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The study aim was to explore the anatomy, histopathology, and molecular biological function of the fascias posterior to the interperitoneal colon and its mesocolon to provide information for improving complete mesocolic excision. To accomplish this aim, we performed intraoperative observations in 60 interperitoneal colon-cancer patients accepted for complete mesocolic excision and conducted local anatomy observations for five embalmed cadavers. An additional two embalmed child cadaver specimens were studied with large slices and paraffin sections. Ten of the 60 patients were examined with a lymph node tracer technique in vivo, while fresh specimens from these patients were assessed by histopathological examination and transwell cell migration assays in vitro. The anatomical and histopathological findings showed that the fascias posterior to the interperitoneal colon and its associated mesocolon were composed of two independent layers: the visceral and parietal fascias. These two fascias were primarily composed of collagen fibers, with the parietal fascia containing a small amount of muscle fiber. The in vivo test showed that the visceral fascia surrounded the colon and its associated mesocolon, including vessels and lymphatics, and that it had no lymphatic flow through it into the rear tissues. Moreover, the in vitro assays showed the visceral fascia was able to block tumor cell migration. Although many surgical scholars have known of the existence of fascia tissue posterior to the intraperitoneal colon, the detailed structure has been ignored and been unclear. As shown by our findings, the visceral and parietal fascias are truly formed structures that have not been previously reported. A thorough understanding of fascial structures and the function of the visceral fascia barrier in blocking tumor cells will facilitate surgeons when performing high-quality complete mesocolic excision procedures. [ABSTRACT FROM AUTHOR]

We have investigated the role of MSH2, a mismatch repair gene in cell proliferation, cell cycle control and cell invasiveness in the SW480 human colorectal cancer cell line. RNAi-mediated inhibition of MSH2 expression was achieved using MSH2 shRNA lentiviral expression vectors. Effective knockdown of endogenous MSH2 expression was determined by real-time PCR analysis. The most efficient MSH2 knockdown vector was selected for subsequent studies using SW480 cells. Endogenous MSH2 mRNA levels decreased after lentiviral delivery of the MSH2-RNAi, indicating efficient silencing of MSH2 expression in SW480 cells. Cell proliferation, cell cycle progression and cell invasiveness were quantified by MTT assays, flow cytometry and transwell assays, respectively. RNAi-mediated inhibition of MSH2 expression in SW480 cells resulted in decreased cell proliferation, cell cycle arrest at the G0/G1 phase and decreased cell invasiveness. Taken together, these results provide evidence that MSH2 stimulates cell proliferation, promotes cell cycle progression and positively regulates cell invasiveness. [ABSTRACT FROM AUTHOR]

Background: The advantage or disadvantage of laparoscopic appendectomy for acute appendicitis remains unclear. Patients and Methods: Data were collected prospectively from 129 consecutive patients with appendicitis between June 2008 and December 2009. The clinical outcomes of acute appendicitis after laparoscopic and open operation were compared. Furthermore, the outcomes of laparoscopic procedure for acute and chronic appendicitis were compared. Results: The length of hospitalization and incidence of intra-abdominal abscess were significantly decreased in patients with laparoscopic group after operation as compared to open operation. The mean operation time, the time of first anal exsufflation, and oral intake after operation were longer for acute appendicitis patients than for chronic appendicitis in laparoscopic group. The incidence of postoperative intestinal obstruction in patients with acute appendicitis was higher after laparoscopic surgery than after open procedure. Conclusions: Laparoscopic appendectomy for acute appendicitis is feasible and safe. However, laparoscopic appendectomy for acute appendicitis might cause more postoperative complications including intra-abdominal abscess and small intestinal obstruction compared to laparoscopic appendectomy for chronic appendicitis. These complications could potentially be avoided by improving techniques in operation. [ABSTRACT FROM AUTHOR]

Abstract: Background: Kindlin-2 has been confirmed as an essential element of bidirectional integrin signaling. In recent years, the relationship between Kindlin-2 expression and cancers has been a focus of interest. However, the relationship between Kindlin-2 expression in gastric cancer and tumor invasion, metastasis, and the outcome of patients have not been studied. Methods: Kindlin-2 expression at protein and RNA levels were detected by Western blot and real-time polymerase chain reaction in 40 pairs of gastric cancer samples. In addition, the correlations between Kindlin-2 expression and clinicopathologic factors as well as the prognosis of the patients were analyzed. Multivariate Cox regression was used to study the effect of Kindlin-2 expression on overall and progression-free survival. Results: We found that Kindlin-2 was up-regulated both at RNA (P = .027) and protein levels (P = .014) in gastric cancer tissues. Tumor samples with high Kindlin-2 expression (Kindlin-2/β-actin:tumor tissue/paraneoplastic tissue, ≥2) was observed in 55% of the patients. Moreover, Kindlin-2 expression had a significant positive correlation with tumor stromal invasion (P = .014), lymph node metastasis (P = .007), and TNM stage (P = .014). Patients with high Kindlin-2 expression had significantly poorer overall survival (P = .012) and progression-free survival (P = .012). High Kindlin-2 expression was an independent risk factor of progression-free survival (hazard ratio, 5.2; 95% confidence interval, 1.1–3.3; P = .032). Conclusions: Kindlin-2 may play an important role in the development of gastric cancer and it is a potential factor that could be used to evaluate the outcome of gastric cancer. Kindlin-2 may shed new light on evaluating the prognosis and targeted therapy of gastric cancer. [Copyright &y& Elsevier]

Abstract: Background: Several studies have shown that metabolic syndrome (MS) was a risk factor for colorectal cancer, but few studies have reported the relationship between MS and the prognosis of colorectal cancer. Methods: Data were collected from 507 cases of colorectal carcinoma between January 2002 and March 2007 to establish the database. These patients were divided into 2 groups based on the presence of MS. We tested the prognostic value of MS in the patients. The risk of adverse events was examined by Cox proportional hazard modeling. Results: The rates of liver metastasis and tumor recurrence were higher in the group of patients with colorectal cancer accompanied by MS. Moreover, MS is one of the important elements that independently can influence the survival (colonic carcinoma: hazard ratio [HR], 1.633; 95% confidence interval [CI], 1.039–2.565; rectal carcinoma: HR, 1.939, 95% CI, 1.076–3.494) and liver metastasis (colonic carcinoma: HR, 2.619; 95% CI, 1.288–5.324; rectal carcinoma: HR, 2.814; 95% CI, .962–2.888) of both colonic and rectal carcinoma patients, and MS patients have the highest risk with worse survival and liver metastases compared with other parameters. Conclusions: The results suggest that MS may be an important prognostic factor for colorectal cancer, decreasing the incidence of MS may improve the therapeutic efficacy of colorectal cancer. [Copyright &y& Elsevier]

