Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, and its current therapy is limited by chemoresistance and toxicity, underscoring an urgent unmet need for more effective and safer therapeutic strategies. Luteolin, a natural flavonoid with potent antiangiogenic properties, offers therapeutic promise, but its clinical utility is hampered by poor aqueous solubility. Here, we developed a dual-responsive polymeric nanoparticle platform by covalently conjugating Luteolin into a biocompatible poly(ethylene glycol) (PEG)-based polyurethane backbone to form Luteolin@PEG-600 nanoparticles. The resulting spherical nanoparticles (∼161 nm) demonstrated excellent colloidal stability and successfully amorphized Luteolin, greatly improving its apparent aqueous solubility. Crucially, the system remained stable at physiological pH (7.4) while exhibiting accelerated drug release in response to tumor-associated stimuli: acidic pH and reactive oxygen species. In vitro, the Luteolin@PEG-600 nanoparticles suppressed endothelial cell migration and tube formation by inhibiting the VEGF/VEGFR2 signaling pathway. In a CRC xenograft mouse model, the Luteolin@PEG-600 nanoparticles significantly suppressed tumor growth with no apparent systemic toxicity. Histological analysis of tumors confirmed that the treatment induced apoptosis, inhibited proliferation, and markedly reduced microvessel density. Transcriptomic analysis further confirmed that the nanoparticles concurrently downregulated the proangiogenic hypoxia pathway and activated apoptosis. Taken together, our findings demonstrate that this dual-responsive nanoparticle system overcomes Luteolin’s limitations, providing a safe and effective antiangiogenic and antitumor strategy that directly targets the VEGF/VEGFR2–hypoxia axis in CRC. This work validates the Luteolin@PEG-600 nanoparticles as a highly promising nanomedicine candidate for CRC therapy with clear potential for further preclinical development.

While recent studies have highlighted oxidative stress (OS) as a pivotal factor influencing tumor dynamics, its specific interactions within the tumor microenvironment (TME) of colorectal cancer (CRC) remain elusive. This study seeks to unveil the impact of OS on the CRC TME and to develop an advanced OS-related risk signature (OSRRS) model. We analyzed OS-related pathway activities using both single-cell and bulk RNA-seq data. An unsupervised clustering algorithm was utilized to identify OS-related subtypes. Based on genes associated with the OS pathways, we constructed an OSRRS model employing the LASSO Cox analysis. For validation, we employed quantitative real-time polymerase chain reaction (qRT-PCR) coupled with immunohistochemical (IHC) analyses on tissue microarrays (TMA) to confirm the expression of the identified gene. Examination of the single-cell RNA-seq GSE132465 dataset revealed a universal elevation in OS-associated pathway activities within malignant cells. By integrating this with the bulk RNA-seq TCGA-CRC dataset, we identified two unique OS-specific clusters. This led to the establishment of a 12-gene OSRRS using the LASSO Cox method. The robustness of our model was further verified using the GSE39582 and GSE17538 cohorts. Notably, increased expression of the UCN gene was observed in CRC specimens, as confirmed by qRT-PCR and IHC assays on TMA. In this research, we delineated two distinct subtypes of CRC associated with OS. The developed OSRRS holds promise as a candidate prognostic and stratification tool for CRC management. Collectively, these results shed light on the intricate role of OS in CRC pathology.

BackgroundThe focus of this study was to determine the optimal time interval between neoadjuvant chemoradiotherapy (nCRT) and surgery in patients with locally advanced rectal cancer (LARC) who had an unfavorable pathological response, as well as to investigate the correlation between long-term outcomes and the duration of this interval.MethodsThe present study retrospectively analyzed patients with locally advanced rectal cancer who underwent nCRT followed by total mesorectal excision between (TME) January 2018 and September 2021. Patients included in this study had an unfavorable pathological response, confirmed as tumor regression grade (TRG) 2-3. X-tile analysis was subsequently conducted to determine the optimal cut-off value for the time interval between nCRT and surgery. Furthermore, Cox proportional hazards regression analyses were performed to identify independent prognostic factors, and the Kaplan-Meier method was used to estimate long-term survival.ResultsThe study cohort comprised of 114 patients (51.35%) in the longer interval group (>8 weeks), while the remaining 108 patients (48.65%) belonged to the shorter interval group (≤8 weeks). Univariable and multivariate Cox proportional hazards regression analyses revealed that a longer interval time was identified as an independent risk factor for overall survival (HR: 2.14, 95% CI: 1.01-4.55, P=0.048) and disease-free survival (HR: 2.03, 95% CI: 1.09-3.77, P=0.025) among these patients. Moreover, patients in the longer interval group exhibited significantly worse OS and DFS compared to those in the shorter interval group (3-year OS: 87.2% vs 68.2%, P=0.001; 3-year DFS: 80.4% vs 62.7%, P=0.003). Furthermore, similar results were observed in subgroup analyses based on different TRG scores.ConclusionsThe surveillance and monitoring should be promptly conducted following nCRT in order to promptly identify patients with an unfavorable pathological response, who would benefit from timely radical surgery within 8 weeks.

