Comparison of laparoscopic lateral lymph node dissection for rectal cancer with and without routine resection of the visceral branches of internal iliac artery.

PURPOSE: This study aimed to explore the safety and feasibility of the modified lateral lymph node dissection (LLND) with routine resection of the visceral branches of internal iliac vessels (IIVs) for mid-low-lying rectal cancer. MATERIALS AND METHOD: Consecutive patients undergoing LLND for rectal cancer were divided into the routine visceral branches of the IIVs resection group (RVR group) and the NRVR group (without routine resection). The main outcomes were postoperative complications and the number of lateral lymph nodes harvested. RESULTS: From 2012 to 2021, a total of 75 and 57 patients were included in the RVR and NRVR group, respectively. The operative time was reduced in the RVR group (p = 0.020). No significant difference was observed between the two groups for the incidence of total, major, or minor postoperative complications. Pathologically confirmed LLNM were 24 (32%) patients in the RVR group and 12 (21.1%) in the NRVR group (p = 0.162). The number of lateral lymph nodes harvested had no significant difference between two groups (11 vs. 12, p = 0.329). CONCLUSION: LLND with routine resection of visceral branches of IIVs is safe and feasible, which brings no major complication or long-term urinary disorder.

Neoadjuvant chemotherapy (CAPOX) alone for low- and intermediate-risk stage II/III rectal cancer: Long-term follow-up of a prospective single-arm study.

BACKGROUND: Stratified treatment has been recommended for rectal cancer. Our previous multicenter randomized trial showed that low-/intermediate-risk rectal cancer patients did not benefit much from neoadjuvant chemoradiotherapy. In our phase II study, we found that stage II/III rectal cancer patients with low-/intermediate risks can be managed by neoadjuvant chemotherapy alone and achieve a good response. The current study aimed to report the long-term survival outcomes in the expanded phase II trial. METHOD: Consecutive patients diagnosed with mid-low stage II/III rectal cancer with low/intermediate risk factors were included. Four cycles of neoadjuvant chemotherapy (CAPOX) were given, and MRI was used for tumour response detection. The primary endpoint was disease-free survival. The secondary endpoints were tumour response to NCT, tumour-related death, and overall survival. RESULTS: This study enrolled 121 eligible patients. The good tumour response rate based on MRI was 82.6 %, with a pathological complete response (pCR) rate of 18.3 %. The disease-free survival rate was 82.6 %, and the overall survival rate was 96.7 % after a median follow-up time of 40 months. Two patients (1.7 %) suffered local recurrence, and 15 patients (12.4 %) suffered distant metastasis. The median disease-free survival and overall survival were 37 (9-60) and 40 (16-60) months, respectively. Tumour longitudinal length reduction and tumour regression grade on MRI were identified as predictors for poor tumour response to neoadjuvant chemotherapy. CONCLUSION: In stage II/III rectal cancer patients with low-/intermediate risks, neoadjuvant chemotherapy alone may result in an acceptable tumour response and disease-free survival. Tumour response might be predicted early.

Guideline- Versus Non-Guideline-Based Neoadjuvant Management of Clinical T4 Rectal Cancer.

(1) Background: Practice guidelines recommend neoadjuvant treatment for clinical T4 rectal cancer. The primary objective of this retrospective study was to assess whether compliance with guidelines correlates with patient outcomes. Secondarily, we evaluated predictors of adherence to guidelines and mortality. (2) Methods: A total of 397 qualified rectal cancer (RC) patients from 2017 to 2020 at West China Hospital of Sichuan University were included. Patients were divided into two groups depending on adherence to neoadjuvant treatment guidelines. The main endpoints were overall survival (OS) and disease special survival (DSS). We analyzed factors associated with guideline adherence and mortality. (3) Results: Compliance with guidelines was only 39.55%. Patients' neoadjuvant therapy treated not according to the guidelines for clinical T4 RC was not associated with an overall survival (95.7% vs. 88.9%) and disease special survival (96.3% vs. 91.1%) benefit. Patients were more likely to get recommended therapy with positive patient compliance. Staging Ⅲ, medium/high differentiation and objective compliance were associated with increased risk of mortality. (4) Conclusions: Guideline adherence for clinical T4 RC in our system is low. Compliance with the relevant guidelines for neoadjuvant therapy seems not to lead to better overall survival for patients with clinical T4 RC.

