ABHD6 suppresses colorectal cancer progression via AKT signaling pathway.

Colorectal cancer (CRC) continues to be a prevalent malignancy, posing a significant risk to human health. The involvement of alpha/beta hydrolase domain 6 (ABHD6), a serine hydrolase family member, in CRC development was suggested by our analysis of clinical data. However, the role of ABHD6 in CRC remains unclear. This study seeks to elucidate the clinical relevance, biological function, and potential molecular mechanisms of ABHD6 in CRC. We investigated the role of ABHD6 in clinical settings, conducting proliferation, migration, and cell cycle assays. To determine the influence of ABHD6 expression levels on Oxaliplatin sensitivity, we also performed apoptosis assays. RNA sequencing and KEGG analysis were utilized to uncover the potential molecular mechanisms of ABHD6. Furthermore, we validated its expression levels using Western blot and reactive oxygen species (ROS) detection assays. Our results demonstrated that ABHD6 expression in CRC tissues was notably lower compared to adjacent normal tissues. This low expression correlated with a poorer prognosis for CRC patients. Moreover, ABHD6 overexpression impeded CRC cell proliferation and migration while inducing G0/G1 cell cycle arrest. In vivo experiments revealed that downregulation of ABHD6 resulted in an increase in tumor weight and volume. Mechanistically, ABHD6 overexpression inhibited the activation of the AKT signaling pathway and decreased ROS levels in CRC cells, suggesting the role of ABHD6 in CRC progression via the AKT signaling pathway. Our findings demonstrate that ABHD6 functions as a tumor suppressor, primarily by inhibiting the AKT signaling pathway. This role establishes ABHD6 as a promising prognostic biomarker and a potential therapeutic target for CRC patients.

Machine learning-based prediction models affecting the recovery of postoperative bowel function for patients undergoing colorectal surgeries.

PURPOSE: The debate surrounding factors influencing postoperative flatus and defecation in patients undergoing colorectal resection prompted this study. Our objective was to identify independent risk factors and develop prediction models for postoperative bowel function in patients undergoing colorectal surgeries. METHODS: A retrospective analysis of medical records was conducted for patients who undergoing colorectal surgeries at Peking University People's Hospital from January 2015 to October 2021. Machine learning algorithms were employed to identify risk factors and construct prediction models for the time of the first postoperative flatus and defecation. The prediction models were evaluated using sensitivity, specificity, the Youden index, and the area under the receiver operating characteristic curve (AUC) through logistic regression, random forest, Naïve Bayes, and extreme gradient boosting algorithms. RESULTS: The study included 1358 patients for postoperative flatus timing analysis and 1430 patients for postoperative defecation timing analysis between January 2015 and December 2020 as part of the training phase. Additionally, a validation set comprised 200 patients who undergoing colorectal surgeries from January to October 2021. The logistic regression prediction model exhibited the highest AUC (0.78) for predicting the timing of the first postoperative flatus. Identified independent risk factors influencing the time of first postoperative flatus were Age (p < 0.01), oral laxatives for bowel preparation (p = 0.01), probiotics (p = 0.02), oral antibiotics for bowel preparation (p = 0.02), duration of operation (p = 0.02), postoperative fortified antibiotics (p = 0.02), and time of first postoperative feeding (p < 0.01). Furthermore, logistic regression achieved an AUC of 0.72 for predicting the time of first postoperative defecation, with age (p < 0.01), oral antibiotics for bowel preparation (p = 0.01), probiotics (p = 0.01), and time of first postoperative feeding (p < 0.01) identified as independent risk factors. CONCLUSIONS: The study suggests that he use of probiotics and early recovery of diet may enhance the recovery of bowel function in patients undergoing colorectal surgeries. Among the various analytical methods used, logistic regression emerged as the most effective approach for predicting the timing of the first postoperative flatus and defecation in this patient population.

Young adults with colon cancer: clinical features and surgical outcomes.

