Search

Abstract Clinical trials and studies have implicated that E3 ubiquitin ligase BTBD3 (BTB Domain Containing 3) is a cancer-associated gene. However, the role and underlying mechanism of BTBD3 in colorectal cancer (CRC) is not fully understood yet. Herein, our study demonstrated that the mRNA and protein levels of BTBD3 were decreased in CRC tissues and associated with TYPO3 and Wnt/β-catenin pathway. Our results showed that circRAE1 knockdown and TYRO3 overexpression activated Wnt/β-catenin signaling pathway and the EMT process-associated markers, indicating that circRAE1/miR-388-3p/TYRO3 axis exacerbated tumorigenesis of CRC by activating Wnt/β-catenin signaling pathway. In addition, overexpression of BTBD3 reduced CRC cell migration and invasion in vitro and inhibited tumor growth in vivo. Our data demonstrated that BTBD3 suppressed CRC progression through negative regulation of the circRAE1/miR-388-3p/TYRO3 axis and the Wnt/β-catenin pathway. Our data further confirmed that BTBD3 bound and ubiquitinated β-catenin and led to β-catenin degradation, therefore blocked the Wnt/β-catenin pathway and suppressed the CRC tumorigenesis. This study explored the mechanism of BTBD3 involved in CRC tumorigenesis and provided a new theoretical basis for the prevention and treatment of CRC.

Abstract Purpose To explore the impact of excluding the external iliac node (EIN) from the clinical target volume (CTV) during preoperative radiotherapy in T4b rectal cancer with anterior structure invasion. Methods We retrospectively identified 132 patients with T4b rectal cancer involving the anterior structures who received radiotherapy followed by surgery between May 2010 and June 2019. Twenty-nine patients received EIN irradiation (EIN group), and 103 did not (NEIN group). Failure patterns, survival and toxicities were compared between the two groups. Results The most common failure was distant metastasis (23.5%). 11 (8.3%) patients developed locoregional recurrence, 10 (9.7%) patients were in the NEIN group, and 1 (3.4%) was in the EIN group (P = 0.34). The EIN region failure was rare (1/132, 0.8%). The locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS) and progression-free survival (PFS) rates were 96.3% vs. 90.5%, 82.1% vs.73.7%, 75.9% vs. 78.0% and 72.4% vs. 68.3% (all P > 0.05) for the EIN group and NEIN group, respectively. The incidence of grade 3–4 acute toxicity in the lower intestine was significantly higher in the EIN group than in the NEIN group (13.8% vs. 1.9%, P = 0.02). The Dmax, V35 and V45 of the small bowel was decreased in the NEIN group compared to the EIN group. Conclusions Exclusion of the EIN from the CTV in T4b rectal cancer with anterior structure invasion could reduce lower intestinal toxicity without compromising oncological outcomes. These results need further evaluation in future studies.

Abstract Introduction In this study, we aimed to evaluate the predictive value of circulating lymphocyte subsets and inflammatory indexes in response to neoadjuvant chemoradiotherapy (NCRT) in patients with rectal mucinous adenocarcinomas (MACs). Methods Rectal MAC patients who underwent NCRT and curative resection at Fujian Medical University Union Hospital's Department of Colorectal Surgery between 2016 and 2020 were included in the study. Patients were categorized into good and poor response groups based on their pathological response to NCRT. An independent risk factor‐based nomogram model was constructed by utilizing multivariate logistic regression analysis. Additionally, the extreme gradient boosting (XGB) algorithm was applied to build a machine learning (ML)‐based predictive model. Feature importance was quantified using the Shapley additive explanations method. Results Out of the 283 participants involved in this research, 190 (67.1%) experienced an unfavorable outcome. To identify the independent risk factors, logistic regression analysis was performed, considering variables such as tumor length, pretreatment clinical T stage, PNI, and Th/Tc ratio. Subsequently, a nomogram model was constructed, achieving a C‐index of 0.756. The ML model exhibited higher prediction accuracy than the nomogram model, achieving an AUROC of 0.824 in the training set and 0.762 in the tuning set. The top five important parameters of the ML model were identified as the Th/Tc ratio, neutrophil to lymphocyte, Th lymphocytes, Gross type, and T lymphocytes. Conclusion Radiochemotherapy sensitivity is markedly influenced by systemic inflammation and lymphocyte‐mediated immune responses in rectal MAC patients. Our ML model integrating clinical characteristics, circulating lymphocyte subsets, and inflammatory indexes is a potential assessment tool that can provide a reference for individualized treatment for rectal MAC patients.

Abstract Background Rectovaginal fistula (RVF) is an abnormal channel formed by epithelial tissue between the anterior wall of the rectum and the posterior wall of the vagina, which manifests as vaginal gassing and defecation. It is one of the common complications of female pelvic surgeries. With the increased number of proctectomies for rectal cancer, the number of postoperative rectovaginal fistulas also increases. Once RVF occurs, the failure rate is still high with various treatments available. RVF causes great suffering to women and is still a major problem in treatment. Therefore, it is significant for female rectal cancer patients to prevent RVF after rectal cancer surgery. In this study, we introduce a new method to prevent RVF during rectal cancer radical operation. Methods In this randomized controlled trial (RCT), all operations are performed according to the principle of total mesorectal excision (TME) radical resection in rectal cancer surgery. All eligible participants will be divided into two groups: the experimental group and the control group. Experimental group: the anterior rectal wall of about 1 cm distal to the anastomosis was dislocated. Before the anastomosis of the rectal end, a fat flap (usually left side) containing the ovarian vascular pedicle was dislocated, measured by 10–15 cm in length and 2 cm in width. The fat flap containing the ovarian vascular pedicle was packed and fixed anterior to the anastomotic stoma with fibrin glue. Control group: surgery will be carried out in accordance with the TME principle. Participants will be compared on several variables, including the incidence of RVF after operation (primary outcomes), the occurrence time of postoperative RVF, the occurrence time of RVF after stoma closure, and other postoperative complications, such as anastomotic leakage, chylous leakage, and intestinal obstruction (secondary outcomes). The follow-up data collection will be conducted according to the follow-up time point, and the baseline data will also be collected for follow-up analysis. By comparing the incidence of rectovaginal leakage between the experimental group and the control group, we aim to explore the feasibility of this method for the prevention of postoperative RVF. Discussion This RCT will explore the feasibility of packing with a laparoscopic dislocated fat flap containing an ovarian vascular pedicle anterior to the anastomotic stoma after rectal cancer surgery to prevent RVF. Trial registration Chinese Clinical Trial Registry (ChiCTR) registration ChiCTR2000031449. Registered on June 26, 2019. All items of the WHO Trial registration data set can be found within the protocol.

