Risk factors for anastomotic leak and postoperative morbidity after right hemicolectomy for colon cancer: results from a prospective, multi-centre, snapshot study in China.

BACKGROUND: Right hemicolectomy is the standard treatment for right-sided colon cancer. There is variation in the technical aspects of performing right hemicolectomy as well as in short-term outcomes. It is therefore necessary to explore best clinical practice following right hemicolectomy in expert centres. METHODS: This snapshot study of right hemicolectomy for colon cancer in China was a prospective, multicentre cohort study in which 52 tertiary hospitals participated. Eligible patients with stage I-III right-sided colon cancer who underwent elective right hemicolectomy were consecutively enrolled in all centres over 10 months. The primary endpoint was the incidence of postoperative 30-day anastomotic leak. RESULTS: Of the 1854 patients, 89.9 per cent underwent laparoscopic surgery and 52.3 per cent underwent D3 lymph node dissection. The overall 30-day morbidity and mortality were 11.7 and 0.2 per cent, respectively. The 30-day anastomotic leak rate was 1.4 per cent. In multivariate analysis, ASA grade > II (P < 0.001), intraoperative blood loss > 50 ml (P = 0.044) and D3 lymph node dissection (P = 0.008) were identified as independent risk factors for postoperative morbidity. Extracorporeal side-to-side anastomosis (P = 0.031), intraoperative blood loss > 50 ml (P = 0.004) and neoadjuvant chemotherapy (P = 0.004) were identified as independent risk factors for anastomotic leak. CONCLUSION: In high-volume expert centres in China, laparoscopic resection with D3 lymph node dissection was performed in most patients with right-sided colon cancer, and overall postoperative morbidity and mortality was low. Further studies are needed to explore the optimal technique for right hemicolectomy in order to improve outcomes further.

The survival prediction of advanced colorectal cancer received neoadjuvant therapy-a study of SEER database.

PURPOSE: The aim of study was to screen factors associated with the overall survival of colorectal cancer patients with lymph nodes metastasis who received neoadjuvant therapy and construct a nomogram model. METHODS: All enrolled subjects of the SEER database were randomly assigned to the training and testing group in a ratio of 3:2. The patients of Tangdu Hospital were seemed as validation group. Univariate cox regression analysis, lasso regression and random forest survival were used to screen variables related to the survival of advanced CRC patients received neoadjuvant therapy in the training group. Area under curves were adopted to evaluate the 1,3,5-year prediction value of the optimal model in three cohorts. Calibration curves were drawn to observe the prediction accuracy of the nomogram model. Decision curve analysis was used to assess the potential clinical value of the nomogram model. RESULTS: A total of 1833 subjects were enrolled in this study. After random allocation, 1055 cases of the SEER database served as the training group, 704 cases as the testing group and 74 patients from our center as the external validation group. Variables were screened by univariate cox regression used to construct a nomogram survival prediction model, including M, age, chemotherapy, CEA, perineural invasion, tumor size, LODDS, liver metastasis and radiation. The AUCs of the model for predicting 1-year OS in the training group, testing and validation group were 0.765 (0.703,0.827), 0.772 (0.697,0.847) and 0.742 (0.601,0.883), predicting 3-year OS were 0.761 (0.725,0.780), 0.742 (0.699,0.785), 0.733 (0.560,0.905) and 5-year OS were 0.742 (0.711,0.773), 0.746 (0.709,0.783), 0.838 (0.670,0.980), respectively. The calibration curves showed the difference between prediction probability of the model and the actual survival was not significant in three cohorts and the decision curve analysis revealed the practice clinical application value. And the prediction value of model was better for young CRC than older CRC patients. CONCLUSION: A nomogram model including LODDS for the prognosis of advanced CRC received neoadjuvant therapy was constructed and verified based on the SEER database and single center practice. The accuracy and potential clinical application value of the model performed well, and the model had better predictive value for EOCRC than LOCRC.

Clinical and biological heterogeneities in triple-negative breast cancer reveals a non-negligible role of HER2-low.