BACKGROUND: The clinicopathological features, surgical outcomes, and long-term survival of patients with young-onset colon cancer (≤ 40 years old) remain controversial. METHODS: The clinicopathologic and follow-up data of patients aged < 40 years with colon cancer between January 2014 and January 2022 were reviewed. The primary objectives were clinical features and surgical outcomes. Long-term survival was investigated as a secondary objective. RESULTS: Seventy patients were included in the study, and no significant rising trend (Z=0, P=1) of these patients was observed over the 8-year study period. Stage IV disease was accompanied by more ulcerative or infiltrating type (84.2% vs. 52.9%, P=0.017) and lymphovascular or perineural invasion (64.7% vs. 25.5%, P=0.003) than stage I-III disease. After a median follow-up time of 41 months (range 8-99 months), the 1-, 3-, and 5-year estimated overall survival (OS) rates were 92.6%, 79.5%, and 76.4%, respectively. The 1-, 3-, and 5-year progression-free survival (PFS) rates were 79.6%, 71.7%, and 71.7%, respectively. Multivariate Cox regression showed that M+ stage (hazard ratio [HR], 3.942; 95% confidence interval [CI], 1.176-13.220, P=0.026) was the only independent risk factor affecting OS. Meanwhile, tumor deposits (HR, 4.807; 95% CI, 1.942-15.488, P=0.009), poor differentiation (HR, 2.925; 95% CI, 1.012-8.454, P=0.047), and M+ stage (HR, 3.540; 95% CI, 1.118-11.202, P=0.032) independently affected PFS. CONCLUSIONS: The differences in the clinical features, surgical outcomes, and long-term survival between young adults and elderly colon cancer patients need further investigation.

Lymph node metastasis in T1-2 colorectal cancer: a population-based study.

BACKGROUND: We performed this study to identify predictive factors for lymph node metastasis (LNM) and analyze the impact of LNM on the prognosis of patients with T1-2 colorectal cancer (CRC), with the intention of providing guidance for the treatment. METHODS: The Surveillance Epidemiology and End Result database was used to identify 20,492 patients diagnosed with T1-2 stage CRC between 2010 and 2019, who underwent surgery and lymph node evaluation and had complete prognostic information. Clinicopathological data of patients with T1-2 stage colorectal cancer treated with surgery at Peking University People's Hospital from 2017 to 2021 with complete clinical information were retrieved. We identify and confirm the risk factors for positive lymph node involvement, and the results of follow-up were analyzed. RESULTS: Age, preoperative carcinoembryonic antigen (CEA) level, perineural invasion, and primary tumor site were independent risk factors for LNM in T1-2 CRC based on the analysis of the SEER database, while tumor size and histology of mucinous carcinoma were also independent risk factors in T1 CRC. We then make the nomogram model for predicting LNM risk and showed an acceptable consistency and calibration capability. Survival analysis showed that LNM was an independent prognostic indicator of 5-year disease-specific survival (P = 0.013) and disease-free survival (P < 0.001) in patients with T1 and T2 CRC. CONCLUSION: Age, CEA level and primary tumor site should be taken into consideration before making the surgical decision in T1-2 CRC patients. The tumor size and histology of mucinous carcinoma also need to be thought about in T1 CRC. Conventional imaging tests do not appear to provide a precise assessment for this issue.

Laparoscopic Versus Open Surgery for Rectal Gastrointestinal Stromal Tumor: A Multicenter Propensity Score-Matched Analysis.

