Necroptosis-related lncRNA-based novel signature to predict the prognosis and immune landscape in soft tissue sarcomas.

BACKGROUND: Necroptosis-related long noncoding RNAs (lncRNAs) play crucial roles in cancer initiation and progression. Nevertheless, the role and mechanism of necroptosis-related lncRNAs in soft tissue sarcomas (STS) is so far unknown and needs to be explored further. METHODS: Clinical and genomic data were obtained from the UCSC Xena database. All STS patients' subclusters were performed by unsupervised consensus clustering method based on the prognosis-specific lncRNAs, and then assessed their survival advantage and immune infiltrates. In addition, we explored the pathways and biological processes in subclusters through gene set enrichment analysis. At last, we established the necroptosis-related lncRNA-based risk signature (NRLncSig) using the least absolute shrinkage and selection operator (LASSO) method, and explored the prediction performance and immune microenvironment of this signature in STS. RESULTS: A total of 911 normal soft tissue samples and 259 STS patients were included in current study. 39 prognosis-specific necroptosis-related lncRNAs were selected. Cluster 2 had a worse survival than the cluster 1 and characterized by different immune landscape in STS. A worse outcome in the high-risk group was observed by survival analysis and indicated an immunosuppressive microenvironment. The ROC curve analyses illustrated that the NRLncSig performing competitively in prediction of prognosis for STS patients. In addition, the nomogram presents excellent performance in predicting prognosis, which may be more beneficial towards STS patients' treatment. CONCLUSIONS: Our result indicated that the NRLncSig could be a good independent predictor of prognosis, and significantly connected with immune microenvironment, thereby providing new insights into the roles of necroptosis-related lncRNAs in STS.

Development and verification of a novel immunogenic cell death-related signature for predicting the prognosis and immune infiltration in triple-negative breast cancer.

BACKGROUND: Insufficient understanding of the pathogenesis and tumor immunology of triple-negative breast cancer (TNBC) has limited the development of immunotherapy. The importance of tumor microenvironment (TME) in immunotyping, prognostic assessment and immunotherapy efficacy of cancer has been emphasized, however, potential immunogenic cell death (ICD) related genes function in TME of TNBC has been rarely investigated. AIMS: To initially explore the role and related mechanisms of ICD in TNBC, especially the role played in the TME of TNBC, and to identify different relevant subtypes based on ICD, and then develop an ICD-related risk score to predict each TNBC patient TME status, prognosis and immunotherapy response. METHODS AND RESULTS: In this study, we identified distinct ICD-related modification patterns based on 158 TNBC cases in the TCGA-TNBC cohort. We then investigated the possible correlation between ICD-related modification patterns and TME cell infiltration characteristics in TNBC. By using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analysis, we created a risk scoring system (ICD score) to quantifiably evaluate the impact of ICD-related modification patterns in individual TNBC patient. Two different ICD-related modification patterns were found with significant differences in immune infiltration. Lower ICD score was correlated with higher immune infiltration, tumor mutational burden and significantly enriched in immune-related pathways, indicating a strong ability to activate immune response, which might account for relatively favorable prognosis of TNBC patients and could serve as a predictor to select suitable candidates for immunotherapy. We used two independent cohorts, GSE58812 cohort and Metabric cohort to validate prognosis and immunohistochemistry for preliminary in vitro validation. CONCLUSION: This study evidenced that the ICD-related modification patterns might exert pivotal roles in the immune infiltration landscape of TNBC and ICD score might act as potential predictors of prognostic assessment and immunotherapy response. This research provides unique insights for individualize immune treatment strategies and promising immunotherapy candidates screening.

Immunological role and prognostic value of the SKA family in pan-cancer analysis.