BACKGROUND: HER2-low could be found in some patients with triple-negative breast cancer (TNBC). However, its potential impacts on clinical features and tumor biological characteristics in TNBC remain unclear. METHODS: We enrolled 251 consecutive TNBC patients retrospectively, including 157 HER2-low (HER2low) and 94 HER2-negtive (HER2neg) patients to investigate the clinical and prognostic features. Then, we performed single-cell RNA sequencing (scRNA-seq) with another seven TNBC samples (HER2neg vs. HER2low, 4 vs. 3) prospectively to further explore the differences of tumor biological properties between the two TNBC phenotypes. The underlying molecular distinctions were also explored and then verified in the additional TNBC samples. RESULTS: Compared with HER2neg TNBC, HER2low TNBC patients exhibited malignant clinical features with larger tumor size (P = 0.04), more lymph nodes involvement (P = 0.02), higher histological grade of lesions (P < 0.001), higher Ki67 status (P < 0.01), and a worse prognosis (P < 0.001; HR [CI 95%] = 3.44 [2.10-5.62]). Cox proportional hazards analysis showed that neoadjuvant systemic therapy, lymph nodes involvement and Ki67 levels were prognostic factors in HER2low TNBC but not in HER2neg TNBC patients. ScRNA-seq revealed that HER2low TNBC which showed more metabolically active and aggressive hallmarks, while HER2neg TNBC exhibited signatures more involved in immune activities with higher expressions of immunoglobulin-related genes (IGHG1, IGHG4, IGKC, IGLC2); this was further confirmed by immunofluorescence in clinical TNBC samples. Furthermore, HER2low and HER2neg TNBC exhibited distinct tumor evolutionary characteristics. Moreover, HER2neg TNBC revealed a potentially more active immune microenvironment than HER2low TNBC, as evidenced by positively active regulation of macrophage polarization, abundant CD8+ effector T cells, enriched diversity of T-cell receptors and higher levels of immunotherapy-targeted markers, which contributed to achieve immunotherapeutic response. CONCLUSIONS: This study suggests that HER2low TNBC patients harbor more malignant clinical behavior and aggressive tumor biological properties than the HER2neg phenotype. The heterogeneity of HER2 may be a non-negligible factor in the clinical management of TNBC patients. Our data provide new insights into the development of a more refined classification and tailored therapeutic strategies for TNBC patients.

Mitochondrial DNA haplogroup M7: A predictor of poor prognosis for colorectal cancer patients in Chinese population.

Haplogroups and single-nucleotide polymorphisms (SNP) of mitochondrial DNA (mtDNA) were associated with the prognosis of many types of cancer patients. However, whether mtDNA haplogroups contribute to clinical outcomes of colorectal cancer (CRC) in Chinese population remains to be determined. In this study, mtDNA of tissue samples from 445 CRC patients from Northwestern China was sequenced to evaluate the association between haplogroup and prognosis. The mtDNA sequencing data of 1015 CRC patients from Southern China were collected for validation. We found patients with mtDNA haplogroup M7 had a significantly higher death risk when compared with patients with other haplogroups in both Northwestern (Hazard ratio [HR] = 3.093, 95% CI = 1.768-5.411, p < 0.001) and Southern (HR = 1.607, 95% CI = 1.050-2.459, p = 0.029) China. Then, a haplogroup M7-based mtSNP classifier was selected by using LASSO Cox regression analysis. A nomogram comprising the mtSNP classifier and clinicopathological variables was developed to predict the prognosis of CRC patients (area under the curve [AUC] 0.735, 95% CI = 0.679-0.791). Furthermore, patients with high- and low-risk scores calculated by the haplogroup M7-based mtSNP classifier exhibited significantly different overall survival (OS) and recurrence-free survival (RFS) (all p < 0.001). Finally, RNA-seq and immunohistochemical analyses indicated the poor prognosis of patients with haplogroup M7 may be related to mitochondrial dysfunction and immune abnormalities in CRC tissues. In conclusion, the haplogroup M7 and haplogroup M7-based mtSNP classifier seems to be a practical and reliable prognostic predictor for CRC patients, which provides a potential tool of clinical decision-making for patients with haplogroup M7 in Chinese population.

BEX1 supports the stemness of hepatoblastoma by facilitating Warburg effect in a PPARγ/PDK1 dependent manner.