Evidence from Europe shows that perioperative chemotherapy may be beneficial for the treatment of locally advanced gastric cancer, but reliable and robust data is lacking. To rectify this, the phase 3 RESONANCE trial investigated the efficacy and safety of S-1 plus oxaliplatin (SOX) as a perioperative chemotherapy regimen for gastric cancer. This randomized, open-label trial enrolled patients from 19 medical centers with stage II/III resectable gastric cancer who were centrally randomly assigned to either perioperative chemotherapy (PC) arm or adjuvant chemotherapy (AC) arm. Patients in the PC arm received two to four cycles of SOX followed by surgery and four to six cycles of SOX. Patients in the AC arm received upfront surgery and eight cycles of SOX. 386 patients in each group were enrolled and 756 (382 in PC and 374 in AC) were included in the mITT population. The three-year DFS rate was 61.7% in the PC arm and 53.8% in the AC arm (log-rank p = 0.019). The R0 resection rate in the PC arm was significantly higher than that in the AC arm (94.9% vs. 83.7%, p < 0.0001). There was no difference between two arms in surgical outcomes or postoperative complications. Safety-related data were like the known safety profile. In conclusion, from a clinical perspective, this trial indicated a trend towards higher three-year disease-free survival rate with perioperative SOX in stage II/III resectable gastric cancer with well-tolerated toxicity compared to adjuvant SOX, which might provide a theoretical basis for applying perioperative SOX in advanced gastric cancer patients. (ClinicalTrials.gov NCT01583361) [ABSTRACT FROM AUTHOR]

Background: Immunotherapy brings new hope to patients with advanced gastric cancer. However, liver metastases can reduce the efficacy of immunotherapy in patients. Tumor-associated macrophages (TAMs) may be the cause of this reduction in efficacy. SPP1 + TAMs are considered to have immunosuppressive properties. We aimed to investigate the involvement of SPP1 + TAMs in the metastasis of gastric cancer. Methods: The single-cell transcriptome was combined with batched BULK datasets for analysis. Animal models were used to verify the analysis results. Results: We reveal the interaction of SPP1 + TAMs with CD8 + exhausted T cells in metastatic cancer. Among these interactions, GDF15-TGFBR2 may play a key immunosuppressive role. We constructed an LR score to quantify interactions based on ligands and receptors. The LR score is highly correlated with various immune features and clinical molecular subtypes. The LR score may also guide the prediction of the efficacy of immunotherapy and prognosis. Conclusions: The crosstalk between SPP1 + TAMs and CD8 + exhausted T cells plays a key immunosuppressive role in the gastric metastatic cancer microenvironment. [ABSTRACT FROM AUTHOR]

Simple Summary: Gastric cancer (GC) is a severe disease with high mortality. There is an immediate demand for GC prognostic markers. The biological role of the lethal (3) malignant brain tumor-like 3 (L3MBTL3) has been investigated in human malignancies, but its involvement in GC is not well understood. This research seeks to better understand L3MBTL3's prognostic significance and expression profiles in GC. We examined the expression and prognostic significance of L3MBTL3 in GC using bioinformatic analysis. A functional enrichment analysis was conducted to explore the potential mechanisms. The correlations between L3MBTL3 and immune infiltration were determined based on the TIMER database. Our work revealed that L3MBTL3 is a promising diagnostic and prognostic marker for GC, opening new avenues for research and treatment. Recent research has linked lethal (3) malignant brain tumor-like 3 (L3MBTL3) to cancer aggressiveness and a dismal prognosis, but its function in gastric cancer (GC) is unclear. This research investigated the association between L3MBTL3 expression and clinicopathological characteristics of GC cases, as well as its prognostic value and biological function based on large-scale databases and clinical samples. The results showed that L3MBTL3 expression was upregulated in malignant GC tissues, which was associated with a shortened survival time and poor clinicopathological characteristics, including TNM staging. A functional enrichment analysis including GO/KEGG and GSEA illustrated the enrichment of different L3MBTL3-associated pathways involved in carcinogenesis and immune response. In addition, the correlations between L3MBTL3 and tumor-infiltrating immune cells were determined based on the TIMER database; the results showed that L3MBTL3 was associated with the immune infiltration of macrophages and their polarization from M1 to M2. Furthermore, our findings suggested a possible function for L3MBTL3 in the regulation of the tumor immune microenvironment of GC. In summary, L3MBTL3 has diagnostic potential, and it also offers new insights into the development of aggressiveness and prognosis in GC. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most prevalent and second most lethal cancer globally, with gene mutations and tumor metastasis contributing to its poor prognosis. Single-cell sequencing technology enables high-throughput analysis of the genome, transcriptome, and epigenetic landscapes at the single-cell level. It offers significant insights into analyzing the tumor immune microenvironment, detecting tumor heterogeneity, exploring metastasis mechanisms, and monitoring circulating tumor cells (CTCs). This article provides a brief overview of the technical procedure and data processing involved in single-cell sequencing. It also reviews the current applications of single-cell sequencing in CRC research, aiming to enhance the understanding of intratumoral heterogeneity, CRC development, CTCs, and novel drug targets. By exploring the diverse molecular and clinicopathological characteristics of tumor heterogeneity using single-cell sequencing, valuable insights can be gained into early diagnosis, therapy, and prognosis of CRC. Thus, this review serves as a valuable resource for identifying prognostic markers, discovering new therapeutic targets, and advancing personalized therapy in CRC. [ABSTRACT FROM AUTHOR]

In recent years, the tumour microenvironment (TME) of solid tumours has attracted more and more attention from researchers, especially those non-tumour components such as immune cells. Infiltration of various immune cells causes tumour immune microenvironment (TIME) heterogeneity, and results in different therapeutic effects. Accumulating evidence showed that DNA methylation plays a crucial role in remodelling TIME and is associated with the response towards immune checkpoint inhibitors (ICIs). During carcinogenesis, DNA methylation profoundly changes, specifically, there is a global loss of DNA methylation and increased DNA methylation at the promoters of suppressor genes. Immune cell differentiation is disturbed, and exclusion of immune cells from the TME occurs at least in part due to DNA methylation reprogramming. Therefore, pharmaceutical interventions targeting DNA methylation are promising. DNA methyltransferase inhibitors (DNMTis) enhance antitumor immunity by inducing transcription of transposable elements and consequent viral mimicry. DNMTis upregulate the expression of tumour antigens, mediate immune cells recruitment and reactivate exhausted immune cells. In preclinical studies, DNMTis have shown synergistic effect when combined with immunotherapies, suggesting new strategies to treat refractory solid tumours. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Postoperative acute kidney injury in patients undergoing abdominal surgery is not rare and often results in bad outcomes for patients. The incidence of postoperative acute kidney injury is hard to evaluate reliably due to its non-unified definitions in different studies. Risk factors for acute kidney injury specific to abdominal surgery include preoperative renal insufficiency, intraabdominal hypertension, blood transfusion, bowel preparation, perioperative dehydration, contrast agent and nephrotoxic drug use. Among these, preoperative renal insufficiency is the strongest predictor of acute kidney injury. The peri-operative management of high-risk patients should include meticulous selection of fluid solutions. Balanced crystalloid solutions and albumin are generally thought to be relatively safe, while the safety of hydroxyethyl starch solutions has been controversial. The purpose of the present review is to discuss the current knowledge regarding postoperative acute kidney injury in abdominal surgical settings to help surgeons make better decisions concerning the peri-operative management. [ABSTRACT FROM AUTHOR]