Can neoadjuvant chemoradiotherapy combined with immunotherapy benefit patients with microsatellite stable locally advanced rectal cancer? a pooled and integration analysis.

Objective: To assess the clinical efficacy of neoadjuvant chemoradiotherapy combined with immunotherapy for patients with microsatellite stable (MSS) locally advanced rectal cancer and provide evidence to support clinical decision-making. Methods: A systematic search was conducted on the PubMed, Embase, Cochrane Collaboration databases, conference summaries, and Chinese databases for clinical studies that investigated neoadjuvant chemoradiotherapy combined with immunotherapy for the treatment of locally advanced rectal cancer with MSS status. The search spanned from the inception of each database through July 2023. Data from the identified studies were extracted using a pre-designed table, and efficacy outcomes were analyzed. An integrated analysis was conducted using Stata 12.0 software. Results: Eight studies were included, comprising 204 patients with locally advanced MSS rectal cancer who received chemoradiotherapy combined with immunotherapy. The integrated analysis revealed a pathologic complete remission rate of 0.33, a sphincter preservation rate of 0.86, an R0 resection rate of 0.83, a major pathologic remission rate of 0.33, and a clinical complete remission rate of 0.30. Conclusion: Neoadjuvant chemoradiotherapy combined with immunotherapy demonstrates significant short-term efficacy in MSS-type locally advanced rectal cancer, notably enhancing the pathologic complete remission and sphincter preservation rates. This combination is a recommended treatment for patients with MSS-type rectal cancer.

An attention-based neural network model for automatic partition of abdominal lymph nodes in CT imaging.

Background: Abdominal lymph node partition is highly relevant to colorectal cancer (CRC) metastasis, which may further affect patient prognosis and survival quality. In the traditional diagnostic process, medical radiologists must partition all lymph nodes from the computed tomography (CT) images for further diagnostics. The manual interpretation of abdominal nodes is experience-dependent and time-consuming, especially for node partition. Therefore, automated partition methods are desirable to make the diagnostic process more accessible. Automatic abdominal lymph node partition is a challenging task due to the subtle morphological features of the nodes and the complex relative position information of the abdominal structure. Methods: In this paper, a node-oriented dataset containing 6,880 nodes with partition labels was constructed by seasoned professionals through 2-round annotation due to there being no dataset with node-oriented labels to perform the partition task. In addition, specific masking strategies and attention mechanisms were proposed for the primary deep neural networks (DNNs). The specific masking strategy could utilize the positional and morphological information more substantially, which intensively exploits prior knowledge and hones the relative positional information in the lower abdomen. The comprehensive attention mechanism could introduce direction-aware information to enhance the inter-channel relationship of features and capture rich contextual relationships with multi-scale kernels. Results: The experiments were based on the node-oriented dataset. The proposed method achieved superior performance [accuracy (ACC): 89.74%; F1 score (F1): 85.95%; area under the curve (AUC): 88.23%], which is significantly higher than the baseline model with several masking strategies (ACC: 62.05-86.16%; F1: 51.77-80.86%; AUC: 60.44-83.94%). For exploration of attention, the proposed method also outperformed the state-of-the-art convolutional block attention module (CBAM; ACC: 88.90%; F1: 84.09%; AUC: 86.86%) with the same proposed input form. Conclusions: Experimental results indicate that the innovative method performs better in experimental metrics than other prevalent methods. The proposed method is expected to be introduced in future medical scenarios, which will help doctors to optimize the diagnosis workflow and improve partition sensitivity.

