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Volume 75 - 2012 - Fasc.2 - Original articles

Factors influencing the prognosis of patients with intrahepatic cholangiocarcino- ma

Background and aims : The outcome of surgical treatment of patients with intrahepatic cholangiocarcinoma (ICC) is poor. This study was designed to analyze prognostic factors following surgical treatment for ICC. Patients and methods : A structured telephone interview was con- ducted in 132 patients who were surgically treated for ICC. Fifteen clinical and pathological factors that may influence post-operative survival were analyzed by using Cox proportional hazards model. Results : The accumulative 1-, 3-, 5-year survival rate of the 132 patients was 51.3%, 21.6%, and 11.8% respectively. The mean survival time in patients with elevated serum carbohydrate antigen (CA) 19-9 at the time of the operation was shorter than in patients with normal serum CA19-9 (9.6 ± 24.7 vs 16.1 ± 6 months, P < 0.01). The median survival time in patients with well-differentiated carcinoma was longer than in those with poorly differentiated ICC (23.9 ± 7.8 vs. 11.2 ± 5.0 months, P < 0.01). Patients who were treat- ed with hepatectomy and lymph node dissection had a longer sur- vival time than those treated with hepatectomy only (16.0 ± 5.8 vs 10.2 ± 3.6 months, P < 0.01). Multivariate analysis showed that mode of surgical treatment, lymph node metastasis, serum level of CA 19-9 and pathological differentiation grade of ICC predicted postoperative survival. Conclusions : Hepatectomy with lymph node dissection is associated with an improved survival for patients with ICC. This strategy may be recommended for the surgical treatment of ICC. (Acta gastroenterol. belg., 2012, 75, 215-218).

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Small bowel metastases from melanoma : does videocapsule provide additional information after FDG positron emission tomography ?

Finding small bowel metastases of melanoma can be important because surgical removal of unique small bowel metastasis of melanoma could improve survival. In this study, we evaluated if capsule endoscopy provides additional information after Pet CT has been performed. In this series of 9 patients collected from 3 university centers, capsule endoscopy influenced the therapeutic decision (to perform or not a surgical segmental resection) in 2/9 patients. All metastatic lesions were found in the proximal bowel. Capsule identified jejunum metastases in one case while Pet CT was negative, and identified metastases while Pet CT result was not conclusive. In one case PET CT identified mesenteric metastases while capsule was negative. SBCE influenced therapeutic decision in 2/9 patients concerning the decision of performing small bowel resection or not. In 1 patient SBCE changed the stage of the disease without affecting medical therapeutic strategy. The prognosis of patients with positive PET and/or capsule findings is very limited (2/3 died within the year). In selected patients, capsule endoscopy can provide complementary information once PET CT has been performed. (Acta gastroenterol. belg., 2012, 75, 219-221).

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Association between single nucleotide polymorphisms of the transient receptor potential vanilloid 1 (TRPV-1) gene and patients with irritable bowel syndrome in Korean populations

Background and study aims : Transient receptor potential vanil- loid type 1 (TRPV1) plays a crucial role in pain perception and its expression is up-regulated in patients with irritable bowel syn- drome (IBS). The aim of this study was to investigate the potential association between Single nucleotide polymorphism (SNPs) of the TRPV-1 gene and patients with IBS. Patients and methods : We chose to focus on three SNPs in the human TRPV1 coding region (rs222749, rs9894618 and rs222747) in 80 healthy controls and 103 IBS patients. We developed the high resolution melting (HRM) method to determine the genotyping of rs222747 and rs9894618 and the genotyping of rs222749 was also determined by direct sequencing method. Results : The CG genotype of rs222747 was 58.8% in controls and 45.6% in the IBS group. The GG genotype of rs222747 was 15.0% in controls and 20.4% in the IBS group. The CT genotype of rs222749 was 31.3% in controls and 32.0% in the IBS group. The CC genotype of rs9894618 was 98.8% in controls and 100.0% in the IBS group. There was no significant difference in allele fre- quency of these three SNPs of the TRPV1 gene between controls and the IBS group. AlsO. no significant difference was observed between the IBS subtypes. Conclusions : These results suggest that the SNPs of the TRPV1 gene may not be associated with IBS in Korean populations. Further studies with large cases are needed to validate the results of the present study. (Acta gastroenterol. belg., 2012, 75, 222-227).