Tumors arising from Meckel's diverticulum (MD) reported in the literature are mainly carcinoid and gastrointestinal stromal tumors. We herein report a rare case of adenocarcinoma arising from intestinal mucosa in an MD with multiple liver metastases at the onset of symptoms. A 57-year-old female complaining of bloody stool for 2 weeks was admitted to our hospital. Colonoscopy revealed massive bloody fluids but did not find any neoplasm. Computed tomography (CT) found a heterogeneous mass at the distal ileum and multiple liver metastases. A segmental ileal resection with local mesentery excision was performed to control the bleeding. During surgery, a tumor arising from a diverticulum in the antimesenteric border of ileum was observed. Histologic examination revealed moderate to poorly differentiated adenocarcinoma. Majority of the MD remain asymptomatic and are diagnosed incidentally during small bowel contrast study, laparoscopy or laparotomy done for unrelated conditions, or until complications arise from the diverticulum. Malignancies are reported to account for only 0.5%-3.2% of the complications. The occurrence of adenocarcinoma in an MD is exceedingly rare. In the few cases described so far, the prognosis of adenocarcinoma within an MD has been poor due to the advanced stage as seen at the time of surgery. Despite the availability of many publications, there is a little consensus concerning the management of an incidental finding of MD. Adenocarcinoma in an MD is extremely sporadic and prognosis has been reported as very poor. However, early diagnosis is challenging. When found incidentally during laparotomy, MD should be carefully examined and best treated with prophylactic resection. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the ability of CT and endoscopic sonography (EUS) in predicting the malignant risk of 1–2-cm gastric gastrointestinal stromal tumors (gGISTs) and to clarify whether radiomics could be applied for risk stratification. Methods: A total of 151 pathologically confirmed 1–2-cm gGISTs from seven institutions were identified by contrast-enhanced CT scans between January 2010 and March 2021. A detailed description of EUS morphological features was available for 73 gGISTs. The association between EUS or CT high-risk features and pathological malignant potential was evaluated. gGISTs were randomly divided into three groups to build the radiomics model, including 74 in the training cohort, 37 in validation cohort, and 40 in testing cohort. The ROIs covering the whole tumor volume were delineated on the CT images of the portal venous phase. The Pearson test and least absolute shrinkage and selection operator (LASSO) algorithm were used for feature selection, and the ROC curves were used to evaluate the model performance. Results: The presence of EUS- and CT-based morphological high-risk features, including calcification, necrosis, intratumoral heterogeneity, irregular border, or surface ulceration, did not differ between very-low and intermediate risk 1–2-cm gGISTs (p > 0.05). The radiomics model consisting of five radiomics features showed favorable performance in discrimination of malignant 1–2-cm gGISTs, with the AUC of the training, validation, and testing cohort as 0.866, 0.812, and 0.766, respectively. Conclusions: Instead of CT- and EUS-based morphological high-risk features, the CT radiomics model could potentially be applied for preoperative risk stratification of 1–2-cm gGISTs. Key Points: • The presence of EUS- and CT-based morphological high-risk factors, including calcification, necrosis, intratumoral heterogeneity, irregular border, or surface ulceration, did not correlate with the pathological malignant potential of 1–2-cm gGISTs. • The CT radiomics model could potentially be applied for preoperative risk stratification of 1–2-cm gGISTs. [ABSTRACT FROM AUTHOR]

The biological role of the spen paralogue and orthologue C-terminal domain containing 1 (SPOCD1) has been investigated in human malignancies, but its function in colorectal cancer (CRC) is unclear. This study investigated the association between SPOCD1 expression and clinicopathological features of CRC cases, as well as its prognostic value and biological function based on large-scale databases and clinical samples. The results showed that the expression level of SPOCD1 was elevated in CRC, which was generally associated with shortened survival time and poor clinical indexes, including advanced T, N, and pathologic stages. Multivariate Cox regression analysis showed that elevated SPOCD1 expression was an independent factor for poor prognosis in CRC patients. Functional enrichment analysis of SPOCD1 and its co-expressed genes revealed that SPOCD1 could act as an oncogene by regulating gene expression in essential functions and pathways of tumorigenesis, such as extracellular matrix organization, chemokine signaling pathways, and calcium signaling pathways. In addition, immune cell infiltration results showed that SPOCD1 expression was associated with various immune cells, especially macrophages. Furthermore, our findings suggested a possible function for SPOCD1 in the polarization of macrophages from M1 to M2 in CRC. In conclusion, SPOCD1 is a promising diagnostic and prognostic marker for CRC, opening new avenues for research and treatment. [ABSTRACT FROM AUTHOR]

Background Extramural venous invasion (EMVI) is defined histologically as the active invasion of tumor cells to the lumens of mesenteric vessels beyond the muscularis propria in advanced gastrointestinal cancer, resulting in distant metastases. Purpose To determine the association between synchronous metastatic disease in patients with T4 gastric cancer and EMVI detected on contrast-enhanced multiple-row detector computed tomography (MDCT). Material and Methods A total of 152 patients with T4 gastric carcinoma were retrospectively reviewed and divided into EMVI-positive and EMVI-negative groups where EMVI, as detected on MDCT, was defined as a tubular or nodular soft tissue thickening extending from the tumor along the vessels of the mesentery. Synchronous metastases were detected by MDCT and/or confirmed by postoperative diagnosis. Logistic regression analyses were performed to analyze the predictive factors of synchronous metastases in gastric cancer. Results Synchronous metastases were found in 47 of 152 (30.9%) patients with T4 gastric cancer. Thirty-one of 77 (40.3%) patients in the EMVI-positive group had evidence of metastases compared to 16 (21.3%) of 75 patients in the EMVI-negative group ( P = 0.019). Synchronous metastases were significantly associated with EMVI with an odds ratio (OR) of 2.250 (95% CI, 1.072-4.724). Conclusion EMVI-positive tumors, as an adverse imaging feature, were significantly associated with synchronous metastases in patients with T4 gastric cancer. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate a new strategy for profiling proteomic changes in colorectal cancer (CRC). Methodes: We used laser capture microdissection (LCM) to obtain cells from 20 CRC and paired normal mucosal tissues. The differential proteins between the microdissected tumor cells and normal mucosa epithelia were analyzed by acetylation stable isotopic labeling coupled with L linear ion trap Fourier transform ion cyclotron resonance mass spectrometry (LTQ-FT MS). Western blotting was used to assess the differential expression of proteins. We used bioinformatics tools for cluster and ingenuity pathway analysis of the differential proteins. Results: In total, 798 confident proteins were quantified and 137 proteins were differentially expressed by at least twofold, including 67 that were upregulated and 70 that were downregulated in cancer. Two differential proteins, solute carrier family 12 member 2 (SLC12A2) and Ras-related protein Rab-10, were validated by Western blotting, and the results were consistent with acetylation stable isotopic labeling analysis. According to gene ontology analysis, CRC-related differential proteins covered a wide range of subcellular locations and were involved in many biological processes. According to ingenuity pathway analysis of the differential proteins, the most relevant canonical pathway associated with CRC was the 14-3-3-mediated signaling pathway, and seven reliable functional networks including cellular growth and proliferation, amino acid metabolism, inflammatory response, embryonic development, carbohydrate metabolism, cellular assembly and organization, and cell morphology were obtained. Conclusions: Combination of LCM, acetylation stable isotopic labeling analysis and LTQ-FT MS is effective for profiling proteomic changes in CRC cells. [ABSTRACT FROM AUTHOR]