Background: The spindle and kinetochore associated (SKA) complex, which plays important roles in proper chromosome segregation during mitosis by maintaining the stabilization of kinetochore-spindle microtubule attachment during mitosis, has recently been reported to exert regulatory effects on the initiation and progression of various human cancer types. Nevertheless, the prognostic significance and immune infiltration of the SKA family across cancers have not been well elucidated. Methods: Using data from three large public datasets, including The Cancer Genome Atlas, Genotype-Tissue Expression, and Gene Expression Omnibus databases, a novel scoring system (termed the SKA score) was developed to quantify the SKA family level across cancers. We then evaluated the prognostic impact of the SKA score on survival and assessed the effect of the SKA score on immunotherapy at the pan-cancer level using multiomics bioinformatic analyses. The correlation of the SKA score and the tumor microenvironment (TME) was also explored in depth. Potential small molecular compounds and chemotherapeutic agents were assessed by CTRP and GDSC analyses. Immunohistochemistry was performed to verify the expression of the SKA family genes. Results: Our results demonstrated a close correlation between the SKA score and tumor development and prognosis in multiple cancers. The SKA score was positively related to cell cycle pathways and DNA replication across cancers, such as E2F targets, the G2M checkpoint, MYC targets V1/V2, mitotic spindles and DNA repair. Additionally, the SKA score was negatively related to the infiltration of various immune cells with antitumor effects in the TME. In addition, the potential value of the SKA score was identified to predict immunotherapy response for melanoma and bladder cancer. We also demonstrated a correlation between SKA1/2/3 and the response to drug treatment across cancers and the promising potential of the SKA complex and its genes as therapeutic targets in cancer. Immunohistochemistry demonstrated that the expression differences of SKA1/2/3 were significant between the breast cancer group and the paracancerous group. Conclusion: The SKA score plays a critical role in 33 cancer types and is highly related to tumor prognosis. Patients with elevated SKA scores have a clear immunosuppressive TME. The SKA score may serve as a predictor for patients receiving anti-PD-1/L1 therapy.

Construction of a novel signature and prediction of the immune landscape in gastric cancer based on necroptosis-related genes.

Necroptosis, a type of programmed cell death, has become a potential therapeutic target for solid tumors. Nevertheless, the potential roles of necroptosis-related genes (NRGs) in gastric cancer (GC) remain unknown. The objective of the present study was to create a necroptosis-related prognostic signature that can provide more accurate assessment of prognosis in GC. Using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data, we identified differentially expressed NRGs. Univariate analysis and Lasso regression were performed to determine the prognostic signature. Risk scores were calculated and all GC patients were divided into high- and low-risk score group according to the median risk score value. The robustness of this signature was externally validated with data from GSE84437 cohort (n = 431). Survival analysis revealed high-risk score patients had a worse prognosis. Results evidenced that the signature was an independent prognosis factor for survival. Single-sample sequence set enrichment analysis (ssGSEA) exhibited different enrichment of immune cells and immune-related pathways in the two risk groups. Furthermore, a predictive nomogram was generated and showed excellent predictive performance based on discrimination and calibration. In addition, the risk score positively correlated with tumor mutational burden and was associated with sensitivity to multiple anti-cancer drugs. Overall, our work demonstrates a close relationship between necroptosis and the prognosis of GC. The signature we constructed with potential clinical application value, can be used for prognosis prediction and being a potential therapeutic responses indicator in GC patients.

An Oxidative Stress-Related Genes Signature for Predicting Survival in Bladder Cancer: Based on TCGA Database and Bioinformatics.

Background: Oxidative stress (OS) responses have been linked to oncogenesis and tumor progression and have recently been regarded as a potential strategy for tumor therapy. However, OS-related therapeutic targets have not been identified to date in the bladder cancer (BC). Methods: The mRNA expression and clinical data of BC were downloaded from the public database. Prognostic risk score signature was constructed using LASSO Cox regression analysis. External validation was performed in GSE15307 cohort. ESTIMATE, CIBERSORT, and ssGSEA algorithm were used to analyze immune cell infiltration and immune microenvironment. Next, functional enrichment analysis was performed to elucidate the mechanism underlying the signature. Additionally, we performed a nomogram to forecast the survival rate of individual BC patients. Results: An OS-related genes (OSRGs) signature was constructed. Overall survival was lower in the high-risk group than in the low-risk group, according to survival analyses. The area under the curve (AUC) of ROC curves further validated the prognostic signature's strong prediction performance in these two cohorts. The risk score was verified as an independent risk factor for BC by independent prognostic analysis. Moreover, as compared to TNM stage alone, a nomogram that integrated the risk score with TNM stage showed a much superior predictive value. Immune infiltration and tumor microenvironment studies indicated that immune cells and functions may play a significant role in carcinogenesis and development. The levels of expression of prognostic genes were shown to be substantially linked with drug sensitivity. Conclusion: We developed a novel OSRGs signature for predicting overall survival and impacting the immune status in patients with BC. New nomogram can help clinicians predict the survival rate of BC patients. These findings shed new light on the potential usage of OSRGs signature in BC patients.