Abstract Background The prognostic nutritional index (PNI), alkaline phosphatase (ALP), and lymph node ratio (LNR) are reportedly related to prognosis. The aim of this study was to elucidate the clinical importance of the LNR and hematological parameters in patients with high grade rectal neuroendocrine neoplasms (HG-RNENs) who were undergoing radical resection. Methods We reviewed the medical records of patients with HG-RNENs from 17 large-scale medical centers in China (January 1, 2010–April 30, 2022). A nomogram was constructed by using a proportional hazard model. Bootstrap method was used to draw calibration plots to validate the reproducibility of the model. Concordance index (C-Index), decision curve analysis (DCA), and time-dependent area under the receiver operating characteristic curve (TD-AUC) analysis were used to compare the prognostic predictive power of the new model with American Joint Committee on Cancer (AJCC) TNM staging and European Neuroendocrine Tumor Society (ENETS) TNM staging. Results A total of 85 patients with HG-RNENs were enrolled in this study. In the 45 patients with HG-RNENs who underwent radical resection, PNI ≤ 49.13 (HR: 3.997, 95% CI: 1.379–11.581, P = 0.011), ALP > 100.0 U/L (HR: 3.051, 95% CI: 1.011–9.205, P = 0.048), and LNR > 0.40 (HR: 6.639, 95% CI: 2.224–19.817, P = 0.0007) were independent predictors of relapse-free survival. The calibration plots suggested that the nomogram constructed based on the three aforementioned factors had good reproducibility. The novel nomogram revealed a C-index superior to AJCC TNM staging (0.782 vs 0.712) and ENETS TNM staging (0.782 vs 0.657). Also, the new model performed better compared to AJCC TNM staging and ENETS TNM staging in DCA and TD-AUC analyses. Conclusions LNR, ALP, and PNI were independent prognostic factors in patients with HG-RNENs after radical resection, and the combined indicator had better predictive efficacy compared with AJCC TNM staging and ENETS TNM staging.

Abstract Background The recommended operation for cecum cancer (CC) is right hemicolectomy (RH) in some Western countries while the principle of D3 lymphadenectomy in Japan recommends resecting approximately 10 cm from the tumor edge. Therefore, the optimal surgical approach for cecum cancer (CC) remains controversial. We conducted this retrospective study to explore the pattern of lymph node metastasis and better surgical procedures for CC. Methods A total of 224 cecum cancer patients from January 1, 2014, to December 31, 2021, were retrospectively included in the final study. The pattern of lymph node metastasis (LNM) was investigated. Results A total of 113 (50.4%, 113/224) patients had pathologically confirmed LNM. The most frequent metastatic site was no. 201 lymph node (46%, 103/224), while 20 (8.9%, 20/224) patients had LNM in no. 202 lymph node, and 8 (3.6%, 8/224) patients had LNM in no. 203 lymph node. Only 1 (0.4%, 1/224) patient had LNM in no. 221 lymph node, four (1.8, 4/224%) patients had LNM in no. 223 lymph node, and no patients had LNM in no. 222 lymph node. LNM in no. 223 lymph node was significantly associated with a poor prognosis. Multivariate analysis indicated that LNM in no. 223 lymph node (HR = 4.59, 95% CI 1.18–17.86, P = 0.028) was the only independent risk factor associated with worse disease-free survival (DFS). Conclusions The LNM in no. 223 lymph node for cecum cancer was rare. Therefore, standard right hemicolectomy excision is too extensive for most CC cases.

Abstracts Background Preclinical studies suggest that glucocorticoids (GCs) promote the proliferation and development of colorectal cancer. Because GCs are broadly prescribed for treatment-related adverse events in patients with locally advanced rectal cancer (LARC) receiving neoadjuvant chemoradiotherapy (NCRT), it’s essential to assess the effect of GCs on clinical outcomes. Methods LARC cases treated with NCRT followed by surgery were assessed retrospectively. Evaluation of the relationship between GCs use (GCs vs. non-GCs) and neoadjuvant rectal (NAR) score (as a three-level categorical dependent variable) was performed using multivariable multinomial logistic regression (MLR). We also examined the relationship between the accumulated dose of GCs and NAR using multivariate MLR. Survival analysis of disease-free survival (DFS) and overall survival (OS) was performed using the Kaplan–Meier method. Multivariate Cox regression was used to assess confounding factors that could influence OS and DFS. Results This retrospective cohort study included 790 patients with newly diagnosed non-metastatic LARC (T3-4/N + M0) who received NCRT followed by surgery between January 2012 and April 2017. The end of the follow-up period was May 11, 2022. Among the 790 patients with LARC, 342 (43.2%) received GCs treatment and 448 (56.8%) did not during the NCRT-to-surgery period. GCs medication was significantly different between mid-NAR (8–16) and low-NAR ( 16) and low-NAR (0.563; 0.352–0.900; 0.016). Patients exposed to GCs, had a decreased 5-year OS (GCs vs. non-GCs = 80.01% (95% CI, 75.87%–84.37%) vs. 85.30% (82.06%–88.67%), P = 0.023) and poorer 5-year DFS (73.99% (69.45%–78.82%) vs. 78.7% (75.14%–82.78%), P = 0.045). The accumulated dose of GCs was an independent risk factor for OS (hazard ratio [HR], 1.007 [1.001–1.014], 0.036) and DFS (1.010 [1.004–1.017], 0.001). Conclusions and relevance Our study revealed that GCs were associated with reduced efficacy of NCRT and worse clinical outcomes in patients with LARC during the NCRT-to-surgery period.

Abstract Background N7-methylguanosine (m7G) is present in a wide variety of organisms and has important roles. m7G has been reported to be involved in multiple biological processes, and recent studies have reported that changes in RNA modifications result in tumor cellular transformation and cancer, such as colon adenocarcinoma, lung cancer, and intrahepatic cholangiocarcinoma. However, little is known about the function of the m7G in colon adenocarcinoma. Methods We established two clusters based on the expression of all genes associated with m7G to explore the expression pattern of 31 key regulatory factors of m7G RNA and assess the prognostic value of regulatory factors. Wilcoxon test and differential box line plots were applied for bioinformatics analysis. Receiver Operating and Kaplan‒Meier curves were utilized to evaluate the prognostic value. Finally, four genes' expression in the colon cancer cell line was confirmed by qRT-PCR. Results From The Cancer Genome Atlas database, we found that the expression levels of 25 out of the 31 key N7-methylguanosine RNA modification regulators were significantly different in colon adenocarcinoma. According to 25 methylation regulators’ expression, we identified two subgroups by consensus clustering, in which the prognosis was worse in Group 2 than in Group 1 and was significantly correlated with age. Cluster 2 was significantly enriched in tumor-associated pathways, and immune cells were highly infiltrated in Cluster 1 but weakly infiltrated in Cluster 2. Further results indicated that this risk profile may serve as a standalone predictive factor for colon adenocarcinoma, and the four genetic risk profiles’ prognostic relatedness was successfully verified through Gene Expression Omnibus dataset. At last, A nomogram for prognosis was created according to age, sex, histological grading, clinicopathological staging, and hazard score to accurately predict patient prognosis in colon adenocarcinoma. We successfully validated the differential expression of four genes using qRT-PCR. Conclusions In the present study, we revealed the important contribution of key regulators associated with m7G RNA modifications based on all gene expression in colon adenocarcinoma and developed a signature of risk that serves as a promising prognostic marker for patients with colon adenocarcinoma.