Background: To investigate the association between computed tomography (CT)-detected extramural venous invasion (EMVI)-related genes and immunotherapy resistance and immune escape in patients with gastric cancer (GC). Methods: Thirteen patients with pathologically proven locally advanced GC who had undergone preoperative abdominal contrast-enhanced CT and radical resection surgery were included in this study. Transcriptome sequencing was multidetector performed on the cancerous tissue obtained during surgery, and EMVI-related genes (P value for association < 0.001) were selected. A single-sample gene set enrichment analysis algorithm was also used to divide all GC samples (n = 377) in The Cancer Genome Atlas (TCGA) database into high and low EMVI-immune related groups based on immune-related differential genes. Cluster analysis was used to classify EMVI-immune-related genotypes, and survival among patients was validated in TCGA and Gene Expression Omnibus (GEO) cohorts. The EMVI scores were calculated using principal component analysis (PCA), and GC samples were divided into high and low EMVI score groups. Microsatellite instability (MSI) status, tumor mutation burden (TMB), response rate to immune checkpoint inhibitors (ICIs), immune escape were compared between the high and low EMVI score groups. Hub gene of the model in pan-cancer analysis was also performed. Results: There were 17 EMVI-immune-related genes used for cluster analysis. PCA identified 8 genes (PCH17, SEMA6B, GJA4, CD34, ACVRL1, SOX17, CXCL12, DYSF) that were used to calculate EMVI scores. High EMVI score groups had lower MSI, TMB and response rate of ICIs, status but higher immune escape status. Among the 8 genes used for EMVI scores, CXCL12 and SOX17 were at the core of the protein–protein interaction (PPI) network and had a higher priority in pan-cancer analysis. Immunohistochemical analysis showed that the expression of CXCL12 and SOX17 was significantly higher in CT-detected EMVI-positive samples than in EMVI-negative samples (P < 0.0001). Conclusion: A CT-detected EMVI gene signature could be a potential negative biomarker for ICIs treatment, as the signature is negatively correlated with TMB, and MSI, resulting in poorer prognosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BACKGROUND: Previous studies on how complete mesocolic excision (CME) affects prognosis indicate fundamental limitations that prevent the procedure from being completely accepted in practice. This study evaluated 5-year survival in colon cancer patients who underwent CME in a strict quality-controlled trial. STUDY DESIGN: A prospective, nonrandomized, double-blind, controlled trial recruited patients who underwent open radical resection for colon cancer between November 2012 and November 2017. Third-party experts evaluated whether patients had undergone mesocolic dissection and/or central ligation by looking at photographs of both surgical field and specimen, and then divided patients into CME and non-CME (NCME) groups. The primary outcome was the 5-year local recurrence-free survival rate. Clinicopathological and follow-up data were recorded. RESULTS: There were 261 patients with a median follow-up time of 57 months assigned to the CME group, and 129 patients with a median follow-up time of 59 months were assigned to the NCME group. The 5-year local recurrence-free survival rate of patients with Union Internationale Contre le Cancer stage I to III cancer did not differ significantly between the groups. For stage I to III cancer and stage III cancer, the absolute risk reduction of 5-year cumulative death and disease progression after CME were 9.1% (95% CI 1% to 17%; p = 0.033) and 16.1% (95% CI 1% to 31%; p = 0.040), respectively. Meanwhile, CME also could reduce 14% 5-year cumulative incidence recurrence for Union Internationale Contre le Cancer stage III cancer compared with NCME (CME, 27.3% vs NCME, 41.3%; p = 0.042) after adjusting for the effect of non-cancer-related death. CONCLUSIONS: CME should be considered as a standard surgical procedure in affected patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: As the most widespread mRNAs modification, N6‐methyladenosine (m6A) is dynamically and reversibly modulated by methyltransferases and demethylases. ALKBH5 is a major demethylase, and plays vital roles in the progression of cancers. However, the role and mechanisms of ALKBH5 in colorectal cancer (CRC) is unclear. Results: Herein, we discovered that in CRC, downregulated ALKBH5 was closely related to poor prognosis of CRC patients. Functionally, our results demonstrated that knockdown of ALKBH5 enhanced the proliferation, migration and invasion of LOVO and RKO in vitro, while overexpression of ALKBH5 inhibited the functions of these cells. The results also demonstrated that knockdown of ALKBH5 promoted subcutaneous tumorigenesis of LOVO in vivo, while overexpression of ALKBH5 suppressed this ability. Mechanistically, results from joint analyses of MeRIP‐seq and RNA‐seq indicated that PHF20 mRNA was a key molecule that was regulated by ALKBH5‐mediated m6A modification. Further experiments indicated that ALKBH5 may inhibit stability of PHF20 mRNA by removing the m6A modification of PHF20 mRNA 3′UTR. Conclusions: ALKBH5 suppresses CRC progression by decreasing PHF20 mRNA methylation. ALKBH5‐mediated m6A modification of PHF20 mRNA can serve as a hopeful strategy for the intervention and treatment of CRC. [ABSTRACT FROM AUTHOR]

Purpose: To determine the 1-year progression-free survival (PFS) of extramural venous invasion (EMVI), detected with contrast-enhanced multiple-row detector computed tomography (ceMDCT), in patients with stage III gastric cancer. Methods: Between January 2009 and December 2013, 117 patients with pathological-proved stage III gastric cancer based on the criteria of the AJCC 7th were included in this retrospective study. All patients underwent adjuvant chemotherapy postoperatively and had been monitored with the follow-up chest/abdomen/pelvis ceMDCT on 3, 6, and 12 months post-operation. Two radiologists reviewed preoperative images regarding the presence of EMVI, categories of tumor and categories of lymph node. Conventional prognostic histological factors including pathological T/N status, tumor location/growth pattern, histological type/tumor differentiation, and tumor size were also recorded. Disease progression was defined as the presence of radiological or/and pathology-confirmed metachronous metastases, local recurrence, or gastric cancer-related death. The 1-year PFS for both EMVI-positive and EMVI-negative was calculated using the Kaplan-Meier product limit. Hazard ratios for 1-year PFS were generated using a Cox proportional hazard regression on ceMDCT tumor characteristics. Results: The prevalence of EMVI detected with ceMDCT was 43.6% (51/117) in patients with stage III gastric cancer. The EMVI-positive patients had significantly lower 1-year PFS rates (45.1%), than the EMVI-negative patients (75.8%), (Log-rank test, P = 0.0008). In a Cox proportional hazards regression analysis, EMVI and tumor location/growth pattern were identified as independent prognostic factors of 1-year PFS with hazard ratio of 2.272 (95% CI 1.133-4.556, P = 0.021) and 1.982 (95% CI 1.040-3.780, P = 0.039), respectively. Conclusion: EMVI status, detected with ceMDCT, could be used to counsel patients regarding ongoing risks of metastatic disease, implications for surveillance, and systemic chemotherapy. [ABSTRACT FROM AUTHOR]