Requirement of WDR70 for POLE3-mediated DNA double-strand breaks repair.

H2BK120ub1 triggers several prominent downstream histone modification pathways and changes in chromatin structure, therefore involving it into multiple critical cellular processes including DNA transcription and DNA damage repair. Although it has been reported that H2BK120ub1 is mediated by RNF20/40 and CRL4WDR70, less is known about the underlying regulation mechanism for H2BK120ub1 by WDR70. By using a series of biochemical and cell-based studies, we find that WDR70 promotes H2BK120ub1 by interacting with RNF20/40 complex, and deposition of H2BK120ub1 and H3K79me2 in POLE3 loci is highly sensitive to POLE3 transcription. Moreover, we demonstrate that POLE3 interacts CHRAC1 to promote DNA repair by regulation on the expression of homology-directed repair proteins and KU80 recruitment and identify CHRAC1 D121Y mutation in colorectal cancer, which leads to the defect in DNA repair due to attenuated the interaction with POLE3. These findings highlight a previously unknown role for WDR70 in maintenance of genomic stability and imply POLE3 and CHRAC1 as potential therapeutic targets in cancer.

eIF3i promotes colorectal cancer cell survival via augmenting PHGDH translation.

Translational regulation is one of the decisive steps in gene expression, and its dysregulation is closely related to tumorigenesis. Eukaryotic translation initiation factor 3 subunit i (eIF3i) promotes tumor growth by selectively regulating gene translation, but the underlying mechanisms are largely unknown. Here, we show that eIF3i is significantly increased in colorectal cancer (CRC) and reinforces the proliferation of CRC cells. Using ribosome profiling and proteomics analysis, several genes regulated by eIF3i at the translation level were identified, including D-3-phosphoglycerate dehydrogenase (PHGDH), a rate-limiting enzyme in the de novo serine synthesis pathway that participates in metabolic reprogramming of tumor cells. PHGDH knockdown significantly represses CRC cell proliferation and partially attenuates the excessive growth induced by eIF3i overexpression. Mechanistically, METTL3-mediated N6-methyladenosine modification on PHGDH mRNA promotes its binding with eIF3i, ultimately leading to a higher translational rate. In addition, knocking down eIF3i and PHGDH impedes tumor growth in vivo. Collectively, this study not only uncovered a novel regulatory mechanism for PHGDH translation but also demonstrated that eIF3i is a critical metabolic regulator in human cancer.

Closure of pelvic peritoneum with bladder peritoneum flap reconstruction after laparoscopic extralevator abdominoperineal excision: A prospective stage II study.

BACKGROUND: Extralevator abdominoperineal resection (ELAPE) has increased perineal wound complications due to the extended resection area. Closure of the pelvic peritoneum (CPP) may exclude the abdominal content from descending into the pelvic cavity and reduce the incidence of perineal complications after ELAPE. We have previously introduced bladder peritoneum flap reconstruction (BLAPER) as a novel method for patients in whom traditional CPP is not possible. The aim of the present study was to report the development and preliminary outcomes of BLAPER. METHODS: This is a prospective single-arm study at the development and exploration phase and fulfills the IDEAL framework stage II. Ultralow rectal cancer patients with rigid pelvis who underwent ELAPE with BLAPER were enrolled. Primary outcomes were intraoperative complications and postoperative complications within 1 month after surgery. RESULTS: Among 27 patients included, the overall success rate of BLAPER was 96.3% (26/27). Indocyanine green fluorescence imaging and antiadhesive barrier placement were introduced to improve the BLAPER technique. The incidence of major pelvic wound complications was 7.7%. No patient who underwent BLAPER has suffered small bowel obstruction (SBO), presence of small bowel in the retrourogenital space, or perineal hernia (PH). CONCLUSIONS: BLAPER is safe and may prevent the small bowel from descending into the retrourogenital space and subsequently developing PH and SBO without increasing the intraoperative and postoperative complications. BLAPER may serve as an option when the primary suture of the pelvic peritoneum is not feasible.