The difficulty of wound healing due to skin defects has been a great challenge due to the complex inflammatory microenvironment. Delayed wound healing severely affects the quality of life of patients and represents a significant economic burden for public health systems worldwide. Therefore, there is an urgent need for the development of novel wound dressings that can efficiently resist drug-resistant bacteria and have superior wound repair capabilities in clinical applications. In this study, we designed an adhesive antimicrobial hydrogel dressing (GMH) based on methacrylic-anhydride-modified gelatin and oxidized hyaluronic acid formed by Schiff base and UV-induced double cross-linking for infected wound repair. By inserting PDA nanoparticles into the hydrogel (GMH/PDA), the hydrogel has the capability of photothermal conversion and exhibits good photothermal antimicrobial properties under near-infrared (NIR) light irradiation, which helps to reduce the inflammatory response and avoid bacterial infections during the wound healing process. In addition, GMH/PDA hydrogel exhibits excellent injectability, allowing the hydrogel dressings to be adapted to complex wound surfaces, making them promising candidates for wound therapy. In conclusion, the multifunctional injectable GMH/PDA hydrogel possesses high antimicrobial efficiency, antioxidant properties and good biocompatibility, making them promising candidates for the treatment of infected skin wounds.

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Colorectal cancer is the second common cause of cancer death. Immunotherapy has became a new therapy apart from traditional therapy such as surgery,etc. There are controversial about the efficiency and adverse reaction of anti-PD-1/PD-L1 drugs. In this article, the research and application of PD-1 pathway blockage are reviewed from the aspects of PD-1 pathway and blockage, clinical applications of anti-PD-1/PD-L1 drugs in colorectal cancer, treatment resistance, adverse reactions and biomarkers of effective prediction.

NOSES I is mainly applicable to patients with small tumors located in the lower rectum. NOSES I has no differences regarding the extent of resection and lymph node dissection when compared with the conventional laparoscopic radical resection of rectal cancer. The main differences between conventional laparoscopic surgery and NOSES I are digestive tract reconstruction and specimen extraction. The main operating procedures of NOSES I include transanal rectal eversion, extracorporeal specimen removal, and totally laparoscopic end-to-end anastomosis between sigmoid colon and rectum. In addition, this technique may facilitate to determine the distance from the distal edge of the tumor to the dentate line under direct vision and avoid positive distal resection margin, thereby greatly improve the possibility of ultralow anastomosis. At present, NOSES I mainly includes two approaches of digestive tract reconstruction, namely NOSES IA and NOSES IB. There are some slight differences between these two approaches. NOSES IA involves the application of nontouch technique, but NOSES IB does not. Therefore, the indication of NOSES IB is wider than NOSES IA, but both of the approaches achieve the same surgical outcome. On the basis of ensuring the radical resection, NOSES I has obvious advantages such as less trauma, faster recovery, better cosmetic effect, etc., which is a worthy technique to be mastered and popularized by surgeons.

PurposeTotal laparoscopic anterior resection (tLAR) has been gradually applied in the treatment of rectal cancer (RC). This study aims to develop a scoring system to predict the surgical difficulty of tLAR.MethodsRC patients treated with tLAR were collected. The blood loss and duration of excision (BLADE) scoring system was built to assess the surgical difficulty by using restricted cubic spline regression. Multivariate logistic regression was used to evaluate the effect of the BLADE score on postoperative complications. The random forest (RF) algorithm was used to establish a preoperative predictive model for the BLADE score.ResultsA total of 1,994 RC patients were randomly selected for the training set and the test set, and 325 RC patients were identified as the external validation set. The BLADE score, which was built based on the thresholds of blood loss (60 ml) and duration of surgical excision (165 min), was the most important risk factor for postoperative complications. The areas under the curve of the predictive RF model were 0.786 in the training set, 0.640 in the test set, and 0.665 in the external validation set.ConclusionThis preoperative predictive model for the BLADE score presents clinical feasibility and reliability in identifying the candidates to receive tLAR and in making surgical plans for RC patients.