BACKGROUND: The safety and feasibility of laparoscopic surgery for the management of rectal gastrointestinal stromal tumors are unknown. OBJECTIVE: This study aimed to compare the surgical and oncologic results of laparoscopic versus open surgery for the treatment of rectal gastrointestinal stromal tumors. DESIGN: This was a retrospective multicenter propensity score-matched study to minimize heterogeneity between groups and focus on the difference between surgery strategies. SETTINGS: Eleven Chinese tertiary hospitals participated in this study. PATIENTS: A total of 364 patients with pathologically confirmed rectal gastrointestinal stromal tumors were retrospectively analyzed. MAIN OUTCOME MEASURES: Relapse-free survival, postoperative hospital stay length, and 30-day postoperative complication rate were the main outcome measures. RESULTS: We enrolled 214 patients who underwent surgical operation for primary localized rectal gastrointestinal stromal tumors. After propensity score matching, 134 cases involved in the comparison (67 laparoscopic vs 67 open surgery) were randomly matched (1:1) by sex, age, tumor size, tumor site, and neoadjuvant therapy. The laparoscopic surgery group had superior relapse-free survival (χ2 = 4.46, p = 0.04), and fewer complications (6.0% vs 25.4%, p = 0.002). No significant difference was found in the length of postoperative hospital stay between the laparoscopic surgery and open surgery groups (9.66 ± 5.42 vs. 10.64 ± 4.93, p = 0.28). Subgroup analysis showed that the laparoscopic surgery group had superior relapse-free survival (χ2 = 4.14, p = 0.04) and fewer complications after surgery (2.9% vs 24.4%, p = 0.01) in the rectal gastrointestinal stromal tumors ≤5 cm subgroup. LIMITATIONS: This study was limited by the nature of retrospective reviews and relatively short follow-up period. CONCLUSIONS: Laparoscopic surgery offers a safe and feasible option for the radical resection of primary localized rectal gastrointestinal stromal tumors, especially for patients with rectal gastrointestinal stromal tumors ≤5 cm. See Video Abstract at http://links.lww.com/DCR/B764. CIRUGA LAPAROSCPICA VERSUS CIRUGA ABIERTA PARA TUMORES DEL ESTROMA GASTROINTESTINAL DE RECTO UN ANLISIS MULTICNTRICO EMPAREJADO POR PUNTAJE DE PROPENSIN: ANTECEDENTES:Se desconoce la seguridad y factibilidad de la cirugía laparoscópica para el tratamiento de los tumores del estroma gastrointestinal de recto.OBJETIVO:Comparar los resultados quirúrgicos y oncológicos de la cirugía laparoscópica versus cirugía abierta para el tratamiento de los tumores del estroma gastrointestinal de recto.DISEÑO:Estudio retrospectivo multicéntrico emparejado por puntuación de propensión para minimizar la heterogeneidad entre los grupos y centrarse en las diferencias entre las estrategias quirúrgicas.AJUSTES:Once hospitales terciarios de la China participaron en este estudio.PACIENTES:Se analizaron retrospectivamente un total de 364 pacientes con tumores del estroma gastrointestinal de recto confirmados patológicamente.PRINCIPALES MEDIDAS DE VALORACION:Supervivencia sin recidiva, duración de la estancia hospitalaria postquirúrgica y tasa de complicaciones postquirúrgicas a los 30 días.RESULTADOS:Inscribimos a 214 pacientes que fueron sometidos a cirugía por tumores primariamente localizados del estroma gastrointestinal de recto. Después del emparejamiento por puntaje de propensión, 134 casos involucrados en la comparación (67 laparoscópicos versus 67 cirugía abierta) fueron emparejados aleatoriamente (1: 1) por sexo, edad, tamaño del tumor, sitio del tumor y terapia neoadyuvante. El grupo de cirugía laparoscópica tuvo una supervivencia sin recidiva superior (χ2 = 4,46, p = 0,04) y menos complicaciones (6,0% frente a 25,4%, p = 0,002). No se encontraron diferencias significativas en la duración de la estancia hospitalaria postquirúrgica entre los grupos de cirugía laparoscópica y cirugía abierta (9,66 ± 5,42 frente a 10,64 ± 4,93, p = 0,28). El análisis de subgrupos mostró que el grupo de cirugía laparoscópica tuvo una supervivencia sin recidiva superior (χ2 = 4,14, p = 0,04) y menos complicaciones después de la cirugía (2,9% frente a 24,4%, p = 0,01) en el subgrupo de tumores del estroma gastrointestinal de recto ≤ 5 cm.LIMITACIONES:La naturaleza de la revisión retrospectiva y el período de seguimiento relativamente corto son limitaciones de este estudio.CONCLUSIONES:La cirugía laparoscópica ofrece una opción segura y factible para la resección radical de tumores primariamente localizados del estroma gastrointestinal de recto, especialmente para pacientes con tumores ≤5 cm. Consulte Video Resumen en http://links.lww.com/DCR/B764.

Establishment of the prediction model and biological mechanism exploration for secondary imatinib-resistant in gastrointestinal stromal tumor.

