Background:The tumor microenvironment (TME) plays an important role in regulating gastric cancer (GC) progression. The infiltration of M0 macrophages into the TME negatively affects the prognosis of patients with various tumors. Methods:The data were obtained from the TCGA and GEO databases and our hospital (107 patients). The expression of IQGAP3 was knocked down in AGS and NCI-N87 GC cells. Cell proliferation, migration, and invasion assays were performed. RNA sequencing was performed on GC cells with different IQGAP3 expression. AGS and THP-1 cells were mixed to create a co-cultured subcutaneous tumor model in nude mice. Tumor growth in the mice was observed by using luciferin fluorescence and the tumor tissues were subjected to immunohistochemistry. Results:The expression of IQGAP3 was increased in GC tissues (P < 0.001) and was associated with infiltration of M0 macrophages and a poor prognosis for GC patients (P < 0.01). Knockdown of IQGAP3 resulted in decreased expression of CXCL13 (P < 0.001) and less phosphorylation of pSTAT3 and pERK1/2 (P < 0.001). The expression of CXCL13 was decreased after the pSTAT3 and pERK1/2 phosphorylation inhibitors were added. In the co-culture experiment, the M0/THP-1 ratio decreased significantly in the low-IQGAP3-expression group (P < 0.001). However, adding recombinant human CXCL13 proteins to the low IQGAP3 expression group increased the M0/THP-1 ratio. In vivo, tumor growth and M0 macrophage infiltration were both suppressed in the group with low IQGAP3 expression. Conclusion:IQGAP3 is a potential pro-carcinogenic factor in GC. IQGAP3 promotes the expression and secretion of CXCL13 via the ERK1/2 and STAT3 pathways, thereby causing M0 macrophages to infiltrate the TME.

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:The appropriate ligation level of the inferior mesenteric artery (IMA) in left-sided colorectal cancer (CRC) surgery is debated, with metastasis in No. 253 lymph node (No. 253 LN) being a key determining factor. This study aimed to develop a machine learning model for predicting metastasis in No. 253 LN. METHODS:We retrospectively collected clinical data from 2,118 patients with left-sided CRC and contrast-enhanced CT images from 310 of these patients. From this data, a test set, a training set, and a temporal validation set were constructed. Logistic regression models were used to develop a clinical model, a CT model, and a radiomics model, which were then integrated into a combined model using logical rules. Finally, these models were evaluated using metrics such as the area under the receiver operating characteristic curve (AUC), precision-recall (PR) curves, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS:A clinical model, a CT model, and a radiomics model were constructed using univariate logistic regression. A combined model was developed by integrating the clinical, CT, and radiomics models, with positivity defined as all three models being positive at a 90% sensitivity threshold. The clinical model included six predictive factors: tumor site, endoscopic obstruction, CEA levels, growth type, differentiation grade, and pathological classification. The CT model utilized largest lymph node average CT value, short-axis diameter and long-axis diameter. The radiomics model incorporated maximum gray level intensity within the region of interest, large area high gray level emphasis, small area high gray level emphasis and surface area to volume ratio. In the test set, the AUCs for the clinical, CT, radiomics, and combined models were 0.694, 0.663, 0.72, and 0.663, respectively, while in the temporal validation set, they were 0.743, 0.629, 0.716, and 0.8. Specifically, the combined model demonstrated a sensitivity of 0.8 and a specificity of 0.8 in the temporal validation set. By comparing the PR and DCA curves, the combined model demonstrated better performance. Additionally, the combined model showed moderate improvements in INR and IDI compared to other models. CONCLUSION:A clinical and CT-based radiomics model shows promise in predicting No. 253 LN metastasis in left-sided CRC and provides insights for optimizing IMA ligation strategies.

This case report describes an 80-year-old female patient admitted to the emergency department due to abdominal distension, abdominal pain, and hematemesis persisting for three days. Subsequent postoperative pathological examination confirmed the diagnosis of peritoneal cancer. The occurrence, diagnosis, treatment, and prognosis of primary peritoneal cancer (PPC) are presented in detail. PPC is a type of cancer originating from the primary peritoneal mesothelium organization, causing diffuse malignant tumors in the abdominal and pelvic regions. Due to the lack of specific clinical manifestations for this disease, the importance of early diagnosis and treatment is hereby emphasized. The article also mentions the histological source of this type of cancer and the advantages of preoperative intraperitoneal chemotherapy in improving the efficacy of PPC treatment. Finally, the importance of a comprehensive treatment approach and proficient use of targeted therapy techniques are highlighted to enhance the treatment outcomes of PPC.