BACKGROUND: Hepatoblastoma (HB) is a highly aggressive paediatric malignancy that exhibits a high presence of cancer stem cells (CSCs), which related to tumour recurrence and chemotherapy resistance. Brain expressed X-linked protein 1 (BEX1) plays a pivotal role in ciliogenesis, axon regeneration and differentiation of neural stem cells. However, the role of BEX1 in metabolic and stemness programs in HB remains unclear. METHODS: BEX1 expression in human and mouse HB was analyzed using gene expression profile data from NCBI GEO and immunohistochemical validation. Seahorse extracellular flux analyzer, ultra-high-performance liquid-chromatography mass spectrometry (LC-MS), flow cytometry, qRT-PCR, Western Blot, sphere formation assay, and diluted xenograft tumour formation assay were used to analyze metabolic and stemness features. RESULTS: Our results indicated that overexpression of BEX1 significantly enhanced the Warburg effect in HB cells. Furthermore, glycolysis inhibition largely attenuated the effects of BEX1 on HB cell growth and self-renewal, suggesting that BEX1 promotes stemness maintenance of HB cells by regulating the Warburg effect. Mechanistically, BEX1 enhances Warburg effect through the downregulation of peroxisome proliferator-activated receptor-gamma (PPARγ). Furthermore, pyruvate dehydrogenase kinase isozyme 1 (PDK1) is required for PPARγ-induced inhibition of Warburg effect in HB. In addition, BEX1 supports the stemness of HB by enhancing Warburg effect in a PPARγ/PDK1 dependent manner. CONCLUSIONS: HB patients with high BEX1 and PDK1 expression had a poor prognosis. BEX1 promotes the stemness maintenance of HB cells via modulating the Warburg effect, which depends on PPARγ/PDK1 axis. Pioglitazone could be used to target BEX1-mediated stemness properties in HB by upregulating PPARγ.

DNMT1-mediated methylation of BEX1 regulates stemness and tumorigenicity in liver cancer.

BACKGROUND & AIMS: Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) both exhibit notable cancer stem cell (CSC) features. Moreover, the development of both diseases is closely associated with the presence of CSCs. We investigated the role of brain-expressed X-linked protein 1 (BEX1) in regulating the CSC properties of HB and a subtype of HCC with high CSC features (CSC-HCC). METHODS: Stemness scores were analyzed in 5 murine HCC models. A subpopulation of BEX1-positive cells and BEX1-negative cells were sorted from HCC cell lines, and subjected to transcriptome analysis. The expression and function of BEX1 was examined via western blotting, sphere formation assays, and xenograft tumor models. RESULTS: We identified BEX1 as a novel CSC marker that was required for the self-renewal of liver CSCs. Furthermore, zebularine, a potent DNMT1 inhibitor, can induce the reactivation of BEX1 by removing epigenetic inhibition. Notably, BEX1 was highly expressed in patients with HB and CSC-HCC, but not in patients with non-CSC HCC. Moreover, DNMT1-mediated methylation of the BEX1 promoter resulted in differential BEX1 expression patterns in patients with HB, CSC-HCC, and non-CSC-HCC. Mechanistically, BEX1 interacted with RUNX3 to block its inhibition of ß-catenin transcription, which led to the activation of Wnt/ß-catenin signaling, and stemness maintenance in both HB and CSC-HCC. In contrast, downregulated BEX1 expression released RUNX3 and inhibited the activation of Wnt/ß-catenin signaling in non-CSC-HCC. CONCLUSION: BEX1, under the regulation of DNMT1, is necessary for the self-renewal and maintenance of liver CSCs through activation of Wnt/ß-catenin signaling, rendering BEX1 a potentially valuable therapeutic target in both HB and CSC-HCC. LAY SUMMARY: Cancer stem cells (CSCs) contribute to a high rate of cancer recurrence, as well as resistance to conventional therapies. However, the regulatory mechanisms underlying their self-renewal remains elusive. Herein, we have reported that BEX1 plays a key role in regulating CSC properties in different types of liver cancer. Targeting BEX1-mediated Wnt/ß-catenin signaling may help to address the high rate of recurrence, and heterogeneity of liver cancer.

The lncRNA XIST promotes colorectal cancer cell growth through regulating the miR-497-5p/FOXK1 axis.

