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.

Predictive factors of pancreatic necrosectomy following percutaneous catheter drainage as a primary treatment of patients with infected necrotizing pancreatitis.

Pancreatic necrosectomy (PN) following percutaneous catheter drainage (PCD) is an effective method of treating patients with necrotizing pancreatitis, however, the predictive factors for PN after PCD have not yet been identified. A total of 74 patients with suspected infected necrotizing pancreatitis (INP) and peripancreatic fluid collection were enrolled in the current study between October 2010 and October 2015. These patients received ultrasound or computer topography guided PCD followed by PN. Patients were divided into two groups: i) A PCD-alone group (n=32) and ii) a PCD+necrosectomy group (n=42). Multivariate analysis revealed that reduction of fluid collection after PCD (P=0.021), maximum extent of peripancreatic necrosis (P=0.019) and multiple organ failure (P=0.017) were predictors of PN following PCD. A prediction model was produced to evaluate the aforementioned factors and indicated that the area under the receiver operating characteristic curve was 0.827. The probability of successful PCD was determined using a prognostic nomogram. Thus, the results of the current study demonstrated that a reduction of fluid collection by <50% following PCD, a maximum extent of peripancreatic necrosis of >50% and multiple organ failure are effective predictors of necrosectomy in patients with INP following PCD failure.

Nissen fundoplication vs proton pump inhibitors for laryngopharyngeal reflux based on pH-monitoring and symptom-scale.

AIM: To compare the outcomes between laparoscopic Nissen fundoplication (LNF) and proton pump inhibitors (PPIs) therapy in patients with laryngopharyngeal reflux (LPR) and type I hiatal hernia diagnosed by oropharyngeal pH-monitoring and symptom-scale assessment. METHODS: From February 2014 to January 2015, 70 patients who were diagnosed with LPR and type I hiatal hernia and referred for symptomatic assessment, oropharyngeal pH-monitoring, manometry, and gastrointestinal endoscopy were enrolled in this study. All of the patients met the inclusion criteria. All of the patients underwent LNF or PPIs administration, and completed a 2-year follow-up. Patients' baseline characteristics and primary outcome measures, including comprehensive and single symptoms of LPR, PPIs independence, and satisfaction, and postoperative complications were assessed. The outcomes of LNF and PPIs therapy were analyzed and compared. RESULTS: There were 31 patients in the LNF group and 39 patients in the PPI group. Fifty-three patients (25 in the LNF group and 28 in the PPI group) completed reviews and follow-up. Oropharyngeal pH-monitoring parameters were all abnormal with high acid exposure, a large amount of reflux, and a high Ryan score, associated reflux symptom index (RSI) score. There was a significant improvement in the RSI and LPR symptom scores after the 2-year follow-up in both groups (P < 0.05), as well as typical symptoms of gastroesophageal reflux disease. Improvement in the RSI (P < 0.005) and symptom scores of cough (P = 0.032), mucus (P = 0.011), and throat clearing (P = 0.022) was significantly superior in the LNF group to that in the PPI group. After LNF and PPIs therapy, 13 and 53 patients achieved independence from PPIs therapy (LNF: 44.0% vs PPI: 7.14%, P < 0.001) during follow-up, respectively. Patients in the LNF group were more satisfied with their quality of life than those in the PPI group (LNF: 62.49 ± 28.68 vs PPI: 44.36 ± 32.77, P = 0.004). Body mass index was significantly lower in the LNF group than in the PPI group (LNF: 22.2 ± 3.1 kg/m2vs PPI: 25.1 ± 2.9 kg/m2, P = 0.001). CONCLUSION: Diagnosis of LPR should be assessed with oropharyngeal pH-monitoring, manometry, and the symptom-scale. LNF achieves better improvement than PPIs for LPR with type I hiatal hernia.

Post-translational modifications of α-synuclein contribute to neurodegeneration in the colon of elderly individuals.

Synucleinopathies and abnormalities in the nerves of the enteric nervous system are hypothesized to be involved in age-associated motility disorders. The aim of the present study was to investigate the expression of various antigens, including α­synuclein (Syn) and its post­translational modified forms, in the human colon at various ages. In addition, the study aimed to correlate the expression of Syn with neurodegeneration. Immunohistochemistry was used to detect the expression of neurofilament (NF), Syn, as well as its nitrated (N) form in the healthy colonic tissue of 12 young (34.08±5.12 years), 10 middle­aged (51.80±3.52 years), and 11 elderly (75.82±7.70 years) individuals. To the best of our knowledge, the current study is the first to demonstrate the presence of N­Syn in the colonic tissue. N­Syn was identified in the upper layer of the mucosa and submucosa layer. Furthermore, Syn (wild­type) was present in the mucosa and submucosa. The number of NF­positive neurons in the submucosal layer declined significantly with age (P<0.01). In addition, Syn and N­Syn significantly increased during aging (P<0.01). Furthermore, a negative correlation was identified between neuron number and synucleinopathies, indicating the abnormal accumulation of both wild-type Syn and N­Syn in the mucosa, submucosa, muscle layer and myenteric plexus. The present study demonstrates that the Syn pathology may be linked to colic neuronal degeneration during normal aging, and this link may cause functional deficits.