(1) Background: Understanding vascular patterns is crucial for minimizing bleeding and operating time in colorectal surgeries. This study aimed to develop an anatomical atlas of the inferior mesenteric artery (IMA) and vein (IMV). (2) Methods: A total of 521 patients with left-sided colorectal cancer were included. IMA and IMV patterns were identified using maximum-intensity projection (MIP) and three-dimensional (3D) reconstruction techniques. The accuracy of these techniques was assessed by comparing them with surgical videos. We compared the amount of bleeding and operating time for IMA ligation across different IMA types. (3) Results: Most patients (45.7%) were classified as type I IMA, followed by type II (20.7%), type III (22.6%), and type IV (3.5%). Newly identified type V and type VI patterns were found in 6.5% and 1% of patients, respectively. Of the IMVs, 49.9% drained into the superior mesenteric vein (SMV), 38.4% drained into the splenic vein (SPV), 9.4% drained into the SMV–SPV junction, and only 2.3% drained into the first jejunal vein (J1V). Above the root of the left colic artery (LCA), 13.1% of IMVs had no branches, 50.1% had one, 30.1% had two, and 6.7% had three or more branches. Two patients had two main IMV branches, and ten had IMVs at the edge of the mesocolon with small branches. At the IMA root, 37.2% of LCAs overlapped with the IMV, with 34.0% being lateral, 16.9% distal, 8.7% medial, and both the marginal type of IMV and the persistent descending mesocolon (PDM) type represented 1.4%. MIP had an accuracy of 98.43%, and 3D reconstruction had an accuracy of 100%. Blood loss and operating time were significantly higher in the complex group compared to the simple group for IMA ligation (p < 0.001). (4) Conclusions: A comprehensive anatomical atlas of the IMA and IMV was provided. Complex IMA patterns were associated with increased bleeding and operating time.

Objective: Colon cancer is associated with multiple levels of molecular heterogeneity. RNA processing converts primary transcriptional RNA to mature RNA, which drives tumourigenesis and its maintenance. The characterisation of RNA processing genes in colon cancer urgently needs to be elucidated. Methods: In this study, we obtained 1033 relevant samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to explore the heterogeneity of RNA processing phenotypes in colon cancer. Firstly, Unsupervised hierarchical cluster analysis detected 4 subtypes with specific clinical outcomes and biological features via analysis of 485 RNA processing genes. Next, we adopted the least absolute shrinkage and selection operator (LASSO) as well as Cox regression model with penalty to characterise RNA processing-related prognostic features. Results: An RNA processing-related prognostic risk model based on 10 genes including FXR1, MFAP1, RBM17, SAGE1, SNRPA1, SRRM4, ADAD1, DDX52, ERI1, and EXOSC7 was identified finally. A composite prognostic nomogram was constructed by combining this feature with the remaining clinical variables including TNM, age, sex, and stage. Genetic variation, pathway activation, and immune heterogeneity with risk signatures were also analysed via bioinformatics methods. The outcomes indicated that the high-risk subgroup was associated with higher genomic instability, increased proliferative and cycle characteristics, decreased tumour killer CD8+ T cells and poorer clinical prognosis than the low-risk group. Conclusion: This prognostic classifier based on RNA-edited genes facilitates stratification of colon cancer into specific subgroups according to TNM and clinical outcomes, genetic variation, pathway activation, and immune heterogeneity. It can be used for diagnosis, classification and targeted treatment strategies comparable to current standards in precision medicine. It provides a rationale for elucidation of the role of RNA editing genes and their clinical significance in colon cancer as prognostic markers.