Identification and validation of a hypoxia-related prognostic signature in clear cell renal cell carcinoma patients.

ABSTRACT: Increasing evidence has shown that hypoxia is closely related to the development, progression, and prognosis of clear cell renal cell carcinoma (ccRCC). Nevertheless, reliable prognostic signatures based on hypoxia have not been well-established. This study aimed to establish a hypoxia-related prognostic signature and construct an optimized nomogram for patients with ccRCC.We accessed hallmark gene sets of hypoxia, including 200 genes, and an original RNA seq dataset of ccRCC cases with integrated clinical information obtained by mining the Cancer Genome Atlas database and the International Cancer Genome Consortium (ICGC) database. Univariate Cox regression analysis and multivariate Cox proportional hazards regression were performed to identify prognostic hub genes and further established prognostic model as well as visualized the nomogram. External validation of the optimized nomogram was performed in independent cohorts from the ICGC database.ANKZF1, ETS1, PLAUR, SERPINE1, FBP1, and PFKP were selected as prognostic hypoxia-related hub genes, and the prognostic model effectively distinguishes high-risk and low-risk patients with ccRCC. The results of receiver operating characteristic curve, risk plots, survival analysis, and independent analysis suggested that RiskScore was a useful tool and independent predictive factor. A novel prognosis nomogram optimized via RiskScore showed its promising performance in both the Cancer Genome Atlas-ccRCC cohort and an ICGC-ccRCC cohort.Our study reveals that the differential expressions of hypoxia-related genes are associated with the overall survival of patients with ccRCC. The prognostic model we established showed a good predictive and discerning ability in ccRCC patients. The novel nomogram optimized via RiskScore exhibited a promising predictive ability. It may be able to serve as a visualized tool for guiding clinical decisions and selecting effective individualized treatments.

[Biomechanical analysis of sitting-up movement of knee joint after robot-assisted unicompartmental knee arthroplasty].

OBJECTIVE: To investigate the effect of Navio robot-assisted unicompartmental knee arthroplasty (UKA) on the biomechanics of knee joint during sitting-up movement, and to determine whether UKA can maintain the biomechanical characteristics of knee joint. METHODS: The clinical data of 8 patients with medial compartment osteoarthritis treated with medial fixed platform of Navio robot-assisted UKA between January 2018 and January 2019 and had the complete follow-up data were retrospectively analyzed. There were 4 males and 4 females; the age ranged from 58 to 67 years, with an average of 62.3 years. The disease duration was 6-18 months, with an average of 13 months. The varus deformity ranged from 4° to 6°, with an average of 5°; the knee flexion range of motion was 0°-130°, with an average of 110°. All patients had no extension limitation. The imaging data of bilateral knees during sitting-up movement were collected by biplane C-arm X-ray machine at 3 weeks before operation and 7 months after operation. The three-dimensional models of femur and tibia were established by dual-energy CT scanning, and the three-dimensional models of femur and tibia were matched and synchronized with the femur and tibia in X-ray film by automatic matching tracer software. The biomechanical parameters of femur and tibia were measured, including internal rotation/external rotation, varus/valgus, forward/backward displacement of medial and lateral tibia contact center, and lateral compartment joint space. RESULTS: Eight patients were followed up 5-7 months, with an average of 6.4 months. In the comparison of the affected side before and after operation, except for the difference of varus/valgus which was significant ( t=4.959, P=0.002), the differences in other indicators was not significant ( P>0.05). There were significant differences in varus/valgus and internal rotation/external rotation between healthy and affected sides at 3 weeks before operation ( P<0.05), and the differences in other indicators was not significant ( P>0.05). At 7 months after operation, the difference in the forward and backward displacement of medial tibia contact center was significant ( t=3.798, P=0.007), and the differences in other indicators was not significant ( P>0.05). CONCLUSION: UKA can effectively correct the varus and valgus of the knee joint, and restore the rotational biomechanical characteristics of the affected knee joint. It does not affect the establishment of the lateral compartment joint space, but the medial and lateral tibia contact center still changes.