Purpose This study performed an analysis of clinicopathological characteristics, surgical treatment strategy, and survival for CRC patients with LM between China and the USA. Methods The CRC patients with simultaneous LM were identified from the Surveillance, Epidemiology, and End Results (SEER) registry and the Chinese National Cancer Center (CNCC) database from 2010 to 2017. We assessed 3-year cancer-specific survival (CSS) according to surgical treatment strategy and time period. Results Differences in patient age, gender, primary tumor location, tumor grade, tumor histology, and tumor stage were observed between the USA and China. Compared to the USA, a larger proportion of patients in China underwent both primary site resection (PSR) and hepatic resection (HR) (35.1% vs 15.6%, P < 0.001), and fewer patients underwent only PSR in China (29.1% vs 45.1%, P < 0.001). From 2010 to 2017, the proportion of patient who underwent both PSR and HR has increased from 13.9% to 17.4% in the USA and from 25.4% to 39.4% in China. The 3-year CSS were increasing over time in both the USA and China. The 3-year CSS of patients receiving HR and PSR were significantly higher than those receiving only PSR and patients treated with no surgery in the USA and China. There were no significant differences of 3-year CSS between the USA and China after adjustment ( P = 0.237). Conclusions Despite the distinctions of tumor characteristics and surgical strategy in patients with LM between the USA and China, increased adoption of HR has contributed to the profound improvements of survival during recent decade.