Comparison of the pathological response to 2 or 4 cycles of neoadjuvant CAPOX in II/III rectal cancer patients with low/intermediate risks: study protocol for a prospective, non-inferior, randomized control trial (COPEC trial).

BACKGROUND: For patients with low- and intermediate-risk stage II/III rectal cancer, current studies have reached a consensus that preoperative radiotherapy may be dispensed with, and neoadjuvant chemotherapy (NCT) alone might achieve an accepted local control. Our previous phase II study has evidenced that the morphological response of NCT could be better judged at a relatively early stage. Low- and intermediate-risk stage II/III rectal cancer patients could achieve a high rate of tumor shrinkage and downgrade after only 4 cycles of NCT and obvious tumor morphological changes could be observed after 2 cycles of NCT. However, there is still a lack of more detailed stratification and evidence for pathological criteria. The aim of the present study (comparison of the pathological response to 2 or 4 cycles of neoadjuvant CAPOX in II/III rectal cancer patients with low/intermediate risks, COPEC trial) is to determine the pathological tumor regression grade (pTRG) rate of 2 or 4 cycles of NCT in low- and intermediate-risk stage II/III rectal cancer and verify the feasibility of early identification of chemotherapy-insensitive population. METHODS/DESIGN: This is a multicenter, prospective, non-inferior, randomized controlled trial (RCT) initiated by West China Hospital of Sichuan University and designed to be conducted in fourteen hospitals around China. Eligible patients will be centrally randomized into 2 or 4 cycles of CAPOX in a 1:1 ratio using the central automated randomization system offered by the O-trial online system ( https://plus.o-trial.com/ ) and accept total mesorectal excision after 2 or 4 cycles of CAPOX (oxaliplatin 130 mg/m2, once daily on day 1, every 21 days and capecitabine 1000 mg/m2, twice daily on days 1 to 14, every 21 days). The primary endpoint is the proportion of patients with pathological no-tumor regression (pTRG 3), which is determined postoperatively by each sub-center and verified by the primary center. DISCUSSION: COPEC trial is designed to verify that the preoperative CAPOX chemotherapy for low- and intermediate-risk stage II/III rectal cancer could achieve a good response judgment after 2 cycles and obtain the tumor pathological response rate after 2 cycles of CAPOX. We hope the COPEC trial could help in establishing a consensus standard of low- and intermediate-risk rectal cancer and the early identification of stage II/III rectal patients with low- and intermediate-risk who are poorly responding to NCT. TRIAL REGISTRATION: Clinicaltrial.gov NCT04922853. Registered on June 4, 2021.

The same parastomal hernia repairs rate in the different approaches to colostomy.

PURPOSE: This study aimed to compare the parastomal hernia repairs rate in the different approaches to colostomy and investigate the risk factors for parastomal hernia formation in patients with permanent colostomies. METHODS: Consecutive rectal cancer patients who underwent abdominoperineal resection from June 2014 to July 2020 in West China Hospital were divided into two groups according to their surgical approach for permanent colostomies. The impact of different approaches to colostomy on parastomal hernia repairs was determined by comparing a group of patients receiving an extraperitoneal route to colostomy with a group receiving transperitoneal. Potential variables were evaluated first with univariate and then multivariate analyses to identify the risk factors for the formation of parastomal hernia. RESULTS: Two hundred two subjects in the transperitoneal group and 103 in the extraperitoneal group attended the follow-up visit with a median follow-up period of 33 (25th-75th percentiles, 17-46) months. Clinically and radiologically detectable parastomal hernias were present in 76 of 202 (37.6%) and 14 of 103 (13.6%) subjects in the transperitoneal and extraperitoneal groups during the follow-up period (p＜0.01). Besides, 10 of 76 (13.1%) subjects in the transperitoneal group and 2 of 14 (14.3%) subjects in the extraperitoneal group underwent a parastomal hernia operation during the follow-up (p = 0.82). In addition, the transperitoneal approach of colostomy (p = 0.002), older age (p＜0.001), and higher body mass index (p = 0.013) were identified as independent risk factors for the occurrence of parastomal hernia. CONCLUSIONS: Extraperitoneal colostomy decreased the detectable parastomal hernias but did not reduce the surgical repair rate of parastomal hernias.

