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Background: To detect the risk factors associated with esophagojejunal anastomotic leakage (EJAL) after total gastrectomy for gastric and Siewert type II/III esophagogastric cancer and investigate the effect of laparoscopic anastomosis on EJAL. Methods: The data for 609 patients underwent Roux-en-Y esophagojejunostomy after total gastrectomy between March 2015 and March 2021 were reviewed. Univariate and multivariate analyses were performed to evaluate the risk factors. We adopted propensity score matching to compare the rate of the anastomotic leakage of the laparoscopic and open anastomosis group. Results: EJAL was observed in 48 (7.9%) of 609 patients. Univariate analysis revealed that gender, age, the number of comorbidities, postoperative serum albumin, tumor location, duration of operation were risk factors associated with EJAL. Patients who had the following factors including male, age ≥50 years, the number of comorbidities ≥2, postoperative serum albumin ＜35 g/L, tumor location was esophagogastric junction, duration of operation ≥260 min were more likely to develop EJAL than those who had not. Multivariate analysis revealed that the number of comorbidities (OR 3.214, 95% CI 1.092 – 9.463, p = 0.034) and duration of operation (OR 2.68, 95% CI 1.251 – 5.740, p = 0.011) were independent risk factors associated with EJAL. 161 patients received laparoscopic anastomosis and 448 patients received open anastomosis. The rates of anastomotic leakage in the laparoscopic and open anastomosis groups were comparable after propensity score matching (Laparoscopic 8.1% vs Open 10.6%, p = 0.565). Conclusions: More morbidities and prolonged operative duration were independently associated with EJAL after total gastrectomy for gastric and Siewert type II/III esophagogastric cancer. Laparoscopic anastomosis did not increase the risk of anastomotic leakage, compared with open anastomosis.

Supplementary Figure S2. DNA hypermethylation of the p75NGFR promoter analyzed in 29 cancer types from the TCGA data portal. The relative positions of 9 analyzed methylation probes are indicated within a schematic map of the human p75NGFR gene. The red-labeled one is the same probe with our methyaltion array chip.

Supplementary figure legends.

Supplementary Table S1-S4

The nerve growth factor receptor (NGFR/p75) is a potential tumor suppressor, but its role in colorectal cancer is unknown. Here, the hypermethylation status, biologic function, and clinical relevance were determined for p75NGFR in colorectal cancer. The methylation status and expression of p75NGFR were assessed in colorectal cancer cell lines and clinical tissues by bisulfite genomic sequencing (BGS), qRT-PCR, and immunoblot assay. Methylation of p75NGFR was frequently found in colorectal cancer, leading to its silencing or downregulation, and it was effectively restored by a demethylation agent. The overexpression of p75NGFR in multiple colorectal cancer cell model systems significantly inhibited cell proliferation (concomitant with G1-phase arrest), invasion, and colony formation and induced cell apoptosis. In contrast, p75NGFR knockdown significantly promoted proliferative and invasive phenotypes. Importantly, p75NGFR methylation was observed in the majority of primary colorectal cancer specimens and was associated with histologic grade and preoperative serum CA19-9 levels. Multivariate analysis indicated that patients who lack p75NGFR have reduced overall survival (64% vs. 75%, P = 0.028) and disease-free survival (61% vs. 72%, P = 0.034) compared with p75NGFR-positive patients. In conclusion, p75NGFR is predominantly silenced or downregulated in colorectal cancer, and its biologic activities are consistent with it being a relevant tumor suppressor.Implications: p75NGFR is a candidate tumor suppressor and has independent prognostic potential in colorectal cancer. Mol Cancer Res; 13(1); 107–19. ©2014 AACR.

Objective The benefit of adjuvant chemotherapy is still controversial for stage II gastric cancer patients. This study aims to identify prognostic factors to guide individualized treatment for stage II gastric cancer patients. Methods We retrospectively reviewed 1121 stage II gastric cancer patients who underwent D2 radical gastrectomy from 2007 to 2017 in the Sixth Affiliated Hospital of Sun Yat-sen University, FuJian Medical School Affiliated Union Hospital and Sun Yat-sen University Cancer Center. Propensity score matching was used to ensure that the baseline data were balanced between the adjuvant chemotherapy group and surgery-only group. Kaplan–Meier survival and multivariate Cox regression analyses were carried out to identify independent prognostic factors. Results In univariate analysis, after propensity score matching, age, tumor location, tumor size, CEA, T stage and N stage were associated with overall survival (OS). Multivariate analysis illustrated that age ≥ 60 years old, linitis plastica and T4 were independent risk factors for OS, but lower location and adjuvant chemotherapy were protective factors. Conclusion Stage II gastric cancer patients with adverse prognostic factors (age ≥ 60, linitis plastica and T4) have poor prognosis. Adjuvant chemotherapy may be more beneficial for these patients.