A gastrointestinal stromal tumor (GIST) is mostly driven by the auto-activated, mutant KIT receptor tyrosine kinase gene or by the platelet-derived growth factor receptor alpha. Inhibition of KIT-signaling is the primary molecular target therapy for GIST, which is performed by the drug imatinib clinically. However, more than half of advanced or metastatic GIST develop secondary resistance to imatinib within 2 years after initiation of treatment, and the mechanism of acquired imatinib-resistant in GIST remains unclear. Therefore, we designed the present study, and firstly analyzed the gene expression profile of imatinib-resistant and sensitive GIST from GEO DataSet and identified 44 differential expressed genes. Then, a model including nine genes with their expressed coefficients was identified as a risk score to predict imatinib-resistant GIST. Internal and external validation of the prediction model was performed through the ROC curve, and the area under the curve was 0.967 (95%CI 0.901-1.000) and 0.917 (95%CI 0.753-1.000), separately. Lastly, the effect of immune, m6A, pyroptosis, and ferroptosis-related genes on imatinib-resistant GIST was also assessed because DNA replication was the most enriched biological function of DEGs after functional annotation, pathway enrichment, and protein-protein interaction network analyses. In conclusion, the present study established a novel model to predict secondary imatinib-resistant GIST. Meanwhile, the bioinformatic mining results provided potential and promising targets for imatinib-resistant therapy.

Assessment of adjuvant chemotherapy benefits after complete mesocolic excision in patients with colon cancer: Reanalysis of data from the ESCME trial.

AIM: The benefits of adjuvant chemotherapy (AC) in colon cancer after complete mesocolic excision (CME) have not been evaluated sufficiently. We reanalysed the ESCME trial data to investigate the survival benefits and establish AC stratified indications. METHODS: The data of Stage II and III colon cancer patients who received CME in the ESCME trial were reanalysed. Patients were divided into AC and non-AC (NAC) groups. The primary outcomes measured were differences in 5-year cancer-specific survival and disease-free survival (DFS) between the groups. RESULTS: Of the 206 patients enrolled in the study, 125 patients (AC, 49; NAC, 76) had Stage II cancer and 111 (AC, 86; NAC, 25) had Stage III cancer. There were no significant differences in the adjusted 5-year cancer-specific survival and DFS between the AC and NAC groups. Poor differentiation (hazard ratio [HR] 2.947; 95% CI 1.218-7.131) and RAS mutation (HR 3.140; 95% CI 1.363-7.234) affected the 5-year DFS significantly in multivariate Cox regression analysis for Stage II and III cancer, respectively. In subgroup analysis, AC significantly improved 5-year DFS (HR 0.369; 95% CI 0.140-0.978) for Stage III cancer with lymphovascular/perineural invasion compared to NAC. CONCLUSION: The current indication and benefits of AC for colon cancer patients after CME should be re-evaluated. AC is more appropriate for Stage III cancer with lymphovascular/perineural invasion.

Safety and Efficacy of Laparoscopic Surgery versus Open Surgery in Elderly Patients with Colon Cancer: A Propensity Score Matching Cohort Study.

INTRODUCTION: The safety of laparoscopic surgery (LS) and its effect on survival have not been sufficiently assessed in elderly colon cancer patients. METHODS: Clinicopathologic data of patients aged ≥75 years who underwent colectomy for primary colon cancer, between January 2018 and June 2021, were reviewed. Patients were divided into the LS and open surgery (OS) groups according to the intention-to-treat principle and were compared using propensity score matching. The primary outcomes were differences in surgical safety and 3-year survival. RESULTS: There were 98 patients with a median age of 82 years and 85 patients with a median age of 80 years assigned to the OS and LS groups, respectively. Propensity score matching revealed that LS did not prolong the operative time (190 vs. 180 min, p = 0.209) and was linked to less intraoperative blood loss (50 vs. 100 mL, p = 0.039) and shorter postoperative hospital stay (8 vs. 10 days, p = 0.005), compared to OS. In addition, LS was not accompanied by more stress response when the variations exhibited in laboratory tests and the Barthel index pre- and postsurgery were considered. There were no significant differences in the adjusted 3-year overall survival (86.0% vs. 81.2%, p = 0.795) and disease-free survival (86.6% vs. 87.9%, p = 0.356) between the groups. CONCLUSION: LS enhanced postoperative recovery without increasing surgical risks, compared to OS, in colon cancer patients aged ≥75 years. Furthermore, no significant differences in the 3-year adjusted survival were observed between the groups.