Abstract Background Anastomotic leakage (AL) is one of the most serious postoperative complications after colorectal anastomosis. This study aims to evaluate the feasibility and diagnostic accuracy of magnetic resonance imaging (MRI) in the early detection of AL in patients with clinically suspected AL after rectal anterior resection. Methods This was a prospective study including patients who underwent anterior resection and postoperative MRI examination. AL was diagnosed by comprehensive indictors, which were mainly confirmed by clinical signs, symptoms, and retrograde contrast enema (RCE) radiography. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of diagnosing AL with MRI were calculated. Results In total, 347 patients received anterior resection for rectal cancer, and 28 patients were suspected to have AL. Finally, 23 patients were included and received MRI examination. The median time interval from surgery to MRI was 10 days (3–21 days). The median distance from anastomosis to anal verge was 4.0 cm (2.0–10 cm), and 11 patients underwent diverted ileostomy. Eighteen patients had an anastomotic leak, including one patient who had a pelvic abscess and five patients who had no evidence of AL in the MRI examination. The overall sensitivity and specificity were 94.4% (95% CI 70.6% to 99.7%) and 80% (95% CI 29.8% to 98.9%), respectively. The PPV was 0.94 (95% CI 0.71 to 0.99) and the NPV was 0.80 (95% CI 0.29 to 0.99). For patients who had anastomosis less than 5 cm, the diagnostic accuracy of MRI was 93.7% (15/16). T2-weighted imaging with fat suppression can effectively reveal the leak track. Conclusions The accuracy of plain MRI examination in diagnosing AL was favorable for patients with a suspected AL. T2-weighted imaging with fat suppression was the best imaging modality to diagnose AL. A multicenter prospective study with more samples is needed to further determine the safety and feasibility of MRI in the diagnosis of AL.

Abstract. Background:. Pre-operative assessment with high-resolution magnetic resonance imaging (MRI) is useful for assessing the risk of local recurrence (LR) and survival in rectal cancer. However, few studies have explored the clinical importance of the morphology of the anterior mesorectum, especially in patients with anterior cancer. Hence, the study aimed to investigate the impact of the morphology of the anterior mesorectum on LR in patients with primary rectal cancer. Methods:. A retrospective study was performed on 176 patients who underwent neoadjuvant treatment and curative-intent surgery. Patients were divided into two groups according to the morphology of the anterior mesorectum on sagittal MRI: (1) linear type: the anterior mesorectum was thin and linear; and (2) triangular type: the anterior mesorectum was thick and had a unique triangular shape. Clinicopathological and LR data were compared between patients with linear type anterior mesorectal morphology and patients with triangular type anterior mesorectal morphology. Results:. Morphometric analysis showed that 90 (51.1%) patients had linear type anterior mesorectal morphology, while 86 (48.9%) had triangular type anterior mesorectal morphology. Compared to triangular type anterior mesorectal morphology, linear type anterior mesorectal morphology was more common in females and was associated with a higher risk of circumferential resection margin involvement measured by MRI (35.6% [32/90] vs. 16.3% [14/86], P = 0.004) and a higher 5-year LR rate (12.2% vs. 3.5%, P = 0.030). In addition, the combination of linear type anterior mesorectal morphology and anterior tumors was confirmed as an independent risk factor for LR (odds ratio = 4.283, P = 0.014). Conclusions:. The classification established in this study was a simple way to describe morphological characteristics of the anterior mesorectum. The combination of linear type anterior mesorectal morphology and anterior tumors was an independent risk factor for LR and may act as a tool to assist with LR risk stratification and treatment selection.

Abstract Purpose The incidence of early-onset colorectal cancer (EO-CRC), which occurs in people under age 50, has been increasing annually. The aim of this study was to provide an up-to-date estimate of the global EO-CRC burden. Methods We used Global Burden of Disease Study data and methodologies to describe changes in the EO-CRC burden from 1990 to 2019, including incidence, prevalence, mortality, and disability-adjusted life years (DALYs). The driving factors for cancer burden variation were further analyzed using decomposition analysis. Frontier analysis was used to visually demonstrate the potential for burden reduction in each country or region based on their development levels. Results The global EO-CRC incidence more than doubled, increasing from 95,737 (95% uncertainty interval (UI): 90,838–101.042) /100,000 in 1990 to 226,782 (95% UI: 207,495–248,604) /100,000 in 2019. Additionally, related deaths increased from 50,997 (95% UI: 47,692–54,410) /100,000 to 87,014 (95% UI: 80,259–94,339) /100,000, and DALYs increased from 256,1842 (95% UI: 239,4962–2,735,823) /100,000 to 4,297,573 (95% UI: 3,965,485–4,650,790) /100,000. Regarding age-standardized rates, incidence and prevalence increased significantly, while mortality and DALYs rate were basically unchanged. Decomposition analysis showed a significant increase in DALYs in the middle sociodemographic index (SDI) quintile region, in which aging and population growth played a major driving role. Frontier analysis showed that countries or regions with a higher SDI quintile tend to have greater improvement potential. Conclusion The current EO-CRC burden was found to be the greatest in the high-middle SDI quintile region and East Asia, which may need to adjust screening guidelines accordingly and introduce more effective interventions.