To the Editor: Natural orifice specimen extraction surgery (NOSES) is an actively developing approach for extracting specimens and performing non-incisional colorectal cancer surgery. Previous studies have shown that its effectiveness and safety in the surgical treatment of rectal cancer are similar to those of conventional laparoscopic surgery. NOSES was demonstrated to be a possible alternative approach to conventional laparoscopy, for which a mini-laparotomy is used to extract the specimen, as there were no differences in surgical characteristics and short-term outcomes.[1] Recently, new promising approaches have been demonstrated for rectal tumors extraction with bowel eversion and extra-abdominal resection.[2] While segmental resections for colon cancer have been widely adopted, more opportunities for NOSES implementation for different colon cancer locations become possible. According to Japanese guidelines, localized forms of colon cancer can be resected within 10-cm resection margins, depending on the feeding branch inflow pattern. Thus, the results of NOSES should be analyzed in the context of segmental colon resection. This study evaluated the surgical and short-term outcomes of NOSES in the segmental resections of colon cancer by comparing with those of conventional laparoscopic resection (CLR) in a multicenter retrospective study based on data from Chinese and Russian surgical centers. This retrospective matched case-control study included patients who had undergone surgical treatment for colon cancer using either NOSES or CLR between 2014 and 2020 in two surgical centers in Moscow, Russia, and Beijing, China. The selection criteria for inclusion in the study were: (1) 18–80 years of age, (2) adenocarcinoma of the colon, (3) tumors diagnosed at the preoperative stage as cTis-3, cN0–N2, (4) tumors ≤ 5 cm in diameter, and (5) a body mass index (BMI) ≤ 35 kg/m2. Patients were excluded if multiple primary cancer, or any signs of laparotomy were present. Firstly, patients were matched based on their clinical diagnosis. Secondly, patients were filtered based on sex, then age was considered (a 5-year difference was acceptable), and lastly, height and weight were matched. If the patients were similar according to these criteria, a matching pair "NOSES-CLR" was formed for further analysis. After matching the inclusion criteria, 92 pairs were formed for comparative analysis. Three pairs were excluded because of the need for conversion from CLR to open surgery: adhesions, found intraoperatively (n = 1), locally advanced tumors, hardly managed laparoscopically (n = 2). Patients diagnosed with pT4b intraoperatively were not excluded from the study if radical R0 surgery was performed laparoscopically. The final study group included 89 patients who had undergone natural orifice specimen extraction. The final control group included 89 patients who underwent conventional laparoscopy. We assessed the surgical outcomes, intraoperative and postoperative complications, and recovery rates in both groups. The patients were adjusted for sex, age, BMI, and tumor size and location. The surgeries were performed by five chief surgeons who had more than 10 years of experience in laparoscopic colorectal surgery. Preoperative staging was based on colonoscopy with biopsy and histological assessment, chest computed tomography (CT), abdominal CT and/or ultrasonography, and pelvic CT and/or magnetic resonance imaging (MRI). Patients who met the abovementioned criteria for inclusion were offered the NOSES procedure preoperatively. This study was approved by the local ethics committee of each hospital and followed the principles of the Declaration of Helsinki. Informed consent for participation in the study was obtained from each of the patients. The preoperative and postoperative assessment of the patients was the same in both groups. Although resection was performed in the same way in both groups, different specimen extraction approaches were used. The size of the removed colon was defined by margins of ≤ 10 cm on the proximal and distal sides of the colon from the tumor. The mesocolon segment associated with the resected colon was excised within the fascial envelope. The D3 lymph node area was removed along the main feeding arteries with superior mesenteric or inferior mesenteric artery dissection, where appropriate. The surgeons were free to choose the number of laparoscopic ports and the site of placement. The right-sided colectomy procedure included mobilization of the right colon and its mesentery, ligation of the feeding vessels confirmed by CT at the root of the colic vessels with D2 or D3 lymph node dissection, where appropriate with complete lymph node dissection. The colic branches that did not feed the resected part of the colon were preserved. NOSES was planned preoperatively, with the transvaginal approach indicated for most right-sided colon resections. In male patients, the specimen after right hemicolectomy was extracted via colotomy in the upper rectum. The procedures for a left-sided colectomy or sigmoid colon resection were performed with isolation and transection of the vascular pedicle with preservation of the left colic artery and/or superior rectal artery, D2 or D3 lymph node dissection, and colonic or colorectal anastomosis. In the NOSES group, the specimens were extracted through the rectal stump or through a separate vaginal incision. The transanal extraction procedure included introduction of a sterile plastic sleeve through the anus and rectum, followed by specimen elimination through the sleeve. Transvaginal extraction involved a 3 to 4 cm transverse posterior colpotomy, the introduction of a sterile plastic sleeve through the vaginal incision, and extraction of the specimen. In the CLR approach, specimens were extracted via midline mini-laparotomy or Pfannenstiel incision. The primary endpoints of the study were the surgical outcomes, recovery rates and the rate of short-term intrahospital complications. The secondary endpoints were the clinicopathological data, the procedure characteristics, length of surgery, blood loss volume, time to first flatus and defecation, length of hospital stay, the resection margin, and the lymph node harvest. Statistical analysis was performed using Pearson's chi-squared test or Fisher's exact test, and the Mann–Whitney U test was performed to determine whether the differences were statistically significant. The differences in categorical data were analyzed using Student's t-test. Quantitative data are reported as the mean and standard error mean (95% Confidence interval [CI]). The statistical analysis was performed using SPSS 26 (SPSS Inc., Chicago, Illinois, USA). No statistically significant differences were observed among the clinical and morphological characteristics of the patients [Supplementary Table 1, https://links.lww.com/CM9/B559]. NOSES was associated with a tendency for a greater number of harvested lymph nodes (25.70 ± 1.41 vs. 27.75 ± 1.54, P = 0.37). It decreased the length of surgery, but the difference was not statistically significant (165.93 ± 6.35 min vs. 181.25 ± 7.02 min, P = 0.15). Blood loss was significantly lower in the NOSES group (40.17 ± 2.81 mL vs. 52.25 ± 4.12 mL, P = 0.03). In patients treated with NOSES, the first defecation was observed earlier (3.85 ± 0.18 days vs. 4.29 ± 0.17 days, P = 0.02). The patients from NOSES group had shorter hospital stays (8.37 ± 0.44 days vs. 9.93 ± 0.46 days, P <0.01). No intraoperative complications were observed in either of the groups, and there were no significant differences in the postoperative complication rates. In the NOSES group, reoperations were performed to prevent stoma formation due of anastomotic leakage. In the CLR group, one patient underwent surgery due to anastomotic leakage. Three cases of anastomotic leakage were diagnosed in the NOSES group, and one in the CLR group. There were two cases of wound infection at the sites of the mini-laparotomy incisions in the CLR group. The incidence of short-term complications was not significantly higher in neither group. No 30-day mortality was observed in either group [Supplementary Table 1, https://links.lww.com/CM9/B559]. NOSES was introduced as a promising alternative approach to specimen extraction, allowing non-incisional radical surgery for colorectal cancer, mostly for distal sigmoid and rectal cancer surgery.[1] However, there have been few studies of NOSES for colon cancer. The implementation of NOSES in left-colon cancer treatment in a prospective randomized control study of 40 patients showed that the postoperative anorectal function, complications, and hospital stay were similar in the CLR and NOSES groups.[3] A propensity score-matched analysis of 45 patients who underwent transcolonic natural orifice specimen extraction after right hemicolectomy for ascending colon cancer showed less postoperative pain, less need for analgesia, and a lower inflammatory response, while the 3-year overall survival was the same.[4] Therefore, the use of this method in segmental colonic resection with complete mesocolon excision for colon cancer, and its oncological safety, is promising, but requires further study. The learning curve associated with NOSES, is one of the factors, limiting the wide implementation of NOSES in colorectal cancer. However, we showed that NOSES decreases the length of operations. Moreover, NOSES resulted in less blood loss in our study. Another factor limiting NOSES adoption is the need for extended resections in colon cancer surgery. In our study, the lymph node number was observed to be slightly higher in the NOSES group, despite the economic segmental resections, performed in both institutions—an average of 27 lymph nodes were found in specimens extracted through the natural orifice in the NOSES group. In addition, no positive resection margins were observed in this group. Therefore, segmental resections with natural orifice specimen extraction can be adopted. Importantly to mention, the time to first flatus and blood loss decreased, resulting in better recovery rates. However, the influence of the patients' physical status and tumor characteristics should be analyzed to prove that extraction type is a significant factor in the studied outcomes. The results of recent meta-analysis and a systematic review support the equivalence of NOSES and CLR in terms of the postoperative outcomes and survival rates, leading to better quality of life. In addition, NOSES was significantly associated with lower intraoperative bleeding (P <0.001). In our study, the primary and secondary outcomes were better in the NOSES group, which is consistent with the meta-analysis by Brincat et al.[5] Our study has several limitations. It was a retrospective comparative study, and randomized prospective controlled studies are necessary to confirm our results. In some cases, tumors extracted through a natural orifice were found to be pT4, but still included in the study as they met the inclusion criteria and were misdiagnosed preoperatively and were found to be feasible for NOSES. Thus, it is important to determine whether this approach is possible in T4 cancer to improve short-term outcomes and survival rates. In summary, this study showed that the NOSES technique is better than CLR in terms of surgical and short-term postoperative outcomes. Both approaches are associated with a similar number of complications; however, NOSES improves the surgical results and recovery rates. NOSES should be considered for wide implementation in segmental colectomies for colon cancer. Conflicts of interest None.