Pathological and oncological outcomes of pylorus-preserving versus conventional distal gastrectomy in early gastric cancer: a systematic review and meta-analysis.

BACKGROUND: Pylorus-preserving gastrectomy (PPG) is a function-preserving surgery for the treatment of early gastric cancer (EGC) in the middle third of the stomach. According to the literature reports, PPG decreases the incidence of dumping syndrome, bile reflux, gallstone formation, and nutritional deficit compared with conventional distal gastrectomy (CDG). However, the debates about PPG have been dominated by the incomplete lymphadenectomy and oncological safety. We carried out a systematic review and meta-analysis to evaluate the pathological and oncological outcomes of PPG. METHODS: The protocol was registered in PROSPERO under number CRD42022304677. Databases including PubMed, Embase, Web of Science, and the Cochrane Register of Controlled Trials were searched before February 21, 2022. The outcomes included the pooled odds ratios (ORs) for dichotomous variables and weighted mean differences (WMDs) for continuous variables. For all outcomes, 95% confidence intervals (CIs) were calculated. Meta-analysis was performed using STATA software (Stata 14, Stata Corporation, Texas) and Review Manager 5.4. RESULTS: A total of 4500 patients from 16 studies were included. Compared with the CDG group, the PPG group had fewer lymph nodes harvested (WMD= -3.09; 95% CI -4.75 to -1.43; P < 0.001). Differences in the number of resected lymph nodes were observed at stations No. 5, No. 6, No. 9, and No. 11p. There were no differences in lymph node metastasis at each station. Shorter proximal resection margins (WMD = -0.554; 95% CI -0.999 to -0.108; P = 0.015) and distal resection margins (WMD = -1.569; 95% CI -3.132 to -0.007; P = 0.049) were observed in the PPG group. There were no significant differences in pathological T1a stage (OR = 0.99; 95% CI 0.80 to 1.23; P = 0.88), T1b stage (OR = 1.01; 95% CI 0.81 to 1.26; P = 0.88), N0 stage (OR = 0.97; 95% CI 0.63 to 1.48; P = 0.88), tumor size (WMD = -0.10; 95% CI -0.25 to 0.05; P = 0.187), differentiated carcinoma (OR = 1.04; 95% CI 0.74 to 1.47; P = 0.812) or signet ring cell carcinoma (OR = 1.22; 95% CI 0.90 to 1.64; P = 0.198). No significant differences were observed between the groups in terms of overall survival (HR = 0.63; 95% CI 0.24 to 1.67; P = 0.852) or recurrence-free survival (HR = 0.29; 95% CI 0.03 to 2.67; P = 0.900). CONCLUSIONS: The meta-analysis of existing evidence demonstrated that the survival outcomes of PPG may be comparable to those of CDG. However, fewer lymph nodes at stations in No. 5, No. 6, No. 9, and No. 11p were harvested with PPG. We also found shorter proximal resection margins and distal resection margins for PPG, meaning more remnant stomachs would be preserved in PPG.

Quantitative proteomic analysis of aberrant expressed lysine acetylation in gastrointestinal stromal tumors.

BACKGROUND: Gastrointestinal stromal tumor (GIST) is a common digestive tract tumor with high rate of metastasis and recurrence. Currently, we understand the genome, transcriptome and proteome in GIST. However, posttranscriptional modification features in GIST remain unclear. In the present study, we aimed to construct a complete profile of acetylome in GIST. METHODS: Five common protein modifications, including acetylation, succinylation, crotonylation, 2-hydroxyisobutyrylation, and malonylation were tested among GIST subgroups and significantly differentially- expressed lysine acetylation was found. The acetylated peptides labeled with Tandem Mass Tag (TMT)under high sensitive mass spectrometry, and some proteins with acetylation sites were identified. Subsequently, these proteins and peptides were classified into high/moderate (H/M) risk and low (L) risk groups according to the modified NIH classification standard. Furthermore, cell components, molecular function, biological processes, KEGG pathways and protein interaction networks were analyzed. RESULTS: A total of 2904 acetylation sites from 1319 proteins were identified, of which quantitative information of 2548 sites from 1169 proteins was obtained. Finally, the differentially-expressed lysine acetylation sites were assessed and we found that 42 acetylated sites of 38 proteins were upregulated in the H/M risk group compared with the L risk group, while 48 acetylated sites of 44 proteins were downregulated, of which Ki67 K1063Ac and FCHSD2 K24Ac were the two acetylated proteins that were most changed. CONCLUSIONS: Our novel findings provide further understanding of acetylome in GIST and might demonstrate the possibility in the acetylation targeted diagnosis and therapy of GIST.