Abstract Background This study aimed to assess the clinical implications of the advanced lung cancer inflammation index (ALI) in patients with right-sided colon cancer (RCC) after complete mesocolic excision (CME). Methods A total of 441 patients with RCC who underwent CME were included. The optimal cut-off value for the ALI was determined using the X-tile software. Logistic and Cox regression analyses were used to identify risk factors for postoperative complications and long-term outcomes. Predictive nomograms for overall survival (OS) and disease-free survival (DFS) were constructed after propensity score matching (PSM), and their performance was assessed using the net reclassification improvement index (NRI), integrated discrimination improvement index (IDI), and time-dependent receiver operating characteristic (time-ROC) curve analysis. Results The optimal preoperative ALI cut-off value was 36.3. After PSM, ASA classification 3/4, operative duration, and a low ALI were independently associated with postoperative complications in the multivariate analysis (all P60 years, a carbohydrate antigen 19-9 (CA19-9) level >37 U/mL, pathological N+ stage, and a low ALI were independently correlated with OS (all P37 U/mL, pathological N+ stage, lymphovascular invasion, and a low ALI were independent predictors of DFS (all P

Abstract Background Distant metastasis has been the main failure pattern for locoregionally advanced rectal cancer (LARC) patients, and intensified neoadjuvant chemotherapy has become a popular research topic. The present study aimed to compare the survival outcomes, acute toxicities and surgical complications in LARC patients who received preoperative chemoradiotherapy with triweekly oxaliplatin and capecitabine (triweekly XELOX) or capecitabine. Methods: Between 2007 and 2017, patients with clinically staged II-III rectal cancer who were treated with preoperative chemoradiotherapy using either triweekly XELOX (oxaliplatin 130 mg/m2 plus capecitabine 825 mg/m2) or capecitabine were included. Variables potentially influencing chemotherapy treatment selection were used to generate propensity scores (PS). The association between chemotherapy regimens and survival endpoints, including distant metastasis-free survival (DMFS), overall survival (OS) and disease-free survival (DFS), were evaluated and adjusted with PS. The acute toxicities and surgical complications were also compared. Results A total of 810 patients were included in the analysis; 277 (34.2%) patients received triweekly XELOX, and 533 (65.8%) received capecitabine. The pathological complete response (pCR) rates were 20.2 and 19.9% (P = 0.912) for the groups treated with triweekly XELOX and capecitabine, respectively. The 5-year DMFS, OS and DFS with triweekly XELOX versus capecitabine were 75.6% vs. 77.6% (P = 0.555), 79.2% vs. 83.3% (P = 0.101), and 69.9% vs. 73.7% (P = 0.283), respectively. Triweekly XELOX was not associated with an increased risk of severe toxicity during chemoradiotherapy, but it increased the risk of postoperative complications compared to capecitabine. After PS adjustment, the differences between the two groups remained insignificant in pCR rate, survival outcomes, and acute toxicities, and the difference in surgical complications disappeared. Conclusions Triweekly XELOX or capecitabine concurrent with neoadjuvant radiotherapy leads to similar long-term survival outcomes, acute toxicities and surgical complications in LARC patients.

Abstract Background and purpose We aimed to explore the necessity of the external iliac lymph nodes (EIN) along with inguinal nodes (IN) region in clinical target volume (CTV) for rectal carcinomas covering the anal canal region. Materials and methods This research premise enrolled 399 patients who had primary low rectal cancer detected below the peritoneal reflection via magnetic resonance imaging (MRI) and were treated with neoadjuvant radiotherapy (NRT), without elective EIN along with IN irradiation. We stratified the patients into two groups based on whether the lower edge of the rectal tumor extended to the anal canal (P group, n = 109) or not (Rb group, n = 290). Comparison of overall survival (OS), locoregional recurrence-free survival (LRFS), disease-free survival (DFS), as well as distant metastasis-free survival (DMFS) were performed via inverse probability of treatment weighting (IPTW) along with multivariable analyses. We compared the EIN and IN failure rates between the two groups via the Fisher and Gray’s test. Results P group showed a similar adjusted proportion along with five-year cumulative rate of EIN failure compared with the Rb group. The adjusted proportion and five-year cumulative rate of IN failure in the P group was higher in comparison to the Rb group. There were no remarkable differences in the adjusted five-year OS, DFS, DMFS or LRFS between the two groups. Anal canal involvement (ACI) exhibited no effect on OS, LRFS, DFS, or DMFS. Conclusions During NRT for rectal cancer with ACI, it may be possible to exclude the EIN and IN from the CTV.

Abstract Background Lymph node (LN) metastasis is crucial in determining the prognosis and treatment options for colon cancer patients. Our work was to study whether the lymph nodes beyond D3 station in transverse colon cancer, especially 206 LN, should be dissected. Methods A total of 225 patients within our department were reviewed. The primary and secondary endpoints were overall survival (OS) and disease‐free survival (DFS). We employed Propensity score weighting (PSW) for weighing participants to balance observed confounders between the 206D+ group and the 206D− group. Results The rate of metastasis in station 206 was 9.3%. Only T stage (OR, 3.009; 95% CI, 1.018–8.892), N stage (OR, 9.818; 95% CI, 1.158–83.227), and M stage (OR, 26.126; 95% CI, 1.274–535.945) were an independent risk factor for 206 station metastasis in multivariate logistic analysis. The 206D+ group had a similarly survival than the 206D− group (3‐year DFS, 89.6% v 85.9%; p = 0.389; 3‐year OS, 94.6% v 85.3% p = 0.989). PSW further verified it. Metastasis of 206 station LN is not an independent prognostic factor, but a predictive factor of DFS. Conclusion Station 206 LN positive is a predictive factor for DFS. Only the patient with T1‐3, N+ who is at a high risk of 206 station LN metastases should consider dissecting 206 station LN.

Introduction Short-course radiotherapy (SCRT) with systemic therapy has the potential to further improve the long-term efficacy in patients with locally advanced rectal cancer (LARC). To maximise the benefits of neoadjuvant therapy for improved prognosis, it is important to determine the optimal mix of chemotherapy, immunotherapy and SCRT.Methods and analysis Fifty treatment-naïve patients with operable LARC (T3–4 and/or N+) will be recruited. Patients will be synchronously treated with capecitabine plus oxaliplatin (CAPOX) chemotherapy, tislelizumab and preoperative split-course hypofraction radiotherapy (SCHR) (5×7 Gy) before surgery. Chemotherapy for CAPOX starts on day 1 of every 21-day cycle: on day 1, oxaliplatin 130 mg/m2 will be injected intravenously. On days 1–14, capecitabine 1000 mg/m2 was ingested two times a day. Simultaneously, tocilizumab 200 mg will be given intravenously on the first day of every 21-day cycle. A single 7 Gy SCHR treatment (day 7 of each 21-day cycle) will be delivered five times during the seventh day of treatment. The primary endpoint will be pathological complete response. The secondary outcomes will be the 3-year disease-free survival, local recurrence rate, overall survival, sphincter-sparing surgery rate, R0 resection rate, predictive biomarkers and quality of life.Ethics and dissemination The study protocol was approved by the Ethics Committee of Xiehe Affiliated Hospital of Fujian Medical University (XAHFMU) (No. 2021YF025-01). Results from our study will be disseminated in international peer-reviewed journals. All study procedures were developed in order to assure data protection and confidentiality.Trial registration number NCT05176964.