Which site is better for prophylactic ileostomy after laparoscopic rectal cancer surgery? By the specimen extraction site or new site: A systematic review and meta-analysis.

Background: There is controversy about the outcomes of prophylactic ileostomy via the specimen extraction site (SES) after laparoscopic rectal cancer surgery (LRCS). We, therefore, performed a meta-analysis to determine the efficacy and safety of stoma through the SES versus new site (NS). Methods: All relevant studies from 1997 to 2022 were searched in the PubMed, EMBASE, Cochrane Library, CNKI, VIP databases. This meta-analysis was performed using RevMan software 5.3 for statistical analysis. Results: 7 studies with 1736 patients were included. The present meta-analysis noted that prophylactic ileostomy via SES was associated with a higher risk of overall stoma-related complications, especially parastomal hernia (OR, 2.39, 95% CI 1.43-4.00; p=0.0008). No statistical difference was found in terms of wound infection, ileus, stoma edema, stoma prolapse, stoma necrosis, stoma infection, stoma bleeding, stoma stenosis, skin inflammation around the stoma, stoma retraction and postoperative pain score on postoperative day 1 and 3 between SES group and NS group. However, prophylactic ileostomy via SES was associated with lesser blood loss (MD = -0.38, 95% CI: -0.62 - -0.13; p=0.003), shorter operation time(MD = -0.43, 95% CI: -0.54 - -0.32 min; p<0.00001), shorter post-operative hospital stay (MD = -0.26, 95% CI: -0.43 - -0.08; p=0.004), shorter time to first flatus(MD = -0.23, 95% CI: -0.39 - -0.08; p=0.003) and lower postoperative pain score on postoperative day 2. Conclusion: Prophylactic ileostomy via SES after LRCS reduces new incision, decreases operative time, promotes postoperative recovery, and improves cosmetic outcomes, but may increase the incidence of parastomal hernias. The vast majority of parastomal hernias can be repaired by closing the ileostomy, therefore SES remain an option for temporary ileostomy after LRCS.

DOG1 as a novel antibody-drug conjugate target for the treatment of multiple gastrointestinal tumors and liver metastasis.

Discovered On Gastrointestinal stromal tumors protein 1 (DOG1), a major calcium-activated chloride channel, has been used as a common diagnostic marker for gastrointestinal stromal tumors. However, the therapeutic application of DOG1 was not well defined. Here, we aim to investigate its potential as a therapeutic target for an antibody-drug conjugate (ADC) in various cancers of the alimentary tract and metastasis. The DOG1 expression profile was determined among TCGA samples and tissue microarrays. High levels of DOG1 expression were ubiquitously observed in multiple cancer samples from the alimentary tract determined by TCGA samples and tissue microarrays. Circulating tumor cells isolated from metastatic colon cancer patients were also positive for DOG1 expression. The mechanisms of anti-DOG1 antibody were investigated by dual-luciferase reporter assay. The anti-DOG1 antibody could inhibit proliferation and metastasis via p53 signaling in limited cancer cell lines. The anti-DOG1 antibody was conjugated with a microtubule inhibitor DM4, to construct a new anti-DOG1-DM4-ADC to strengthen its activity. The anti-DOG1-DM4-ADC showed cytotoxicity at the nanomolar level in vitro. In the murine xenograft tumor models, treatment of anti-DOG1-DM4-ADC achieved a significant tumor growth inhibition rate. Our study indicates that anti-DOG1-DM4-ADC may be promising therapeutic molecules for DOG1-positive alimentary tract tumors and may be effective in inhibiting recurrence after curative resection of liver metastases of colorectal origin.

