To investigate the impact of relative locations of multiple foci and microsatellite status of sporadic, synchronous, multiple, primary, colorectal carcinomas on clinicopathological features and prognosis. Methods: The clinicopathologic and prognostic data of 278 patients with sporadic, synchronous, multiple, primary, colorectal carcinomas who had been admitted to the Department of Colorectal Surgery at Zhejiang Cancer Hospital from January 2008 to July 2022 were retrospectively collected. The patients were categorized into three groups based on the relative locations of their multiple cancer foci: (1) a right-sided group that comprised patients with multiple cancer foci in the cecum, ascending colon, hepatic flexure of the colon, and transverse colon; (2) a left-sided group that comprised patients with multiple cancer foci in the splenic flexure of the colon, descending colon, sigmoid colon, and rectum; and (3) a left- and right-sided group that comprised patients with multiple cancer foci in the right half of the colon and left half of the colon/rectum. Additionally, the patients were further divided into two groups based on microsatellite status: a high microsatellite instability (MSI-H) and a low MSI/stable MSI (MSI/L&MSS) group. We compared differences in clinical characteristics and prognostic indicators between these groups. The χ2 test was utilized to compare selected clinical characteristics, whereas Kaplan-Meier survival analyses and log-rank tests were performed to compare their effects on prognosis. Result: Among 278 patients with SSCRC, 256 (92.1%) presented with two cancer foci and 22 (7.9%) with more than two foci. Additionally, 255 patients (91.7%) had adenocarcinomas, whereas the remaining 23 (8.3%) had mucinous adenocarcinomas. Lymph node metastases were identified in 136 patients (48.9%); the cancer foci had infiltrated beyond the muscular layer in 238 (85.6%); and 147 patients (52.9%) were diagnosed with TNM Stage III-IV disease. There were 155 patients (55.8%) in the left-sided group, 55 (19.8%) in the right-sided group, and 68 (24.5%) in the left- and right-sided group. Immunohistochemical examination of all four mismatch repair proteins were performed in 199 cases, revealing that 166 of these patients had MSI/L&MSS and 33 MSI-H disease. In the left-sided, left- and right-sided, and right-sided groups, the proportion of women was 16.8% (26/155), 26.5% (18/68), and 49.1% (27/55), respectively; these differences are statistically significant (χ2=22.335, P<0.001). The proportions of patients with more than three cancer foci were 5.2% (8/155), 16.2% (11/68), and 5.5% (3/55), respectively; these differences are statistically significant (χ2=8.438, P=0.015). The proportions of mucinous adenocarcinomas were 4.5% (7/155), 8.8% (6/68), and 18.2% (10/55), respectively; these differences are statistically significant (χ2=10.026, P=0.007). The proportions of patients with lymph node metastases were 55.5% (86/155), 48.5% (33/68), and 30.9% (17/55); these differences are statistically significant (χ2=9.817, P=0.007). The proportions of patients with Stage T3 & T4 disease in each group according to location were 81.3% (126/155), 88.2% (60/68), and 94.5% (52/55), respectively; these differences are statistically significant (χ2=6.293,P=0.043). The proportions of TNM Stage III-IV tumors were 59.4% (92/155), 54.4% (37/68), and 32.7% (18/55), respectively; these differences are statistically significant (χ2=11.637, P=0.003). Age, size of cancer foci, presence of distant metastasis, adenoma, nerve invasion, and vascular invasion did not differ significantly between the three groups (all P>0.05). Compared with those with MSI-H, patients with MSI/L&MSS disease were more likely to be aged >65 years and male (50.6% [84/166] vs. 15.2% [5/33], χ2=13.994,P<0.001; 80.7% [134/166] vs. 54.5% [18/33], χ2=10.457,P=0.001), more likely to be in the left-sided group (63.3% [105/166] vs. 24.2% [8/33], χ2=18.232, P<0.001), had a higher proportion of cancer foci of diameter <4 cm (54.8% [91/166] vs. 33.3% [11/33], χ2=5.086,P=0.024), and a lower proportion of mucinous adenocarcinomas (4.2% [7/166] vs. 27.3% [9/33], χ2=19.791,P<0.001), more likely to develop distant metastases (22.3% [37/166] vs. 6.1% [2/33], χ2=4.601,P=0.032), more likely to have lymph node metastases (57.2% [95/166) vs. 24.2% [8/33], χ2=11.996,P<0.001) and nerve invasion (28.9% [48/166] vs. 6.1% [2/33], χ2=7.643, P=0.006), had a higher proportion of TNM Stage III-IV disease (60.2% [100/166] vs. 24.2% [8/33], χ2=14.374, P<0.001), and a smaller proportion of family history of tumors (28.9% [48/166] vs. 60.6% [20/33], χ2=12.228, P<0.001). All the above-listed differences are statistically significant (all P<0.05). The differences in number of cancer foci, depth of infiltration, presence or absence of adenomas, and vascular invasion were not statistically significant (all P>0.05). In the 33 patients with MSI-H status and mismatch repair protein loss, the highest frequency of deletion was found in PMS-2 (66.7%, 22/33), followed by MLH-1 (57.6%, 19/33), whereas the proportions of MSH-2 (33.3%, 11/33) and MSH-6 (24.2%, 8/33) deletions were relatively low. There were statistically significant differences in the 3-year overall survival rates among the groups according to relative locations of cancer foci. The 3-year overall survival rates were 96.8%, 79.6%, and 88.5% in the right-sided, left- and right-sided, and left-sided groups, respectively (P=0.021). As to microsatellite status, the 3-year overall survival rate of patients with MSI-H disease was 93.8%, which is significantly better than the 78.4% for those with MSI/L & MSS (P=0.026). Conclusions: Among sporadic, synchronous, multiple, primary, colorectal carcinomas, those with right-sided disease had the deepest local infiltration, whereas those with left-sided disease had the greatest number of lymph node metastases, most advanced clinical TNM stage, lowest percentage of MSI-H disease, and the poorest prognosis.