Abstract Background Intraoperative near-infrared fluorescence (NIR) imaging with indocyanine green (ICG) can demonstrate real-time lymphatic drainage and thus improve the accuracy and completeness of lymphadenectomy in colorectal cancer surgery. However, it has not been utilized in the inguinal lymphadenectomy in rectal cancer. This study aimed to describe a case of combined laparoscopic lymphadenectomy of left lateral pelvic and inguinal nodal metastases using NIR imaging with ICG imaging guidance for a rectal cancer patient with left lateral pelvic and inguinal lymph node metastases. Case presentation A 26-year-old man presented rectal cancer located 7 cm from the anal verge and enlarged lymph nodes in the left inguinal area. Pretreatment workup revealed rectal cancer with left lateral pelvic and inguinal lymph node metastases. The patient received preoperative chemoradiotherapy (pCRT), including radiation (total dose of 50.4 Gy in 28 fractions) to the whole pelvis and bilateral inguinal regions together with eight cycles of FOLFOX (oxaliplatin, fluoropyrimidine, and leucovorin) and three cycles of bevacizumab targeted chemotherapy. After pCRT, both colonoscopy and MR scan revealed a significant response of the primary tumor to pCRT, while MR scan revealed enlarged left lateral pelvic and inguinal lymph nodes. After four months from the completion of radiation (2 months after the last course of bevacizumab targeted therapy), the patient underwent laparoscopic-assisted ultra-low anterior resection and lymphadenectomy of left lateral pelvic and inguinal nodal metastases using ICG-NIR fluorescence imaging. The combined procedure was performed successfully without perioperative complication. Total operative time was 480 min and estimated blood loss 50 mL. Totally 34 lymph nodes were retrieved. Conclusions This is the first report of the safety and feasibility of ICG-NIR fluorescence imaging-guided laparoscopic lymphadenectomy of left lateral pelvic and inguinal nodal metastases in managing low rectal cancer with lateral pelvic and inguinal LNs metastases.

Abstract. Background:. Postoperative chylous ascites is an infrequent condition after colorectal surgery and is easily treatable. However, its effect on the long-term oncological prognosis is not well established. This study aimed to investigate the short-term and long-term impact of chylous ascites treated with neoadjuvant therapy followed by rectal cancer surgery and to evaluate the incidence of chylous ascites after different surgical approaches. Methods:. A total of 898 locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy followed by surgery between January 2010 and December 2018 were included. The clinicopathological data and outcomes of the patients with chylous ascites were compared with those of the patients without chylous ascites. The primary endpoint was recurrence-free survival (RFS). To balance baseline confounders between groups, propensity score matching (PSM) was performed for each patient with a logistic regression model. Results:. Chylous ascites was detected in 3.8% (34/898) of the patients. The incidence of chylous ascites was highest after robotic surgery (6.9%, 6/86), followed by laparoscopic surgery (4.2%, 26/618) and open surgery (1.0%, 2/192, P = 0.021). The patients with chylous ascites had a significantly higher number of lymph nodes harvested (15.6 vs. 12.8, P = 0.009) and a 3-day longer postoperative hospital stay (P = 0.017). The 5-year RFS rate was 64.5% in the chylous ascites group, which was significantly lower than the rate in the no chylous ascites group (79.9%; P = 0.007). The results remained unchanged after PSM was performed. The chylous ascites group showed a nonsignificant trend towards a higher peritoneal metastasis risk (5.9% vs. 1.6%, P = 0.120). Univariate analysis and multivariate analysis confirmed chylous ascites (hazard ratio= 3.038, P < 0.001) as an independent negative prognostic factor for RFS. Conclusions:. Considering the higher incidence of chylous ascites after laparoscopic and robotic surgery and its adverse prognosis, we recommend sufficient coagulation of the lymphatic tissue near the vessel origins, especially during minimally invasive surgery.

Background: Lynch syndrome is a genetic disease resulting from mismatch repair gene mutation. Vaccine therapy can enhance the immunogenicity of Lynch syndrome and improve the therapeutic efficacy of immunotherapy. However, there is no approved Lynch syndrome vaccine coming onto the market.Methods: Herein, we used gene knockdown method to construct Lynch syndrome cell model, paving way for us to develop Lynch syndrome tumor lysate vaccine. Then the isograft technique was employed for constructing the tumor-bearing mouse model of Lynch syndrome. And this isograft model was treated with PD-1 monoclonal antibody and tumor vaccine, respectively. Flow cytometry was used for detecting the proportion of immune cells and immunosuppressive cells, and ELISA was used for detecting the contents of chemokines and cytokines in the blood circulation system and tumor tissues of mice. Finally, IHC was used to detect the effects of tumor vaccines as well as PD-1 antibody on tumor tissue proliferation and angiogenesis.Results: The results demonstrated that tumor vaccine could prolong the overall survival of mice, and improve the disease-free survival rate of mice. The vaccine could increase the proportion of inflammatory cells and decrease the proportion of anti-inflammatory cells in the blood circulation system of mice. In addition, tumor vaccine could also improve inflammatory infiltration in the tumor microenvironment and reduce the proportion of immunosuppressive cells. The results of IHC showed that tumor vaccine could inhibit angiogenesis and tumor cell proliferation in mouse tumor tissues.Conclusion: In colon cancer associated with Lynch syndrome, tumor vaccine can hinder the growth of tumor cells, and assist immunotherapy whose therapeutic effect on this kind of cancer is thus enhanced.

Abstract Background Neuroligin1 (NLGN1) is a main component of excitatory glutamatergic synapses complex and is important for synapse assembly and function. The clinical value of NLGN1 in colorectal cancer (CRC) is not clear. Methods We obtained the expression data of 1143 CRC patients from 3 independent Gene Expression Omnibus (GEO) datasets (GSE32323, GSE24551, GSE39582) and The Cancer Genome Atlas (TCGA) to make the comparison of the NLGN1 expression level between CRC tissues and matched noncancerous tissues, and to evaluate its value in predicting survival of CRC patients. At the protein level, these results were further confirmed by immunohistochemical staining of 52 CRC samples in our own centre. Finally, the function of NLGN1 was explored by gene set enrichment analysis (GSEA). Results Increased mRNA and protein levels of NLGN1 expression were associated with worse overall survival or recurrence-free survival in CRC patients from 2 GEO datasets, the TCGA database, and our cohort. In addition, multivariate regression analysis showed that NLGN1 was an independent poor prognostic factor of survival in patients with CRC in TCGA database (OR = 2.524, P = 0.010). Functional analysis revealed that NLGN1 was correlated with function involving the Hedgehog signaling pathway, mismatch repair process, and some material metabolism processes. Conclusions This study is the first to implicate and verify NLGN1 as a new poor prognostic marker for CRC.