BACKGROUND: Recent studies suggest that long noncoding RNAs (lncRNAs) play an important role in tumorigenesis. As a newly identified lncRNA, the role of XIST in colorectal cancer (CRC) has not been established. Here, we sought to characterize the role of XIST and its associated regulatory network in CRC cells. METHODS: Expression of XIST mRNA, miR-497-5p, and forkhead box k1 (FOXK1) in CRC cells and tissues were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Proliferation and apoptosis of CRC cells were determined using the CCK-8 cell counting assay and flow cytometry. The rate of cell migration and invasion was determined using a transwell assay. The relationships between XIST, miR-497-5p, and FOXK1 were predicted and confirmed using a dual-luciferase reporter assay. Expression of FOXK1 protein was quantified by Western blot. RESULTS: XIST and FOXK1 expression were significantly upregulated in CRC tissues and cell lines, while miR-497-5p expression was downregulated. XIST knockdown significantly suppressed CRC cell proliferation, migration, and invasion. Silencing of XIST also reversed the downregulation of miR-497-5p and upregulation of FOXK1. Moreover, blocking XIST expression was shown to inhibit CRC tumor growth in vivo and the effects were antagonized by the loss of miR-497-5p. miR-497-5p was shown to act as a sponge of XIST and also targeted FOXK1 in CRC cells. CONCLUSIONS: XIST was shown to promote the malignancy of CRC cells by competitively binding to miR-497-5p, resulting in an increase in FOXK1 expression. These results suggest that targeting of XIST may represent a possible treatment for CRC.

Upregulation of mtSSB by interleukin-6 promotes cell growth through mitochondrial biogenesis-mediated telomerase activation in colorectal cancer.

It is now widely accepted that mitochondrial biogenesis is inhibited in most cancer cells. Interestingly, one of the possible exceptions is colorectal cancer (CRC), in which the content of mitochondria has been found to be higher than in normal colon mucosa. However, to date, the causes and effects of this phenomenon are still unclear. In the present study, we systematically investigated the functional role of mitochondrial single-strand DNA binding protein (mtSSB), a key molecule in the regulation of mitochondrial DNA (mtDNA) replication, in the mitochondrial biogenesis and CRC cell growth. Our results demonstrated that mtSSB was frequently upregulated in CRC tissues and that upregulated mtSSB was associated with poor prognosis in CRC patients. Furthermore, overexpression of mtSSB promoted CRC cell growth in vitro by regulating cell proliferation. The in vivo assay confirmed these results, indicating that the forced expression of mtSSB significantly increases the growth capacity of xenograft tumors. Mechanistically, the survival advantage conferred by mtSSB was primarily caused by increased mitochondrial biogenesis and subsequent ROS production, which induced telomerase reverse transcriptase (TERT) expression and telomere elongation via Akt/mTOR pathway in CRC cells. In addition, FOXP1, a member of the forkhead box family, was identified as a new transcription factor for mtSSB. Moreover, our results also demonstrate that proinflammatory IL-6/STAT3 signaling facilitates mtSSB expression and CRC cell proliferation via inducing FOXP1 expression. Collectively, our findings demonstrate that mtSSB induced by inflammation plays a critical role in the regulation of mitochondrial biogenesis, telomerase activation, and subsequent CRC proliferation, providing a strong evidence for mtSSB as drug target in CRC treatment.

Effect of Laparoscopic vs Open Distal Gastrectomy on 3-Year Disease-Free Survival in Patients With Locally Advanced Gastric Cancer: The CLASS-01 Randomized Clinical Trial.

