The expression of LRRN4 was correlated with the progression and prognosis of colon adenocarcinoma (COAD) patients.

Our present study aims to investigate the value of LRRN4 in the progression and prognosis of COAD patients. All COAD and adjacent sample data was downloaded from TCGA database. Survival analysis was performed according to Kaplan-Meier method. The real-time quantitative PCR and immunohistochemistry analysis were conducted for validation in cell lines and tissues. The GSEA was conducted to find functional KEGG pathways. Multivariate Cox regression proportional hazard mode was used to determine whether LRRN4 expression was an independent prognostic factor. The LRRN4 expression in COAD samples were significantly higher than that in adjacent samples, which was consistent with our experiments in cell lines and tissues. Along with the increase of TNM Stage, LRRN4 expression had an increasing tendency. The COAD patients with high LRRN4 expression showed undesirable prognoses. Additionally, the TGF-ß signaling pathway, WNT signaling pathway and other 25 pathways were significantly activated in the high LRRN4 expression group. In conclusion, high LRRN4 expression was closely related to the onset of COAD and it was a poor prognostic factor for COAD patients.

Efficacy evaluation of pepsin in laparoscopic antireflux surgery for gastroesophageal reflux disease.

BACKGROUND: The false positive rate of the PPI test for the diagnosis of typical symptoms of gastroesophageal reflux disease (GERD) is extremely high. OBJECTIVE: This study aims to investigate the effect of the pepsin test on GERD and laparoscopy-assisted anti-reflux surgery for GERD. METHODS: A total of 30 GERD patients were enrolled into this study, and the pre-diagnosis of GERD was determined by symptom evaluation, impedance-pH examination, gastroscopy and pepsin test. All patients underwent surgery. RESULTS: Among the 30 GERD patients, 18 patients were male and 12 were female, and their average age was 58.2 + 12.6 years old. The patients were treated with laparoscopic fundoplication and hiatus hernia repair after preoperative assessment. A total of 28 patients were followed up, one patient developed recurrent symptoms, and one patient developed postoperative dysphagia and received non-operative treatment. Furthermore, the symptom scores were significantly lower at postoperative pepsin detection when compared to the scores before the operation (pepsin: preoperative: 148.8 ± 82.6, postoperative: 30.7 ± 24.6; t= 4.848, P= 0.000). CONCLUSIONS: Laparoscopic fundoplication and hiatus hernia repair may effectively control the symptoms of GERD. Furthermore, the detection of pepsin is non-invasive and easy to operate.

Overexpression of cancer susceptibility candidate 2 inhibited progression of hepatocellular carcinoma cells.

OBJECTIVE: Our study was aimed to investigate the effect of cancer susceptibility candidate 2 (CASC2) on the proliferation, cell cycle, apoptosis, and metastasis of hepatocellular carcinoma (HCC) cells. METHODS: CASC2 expression in tumor tissues and HCC cells was tested by quantitative real-time polymerase chain reaction. After manipulating the expression of CASC2 in Hep3B and HepG2 cells, cells viability, including proliferation, apoptosis, cell-cycle distribution, migration, and invasion were examined by colony formation assay, flow cytometry, wound-healing assay, and transwell assay, respectively. The expression levels of proteins associated with the cell cycle and AKT/mTOR pathway were measured by the western blot. Stably transfected HepG2 cells were used to construct nude mice models, and tumorigenesis was evaluated to investigate the in vivo functions of CASC2 in HCC progression. RESULTS: In tissues and cells of HCC, decreased CASC2 expressions were confirmed. Overexpression of CASC2 made cell cycle stagnated at G0/G1 phase and induced apoptosis. Meanwhile, the overexpression of CASC2 played significant roles in inhibiting the proliferation, migration, and invasion of HCC cells. Furthermore, In vivo experiment indicated that CASC2 restrained the growth of tumors. CONCLUSION: Our study suggested that CASC2 promoted cell apoptosis and suppressed cell growth and metastasis in HCC, indicating that CASC2 might be a useful biomarker of HCC.

