Laparoscopic total extraperitoneal (TEP) inguinal hernia repair with preperitoneal closed-suction drainage reduced postoperative complications.

BACKGROUND: Although laparoscopic total extraperitoneal (TEP) inguinal hernia repair has the advantages of less bleeding, less trauma, less pain, and fast recovery, there are several issues that need to be addressed. This study aims to evaluate the effectiveness of preperitoneal closed­suction drainage on reducing postoperative complications in TEP inguinal hernia repair. METHODS: A retrospective analysis of 122 patients who underwent TEP inguinal hernia repair between June 2018 and June 2021 was performed. The patients were divided into the drainage group and the non-drainage group according to whether the drainage tube was placed or not. Clinical data, surgical procedures and outcome of these patients were collected and analyzed to assess the effectiveness of drainage. RESULTS: A total of 122 patients undergoing TEP surgery were screened, of which 22 were excluded. Most of the patients were male with right indirect inguinal hernia. There was no difference in the mean length of hospital stay between the two groups. Postoperative pain was alleviated by preperitoneal closed­suction drainage 24 h after operation (p = 0.03). The rate of complications such as scrotal edema, seroma and urinary retention in the drainage group was significantly lower than that in the non-drainage group (p < 0.05). Multivariate regression analysis showed that drainage was beneficial to reduce postoperative complications (OR, 0.015; 95% CI, 0.002-0.140; p < 0.01). In addition, it was worth noting that in subgroup analysis, patients with hernia sac volume > 10 cm3 might receive more clinical benefits by placing drainage tube. CONCLUSION: In TEP inguinal hernia repair, placing drainage tube is a simple and feasible traditional surgical treatment, which can promote postoperative recovery without increasing the risk of infection, especially in patients with large hernia sac volume.

Transcriptome analysis of mesenteric arterioles changes and its mechanisms in cirrhotic rats with portal hypertension.

Portal hypertension (PHT) is a major cause of liver cirrhosis. The formation of portosystemic collateral vessels and splanchnic vasodilation contribute to the development of hyperdynamic circulation, which in turn aggravates PHT and increases the risk of complications. To investigate the changes in mesenteric arterioles in PHT, cirrhotic rat models were established by ligating the common bile ducts. After 4 weeks, the cirrhotic rats suffered from severe PHT and splanchnic hyperdynamic circulation, characterized by increased portal pressure (PP), cardiac output (CO), cardiac index (CI), and superior mesenteric artery (SMA) flow. Mesenteric arterioles in cirrhotic rats displayed remarkable vasodilation, vascular remodeling, and hypocontractility. RNA sequencing was performed based on these findings. A total of 1,637 differentially expressed genes (DEGs) were detected, with 889 up-regulated and 748 down-regulated genes. Signaling pathways related to vascular changes were enriched, including the vascular endothelial growth factor (VEGF), phosphatidylinositol-3-kinase-AKT (PI3K-AKT), and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) signaling pathway, among others. Moreover, the top ten hub genes were screened according to the degree nodes in the protein-protein interaction (PPI) network. Functional enrichment analyses indicated that the hub genes were involved in cell cycle regulation, mitosis, and cellular response to oxidative stress and nitric oxide (NO). In addition, promising candidate drugs for ameliorating PHT, such as resveratrol, were predicted based on hub genes. Taken together, our study highlighted remarkable changes in the mesenteric arterioles of cirrhotic rats with PHT. Transcriptome analyses revealed the potential molecular mechanisms of vascular changes in splanchnic hyperdynamic circulation.

Construction and comprehensive analysis of a lncRNA-mRNA interactive network to reveal a potential lncRNA for hepatic encephalopathy development.