Risk factors of early postoperative bowel obstruction for patients undergoing selective colorectal surgeries.

OBJECTIVE: Postoperative bowel obstruction was one of the most severe complications in patients who received colorectal surgeries. This study aimed to explore risk factors of early postoperative obstruction and to construct a nomogram to predict the possibility of occurrence. METHODS: The records of 1437 patients who underwent elective colorectal surgery in Peking University People's Hospital from 2015 to 2020 were retrospectively collected. Risk factors of early postoperative bowel obstruction were identified by logistic regression analysis and a nomogram was then constructed. Bootstrap was applied to verify the stability of the model. RESULTS: COPD, hypothyroidism, probiotic indications, duration of antibiotics, and time to postoperative feeding were identified as independent risk factors and were put into a nomogram for predicting early postoperative bowel obstruction. The nomogram showed robust discrimination, with the area under the receiver operating characteristic curve was 0.894 and was well-calibrated. CONCLUSION: A nomogram including independent risk factors of COPD, hypothyroidism, probiotic indications, duration of antibiotics, and time to postoperative feeding were established to predict the risk of early postoperative bowel obstruction.

Development and validation of a novel diagnostic model for initially clinical diagnosed gastrointestinal stromal tumors using an extreme gradient-boosting machine.

INTRODUCTION: Gastrointestinal stromal tumor (GIST) is the most common gastrointestinal soft tissue tumor. Clinical diagnosis mainly relies on enhanced CT, endoscopy and endoscopic ultrasound (EUS), but the misdiagnosis rate is still high without fine needle aspiration biopsy. We aim to develop a novel diagnostic model by analyzing the preoperative data of the patients. METHODS: We used the data of patients who were initially diagnosed as gastric GIST and underwent partial gastrectomy. The patients were randomly divided into training dataset and test dataset at a ratio of 3 to 1. After pre-experimental screening, max depth = 2, eta = 0.1, gamma = 0.5, and nrounds = 200 were defined as the best parameters, and in this way we developed the initial extreme gradient-boosting (XGBoost) model. Based on the importance of the features in the initial model, we improved the model by excluding the hematological features. In this way we obtained the final XGBoost model and underwent validation using the test dataset. RESULTS: In the initial XGBoost model, we found that the hematological indicators (including inflammation and nutritional indicators) examined before the surgery had little effect on the outcome, so we subsequently excluded the hematological indicators. Similarly, we also screened the features from enhanced CT and ultrasound gastroscopy, and finally determined the 6 most important predictors for GIST diagnosis, including the ratio of long and short diameter under CT, the CT value of the tumor, the enhancement of the tumor in arterial period and venous period, existence of liquid area and calcific area inside the tumor under EUS. Round or round-like tumors with a CT value of around 30 (25-37) and delayed enhancement, as well as liquid but not calcific area inside the tumor best indicate the diagnosis of GIST. CONCLUSIONS: We developed a model to further differential diagnose GIST from other tumors in initially clinical diagnosed gastric GIST patients by analyzing the results of clinical examinations that most patients should have completed before surgical resection.

Perineal wound complication risk factors and effects on survival after abdominoperineal resection of rectal cancer: a single-centre retrospective study.