BackgroundThe aim of this study was to compare the short- and long-term outcomes of splenic flexure colectomy (SFC), left hemicolectomy (LHC) and extended left hemicolectomy (ELHC) for splenic flexure colon cancer.MethodsBetween January 2011 and December 2018, 117 patients with splenic flexure cancer were enrolled in the study. We retrospectively compared the postoperative, pathological and long-term outcomes of patients with splenic flexure cancer.ResultsOf the 117 patients, 73 (62.4%) underwent SFC, 22 (18.8%) underwent LHC, and 22 (18.8%) underwent ELHC. No statistically significant differences were found among the groups regarding postoperative complications, pathological data or recurrence. No metastatic lymph nodes at the root of the inferior mesenteric artery (IMA) were observed; lymph node metastasis appeared at the root of the middle colic artery (MCA), but in a low proportion of cases (4.4%). Looking at long-term prognosis, no differences were observed among the three groups regarding both 5-year overall survival (94.0% vs 90.2% vs 94.1%) and disease-free survival (88.2% vs 90.2% vs 83.0%).ConclusionOur retrospective review suggests that splenic flexure colectomy in minimally invasive surgery is a safe and effective treatment option for splenic flexure colon cancer. The rate of metastatic lymph nodes at the root of the central artery and gastroepiploic arcade node was relatively low.

Introduction Total mesorectal excision (TME) has been the gold standard for the surgical treatment of mid-low rectal cancer, but traditional TME removal of Denonvilliers’ fascia (DVF) is too low and is prone to damage the connecting branches of the bilateral neurovascular bundles, which can lead to posturogenital dysfunction. A recently published multicenter randomised controlled trial revealed that TME with complete preservation of DVF (CP-DVF) has protective effects on postoperative urogenital function for male patients with rectal cancer with specific staging and location (preoperative staging T1-4N0-2M0, but T1-2 for anterior rectal wall). Our previous studies have confirmed that TME with partial preservation of DVF (PP-DVF) could also achieve satisfactory results regardless of the circumferential location of the tumour. However, there is a lack of randomised controlled trials to prove that the efficacy of TME with PP-DVF is equivalent to that with CP-DVF with respect to postoperative urogenital function.Methods and analysis This study is a prospective, multicentre, equivalent design, open-label randomised clinical trial in which 278 male patients with low rectal cancer will be recruited from 11 large-scale gastrointestinal medical centres in China. Patients will be randomly assigned to undergo PP-DVF or CP-DVF. We will test the hypothesis that PP-DVF is similar to CP-DVF with respect to sexual function at postoperative month 12 (5-item version of the International Erectile Function Index Questionnaire and ejaculation function classification). The secondary outcomes include the assessment of urinary function, surgical safety and oncological outcomes.Ethics and dissemination This trial has been approved by the Institutional Review Board of Fujian Medical University Union Hospital (2020YF016-01) and is filed on record by all other centres. Written informed consent will be obtained from all eligible participants before enrolment. The trial’s results will be disseminated via peer-reviewed scientific journals and conference presentations.Trial registration number ChiCTR2000034892.

Abstract Background SPINK4 is known as a gastrointestinal peptide in the gastrointestinal tract and is abundantly expressed in human goblet cells. The clinical significance of SPINK4 in colorectal cancer (CRC) is largely unknown. Methods We retrieved the expression data of 1168 CRC patients from 3 Gene Expression Omnibus (GEO) datasets (GSE24551, GSE39582, GSE32323) and The Cancer Genome Atlas (TCGA) to compare the expression level of SPINK4 between CRC tissues and normal colorectal tissues and to evaluate its value in predicting the survival of CRC patients. At the protein level, these results were further confirmed by data mining in the Human Protein Atlas and by immunohistochemical staining of samples from 81 CRC cases in our own center. Results SPINK4 expression was downregulated in CRC compared with that in normal tissues, and decreased SPINK4 expression at both the mRNA and protein levels was associated with poor prognosis in CRC patients from all 3 GEO datasets, the TCGA database and our cohort. Additionally, lower SPINK4 expression was significantly related to higher TNM stage. Moreover, in multivariate regression, SPINK4 was confirmed as an independent indicator of poor survival in CRC patients in all databases and in our own cohort. Conclusions We concluded that reduced expression of SPINK4 relates to poor survival in CRC, functioning as a novel indicator.

RAS is the most common mutated gene in colorectal cancer (CRC), and its occurrence is associated with primary and acquired resistance to anti-epidermal growth factor receptor (EGFR) blockade. Cancer community ecology, such as the competitive exclusion principle, is a valuable focus and would contribute to the understanding of drug resistance. We have presented several articles on RAS mutant clonal evolution monitoring during anti-EGFR treatment in CRC. In these articles, the availability of serially collected samples provided a unique opportunity to model the tumor evolutionary process from the perspective of cancer community ecology in those patients upon treatment. In this perspective article, we presented a theoretical basis and evidence from several experimental or phase II clinical trials for the contemporary application of ecological mechanisms in CRC treatment. In general, a reduction in targetable RAS wild-type cells to a maximum tolerated extent, such as continuous treatment, might lead to the competitive release of inextirpable RAS mutant cells and cancer progression. A full understanding of subclonal competition might be beneficial in managing CRC. Several ecological strategies, including anti-EGFR treatment reintroduced at an appropriate point of time for RAS mutant patients, intermittent treatment instead of continuous treatment, the appropriate sequence of nonselective targeted therapy, and combination therapy, were proposed.