To determine the morbidity, mortality, and pathologic outcomes of transanal total mesorectal resection (taTME) versus laparoscopic total mesorectal excision (laTME) among patients with rectal cancer with clinical stage I to III rectal cancer below the peritoneal reflection.Studies with sufficient numbers of patients allowing clinical acceptance of taTME for rectal cancer are lacking. Thus, we launched a randomized clinical trial to compare the safety and efficacy of taTME versus laTME.A randomized, open-label, phase 3, noninferiority trial was performed at 16 different hospitals in 10 Chinese provinces. The primary endpoints were 3-year disease-free survival and 5-year overall survival. The morbidity and mortality within 30 days after surgery, and pathologic outcomes were compared based on a modified intention-to-treat principle; this analysis was preplanned.Between April 13, 2016, and June 1, 2021, 1115 patients were randomized 1:1 to receive taTME or laTME. After exclusion of 26 cases, modified intention-to-treat set of taTME versus laTME groups included 544 versus 545 patients. There were no significant differences between taTME and laTME groups in intraoperative complications [26 (4.8%) vs 33 (6.1%); difference, -1.3%; 95% confidence interval (CI), -4.2% to 1.7%; P=0.42], postoperative morbidity [73 (13.4%) vs 66 (12.1%); difference, 1.2%; 95% CI, -2.8% to 5.2%; P=0.53), or mortality [1 (0.2%) vs 1 (0.2%)]. Successful resection occurred in 538 (98.9%) versus 538 (98.7%) patients in taTME versus laTME groups (difference, 0.2%; 95% CI, -1.9% to 2.2%; P0.99).Experienced surgeons can safely perform taTME in selected patients with rectal cancer.

Purpose: Previous studies proposed that the multidisciplinary team (MDT) consultation could improve tumor staging accuracy and outcomes of patients with gastric malignancy. However, evidence-based reports remain limited. This study aimed to determine the effectiveness of MDT for tumor staging accuracy and outcomes of patients with resectable gastric cancer, and to explore the potential factors affecting its effectiveness. Methods: This retrospective study enrolled 719 gastric cancer patients who underwent gastrectomy in our hospital. After propensity score matching, 378 patients were selected, including 189 in the non-MDT group and 189 in the MDT group. Data regarding baseline characteristics, staging, treatments, and survival were analyzed. Results: The data showed that the staging accuracy in the MDT group and non-MDT group was comparable (53% vs 61% for T stage, 46.1% vs 35.3% for N stage, and 78.3% vs 78.7% for M stage). The MDT group had a higher proportion of preoperative chemotherapy (39.2% vs 28%, p=0.03) and laparoscopic surgery (82.5% vs 72%, p=0.02) than the non-MDT group. However, the achievement of R0 resection was similar in the two groups (93.7% vs 88.9%, p=0.73). There was no significant difference in the 1-year and 3-year overall survival rates between the two groups. Moreover, we observed poor patient compliance when the MDT recommended further examinations, radiotherapy, or chemotherapy before surgical interventions. Conclusion: MDT consultation has limited effects on improving the staging accuracy and treatment outcomes including survival of patients with resectable gastric cancer. Poor patient compliance may be a factor affecting the effectiveness of MDT consultation.

Background Nutritional status and quality of life deteriorate significantly after total gastrectomy for patients with gastric cancer. The numerous types of reconstruction proposed by medical researchers around the world have limited effect. This prospective, randomized clinical trial compared functional jejunal interposition with Roux-en-Y anastomosis to identify the optimal reconstruction procedure. Methods This was a multi-center, prospective, randomized control trial. The enrolled patients were randomly assigned into the functional jejunal interposition group and the Roux-en-Y group. All patients were followed up at regular intervals after surgery. The endpoints were postoperative nutritional status, quality of life, and long-term postoperative complications. Results A total of 113 patients were enrolled from August 2012 to September 2017. Until March 2018, the median follow-up period was 18 months. At 12 months after surgery, food intake per meal (P = 0.021), Prognosis Nutritional Index (P = 0.015), weight loss (P = 0.019), and Gastrointestinal Symptom Rating Scale score (P = 0.015) of the functional jejunal interposition group were significantly worse than those of the Roux-en-Y group. There was no significant difference in operative time, intraoperative blood loss, perioperative complications, time of first flatus and defecation after surgery, postoperative plasma nutritional parameters, Visick score, Eastern Cooperative Group physical condition score, and survival rate. Conclusion For patients with long-term survival after total gastrectomy for gastric cancer, the Roux-en-Y anastomosis is a better choice compared with functional jejunal interposition.