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Expression of IFNAR2 mRNA in peripheral blood mononuclear cells of patients with HCV infection

Background : To investigate the differences of interferon-a/ss receptor 2 (IFNAR2) mRNA expression level in peripheral blood mononuclear cells (PBMCs) between different stages of hepatitis C virus (HCV) infection and to determine the correlation with the effectiveness of interferon therapy. Methodology : 58 patients, positive for anti-HCV antibodies, were divided into three groups depending on their clinical symp- toms : acute hepatitis (4 cases), chronic hepatitis (46 cases) and liver cirrhosis (8 cases). 15 volunteers served as healthy controls. PBMCs were purified by density gradient centrifugation and IFNAR2 mRNA was amplified from these cells by a reverse tran- scription-polymerase chain reaction (RT-PCR) assay. Results : The detection rate of IFNAR2 mRNA was 87.9% (51/58 cases) in the PBMCs of patients with HCV infection, signif- icantly higher than that in the control group (33.3%, 5/15 cases ; P < 0.05). While the positive rate was 93.5% (43/46 cases) in the chronic hepatitis group, which was significantly higher than that in the liver cirrhosis group (50%, 4/8 cases ; P < 0.05). Furthermore, there is no significant difference in the positive rates for HCV-RNA of PBMCs among groups (P > 0.05). The positive rate of IFNAR2 mRNA in PBMCs was not correlated with the viral load of HCV- RNA in serum (P > 0.05). However, higher expression of IFNAR2 mRNA in the PBMCs did correlate with the effectiveness of inter- feron therapy (P < 0.05). Conclusions : HCV infection up-regulates the expression of IFNAR2 mRNA in PBMCs. IFNAR2 mRNA expression in the chronic hepatitis group was higher than that in the liver cirrhosis group, and significantly correlated with the effectiveness of inter- feron therapy, which was independent of the viral load. (Acta gastroenterol. belg., 2012, 75, 228-233).

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Nitric Oxide donor drugs improve the distribution and engraftment of trans- planted hepatocytes in the liver

Background : Hepatocyte transplantation could be an alterna- tive to liver transplantation for the treatment of metabolic diseases, however this therapy is still limited by the loss of transplanted cells in the portal radicles before their entry into the sinusoids to engraft. Therefore, we investigated the effect of glyceryl trinitrate on hepatic sinusoids and on the efficacy of cell engraftment in a syngenic mice model. Methods : We first assessed the effect of GTN portal infusion on the parenchymal spreading of colored microspheres. Hepatocytes transplantation in a syngenic mice model was then performed con- comitantly with GTN infusion. The distribution of transplanted hepatocytes and their ultimate engraftment were analysed. Results : After GTN perfusion 27% of microspheres shifted from the portal to the sinusoidal zone. Transplanted hepatocytes distri- bution changed significantly in the portal and parenchymal zones from respectively 53 ± 2% and 46.8 ± 2% in control animals to 32.5 ± 2.4% and 67.5 ± 2.4% in GTN-treated animals. At days 7 and 15, we noted a significantly better engraftment in GTN group vs. controls (60 ± 4 vs. 37 ± 2 transplanted hepatocytes in 20 fields × 400). Conclusions : Portal perfusion of GTN improved the access of microspheres and transplanted hepatocytes to the sinusoidal bed and also improved the percentage of cell engraftment in the liver. These results suggest that drug dilatation of portal pedicles prior to transplantation increases the efficiency of hepatocyte grafting. (Acta gastroenterol. belg., 2012, 75, 234-239).

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Effects of sitagliptin in diabetic patients with nonalcoholic steatohepatitis

Background & Aims : Preliminary evidence suggests that inhibi- tion of dipeptidyl peptidase (DPP)-IV preserves pancreatic beta cell function in patients with type 2 diabetes (T2D). However, its effects on liver histology in nonalcoholic steatohepatitis (NASH), hepatic complication of diabetes, have not yet been adequately explored. The present open-label, single-arm observational pilot study investigated the effects of one year of treatment with a dipep- tidyl peptidase-IV inhibitor, sitagliptin, on liver histology, body mass index (BMI), and laboratory parameters in NASH patients with T2D. Patients and Methods : Paired liver biopsies from 15 diabetic patients with NASH (7 males, 8 females ; mean age : 49.7 ± 8.1 years (range : 36-62)) before and after one year of therapy with sitagliptin 100 mg once daily were studied. Clinical and laboratory parameters were recorded. Results : Treatment with sitagliptin resulted in a significant decrease in ballooning (P = 0.014) and NASH scores (P = 0.04), while the reduction in the steatosis score was of borderline statisti- cal significance (P = 0.054). These effects were accompanied by a significant reduction in body mass index, AST, and ALT levels. Conclusion : Our study suggests that sitagliptin ameliorates liver enzymes and hepatocyte ballooning in NASH patients with T2D and may have therapeutic implications. (Acta gastroenterol. belg., 2012, 75, 240-244).

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