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.

Endostar, a novel human recombinant endostatin, attenuates liver fibrosis in CCl4-induced mice.

Decreasing hepatic fibrosis remains one of the major therapeutic challenges in hepatology. The present study aims to evaluate the effect of Endostar on both CCl4-induced liver fibrosis in mice and a hepatic stellate cell (HSC) line. Two main models were studied: (i) a liver fibrosis model was induced in BALB/c mice using CCl4 by intraperitoneal injection for six weeks. Six animal groups were studied: group 1: normal animals; group 2: CCl4-induced liver fibrosis; group 3: CCl4 + Endostar 20 mg/kg/d, six weeks; group 4: CCl4 + Endostar 10 mg/kg/d, six weeks; group 5: CCl4 + Endostar 20 mg/kg/d, four weeks; group 6: CCl4 + Endostar 10 mg/kg/d, four weeks corresponded to different Endostar doses and duration of administration. Liver fibrosis was evaluated by histopathological staining and liver hydroxyproline content. Expressions of collagen type I, α-smooth muscle actin (α-SMA), TGF-ß1 and VEGFR were measured by real-time polymerase chain reaction (PCR). (ii) A liver cell model. HSC-T6 cells were cultured with or without Endostar for 12 h or 24 h. Expressions of collagen type I, α-SMA, and TGF-ß1 were measured by real-time PCR. Collagen I and transforming growth factor ß1 (TGF-ß1) contents in cell supernatant were measured by enzyme-linked immunosorbent assay. As compared to the group without Endostar, liver fibrosis scores and hydroxyproline content were decreased in both Endostar groups (P < 0.05). Moreover, Endostar inhibited the hepatic expression of α-SMA, TGF-ß1, Collagen-1, VEGFR1, and VEGFR2 mRNA (P < 0.05). In the HSC-T6 cell line model, Endostar profoundly inhibited the expression of α-SMA, Collagen-1, and TGF-ß1 mRNA. Expressions of Collagen-1 and TGF-ß1 protein were decreased in the Endostar group as compared to the normal controls in the supernatant of HSC-T6 cells (P < 0.05). Endostar decreased both liver fibrosis in CCl4-induced mice and collagen synthesis in HSCs in vitro. Therefore, this recombinant human endostatin is a promising compound for counteracting liver fibrosis.

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.

Antiviral therapy for hepatitis B in special populations.

There has been much progress in antiviral therapy for chronic hepatitis B; however, antiviral therapy for hepatitis B in special populations is still very challenging. Here, we review antiviral therapy for hepatitis B in special populations, including children and pregnant patients, patients with hepatitis-B-related cirrhosis, patients with acute hepatitis B and chronic hepatitis B surface antigen carriers who receive immunosuppressive or cytotoxic therapy. Major advances have been made in antiviral therapy for hepatitis B in these special populations because of recent increasing availability of oral nucleoside/nucleotide analogues that are well-tolerated and highly effective; however, the findings are mostly based on small uncontrolled short-term studies. More well-designed clinical studies on antiviral therapy for hepatitis B in these special populations are urgently needed to obtain more evidence-based high-quality data.

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.

The urotension II antagonist SB-710411 arrests fibrosis in CCL4 cirrhotic rats.

Urotensin II (UII) is a relatively novel peptide that functions as a potent vasoactive mediator throughout the human body, and also possesses mitogenic and fibrogenic potential. Recent reports showed increased plasma levels of UII in human cirrhotic populations; these levels were correlated with the severity of the disease. We therefore hypothesized that the blockade of UII signaling would arrest the progression of hepatic fibrosis in a rat model of cirrhosis. Cirrhosis was induced in rats by carbon tetrachloride. SB-710411 was used as the UII antagonist. Treatment lasted 8 weeks. Plasma hyaluronic acid (HA) and laminin (LN) were evaluated by radioimmunoassay, and plasma UII was determined by ELISA for the quantity of hydroxyproline (Hyp) in the liver tissues. Fibrosis was assessed histologically. The activated hepatic stellate cells (HSCs) were assessed by α-smooth muscle actin innunostaining. The relative mRNA expression of UII/G protein-coupled receptor (UT), collagen I, collagen III, transforming growth factor ß1 (TGF-ß1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the liver was determined by real-time reverse transcriptase-polymerase chain reaction. Western blot analysis was used to assess liver levels of UT. The mitogenic activity of UII on HSC-T6 cells was also evaluated. Animals with cirrhosis showed increased plasma UII. UII/UT mRNA expression was up-regulated in the liver. Plasma levels of UII were also positively correlated with HA, LN and Hyp. In vivo, treatment with SB-710411 significantly reduced fibrosis development and down-regulated the profibrogenic cytokines TGF-ß1 and TIMP-1. In vitro, UII induced the proliferation of HSCs. This mitogenic effect was significantly inhibited by 10-3 M SB-710411 (p<0.05). These data suggest that the selective blockade of UT has an arresting effect on fibrosis progression in vivo, and inhibits UII-mediated HSC proliferation in vitro.