Standard treatment of colorectal cancer (CRC) improves the prognosis of CRC patients, but it is still intractable to control the progression of metastatic CRC. Immune microenvironment and immunotherapies of CRC have received extensive attention in recent years, but present immunotherapies of CRC have mainly focused on T cells and therapeutic response is only observed in a small proportion of patients. Innate immune cells are the first-line of defense in the development of malignancies. Natural killer (NK) cells, NKT cells and γδT cells are three types of innate cells of lymphoid origin and show cytotoxicity against various tumor cells including CRC. Besides, in the development of CRC, they can also be inhibited or express regulatory type, promoting tumor progression. Researches about anti-tumorigenic and pro-tumorigenic mechanisms of these cells are ongoing and regulation of these cells is also being unearthed. Meanwhile, immunotherapies using these cells more or less have shown efficacy in animal models and some of them are under exploration in clinical trials. This review provides an overview of intrinsic properties of NK cell, NKT cell and γδT cell, and summarizes current related promising treatment strategies. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the prognostic value and staging accuracy of the metastatic lymph node ratio (rN) staging system for colorectal cancer. Methods: A total of 1,127 patients with colorectal cancer who underwent curative surgery between 2000 and 2011 at our institute were analyzed. Lymph nodes status was assigned according to American Joint Committee on Cancer (AJCC) pN system and rN system. Patients with colon cancer (group 1, n = 652) and rectal cancer (group 2, n = 475) were analyzed separately. Results: The rN staging system was generated using 0.2 and 0.6 as the cutoff values of lymph node ratio and then compared with AJCC pN stages. Linear regression model revealed that the number of retrieved lymph node was related to number of metastatic lymph nodes. After a median follow-up of 46 months, the 5-year survival rates of patients with more than 12 lymph nodes (LNs) retrieved were better than cases with fewer than 12 LNs, while the differences were not obvious in rN classification. Conclusions : The rN category is a better prognostic tool than the AJCC pN category for colorectal cancer patients after curative surgery. [ABSTRACT FROM AUTHOR]

Fournier's gangrene (FG) is an extremely rare necrotizing fasciitis that is insidious, rapidly spreading and life-threatening. FGs due to rectal cancer occur rarely and there is a lack of clinical reference. In the present study, a severe FG due to rectal cancer perforation was described and the features of this rare disease were summarized with a literature review. A 57-year-old man was admitted because of rectal cancer-induced FG. The patient was misdiagnosed with extensive perianal abscess until the intraoperative biopsy confirmed that rectal cancer was the culprit. Incision, debridement and drainage were carried out to reduce infectious burdens. After that, the patient was transferred to Peking University People's Hospital for the subsequent therapy. Empirical broad-spectrum antibiotic therapy was used at the initial stage. Diversional transverse loop colostomy was performed to control infection and resume oral feeding. After four rounds of vacuum-assisted closure (VAC) therapy, radical resection and wound closure were accomplished. The scrotal defect was repaired by a skin flap. Pathological results indicated a moderately differentiated adenocarcinoma with perforation. The patient was discharged from the hospital on postoperative day 15 without any post-operative complications. No signs of recurrence were observed during a 22-month follow-up. In the setting of rectal cancer-induced FGs, the liquid resuscitation, broad-spectrum antibiotic therapy, and prompt debridement are the cornerstones of the initial management. Diversional colostomy and VAC therapy were effective in the management of severe infection and large wounds. The present case report also provided a clinical reference for the implementation of staged surgeries and the perioperative multidisciplinary management of FGs. [ABSTRACT FROM AUTHOR]

• Mg, Zn, and Fe degradation effects on human colon carcinoma cells were studied. • The original extracts of Mg, Zn, and Fe can cause carcinoma cell death. • After dilution, the extracts of Mg and Fe show inhibitory effects on carcinoma cells while Zn does not. Biodegradable metals (Mg, Zn, and Fe) have potential applications in replacing titanium (Ti) for making surgical staples in colonic anastomosis. In this study, the effect of metals' degradation on colon carcinoma cells (HCT116) was carefully investigated by the extract method based on the results of the immersion test. It was found that all cells died in the original extracts. After dilution, 10 % extracts of Mg and Fe significantly inhibited the proliferation, invasion, and migration of cells, and the Fe extract also promoted the cell apoptotic rate. In contrast, cells showed no sensitivity to zinc ions at the same dilution ratio. These results indicate Mg and Fe might have great potential applications for suppressing colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) have emerged as vital regulators of the initiation and progression of diverse kinds of human cancers. In this study, we explored the role of hsa_circ_0000231 and its downstream pathway in CRC. Methods: The expression profile of circRNAs in 5 pairs of CRC tissues and adjacent normal tissues were analyzed by Microarray. Quantitative real-time PCR and in situ hybridization and Base Scope Assay were used to determine the level and prognostic values of hsa_circ_0000231. Then, functional experiments in vitro and in vivo were performed to investigate the effects of hsa_circ_0000231 on cell proliferation. Mechanistically, fluorescent in situ hybridization, dual luciferase reporter assay, RNA pull-down and RNA immunoprecipitation experiments were performed to confirm the interaction between hsa_circ_0000231 and IGF2BP3 or has_miR-375. Results: We acquired data through circRNA microarray profiles, showing that the expression of hsa_circ_0000231 was upregulated in CRC primary tissues compared to adjacent normal tissues, which was indicated poor prognosis of patients with CRC. Functional analysis indicated that inhibition of hsa_circ_0000231 in CRC cell lines could suppress CRC cell proliferation as well as tumorigenesis in vitro and in vivo. The mechanistic analysis showed that hsa_circ_0000231 might, on the one hand, act as a competing endogenous RNA of miR-375 to promote cyclin D2 (CCND2) and, on the other hand, bind to the IGF2BP3 protein to prevent CCND2 degradation. Conclusions: The findings suggested that hsa_circ_0000231 facilitated CRC progression by sponging miR-375 or binding to IGF2BP3 to modulate CCND2, implying that hsa_circ_0000231 might be a potential new diagnostic and therapeutic biomarker of CRC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Computed tomography (CT)‐detected extramural venous invasion (EMVI) has been identified as an independent factor that can be used for risk stratification and prediction of prognosis in patients with gastric cancer (GC). Overall survival (OS) is identified as the most important prognostic indicator for GC patients. However, the molecular mechanism of EMVI development and its potential relationship with OS in GC are not fully understood. In this radiogenomics‐based study, we sought to investigate the molecular mechanism underlying CT‐detected EMVI in patients with GC, and aimed to construct a genomic signature based on EMVI‐related genes with the goal of using this signature to predict the OS. Materials and Methods: Whole mRNA genome sequencing of frozen tumor samples from 13 locally advanced GC patients was performed to identify EMVI‐related genes. EMVI‐prognostic hub genes were selected based on overlapping EMVI‐related differentially expressed genes and OS‐related genes, using a training cohort of 176 GC patients who were included in The Cancer Genome Atlas database. Another 174 GC patients from this database comprised the external validation cohort. A risk stratification model using a seven‐gene signature was constructed through the use of a least absolute shrinkage and selection operator Cox regression model. Results: Patients with high risk score showed significantly reduced OS (training cohort, p = 1.143e‐04; validation cohort, p = 2.429e‐02). Risk score was an independent predictor of OS in multivariate Cox regression analyses (training cohort, HR = 2.758; 95% CI: 1.825–4.169; validation cohort, HR = 2.173; 95% CI: 1.347–3.505; p < 0.001 for both). Gene functions/pathways of the seven‐gene signature mainly included cell proliferation, cell adhesion, regulation of metal ion transport, and epithelial to mesenchymal transition. Conclusions: A CT‐detected EMVI‐related gene model could be used to predict the prognosis in GC patients, potentially providing clinicians with additional information regarding appropriate therapeutic strategy and medical decision‐making. [ABSTRACT FROM AUTHOR]