Day-case loop ileostomy reversal based on the community hospital joined enhanced recovery after surgery (CHJ-ERAS) program in China: Safe and feasible.

BACKGROUND: This study was performed to determine the feasibility of Day-case loop ileostomy reversal (DLIR) in China based on the community hospital joined enhanced recovery after surgery (CHJ-ERAS) program. METHOD: Patients who underwent loop ileostomy were enrolled in the CHJ-ERAS program for DLIR after rigorous evaluation. The primary outcome was the results of short-term follow-ups. RESULTS: From August 2017 to April 2022, 216 patients have been enrolled in the CHJ-ERAS program for DLIR. After DLIR, 14 patients (14/216, 6.5%) have recorded 17 episodes of postoperative complications within 1 month after surgery, including 10 readmission and 2 reoperation. Compared with in-patient loop ileostomy reversal, DLIR based on CHJ-ERAS did not increase the postoperative complications and reoperations. CONCLUSION: The CMJ-ERAS program for DLIR in our center is a safe and feasible alternative option for inpatient LIR and an acceptable transitional approach for the development of day-case DLIR in developing countries.

Methylene blue can increase the number of lymph nodes harvested in colorectal cancer: a meta-analysis.

AIM: The lymph node (LN) status plays an important role in colorectal cancer (CRC), which depends on adequate LN harvest. In some studies, methylene blue has been used to increase the number of LNs harvested in vitro. The purpose was to evaluate the effect of methylene blue staining on LN harvest during radical resection of CRC. METHODS: The Cochrane Library, MEDLINE, Embase, PubMed, and Web of Science were searched from the dates of inception until 15 October 2022. Studies were included if they were randomized controlled trials or nonrandomized controlled trials for radical resection of rectal cancer according to the principle of total mesorectal excision that compared the use of methylene blue with blank control in LN harvest. The primary outcomes were the number of LNs harvested and the incidence of fewer than 12 LNs harvested. RESULT: Of 328 articles found, a meta-analysis was conducted of 15 studies (2 randomized controlled trials and 13 non-randomized controlled trials) composed of 3104 patients. Meta-analysis showed that methylene blue could not only significantly increase the number of LNs harvested in CRC specimens (stained group 28.23 vs unstained group 16.15; weighted mean difference 12.08; 95% CI, 8.03-16.12; p < 0.001; I2 = 95%), but also reduce the incidence of fewer than 12 LNs harvested (methylene blue-stained group 7.91% vs unstained group 30.90%; OR 0.12; 95% CI, 0.05-0.26; p < 0.001; I2 = 78%). CONCLUSION: Methylene blue can increase the number of LNs harvested in CRC, reduce the incidence of fewer than 12 LNs harvested, and ensure the accuracy of LN staging.

Survival outcomes of stage I colorectal cancer: development and validation of the ACEPLY model using two prospective cohorts.