BACKGROUND:Lactate accumulation leads to an acidic tumor microenvironment (TME), in turn promoting colorectal cancer (CRC) progression. Tumor-associated macrophages (TAMs) are the predominant cells in TME. This study aimed to reveal the regulation mechanism of CRC cell-derived lactate on TAMs and explore the mechanism underlying lactate accumulation-induced aggravation in CRC.METHODS:Cell growth and metastasis were evaluated by colony formation, Transwell, and wound healing assays. Western blot and RT-qPCR were applied to determine the protein and mRNA expression. Flow cytometry was used to analyze the polarization state and apoptotic rate of macrophages induced in THP-1 cells. The lactate in the cell supernatant was quantified using an ELISA kit. Immunofluorescence was performed to visualize the location of High Mobility Group Box 1 (HMGB1). H&E and Ki67 staining assays were used to assess tumorigenesis in nude mice bearing ectopic tumors.RESULTS:Cell growth and metastasis were promoted in the hypoxic CRC cells. The hypoxic cell supernatant stimulated the M2-type polarization of macrophages. The lactate level increased in hypoxic cancer cells. However, the inhibition of lactate using 3-hydroxy-butyrate (3-OBA) reversed the effects of hypoxia. Also, macrophages showed no promoting effect on cancer cell growth and migration in the presence of 3-OBA. HMGB1 was secreted into the extracellular space of lactate-induced macrophages, further enhancing the malignant behaviors of cancer cells. ERK, EMT, and Wnt signaling pathways were activated in cancer cells due to HMGB1 upregulation.CONCLUSIONS:The lactate metabolized by cancer cells stimulated M2 polarization and HMGB1 secretion by macrophages, aggravating the carcinogenic behaviors of cancer cells.

目的:观察气血方、养阴方、健脾方对高危Ⅱ期及Ⅲ期结直肠癌术后患者复发转移的影响.方法:采用多中心随机对照方法,选择高危Ⅱ期及Ⅲ期结直肠癌术后患者303例按照2:1的比例随机分为试验组202例及对照组101例,两组均接受4～9个周期奥沙利铂联合卡培他滨(CapeOx)方案辅助化疗,试验组根据证型加用气血方、养阴方、健脾方,观察两组1、2、5年无病生存率(DFS)、卡氏评分(KPS)、中医证候积分和不良反应.结果:最终纳入281例患者,随机分配至试验组190例,对照组91例.经过48个月的中位随访时间,试验组中74例(38.9％)出现复发,对照组中40例(44.0％)出现了复发,试验组1、2、5年DFS分别为94.2％(179/190)、84.2％(160/190)、61.1％(116/190),优于对照组的91.2％(83/91)、81.3％(74/91)、56.0％(51/91).亚组分析中,试验组阴虚证患者干预后5年DFS差异有统计学意义(P=0.037).两组不良反应总发生率差异无统计学意义,试验组的恶心/呕吐等消化道不良反应发生率显著低于对照组(P=0.014).结论:气血方、养阴方、健脾方联合化疗可降低高危Ⅱ期及Ⅲ期结直肠癌术后患者复发转移风险,阴虚证患者是应用中医药抗结直肠癌术后复发转移的潜在优势人群.