Objective. N-myc downstream regulated gene-1 (NDRG1) is known as a differentiation-related gene that plays important roles in cell differentiation, organ formation, and embryonic development. NDRG1 was recently found to significantly down regulate in a variety of different neoplasms. Its significance in gastric cancer has not been studied. Materials and methods. NDRG1 was detected at its protein level by immunohistochemistry in formalin-fixed and paraffin-embedded sections with a total of 110 pair gastric cancer specimens including tumor and corresponding paraneoplastic tissues; NDRG1 mRNA was detected by real time-polymerase chain reaction. Meanwhile, the correlations between NDRG1 and clinicopathological factors were observed. Overexpression of NDRG1 has influence on the biological behavior of gastric cancer cell, which was detected by cell growth assay, apoptosis assay, and in vitro motility and invasion assay. Results. NDRG1 protein was down regulated in gastric cancer tissues, and the NDRG1 low expression rate was 73.6% (79/110). Moreover, NDRG1 expression has a significant inverse correlation with tumor stromal invasion, lymph node metastasis, pathological stage, but not with distant metastasis. The patients with low NDRG1 expression had a significantly shorter survival opportunity than those with high NDRG1 expression. In addition, overexpression of NDRG1 induced early apoptosis and inhibited SGC7901 cell proliferation and its motility and invasion capability. Conclusions. NDRG1 plays a significant role in carcinogenesis and preventing the metastasis and invasion of gastric cancer cells. NDRG1 could be developed as a marker contributing to diagnosis and evaluating prognosis in gastric cancer, as well as a potential therapeutic target of gastric cancer. [ABSTRACT FROM AUTHOR]

Purpose: To develop and evaluate a preoperative risk stratification model for predicting disease-free survival (DFS) based on contrast-enhanced multidetector computed tomography (ceMDCT) images in patients with gastric cancer (GC) undergoing radical surgery. Methods: We retrospectively enrolled patients with GC who underwent ceMDCT followed by radical surgery. A preoperative risk stratification model was constructed (including risk factor selection, risk status scoring, and risk level assignment) using Cox proportional hazard regression and log-rank analyses in the training cohort; the model was tested in the validation cohort. A nomogram was used to compare the preoperative risk stratification model with a postoperative DFS prediction model. Results: A total of 462 patients (training/validation: 271/191) were included. The ceMDCT features of T category (score of 0 or 2), N category (0, 1, 2, or 3), extramural vessel invasion (0 or 2), and tumor location (0 or 1) were selected to construct the preoperative risk stratification model, with 4 risk levels defined based on risk score. There were significant differences in DFS among the risk levels in both cohorts (p < 0.001). The predictive value of the preoperative model was similar to that of the postoperative model, with concordance indices of 0.791 (95% CI, 0.743–0.837) and 0.739 (95% CI, 0.666–0.812), respectively, in the training cohort and 0.762 (95% CI, 0.696–0.828) and 0.738 (95% CI, 0.684–0.792), respectively, in the validation cohort. Conclusion: A preoperative risk stratification model based on ceMDCT images could be used to predict DFS and thus classify GC cases into various risk levels. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The application of side-to-end anastomosis (SEA) in sphincter-preserving resection (SPR) is controversial. We performed a meta-analysis to compare the safety and efficacy of SEA with colonic J-pouch (CJP) anastomosis, which had been proven effective in improving postoperative bowel function. Methods: The protocol was registered in PROSPERO under number CRD42020206764. PubMed, Embase, Web of Science, and the Cochrane Register of Controlled Trials databases were searched. The inclusion criteria were randomized controlled trials (RCTs) that evaluated the safety or efficacy of SEA in comparison with CJP anastomosis. The outcomes included the pooled risk ratio (RR) for dichotomous variables and weighted mean differences (WMDs) for continuous variables. All outcomes were calculated with 95% confidence intervals (CI) by STATA software (Stata 14, Stata Corporation, TX, USA). Results: A total of 864 patients from 10 RCTs were included in the meta-analysis. Patients undergoing SEA had a higher defecation frequency at 12 months after SPR (WMD = 0.20; 95% CI, 0.14–0.26; P < 0.01) than those undergoing CJP anastomosis with low heterogeneity (I2 = 0%, P = 0.54) and a lower incidence of incomplete defecation at 3 months after surgery (RR = 0.28; 95% CI, 0.09–0.86; P = 0.03). A shorter operating time (WMD = − 17.65; 95% CI, − 23.28 to − 12.02; P < 0.01) was also observed in the SEA group without significant heterogeneity (I2 = 0%, P = 0.54). A higher anorectal resting pressure (WMD = 6.25; 95% CI, 0.17–12.32; P = 0.04) was found in the SEA group but the heterogeneity was high (I2 = 84.5%, P = 0.84). No significant differences were observed between the groups in terms of efficacy outcomes including defecation frequency, the incidence of urgency, incomplete defecation, the use of pads, enema, medications, anorectal squeeze pressure and maximum rectal volume, or safety outcomes including operating time, blood loss, the use of protective stoma, postoperative complications, clinical outcomes, and oncological outcomes. Conclusions: The present evidence suggests that SEA is an effective anastomotic strategy to achieve similar postoperative bowel function without increasing the risk of complications compared with CJP anastomosis. The advantages of SEA include a shorter operating time, a lower incidence of incomplete defecation at 3 months after surgery, and better sphincter function. However, close attention should be paid to the long-term defecation frequency after SPR. [ABSTRACT FROM AUTHOR]

Background: Aging is the major risk factor for most human cancers. We aim to develop and validate a reliable aging-related gene pair signature (ARGPs) to predict the prognosis of gastric cancer (GC) patients.Methods: The mRNA expression data and clinical information were obtained from two public databases, The Cancer Genome Atlas (TCGA) dataset, and Gene Expression Omnibus (GEO) dataset, respectively. The best prognostic signature was established using Cox regression analysis (univariate and least absolute shrinkage and selection operator). The optimal cut-off value to distinguish between high- and low-risk patients was found by time-dependent receiver operating characteristic (ROC). The prognostic ability of the ARGPS was evaluated by a log-rank test and a Cox proportional hazards regression model.Results: The 24 ARGPs were constructed for GC prognosis. Using the optimal cut-off value - 0.270, all patients were stratified into high risk and low risk. In both TCGA and GEO cohorts, the results of Kaplan-Meier analysis showed that the high-risk group has a poor prognosis (P < 0.001, P = 0.002, respectively). Then, we conducted a subgroup analysis of age, gender, grade and stage, and reached the same conclusion. After adjusting for a variety of clinical and pathological factors, the results of multivariate COX regression analysis showed that the ARGPs is still an independent prognostic factor of OS (HR, 4.919; 95% CI 3.345-7.235; P < 0.001). In comparing with previous signature, the novel signature was superior, with an area under the receiver operating characteristic curve (AUC) value of 0.845 vs. 0.684 vs. 0.695. The results of immune infiltration analysis showed that the abundance of T cells follicular helper was significantly higher in the low-risk group, while the abundance of monocytes was the opposite. Finally, we identified and incorporated independent prognostic factors and developed a superior nomogram to predict the prognosis of GC patients.Conclusion: Our study has developed a robust prognostic signature that can accurately predict the prognostic outcome of GC patients. [ABSTRACT FROM AUTHOR]