Background Survival benefit of neoadjuvant chemotherapy (NAC) for advanced gastric cancer (AGC) is a debatable issue. Studies have shown that the survival benefit of NAC is dependent on the pathological response to chemotherapy drugs. For those who achieve pathological complete response (pCR), NAC significantly prolonged prolapsed-free survival and overall survival. For those with poor response, NAC yielded no survival benefit, only toxicity and increased risk for tumor progression during chemotherapy, which may hinder surgical resection. Thus, predicting pCR to NAC is of great clinical significance and can help achieve individualized treatment in AGC patients. Aim To establish a nomogram for predicting pCR to NAC for AGC patients. Methods Two-hundred and eight patients diagnosed with AGC who received NAC followed by resection surgery from March 2012 to July 2019 were enrolled in this study. Their clinical data were retrospectively analyzed by logistic regression analysis to determine the possible predictors for pCR. Based on these predictors, a nomogram model was developed and internally validated using the bootstrap method. Results pCR was confirmed in 27 patients (27/208, 13.0%). Multivariate logistic regression analysis showed that higher carcinoembryonic antigen level, lymphocyte ratio, lower monocyte count and tumor differentiation grade were associated with higher pCR. Concordance statistic of the established nomogram was 0.767. Conclusion A nomogram predicting pCR to NAC was established. Since this nomogram exhibited satisfactory predictive power despite utilizing easily available pretreatment parameters, it can be inferred that this nomogram is practical for the development of personalized treatment strategy for AGC patients.

Background Gastric cancer is one of the most common malignancies, and has a high mortality rate. miR-495 acts as a suppressor in some cancers and HMGA2 (high mobility group AT-hook 2) is a facilitator for cell growth and epithelial-mesenchymal transition (EMT), but little is known about their effect in gastric cancer. This study aimed to investigate the role and mechanism of miR-495 in gastric cancer. Material/Methods miR-495 levels were quantitatively analyzed in gastric cancer tissue and GES-1, SGC-7901, BGC-823, and HGC-27 cell lines by qRT-PCR. Levels of miR-495 and HMGA2 were altered by cell transfection, after which cell migration and invasion were examined by Transwell and E-cadherin (CDH1); vimentin (VIM), and alpha smooth muscle actin (ACTA2) were detected by qRT-PCR and Western blotting. The interaction between miR-495 and HMGA2 was verified by dual-luciferase reporter assay. Results miR-495 was significantly downregulated in cancer tissue and cell lines (p

Objective Peritoneal dissemination is difficult to diagnose by conventional imaging technologies. We aimed to construct a nomogram to predict peritoneal dissemination in gastric cancer (GC) patients. Methods We retrospectively analyzed 1,112 GC patients in Sun Yat-sen University Cancer Center between 2001 and 2010 as the development set and 474 patients from The Sixth Affiliated Hospital, Sun Yat-sen University between 2010 and 2016 as the validation set. The clinicopathological variables associated with gastric cancer with peritoneal dissemination (GCPD) were analyzed. We used logistic regression analysis to identify independent risk factors for peritoneal dissemination. Then, we constructed a nomogram for the prediction of GCPD and defined its predictive value with a receiver operating characteristic (ROC) curve. External validation was performed to validate the applicability of the nomogram. Results In total, 250 patients were histologically identified as having peritoneal dissemination. Logistic regression analysis demonstrated that age, sex, tumor location, tumor size, signet-ring cell carcinoma (SRCC), T stage, N stage and Borrmann classification IV (Borrmann IV) were independent risk factors for peritoneal dissemination. We constructed a nomogram consisting of these eight factors to predict GCPD and found an optimistic predictive capability, with a C-index of 0.791, an area under the curve (AUC) of 0.791, and a 95% confidence interval (95% CI) of 0.762-0.820. The results found in the external validation set were also promising. Conclusions We constructed a highly sensitive nomogram that can assist clinicians in the early diagnosis of GCPD and serve as a reference for optimizing clinical management strategies.