BACKGROUND: Approximately 10% of stage I colorectal cancer (CRC) patients experience unfavorable clinical outcomes after surgery. However, little is known about the subset of stage I patients who are predisposed to high risk of recurrence or death. Previous evidence was limited by small sample sizes and lack of validation. METHODS: We aimed to identify early indicators and develop a risk stratification model to inform prognosis of stage I patients by employing two large prospective cohorts. Prognostic factors for stage II tumors, including T stage, number of nodes examined, preoperative carcinoma embryonic antigen (CEA), lymphovascular invasion, perineural invasion (PNI), and tumor grade were investigated in the discovery cohort, and significant findings were further validated in the other cohort. We adopted disease-free survival (DFS) as the primary outcome for maximum statistical power and recurrence rate and overall survival (OS) as secondary outcomes. Hazard ratios (HRs) were estimated from Cox proportional hazard models, which were subsequently utilized to develop a multivariable model to predict DFS. Predictive performance was assessed in relation to discrimination, calibration and net benefit. RESULTS: A total of 728 and 413 patients were included for discovery and validation. Overall, 6.7% and 4.1% of the patients developed recurrences during follow-up. We identified consistent significant effects of PNI and higher preoperative CEA on inferior DFS in both the discovery (PNI: HR = 4.26, 95% CI: 1.70-10.67, p = 0.002; CEA: HR = 1.46, 95% CI: 1.13-1.87, p = 0.003) and the validation analysis (PNI: HR = 3.31, 95% CI: 1.01-10.89, p = 0.049; CEA: HR = 1.58, 95% CI: 1.10-2.28, p = 0.014). They were also significantly associated with recurrence rate. Age at diagnosis was a prominent determinant of OS. A prediction model on DFS using Age at diagnosis, CEA, PNI, and number of LYmph nodes examined (ACEPLY) showed significant discriminative performance (C-index: 0.69, 95% CI:0.60-0.77) in the external validation cohort. Decision curve analysis demonstrated added clinical benefit of applying the model for risk stratification. CONCLUSIONS: PNI and preoperative CEA are useful indicators for inferior survival outcomes of stage I CRC. Identification of stage I patients at high risk of recurrence is feasible using the ACEPLY model, although the predictive performance is yet to be improved.

The effect of BMI on long-term outcome in patients with rectal cancer and establishment of a nomogram prediction model.

BACKGROUND: The effects of body mass index (BMI) in patients with rectal cancer have been poorly studied and are still controversial. In this study, we aimed to assess the effect of BMI on the long-term outcome in patients with rectal cancer after radical surgery. MATERIALS AND METHODS: Between April 2012 and December 2020, patients who received total mesorectal excision (TME) surgery were enrolled in the study. Patients were divided into four groups according to BMI level. Kaplan-Meier survival curves with log-rank tests were used to analyze overall survival (OS), Disease-free survival (DFS), local recurrence-free survival and distant metastasis-free survival. Univariate and multivariate analyses were performed to identify the risk factors associated with the long-term outcome. Nomograms were developed to predict the OS and DFS based on independent prognostic factors. RESULTS: A total of 688 patients were included in this study. The median follow-up time was 69 months. The 5-year OS rates of the control, underweight, overweight and obese groups were 79.2%, 62.2%, 88.7% and 86.3%, respectively. The 5-year DFS rates were 74.8%, 58.2%, 80.5% and 81.4%, respectively. Overweight (HR 0.534; 95% CI 0.332-0.860, p = 0.010) was an independent protective factor for OS and DFS (HR 0.675; 95% CI 0.461-0.989, p = 0.044). Underweight was an independent risk factor for DFS (HR = 1.623; 95% CI 1.034-2.548; p = 0.035), and had a trend to be an independent risk factor for OS (HR 1.594; 95% 0.954-2.663; p = 0.075). Nomograms were established to predict the 2-year OS, 5-year OS, 2-year DFS and 5-year DFS with an area under curve (AUC) of 0.767, 0.712, 0.746 and 0.734, respectively. CONCLUSIONS: For rectal cancer patients after radical surgery, overweight was an independent protective factor for OS and DFS. Underweight was an independent risk factor for DFS and had a trend to be an independent risk factor for OS. Nomograms incorporating BMI and other prognostic factors could be helpful to predict long-term outcome.

The diagnostic value of exosomal circular RNAs in cancer patients: A systematic review and meta-analysis.