Little is known about the role of lncRNA-mRNA regulatory relationships in hepatic encephalopathy (HE). Here, we aimed to construct the potential lncRNA and mRNA interactive network in forecasting HE development in patients with liver cirrhosis using different bioinformatic analysis method. Through analyses, we found that AL137857.1 had the most connections with other mRNAs and was deemed as a hub lncRNA. It was obviously upregulated in HE patients, which was also validated by another independent dataset. GO and KEGG analyses suggested that AL137857.1 was involved in microglial cell activation, phagocytosis, cytokine biosynthetic process, interleukin-6 production and tumor necrosis factor production. In vitro experiments suggested LPS could stimulate microglia to generate AL137857.1. In addition, we found that inhibition of AL137857.1 suppressed the expression of a series of inflammatory cytokines, including IL-1, IL-6, TNF-α, Cox2 and iNOS. Conversely, AL137857.1 over-expression induced a marked increase in these factors. Finally, AL137857.1 was demonstrated to be highly associated with the ability of microglial phagocytosis. Taken together, we have constructed a lncRNA-mRNA regulatory network associated with HE and explored the biological significance of mRNAs in the network, then discovered a novel lncRNA AL137857.1 in HE that might act as a potential regulator of the downstream inflammatory cytokines.

Salivary biomarkers-assisted ultrasound-based differentiation of malignant and benign thyroid nodules.

BACKGROUND: The incidence of papillary thyroid cancer (PTC) is increasing annually. ultrasonography (US) is the current primary method for evaluating thyroid nodules; however, there have been persisting challenges in diagnosing borderline malignancies. This paper aimed to establish the differential diagnostic value of salivary biomarkers for thyroid nodules geared towards improving the efficacy of US. METHODS: We recruited a total of 44 PTC patients and 42 benign thyroid tumor (BTT) patients to this study. The distribution of tumor markers and thyroid hormones in saliva and serum were compared between groups; then, uni-/multi-variate logistic analyses were used to determine the risk factors of PTC. Further, we estimated the differential diagnostic value of biomarkers in thyroid nodules, especially in borderline scenarios. Finally, a multi-index diagnostic model was constructed constituting biomarkers and US. RESULTS: The distributions of serum thyroglobulin (TG), salivary triiodothyronine (T3), free-triiodothyronine (FT3), and free-thyroxine (FT4) were significantly different in BTT and PTC (P<0.05); salivary FT3 was identified as an independent risk factor for PTC. By analyzing the diagnostic accuracy of various Thyroid Imaging Reporting and Data System (TI-RADS) categories, category 4A was shown to have the lowest diagnostic accuracy (48.39%) with the largest proportion (31 people, 36.05%). In 4A patients, the K-nearest neighbor (KNN) algorithm attained the highest sensitivity of 87.50% and specificity of 100.00% among the machine learning-based multi-biomarkers models. Eventually, by combing the US with the KNN-based biomarkers model, the sensitivity and specificity reached 90.91% and 83.33%, respectively. CONCLUSIONS: Salivary biomarkers exhibit good potential in the differential diagnosis of borderline thyroid nodules and they significantly improve the prediction accuracy of the US. Additionally, we found that salivary FT3 is an independent risk factor for PTC and may be used as a key marker for PTC diagnosis.

Prognostic Value of Serum Osteoprotegerin Level in Patients With Hepatocellular Carcinoma Following Surgical Resection.

BACKGROUND: Multiple studies have reported that tissue or serum osteoprotegerin (OPG) level is a prognostic factor for patients with cancer. However, little is known about the role of serum OPG in hepatocellular carcinoma (HCC). In this study, we aimed to investigate whether serum OPG concentration has an effect on HCC patients' prognosis. METHODS: A total of 386 eligible HCC patients undergoing radical hepatectomy were enrolled from Shanghai Ninth People's Hospital and Zhongshan Hospital between 2010 and 2018. Kaplan-Meier curves, Cox regression model, and the restricted mean survival time (RMST) were used to estimate the association of OPG and HCC patients' survival outcome. In addition, sensitivity analyses were carried out including subgroup analysis and propensity score matching (PSM). RESULTS: Patients were separated into two groups according to the cut-off value of OPG calculated by X-tile. Multivariate Cox analysis showed that patients with high OPG level had worse overall survival (OS) (HR: 1.93; 95% CI: 1.40-2.66, p<0.001) and disease-free survival (DFS) (HR: 1.85; 95% CI: 1.39-2.47, p<0.001) before matching. On average, RMST ratio between high and low OPG turned out to be 0.797 (95% CI: 0.716-0.887, p<0.001). In the matched population, we found that OPG level was negatively associated with OS (HR: 1.85; 95% CI: 1.25-2.74, p=0.002) and DFS (HR: 1.71; 95% CI: 1.20-2.44, p=0.003). In addition, a similar trend was further confirmed by subgroup analyses. CONCLUSION: In a word, HCC patients with high OPG level had poorer survival rates compared with HCC patients with low OPG level. This factor could act as a potential prognostic predictor for HCC patients who underwent radical resection in the future.