Strategy and management of severe hemorrhage complicating pancreatitis and post-pancreatectomy.

PURPOSE: Transcatheter arterial embolization (TAE) is increasingly used as the first-line treatment for hemorrhage complicating pancreatitis and post-pancreatectomy. However, the optimal therapeutic strategy remains unclear. METHODS: Among 1924 consecutive patients, 40 patients with severe pancreatic hemorrhage in Xuanwu Hospital were enrolled between 2005 and 2017. Patients underwent angiography and direct TAE for primary diagnosis and treatment of bleeding. Repeat TAE, watch and wait, and laparotomy were used as the other therapeutic options. Patient data, technical success, and 90-day survival were identified. RESULTS: Pancreatic diseases underlying hemorrhage included acute pancreatitis (n=19, 47.5%), chronic pancreatitis (n=12, 30%), and pancreatic cancer (n=9, 22.5%). A history of percutaneous catheter drainage or pancreatic surgery was seen in 29 patients (72.5%). There were 48 angiographies, 31 embolizations, and 5 laparotomies performed. Rebleeding occurred in 8 patients (20%); 4 of whom underwent re-embolization, 3 had laparotomy, and 1 had conservative treatment. Successful clinical hemostasis was achieved in 37 patients. Complications were observed in only 2 patients with renal failure and 1 patient with hepatic insufficiency. In total, 25 patients (62.5%) were alive at the 90-day follow-up. CONCLUSION: Endovascular management is effective for achieving hemostasis in severe pancreatic hemorrhage with a high success rate and low recurrence, and laparotomy is not suitable for rebleeding cases.

Systematic review and meta-analysis of laparoscopic mesh versus suture repair of hiatus hernia: objective and subjective outcomes.

BACKGROUND: Hiatus hernia (HH) contributes to the pathophysiology of gastroesophageal reflux disease (GERD). Mesh-augmentation of surgical repair might be associated with a reduced risk of recurrence and GERD. However, recurrence rates, mesh-associated complications and quality of life (QOL) after mesh versus suture repair are debated. The aim of this meta-analysis was to determine HH recurrence following mesh-augmentation versus suture repair. Secondary aims were to compare complications, mortality, QOL and GERD symptoms following different repair techniques. METHODS: A systematic literature search of the PubMed, Medline, Embase, Cochrane Library, and Springer database was performed to identify relevant studies comparing mesh-augmentation versus suture repair of the esophageal hiatus. Data pertinent to the benefit versus risk outcomes for these techniques were extracted and compared by meta-analysis. The odd ratio (OR) and mean differences (MD) with 95% confidence intervals were calculated. RESULTS: Eleven studies (4 randomized, 9 non-randomized) comparing mesh (n = 719) versus suture (n = 755) repair were identified. Mesh-augmentation was associated with a reduced overall recurrence rate compared to suture repair [2.6 vs. 9.4%, OR 0.23 (95% CI 0.14-0.39), P < 0.00001]. There was no significant difference in the incidence of complications (P = 0.400) between groups. Improvement in QOL measured by SF-36 was greater following biological mesh-augmentation compared to suture repair (MD = 13.68, 95% CI 2.51-24.85, P = 0.020), as well as GERD-HRQL. No differences were seen for the GIQLI scores with permanent mesh (P = 0.530). Dysphagia improvements were better following suture repair (MD = 1.47, 95% CI 0.20-2.74, P = 0.020). CONCLUSIONS: Mesh repair of HH conferred some advantages and disadvantages at short-term follow-up. Compared to a suture repair alone, mesh-augmentation might be associated with less short-term recurrences, and biological mesh was associated with improved short-term QOL. However, these advantages were offset by more dysphagia. Long-term outcomes are still needed to determine the place of mesh repair of HH.

Step-up mini-invasive surgery for infected pancreatic necrosis: Results from prospective cohort study.