BACKGROUND:We previously identified a novel lncRNA, CRART16, that could induce cetuximab resistance in colorectal cancer cells. This study explored the relationship of CRART16 expression to gastric cancer progression and the molecular mechanisms involved.METHODS:We evaluated CRART16 expression in gastric cancer tissues and adjacent normal tissues from the TCGA database and our hospital. Besides, we assessed its relationship with the overall survival (OS) of patients with gastric cancer. The effects of CRART16 on gastric cancer angiogenesis were determined by endothelial tube formation assay, spheroid sprouting assay, HUVEC invasion assay, and chick embryo chorioallantoic membrane (CAM) assay. The involvement of the lncRNA CRART16/miR-122-5p/FOS axis was analyzed by western blotting and dual-luciferase reporter assay. The functions of CRART16 were confirmed in xenograft mouse models.RESULTS:We found that CRART16 was substantially overexpressed in gastric cancer tissues compared with normal tissues, based on the TCGA database and our clinical samples. High expression of CRART16 correlated with more advanced tumor stages and poor prognosis. Overexpression of CRART16 in gastric cancer cells promoted proliferation, colony formation, angiogenesis, and bevacizumab resistance in vitro, and it promoted tumor growth and angiogenesis in vivo, and vice versa. CRART16 was found to downregulate miR-122-5p by acting as a sponge, upregulating the target oncogene FOS. Afterward, the increased FOS expression led to the upregulation of VEGFD.CONCLUSION:Our findings demonstrate that CRART16 promotes angiogenesis in vitro and in vivo, and CRART16 is a prognostic marker and therapeutic target in gastric cancer.

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:通过多层CT血管成像技术(MSCTA)回顾性分析左结肠动脉(LCA)与肠系膜下静脉(IMV)的解剖位置分型、IMV回流变异情况及IMV于根部以上水平的分支情况.方法:回顾性收集2018年9月至2021年11月92例患者(其中左半结肠癌8例、乙状结肠癌25例、直肠癌59例)的腹部CT增强扫描结果,并进行血管重建与术后录像复习.其中男56例,女36例,中位年龄63(54,72)岁.分别记录肠系膜下动脉(IMA)的分型、LCA/IMV分型及LCA、IMV至IMA根部的距离,IMV的回流汇入位置,IMV于根部以上的分支数量.通过卡方检验分析患者各指标之间与LCA/IMV解剖位置分型的相关关系.结果:MSCTA技术准确判断肠系膜动脉分型情况及LCA与IMV的位置关系准确率达98.91％.其中95.65％(88/92)的病例存在LCA,4例患者LCA缺如;1例患者IMV属于边缘型,85.06％(74/87)的IMV行走于LCA后方,余者走行于前方.IMA根部距LCA的距离平均为(30.11±11.85)mm,距IMV的距离平均为(24.77±10.36)mm.于IMA根部水平LCA走行于IMV外侧者最多,占37.50％(33/88),其次为交叉型(30.68％,27/88)、远侧型(17.05％,15/88)与内侧型(13.64％,12/88).IMV、LCA边缘型最为少见,仅占1.14％(1/88).LCA内侧型中,IMV距IMA根部的距离远于其他各型(P<0.05).LCA远侧型中,LCA距IMA根部的距离远于其他各型(P<0.05).IMV汇入脾静脉是最常见的回流模式,占55.43％(51/92);34.78％(32/92)的IMV汇入肠系膜上静脉;6.52％(6/92)的IMV汇入SMV与脾静脉交汇位置;3.26％(3/92)的IMV汇入空肠第一支静脉.IMA根部水平以上IMV有2个分支的最多,占51.09％(47/92);1个分支者次之,占25.00％(23/92);3个及以上分支者占20.65％(19/92);0个分支仅占3.26％(3/92).单因素分析显示,LCA/IMV解剖位置分型与患者性别、身高、体重、BMI、IMV回流方式、IMV与LCA的前后关系等均不相关.结论:MSCTA技术能准确判断IMA、LCA与IMV的解剖位置分型.肠系膜下动、静脉血管解剖变异形式多样,LCA/IMV解剖位置分型与人体相关指标无明确相关关系,因此腹腔镜结直肠癌根治术前通过MSCTA技术了解上述情况十分必要.

Despite advances in rectal cancer treatments, its local recurrence rate is still 4-10 percent. And an evidence-based definition of early recurrence is lacking. Our study hopes to establish a clear threshold to distinguish early and late recurrence, and analyze risk and prognostic factors for them. Rectal cancer patients who underwent proctectomy from 2009 to 2019 were included. Patients who received neoadjuvant treatment and with incomplete records were excluded. The optimal interval was obtained using the minimum P value approach. Risk factors for early recurrence were analyzed by logistic regression models, and prognostic factors associated with additional surgery were assessed by Cox proportional hazards models. The optimal interval for the definition of early recurrence was 26 months based on the subsequent prognosis (P < 0.001). The 5-year survival rate of early and late recurrence cohort was 32.5% and 57.1%, respectively (P < 0.001). Adjuvant radiotherapy was the independent protective factor for early recurrence. And the presence of lymphovascular invasion, positive surgical margin, and no re-neoadjuvant radiotherapy were independent prognostic factors for the survival of LRRC patients under additional surgery.