MiRNA-based model for predicting the TMB level in colon adenocarcinoma based on a LASSO logistic regression method.

ABSTRACT: Some patients with advanced colon adenocarcinoma (COAD) are not sensitive to radiotherapy and chemotherapy, and as such, immunotherapy has become the most popular option for these patients. However, different patients respond differently to immunotherapy. Tumor mutational burden (TMB) has been used as a predictor of the response of advanced COAD patients to immunotherapy. A high TMB typically indicates that the patient's immune system will respond well to immunotherapy. In addition, while microRNAs (miRNA) have been shown to play an important role in treatment responses associated with the immune system, the relationship between miRNA expression levels and TMB has not been clarified in COAD.We downloaded miRNA data and mutational files of COAD from the Cancer Genome Atlas database. Differentially expressed miRNAs were screened in the training group, and miRNAs used to construct the model were further identified using the LASSO logistic regression method. After building the miRNA-based model, we explored the correlation between the model and TMB. The model was verified by a receiver operating characteristic curve, and the correlation between it and 3 widely used immune checkpoints (programmed death receptor-1, programmed death-ligand 1, and cytotoxic T-lymphocyte associated protein-4) was explored. Functional enrichment analysis of the selected miRNAs was performed, and these respective miRNA target genes were predicted using online tools.Our results showed that a total of 32 differentially expressed miRNAs were used in the construction of the model. The accuracies of the models of the 2 datasets (training and test sets) were 0.987 and 0.934, respectively. Correlation analysis showed that the correlation of the model with programmed death-ligand 1 and cytotoxic T-lymphocyte associated protein-4, as well as TMB, was high, but there was no correlation with programmed death receptor-1. The results of functional enrichment analysis indicated that these 32 miRNAs were involved in many immune-related biological processes and tumor-related pathways.Therefore, this study demonstrated that differentially expressed miRNAs can be used to predict the TMB level, which can help identify advanced COAD patients who will respond well to immunotherapy. The miRNA-based model may be used as a tool to predict the TMB level in patients with advanced COAD.

PLCG2 as a potential indicator of tumor microenvironment remodeling in soft tissue sarcoma.

ABSTRACT: The tumor microenvironment (TME) plays an important role in the occurrence and development of soft tissue sarcoma (STS). A number of studies have shown that to inhibit tumor growth, the TME can be remodeled into an environment unsuitable for tumor proliferation. However, a lack of understanding exists regarding the dynamic regulation of TME.In this study, we used CIBERSORT and ESTIMATE calculation methods from the Cancer Genome Atlas (TCGA) database to calculate the proportion of tumor infiltrating immune cells (TICs) and the number of immune and stromal components in 263 STS samples. Differential expression genes (DEGs) shared by Immune Score and Stromal Score were obtained via difference analysis. Univariate Cox regression analysis and construction of protein-protein interaction (PPI) networks were applied to the DEGs.Through intersection analysis of univariate COX and PPI, PLCG2 was determined as the indicator. Further analysis showed that PLCG2 expression was positively correlated with the survival of STS patients. Gene set enrichment analysis (GSEA) showed that genes in the highly expressed PLCG2 group were enriched in immune-related activities. In the low-expression PLCG2 group, genes were enriched in the E2F, G2M, and MYC pathways. Difference analysis and correlation analysis showed that CD8+ T cells, gamma delta T cells, monocytes, and M1 macrophages were positively correlated with PLCG2 expression, indicating that PLCG2 may represent the immune status of TME.Therefore, the level of PLCG2 may aid in determining the prognosis of STS patients, especially the status of TME. These data provide additional insights into the remodeling of TME.

Identification and prognostic value of a glycolysis-related gene signature in patients with bladder cancer.