Importance: Laparoscopic distal gastrectomy is accepted as a more effective approach to conventional open distal gastrectomy for early-stage gastric cancer. However, efficacy for locally advanced gastric cancer remains uncertain. Objective: To compare 3-year disease-free survival for patients with locally advanced gastric cancer after laparoscopic distal gastrectomy or open distal gastrectomy. Design, Setting, and Patients: The study was a noninferiority, open-label, randomized clinical trial at 14 centers in China. A total of 1056 eligible patients with clinical stage T2, T3, or T4a gastric cancer without bulky nodes or distant metastases were enrolled from September 2012 to December 2014. Final follow-up was on December 31, 2017. Interventions: Participants were randomized in a 1:1 ratio after stratification by site, age, cancer stage, and histology to undergo either laparoscopic distal gastrectomy (n = 528) or open distal gastrectomy (n = 528) with D2 lymphadenectomy. Main Outcomes and Measures: The primary end point was 3-year disease-free survival with a noninferiority margin of -10% to compare laparoscopic distal gastrectomy with open distal gastrectomy. Secondary end points of 3-year overall survival and recurrence patterns were tested for superiority. Results: Among 1056 patients, 1039 (98.4%; mean age, 56.2 years; 313 [30.1%] women) had surgery (laparoscopic distal gastrectomy [n=519] vs open distal gastrectomy [n=520]), and 999 (94.6%) completed the study. Three-year disease-free survival rate was 76.5% in the laparoscopic distal gastrectomy group and 77.8% in the open distal gastrectomy group, absolute difference of -1.3% and a 1-sided 97.5% CI of -6.5% to ∞, not crossing the prespecified noninferiority margin. Three-year overall survival rate (laparoscopic distal gastrectomy vs open distal gastrectomy: 83.1% vs 85.2%; adjusted hazard ratio, 1.19; 95% CI, 0.87 to 1.64; P = .28) and cumulative incidence of recurrence over the 3-year period (laparoscopic distal gastrectomy vs open distal gastrectomy: 18.8% vs 16.5%; subhazard ratio, 1.15; 95% CI, 0.86 to 1.54; P = .35) did not significantly differ between laparoscopic distal gastrectomy and open distal gastrectomy groups. Conclusions and Relevance: Among patients with a preoperative clinical stage indicating locally advanced gastric cancer, laparoscopic distal gastrectomy, compared with open distal gastrectomy, did not result in inferior disease-free survival at 3 years. Trial Registration: ClinicalTrials.gov Identifier: NCT01609309.

Association of AlkB homolog 3 expression with tumor recurrence and unfavorable prognosis in hepatocellular carcinoma.

BACKGROUND AND AIM: The mammalian AlkB homolog protein family has been reported to promote tumor cell invasion and metastasis of human cancer. However, the expression status and clinical significance of AlkB homolog 3 (ALKBH3) in hepatocellular carcinoma (HCC) have not been reported yet. METHODS: In the present study, we investigated the protein expression of ALKBH3 by immunohistochemistry assay and evaluated its association with tumor progression, recurrence, and prognosis in 272 patients with HCC. In addition, we explored ALKBH3 function via gene overexpression and knockdown of ALKBH3. RESULTS: AlkB homolog 3 was overexpressed in HCC compared with adjacent non-tumorous specimens. Moreover, ALKBH3 expression was closely related to tumor differentiation and tumor-node-metastasis stage. Interestingly, the ALKBH3 high expression in tumor tissues of HCC patients had more poor disease-free survival and overall survival than low-expression patients. Consistently, we found that knockdown of ALKBH3 inhibits HCC cell proliferation in vitro and xenograft tumor formation in vivo and overexpressing ALKBH3 showed the opposite results. ALKBH3 knockdown may inhibit cell proliferation, presumably through p21/p27-mediated cell-cycle arrest at G1 phase in human HCC. ALKBH3 may also play some role on chemosensitivity to certain genotoxic reagents, such as cisplatin (CDDP) and epirubicin. CONCLUSIONS: These findings reveal an important role of ALKBH3 in HCC, indicating that ALKBH3 could be used as a new therapeutic target in future.

Elevated Serum Triglycerides in the Prognostic Assessment of Acute Pancreatitis: A Systematic Review and Meta-Analysis of Observational Studies.

BACKGROUND: Hypertriglyceridemia has been positively associated with the risk of acute pancreatitis (AP), but whether increased triglyceride (TG) levels are associated with the severity of AP remains unknown. To this, a meta-analysis was conducted to assess the effect of elevated serum TG on the prognosis of AP. METHODS: We searched PubMed, EMBASE, and the Cochrane library to identify all eligible studies (up to September 2016). We pooled the odds ratios (ORs) or standardized mean difference from individual studies using a random-effects model to investigate associations between levels of TG and the prognosis of AP. RESULTS: A total of 15 studies were included in the meta-analysis, including a total of 1564 patients with triglyceride-related acute pancreatitis (TGAP) and 5721 patients with nontriglyceride-related acute pancreatitis (NTGAP). The occurrence of renal failure [OR=3.18; 95% confidence interval (CI): 1.92, 5.27; P<0.00001], respiratory failure (OR=2.88; 95% CI: 1.61, 5.13; P<0.0001), and shock (OR=3.78; 95% CI: 1.69, 8.44; P<0.0001) was statistically significantly higher in TGAP group than in NTGAP group. Furthermore, mortality (OR=1.90; 95% CI: 1.05, 3.45; P<0.01), systemic inflammatory response syndrome (OR=2.03; 95% CI: 1.49, 2.75; P<0.00001), and Acute Physiology and Chronic Health Evaluation (APACHE-II) scores (standardized mean difference=2.72; 95% CI: 1.00, 4.45; P<0.001) were also statistically significantly higher in TGAP group than in NTGAP group. CONCLUSION: Elevated serum TGs are related to a worse prognosis of AP.