AimTo evaluate the evidence concerning the quality of surgical resection in laparoscopic (LapTME), robotic (RobTME) and transanal (TaTME) total mesorectal excision for mid-/low rectal cancer.MethodsA systematic literature search of the PubMed, EMBASE and Cochrane Central Register of Controlled Trials databases was performed. A Bayesian network meta-analysis was utilized to compare surgical resection involved in these 3 surgical techniques by using ADDIS software. Rates of positive circumferential resection margins (CRMs) were the primary endpoint.ResultsA total of 34 articles, 2 randomized clinical trials (RCTs) and 32 non-RCTs, were included in this meta-analysis. Pooled data showed CRM positivity in 114 of 1763 LapTME procedures (6.5%), 54 of 1051 RobTME procedures (5.1%) and 60 of 1276 TaTME procedures (4.7%). There was no statistically significant difference among these 3 surgical approaches in terms of CRM involvement rates and all other surgical resection quality outcomes. The incomplete mesorectal excision rates were 9.6% (69/720) in the LapTME group, 1.9% (11/584) in the RobTME group and 5.6% (45/797) in the TaTME group. Pooled network analysis observed a higher but not statistically significant risk of incomplete mesorectum when comparing both LapTME with RobTME (OR = 1.99; 95% CI = 0.48-11.17) and LapTME with TaTME (OR = 1.90; 95% CI = 0.99-5.25). By comparison, RobTME was most likely to be ranked the best or second best in terms of CRM involvement, complete mesorectal excision, rate of distal resection margin (DRM) involvement and length of DRMs. In addition, RobTME achieved a greater mean tumor distance to the CRM than TaTME. It is worth noting that TaTME was most likely to be ranked the worst in terms of CRM involvement for intersphincteric resection of low rectal cancer.ConclusionOverall, RobTME was most likely to be ranked the best in terms of the quality of surgical resection for the treatment of mid-/low rectal cancer. TaTME should be performed with caution in the treatment of low rectal cancer.

PurposeTo investigate the relationship between the left trunk of the inferior mesenteric plexus (IMP) and the vascular sheath of the inferior mesenteric artery (IMA) and to explore anatomical evidence for autonomic nerve preservation during high ligation of the IMA in colorectal cancer surgery.MethodsWe evaluated the relationship in 23 consecutive cases of laparoscopic or robotic colorectal surgery with high ligation of the IMA at our institute. Anatomical dissection was performed on 5 formalin-fixed abdominal specimens. A novel anatomical evidence-based operative technique was proposed.ResultsAnatomical observation showed that the left trunk of the IMP was closely connected with the IMA and was involved in the composition of the vascular sheath. Based on anatomical evidence, we present a novel operative technique for nerve-sparing high ligation of the IMA that was successfully performed in 45 colorectal cancer surgeries with no intraoperative complications and satisfactory postoperative urogenital functional outcomes.ConclusionThe left trunk of the IMP is involved in the composition of the IMA vascular sheath. This novel anatomical evidence-based operative technique for nerve-sparing high ligation of the IMA is technically safe and feasible.

Long noncoding RNAs (lncRNAs) are emerging as critical regulators of cancer. There is a comparable number of lncRNAs to protein‐coding genes, but the expression patterns, functions, and molecular mechanisms of most lncRNAs in colorectal cancer (CRC) remain unclear. In this study, we report the identification of a novel lncRNA, named long noncoding RNA regulating IL‐6 transcription (LNRRIL6), which is upregulated in CRC tissues and cell lines. Increased LNRRIL6 expression is associated with aggressive clinicopathological characteristics and poor prognosis of CRC patients. Functional experiments showed that enhanced expression of LNRRIL6 promotes CRC cell proliferation and survival in vitro and CRC tumor growth in vivo. Conversely, depletion of LNRRIL6 inhibits CRC cell proliferation and survival in vitro and CRC tumor growth in vivo. Mechanistically, we revealed that LNRRIL6 physically binds to the IL‐6 promoter, thereby increasing IL‐6 transcription, inducing IL‐6 autocrine signaling, and activating the IL‐6/STAT3 pathway. The expression of IL‐6 is positively associated with that of LNRRIL6 in CRC tissues. Blocking the IL‐6/STAT3 pathway using the FDA‐approved IL‐6‐receptor antagonist antibody, tocilizumab, abolished the oncogenic role of LNRRIL6 in CRC. Taken together, these findings identify a novel lncRNA, LNRRIL6, that promotes CRC cell survival through activation of the IL‐6/STAT3 pathway and suggest that LNRRIL6 may be a potential prognostic biomarker and therapeutic target for CRC.

Abstract Background Circular RNAs (circRNAs), a novel type of noncoding RNAs, play critical roles in the initiation and progression of cancer. Emerging studies also shows that circRNAs may function as potential markers for cancer diagnosis and treatment. However, the diagnostic value of circRNAs in colorectal cancer (CRC) remains need to be unearthed. Methods CircRNA microarray was performed to detect the differentially expressed circRNAs in eight plasma samples, including four colorectal cancer (CRC) and four normal samples. Besides, the results of microarray were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, ROC curve evaluation was performed to calculate the diagnostic value of significantly dysregulated circRNAs. In order to predict the potential mechanism of the significant circRNAs, circRNA–miRNA–mRNA network was constructed based on the TargetScan, miRTarBase and MIRDB database, as well as CircInteractome online software. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to further predict the function of meaningful circRNAs. Results Totally three differentially expressed circRNAs were identified in CRC plasma compared to normal plasma by circRNA microarray analysis, and the results was validated by qRT-PCR. Hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445 were identified and ROC curves analysis was used to calculate the single and joint diagnostic value. Furthermore, GO and KEGG analyses revealed that functions were mainly cancer-related, which indicated that the circRNAs were meaningfully associated with CRC cell proliferation and metastasis. Conclusion In conclusion, we have identified three circRNAs that are dysregulated in CRC plasma, including hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445. ROC curves showed that these circRNAs might have diagnostic value for colorectal cancer. Furthermore, bioinformatics analysis indicated that the above-mentioned circRNAs might be involved in the development of CRC.

Purpose/aim: Preoperative chemoradiotherapy (pre-CRT) and total mesorectal excision (TME) have become the standard of care for patients with locally advanced rectal cancer (LARC). Nevertheless, it is a controversial issue whether pre-CRT in cT3N0M0 patients would result in potential overtreatment. Materials and methods: In total, 183 clinical stage IIA rectal cancer patients treated with and without pre-CRT between 2011 and 2014 were retrospectively analyzed. Capecitabine/FOLFOX/CAPOX chemotherapy was co-administered with preoperative radiotherapy. Surgical resection with laparoscopic or open TME was conducted 8–12 weeks after completion of the pre-CRT. Postoperative radiotherapy was routinely given to patients with pT4 lesion or circumferential margin (CRM) and/or distal resection margin (DRM) involvement. Results: In total, 108 (59%) patients received pre-CRT and 75 (41%) underwent surgery first. The pre-CRT patients presented with less-advanced pathological T stage tumors compared with the surgery-first patients (p

Abstract The lungs are the second most common site of metastasis for colorectal cancer (CRC) after the liver. Rectal cancer is associated with a higher incidence of lung metastases compared to colon cancer. In China, the proportion of rectal cancer cases is around 50%, much higher than that in Western countries (nearly 30%). However, there is no available consensus or guideline focusing on CRC with lung metastases. We conducted an extensive discussion and reached a consensus of management for lung metastases in CRC based on current research reports and the experts’ clinical experiences and knowledge. This consensus provided detailed approaches of diagnosis and differential diagnosis and provided general guidelines for multidisciplinary therapy (MDT) of lung metastases. We also focused on recommendations of MDT management of synchronous lung metastases and initial metachronous lung metastases. This consensus might improve clinical practice of CRC with lung metastases in China and will encourage oncologists to conduct more clinical trials to obtain high-level evidences about managing lung metastases.