Purpose Colorectal cancer is a common malignant tumor worldwide. In China, the ratio of rectal cancer to colon cancer in terms of incidence is close to 1: 1. Low rectal cancer accounts for more than half of all cases of rectal cancer. In recent years, the proportion of rectal cancer has trended downward, however the incidence of rectal cancer in younger adults is increasing. The CACA Guidelines for Holistic Integrative Management of Rectal Cancer were edited to help improve the diagnosis and comprehensive treatment in China. Methods This guideline has been prepared by consensuses reached by the CACA Committee of Colorectal Cancer Society, based on a careful review of the latest evidence including China’s studies, and referred to domestic and international relative guidelines, also considered China’s specific national conditions and clinical practice. Results The CACA Guidelines for Holistic Integrative Management of Rectal Cancer include the epidemiology of rectal cancer, prevention and screening, diagnosis, treatment of nonmetastatic and metastatic rectal cancer, follow-up, and whole-course rehabilitation management. Conclusion Committee of Colorectal Cancer Society, Chinese Anti-Cancer Association, standardizes the diagnosis and treatment of rectal cancer in China through the formulation of the CACA Guidelines.

Background: Total laparoscopic anterior resection (tLAR) and natural orifice specimen extraction surgery (NOSES) has been widely adopted in the treatment of rectal cancer (RC). However, no study has been performed to predict the short-term outcomes of tLAR using machine learning algorithms to analyze a national cohort.Methods: Data from consecutive RC patients who underwent tLAR were collected from the China NOSES Database (CNDB). The random forest (RF), extreme gradient boosting (XGBoost), support vector machine (SVM), deep neural network (DNN), logistic regression (LR) and K-nearest neighbor (KNN) algorithms were used to develop risk models to predict short-term complications of tLAR. The area under the receiver operating characteristic curve (AUROC), Gini coefficient, specificity and sensitivity were calculated to assess the performance of each risk model. The selected factors from the models were evaluated by relative importance.Results: A total of 4313 RC patients were identified, and 667 patients (15.5%) developed postoperative complications. The machine learning model of XGBoost showed more promising results in the prediction of complication than other models (AUROC 0.90, P < 0.001). The performance was similar when internal and external validation was used. In the XGBoost model, the top four influential factors were the distance from the lower edge of the tumor to the anus, age at diagnosis, surgical time and comorbidities. In risk stratification analysis, the rate of postoperative complications in the high-risk group was significantly higher than in the medium-and low-risk groups (P < 0.001).Conclusion: The machine learning model shows potential benefits in predicting the risk of complications in RC patients after tLAR. This novel approach can provide reliable individual information for surgical treatment recommendations.& COPY; 2023 Published by Elsevier Ltd.