Introduction Although neoadjuvant chemo-radiotherapy (CRT) achieves low local recurrence rates in locally advanced rectal cancer (LARC), it raises a lot of concerns about long-term anal and sexual functions. We explored the efficacy of preoperative chemotherapy with mFOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) in patients with LARC. Patients and Methods Patients with LARC evaluated by pelvic magnetic resonance imaging (MRI) were enrolled in this trial. All received 4 to 6 cycles of mFOLFOXIRI. MRI was performed to assess clinical response after chemotherapy. Patients with mesorectal fascia-positive or ycT4a/b after re-evaluation would receive radiation before surgery, whereas responders would have immediate total mesorectal excision (TME). Adjuvant chemotherapy with mFOLFOX6 (folinic acid, 5-fluorouracil, and oxaliplatin) was recommended. The primary endpoint was the proportion of tumor downstaging to ypT0-2N0M0. The secondary endpoints were pathologic complete response rate (pCR), 3-year disease-free survival rate, and safety. Results Overall, 106 patients were enrolled and received neoadjuvant mFOLFOXIRI chemotherapy. A total of 103 participants underwent TME surgery. Among 103 patients who completed at least 4 cycles of preoperative chemotherapy, 2 received short-term radiation before TME, and 12 underwent long-term CRT after MRI evaluation. The pCR rate was 20.4%, and the tumor downstaging rate was 42.7%. Among patients without preoperative long-term radiotherapy, the pCR rate and tumor downstaging rate were 17.4% and 41.3%, respectively. Among the per-protocol population, the tumor downstaging rate was 48.1%, and the pCR rate was 20.3%. The chemotherapy-related toxicity was well-tolerated. Conclusion Neoadjuvant chemotherapy with mFOLFOXIRI and selective radiation does not seem to compromise outcomes in LARC. It could be a reasonable alternative to CRT in previously untreated patients with LARC.

Novel drugs are urgently needed for gastric cancer (GC) treatment. The thioredoxin-thioredoxin reductase (TRX-TRXR) system has been found to play a critical role in GC tumorigenesis and progression. Thus, agents that target the TRX-TRXR system may be highly efficacious as GC treatments. In this study, we showed that chaetocin, a natural product isolated from the Chaetomium species of fungi, inhibited proliferation, induced G2/M phase arrest and caspase-dependent apoptosis in both in vitro and in vivo models (cell xenografts and patient-derived xenografts) of GC. Chaetocin inactivated TRXR-1, resulting in the accumulation of reactive oxygen species (ROS) in GC cells; overexpression of TRX-1 as well as cotreatment of GC cells with the ROS scavenger N-acetyl-L-cysteine attenuated chaetocin-induced apoptosis; chaetocin-induced apoptosis was significantly increased when GC cells were cotreated with auranofin. Moreover, chaetocin was shown to inactivate the PI3K/AKT pathway by inducing ROS generation; AKT-1 overexpression also attenuated chaetocin-induced apoptosis. Taken together, these results reveal that chaetocin induces the excessive accumulation of ROS via inhibition of TRXR-1. This is followed by PI3K/AKT pathway inactivation, which ultimately inhibits proliferation and induces caspase-dependent apoptosis in GC cells. Chaetocin therefore may be a potential agent for GC treatment.

PURPOSE In the multicenter, open-label, phase III FOWARC trial, modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus radiotherapy resulted in a higher pathologic complete response rate than fluorouracil plus radiotherapy in Chinese patients with locally advanced rectal cancer. Here, we report the final results. METHODS Adults ages 18 to 75 years with stage II/III rectal cancer were randomly assigned (1:1:1) to five cycles of infusional fluorouracil (leucovorin 400 mg/m2, fluorouracil 400 mg/m2, and fluorouracil 2.4 g/m2 over 48 hours) plus radiotherapy (46.0 to 50.4 Gy delivered in 23 to 25 fractions during cycles 2 to 4) followed by surgery and seven cycles of infusional fluorouracil, the same treatment plus intravenous oxaliplatin 85 mg/m2 on day 1 of each cycle (mFOLFOX6), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. The primary end point was 3-year disease-free survival (DFS). RESULTS In total, 495 patients were randomly assigned to treatment. After a median follow-up of 45.2 months, DFS events were reported in 46, 39, and 46 patients in the fluorouracil plus radiotherapy, mFOLFOX6 plus radiotherapy, and mFOLFOX6 arms. In each arm, the probability of 3-year DFS was 72.9%, 77.2%, and 73.5% ( P = .709 by the log-rank test), the 3-year probability of local recurrence after R0/1 resection was 8.0%, 7.0%, and 8.3% ( P = .873 by the log-rank test), and the 3-year overall survival rate was 91.3%, 89.1%, and 90.7% ( P = .971 by log-rank test), respectively. CONCLUSION mFOLFOX6, with or without radiation, did not significantly improve 3-year DFS versus fluorouracil with radiation in patients with locally advanced rectal cancer. No significant difference in outcomes was found between mFOLFOX6 without radiotherapy and fluorouracil with radiotherapy, which requires additional investigation of the role of radiotherapy in these regimens.