Oxaliplatin, fluorouracil plus leucovorin (FOLFOX) regimen is the first-line chemotherapy of patients with metastatic colorectal cancer (mCRC). However, studies are limited regarding long non-coding RNAs (lncRNAs) associated with FOLFOX chemotherapy response and prognosis. This study aimed to identify lncRNAs associated with FOLFOX chemotherapy response and prognosis in mCRC patients and to construct a predictive model. We analyzed lncRNA expression in 11 mCRC patients treated with FOLFOX chemotherapy before surgery (four sensitive, seven resistant) by Gene Array Chip. The top eight lncRNAs (AC007193.8, CTD-2008N3.1, FLJ36777, RP11-509J21.4, RP3-508I15.20, LOC100130950, RP5-1042K10.13, and LINC00476) for chemotherapy response were identified according to weighted correlation network analysis (WGCNA). A competitive endogenous RNA (ceRNA) network was then constructed. The crucial functions of the eight lncRNAs enriched in chemotherapy resistance were mitogen-activated protein kinase (MAPK) and proteoglycans signaling pathway. Receiver operating characteristic (ROC) analysis demonstrated that the eight lncRNAs were potent predictors for chemotherapy resistance of mCRC patients. To further identify a signature model lncRNA chemotherapy response and prognosis, the validation set consisted of 196 CRC patients from our center was used to validate lncRNAs expression and prognosis by quantitative PCR (qPCR). The expression of the eight lncRNAs expression between CRC cancerous and adjacent non-cancerous tissues was also verified in the validation data set to determine the prognostic value. A generalized linear model was established to predict the probability of chemotherapy resistance and survival. Our findings showed that the eight-lncRNA signature may be a novel biomarker for the prediction of FOLFOX chemotherapy response and prognosis of mCRC patients.

This paper accompanies the paper titled ''Defining and predicting early recurrence in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy'' presented by the same authors to the European Journal of Surgical Oncology [1]. The present article describes the relevant clinical data of patterns of initial recurrence after curative surgery for rectal cancer with neoadjuvant therapy. This data was collected from the hospital records, Chinese Population Registration and Health Insurance System.

BackgroundFOLFOX chemotherapy is one of the most commonly used treatments for colorectal cancer (CRC) patients. However, the efficacy and tolerance of FOLFOX therapy varies between patients. The purpose of this study was to explore hub genes associated with primary chemotherapy-resistance and to explore the possible mechanisms involved from non-European patients.MethodA weighted gene co-expression network was constructed to identify gene modules associated with chemotherapy resistance in mCRC from China.ResultsA Gene Array Chip was used to detect mRNA expression in 11 mCRC patients receiving preoperative FOLFOX chemotherapy. The immune response was associated with chemotherapy-resistance in microarray data. Through the use of WGCNA, we demonstrated that the crucial functions enriched in chemotherapy-resistance modules were cell proliferation, MAPK signaling pathways, and PI3K signaling pathways. Additionally, we identified and validated FBXW4 as a new effective predictor for chemotherapy sensitivity and a prognostic factor for survival of CRC patients by using our own data and GSE69657. Furthermore, a meta-analysis of 15 Gene Expression Omnibus–sourced datasets showed that FBXW4 messenger RNA levels were significantly lower in CRC tissues than in normal colon tissues. An analysis of the data from the R2: Genomics Analysis and Visualization Platform showed that low FBXW4 expression was correlated with a significantly worse event- and relapse-free survival. Gene set enrichment analysis showed that the mechanism of FBXW4-mediated chemotherapy resistance may involve the DNA replication signal pathway and the cell cycle.ConclusionFBXW4 is associated with chemotherapy resistance and prognosis of CRC probably by regulating DNA replication signaling pathways and the cell cycle.

Aims. To evaluate the impact of body mass index (BMI) on the surgical outcome of laparoscopic total mesorectal excision (laTME) for locally advanced rectal cancer (LARC, clinically staged as UICC stage II/III) after neoadjuvant chemoradiotherapy (nCRT). Methods. 312 LARC patients undergoing laTME after nCRT were divided into nonobese (BMI

Aims. To compare the surgical and oncological outcomes of rectal mucinous adenocarcinomas treated with neoadjuvant chemoradiotherapy versus surgery alone. Methods. A total of 167 locally advanced rectal mucinous adenocarcinoma patients treated with neoadjuvant chemoradiotherapy and surgery alone between 2008 and 2014 were matched using propensity score; the surgical and oncological outcomes were compared. Results. Ninety-six patients were matched. Postoperative morbidity was similar between groups. Sphincter preservation rate was higher in patients receiving neoadjuvant chemoradiotherapy (79.2% versus 60.4%, P=0.045), especially for tumors ≥ 3 cm but ≤5 cm from the anal verge (75.0% versus 44.0%, P=0.036). With a median follow-up of 54.8 months, the 5-year overall survival rate (neoadjuvant chemoradiotherapy versus surgery alone: 79.6% versus 67.1%; P=0.599) and disease-free survival rate (75.6% versus 64.2%; P=0.888) were similar. The 5-year local recurrence rate was lower in patients receiving neoadjuvant chemoradiotherapy (7.7% versus 26.0%, P=0.036), while no difference was observed in distant metastasis. A poor response to chemoradiation was associated with higher local recurrence (P=0.037). Conclusions. Compared with surgery alone, neoadjuvant chemoradiotherapy was found to increase the sphincter preservation rate and reduce local recurrence, thus being beneficial for locally advanced rectal mucinous adenocarcinoma patients.

Aim. To evaluate the influence of interval between neoadjuvant chemoradiotherapy (NCRT) and surgery on oncological outcome. Methods. A systematic search was conducted in PubMed, the Cochrane Library, and Embase databases for publications reporting oncological outcomes of patients following rectal cancer surgery performed at different NCRT-surgery intervals. Relative risk (RR) of pathological complete response (pCR) among different intervals was pooled. Results. Fifteen retrospective cohort studies representing 4431 patients met the inclusion criteria. There was a significantly increased rate of pCR in patients treated with surgery followed 7 or 8 weeks later (RR, 1.45; 95% CI, 1.18–1.78; and P