Serum GGT/ALT ratio predicts vascular invasion in HBV-related HCC.

BACKGROUND: The gamma-glutamyl transferase (GGT) to alanine aminotransferase (ALT) ratio has been reported as an effective predictor of the severity of hepatitis and HCC. The purpose of this study was to determine the role of the GGT/ALT ratio in the prediction of vascular invasion and survival outcomes in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: The risk factors for vascular invasion were determined by univariate/multivariate logistic analysis. The cut-off value of GGT/ALT in predicting vascular invasion was calculated using the receiver operating characteristic (ROC) curve. The prognostic value of GGT/ALT was examined by Cox analysis and Kaplan-Meier curves. Sensitivity analysis, such as subgroup analysis and propensity score matching (PSM), was performed to reduce potential confounding bias. RESULTS: A high GGT/ALT ratio was identified as an independent risk factor for vascular invasion (P = 0.03). The correlation analysis suggested that higher GGT/ALT was associated with more severe tumour burdens, including vascular invasion (P < 0.001), tumour volume > 5 cm (P < 0.001), poor pathological differentiation (P = 0.042), more severe BCLC (P < 0.001) and ALBI grade (P = 0.007). In the survival analysis, a high GGT/ALT ratio was associated with poor overall survival (OS) (HR: 1.38; 95% CI 1.03, 1.87; P < 0.0001) and disease-free survival (DFS) (HR: 1.32; 95% CI 1.03, 1.87; P < 0.0001). In the subgroup analysis, similar results were consistently observed across most subgroups. In PSM analysis, GGT/ALT remained independently associated with vascular invasion (OR, 186; 95% CI 1.23, 3.33). CONCLUSION: The GGT/ALT ratio was a potential effective factor in the prediction of vascular invasion and prognosis in patients with HBV-related HCC.

TRIM26 Induces Ferroptosis to Inhibit Hepatic Stellate Cell Activation and Mitigate Liver Fibrosis Through Mediating SLC7A11 Ubiquitination.

Hepatic stellate cells (HSCs) are activated by inflammatory mediators to secrete extracellular matrix for collagen deposition, leading to liver fibrosis. Ferroptosis is iron- and lipid hydroperoxide-dependent programmed cell death, which has recently been targeted for inhibiting liver fibrogenic processes. Tripartite motif-containing protein 26 (TRIM26) is an E3 ubiquitin ligase that functions as a tumor suppressor in hepatocellular carcinoma, while little is known about its function in liver fibrosis. In the present study, the differential expression of TRIM26 in normal and fibrotic liver tissues was examined based on both online databases and specimens collected from patient cohort. The effects of TRIM26 on HSCs ferroptosis were examined in vitro through evaluating cell proliferation, lipid peroxidation, and expression of key ferroptosis-related factors. In vivo function of TRIM26 in liver fibrosis was examined based on CCl4-induced mice model. We found that TRIM26 was downregulated in fibrotic liver tissues. The overexpression of TRIM26 inhibited HSCs proliferation, promoted lipid peroxidation, manipulated ferroptosis-related factor expressions, and counteracted the effect of iron inhibitor deferoxamine. Moreover, TRIM26 physically interacted with solute carrier family-7 member-11 (SLC7A11), a critical protein for lipid reactive oxygen species (ROS) scavenging, and mediated its ubiquitination. In addition, TRIM26 overexpression induced HSCs ferroptosis and mitigated CCl4-induced liver fibrosis in mice. In conclusion, TRIM26 promotes HSCs ferroptosis to suppress liver fibrosis through mediating the ubiquitination of SLC7A11. The TRIM26-targeted SLC7A11 suppression can be a novel therapeutic strategy for liver fibrosis.

Prognostic and Predictive Value of m6A "Eraser" Related Gene Signature in Gastric Cancer.