ABSTRACT: Bladder cancer (BC) is one of the most common malignancies worldwide. Several biomarkers related to the prognosis of patients with BC have previously been identified. However, these prognostic models use only one gene and are thus not reliable or accurate enough. The purpose of our study was to develop an innovative gene signature that has greater prognostic value in BC. So, in this study, we performed mRNA expression profiling of glycolysis-related genes in BC (n = 407) cohorts by mining data from The Cancer Genome Atlas (TCGA) database. The glycolysis-related gene sets were confirmed using the Gene Set Enrichment Analysis (GSEA). Using Cox regression analysis, a risk score staging model was built based on the genes that were determined to be significantly associated with BC outcome. Eventually, the system of risk score was structured to predict a patient's survival, and we identified four genes (CHPF, AK3, GALK1, and NUP188) that were associated with the outcomes of BC patients. According to the above-mentioned gene signature, patients were divided into two risk subgroups. The analysis showed that our constructed risk model was independent of clinical features and that the risk score was a highly powerful tool for predicting the overall survival (OS) of BC patients. Taking together, we identified a gene signature associated with glycolysis that could effectively predict the prognosis of BC patients. Our findings offer a new perspective for the clinical research and treatment of BC.

Exosomal miRNA-16-5p Derived From M1 Macrophages Enhances T Cell-Dependent Immune Response by Regulating PD-L1 in Gastric Cancer.

Macrophages have an affinity to developing tumors and have been shown to play a role in tumor combat and immune surveillance. However, the exact mechanism by which macrophages participate in the anti-tumor immune response remains unclear. Hence, the current study aimed to identify the effect of macrophages on gastric cancer (GC) cells via exosomes. Paired cancerous, tumor-adjacent, and non-cancerous stomach tissues were initially from 68 GC patients. T cells were isolated from peripheral blood mononuclear cells (PBMCs) obtained from both the GC patients as well as the healthy donors. Next, the exosomes were isolated from LPS and IFN-γ-induced PBMCs (M1 macrophages) and co-cultured with human GC cells. Another co-culture system comprised of CD3+ T cells and exosomes-treated GC cells was then performed. BALB/c mice and NOD/SCID nude mice were prepared for effects of exosomal miR-16-5p on tumor growth and anti-tumor immune response in GC in vivo. A relationship between M1 macrophages and the poor survival of GC patients was identified, while they secreted exosomes to inhibit GC development and activate a T cell-dependent immune response. Our results revealed that miR-16-5p was transferred intercellularly from M1 macrophages to GC cells via exosomes and targeted PD-L1. M1 macrophage-derived exosomes containing miR-16-5p were found to trigger a T cell immune response which inhibited tumor formation both in vitro and in vivo by decreasing the expression of PD-L1. Taken together, the key findings of the current study suggest that M1 macrophage-derived exosomes carrying miR-16-5p exert an inhibitory effect on GC progression through activation of T cell immune response via PD-L1. Our study highlights the promise of M1 macrophages as a potential cell-based therapy for GC treatment by increasing miR-16-5p in exosomes.

Nomogram for predicting overall survival in stage II-III colorectal cancer.

PURPOSE: The overall survival (OS) of patients diagnosed with stage II-III colorectal cancer (CRC) can vary greatly, even between patients with the same tumor stage. We aimed to design a nomogram to predict OS in resected, stage II-III CRC and stratify patients with CRC into different risk groups. PATIENTS AND METHODS: Based on data from 873 patients with CRC, we used univariate Cox regression analysis to select the significant prognostic features, which were subjected to the least absolute shrinkage and selection operator (LASSO) regression algorithm for feature selection. Cross-validation was used to confirm suitable tuning parameters (λ) for LASSO logistic regression. Then, the nomogram was used to estimate 3- and 5-year OS based on the multivariable Cox regression model. The survival curves of the two groups were produced using the Kaplan-Meier method. Risk group stratification was performed to assess the predictive capacity of the nomogram. RESULTS: Preoperative mean platelet volume, preoperative platelet distribution width, monocytes, and postoperative adjuvant chemotherapy were identified as independent prognostic factors by LASSO regression and integrated for the construction of the nomogram. The nomogram provided good discrimination, with C-indices of 0.67 and 0.69 for the training and validation sets, respectively. Calibration plots illustrated excellent agreement between the nomogram predictions and actual observations for 3- and 5-year OS. Moreover, a significant difference in OS was shown between patients stratified into different risk groups (P < .001). CONCLUSION: We constructed and validated an original predictive nomogram for OS in patients with CRC after surgery, facilitating physicians to appraise the individual survival of postoperative patients accurately and identify high-risk patients who need more aggressive treatment and follow-up strategies.