Surgery is the main treatment option for patients with local gastric cancer. However, surgery alone is usually not sufficient for stomach cancer patients, and combined therapies are recommended for these patients. In recent studies, some preoperative treatments have shown benefits. However, the treatment selection is still uncertain because previous studies failed to obtain a statistically significant difference between preoperative chemotherapy and preoperative chemoradiotherapy. Therefore, we plan to perform a systematic review and meta-analysis to compare the benefits among these preoperative treatments. This review includes randomized controlled trials with or without blinding as well as published studies, high-quality unpublished studies, full articles and meeting abstracts with an English context if sufficient results were provided for analysis. Data sources include the Cochrane Central Register of Controlled Trials, Embase, MEDLINE, major relevant international conferences and manual screening of references. Patients with a diagnosis of resectable primary gastric or EGJ adenocarcinoma (stage II or higher) who underwent surgery alone or preoperative treatment followed by surgery and who were pathologically confirmed as proposed by the AJCC 2017 guidelines without age, sex, race, subtypes of adenocarcinoma and molecular pathology limitations will be included. The following three interventions will be included: surgery alone, neoadjuvant chemistry followed by surgery and neoadjuvant chemoradiotherapy followed by surgery. All-cause mortality, overall survival (OS, the time interval from diagnosis to death) and/or progression-free survival (PFS, the time interval from diagnosis to disease progression or death from any cause) will be defined as major results of concern. The clinical and pathological response rate (according to RECIST and tumour regression score), R0 resection rate, quality of life and grade 3 or above adverse events (according to the National Cancer Institute Common Terminology Criteria for Adverse Events, NCI-CTCAE) will be defined as the secondary outcomes. The aim of this systematic review is to compare the benefits of different preoperative treatments for patients with locoregional stomach cancer. This systematic review will improve the understanding of the relative efficacy of these treatment options by providing the latest evidence on the efficacy of various treatment options in the management of gastric cancer patients and may guide clinical practice. PROSPERO CRD4202123718

在美国,痔是第三常见的门诊胃肠道诊断,每年有近400万门诊和急诊就诊,常见症状表现为便血、肛门坠痛不适、肛周肿物等[1].痔的发生被认为是多种致病因素共同作用的结果,由于无法具体评估每种因素在痔发生过程中所起作用的比例大小,所以关于痔的发病机制存在多种观点[2-3].有观点认为,痔是一种外周血管性疾病.直肠肛管血管丛(anorectal vascular plexus, AVP)即直肠肛管移行区域的黏膜下血管丛,具有防止肠液溢出肛门的机械性自制作用,因痔患者的AVP通常位于病灶黏膜下,其又被称为"痔血管丛"或"直肠海绵体",在内镜下常表现为迂曲扩张的血管团[4-5].

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.

Previous studies have shown that secreted protein acidic and rich in cysteine (SPARC) proteins can inhibit the development of cancer cells in various ways, such as by inhibiting angiogenesis and inhibiting cell proliferation. In fact, SPARC proteins may have an effect on the chemoresistance of gastric cancer cells to 5-Fluorouracil (5-FU), which needs further research in the future. Therefore, the purpose of this study was to explore the relationship between SPARC proteins and the chemosensitivity of gastric cancer cells to 5-FU. In vitro, after SPARC protein levels were regulated by plasmid, siRNA and human recombinant SPARC protein transfection in MGC-803, SGC-7901 and BGC-823 cells, we detected epithelial-mesenchymal transition (EMT), apoptosis markers and cell viability after 5-FU treatment. In vivo, we implanted BGC-823 cells with stable SPARC overexpression into nude mice. Tumour size was measured to assess the effect of SPARC protein on tumour formation and 5-FU chemosensitivity. In SGC-7901 and BGC-823 cells, both endogenous and exogenous upregulation of SPARC protein levels decreased cell viability, destroyed cytoskeletal F-actin, inhibited cell migration, and downregulated a series of transcription factors to inhibit cell EMT; it also upregulated cell apoptosis-related proteins to promote cell apoptosis. However, we obtained opposite results in SPARC knockdown MGC-803 cells. In vivo, compared with the control group, the group engrafted with BGC-823 cells stably overexpressing SPARC had a significant smaller tumour size. After 5-FU treatment, the new tumour gradually decreased in size. Our results show that the SPARC protein could enhance 5-FU chemosensitivity in gastric cancer cell lines by inhibiting EMT and promoting cell apoptosis.

