Expression, oncological and immunological characterizations of BZW1/2 in pancreatic adenocarcinoma.

Background: Despite the progress in early diagnosis and treatment, prognosis of pancreatic adenocarcinoma (PAAD) is still poor. Basic leucine zipper and W2 domain-containing protein 1 (BZW1) and protein 2 (BZW2) are attached to the basic leucine zipper (bZIP) superfamily. Recently, BZW1 was identified as an important role in glycolysis of PAAD. However, the comprehensive reports about BZW1/2 in PAAD are not sufficient. Methods: RNA-seq data in the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were retrospectively analyzed. We explored the expression of BZW1/2 in PAAD tissues and the associations between BZW1/2 and prognosis. In addition, the potential roles of BZW1/2 in tumor microenvironment (TME) of PAAD were analyzed. Finally, clinicopathological data of 49 patients with PAAD in our institution were collected. Immunohistochemistry was used to determine the expression of BZW1/2 in PAAD samples. Results: BZW1 and BZW2 were upregulated in PAAD tissues compared to normal tissues (p < 0.05). The expression of BZW1/2 were not significantly correlated with gender, grade and stage of PAAD (p > 0.05). High expression of BZW2 was an independent predictor for poor prognosis of PAAD (HR 1.834, 95%CI 1.303-2.581, p = 0.001). And a nomogram to predict overall survival (OS) of PAAD was established with a C-index of 0.685. BZW1 and BZW2 expression were positively associated with T cell mediated immune response to tumor cell and Th2 cells in xCell database. Tumor Immune Single-Cell Hub (TISCH) analyses indicated that BZW1 and BZW2 were mainly expressed in B cells and malignant cells. External cohort furtherly validated that high expression of BZW1 and BZW2 were predictors for poor prognosis of PAAD. Conclusion: We found that BZW1 and BZW2 are highly expressed in malignant cells and B cells in the TME of PAAD. BZW2 is an independent predictor for OS of PAAD. BZW1 and BZW2 expression are positively associated with T cell mediated immune response to tumor cell and Th2 cells in PAAD.

Preoperative Oral Carbohydrate Levels in Patients with Type 2 Diabetes Mellitus: The Clinical Guiding Significance of Free Fatty Acids.

Background: It is still controversial whether preoperative oral carbohydrate (POC) should be applied to patients with type 2 diabetes mellitus (T2DM) in the enhanced recovery after surgery (ERAS) protocol. There is no relevant consensus or indicators to provide guidance as to whether T2DM patients should take POC. Methods: In total, 164 T2DM patients who underwent laparoscopic hepatectomy were analyzed. According to the level of blood free fatty acids (FFAs) and whether the patients received POC, the patients were divided into 6 groups: the low FFA carbohydrate group (LFFAC group), low FFA fasting water group (LFFAF group), medium FFA carbohydrate group (MFFAC group), medium FFA fasting water group (MFFAF group), high FFA carbohydrate group (HFFAC group) and high FFA fasting water group (HFFAF group). Results: Patients with low FFA levels showed better perioperative blood glucose control and a lower incidence of postoperative complications than those in the medium and high FFA groups, especially when patients received POC. Further analyses revealed that the postoperative plasma concentrations of IL-6 and TNF-α were significantly decreased in the POC group compared with the fasting water group, except for patients with high FFA levels. Receiver operating characteristic (ROC) curve analysis revealed that when the FFA concentration was higher than 0.745 mmol/L, the risk of poor blood glucose control during the perioperative period was increased. Conclusions: FFAs have clinical guiding significance for the application of POC in patients with T2DM under ERAS administration. T2DM patients with low FFAs are more suitable for receiving POC.

Identification of Critical Pathways and Potential Key Genes in Poorly Differentiated Pancreatic Adenocarcinoma.