Death-associated protein kinase 1 (DAPK1), as a calcium/calmodulin (CaM) regulated serine/threonine kinase, functions in apoptotic and autophagy pathways and represents an interesting drug target for inflammatory bowel disease and Alzheimer’s disease. The crystal structure of the DAPK1 catalytic domain and the autoregulatory domain (ARD) in complex with CaM provides an understanding of CaM-dependent regulation of DAPK1 activity. However, the molecular basis of how distinct Trp305 (W305Y and W305D) mutations in the ARD modulate different DAPK1 activities remains unknown. Here, we performed multiple, μs-length molecular dynamics (MD) simulations of the DAPK1–CaM complex in three different (wild-type, W305Y, and W305D) states. MD simulations showed that the overall structural complex did not change significantly in the wild-type and W305Y systems, but underwent obvious conformational alteration in the W305D system. Dynamical cross-correlation and principal component analyses revealed that the W305D mutation enhanced the anti-correlated motions between the DAPK1 and CaM and sampled a broader distribution of conformational space relative to the wild-type and W305Y systems. Structural and energetical analyses further exhibited that CaM binding was unfavored in response to the W305D mutation, resulting in the decreased binding of CaM to the W305D mutant. Furthermore, the hydrogen bonds and salt bridges responsible for the loss of CaM binding on the interface of the DAPK1–CaM complex were identified in the W305D mutant. This result may provide insights into the key role of Trp305 in the regulation of CaM-mediated DAPK1 activity.

Background:Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) is commonly considered an oncogene in various cancers. The long noncoding RNA NEAT1 has been reported to be overexpressed in colorectal cancer (CRC). However, the exact role of NEAT1 in CRC remains unknown. Our research aimed to explore the function of NEAT1 in the tumorigenesis and the development of CRC.Methods:Real-time quantitative PCR (qRT-PCR) was used to detect the NEAT1, miR-216b, and YIN-YANG-1 (YY1) mRNA levels in CRC tissues and cells, then immunohistochemistry (IHC) was used to detect the expression of YY1 in CRC tissues. Luciferase reporter, qPCR, western blot, and DNA pulldown assays were conducted to study the relationships between NEAT1, miR-216b, and YY1. Flow cytometry analysis was performed for cell cycle and apoptosis analyses, and a colony formation assay was performed to test cell proliferation. Transwell assays were performed to detect cell invasion and migration.Results:The NEAT1 expression was significantly upregulated in CRC tissues compared with its expression in normal tissues, and downregulation of NEAT1 suppressed the proliferation, migration, and invasion of CRC cells. Moreover, we found NEAT1 decreased the miR-216b level directly, and the suppression of miR-216b could inhibit the function of downstream YY1. However, overexpression of YY1 accelerated CRC cell proliferation, migration, and invasion.Conclusion:Our results indicated that NEAT1 acted as an oncogene in CRC and promoted the progression of CRC by directly sponging miR-216 b expression to activate the expression of YY1. The NEAT1/miR-216b/YY1 axis may be a novel therapeutic target for CRC.