BACKGROUND: N6-methyladenosine (m6A) RNA modification plays a critical role in gastric cancer (GC). However, the relationship between the m6A "eraser", FTO, and ALKBH5, and the prognosis of GC still remains unclear. This study aimed to evaluate the effect of FTO and ALKBH5 on the prognosis of patients and their potential roles in GC. MATERIALS AND METHODS: A total of 738 GC samples with clinical information obtained from two independent datasets were included and divided into training set and testing set. Differential expression analysis of the m6A "eraser" related genes was performed. The LASSO Cox regression model was constructed to analyze the m6A "eraser" related risk genes. The univariate and multivariate Cox regression model were employed to identify the independent prognostic factors. Kaplan-Meier method was used for survival analysis. A nomogram model was then carried out to predict the prognosis of GC patients. Additionally, GO and KEGG analyses were conducted to identify the potential role of the m6A "eraser" related genes in GC. The relative proportion of 22 different genotypes in immune infiltrating cells was calculated by CIBERSORT algorithm. RESULTS: In total, nine m6A "eraser" related risk genes and risk scores were obtained and calculated. Patients in high-risk group demonstrated significantly worse prognosis than those in low-risk group. Age, stage, and risk score were considered as independent prognostic factors. The nomogram model constructed accurately predicted the 3-year and 5-year overall survival (OS) of patients. Furthermore, m6A "eraser" might play a functional role in GC. The expression of m6A "eraser" leads to changes in tumor immune microenvironment. CONCLUSIONS: FTO and ALKBH5 showed association with the prognosis of GC. The m6A "eraser" related genes, which is considered as a reliable prognostic and predictive tool, assists in predicting the OS in GC patients.

Enhanced Meningeal Lymphatic Drainage Ameliorates Neuroinflammation and Hepatic Encephalopathy in Cirrhotic Rats.

BACKGROUND & AIMS: Hepatic encephalopathy (HE) is a serious neurologic complication in patients with liver cirrhosis. Very little is known about the role of the meningeal lymphatic system in HE. We tested our hypothesis that enhancement of meningeal lymphatic drainage could decrease neuroinflammation and ameliorate HE. METHODS: A 4-week bile duct ligation model was used to develop cirrhosis with HE in rats. Brain inflammation in patients with HE was evaluated by using archived GSE41919. The motor function of rats was assessed by the rotarod test. Adeno-associated virus 8-vascular endothelial growth factor C (AAV8-VEGF-C) was injected into the cisterna magna of HE rats 1 day after surgery to induce meningeal lymphangiogenesis. RESULTS: Cirrhotic rats with HE showed significantly increased microglia activation in the middle region of the cortex (P < .001) as well as increased neuroinflammation, as indicated by significant increases in interleukin 1ß, interferon γ, tumor necrosis factor α, and ionized calcium binding adaptor molecule 1 (Iba1) expression levels in at least 1 of the 3 regions of the cortex. Motor function was also impaired in rats with HE (P < .05). Human brains of patients with cirrhosis with HE also exhibited up-regulation of proinflammatory genes (NFKB1, IbA1, TNF-α, and IL1ß) (n = 6). AAV8-VEGF-C injection significantly increased meningeal lymphangiogenesis (P = .035) and tracer dye uptake in the anterior and middle regions of the cortex (P = .006 and .003, respectively), their corresponding meninges (P = .086 and .006, respectively), and the draining lymph nodes (P = .02). Furthermore, AAV8-VEGF-C decreased microglia activation (P < .001) and neuroinflammation and ameliorated motor dysfunction (P = .024). CONCLUSIONS: Promoting meningeal lymphatic drainage and enhancing waste clearance improves HE. Manipulation of meningeal lymphangiogenesis could be a new therapeutic strategy for the treatment of HE.

Preoperative prediction of microvascular invasion in non-metastatic hepatocellular carcinoma based on nomogram analysis.