Leukocyte mitochondrial DNA content: a novel biomarker associated with prognosis and therapeutic outcome in colorectal cancer.

Compelling evidence has indicated a significant association between leukocyte mitochondrial DNA (mtDNA) content and incidence risks of several malignancies in a cancer-specific manner. However, to date, whether leukocyte mtDNA content can predict clinical outcome of cancer patients has never been investigated. In the present study, we measured leukocyte mtDNA content using real-time PCR-based method in a total of 598 colorectal cancer (CRC) patients and explored its prognostic values. To explore potential mechanism, we detected the immunophenotypes of peripheral blood mononuclear cells and plasma concentrations of several cytokines in CRC patients. We found that patients with high mtDNA content showed significantly worse overall survival (OS) and relapse-free survival (RFS) than those with low mtDNA content in all patient sets. Furthermore, mtDNA content and tumor node metastasis (TNM) stage exhibited a notable joint effect in prognosis prediction. Integration of TNM stage and leukocyte mtDNA content significantly improved the prognosis prediction efficacy for CRC. Importantly, patients with high mtDNA content showed OS and RFS benefits from adjuvant chemotherapy. In addition, we found that patients with high mtDNA content had a higher frequency of CD4(+)CD25(+)FOXP3(+) regulatory T cells, higher plasma interleukin-2 and transforming growth factor-ß1 and lower tumor necrosis factor-α concentration than those with low mtDNA content, suggesting a stronger immunosuppressive phenotype. In conclusion, our study for the first time demonstrates that leukocyte mtDNA content is an independent prognostic marker complementing TNM stage and associated with immunosuppression in CRC patients. Additionally, leukocyte mtDNA content might serve as a potential biomarker to select CRC patients who will benefit from adjuvant chemotherapy.

Genetic variations in genes of metabolic enzymes predict postoperational prognosis of patients with colorectal cancer.

BACKGROUND: Genetic alterations in tricarboxylic acid (TCA) cycle metabolic enzymes were recently linked to various cancers. However, the associations of single nucleotide polymorphisms (SNPs) in genes of these enzymes have not been well studied. METHODS: We genotyped 16 SNPs from 7 genes encoding TCA cycle metabolic enzymes in 697 colorectal carcinoma (CRC) patients receiving surgical resection and analyzed their associations with clinical outcomes by multivariate Cox proportional hazard model. Then, the significant results were validated in another cohort of 256 CRC patients. RESULTS: We identified 4 SNPs in 2 genes had significant associations with CRC death risk and 5 SNPs in 3 genes had significant associations with CRC recurrence risk. Similar significant results were confirmed for rs4131826 in SDHC gene, rs544184 in SDHD gene and rs12071124 in FH gene in a validation cohort. Further analysis indicated that unfavorable genotypes exhibited a significant cumulative effect on overall and recurrence-free survival in a dose-dependent manner. Moreover, survival tree analysis indicated that SNP rs4131826 in SDHC gene and SNP rs12071124 in FH gene were the primary factors contributing to the different overall survival time and recurrence-free survival time of CRC patients, respectively. Immunohistochemical analysis further validated the effect of rs4131826 and rs544184 on expression of SDHC and SDHD in tissue samples. CONCLUSIONS: Our study suggests that SNPs in TCA cycle metabolic enzymes might be significantly associated with clinical outcomes in Chinese population diagnosed with CRC. Further functional and validated studies are warranted to expend our results to clinical utility.

Functional polymorphisms of ATP citrate lyase gene predicts clinical outcome of patients with advanced colorectal cancer.