Backgroud: Malnutrition has been confirmed to play an important role in colorectal cancer (CRC) progression via the gut microenvironment. However, the characteristics of the gut microbiota or its potential biological mechanism in CRC remain inconclusive. Methods: In this work, Patient-Generated Subjective Global Assessment (PG-SGA) tool and 16sRNA sequencing were prepared to detect the variation in gut microbiota and the association between nutrition status and gut microbiota. RDA/CCA analysis was used to evaluate the relationship between faecal microbiota from malnourished CRC and clinical nutrition indicators. To investigate the mechanism of the gut microbiota in CRC, faecal samples from malnourished CRC patients were transplanted into C57BL/6J and DSS/AOM mouse models. Moreover, FACS and IHC were prepared to detect the infiltration of B cells and macrophages. qPCR and Elisa assays were performed to explore the expression of cytokines. Result: We found dramatic variation in the faecal microbiota among patients with different nutritional statuses, discovering that specific microbiota species, namely, Atopobium vaginae, Selenomonas sputigena and Faecalibacterium prausnitzii, may be considered diagnostic biomarkers in malnutrition and indicate poor prognosis. High expression level of A. vaginae in CRC tissues revealed the poorer overall survival compared with low expression level (Mean survival: 23.0 months vs 29.0 months). Faecal from malnourished colorectal cancer were found to be protumorigenic. More importantly, our evidence suggests that after faecal microbiota transplantation, B cells and macrophages are recruited to activate specific tumour immunity in CRC. Depletion of B cells significantly suppressed faecal microbiota-induced M2b polarization as well as the protumorigenic activity of tumour-associated macrophages in vivo. Conclusion: Faecal microbiota in CRC under malnutrition conditions exhibits specific characteristics that accelerate CRC progression and regulate B cells and macrophages. The use of specific faecal microbial species could be a feasible approach for identifying the malnutrition status of patients and demonstrating the poor prognosis of CRC. (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

目的 探讨直肠癌患者PANDAR mRNA表达与临床病理特征及预后的关系.方法 选取2015年1月-2016年12月在中国科学院大学附属肿瘤医院接受直肠癌根治术的120例患者为研究对象,比较直肠癌组织与癌旁正常组织中PAN-DAR mRNA表达水平,以及直肠癌组织PANDAR mRNA高、低表达患者临床病理特征及预后,采用多因素logistic回归分析直肠癌患者PANDAR mRNA表达的影响因素.结果 直肠癌组织中PANDAR mRNA表达水平明显高于癌旁正常组织(P＜0.05).PANDAR mRNA高表达(表达水平＞5.25)65例,低表达(表达水平≤5.25)55例.直肠癌组织PANDAR mRNA高、低表达患者在远处转移、淋巴结转移、肿瘤浸润深度、MRI-T分期、MRI-N分期等方面比较,差异均有统计学意义(均P＜0.05);在性别、年龄、肿瘤直径、肿瘤组织分化、MRI-环周切缘状态等方面比较,差异均无统计学意义(均P＞0.05).MRI-T分期(OR=6.071,95％CI:1.281～28.783,P＜0.05)、MRI-N分期(OR=12.481,95％CI:2.046～76.148,P＜0.05)是直肠癌患者PANDAR mRNA表达的独立影响因素.术后随访48个月,PANDAR mRNA低表达患者4年总体生存率明显高于PANDAR mRNA高表达者,差异有统计学意义(39.2％比19.8％,P＜0.05).结论 PANDAR在直肠癌组织中呈高表达,与MRI-T分期、MRI-N分期等临床病理特征及预后相关.

目的 探讨结直肠神经内分泌癌(NEC)患者临床病理特征与预后的关系.方法 选取2012年1月1日至2020年7月31日在浙江省肿瘤医院接受手术治疗且术后病理证实为结直肠NEC的28例患者为研究对象,分析其临床病理特征与预后的关系.结果 就诊时是否发生转移以及不同肿瘤类型、Ki-67增殖指数的患者术后3年累计生存率比较,差异均有统计学意义(均P<0.05);不同性别、年龄、肿瘤直径以及突触素、嗜铬粒素A、神经元特异性烯醇化酶表达是否阳性患者术后3年累计生存率比较,差异均无统计学意义(均P>0.05).28例患者术后3年累计生存率为50.0％,就诊时发生转移患者的预后明显差于未转移患者(P<0.05),混合性腺神经内分泌癌(MANEC)患者的预后明显差于单纯NEC患者(P<0.05),Ki-67增殖指数>55％的患者预后明显差于≤55％的患者(P<0.05).结论 就诊时发生转移、MANEC、Ki-67增殖指数增高的结直肠NEC患者预后较差.