PURPOSE: The presence of microvascular invasion (MVI) is an unfavorable prognostic factor for hepatocellular carcinoma (HCC). This study aimed to construct a nomogram-based preoperative prediction model of MVI, thereby assisting to preoperatively select proper surgical procedures. METHODS: A total of 714 non-metastatic HCC patients undergoing radical hepatectomy were retrospectively selected from Zhongshan Hospital between 2010 and 2018, followed by random assignment into training (N = 520) and validation cohorts (N = 194). Nomogram-based prediction model for MVI risk was constructed by incorporating independent risk factors of MVI presence identified from multivariate backward logistic regression analysis in the training cohort. The performance of nomogram was evaluated by calibration curve and ROC curve. Finally, decision curve analysis (DCA) was used to determine the clinical utility of the nomogram. RESULTS: In total, 503 (70.4%) patients presented MVI. Multivariate analysis in the training cohort revealed that age (OR: 0.98), alpha-fetoprotein (≥400 ng/mL) (OR: 2.34), tumor size (>5 cm) (OR: 3.15), cirrhosis (OR: 2.03) and γ-glutamyl transpeptidase (OR: 1.61) were significantly associated with MVI presence. The incorporation of five risk factors into a nomogram-based preoperative estimation of MVI risk demonstrated satisfactory discriminative capacity, with C-index of 0.702 and 0.690 in training and validation cohorts, respectively. Calibration curve showed good agreement between actual and predicted MVI risks. Finally, DCA revealed the clinical utility of the nomogram. CONCLUSION: The nomogram showed a satisfactory discriminative capacity of MVI risk in HCC patients, and could be used to preoperatively estimate MVI risk, thereby establishing more rational therapeutic strategies.

Prognostic value of the creatinine-albumin ratio in acute pancreatitis debridement.

BACKGROUND: Increases in the levels of serum C-reactive protein (CRP) and creatinine (Cr) and decreases in those of albumin (Alb) are commonly observed in acute pancreatitis (AP). We aimed to evaluate the efficacy of the Cr/Alb and CRP/Alb ratios in the prediction of surgical treatment effect in AP patients. METHODS: This study retrospectively analyzed clinical data obtained from 140 AP patients who underwent debridement from January 2008 to November 2018 in Shanghai Ruijin Hospital. The Cr/Alb and CRP/Alb ratios at admission and before surgery were assessed in the analysis of clinical statistics, prediction of prognoses, and logistic regression analysis. RESULTS: The admission Cr/Alb had the best predictive value of the four ratios. This value was significantly higher in patients with re-operation and those who died (P < 0.05) and was correlated with the Acute Physiology and Chronic Health Evaluation (APACHE II) score, admission CRP/Alb, preoperative Cr/Alb, and post-operative complications. The admission Cr/Alb could predict the risk of AP-related re-operation and mortality with sensitivities, specificities and areas under the curve of 86.3%, 61.7% and 0.824, and 73.4%, 81.3% and 0.794, respectively. At a cut-off value of 3.43, admission Cr/Alb values were indicative of a worse clinical state, including impaired laboratory test values, APACHE II scores, rates of post-operative complications and re-operation, and mortality (P < 0.05). In the logistic regression analysis, admission Cr/Alb values were independently related to the APACHE II score, post-operative renal failure, and mortality. CONCLUSION: Cr/Alb is a novel but promising, easy-to-measure, reproducible, non-invasive prognostic score for the prediction of the effect of debridement in AP patients.

Personalized four-category staging for predicting prognosis in patients with small bowel Adenocarcinoma: an international development and validation study.

BACKGROUND: Log odds of positive lymph nodes (LODDS) classification showed superiority over 8th edition N staging in predicting survival of small bowel adenocarcinoma (SBA) patients. The aim of this study was to develop and validate the Tumor, LODDS, and Metastasis (TLM) staging of SBA. METHODS: Totally 1789 SBA patients from the Surveillance, Epidemiology, and End Results (SEER) database between 1988-2010, 437 patients from SEER database between 2011-2013 and 166 patients from multicenters were categorized into development, validation and test cohort, respectively. The TLM staging was developed in the development cohort using Ensemble Algorithm for Clustering Cancer Data (EACCD) method. C-index was used to assess the performance of the TLM staging in predicting cancer-specific survival (CSS) and was compared with the traditional 8th edition TNM staging. FINDINGS: Four-category TLM staging designed for the development cohort showed higher discriminatory power than TNM staging in predicting CSS in the development cohort (0.682 vs. 0.650, P < 0.001), validation cohort (0.682 vs. 0.654, P = 0.022), and test cohort (0.659 vs. 0.611, P = 0.023), respectively. TLM staging continued to show its higher predictive efficacy than the 8th TNM in TNM stage II/III patients or in patients with lymph node yield less than 8. INTERPRETATION: TLM staging showed a better prognostic performance than the 8th TNM staging especially TNM stage II/III or patients with lymph node yield less than 8 and therefore, could serve to complement the TNM staging in patients with SBA. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Prognostic and Predictive Value of a Long Non-coding RNA Signature in Glioma: A lncRNA Expression Analysis.