Background Multivisceral resection may be the exclusive radical procedure for cT4b gastric cancer patients. However, most surgeons refuse to select surgery because of the theoretical higher mortality, morbidity and poorer prognosis. Methods We retrospectively reviewed cT4b gastric cancer patients who underwent surgery from January 1,1997 to December 31,2018. The primary endpoint was overall survival. Short-term results and prognostic values of clinical and pathologic factors were also analyzed. Results Patients underwent multivisceral resection had an acceptable mortality and morbidity. The overall 5-year survival rate of multivisceral resection was higher than that of palliative surgery (P < 0.05). And independent prognostic factors of multivisceral resection were R+ resection, extensive lymph node involved (>15), vascular cancer emboli, and postoperative chemotherapy. Conclusions: cT4b gastric cancer patients underwent multivisceral resection experience acceptable mortality and morbidity. The independent prognostic factors for multivisceral resection were completeness of resection, extensive lymph node involvement (>15), vascular cancer emboli, and postoperative chemotherapy.

Background Fibroblasts are the predominant cell type in the stroma of tumor, and cancer-associated fibroblasts (CAFs) promote cancer chemoresistance by secreting various bioactive molecules. However, the differential expression between CAFs and normal fibroblasts (NFs) and how can CAFs uniquely impact cancer cells are still unexplored. Methods Primary CAFs and NFs were cultured from gastric cancer specimens, and their variant expression was analyzed by RNA-sequencing. Chemoresistance was evaluated by measuring cell viability, apoptosis, and 3D-coculture techniques. Results CAFs were isolated from gastric cancers and defined by specific cell-surface markers. CAFs decreased the sensitivity of gastric cancer cells to 5-FU. RNA-sequencing showed that CAFs expressed a higher level of NRP2 than NFs. And the high expression of NRP2 was correlated with worse oncological outcomes in gastric cancer patients. Further study showed that the knockdown of NRP2 eradicated the resistance to 5-FU. And the secretion of stromal cell-derived factor-1 (SDF-1) was reduced following NRP2 knockdown. Furthermore, we found that the increased sensitivity to 5-FU was induced by DNA damage. And this process was mediated by predominant effectors of the Hippo pathway, YAP/TAZ. Conclusions The present study indicated that CAFs within gastric cancers promote chemoresistance through the expression of NRP2. The secretion of SDF-1 that mediated by VEGF/NRP2 signaling in CAFs and the activation of Hippo pathway in cancer cells in large part participated in this project.

Objective:To investigate the risk factors of low anterior resection syndrome (LARS)after low anterior resection of rectal cancer (Dixon).Methods:This retrospective study was conducted in Peking University First Hospital and Traditional Chinese Medicine Hospital of Shanxi Provice from Jan 2012 to Jun 2019. A cohort of 504 patients with rectal cancer was enrolled in the study. All the patients underwent anterior resection. The relationship between clinical-pathological data were analyzed retrospectively. Univariate analysis using χ 2 test. Logistic regression analysis was used to screen the influencing factors of LARS, and the Nomogram method was used to score each factors. Results:Univariate analysis showed that BMI≥28 kg/m 2(χ 2=9.450, P=0.002), the distance from the lower edge of the tumors to the anus <6 cm (χ 2=12.070, P=0.001), high ligation of the inferior mesenteric artery (IMA) (χ 2=8.279, P=0.004), preoperative neoadjuvant therapy (χ 2=11.230, P=0.001), postoperative anastomotic leakage (χ 2=11.840, P=0.001) were associated with severe LARS.Multivariate analysis showed that the distance from the lower edge of the tumors to the anus <6 cm ( OR=1.861, 95% CI: 1.289-2.688, P=0.001), BMI≥28 kg/m 2 ( OR=1.747, 95% CI: 1.022-2.987, P=0.041), high IMA ligation ( OR=1.688, 95% CI: 1.157-2.463, P=0.007), preoperative neoadjuvant therapy ( OR=2.719, 95% CI: 1.343-5.505, P=0.005) were independent risk factors for LARS. Nomogram model showed that the total factor ranged from 2 to 212, and the corresponding risk rate ranged from 30% to 80%. The patients with higher score have greater risk for severe LARS. The area under the predictive power curve of Nomogram model (AUC) was 0.749 (95% CI: 0.705-0.793, P<0.001). Conclusion:Lower tumor location, obesity, preoperative neoadjuvant therapy, high IMA ligation and postoperative anastomotic leakage increase the risk of severe LARS.