目的 探讨局部晚期直肠癌(LARC)患者术前同步放射治疗及化学治疗联合热疗的临床疗效.方法 选取2009年7月至2013年12月在浙江省肿瘤医院确诊为LARC(美国癌症联合委员会分期T3～T4伴或不伴淋巴结转移)的67例患者为研究对象,行术前新辅助放射治疗及化学治疗联合热疗,放射治疗总剂量为50 Gy,放射治疗前1 h内进行热疗(每周2次),持续5周.放射治疗结束4～6周后对LARC患者进行手术治疗.对所有患者的临床疗效进行评价,并采用Kaplan-Meier绘制生存曲线进行分析.结果 67例患者中共64例患者接受手术治疗,且均恢复顺利出院;余3例因拒绝切除肛门而放弃手术治疗.96.9％(62/64)的患者达到R0切除,89.1％(57/64)的患者出现局部降期,23.4％(15/64)的患者病理完全缓解(pCR),76.6％(49/64)的患者病理示无淋巴结转移(ypN-),Ⅲ级不良反应发生率为14.9％(10/67).术后随访3～72个月,5年总生存率为81.2％(52/64),5年肿瘤无病生存率为70.3％(45/64).同时,pCR患者的生存曲线明显优于非pCR患者(χ2=4.132,P=0.042),ypT0～T2患者的生存曲线明显优于ypT3～T4患者(χ2=14.791,P<0.001),ypN-患者的生存曲线明显优于ypN+患者(χ2=12.402,P<0.001).结论 新辅助放射治疗及化学治疗联合热疗治疗LARC可以显著提高LARC患者的pCR、R0切除率及保肛率,肿瘤退缩明显,且不会增加治疗相关不良反应,患者耐受性较好.

BACKGROUND:Colon cancer (CRC) is a common type of tumour, and IQGAP family proteins play an important role in many tumours. However, their roles in CRC remain unclear. METHODS:First, we searched many public databases to comprehensively analyze expression of IQGAPs in CRC. Next, real-time PCR, immunohistochemical (IHC), transwell, siRNA transfection and Western blot assays were used to evaluate relationships among IQGAP3 expression, clinical pathological parameters and CRC prognosis, and the underlying molecular mechanism was investigated. RESULTS:IQGAP3 was elevated in CRC tissues, whereas there was no significant change in expression of IQGAP1 or IQGAP2. Additionally, IQGAP3 expression in CRC tissues was associated with tumour progression, invasion and poor prognosis. In mechanistic studies, we found that IQGAP3 was positively coexpressed with PIK3C2B. In an in vitro assay, the PIK3C2B expression level was increased after exogenous overexpression of IQGAP3, resulting in the promotion of cell invasion, which was blocked by pretransfecting cells with PIK3C2B siRNA. Furthermore, we found that high expression of IQGAP3 and PIK3C2B correlated with tumour stage and vessel invasion in human CRC, whereby patients with high expression of both in tumours had a worse prognosis compared with patients with single-positive or double-negative tumours. CONCLUSION:The results of our current study and corresponding previous studies provide evidence that IQGAP3 is elevated in CRC and promotes colon cancer growth and metastasis by regulating PIK3C2B activation.

目的 分析可切除直肠癌肺转移的临床特点及异时性肺转移发生率的影响因素.方法 回顾性分析2007年1月至2014年12月中国科学院大学附属肿瘤医院收治的直肠癌肺转移并接受胸腔镜辅助下手术切除患者的临床资料,对患者的临床病理特征进行统计分析.结果 根据纳入及排除标准共筛选出75例患者作为研究对象,其中术前即存在同时性肺转移11例,术后发生异时性肺转移64例.肺转移患者中52例(69.3％)接受胸腔镜辅助下肺楔形切除术,4例(5.3％)接受肺段切除术,19例(25.3％)接受肺叶切除术.在根治性手术后5年内,T3/4患者较T1/2患者异时性肺转移发生率更高(P<0.05),而在不同年龄、性别、手术方式、淋巴结转移状态、术前新辅助放化疗、术后辅助放疗、术后辅助化疗的亚组分析中异时性肺转移发生率差异均无统计学意义(均P>0.05).结论 胸腔镜辅助下肺楔形切除术是可切除直肠癌肺转移最为常用的手术方式,肿瘤T分期较晚者术后5年内异时性肺转移发生率更高.