PURPOSE: This study determined the risk factors associated with perineal wound complications (PWCs) and investigated their effect on overall survival in patients with rectal cancer who underwent abdominoperineal resection (APR). METHODS: The clinicopathologic and follow-up data of patients who underwent APR for primary rectal cancer between 1998 and 2018 were reviewed. PWCs were defined as any perineal wound that required surgical intervention, antibiotics, or delayed healing for more than 2 weeks. The primary objective was identifying the risk factors of PWC after APR. The effect of PWC on survival was also investigated as a secondary objective. RESULTS: Two hundred and twenty patients were included in the final analyses and 49 had PWCs. An operative time of > 285 min (odds ratio: 2.440, 95% confidence interval (CI): 1.257-4.889) was found to be independently associated with PWCs. When the follow-up time was > 60 months, patients with PWCs had a significantly lower overall survival rate than patients without PWC (n = 156; mean over survival: 187 and 164 months in patients without and with PWCs, respectively; P = 0.045). Poor differentiation (hazard ratio (HR): 1.893, 95% CI: 1.127-3.179), lymph node metastasis (HR: 2.063, 95% CI: 1.228-3.467), and distant metastasis (HR: 3.046, 95% CI: 1.551-5.983) were associated with poor prognosis. CONCLUSION: Prolonged operative time increases the risk of PWCs, and patients with PWCs have a lower long-term survival rate than patients without PWCs. Therefore, surgeons should aim to reduce the operative time to minimise the risk of PWC in patients undergoing APR for rectal cancer.

Efficacy and Safety of Complete Mesocolic Excision in Patients With Colon Cancer: Three-year Results From a Prospective, Nonrandomized, Double-blind, Controlled Trial.

OBJECTIVE: The aim of the study was to evaluate the oncological outcomes of complete mesocolic excision (CME) in colon cancer patients. SUMMARY BACKGROUND DATA: CME is considered a standard procedure for colon cancer patients. However, previous evidence regarding the effect of CME on prognosis has fundamental limitations that prevent it from being fully accepted. METHODS: Patients who underwent radical resection for colon cancer were enrolled between November 2012 and March 2016. According to the principles of CME, patients were stratified into 2 groups based on intraoperative surgical fields and specimen photographs. The primary outcome was local recurrence-free survival (LRFS). The clinicopathological data and follow-up information were collected and recorded. The final follow-up date was April 2016. The trial was registered in ClinicalTrials.gov (identifier: NCT01724775). RESULTS: There were 220 patients in the CME group and 110 patients in the noncomplete mesocolic excision (NCME) group. Baseline characteristics were well balanced. Compared with NCME, CME was associated with a greater number of total lymph nodes (24 vs 20, P = 0.002). Postoperative complications did not differ between the 2 groups. CME had a positive effect on LRFS compared with NCME (100.0% vs 90.2%, log-rank P < 0.001). Mesocolic dissection (100.0% vs 87.9%, log-rank P < 0.001) and nontumor deposits (97.2% vs 91.6%, log-rank P < 0.022) were also associated with improved LRFS. CONCLUSIONS: Our findings demonstrate that, compared with NCME, CME improves 3-year LRFS without increasing surgical risks.

The cut-off value of tumor size and appropriate timing of follow-up for management of minimal EUS-suspected gastric gastrointestinal stromal tumors.

BACKGROUD: The detectable rate of minimal gastric GISTs has continuously increased. While the surveillance and management of GIST <2 cm have been deemed controversial or lack evidence-based approaches.  The aim of the current study is to propose a cut-off value of tumor size for treatment policy and the appropriate timing for endoscopic ultrasonography (EUS) follow-up in the minimal EUS-suspected gastric GIST patients. METHODS: A single-institution retrospective study was performed. 69 patients with EUS-suspected gastric GISTs were studied from November 2008 to March 2015. 69 patients with minimal gastric GISTs ≤2 cm diagnosed by EUS were followed for a mean period of 29 months (range, 12 to 70). An at least 20% increase of the maximal diameter of the tumors was set as a significant change. RESULTS: During follow-up, Of the 69 minimal EUS-suspected GISTs, 16 (23.2%) showed significant changes in size. 11 out of 69 GISTs (15.9%), 6 out of 43 GISTs (14.0%), 7 out of 30 GISTs (23.3%) showed significant changes in size, at 1 year, 2 years, and more than 3 years respectively. The receiver operating characteristic curve analysis showed that the tumor size cut-off was 9.5 mm. Only 4.7 and 3.7% of gastric EUS-suspected GISTs of <9.5 mm in size showed significant changes at 1 year and 2 years, while 9.5% at more than 3 years. 34.6, 31.3 and 55.6% of gastric EUS-suspected GISTs of ≥ 9.5 mm in size showed significant changes at 1 year, 2 years and more than 3 years. CONCLUSIONS: Minimal EUS-suspected GISTs, larger than 9.5 mm may be associated with significant progression. The patients with a ≥ 9.5 mm GIST should have a EUS 6-12months, while <9.5 mm GIST may have a EUS extended to every 2-3 years.