Background: Gastric cancer is the fourth most common malignant disease. Both CDK10 and long noncoding RNAs (lncRNAs) have been found to exert biological functions in multiple cancers. However, it is still unclear whether CDK10 represses tumor progression in gastric cancer by reducing potential targeting lncRNAs. Methods: The functions of CDK10 and lncRNA-C5ORF42-5 in proliferation, invasion and migration were assessed by MTS assays, colony formation assays, cell cycle and apoptosis assays, Transwell assays, wound healing assays and animal experiments. We used high-throughput sequencing to confirm the existence of lncRNA-C5ORF42-5 and quantitative real-time PCR was used to evaluate lncRNA expression. Then, with RNA-seq sequencing as well as GO function and KEGG enrichment analysis, we identified the signaling pathways in which lncRNA-C5ORF42-5 was involved in gastric cancer. Finally, western blotting was used to identify the genes regulated by lncRNA-C5ORF42-5. Results: Our results showed that CDK10 is expressed at relatively low levels in gastric cancer cell lines and inhibits the progression of gastric cancer cells both in vitro and in vivo. Next, based on high-throughput sequencing, we identified a novel lncRNA, lncRNA-C5ORF42-5, in the stable CDK10-overexpressing cell line compared with the CDK-knockdown cell line and their controls. Additionally, we confirmed that lncRNA-C5ORF42-5 acts as an oncogene to promote metastasis in gastric cancer in vitro and in vivo. We then ascertained that lncRNA-C5ORF42-5 is a major contributor to the function of CDK10 in gastric cancer metastasis by upregulating lncRNA-C5ORF42-5 to reverse the effects of CDK10 overexpression. Finally, we explored the mechanism by which lncRNA-C5ORF42-5 overexpression affects gastric cancer cells to elucidate whether lncRNA-C5ORF42-5 may increase the activity of the SMAD pathway of BMP signaling and promote the expression of EMT-related proteins, such as E-cadherin. Additionally, overexpression of lncRNA-C5ORF42-5 affected the phosphorylation levels of AKT and ERK. Conclusion: Our findings suggest that CDK10 overexpression represses gastric cancer tumor progression by reducing lncRNA-C5ORF42-5 and hindering activation of the related proteins in metastatic signaling pathways, which provides new insight into developing effective therapeutic strategies in the treatment of metastatic gastric cancer.

OBJECTIVE To evaluate the effect of art therapy on cancer patients' quality of life and physical and psychological symptoms. METHODS The databases PubMed, Embase, Web of Science, The Cochrane Library, Clinical Trial.gov, the China National Knowledge Infrastructure (CNKI), Wanfang and the Chinese Biomedical Literature Database (CBM) were searched from their inception up to 20 August 2019. Trials examining the effects of art therapy on physical and psychological symptoms and quality of life versus a control group were included. The methodological quality of the included randomised controlled trials was assessed using the risk of bias tool of Cochrane Handbook. Meanwhile, the Newcastle-Ottawa Quality Assessment Scale (NOS) was used to evaluate the methodological quality of the non-randomised studies. RESULTS Twelve studies involving 587 cancer patients were included. The results revealed that art therapy significantly reduced anxiety symptoms (standard mean difference [SMD] = -0.46, 95% confidence interval [CI] [-0.90, 0.02], p = .04), depression symptoms (SMD = -0.47, 95% CI [-0.72, 0.21], p