Overexpressed lncRNA GATA6-AS1 Inhibits LNM and EMT via FZD4 through the Wnt/ß-Catenin Signaling Pathway in GC.

Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide. Accumulating evidence reveals the significance of long non-coding RNAs (lncRNAs) in various cancers. The current study aimed to evaluate the role of GATA6 antisense RNA 1 (GATA6-AS1) in the epithelial-mesenchymal transition (EMT) and lymph node metastasis (LNM) in GC. GC-related microarray datasets were initially retrieved from the GEO with differentially expressed lncRNAs screened, followed by evaluation of the regulatory relationship between Frizzled 4 (FZD4) and GATA6-AS1. The detailed regulatory mechanism by which GATA6-AS1 influences the Wnt/ß-catenin signaling pathway and GC cell biological behaviors was investigated by treating SGC7901 cells with overexpressed GATA6-AS1, specific antisense oligonucleotide against GATA6-AS1, and lithium chloride (LiCl; activator of the Wnt/ß-catenin signaling pathway). Finally, xenograft nude mice were used to assay tumor growth and LNM in vivo. GATA6-AS1 was poorly expressed, but FZD4 was highly expressed in GC tissues and cells. Elevated GATA6-AS1 reduced FZD4 expression by recruiting enhancer of zeste homolog 2 (EZH2) and trimethylation at lysine 27 of histone H3 (H3K27me3) to the FZD4 promoter region via the inactivated Wnt/ß-catenin signaling pathway, whereby cell invasion, migration, and proliferation, tumor growth, and LNM in nude mice were reduced. Taken together, overexpressed GATA6-AS1 downregulated the expression of FZD4 to inactivate the Wnt/ß-catenin signaling pathway, which ultimately inhibited GC progression.

A nomogram to predict vascular invasion before resection of colorectal cancer.

Vascular invasion (VI) is an important feature for systemic recurrence and an indicator for the application of adjuvant therapy in colorectal cancer (CRC). Preoperative knowledge of VI is important in determining whether adjuvant therapy is necessary, as well as the adequacy of surgical resection. In the present study, a predictive nomogram for VI in patients with CRC was constructed. The prediction model consisted of 664 eligible patients with CRC, who were divided into a training set (n=468) and a validation set (n=196). Data were collected between August 2013 and April 2018. The feature selection model was established using the least absolute shrinkage and selection operator regression model. Multivariable logistic regression analysis was used to construct the predictive nomogram. The performance of the nomogram was evaluated by calibration, discrimination and clinical usefulness. Differentiation, computed tomography (CT)-based on N stage (CT N stage), hemameba and tumor distance from the anus (cm) were integrated into the nomogram. The nomogram exhibited good discrimination, with an area under the curve (AUC) of 0.731 and good calibration. Application of the nomogram in the validation cohort showed acceptable discrimination, with an AUC of 0.710 and good calibration. Decision curve analysis revealed that the nomogram was clinically useful. These findings suggests, to the best of our knowledge, that this may be the first nomogram for individual preoperative prediction of VI in patients with CRC, which may promote preoperative optimization strategies for this selected group of patients.

Alcohol accumulation promotes esophagitis via pyroptosis activation.

Gastroesophageal reflux impairs the mucosal barrier in the distal esophagus, allowing chronic exposure of the squamous epithelium to multitudinous stimulations and inducing chronic inflammation. Esophagitis is a response to inflammation of the esophageal squamous mucosa. Our study clarified that alcohol accumulation could aggravate the progress of esophagitis by inducing pyroptosis; however, Ac-YVAD-CMK, an inhibitor of caspase-1, could effectively suppress the expression of IL-1ß and IL-18 both in vivo and in vitro, reducing the inflammatory response, which is promised to be an agent to inhibit the progression of esophagitis. Additionally, caspase-1-derived pyroptosis is involved in esophageal cancer.

Application of the laparoscopic technique in perihilar cholangiocarcinoma surgery.