OBJECTIVES: To investigate the clinical efficacy and success predictors of mini-invasive techniques in the treatment of infected pancreatic necrosis (IPN). METHODS: IPN patients admitted to our clinic for treatment by mini-invasive techniques were included in this study prospectively. Treatment was divided into four sequential phases: percutaneous catheter drainage (PCD), mini-incision drainage (MID), video assisted debridement (VAD) and open surgery. Patients progressed to next phase if the infection cannot be controlled. The frequency of surgery, treatment duration, cure rate, incidence of complication and overall mortality were recorded. Risk factors for failure of PCD and MID procedures were detected by logistic regression including demographics, disease severity and morphologic characteristics. RESULTS: From January 2012 to March 2015, a total of 54 consecutive IPN patients were treated, with an average age of 51.2 ± 3.1 years. Of the 54 cases, 18 (33.3%) were cured after PCD; 13 (24.1%) with uncontrolled infection were cured after MID; and the remaining 19 cases (35.2%) were cured after VAD. No open surgery was performed. Overall mortality was 7.4% (4/54), and the incidence of complications was 12.9% (7/54). In multivariable regression, the following factors were associated with high failure rate for both PCD and MID: heterogeneous fluid collection (odds ratio (OR) = 3.14; 95% confidence interval (CI): 1.32 ï½ž 4.25, P = 0.001 for PCD; OR = 2.99; 95% CI: 1.52 ï½ž 5.10, P = 0.006 for MID), multiple infected collections (OR = 4.51; 95% CI: 2.94 ï½ž 8.63; P = 0.000 for PCD; OR = 4.17; 95% CI: 2.77 ï½ž 8.12, P = 0.000 for MID), CT severity index (0 ï½ž 3/4 ï½ž 6/7 ï½ž 10: OR = 2.16; 95% CI: 1.83 ï½ž 3.62, P = 0.031 for PCD; OR = 2.72; 95% CI: 1.78 ï½ž 4.10, P = 0.005 for MID). CONCLUSIONS: Step-up mini-invasive techniques can be considered a first choice in the treatment of IPN. CT is effective to predict success of PCD and MID.

NIM811 downregulates transforming growth factor­ß signal transduction in vivo and in vitro.

Liver fibrosis is the common histological feature of a number of chronic liver diseases, and leads to cirrhosis and hepatocellular carcinoma (HCC). It has been demonstrated that N­methyl­4­isoleucine cyclosporine (NIM811) attenuates CCl4­induced liver fibrosis and inflammation in rats. The present study investigated whether NIM811 downregulated transforming growth factor (TGF)­ß signaling in rats with CCl4­induced liver fibrosis and in HSC­T6 cells. Liver tissues were obtained from rats with CCl4­induced liver fibrosis, with or without NIM811 treatment. HSC­T6 cells were cultured with or without NIM811 for 18 h under serum­free conditions. Expression of collagen I, α­smooth muscle actin (α­SMA), TGF­ß1, TGF­ß receptor I (TßR­I) and TGF­ß pathway downstream signaling molecules were measured by reverse transcription­quantitative polymerase chain reaction and/or western blotting. Collagen I and TGF­ß1 content in the cell supernatant was measured by ELISA. NIM811 profoundly inhibited collagen I, α­SMA, TGF­ß1 and TßR­I expression in the liver of CCl4­treated rats. Phosphorylation of Smad2, 3 and 1/5/8 was decreased in the liver of NIM811­treated groups, accompanied by increased In addition, Smad7 expression compared with the CCl4­treated rats. NIM811 inhibited collagen I, TGF­ß1 and TßR­I expression in HSC­T6 cells. Smad1 mRNA and phospho­Smad1/5/8 protein levels decreased following NIM811 treatment, accompanied by increased Smad7 expression in HSC­T6 cells compared with normal controls. Furthermore, NIM811 also inhibited collagen I mRNA expression in the liver of rats with CCl4­induced liver fibrosis and in HSC­T6 cells. The results suggest that the antifibrotic effect of NIM811 was due to the inhibition of TGF­ß1 and its downstream signaling molecules.

Increased expression of urotensin II is associated with poor prognosis in hepatocellular carcinoma.