Background: Billroth I, Billroth II, Roux-en-Y, and Un-cut Roux-en-Y are common reconstruction techniques of distal gastrectomy. Which of these techniques is better has yet to be established. We performed an indirect comparison to evaluate which technique was optimal for preventing reflux symptoms. Methods: The PubMed, Cochrane Collaboration, Embase, ClinicalTrials.gov and Web of Science databases were searched to identify clinical trials that compared at least two of the reconstruction skills among Billroth I, Billroth II, Roux-en-Y, and Un-cut Roux-en-Y. Data on reflux gastritis, intraoperative blood loss, bile reflux and postoperative hospital stays were extracted from the included clinical trials for meta-analysis using a random-effects model. Results: Twenty-four articles that included 5419 individuals were assessed as eligible for meta-analysis. The indirect comparison suggested that Roux-en-Y reconstruction significantly reduces reflux gastritis, and it tended to rank first and had the highest probability of preventing bile reflux. No significant differences were found in intraoperative blood loss and postoperative hospital stays. Conclusion: This indirect comparison suggested some superiority of Roux-en-Y reconstruction after distal gastrectomy. Further perspective clinical trials are required to provide evidence for the optimal reconstruction skill.

A novel single-phase Ni0.9Zn0.1O was synthesized by using a simple hydrothermal method. The crystal structure, morphology and element distribution have been analyzed by X-ray diffraction, transmission electron microscopy and EDS mapping. The results showed that 2D graphene-like and porous structure was successfully grown on the surface of Ni0.9Zn0.1O. The single-phase Ni0.9Zn0.1O was further applied to remove Congo red (CR), which was used as a model of organic pollutants in aqueous solution. Unexpectedly, it is found that the graphene-like single-phase Ni0.9Zn0.1O has the superior adsorption capacity for CR in aqueous solution. The adsorption isotherms and kinetics follow Langmuir and pseudo-second order models, respectively. This study provides great promise of as-prepared Ni0.9Zn0.1O powders as absorbent for removal of organic dyes.

The role of RecQ-like helicase 5 (RECQL5) in gastric cancer (GC) is unclear. This study investigated the expression, clinicopathological association and prognosis of RECQL5 protein in human GC. Firstly, the Oncomine database was used to determine the mRNA expression levels of RECQL5 in GC samples. GC samples and adjacent normal gastric tissue samples were subsequently assessed to determine RECQL5 protein expression levels using immunohistochemistry. The clinicopathological association with RECQL5 expression was analyzed. Multivariate Cox analysis was performed to determine the relationship between RECQL5 expression and survival outcomes. Data from the Oncomine database revealed that RECQL5 mRNA was significantly downregulated in GC tissues compared with that in normal gastric tissues (P

The role of RecQ protein-like 5 (RECQL5) in gastric carcinoma (GC) is still unclear. Here, we investigated the role of RECQL5 in human GC and its potential regulatory network via bioinformatics analysis.Bioinformatic analysis was performed using data in the Oncomine database, Kaplan- Meier Plotter online software, MethHC database, catalogue of somatic mutations in cancer (COSMIC), cbioportal database and String database. Then, we verified the association between RECQL5 expression and GC prognosis by immunohistochemistry (IHC). The independent prognostic factors were determined by Cox multivariate analysis.It was found that both the mRNA and protein expression levels of RECQL5 were downregulated in GC samples (P .05). Low RECQL5 expression indicated a poor prognosis in GC patients and is the independent prognostic factors for GC. No correlation between RECQL5 mRNA and DNA methylation was found using the MethHC database. The analysis of the COSMIC database showed a high proportion of missense mutation in GC. The functional enrichment analysis predicted that RECQL5 plays a role in DNA repair and cellular responses to DNA damage stimulus. RECQL5 might be enriched in homologous recombination pathways and Fanconi anemia pathway. Bioinformatics analysis identified 5 genes, namely POLR2D, POLR2G, DXO, KIN, and EIF2D, that were significantly correlated with RECQL5.The low expression of RECQL5 predicts poor overall survival in GC. RECQL5 may be a novel tumor suppressor for patients with GC.