Chinese consensus guidelines for diagnosis and management of gastrointestinal stromal tumor.

In order to further promote the standardization of diagnosis and treatment of gastrointestinal stromal tumor (GIST) in China, the members of Chinese Society of Clinical Oncology (CSCO) Expert Committee on GIST thoroughly discussed the key contents of the consensus guidelines, and voted on the controversial issue. In final, the Chinese consensus guidelines for the diagnosis and management of GIST (2017 edition) was formed on the basis of 2013 edition consensus guidelines, which is hereby announced. The consensus included the pathological diagnosis, recurrence risk classification evaluation, targeted agent therapy, surgery and principles of surveillance of GIST.

MicroRNA-217 functions as a prognosis predictor and inhibits colorectal cancer cell proliferation and invasion via an AEG-1 dependent mechanism.

BACKGROUND: Recent studies have indicated the possible function of miR-217 in tumorigenesis. However, the roles of miR-217 in colorectal cancer (CRC) are still largely unknown. METHODS: We examined the expression of miR-217 and AEG-1 in 50 CRC tissues and the corresponding noncancerous tissues by qRT-PCR. The clinical significance of miR-217 was analyzed. CRC cell lines with miR-217 upregulation and AEG-1 silencing were established and the effects on tumor growth in vitro and in vivo were assessed. Dual-luciferase reporter gene assays were also performed to investigate the interaction between miR-217 and AEG-1. RESULTS: Our data demonstrated that miR-217 was significantly downregulated in 50 pairs of colorectal cancer tissues. MiR-217 expression levels were closely correlated with tumor differentiation. Moreover, decreased miR-217 expression was also associated with shorter overall survival of CRC patients. MiR-217 overexpression significantly inhibited proliferation, colony formation and invasiveness of CRC cells by promoting apoptosis and G0/G1 phase arrest. Interestingly, ectopic miR-217 expression decreased AEG-1 expression and repressed luciferase reporter activity associated with the AEG-1 3'-untranslated region (UTR). AEG-1 silencing resulted in similar biological behavior changes to those associated with miR-217 overexpression. Finally, in a nude mouse xenografted tumor model, miR-217 overexpression significantly suppressed CRC cell growth. CONCLUSIONS: Our findings suggest that miR-217 has considerable value as a prognostic marker and potential therapeutic target in CRC.

Long noncoding ribonucleic acid specific for distant metastasis of gastric cancer is associated with TRIM16 expression and facilitates tumor cell invasion in vitro.

BACKGROUND AND AIM: Increasing evidence has indicated that long noncoding ribonucleic acids (lncRNAs) play a major role in cancers. Although certain lncRNAs has been reported to play a role in gastric cancer (GC), specific lncRNAs involved in distant metastasis of GC remain unknown. METHODS: Differentially expressed mRNAs and lncRNAs between stage IV and non-stage IV GC were obtained by microarray. Gene ontology and pathway analysis were used to study functions of differential mRNAs. Algorithms were used to predict potential gene targets of cis or trans-acting lncRNAs. Network analysis was performed to analyze each pair of gene-lncRNA, gene-gene, or lncRNA-lncRNA interactions. Expression of lncRNA special for distant metastasis of GC (SDMGC) and target gene TRIM16 were tested in GC tissues and cell lines. RNAi and overexpression were used to observe the biological functions of SDMGC and TRIM16 on GC cells. RESULTS: 502 mRNAs and 440 lncRNAs were found to be differentially expressed. 74 gene ontology terms and 38 pathways were associated with the dysregulated transcripts. Fourteen core factors were determined by network analysis. Expression of SDMGC and TRIM16 was upregulated in the distant metastasis tissues, compared with primary GC tissues, which were positive correlation. Silencing of SDMGC or TRIM16 was demonstrated to decrease cell invasion and migration, while upregulated of SDMGC or TRIM16 could promote cell invasion and migration. However, little effect on proliferation, cell cycle, colony formation, and apoptosis was found. CONCLUSIONS: SDMGC is obviously upregulated in stage IV GC and may represent a new marker and therapeutic target for GC treatment.