Urotensin II (UII) and the urotensin II receptor (UT) exhibit mitogenic effects on tumor growth. Our previous study demonstrated that the UII/UT system is upregulated in hepatocellular carcinoma (HCC) and may enhance the proliferation of human hepatoma cells. However, the clinical significance of UII/UT expression in HCC remains unclear. The present study assessed UII messenger RNA (mRNA) expression in 129 surgical specimens obtained from HCC patients using reverse transcription quantitative-polymerase chain reaction. The association between UII mRNA expression and clinicopathological parameters and overall survival rates was also investigated. The results revealed that UII and UT mRNA expression was significantly increased in HCC tissue compared with adjacent non-cancerous liver tissue (P<0.001). Furthermore, a significant correlation was identified between UII expression and histological differentiation (P<0.01), tumor size (P<0.01) and tumor stage (P=0.026). Kaplan-Meier survival analysis indicated that overall survival time was significantly shorter in patients with high UII expression, compared with those with low UII expression (P<0.001). Multivariate analyses indicated that UII expression was an independent predictor of overall survival (odds ratio, 1.12; P<0.001). In addition, UII mRNA was correlated with vascular endothelial growth factor mRNA expression. Therefore, UII expression is an independent biomarker for the prognosis of patients with HCC and thus, the UII/UT system may present a novel therapeutic target for the treatment of HCC.

Human recombinant endostatin Endostar attenuates hepatic sinusoidal endothelial cell capillarization in CCl4­induced fibrosis in mice.

The aim of the present study was to detect the effect of the recombinant human endostatin Endostar on hepatic sinusoidal capillarization in CCl4­induced murine models of liver fibrosis. The liver fibrosis model was induced in BALB/c mice using intraperitoneal injection of CCl4 for 6 weeks. Animals were divided into the following six treatment groups: Group 1, normal animals; group 2, CCl4­induced liver fibrosis; group 3, CCl4+Endostar 20 mg/kg/day for 6 weeks; group 4, CCl4+Endostar 10 mg/kg/day for 6 weeks; group 5, CCl4+Endostar 20 mg/kg/day for 4 weeks; and group 6, CCl4+Endostar 10 mg/kg/day for 4 weeks. The average number of fenestrae per hepatic sinusoid was determined using transmission electron microscopy. Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) 1 and 2 expression was detected by western blot analysis. There were significant differences in the number of fenestrae per sinusoid between the normal control and untreated model fibrotic mice (P<0.01), and between the untreated model and Endostar­treated mice (P<0.05). Endostar treatment was associated with reduced levels of VEGFR1 and VEGFR2 in liver tissues (P<0.01), as well as with decreased hepatic sinusoidal endothelial cell capillarization in CCl4­induced mouse models of liver fibrosis, and this effect may involve the VEGF pathway. However, further studies are required to confirm its involvement in other causes of liver fibrosis.

Elevated DNA damage response in pancreatic cancer.

Pancreatic cancer is one of the most aggressive and intractable human malignant tumors and a leading cause of cancer-related death across the world, with incidence equaling mortality. Because of the extremely high malignance, this disease is usually diagnosed at its advanced stage and recurs even after surgical excision. Pancreatic adenocarcinoma is generally thought to arise from pathological changes of pancreatic duct, and the pancreatic ductal adenocarcinoma accounts for more than 90 % of malignant neoplasms of the pancreas. To date, scientists have revealed several risk factors for pancreatic cancer, including smoking, family history, and aging. However, the underlying molecular mechanism remains unclear. Meanwhile, more mutations of DNA damage response factors have been identified in familial pancreatic cancers, implying a potential link between DNA damage and pancreatic cancer. DNA damage is a recurring phenomenon in our bodies which could be induced by exogenous agents and endogenous metabolism. Accumulated DNA lesions cause genomic instability which eventually results in tumorigenesis. In this study, we showed obvious DNA damages existed in human pancreatic cancer, which activated DNA damage response and the DNA repair pathway including ataxia-telangiectasia mutated, DNA-PK, CHK1, and CHK2. The persistent DNA damage in pancreatic tissue may be the source for its tumorigenesis.

Multisystem Langerhans cell histiocytosis with liver dysfunction as the first presentation: A case report.