Purpose Total mesorectal excision with fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy is a standard treatment of locally advanced rectal cancer. This study investigated the addition of oxaliplatin with and without preoperative radiotherapy. Methods In this multicenter, open-label, phase III trial, we randomly assigned (1:1:1) Chinese adults (age 18 to 75 years) with locally advanced stage II/III rectal cancer to three treatments: five 2-week cycles of infusional fluorouracil (leucovorin 400 mg/m2, fluorouracil 400 mg/m2, and fluorouracil 2.4 g/m2 over 48 h) plus radiotherapy (46.0 to 50.4 Gy delivered in 23 to 25 fractions during cycles 2 through 4) followed by surgery and seven cycles of infusional fluorouracil, the same treatment plus intravenous oxaliplatin 85 mg/m2 on day 1 of each cycle (modified FOLFOX6 [mFOLFOX6]), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. Random assignment was performed by using computer-generated block randomization codes. The primary end point was 3-year disease-free survival. Secondary end points of histopathologic response and toxicity are reported. Results A total of 495 patients were enrolled from June 2010 to February 2015; 475 were evaluable (fluorouracil-radiotherapy, n = 155; mFOLFOX6-radiotherapy, n = 157; mFOLFOX6, n = 163). In the fluorouracil-radiotherapy, mFOLFOX6-radiotherapy, and mFOLFOX6 groups, the rate of pathologic complete response (pCR) was 14.0%, 27.5%, and 6.6%, and downstaging (ypStage 0 to 1) was achieved by 37.1%, 56.4%, and 35.5% of patients, respectively. Higher toxicity and more postoperative complications were observed in patients who received radiotherapy. Conclusion mFOLFOX6-based preoperative chemoradiotherapy results in a higher pCR rate than fluorouracil-based treatment. Perioperative mFOLFOX6 alone had inferior results and a lower pCR rate than chemoradiotherapy but led to a similar downstaging rate as fluorouracil-radiotherapy, with less toxicity and fewer postoperative complications.

Background and aims Mucosal healing is regarded as a clinical endpoint of Crohn’s disease (CD), and transmural healing is correlated to the concept of deep remission. Current therapies to induce mucosal and transmural healing in CD are not satisfactory. Exclusive enteral nutrition (EEN) is underestimated therapy and its value has not been fully evaluated. Our aim was to investigate the efficacy of oral EEN for inducing mucosal and transmural healing in CD patients. Methods This was a prospective, single-center, open-label study including diagnosed CD children and adults conducted between January 2015 and December 2016 in the Sixth Affiliated Hospital of Sun Yat-sen University. All patients were treated with oral EEN and underwent paired assessment at baseline and completion using C-reaction protein, erythrocyte sedimentation rate, platelets, hemoglobin, body mass index, CD activity index, simple endoscopic score for CD and bowel sonography. Azathioprine was combined to prevent relapse. Results In this prospective observational study, 29 CD patients with an average age of 28.9 years were identified. After oral EEN treatment, 23 patients (79%) achieved complete mucosal healing, and the mean time to reach mucosal healing was 123 days (ranged from 50 to 212 days). Although only five patients (17%) achieved transmural healing, a significant reduction was observed in bowel-wall thickness (9.41 ± 3.06 vs 4.97 ± 1.76 mm, P

Objective To identify independent prognostic factors to be included in a nomogram to predict the prognosis of gastric cancer patients with peritoneal dissemination. Methods This is a retrospective study on 684 patients with a histological diagnosis of gastric cancer with peritoneal dissemination from the Sun Yat-sen University Cancer Center as the development set, and 62 gastric cancer patients from the Sixth Affiliated Hospital of Sun Yat-sen University as the validation group. Chi-square test and Cox regression analysis were used to compare the clinicopathological variables and the prognosis of gastric cancer patients with peritoneal dissemination. The Harrell's concordance index (C-index) and calibration curve were determined for comparisons of predictive ability of the nomogram. Results Univariate and multivariate analyses showed that serum carcinoembryonic antigen (CEA) level (P=0.032), ascites grading (P=0.008), presence of extraperitoneal metastasis (P

Although many advances have been made in the treatment of gastric cancer (GC), numerous difficulties, such as the emergence of chemo-drug resistance, continue to lead to disappointing GC prognoses. Thus, novel alternative strategies are urgently needed. The use of natural products could be a viable option to treat GC. Toosendanin (TSN) is a triterpenoid derived from the bark of Melia toosendanin Sieb. et Zucc that has been shown to be highly cytotoxic to multiple cancer cells. As the underlying impact of TSN on GC and its molecular mechanism remain poorly understood, in this study, we performed a series of experiments involving the use of TSN to treat GC cells. In the present study, we showed that TSN suppressed cell viability, inhibited cell proliferation by causing G1/S arrest and induced caspase-dependent apoptosis in AGS and HGC-27 cells. The possible mechanism of TSN-induced apoptosis may be associated with the activation of the p38 MAPK pathway. These results demonstrated the potential of TSN as a promising therapeutic compound to treat gastric cancer.