The current histologically based grading system for glioma does not accurately predict which patients will have better outcomes or benefit from adjuvant chemotherapy. We proposed that combining the expression profiles of multiple long non-coding RNAs (lncRNAs) into a single model could improve prediction accuracy. We included 1,094 glioma patients from three different datasets. Using the least absolute shrinkage and selection operator (LASSO) Cox regression model, we built a multiple-lncRNA-based classifier on the basis of a training set. The predictive and prognostic accuracy of the classifier was validated using an internal test set and two external independent sets. Using this classifier, we classified patients in the training set into high- or low-risk groups with significantly different overall survival (OS, HR = 8.42, 95% CI = 4.99-14.2, p < 0.0001). The prognostic power of the classifier was then assessed in the other sets. The classifier was an independent prognostic factor and had better prognostic value than clinicopathological risk factors. The patients in the high-risk group were found to have a favorable response to adjuvant chemotherapy (HR = 0.4, 95% CI = 0.25-0.64, p < 0.0001). We built a nomogram that integrated the 10-lncRNA-based classifier and four clinicopathological risk factors to predict 3 and 5 year OS. Gene set variation analysis (GSVA) showed that pathways related to tumorigenesis, undifferentiated cancer, and epithelial-mesenchymal transition were enriched in the high-risk groups. Our classifier built on 10-lncRNAs is a reliable prognostic and predictive tool for OS in glioma patients and could predict which patients would benefit from adjuvant chemotherapy.

Comparative Effectiveness of Radiofrequency Ablation vs. Surgical Resection for Patients With Solitary Hepatocellular Carcinoma Smaller Than 5 cm.

Background: This study aims to compare survival outcome after receiving radiofrequency ablation (RFA) and surgical resection (SR) for solitary hepatocellular carcinoma (HCC) with size large as 5 cm. Methods: The SEER database was queried for patients with HCC tumors who were treated with RFA or SR between 2004 and 2015. Univariate and multivariate Cox analysis was used to assess the influence of potential variables on the patients' outcome. Additionally, propensity score matching (PSM) and multiple imputations (MI) were used as sensitivity analyses. Results: Of 1,985 cases, 934 patients received RFA treatment, while the rest underwent surgical resection. The patients in the RFA group had poorer overall survival (OS) and cancer-specific survival (CSS) than those in the SR group regardless of the tumor size before matching and MI. By using PSM analysis at a 1:1 ratio, 1,302 cases were paired and we have found that SR had a positive impact on OS and CSS of patients with tumors measuring from 3.1 to 5 cm. However, when the tumor size was <3 cm, patients undergoing SR had similar survival benefit with those after RFA. The above results were confirmed after performing PSM analysis at a 1:2 and 1:3 ratio. Conclusion: By applying several effective sensitivity analyses, we demonstrated that OS and CSS were similar between the patients with tumors smaller than 3 cm receiving RFA and SR. But SR may be a superior treatment option with better long-term outcome than RFA in patients with tumor measuring 3.1-5 cm.

Prognosis of colorectal cancer patients is associated with the novel log odds of positive lymph nodes scheme: derivation and external validation.

Background and aim: To construct proper and externally validate cut-off points for log odds of positive lymph nodes scheme (LODDS) staging scheme in colorectal cancer (CRC). Patients and methods: The X-tile approach was used to find the cut-off points for the novel LODDS staging scheme in 240,898 patients from the Surveillance, Epidemiology and End Results (SEER) database and externally validated in 1,878 from the international multicenter cohort. Kaplan-Meier plot and multivariate Cox proportional hazard models were performed to investigate the role of the novel LODDS classification. Results: The prognostic cut-off values were determined as -2.18, and -0.23 (P< 0.001). Patients had 5-year cancer-specific survival rates of 83.8%, 57.4% and 24.4% with increasing LODDS (P< 0.001) in the SEER database. Five-year overall survival rates were 77.2%, 55.0% and 26.7% with increasing LODDS (P< 0.001) in the external international multicenter cohort. Multivariate survival analysis identified both the LODDS classification, the patient's age, the T category, the M status, and the tumor grade as independent prognostic factors in both two independent databases. The analyses of the subgroup of patients stratified by tumor location (colon or rectum), number of retrieved lymph node (< 12 or ≥ 12), TNM stage III, lymph node-negative also confirmed the LODDS as independent prognostic factors (P< 0.001) in both two independent databases. Conclusions: The novel LODDS classification was an independent prognostic factor for patients with CRCs and should be calculated for additional risk group stratification with pN scheme.