INTRODUCTION: The aim of this study is to investigate the feasibility of the application of the laparoscopic technique in perihilar cholangiocarcinoma. METHODS: A total of nine cases of patients who received laparoscopic perihilar cholangiocarcinoma surgery from January 2007 to May 2014 were retrospectively analyzed. The Bismuth subtypes consisted of one case of type I, three cases of type II, two cases of type IIIb, and three cases type IV. RESULTS: Radical resection was conducted in six cases: two cases (type II) with the caudate lobe resection, and two cases (type IIIb) with the left hepatectomy and caudate lobe resection. The mean operation time was 7.3 h (5.5-8.5 h), the mean blood loss was 503 ml (150-850 ml). The pathological tests showed two cases of poorly differentiated adenocarcinoma, three cases of moderately differentiated adenocarcinoma, and four cases of highly differentiated adenocarcinoma. CONCLUSION: Laparoscopic technology in the surgical treatment of perihilar cholangiocarcinoma is an option for the resection approach.

Clinical outcomes of laparoscopic-assisted synchronous bowel anastomoses for synchronous colorectal cancer: initial clinical experience.

The primary aim of this study was to explore the safety and feasibility of laparoscopic-assisted synchronous bowel anastomoses (LSBA) for synchronous colorectal cancer (SCRC). All patients who underwent LSBA for SCRC were retrospectively reviewed and analyzed for clinical and pathological features, technical feasibility and short-term as well as long-term oncological outcomes. Between July 2008 and January 2012, a series of 11 consecutive SCRC patients underwent LSBA. Six patients underwent laparoscopic-assisted right hemicolectomy and anterior resection. Five patients had laparoscopic-assisted right hemicolectomy and sigmoidectomy. There were no intraoperative complications that required open conversions. Mean operation time was 233 (range, 195-285) minutes, and mean estimated blood loss was 224 (range, 100-300) mL. The postoperative course of the patients was uneventful with the mean return to oral intake was 6.9 (range 5-12) days, and mean length of hospital stay was 12.6 (range 9-17) days. All surgical wounds showed good cosmetic outcome, and the mean incision length was 4.1 (range 3.5-5.0) cm. During a median follow-up period of 76 months, no local tumor recurrences were found. LSBA is a potentially feasible and safe procedure for SCRC when performed by an experienced surgeon. Further large clinical controlled trials are warranted to confirm the findings.

The role of AKT1 and autophagy in the protective effect of hydrogen sulphide against hepatic ischemia/reperfusion injury in mice.

Hydrogen sulphide (H 2S) exerts a protective effect in hepatic ischemia-reperfusion (I/R) injury. However, the exact mechanism of H 2S action remains largely unknown. This study was designed to investigate the role of the PtdIns3K-AKT1 pathways and autophagy in the protective effect of H 2S against hepatic I/R injury. Primary cultured mouse hepatocytes and livers with or without NaHS (a donor of H 2S) preconditioning were exposed to anoxia/reoxygenation (A/R) and I/R, respectively. In certain groups, they were also pretreated with LY294002 (AKT1-specific inhibitor), 3-methyladenine (3MA, autophagy inhibitor) or rapamycin (autophagy enhancer), alone or simultaneously. Cell viability, expression of P-AKT1, T-AKT1, LC3 and BECN1 were examined. The severity of liver injury was measured by the levels of serum aminotransferase and inflammatory cytokine, apoptosis and histological examination. GFP-LC3 redistribution and transmission electron microscopy were used to test the activity of autophagy. H 2S preconditioning activated PtdIns3K-AKT1 signaling in hepatocytes. LY294002 could abolish the AKT1 activation and attenuate the protective effect of H 2S on hepatocytes A/R and hepatic I/R injuries. H 2S suppressed hepatic autophagy in vitro and in vivo. Further reducing autophagy by 3MA also diminished the protective effect of H 2S, while rapamycin could reverse the autophagy inhibitory effect and enhance the protective effect of H 2S against hepatocytes A/R and hepatic I/R injuries, consequently. Taken together, H 2S protects against hepatocytic A/R and hepatic I/R injuries, at least in part, through AKT1 activation but not autophagy. An autophagy agonist could be applied to potentiate this hepatoprotective effect by reversing the autophagy inhibition of H 2S.