BACKGROUND: Previous studies have demonstrated that ATP citrate lyase (ACLY) plays an important role in the development of many cancers. Our current study aims to assess the effects of functional single nucleotide polymorphisms (SNPs) in ACLY gene on recurrence and survival of colorectal cancer (CRC) patients. METHODS: A total of 697 resected Chinese CRC patients were included in this study. Two functional single nucleotide polymorphisms in ACLY gene were examined using the Sequenom iPLEX genotyping system. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the prognosis analysis. RESULTS: Multivariate Cox regression analysis showed that there was no significant association between SNPs in ACLY gene and the prognosis of total patient cohort. However, in patients with stage III + IV diseases, the two functional SNPs (rs2304497 and rs9912300) exhibited a significant association with the risks of death (HR = 0.47, 95% CI = 0.24-0.90 and HR = 0.59, 95% CI = 0.37-0.92, respectively) and recurrence (HR = 0.46, 95% CI = 0.24-0.86 and HR = 0.54, CI = 0.35-0.83, respectively). Kaplan-Meier analysis indicated that those CRC patients carrying heterozygous (WV) or homozygous variant (VV) genotypes in rs2304497 and rs9912300 had significantly better overall survival (OS) and recurrence-free survival (RFS). Moreover, we observed remarkable cumulative effects of these two SNPs on overall survival and recurrence-free survival (P for trend = 0.012 and 0.003, respectively). Compared with patients carrying zero unfavorable genotype, those carrying two unfavorable genotypes had a 2.24-fold and 2.33-fold increase of death and recurrence risks, respectively. CONCLUSIONS: The SNPs in ACLY gene may serve as independent prognostic markers for patients with advanced stage CRC.

IL-17 gene polymorphism is associated with susceptibility to gastric cancer.

We conducted a case-control study to investigate the role of three common IL-17A and IL-17F single nucleotide polymorphisms (SNPs) on the susceptibility to gastric cancer. A case-control study was conducted using a Chinese study population of 462 gastric cancer subjects and 462 controls. Polymerase chain reaction restriction fragment length of polymorphism (PCR-RFLP) was taken to genotype rs2275913, rs763780, and rs3748067 within the IL-17 gene. When comparing demographic characteristics of gastric cancer between gastric cancer cases and control groups, cancer cases were more likely to be cigarette smokers and alcohol drinkers, have cancer history in the first relatives, and have higher infection rate of Helicobacter pylori. By conditional regression analysis, individuals carrying IL-17 rs2275913 GA, AA genotype, and A allele were associated with an increased gastric cancer risk. Those carrying rs3748067 CC genotype and C allele had a significantly increased risk for the development of gastric cancer. Moreover, rs2275913 and rs3748067 variations had association with cigarette smoking, alcohol drinking, and H. pylori infection on the risk of gastric cancer. These results suggest that rs2275913 and rs3748067 variations significantly increase gastric cancer risk in a Chinese population.

DBH-YOLO: a surgical instrument detection method based on feature separation in laparoscopic surgery.

PURPOSE: Accurately locating and analysing surgical instruments in laparoscopic surgical videos can assist doctors in postoperative quality assessment. This can provide patients with more scientific and rational solutions for healing surgical complications. Therefore, we propose an end-to-end algorithm for the detection of surgical instruments. METHODS: Dual-Branched Head (DBH) and Overall Intersection over Union Loss (OIoU Loss) are introduced to solve the problem of inaccurate surgical instrument detection, both in terms of localization and classification. An effective method (DBHYOLO) for the detection for laparoscopic surgery in complex scenarios is proposed. This study manually annotates a new laparoscopic gastric cancer resection surgical instrument location dataset LGIL, which provides a better validation platform for surgical instrument detection methods. RESULTS: The proposed method's performance was tested using the m2cai16-tool-locations, LGIL, and Onyeogulu datasets. The mean Average Precision (mAP) values obtained were 96.8%, 95.6%, and 98.4%, respectively, which were higher than the other classical models compared. The improved model is more effective than the benchmark network in distinguishing between surgical instrument classes with high similarity and avoiding too many missed detection cases. CONCLUSIONS: In this paper, the problem of inaccurate detection of surgical instruments is addressed from two different perspectives: classification and localization. And the experimental results on three representative datasets verify the performance of DBH-YOLO. It is shown that this method has a good generalization capability.

Enhancing thromboprophylaxis after colorectal cancer surgery in China: Bridging the gap between evidence and implementation through pathway optimization.