INTRODUCTION: The poorly differentiated pancreatic adenocarcinoma (PDAC) is an extremely lethal neoplasm without effective biomarkers for early detection and prognosis prediction, which is characteristically unresponsive to chemotherapeutic regimens. This study aims at searching for key genes which could be applied as novel prognostic biomarkers and therapeutic targets in PDAC. METHODS: Clinical samples were collected and a comprehensive differential analysis of seven PDAC samples by integrating RNA-seq data of tumor tissues and matched normal tissues from both our cohort and gene expression profiling interactive analysis (GEPIA) were performed to discover potential prognostic genes in PDAC. Pathway enrichment analysis was carried out to determine the biological function of PDAC differentially expressed genes (DEGs), and protein-protein interaction (PPI) network was constructed for functional modules analysis. Real-time PCR was performed to validate expression of hub genes. RESULTS: A total of 126 PDAC-specific expressed genes identified from seven PDAC samples were predominantly enriched in cell adhesion, integral component of membrane, signal transduction and chemical carcinogenesis, IL-17 signaling pathway, indicating that obtained genes might play a unique role in PDAC tumorigenesis. Furthermore, survival analysis revealed that five genes (CEACAM5, KRT6A, KRT6B, KRT7, KRT17) which exhibited high expression levels in tumor tissues were obviously correlated with the prognosis of PDAC patients and KRT7 was positively correlated with KRT6A, KRT6B, KRT17 expression. In addition, real-time PCR demonstrated that the expression level of the hub genes was consistent with RNA-seq analysis. DISCUSSION: The current study suggested that CEACAM5, KRT6A, KRT6B, KRT7, and KRT17 may represent novel prognostic biomarkers as well as novel therapeutic targets for poorly differentiated PDAC.

Identification of critical pathways and potential therapeutic targets in poorly differentiated duodenal papilla adenocarcinoma.

BACKGROUND: Duodenal papilla carcinoma (DPC) is a rare malignancy of the gastrointestinal tract with high recurrence rate, and the pathogenesis of this highly malignant neoplasm is yet to be fully elucidated. This study aims to identify key genes to further understand the biology and pathogenesis underlying the molecular alterations driving DPC, which could be potential diagnostic or therapeutic targets. METHODS: Tumor samples of three DPC patients were collected and integrating RNA-seq analysis of tumor tissues and matched normal tissues were performed to discover differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were carried out to understand the potential bio-functions of the DPC differentially expressed genes (DEGs). Protein-protein interaction (PPI) network was constructed for functional modules analysis and identification of hub genes. qRT-PCR of clinical samples was conducted to validate the expression level of the hub genes. RESULTS: A total of 110 DEGs were identified from our RNA-seq data, GO and KEGG analyses showed that the DEGs were mainly enriched in multiple cancer-related functions and pathways, such as cell proliferation, IL-17signaling pathway, Jak-STAT signaling pathway, PPAR signaling pathway. The PPI network screened out five hub genes including IL-6, LCN2, FABP4, LEP and MMP1, which were identified as core genes in the network and the expression value were validated by qRT-PCR. The hub genes identified in this work were suggested to be potential therapeutic targets of DPC. DISCUSSION: The current study may provide new insight into the exploration of DPC pathogenesis and the screened hub genes may serve as potential diagnostic indicator and novel therapeutic target.

Predictive significance of tumor budding in postoperative liver metastasis of pancreatic neuroendocrine tumors.

BACKGROUND: Although pancreatic neuroendocrine tumors (PNETs) are considered indolent tumors, nearly half of cases metastasize to the liver, which can be lethal. However, effective indicators to predict aggressive behavior have not been well-established. METHODS: In the current study, we explored the prognostic significance of tumor budding in Grade 1-2 PNETs. Hematoxylin-eosin and immunohistochemically stained slides of surgically removed Grade 1-2 PNETs were evaluated. RESULTS: Tumor budding, a histomorphological parameter that corresponds to single cells or small cell clusters (<5 cells), was classified as low (0-10 buds) and high (>10 buds) grade. We observed that tumor budding was correlated with aggressive histopathological parameters, such as T stage, lymph node status, metastasis, and vascular invasion (p < .05). Univariate and multivariate analyses showed that high-grade budding was an independent predictive factor for postoperative liver metastasis (p = .012). Moreover, Grade 1-2 PNETs with high-grade budding was associated with worse overall survival and disease-free survival (p = .0015 and p = .0041, respectively). CONCLUSIONS: We conclude that tumor budding may serve as a valuable parameter in the risk stratification of postoperative liver metastasis and that incorporating tumor budding into histopathological reports may aid in appropriate clinical management.

MiR-26a-5p Inhibits Cell Proliferation and Enhances Doxorubicin Sensitivity in HCC Cells via Targeting AURKA.