BACKGROUND: Recently, serum exosomal circular RNAs (circRNAs) were applied to discriminate cancer patients from healthy individuals, indicating that exosomal circRNAs have the potential to be novel biomarkers for cancer diagnosis. This study aims to summarize the role of exosomal circRNAs in cancer diagnosis by a meta-analysis. METHODS: A comprehensive literature search was conducted up to July 2021 in PubMed, Web of Science, EMBASE, and Cochrane Database. To evaluate the diagnostic value, the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were pooled. Threshold effect followed by subgroup analysis and meta-regression were performed to explore the source of heterogeneity. Sensitivity analysis was performed to assess the stability of this meta-analysis model. Fagan plots and likelihood ratio scattergrams were used to explore the potential clinical significance. RESULTS: Ten eligible studies with 514 controls and 557 patients were included in this diagnostic meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.75 (95% CI: 0.65-0.83), 0.84 (95% CI, 0.78-0.89), 5.87 (95% CI, 3.67-9.38), 0.28 (95% CI, 0.19-0.40), and 21.15 (95% CI, 10.25-43.68), respectively. The AUC was 0.89 (95% CI, 0.86-0.91). Sensitivity analysis showed that four studies had an impact on the pooled results and mainly contributed to the heterogeneity. Fagan's nomogram revealed that the prior probability of 20%, the post probability positive, the post probability negative were 59% and 6%, respectively. CONCLUSION: Our results suggested that exosomal circRNAs might serve as powerful biomarkers in detecting cancers with high sensitivity and specificity. However, more well-designed and multicenter diagnostic tests are needed to validate our results.

Technique to match mesorectal lymph nodes imaging findings to histopathology: node-by-node comparison.

BACKGROUND: Lymph node status is critical for staging rectal cancer and determining neoadjuvant therapy regimens. Establishing a matching between imaging and histopathological lymph nodes is fundamental for predicting lymph node status. This study reports a technique to achieve node-by-node pairing of mesorectal lymph nodes between imaging findings and histopathology. METHODS: Fifty-two patients with histopathologically verified rectal cancer underwent magnetic resonance imaging before surgery. The status of each lymph node in the surgical specimens was analyzed histopathologically and matched with preoperative imaging after the operation. RESULTS: A total of 346 mesorectal lymph nodes were located on imaging evaluation, of which 313 were confirmed histopathologically, and 33 were unmatched. The total success rate of the technique was 90.5%. Node-by-node analysis revealed 280 benign and 33 malignant nodal structures. CONCLUSION: The technique to match mesorectal lymph node imaging findings to histopathology was feasible and effective. It simplified the technical method and had a reasonable success matching rate, which could provide a standardized approach for obtaining a prospective correlation between imaging and histological findings, supporting all subsequent related studies at the level of mesorectal lymph nodes.

Trim28 citrullination maintains mouse embryonic stem cell pluripotency via regulating Nanog and Klf4 transcription.

Protein citrullination, including histone H1 and H3 citrullination, is important for transcriptional regulation, DNA damage response, and pluripotency of embryonic stem cells (ESCs). Tripartite motif containing 28 (Trim28), an embryonic development regulator involved in ESC self-renewal, has recently been identified as a novel substrate for citrullination by Padi4. However, the physiological functions of Trim28 citrullination and its role in regulating the chromatin structure and gene transcription of ESCs remain unknown. In this paper, we show that Trim28 is specifically citrullinated in mouse ESCs (mESCs), and that the loss of Trim28 citrullination induces loss of pluripotency. Mechanistically, Trim28 citrullination enhances the interaction of Trim28 with Smarcad1 and prevents chromatin condensation. Additionally, Trim28 citrullination regulates mESC pluripotency by promoting transcription of Nanog and Klf4 which it does by increasing the enrichment of H3K27ac and H3K4me3 and decreasing the enrichment of H3K9me3 in the transcriptional regulatory region. Thus, our findings suggest that Trim28 citrullination is the key for the epigenetic activation of pluripotency genes and pluripotency maintenance of ESCs. Together, these results uncover a role Trim28 citrullination plays in pluripotency regulation and provide novel insight into how citrullination of proteins other than histones regulates chromatin compaction.