BACKGROUND: The CRC-VTE trial conducted in China revealed a significant occurrence of venous thromboembolism (VTE) in patients following colorectal cancer (CRC) surgery, raising concerns about implementing thromboprophylaxis measures. The present study aimed to identify and analyze inappropriate aspects of current thromboprophylaxis practices. METHODS: This study performed an analysis of the CRC-VTE trial, a prospective multicenter study that enrolled 1836 patients who underwent CRC surgery. The primary objective was to identify independent risk factors for VTE after CRC surgery using multivariate logistic regression analysis. Furthermore, among the cases in which VTE occurred, the appropriateness of thromboprophylaxis was assessed based on several factors, including pharmacologic prophylaxis, time to initiate prophylaxis, drug selection, drug dosage, and duration of pharmacologic prophylaxis. Based on the analysis of the current state of thromboprophylaxis and relevant clinical guidelines, a modified Delphi method was used to develop a clinical pathway for VTE prophylaxis after CRC surgery. RESULTS: In this analysis of 1836 patients, 205 (11.2%) were diagnosed with VTE during follow-up. The multifactorial analysis identified several independent risk factors for VTE, including age (≥70 years), female sex, varicose veins in the lower extremities, intraoperative blood transfusion, and the duration of immobilization exceeding 24 h. None of the patients diagnosed with VTE in the CRC trial received adequate thromboprophylaxis. The main reasons for this inappropriate practice were the omission of thromboprophylaxis, delayed initiation, and insufficient duration of thromboprophylaxis. We developed a specialized clinical pathway for thromboprophylaxis after CRC surgery to address these issues. CONCLUSIONS: This study offers a comprehensive nationwide evaluation of existing thromboprophylaxis practices in patients after CRC surgery in China. A specialized clinical pathway was developed to address the identified gaps and improve the quality of care. This clinical pathway incorporates explicit, tailored, detailed recommendations for thromboprophylaxis after CRC surgery.

Intratumoral bacteria are an important "accomplice" in tumor development and metastasis.

As emerging tumor components, intratumoral bacteria have been found in many solid tumors. Several studies have demonstrated that different cancer subtypes have distinct microbial compositions, and mechanistic studies have shown that intratumoral bacteria may promote cancer initiation and progression through DNA damage, epigenetic modification, inflammatory responses, modulation of host immunity and activation of oncogenes or oncogenic pathways. Moreover, intratumoral bacteria have been shown to modulate tumor metastasis and chemotherapy response. A better understanding of the tumor microenvironment and its associated microbiota will facilitate the design of new metabolically engineered species, opening up a new era of intratumoral bacteria-based cancer therapy. However, many questions remain to be resolved, such as where intratumoral bacteria originate and whether there is a direct causal relationship between intratumoral bacteria and tumor susceptibility. In addition, suitable preclinical models and more advanced detection techniques are crucial for studying the biological functions of intratumoral bacteria. In this review, we summarize the complicated role of intratumoral bacteria in the regulation of cancer development and metastasis and discuss their carcinogenic mechanisms and potential therapeutic aspects.

Temporal-based Swin Transformer network for workflow recognition of surgical video.

PURPOSE: Surgical workflow recognition has emerged as an important part of computer-assisted intervention systems for the modern operating room, which also is a very challenging problem. Although the CNN-based approach achieves excellent performance, it does not learn global and long-range semantic information interactions well due to the inductive bias inherent in convolution. METHODS: In this paper, we propose a temporal-based Swin Transformer network (TSTNet) for the surgical video workflow recognition task. TSTNet contains two main parts: the Swin Transformer and the LSTM. The Swin Transformer incorporates the attention mechanism to encode remote dependencies and learn highly expressive representations. The LSTM is capable of learning long-range dependencies and is used to extract temporal information. The TSTNet organically combines the two components to extract spatiotemporal features that contain more contextual information. In particular, based on a full understanding of the natural features of the surgical video, we propose a priori revision algorithm (PRA) using a priori information about the sequence of the surgical phase. This strategy optimizes the output of TSTNet and further improves the recognition performance. RESULTS: We conduct extensive experiments using the Cholec80 dataset to validate the effectiveness of the TSTNet-PRA method. Our method achieves excellent performance on the Cholec80 dataset, which accuracy is up to 92.8% and greatly exceeds the state-of-the-art methods. CONCLUSION: By modelling remote temporal information and multi-scale visual information, we propose the TSTNet-PRA method. It was evaluated on a large public dataset, showing a high recognition capability superior to other spatiotemporal networks.