Background This study aimed to investigate the association between radiotherapy for cancer and cardiovascular disease (CVD) deaths and evaluate the relative risk for CVD deaths in the general population and among patients with cancer treated with radiotherapy. Methods and Results The statistics of cancers from 16 sites were extracted from the Surveillance, Epidemiology, and End Results database and evaluated. Multivariable Cox proportional hazards regression analysis was used to analyze the association between radiotherapy and cardiovascular‐specific survival. The standardized mortality ratio for CVD deaths was estimated by comparing the observed deaths of patients with cancer treated with radiotherapy to the expected deaths of the general population. Of the 2 214 944 patients identified from the database, 292 102 (13.19%) died from CVD. Multivariable Cox proportional hazards regression analyses demonstrated that radiotherapy was an independent risk factor for cardiovascular‐specific survival among patients with lung and bronchus, cervix uteri, corpus uteri, and urinary bladder cancers. The long‐term cardiovascular‐specific survival of patients with cancer who underwent radiotherapy was significantly lower than that of patients who did not undergo radiotherapy. The incidence of CVD deaths among patients with lung and bronchus, cervix uteri, corpus uteri, and urinary bladder cancers who underwent radiotherapy was higher than that among the general population. Standardized mortality ratio significantly decreased with increasing age at cancer diagnosis, gradually decreased within 10 years of diagnosis and increased after 10 years of diagnosis. Conclusions Radiotherapy is associated with worse cardiovascular‐specific survival in patients with lung and bronchus, cervix uteri, corpus uteri, and urinary bladder cancers. Long‐term surveillance of cardiovascular conditions should be performed after radiotherapy.

Objective:To explore the prognostic impact of neoadjuvant therapy response on survival in patients with locally advanced rectal cancer.Methods:The clinicopathological data of 218 patients with locally advanced rectal cancer (LARC) who received preoperative neoadjuvant chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively collected. Patients were divided into good response (TRG3~4) and poor response (TRG0~2) based on Dowrak/R?del tumor regression grade (TRG) criteria. Cox proportional regression univariate and multivariate analyses were performed to identify the influence factors for disease-free survival (DFS) and overall survival (OS). Kaplan-Meier method was used to plot the survival curve and the Log-rank test was used to compare the differences in tumor survival.Results:A total of 218 patients were enrolled in this study, including 126 patients with good treatment responses and 92 patients with poor treatment responses. Univariate and multivariate Cox regression analysis identified that poor response to neoadjuvant therapy was an independent risk factor for DFS (HR=3.85, 95%CI: 1.40~10.60; P=0.009) and OS (HR=3.81, 95%CI: 1.02~14.20; P=0.046). 5-year DFS was 93.46% in the good response group and 65.04% in the poor response group (χ2=28.23, P＜0.001); and 5-year OS were 95.38% in the good response group and 78.99% in the poor response group (χ2=18.51, P＜0.001).Conclusion:Neoadjuvant therapy response was an independent prognostic factor for DFS and OS in locally advanced rectal cancer patients, and good response predicts better oncology prognosis. This study provides a theoretical basis for further clinical research on risk stratification.

Background: Some recent studies on insulin receptor tyrosine kinase substrate (IRTKS) have focused more on its functions in diseases. However, there is a lack of research on the role of IRTKS in carcinomas and its mechanism remains ambiguous. In this study, we aimed to clarify the role and mechanism of IRTKS in the carcinogenesis of colorectal cancer (CRC).Methods: We analysed the expression of IRTKS in CRC tissues and normal tissues by researching public databases. Cancer tissues and adjacent tissues of 67 CRC patients who had undergone radical resection were collected from our center. Quantitative real-time polymerase chain reaction and immunohistochemistry were performed in 52 and 15 pairs of samples, respectively. In vitro and in vivo experiments were conducted to observe the effect of IRTKS on CRC cells. Gene Set Enrichment Analysis and Metascape platforms were used for functional annotation and enrichment analysis. We detected the protein kinase B (AKT) phosphorylation and cell viability of SW480 transfected with small interfering RNAs (siRNAs) with or without basic fibroblast growth factor (bFGF) through immunoblotting and proliferation assays.Results: The expression of IRTKS in CRC tissues was higher than that in adjacent tissues and normal tissues (all P < 0.05). Disease-free survival of patients with high expression was shorter. Overexpression of IRTKS significantly increased the proliferation rate of CRC cells in vitro and the number of tumor xenografts in vivo. The phosphorylation level of AKT in CRC cells transfected with pLVX-IRTKS was higher than that in the control group. Furthermore, siRNA-IRTKS significantly decreased the proliferation rate of tumor cells and the phosphorylation level of AKT induced by bFGF.Conclusion: IRTKS mediated the bFGF-induced cell proliferation through the phosphorylation of AKT in CRC cells, which may contribute to tumorigenicity in vivo.