[目的]结直肠癌位居浙江省恶性肿瘤发病第3位、死亡第4位,是威胁居民健康和生命的重大公共卫生问题.开展结直肠癌筛查,实现结直肠癌的早期发现、早期诊断和早期治疗是降低结直肠癌负担的有效手段.[方法]2020年浙江省将重点人群结直肠癌筛查项目纳入省政府十方面民生实事,在全省范围内向50～74周岁户籍居民提供免费结直肠癌筛查服务.本文将重点阐述该项目的设计蓝图和实施方案.[结果]项目充分考虑浙江省结直肠癌疾病负担和公共卫生资源状况,结合浙江省结直肠癌筛查经验和工作基础,制定了筛查策略.[结论]浙江省重点人群结直肠癌筛查项目为积极探索适合中国国情的结直肠癌筛查策略提供理论依据和实践基础.

Abstract Background: Malnutrition threatened the clinical outcomes of colorectal cancer (CRC) by reducing patients’ responses to anti-cancer treatments and ultimately shortening thesurvival time. Recently malnutrition has been confirmed to play an important role in CRC progress via gut microbiota. However, roles of gut microbiota in the immunopathogenesis of malnutrition and its underlying mechanisms remain inconclusive. Methods: Patient-Generated Subjective Global Assessment (PG-SGA) was performed to determine the nutrition status in colon cancer patients. 16srRNA sequencing was prepared to explore the dramatic variation of the fecal microbiota among patients with different nutrition status. Fecal microbiota transplantation was used to transplant into C57BL/6J mice model and DSS/AOM mice model. Immunohistochemistry and immunofluorescence were applied to test the CD makers. Fluorescence-activated cell sorting was also prepared to explore the B cells and macrophage from serum and tissues. Enzyme-linked immunosorbent assay and qPCR were used to determine the expression level of cytokines.Results: In this work, we found the specific microbiota species including Atopobium.vaginae, Selenomonas.sputigena and Faecalibacterium.prausnitzii, which may be considered as the diagnostic biomarkers to help improve poor prognosis in CRC. These microbiota were found to be protumorigenic and adversely affect the nutritional status and overall survival of the animal models. More importantly, our evidence suggesting that these fecal microbiota recruited B cells and macrophage to activate the specific tumor immune in CRC. Depletion of B cells significantly suppressed fecal microbiota induced-M2b polarization, as well as the protumorigenic activity of tumor-associated macrophages in vivo.Conclusion: gut microbiome in CRC under malnutrition status could upregulate the activity of B cells and protumorigenic macrophage in CRC. Gut microbiome intervention could be a feasible approach to malnutrition-related CRC treatment.

BACKGROUND:Currently, few specific biomarkers or standard cutoff values are available for circulating tumor cells (CTCs) detection and survival prediction in patients with early stage colorectal cancer (CRC). Guanylyl cyclase C (GCC) presents as a specific expression in intestinal tumor cells and during their metastases, indicating its potential application as a metastatic predictor of CRC. METHODS:The circulating GCC mRNA of 160 colorectal cancer patients at stage I-III was detected via quantitative real-time (qRT)-PCR in our study, and the correlation of GCC mRNA level with tumor metastasis and long-term survival was explored. RESULTS:GCC mRNA was found to be positive in 43 out of 160 CRC patients and negative in ten healthy controls. It was found that GCC mRNA over the baseline (>100 copies/µL and 200 copies/µL) showed a significant correlation with disease-free survival (DFS) and overall survival (OS) in the stage II subgroup. It was further revealed that GCC mRNA over 300 copies/µL or higher than the median value of copy numbers was significantly correlated with reduced OS and DFS in CRC patients. A nomogram model based on variables including GCC mRNA copy number was established for predicting the OS of CRC patients (AUC =0.98). CONCLUSIONS:Circulating GCC mRNA over baseline is a reliable predictor for tumor metastasis and can be a prognostic index in CRC patients.