Gastric cancer is one of the most heterogeneous tumors with multi-level molecular disturbances. Sustaining proliferative signaling and evading growth suppressors are two important hallmarks that enable the cancer cells to become tumorigenic and ultimately malignant, which enable tumor growth. Discovering and understanding the difference in tumor proliferation cycle phenotypes can be used to better classify tumors, and provide classification schemes for disease diagnosis and treatment options, which are more in line with the requirements of today’s precision medicine. We collected 691 eligible samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, combined with transcriptome data, to explore different heterogeneous proliferation cycle phenotypes, and further study the potential genomic changes that may lead to these different phenotypes in this study. Interestingly, two subtypes with different clinical and biological characteristics were identified through cluster analysis of gastric cancer transcriptome data. The repeatability of the classification was confirmed in an independent Gene Expression Omnibus validation cohort, and consistent phenotypes were observed. These two phenotypes showed different clinical outcomes, and tumor mutation burden. This classification helped us to better classify gastric cancer patients and provide targeted treatment based on specific transcriptome data.

Anti-angiogenic therapy represents one of the most promising treatment modalities for human cancers. However, the response to antiangiogenic therapy in gastric cancer (GC) remains dismal. To help identify new strategies for antiangiogenic therapy in GC, we evaluated miR-205–5p expression in GC tissues from TCGA database and our hospital, and its functions in angiogenesis were explored in vitro and in vivo. We investigated miR-205–5p expression and microvessel densities (MVDs) in GC tissues and liver metastases from patients. The function and mechanisms of miR-205–5p were examined in human cell lines and in xenograft mouse models. Associations between miR-205–5p expression and clinical characteristics were analyzed using either Pearson's χ2 test or Fisher's exact test. Differences in overall survival (OS) distributions were evaluated using the log-rank test. Differences in measurement data were compared using Student's t-test and one-way ANOVA. We found that miR-205–5p expression was downregulated in GC tissues and was negatively correlated with CD31 expression in both TCGA and our clinical samples. GC cell lines expressed low levels of miR-205–5p, and miR-205–5p upregulation significantly impaired the proliferation and angiogenesis of GC cells. Moreover, vascular endothelial growth factor A (VEGFA) and fibroblast growth factor 1 (FGF1) expression and activation of extracellular-related kinase (ERK) signaling were suppressed by miR-205–5p. MiR-205–5p inhibition promoted malignant phenotypes by enhancing VEGFA and FGF1 expression, as well as the activation of ERK signaling. Angiogenesis and ERK signaling were decreased in response to VEGFA and FGF1 downregulation induced by miR-205–5p overexpression. The dual-luciferase reporter assay showed that VEGFA and FGF1 were direct targets of miR-205–5p. Xenograft mouse models revealed that miR-205–5p suppressed tumor growth by inhibiting neovascularization. Altogether, these results demonstrate that miR-205–5p suppresses angiogenesis in GC by attenuating the expression of VEGFA and FGF1, indicating that upregulation of miR-205–5p may represent as an antiangiogenic therapy for GC.

AimAccumulated studies have verified that tumor regression is associated with the prognosis of rectal cancer. However, stratified analysis within a certain stage is still unknown. The purpose of our study was to assess the impact of pathologic response on the survival of stageII and III rectal cancer patients after neoadjuvant chemoradiotherapy (nCRT).MethodsClinicopathologic characteristics and tumor regression scores (TRS) were assessed in 236 rectal cancer patients who treated with nCRT followed by surgery. Survival analysis was performed using Cox proportional hazards models.ResultsAmong these patients, the stage of 88 patients was ypII, and 91 patients were with the stage of ypIII. The median follow-up time was 59.8 months. TRS was not an independent prognostic factor in ypII patients while it was significantly associated with the prognosis of ypIII patients (5-year survival rate 67.2% vs. 42.5%, P < 0.001). Furthermore, ypIII patients with the response to nCRT had similar survival to that of ypII patients (5-year survival rate 67.2% vs. 70.5%, P = 0.56). For ypIII patients, multivariable analysis showed that well differentiation, negative surgical margin, and the administration of adjuvant chemotherapy were associated with better survival. The surgical margin and differentiation were prognostic factors for ypII patients.ConclusionsypIII rectal cancer patients with poor response to preoperative treatment are at high risk of worse oncological outcomes.