Langerhans cell histiocytosis (LCH) is a rare disease of unknown etiology characterized by oligoclonal proliferation of Langerhans cells. The diagnosis of LCH is complicated by the fact that it may involve multiple organ systems and its clinical presentation and course varies, ranging from an isolated to a multisystem disease. We report a 35-year-old male with LCH involving multiple systems, including the bones, lungs, spleen, liver and bile ducts, whose first clinical presentation was liver dysfunction. The patient was diagnosed following a skull biopsy that revealed infiltration of Langerhans cells. However, a liver biopsy revealed sclerosing cholangitis (SC) with no signs of Langerhans cell infiltration, and the clinical manifestations of the involved organs were atypical, leading to a delayed diagnosis. The patient was in partial remission following chemotherapy. In conclusion, findings of this case may aid our understanding of the pathophysiology of LCH and in improving its diagnosis and treatment.

Increased expression of urotensin II and GPR14 in patients with cirrhosis and portal hypertension.

Urotensin II (UII) and its receptor (UT or GPR14) are involved in liver fibrosis and portal hypertension. Nevertheless, expression of the UII/UT system in the liver of patients with portal hypertension has not been elucidated. UII and UT gene expression were quantified in liver biopsy samples from patients with hepatitis-B-virus-associated cirrhosis and portal hypertension, and from normal controls by using quantitative real-time PCR. The liver distribution of UT was determined by means of immunohistochemistry and immunofluorescence. Western blot analysis was used to assess liver levels of UT. Simultaneously, we measured intra-operative free portal venous pressure (FPVP) and collected plasma for UII measurement by ELISA. UT expression at the mRNA and protein level was enhanced significantly in the liver of patients with cirrhosis and portal hypertension, compared with that in healthy controls. UT protein expression was concentrated mainly in the Kupffer cells and sinusoidal endothelial cells. In cirrhotic tissue, UII gene expression was increased 5-fold in comparison to that in normal liver tissue. Plasma UII level was higher in cirrhotic patients compared with controls and was correlated with FPVP (r=0.807; P<0.001) and UII mRNA in the liver (r=0.802; P<0.001). These findings suggest that the intrahepatic UII/UT system has an important pathophysiological role in cirrhosis and portal hypertension.

Radiofrequency ablation combined with transarterial chemoembolization for unresectable primary liver cancer.

BACKGROUND: Radiofrequency ablation (RFA) followed by transarterial chemoembolization (TACE) for unresectable primary liver cancer (PLC) has not been widely discussed. In this study, the outcome of the combination of RFA with TACE was retrospectively evaluated. METHODS: From May 2003 to March 2008, 127 consecutive PLC patients with a median age of 56.4 +/- 8.8 years underwent RFA plus TACE. All patients were deemed to have unresectable PLC based on their tumor characteristics. The maximal diameter of the tumor was between 1.5 cm and 10.0 cm. Twenty-six cases with small ( 5.0 cm) tumors were included in this study. RFA was performed using a RITA Medical Systems expandable electrode device, which was followed by first-time TACE administration one to two months later. RESULTS: Technical success of RFA was achieved in all 127 patients with no severe treatment-related complications. RFA was performed percutaneously in 16 (13.5%) cases, by laparoscopic approach in 19 (15.7%), and through laparotomy in the remaining 92 (72.4%). RFA response was classified as complete ablation in 48 cases, nearly complete ablation in 28, and partial ablation in 51. The total 1-, 2-, and 3-year survival rates after RFA were 83.1%, 55.7%, and 43.7%, respectively. The survival rates at 3 years were 78.6%, 28.1%, and 0 for complete ablation, nearly complete ablation, or partial ablation groups, respectively. Three-year disease-free survival rates for the complete ablation and nearly complete ablation groups were 50.3% and 21.3%, respectively. RFA response and liver function were significant variables influencing survival time as analyzed using the Cox regression model. CONCLUSION: RFA could be the first-line exterminate treatment for unresectable PLC, and TACE following RFA may assist in eradicating the peripheral viable tissue and micro-metastasis.