The present study aimed to investigate the expression, clinical association, and prognosis of RecQ protein-like 4 (RECQL4) protein in human gastric cancers (GCs). The expression levels and prognostic value of RECQL4 were initially predicted by using bioinformatics. GC specimens and matched normal gastric tissues were evaluated by immunohistochemistry (IHC), and patient clinicopathological parameters and survival times were analyzed. Multivariate Cox analysis was used to determine the prognostic role of RECQL4 expression. The Oncomine database predicted that RECQL4 mRNA expression levels were significantly increased in GCs as compared with those in normal gastric tissues (P

The aim of the present study was to compare the tumor volume reduction rate (TVRR), as determined by three-dimensional region-of-interest magnetic resonance volumetry, and Response Evaluation Criteria in Solid Tumors (RECIST) data for predicting the pathological tumor response (PTR) of locally advanced rectal cancer (LARC) following treatment with neoadjuvant chemoradiation (CRT). The current cohort consisted of 105 patients with LARC [clinical tumor stage (cT)3–4 or clinical lymph node stage (cN)+] from a prospective randomized trial who had undergone pre-operative CRT and radical proctectomy. Tumor volumes were measured prior to and following CRT to determine TVRR. Furthermore, receiver operating characteristic (ROC) curves of TVRR and RECIST were constructed to predict the PTR in terms of tumor regression grade (TRG) and downstaging. Values for the area under the ROC curve (AUC) were compared and TVRR cut-off levels were determined. RECIST was used to identify 5 (4.8%) cases of complete response, 44 (41.9%) of partial response, 55 (52.4%) of stable disease and 1 (0.9%) of progressive disease. The mean TVRR was 58.6±24.4%, and a good TRG (0–1) and downstaging occurred in 54 (51.4%) and 59 (56.2%) patients, respectively. In addition, TVRR and RECIST were significantly correlated with TRG and downstaging (P

The nerve growth factor receptor (NGFR/p75) is a potential tumor suppressor, but its role in colorectal cancer is unknown. Here, the hypermethylation status, biologic function, and clinical relevance were determined for p75NGFR in colorectal cancer. The methylation status and expression of p75NGFR were assessed in colorectal cancer cell lines and clinical tissues by bisulfite genomic sequencing (BGS), qRT-PCR, and immunoblot assay. Methylation of p75NGFR was frequently found in colorectal cancer, leading to its silencing or downregulation, and it was effectively restored by a demethylation agent. The overexpression of p75NGFR in multiple colorectal cancer cell model systems significantly inhibited cell proliferation (concomitant with G1-phase arrest), invasion, and colony formation and induced cell apoptosis. In contrast, p75NGFR knockdown significantly promoted proliferative and invasive phenotypes. Importantly, p75NGFR methylation was observed in the majority of primary colorectal cancer specimens and was associated with histologic grade and preoperative serum CA19-9 levels. Multivariate analysis indicated that patients who lack p75NGFR have reduced overall survival (64% vs. 75%, P = 0.028) and disease-free survival (61% vs. 72%, P = 0.034) compared with p75NGFR-positive patients. In conclusion, p75NGFR is predominantly silenced or downregulated in colorectal cancer, and its biologic activities are consistent with it being a relevant tumor suppressor. Implications: p75NGFR is a candidate tumor suppressor and has independent prognostic potential in colorectal cancer. Mol Cancer Res; 13(1); 107–19. ©2014 AACR.

To describe and analyze the complications of subcutaneous venous access port for patients with gastrointestinal malignancy.Data of 1 912 patients with gastrointestinal malignancy who accepted chemotherapy in our department via subcutaneous venous access ports, including 127 cases in upper arm, 865 cases in subclavicular vein and 920 cases in internal jugular vein, from June 2007 to April 2016 were analyzed retrospectively. Associated complications and risk factors were emphatically investigated.Postoperative complications were confirmed in 233 patients(12.2%), and complication morbidity was 37.0%(47/127), 15.5%(134/865), 6.7%(62/920) in upper arm group, subclavicular vein group, internal jugular vein group respectively, whose difference was statistically significant (χSubcutaneous venous access port implantation is a preferable access to central vein. Appropriate intubation approach and standardized training may reduce postoperative complications effectively. Internal jugular vein approach is safer and more reliable than upper arm vein and subclavian vein approach.