Population-based analysis on predictors for lymph node metastasis in T1 colon cancer.

BACKGROUND: In this study, we aimed to identify independent predictive factors for lymph node metastasis (LNM) in T1 colon cancer. METHODS: Data of 8056 eligible patients were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database during 2004-2012. We performed logistic regression analysis to identify predictive factors for LNM. Both unadjusted and adjusted Cox regression analyses were used to determine the association between LNM and patient survival. Finally, we used competing risks analysis and the cumulative incidence function (CIF) to further confirm the prognostic role of LNM in cancer-specific survival (CSS). RESULTS: The overall risk of LNM in patients with T1 colon cancer was 12.0% (N = 967). Adjusted logistic regression models revealed that mucinous carcinoma [odds ratio (OR) = 2.26, P < 0.001], moderately differentiated (OR 1.74, P < 0.001), poorly differentiated (OR 5.16, P < 0.001), and undifferentiated carcinoma (OR 3.01, P = 0.003); older age (OR 0.66, P < 0.001 for age 65-79 years, OR 0.44, P < 0.001 for age over 80 years); and carcinoma located in the ascending colon (OR 0.77, P = 0.018) and sigmoid colon (OR 1.24, P = 0.014) were independent predictive factors for LNM. Adjusted Cox regression analysis showed that positive lymph node involvement was significantly associated with CSS [hazard ratio (HR) = 3.02, P < 0.001], which was further robustly confirmed using a competing risks model and the CIF. CONCLUSIONS: This population-based study showed that mucinous carcinoma, tumor grade, age, and primary tumor location were independent predictive factors for LNM in T1 colon cancer. The risk of LNM should be carefully evaluated in patients with T1 colon cancer, before clinical management.

Over expression of METRN predicts poor clinical prognosis in colorectal cancer.

BACKGROUND: The role of meteorin (METRN) in colorectal cancer has not been reported previously. We aimed to explore the relationship between METRN and colorectal cancer (CRC) prognosis. METHODS: Data were retrieved from the Gene Expression Omnibus database. Gene expression values were log2 transformed and normalized by quantile normalization. Missing values were imputed with the R impute package. Differentially expressed genes were analyzed using the R limma package. METRN expression was compared between normal and CRC tissues and among different stages and subtypes of CRC. We assessed the relationship between METRN and KRAS/BRAF mutations in CRC. Five-year overall (OS), disease-free (DFS), and disease-specific survival (DSS) rates were determined by Kaplan-Meier analysis and analyzed by log-rank test. RESULTS: METRN was expressed at a higher level in CRC (p = .0011) than in normal tissues, especially in advanced stages (p = .0343). METRN expression levels were higher in the MSI (dMMR) subtype (p < .001) and usually with BRAF mutations (p < .0001). METRN overexpression was associated with poor prognosis and low OS (p = .01014), DFS (p = .0146), and DSS (p < .0001) rates. CONCLUSION: METRN overexpression is a predictive factor for poor prognosis in patients with CRC.

Combined preoperative albumin-bilirubin (ALBI) and serum γ-glutamyl transpeptidase (GGT) predicts the outcome of hepatocellular carcinoma patients following hepatic resection.