Background: Whether extended lymphadenectomy for right colon cancer leads to increased perioperative complications or improves survival is still controversial. This trial aimed to compare the efficacy and safety of complete mesocolic excision (CME) versus D2 dissection in laparoscopic right hemicolectomy for patients with right colon cancer. This article reports the early safety results from the trial.Methods: This randomised, controlled, phase 3, superiority, trial was done at 17 hospitals in nine provinces of China. Eligible patients were aged 18-75 years with histologically confirmed primary adenocarcinoma located between the caecum and the right third of the transverse colon, without evidence of distant metastases. Central randomisation was done by means of the Clinical Information Management-Central Randomisation System via block randomisation (block size of four). Patients were randomly assigned (1:1) to CME or D2 dissection during laparoscopic right colectomy. Central lymph nodes were dissected in the CME but not in the D2 procedure. Neither investigators nor patients were masked to their group assignment but the quality control committee were masked to group assignment. The primary endpoint was 3-year disease-free survival, but the data for this endpoint are not yet mature; thus, only the secondary outcomes-intraoperative surgical complications and postoperative complications within 30 days of surgery, graded according to the Clavien-Dindo classification, mortality (death from any cause within 30 days of surgery), and central lymph node metastasis rate in the CME group only-are reported in this Article. This early analysis of safety was preplanned. The outcomes were analysed according to a modified intention-to-treat principle (excluding patients who no longer met inclusion criteria after surgery or who did not have surgery). This study is registered with ClinicalTrials.gov, NCT02619942. Study recruitment is complete, and follow-up is ongoing.Findings: Between Jan 11, 2016, and Dec 26, 2019, 1072 patients were enrolled and randomly assigned. After exclusion of 77 patients, 995 patients were included in the modified intention-to-treat population (495 in the CME group and 500 in the D2 dissection group). The postoperative surgical complication rate was 20% (97 of 495 patients) in the CME group versus 22% (109 of 500 patients) in the D2 group (difference, -2·2% [95% CI -7·2 to 2·8]; p=0·39); the frequency of Clavien-Dindo grade I-II complications were similar between groups (91 [18%] vs 92 [18%], difference, -0·0% [95% CI -4·8 to 4·8]; p=1·0) but Clavien-Dindo grade III-IV complications were significantly less frequent in the CME group than in the D2 group (six [1%] vs 17 [3%], -2·2% [-4·1 to -0·3]; p=0·022); no deaths occurred in either group. Of the intraoperative complications, vascular injury was significantly more common in the CME group than in the D2 group (15 [3%] vs six [1%], difference, 1·8 [95% CI 0·04 to 3·6]; p=0·045). Metastases in the central lymph nodes were detected in 13 (3%) of 394 patients who underwent central lymph node biopsy in the CME group; no patient had isolated metastases to central lymph nodes.Interpretation: Although the CME procedure might increase the risk of intraoperative vascular injury, it generally seems to be safe and feasible for experienced surgeons.Funding: The Capital Characteristic Clinical Project of Beijing and the Chinese Academy of Medical Sciences. [ABSTRACT FROM AUTHOR]

A bridging study of INTRIGUE study to assess the efficacy and safety of ripretinib versus sunitinib as second-line treatment in Chinese GIST patients. This was a phase 2, multicenter, randomized, open-label study in China. GIST patients previously treated with imatinib were randomized (1:1) to receive ripretinib 150 mg once daily (QD) by continuous dosing in 42-day cycles or sunitinib 50 mg QD in 42-day cycles (four weeks on/two weeks off). Primary endpoint was progression-free survival (PFS) by independent radiological review (IRR). Between 6 December 2020 and 15 September 2021, 108 patients were randomized to receive ripretinib (n = 54) or sunitinib (n = 54) (all-patient [AP] intention-to-treat [ITT] population). Seventy patients had primary KIT exon 11 mutations (ripretinib, n = 35; sunitinib, n = 35; Ex11 ITT population). By data cut-off (20 July 2022), in AP ITT population, PFS by IRR was comparable between ripretinib and sunitinib arms (HR 0·99, 95 % CI 0·57, 1·69; nominal p = 0·92; median PFS [mPFS] 10·3 vs 8·3 months). In Ex11 ITT population, PFS by IRR was longer for ripretinib than sunitinib (HR 0·46, 95 % CI 0·23, 0·92; nominal p = 0·03; mPFS not reached in ripretinib arm and 4·9 months in sunitinib arm). Fewer patients experienced grade 3/4 treatment-related treatment-emergent adverse events with ripretinib (17%) versus sunitinib (56%). Ripretinib demonstrated similar efficacy and a favorable safety profile versus sunitinib as second-line treatment in Chinese GIST patients. Furthermore, ripretinib provided greater clinically meaningful benefit versus sunitinib in patients with KIT exon 11 mutation. • 2nd-line treatment of GIST in China: ripretinib has similar efficacy as sunitinib. • Ripretinib demonstrated a more favorable safety profile versus sunitinib. • KIT exon 11 mutation patient: greater clinically meaningful benefit with ripretinib. [ABSTRACT FROM AUTHOR]

Purpose: Preoperative and noninvasive prognosis evaluation remains challenging for gastric cancer. Novel preoperative prognostic biomarkers should be investigated. This study aimed to develop multidetector‐row computed tomography (MDCT)‐guided prognostic models to direct follow‐up strategy and improve prognosis. Methods: A retrospective dataset of 353 gastric cancer patients were enrolled from two centers and allocated to three cohorts: training cohort (n = 166), internal validation cohort (n = 83), and external validation cohort (n = 104). Quantitative radiomic features were extracted from MDCT images. The least absolute shrinkage and selection operator penalized Cox regression was adopted to construct a radiomic signature. A radiomic nomogram was established by integrating the radiomic signature and significant clinical risk factors. We also built a preoperative tumor‐node‐metastasis staging model for comparison. All models were evaluated considering the abilities of risk stratification, discrimination, calibration, and clinical use. Results: In the two validation cohorts, the established four‐feature radiomic signature showed robust risk stratification power (P = 0.0260 and 0.0003, log‐rank test). The radiomic nomogram incorporated radiomic signature, extramural vessel invasion, clinical T stage, and clinical N stage, outperforming all the other models (concordance index = 0.720 and 0.727) with good calibration and decision benefits. Also, the 2‐yr disease‐free survival (DFS) prediction was most effective (time‐dependent area under curve = 0.771 and 0.765). Moreover, subgroup analysis indicated that the radiomic signature was more sensitive in risk stratifying patients with advanced clinical T/N stage. Conclusions: The proposed MDCT‐guided radiomic signature was verified as a prognostic factor for gastric cancer. The radiomic nomogram was a noninvasive auxiliary model for preoperative individualized DFS prediction, holding potential in promoting treatment strategy and clinical prognosis. [ABSTRACT FROM AUTHOR]