Objective:To predict cancer-specific survival (CSS), we developed a novel nomogram model and a risk classification system for classifying risk levels of metastatic colorectal cancer (mCRC) patients.Methods:The data was extracted from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database between 2010 to 2015. All eligible cases were randomly divided into training and validating cohorts. Cox proportional hazards model was used to explore the independent risk factors for CSS. A novel nomogram model was developed to predict the CSS and evaluated via internal and external validations.Results:Using the multivariate Cox proportional hazards model, the independent risk factors were identified for CSS. Then a novel nomogram was developed for CSS based on such factors. The concordance indexes (C-index) were 0.718 (95%CI: 0.712~0.725) for this nomogram and 0.722 (95%CI: 0.711~0.732) for the validating cohort, indicating a good discrimination. The calibration plots and decision curve analysis (DCA) showed good consistency and nice potential clinical validity. A risk classification system divided all patients into three groups and Kaplan-Meier curves indicated good stratification and discrimination for CSS among different groups. In the total cohorts, the median CSS of patients in the low-risk, intermediate-risk, and high-risk groups was 36 months (95%CI: 34.987~37.013), 18 months (95%CI: 17.273~18.727), and 5 months (95%CI: 4.503~5.497), respectively.Conclusions:We developed a novel nomogram model to predict the CSS for synchronous mCRC patients. Furthermore, a risk classification system could contribute to accurately assessing the prognosis and guiding treatment.

目的:探讨经自然腔道取标本手术(natural orifice specimen extraction surgery,NOSES)的安全性,并比较3种取标术式在直肠癌治疗中的近期疗效和远期预后.方法:回顾性分析接受腹腔镜NOSES的Ⅰ～Ⅲ期直肠癌患者的临床资料.直肠NOSES手术包括外翻切除式、拉出切除式和切除拖出式3种.比较3种取标本方式的术后并发症、5年无病生存期(disease-free survival,DFS)、5年局部复发率(local recurrence rate,LRR)和5年远处转移率(distant metastasis rate,DMR)等指标.结果:本研究共有268例直肠癌患者符合入组标准,包括83例外翻切除式,75例拉出切除式,110例切除拖出式.肿瘤位置与手术方式的选择具有显著相关性,术后全部患者的并发症发生率为12.3％,其中外翻切除组为18.1％,高于拉出切除组(13.3％)和切除拖出组(7.3％),P=0.073.全部患者5年DFS、LRR及DMR分别是85.0％、4.2％和11.0％.切除拖出组患者5年DFS高于其他两组,外翻切除组患者5年LRR要高于其他两组,而5年DMR在外翻切除组中最低,差异均无统计学意义.结论:直肠癌NOSES 3种术式具有良好安全性和肿瘤学预后,肿瘤位置是选择手术方式的决定因素.

目的 调查国内结直肠外科应用加速康复外科(enhanced recovery after surgery,ERAS)的现状并总结存在的问题.方法 本研究以中国医师协会结直肠肿瘤专委会的会员为调查对象,采用在线问卷形式进行收集,所有受访者自愿参加.受访者通过链接地址进入调查问卷主页进行访问,完成问卷后保存并提交.结果 共发出问卷120份,最终107位受访者完成电子问卷调查.其中73位(68.2％)常规开展ERAS,34位(31.8％)未常规开展ERAS.针对结直肠手术ERAS的11个项目中,受访者ERAS措施开展项目数量主要集中在3～7项,其中开展4项ERAS措施的受访者最多(25位,23.4％);而针对不同ERAS措施开展的调查结果显示,11项ERAS措施中仅有4项ERAS措施的开展人数超过半数.年龄＞45岁的受访者更倾向于术前不进行机械性肠道准备(P＜0.001)和主张术后早期经口进食(P=0.008);医院床位数＞1000张的受访者更倾向于术前口服碳水化合物(P=0.012)和术后多模式镇痛(P＜0.001);每年结直肠手术量＞200例的受访者更倾向于实施术前口服碳水化合物(P=0.018);开展微创手术比例＞50％的受访者更倾向于选择多模式镇痛(P=0.047);而肿瘤专科医院的受访者反而更加推崇缩短术后住院时间,推荐患者早期出院(P=0.014).常规开展ERAS的医院(P＜0.001)、术前口服碳水化合物(P＜0.001)、术前不放置胃管(P=0.019)、术后早期饮水(P=0.012)及术后早期经口进食(P=0.038)均与更短的术后平均住院时间有关.结论 我国结直肠外科领域在ERAS的应用方面尚未普及,在不同医院、不同医生之间存在差异性,仍需要不断推广.