OBJECTIVE: To investigate the role of miR-26a-5p in cell proliferation and doxorubicin sensitivity in hepatocellular carcinoma. METHODS: We evaluated miR-26a-5p expression in hepatocellular carcinoma tissues and cell lines by reverse transcription polymerase chain reaction. Cell Counting Kit-8 was used to examine cell proliferation. Relationship between miR-26a-5p and aurora kinase A was evaluated by luciferase report system. Western blot was used to detect expression of aurora kinase A. RESULTS: In this study, we observed miR-26a-5p was downregulated in hepatocellular carcinoma tissues and cell lines. Gain-of-function experiments showed that proliferation rate of hepatocellular carcinoma cells decreased under condition of miR-26a-5p mimics. We found miR-26a-5p mimics could enhance doxorubicin sensitivity of hepatocellular carcinoma cells. Further study showed that aurora kinase A was target gene of miR-26a-5p. Suppression of aurora kinase A could lead to lower cell proliferation and higher doxorubicin sensitivity of hepatocellular carcinoma cells. CONCLUSION: Our study found that miR-26a-5p could inhibit cell proliferation and enhance doxorubicin sensitivity in hepatocellular carcinoma cells by targeting aurora kinase A.

Laparoscopic splenectomy: posterolateral approach in patients with liver cirrhosis and portal hypertension with platelet count lower than 1 × 109/l.

INTRODUCTION: Laparoscopic splenectomy for massive splenomegaly secondary to liver cirrhosis and portal hypertension in patients with an extremely low platelet count (< 1 × 109/l) presents several challenges. The posterolateral laparoscopic splenectomy approach may be a feasible and safe technique for these patients. AIM: To evaluate the feasibility and safety of the posterolateral laparoscopic splenectomy approach in patients with platelet counts < 1 × 109/l secondary to liver cirrhosis and portal hypertension. MATERIAL AND METHODS: In the period from January 2013 to December 2016, 11 patients with platelet counts < 1 × 109/l secondary to liver cirrhosis and portal hypertension underwent posterolateral laparoscopic splenectomy in our institution. Pre-, peri-, and postoperative medical managements were reviewed retrospectively. RESULTS: Patients' median platelet count was 0.7 × 109/l at the time of inpatient admission. The median operating time was 75 min, and the median intraoperative blood loss was 30 ml. One patient underwent intraoperative transfusion. The median duration of postoperative hospital stay was 5 days. No intra- or postoperative complications ensued, all patients were followed for 12-32 months (median: 24 months), and none had postoperative complications. CONCLUSIONS: The posterolateral laparoscopic splenectomy approach is a feasible, safe technique in the treatment of patients with platelet counts < 1 × 109/l secondary to liver cirrhosis and portal hypertension.

Indoleamine 2, 3-dioxygenase and B7-H1 expressions as prognostic and follow-up markers in human pancreatic carcinoma.

This study was to test hypotheses that indoleamine 2, 3-dioxygenase and B7-H1 expressions can be used as prognostic markers in human pancreatic carcinoma (PC). Ninety-five patients were recruited who had undergone radical surgical resection for PC. IDO and B7-H1 expressions in PC tissue specimens were evaluated by immunohistochemistry (IHC) techniques. The clinical and pathological features of these specimens were analyzed. IDO positive, B7-H1 positive, and combined IDO/B7-H1 positive tumors exhibited significant correlations with lymphocytic infiltration, perineural invasion, TNM status, and pathologic grade (p < .05), which tended to show strong correlations with malignant progression of PC. Also, IDO correlated with diabetes mellitus (DM) and HAD scale and B7-H1 correlated with smoke (p < .05). In addition, the correlation analysis indicated that IDO had a positive correlation with B7-H1 (p < .05). Moreover, the results showed that a combination of IDO and B7-H1 expressions could serve as independent prognostic marker after adjusting by Cox proportional hazards regression models (p < .05). IDO and B7-H1 expressions were observed in patient with PC tissues and are important markers for PC malignant progression. A combination of IDO and B7-H1 expression can be served as an independent prognostic marker for PC.

Laparoscopic Liver Resection can be an Effective Way in Obese Patients: A Single Center of 2-Year Experience.