Background: Liver function is an important prognostic factor for patients with hepatocellular carcinoma. The purpose of this study was to develop and validate a nomogram integrating the albumin-bilirubin (ALBI) and serum γ-glutamyl transpeptidase (GGT) level to predict postoperative overall survival (OS) and disease-free survival (DFS) of hepatocellular carcinoma (HCC). Methods: The effect of combined of ALBI and GGT on HCC prognosis was investigated using univariate and multivariate Cox analyses. The nomogram for OS and DFS were developed, respectively, and their predictive ability was compared with other conventional staging systems, including the American Joint Commission on Cancer (AJCC), Barcelona Clinic Liver Cancer (BCLC) and the Cancer of the Liver Italian Program (CLIP). Results: Combined ALBI and GGT was highly associated with OS (P<0.001) and DFS (P<0.001) of HCC patients treated with hepatic resection. In addition, the C-index of the OS (0.706±0.034) or DFS (0.674±0.032) nomogram in the training cohort was larger than AJCC, BCLC and CLIP. The Akaike information criterion (AICs) of the OS (2178.405) or DFS (2961.018) nomogram in the training cohort was smaller than above staging systems. The results suggested that the OS or DFS nomogram was the most powerful model to predict HCC prognosis. The similar trend was observed in the validation cohort. Conclusion: The novel nomogram integrating ALBI and GGT was highly associated with OS and DFS of postoperative HCC patients.

Comparable rates of lymph node metastasis and survival between diffuse type and intestinal type early gastric cancer patients: a large population-based study.

BACKGROUND AND AIMS: Limited evidence and contradictory results exist regarding the impact of Lauren type, namely diffuse and intestinal types, of lymph node metastasis (LNM) and prognosis for early gastric cancer (EGC). We aimed to compare LNM and prognosis between diffuse and intestinal type EGCs using comprehensive statistical analysis. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify all patients with surgically resected, histologically diagnosed, intestinal or diffuse type EGC. Multivariate logistic regression, multivariate Cox regression, multivariate competing risk model, and propensity score matching were used to analyze association the Lauren type and LNM or prognosis. RESULTS: We identified 5593 EGCs from the SEER database, including 4376 intestinal types and 1217 diffuse types. No positive association was found between LNM and Lauren type (odds ratio, .93; 95% confidence interval [CI], .70-1.24; P = .62) after adjustment for other risk factors. Moreover, diffuse-type EGCs showed a similar prognosis to intestinal type EGCs in both multivariate Cox regression (HR [hazard ratio], .95; 95% CI, .77-1.18; P = .66) and the multivariate competing risk model (subdistribution HR [SHR], .99; 95% CI, .80-1.22; P = .926). Propensity score matching was used, and 733 diffuse types were matched with 733 intestinal types. We did not find any association between the Lauren type and LNM (odds ratio, .98; 95% CI, .71-1.37; P = .934) or prognosis in the univariate Cox regression (HR, .98; 95% CI, .76-1.26; P = .893) and univariate competing risk model (SHR, .98; 95% CI, .76-1.26; P = .893). CONCLUSIONS: Diffuse-type EGC may have a comparable risk of LNM and prognosis to intestinal-type EGC. Nevertheless, these results should be carefully interpreted with caution when choosing endoscopic resection instead of surgery, because the treatment choice for EGC depends on the risk of lymphovascular invasion rather than LNM rate or prognosis.

Comparison of three lymph node staging schemes for predicting the outcome in patients with small bowel adenocarcinoma: A population-based cohort and international multicentre cohort study.

BACKGROUND: The prognostic roles of three common lymph node staging schemes, number of positive lymph nodes (pN), lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS) in small bowel adenocarcinoma (SBA) are unclear. We assessed their prognostic ability in SBA. METHODS: A total of 2128 patients diagnosed with SBA between 1988 and 2010 from the Surveillance, Epidemiology, and End Results (SEER) database and 186 patients from 15 hospitals in France and China were identified. We evaluated the prognostic ability of the schemes in both continuous and stratified patterns using R2, Harrell's C, and time-dependent receiver operating characteristic curve analyses. FINDINGS: For continuous pattern, the LODDS had a better capacity of discrimination and higher accuracy of prognosis than pN and LNR. Similarly, the stratified LODDS classification had a better performance of discrimination and higher accuracy of prognosis than the pN and LNR classification. The multivariable model using the LODDS classification also showed superiorly predictive accuracy and discriminatory capacity to those of the 7th and, 8th TNM node and LNR classification. These results were fully validated in an independent international multicentre cohort. INTERPRETATION: The LODDS scheme showed a better prognostic performance than the LNR or pN schemes in patients with SBA regardless of continuous or stratified pattern. The LODDS scheme could serve as an auxiliary to lymph node staging systems in future revisions of the American Joint Committee on Cancer (AJCC) manual. FUND: This work was funded by the Zhejiang Province Natural Science Fund of China.