BackgroundAlthough radiation therapy (RT) improves local control for rectal cancer (RC), the long-term risks from RT, including development of a secondary malignancy, are controversial. The risk and prognosis of secondary bladder cancer (SBC) in RC patients undergoing RT have not been adequately studied. Our goal is to investigate the impact of RT on the risk of developing SBC and assess their survival outcomes.MethodsThis large population-based study included RC patients as their initial primary cancer from nine registries of the Surveillance, Epidemiology and End Results (SEER) database between 1973 and 2015. The cumulative incidence of SBC was assessed by using Fine and Gray’s competing risk regression. The standardized incidence ratio (SIR) was used to compare the incidence of SBC in RC survivors to the US general population. The Kaplan-Meier method was used to evaluate the 10-year overall survival (OS) and 10-year cancer specific survival (CSS) for patients with SBC.ResultsOf 74,646 RC patients, 24,522 patients were treated with surgery and RT and 50,124 patients were treated with surgery alone. The incidence of SBC was 1.85% among patients who received RT and 1.24% among patients who did not. The incidence of SBC in RC patients who received RT was higher than the US general population (SIR, 1.35; 95% CI, 1.19-1.53, P<0.05), and decreased with increasing age at diagnosis, and increased with time since diagnosis. In competing risk regression analysis, undergoing RT was associated with a higher risk of SBC (hazard ratio [HR], 1.443, 95% confidence interval [CI], 1.209-1.720; P<0.001). The results of the dynamic SIR for SBC revealed that a slightly increased risk of SBC was observed after RT in the early latency, and was significantly related to the variations of age at RC diagnosis and decreased with time progress. The 10-year OS and CSS among SBC patients after RT were comparable to SBC patients after NRT.ConclusionRadiation was associated with an increased risk of developing SBC in RC patients, and special attention should be paid to the surveillance of these patients.

IMPORTANCE Radiotherapy is a common treatment for rectal cancer, yet the risk of second gynecological malignant neoplasms (SGMNs) in patients with rectal cancer undergoing radiotherapy have not been adequately studied. OBJECTIVE To investigate the association between radiotherapy and the risk of individual types of SGMN in patients with rectal cancer and assess survival outcomes. DESIGN, SETTING, AND PARTICIPANTS A large population-based cohort study was designed to identify the risk of SGMNs in patients with rectal cancer diagnosed from January 1973 to December 2015. The statistical analysis was conducted from September 2019 to April 2020. The study was based on the 9 cancer registries of Surveillance, Epidemiology, and End Results database. A total of 20 142 female patients with rectal cancer in localized and regional stage were included. EXPOSURE Receipt of neoadjuvant radiotherapy for rectal cancer. MAIN OUTCOMES AND MEASURES The development of an SGMN defined as any type of GMN occurring more than 5 years after the diagnosis of rectal cancer. The cumulative incidence of SGMNs was estimated by Fine-Gray competing risk regression. Poisson regression was used to evaluate the radiotherapy-associated risk for SGMNs in patients undergoing radiotherapy vs patients not undergoing radiotherapy. The Kaplan-Meier method was used to assess the survival outcomes of patients with SGMNs. RESULTS Of 20 142 patients, 16 802 patients (83.4%) were White and the median age was 65 years (interquartile range, 54-74 years). A total of 5310 (34.3%) patients were treated with surgery and radiotherapy, and 14 832 (65.7%) patients were treated with surgery alone. The cumulative incidence of SGMNs during 30 years of follow-up was 4.53% among patients who received radiotherapy and 1.53% among patients who did not. In competing risk regression analysis, undergoing radiotherapy was associated with a higher risk of developing cancer of the uterine corpus (adjusted hazard ratio, 3.06; 95% CI, 2.14-4.37; P < .001) and ovarian cancer (adjusted hazard ratio, 2.08; 95% CI, 1.22-3.56; P = .007) compared with those who did not receive radiotherapy. The dynamic radiotherapy-associated risks (RR) for cancer of the uterine corpus significantly increased with increasing age at rectal cancer diagnosis (aged 20-49 years: adjusted RR, 0.79; 95% CI, 0.35-1.79; P = .57; aged 50-69 years: adjusted RR, 3.74; 95% CI, 2.63-5.32; P < .001; aged >= 70 years: adjusted RR, 5.13; 95% CI, 2.64-9.97; P < .001) and decreased with increasing latency since rectal cancer diagnosis (60-119 months: adjusted RR, 3.22; 95% CI, 2.12-4.87; P < .001; 120-239 months: adjusted RR, 2.72; 95% CI, 1.75-4.24; P < .001; 240-360 months: adjusted RR, 1.95; 95% CI, 0.67-5.66; P = .22), but the dynamic RR for ovarian cancer increased with increasing latency since rectal cancer diagnosis (60-119 months: adjusted RR, 0.70; 95% CI, 0.26-1.89; P = .48; 120-239 months: adjusted RR, 2.26; 95% CI, 1.09-4.70; P = .03; 240-360 months: adjusted RR, 11.84; 95% CI, 2.18-64.33; P = .004). The 10-year overall survival among patients with radiotherapy-associated cancer of the uterine corpus was significantly lower than that among matched patients with primary cancer of the uterine corpus (21.5% vs 33.6%; P = .01). CONCLUSIONS AND RELEVANCE Radiotherapy for rectal cancer was associated with an increased risk of cancer of the uterine corpus and ovarian cancer. Special attention should be paid to reduce radiotherapy-associated SGMNs and improve their prognosis.