Introduction Adjuvant chemotherapy with the CapeOX regimen is now widely used for treating colorectal cancer. However, prior studies have demonstrated better efficacy of pre-operative/neoadjuvant chemotherapy without increase of safety risks. Methods and Analysis This multicentre, open-label, parallel-group, randomised, controlled, phase III study aims to compare the efficacy and safety of perioperative CapeOX chemotherapy with the postoperative one for treating patients with locally advanced R0 resectable colon cancers in China. In total 1370 eligible patients will be randomised to: the test group, up to four cycles (every 3 weeks is a cycle, Q3W) of chemotherapy plus radical surgery plus up to four cycles of post-operative chemotherapy; or the control group, radical surgery first, then up to eight cycles of chemotherapy. In each cycle, oxaliplatin will be given at a dose of 130 mg/m2 through continuous IV infusion for 2 hours on the first day. From day 1 to day 14, capecitabine will be taken orally every morning and evening at a dose of 1000mg/m2/d. The primary outcome measure is the 3-year disease free survival. The objective response rate, R0 resection rate, overall survival, as well as the adverse events will also be measured as second endpoints. The study may include two periods. If results of period 1 are not favourable, period 2 will be initiated, recruiting genetically sensitive patients and repeating the same process with period 1. Ethics and dissemination Informed consent will be required from, and provided, by all subjects. The study protocol has been approved by the independent ethics committee of Shanghai Fudan University Cancer Centre. This study will clearly demonstrate the potential benefit of perioperative chemotherapy with the CapeOX regimen. Results will be shared among all the participating centres, and with policymakers and the academic community to promote the clinical management of colon cancer. Trial registration number NCT03125980.

Background: Perineural invasion (PNI) and lymphovascular invasion (LVI) are associated with poor prognosis in colorectal cancer, but their clinical significance is still controversial for patients with locally advanced rectal cancer (LARC) who had received neoadjuvant chemoradiotherapy (nCRT) and surgical resection. The aim of this study was to confirm the correlation between PNI and/or LVI and clinical prognosis and to further confirm whether PNI and/or LVI can be used as potential prognostic indicators of adjuvant chemotherapy after nCRT and surgery in LARC. Methods: From February 2002 to December 2012, a total of 181 patients with LARC who had received nCRT and surgical resection were retrospectively reviewed. Overall survival (OS) and disease-free survival (DFS) were determined by the Kaplan-Meier method, log-rank test, and Cox proportional hazard regression model. Results: The median follow-up time was 48 months (range, 3 to 162 months). All the PNI-positive and/or LVI-positive patients showed adverse DFS and OS (P<0.001). In multivariate analysis, PNI and LVI were independent prognostic factors for DFS. PNI, rather than LVI, was also an independent prognostic factor for OS. In a subgroup analysis, PNI-positive, rather than LVI-positive, may benefit from adjuvant chemotherapy. Conclusion: For patients with LARC undergoing nCRT and surgery, PNI-positive and/or LVI positive were associated with poorer DFS and OS. And PNI-positive, rather than LVI-positive, may benefit from adjuvant chemotherapy.

Our animal studies have demonstrated the safety and feasibility of end-to-end intestinal anastomosis using a stent for laparoscopic colonic surgery. Therefore, we designed a non-inferiority trial to investigate the outcomes of stent anastomosis (SA) vs. those of conventional hand-sewn anastomosis (CA). A multicenter randomized controlled trial was conducted between December, 2016 and April, 2018. The primary outcome was the healing condition of the anastomoses, evaluated by endoscopy 6 months postoperatively. The secondary outcomes were the anastomotic completion time, anastomotic leak, intestinal obstruction, peritoneal effusion, and bleeding. Quality of life (QOL) was evaluated by questionnaires. The subjects of this study were 60 patients, randomly divided into a SA group (n = 30) and a CA group (n = 30). There were no differences in anastomotic healing conditions (P = 1.00). The stent procedure was associated with a significantly shorter anastomosis time than the hand-sewn anastomosis (13.517 ± 4.281 vs. 20.333 ± 2.998 min, respectively; P < 0.001). There were no significant differences in anastomotic leakage, intestinal obstruction, peritoneal effusion, or bleeding between the groups. Questionnaires revealed almost no discrepancy between baseline QOL scores and those assessed 2, 4, 8, 12, and 24 weeks postoperatively in either group. Intestinal anastomosis with a stent is a non-inferior strategy for laparoscopic colonic surgery, which requires less time for the anastomosis.