OBJECTIVE: To evaluate the feasibility and safety of laparoscopic liver resection in obese patients, we compared the operative outcomes between obese and nonobese patients, also between laparoscopic liver resection and open liver resection of obese and nonobese patients. MATERIALS AND METHODS: A total of 86 patients suffering from liver resection in our department from January 2013 to December 2014 were divided into 3 groups: the obese patients group for laparoscopic liver resection, the nonobese patients group for laparoscopic liver resection and the obese patients group for open liver resection. Characteristics and clinic data of 3 groups were studied. RESULTS: Characteristics of patients and clinic data were equivalent between the 3 groups. The groups were well matched in age, sex distribution, and liver function (P>0.05). There were no significant differences in the operative time, estimated blood loss, time to oral intake, and postoperative hospital stay in the 3 groups. Tumor diameter of laparoscopic liver resection groups in obese patients was smaller than open liver resections groups in obese patients (P<0.05), but there were no obvious difference of tumor diameter in the laparoscopic liver resection groups of the obese patients and the nonobese patients. CONCLUSIONS: Obesity should not be seen as a contraindication for laparoscopic liver resection, which is a safe and feasible procedure for obese patients.

Laparoscopic Splenectomy and Esophagogastric Devascularization for Liver Cirrhosis and Portal Hypertension Is a Safe, Effective, and Minimally Invasive Operation.

BACKGROUND: In the recent years, laparoscopic splenectomy and esophagogastric devascularization (LSD) for liver cirrhosis and portal hypertension rapidly gained the interest of hepatobiliary surgeons due to its minimal invasion. This study aimed to gather and analyze available data from the observational studies that have compared LSD and open splenectomy and esophagogastric devascularization (OSD) for liver cirrhosis and portal hypertension. MATERIALS AND METHODS: All the studies comparing LSD and OSD for liver cirrhosis and portal hypertension were searched on the available databases, including the Cochrane Central Register of Controlled Trials, Medline, Science Citation Index, EMBASE, China National Knowledge Infrastructure, Wanfang Database, and China Biomedical Database. Data were analyzed using Review Manager software version 5.0. RESULTS: After the literature search, a total of 17 studies were included in the meta-analysis, which involved 1093 patients: 552 in the laparoscopic group and 541 in the open group. The laparoscopic group was shown to have a lower overall postoperative complication rate (0.43; 95% confidence interval [CI; 0.29-0.64]) than the open group (P < .0001), which was not associated with heterogeneity between the studies. The laparoscopic group was shown to have a lower intraoperative blood loss (-320.62; 95% CI [-552.35 to -88.9]), shorter time of oral intake (-29.08 hours; 95% CI [-35.28 to -22.88]), and shorter hospital stay (95% CI [-6.19 to -2.19]) than those of the open group (P < .00001). The operative time of the laparoscopic group was 42.16 minutes longer (95% CI [32.20-52.11]) compared with the open group (P < .00001). There was no significant difference of hospitalization costs between the studies. CONCLUSION: This meta-analysis demonstrated that laparoscopic left lateral resection is a safe and feasible option associated with a reduced overall complication rate. The current evidence suggested that it could be performed routinely in liver centers.

Laparoscopic Versus Open Resection for Liver Cavernous Hemangioma: A Single Center of 2-Year Experience.

OBJECTIVE: To evaluate the feasibility and safety of laparoscopic versus open resection for liver cavernous hemangioma (LCH). MATERIALS AND METHODS: A total of 131 patients suffering from LCH operated in our department between January 2013 and December 2014 were divided into 2 groups: 31 for laparoscopic liver resection (LR) and 100 for open liver resection (OR). RESULTS: Age, sex, presence or absence of chronic liver disease, tumor size, tumor location, type of resection, estimated intraoperative blood loss, operative time, length of postoperative hospital stay, morbidity, and mortality were equivalent between the 2 groups. There were no significant differences in estimated intraoperative blood loss between the LR and OR groups. The operation time of the LR group was longer than the OR group and the hospitalization expenses less than the OR group. However, the time of postoperative hospital stay and time of oral intake were shorter in the LR group than the OR group. The tumor of the LR group was smaller than the OR group. In liver function, alanine aminotransferase after operation of the LR group was lower than the OR group, the same as aspartate transaminase after operation. But there were no significant differences in total bilirubin after operation. CONCLUSIONS: Laparoscopic resection for LCH is a safe and feasible procedure as OR.