Background: Recent studies showed that aberrant expression of miRNAs causes tumor-suppressing or promoting effects in various cancers including gastric cancer (GC). Our previous studies showed that lots of miRNAs and mRNA expressed differentially in GC and normal tissues. However, the critical miRNAs and mRNA need to be clarified. Materials and Methods: Microarray sequencing was used to profile the differential expression of miRNAs and mRNA in GC and normal tissues. Bioinformatics analysis and database prediction were used to search the critical miRNAs and mRNA. Real-time quantitative polymerase chain reaction (RT-qPCR), luciferase reporter assay, immunohistochemistry (IHC), wound healing assay and transwell assay were used to clarify the relationship between the target miRNAs and mRNA. Statistical analysis was used to seek their value of diagnosis and prognosis. Results: We identified microRNA-6165 (miR-6165) as a novel cancer-related miRNA in GC through high-throughput microarray sequencing. By bioinformatics analysis and luciferase reporter assay, we found STRN4 was the target of miR-6165. Via a series of cell experiments, we determined that miR-6165 suppressed GC cells migration and invasion by targeting STRN4. Also, we discovered the potential diagnosis and prognosis value of miR-6165 and STRN4. Conclusion: It was found that miR-6165 might suppress GC migration and invasion by targeting STRN4 in vitro, and the further research should focus more on the potential diagnosis and prognosis value of miR-6165 and STRN4 in gastric cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: Our animal studies have demonstrated the safety and feasibility of end-to-end intestinal anastomosis using a stent for laparoscopic colonic surgery. Therefore, we designed a non-inferiority trial to investigate the outcomes of stent anastomosis (SA) vs. those of conventional hand-sewn anastomosis (CA). Methods: A multicenter randomized controlled trial was conducted between December, 2016 and April, 2018. The primary outcome was the healing condition of the anastomoses, evaluated by endoscopy 6 months postoperatively. The secondary outcomes were the anastomotic completion time, anastomotic leak, intestinal obstruction, peritoneal effusion, and bleeding. Quality of life (QOL) was evaluated by questionnaires. Results: The subjects of this study were 60 patients, randomly divided into a SA group (n = 30) and a CA group (n = 30). There were no differences in anastomotic healing conditions (P = 1.00). The stent procedure was associated with a significantly shorter anastomosis time than the hand-sewn anastomosis (13.517 ± 4.281 vs. 20.333 ± 2.998 min, respectively; P < 0.001). There were no significant differences in anastomotic leakage, intestinal obstruction, peritoneal effusion, or bleeding between the groups. Questionnaires revealed almost no discrepancy between baseline QOL scores and those assessed 2, 4, 8, 12, and 24 weeks postoperatively in either group. Conclusions: Intestinal anastomosis with a stent is a non-inferior strategy for laparoscopic colonic surgery, which requires less time for the anastomosis. [ABSTRACT FROM AUTHOR]

Key Clinical Message: The genome‐wide sequencing information of PJS is still lacking. Our result demonstrates that c.862+2T>C variant on STK11 as an important foundation of molecular mechanism in this familial PJS. Variants in KDR and MLL3 may play important roles in the initiation and development of this familial PJS polyps. The genome‐wide sequencing information of PJS is still lacking. Our result demonstrates that c.862+2T>C variant on STK11 as an important foundation of molecular mechanism in this familial PJS. Variants in KDR and MLL3 may play important roles in the initiation and development of this familial PJS polyps. [ABSTRACT FROM AUTHOR]

Background: Clinical-simulated training has shown benefit in the education of medical students. However, the role of clinical simulation for surgical basic skill training such as suturing techniques remains unclear. Materials and Methods: Forty-two medical students were asked to perform specific suturing tasks at three stations with the different settings within four minutes (Station 1: Synthetic suture pad fixed on the bench, Station 2: Synthetic suture pad fixed on the standardized patient, Station 3: Pig skin fixed on the standardized patient); the OSATS (Objective Structured Assessment of Technical Skill) tool was used to evaluate the performance of students. A questionnaire was distributed to the students following the examination. Results: Mean performance score of Station 3 was significant lower than that of Station 1 and 2 in the general performance including tissue handling, time, and motion. The suturing techniques of students at Station 2 and 3 were not as accurate as that at Station 1. Inappropriate tension was applied to the knot at Station 2 compared with Station 1 and 3. On the questionnaire, 93% of students considered clinical-simulated training of basic surgical skills was necessary and may increase their confidence in future clinical work as surgeons; 98% of students thought the assessment was more objective when OSATS tool was used for evaluation. Conclusion: Clinical simulation examination assessed with OSATS might throw a novel light on the education of basic surgical skills and may be worthy of wider adoption in the surgical education of medical students. [ABSTRACT FROM AUTHOR]

To investigate the expression of chromosome 6 open reading frame 15 (C6orf15) in colon cancer and its effects on clinicopathological features and prognosis. Using the transcriptome and clinical data of colon cancer and normal tissues in The Cancer Genome Atlas (TCGA) database, the expression of C6orf15 mRNA in colon cancer samples and its relationship with clinicopathological characteristics and prognosis were explored. The expression level of C6orf15 protein in 23 colon cancer tissues was detected by immunohistochemistry (IHC). The possible mechanism of C6orf15 involved in the occurrence and development of colon cancer was explored by gene set enrichment analysis (GSEA). Compared with normal tissues, C6orf15 was highly expressed in colon cancer (1.207 ± 0.694 vs 0.276 ± 0.166, t = 8.281, P < 0.01). The expression level of C6orf15 was associated with tumor invasion depth (χ2 = 8.30, P = 0.04), lymph node metastasis (χ2 = 36.97, P < 0.001), distant metastasis (χ2 = 8.69, P = 0.003) and pathological stage (χ2 = 34.17, P < 0.001). High expression of C6orf15 was associated with poor prognosis (χ2 = 6.43, P < 0.05). The results of GSEA showed that C6orf15 promotes the occurrence and development of colon cancer by promoting the ECM receptor interaction pathway, Hedgehog signaling pathway and Wnt signaling pathway. Immunohistochemical results showed that the expression of C6orf15 protein in colon cancer tissues was correlated with the depth of invasion (P = 0.023) and lymph node metastasis (P = 0.048). C6orf15 is highly expressed in colon cancer tissue and is related to adverse pathological features and poor prognosis of colon cancer. It is involved in multiple oncogenic signaling pathways and may serve as a prognostic marker of colon cancer. [ABSTRACT FROM AUTHOR]

Increasing evidence has shown that abnormal expression of miR-4284 participates in the progression of several types of cancer. However, the expression and the role of miR‑4284 in gastric cancer remain largely unknown. Therefore, in the present study the miR‑4284 expression levels in gastric cancer tissues and cell lines, was examined using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and found that miR‑4284 was significantly upregulated in 40 pairs of gastric cancer tissues and five gastric cancer cell lines compared to the corresponding normal tissues and GES‑1 cell line. In addition, increased miR‑4284 expression was positively associated with TNM stage (P=0.035), distal metastasis (P=0.022) and poor prognosis in gastric cancer patients. Furthermore, the overexpression of miR‑4284 expression was shown to promote cell proliferation, clone formation, invasion and migration, while the suppression of miR‑4284 expression induced opposite effects. Additionally, luciferase reporter assay was conducted and showed that ten-eleven translocation 1 (TET1), a tumor suppressor gene that regulating cell survival and metastasis, was a direct target of miR‑4284. Upregulated miR‑4284 decreased the mRNA and protein levels of TET1 in SGC‑7901 cells and downregulated miR‑4284 increased the mRNA and protein levels of TET1 in AGS cells. In addition, miR‑4284 expression was negatively correlated with the TET1 expression in gastric cancer tissues. Moreover, inhibition of TET1 suppressed the effect of miR‑4284 inhibitors on cell proliferation in AGS cells. Therefore, data demonstrated that miR‑4284 could promote tumor cell growth, migration and invasion by directly targeting TET1 in gastric cancer, which may provide a potential therapeutic target for gastric cancer treatment. [ABSTRACT FROM AUTHOR]