Macit Sandikci

No association of pre-microRNA-146a rs2910164 polymorphism and risk of hepatocellular carcinoma development in Turkish population: A case-control study

AIM MicroRNAs (miRNAs) are an abundant class of small non-protein coding RNAs with posttranscriptional regulatory functions as tumor suppressors and oncogenes. Aberrant expression and structural alteration of miRNAs are considered to participate in tumorigenesis and cancer development. It has been suggested that the presence of single nucleotide polymorphisms in precursor miRNAs (pre-miRNAs) can alter miRNA processing, expression, and/or binding to target mRNA and represent another type of genetic variability that can contribute to the susceptibility of human cancers. A G/C polymorphism (rs2910164), which is located in the sequence of miR-146a precursor, results in a change from G:U to C:U in its stem region. METHODS To determine the association of the miR-146a rs2910164 polymorphism on the risk of hepatocellular carcinoma (HCC) development in Turkish population, a hospital-based case-control study was designed consisting of 222 subjects with HCC and 222 cancer-free control subjects matched on age, gender, smoking and alcohol status. The genotype frequency of miR-146a rs2910164 polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS No statistically significant differences were found in the allele or genotype distributions of the miR-146a rs2910164 polymorphism among HCC and cancer-free control subjects (p>0.05). CONCLUSION Our results demonstrate that the miR-146a rs2910164 polymorphism has no major role in genetic susceptibility to hepatocellular carcinogenesis, at least in the population studied here. Independent studies are needed to validate our findings in a larger series, as well as in patients of different ethnic origins.

Potential Benefits of Combined N‐Acetylcysteine and Ciprofloxacin Therapy in Partial Biliary Obstruction

This study investigates the potential benefits of antibiotics and N‐acetylcysteine (NAC), a mucolytic agent, in patients who are candidates for endoscopic retrograde cholangiopancreatography (ERCP) due to partial bile duct obstruction. In total, 102 patients who had choledocholithiasis and choledochal dilatations by abdominal ultrasonography were included in the study. The patients were divided into placebo and NAC therapy groups. Physiological saline (equal volume with NAC solution) and ciprofloxacin (2 × 200 mg/d intravenously) were administered to the placebo group, and NAC (1800 mg/d intravenously) and ciprofloxacin (2 × 200 mg/d intravenously) were administered to the NAC group. In both groups, treatment protocols were administered for 7 days before ERCP. Total and direct bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), C‐reactive protein (CRP), alkaline phosphatase (ALP), gamma‐glutamyl transpeptidase (GGT), white blood cell (WBC) count, and neutrophil percent (NE%) levels were measured before the 7‐day treatment protocol. The same measurements were also evaluated before ERCP. In the NAC group, the levels of ALP, GGT, WBC, CRP, and NE% decreased significantly (P < .001), whereas a significant decrease did not occur in the placebo group. The combined usage of NAC and ciprofloxacin can be an alternative therapeutic option until ERCP is performed in partial cholestatic patients.

Massive lower gastrointestinal hemorrhage secondary to rectal hemorrhoids in elderly patients receiving anticoagulant therapy: case series.

Hemorrhages secondary to hemorrhoids are common but they are usually occult or oozing type with low amounts. Acute massive rectal hemorrhage is usually originated from upper GI (UGI) bleeding [1]. However, lower GI bleeding (LGI) may occasionally cause massive bleeding. In elderly patients, generally the reasons of colonic hemorrhage are diverticulum (17–40%), arteriovenous malformations (2–30%), colitis (9–21%), colonic neoplasms (11–14%), post-polypectomy, and anorectal pathologies (4–10%) [2]. Colonoscopy is the most important diagnostic tool for determining the focus of bleeding [3]. Generally massive LGI hemorrhage secondary to hemorrhoids has been reported in the literature as case presentations after surgical hemorrhoidectomy and rubber band ligation. Massive hemorrhoidal bleeding without any intervention has not been reported [4]. Case Reports

Expression of Mesenchymal, Hematopoietic, and Biliary Cell Markers in Adult Rat Hepatocytes After Partial Hepatectomy

BACKGROUND AND PURPOSE It has been suggested that liver regeneration can occur either by differentiated adult hepatocytes which retain the capability for several rounds of replication or by hepatic progenitor cells, depending on the number of hepatocytes lost. We sought to study the differentiation potential of hepatocytes following partial hepatectomy (PH) in rats. METHODS Using immunohistochemistry and confocal microscopy we studied the distribution of cytokeratin 7 (CK7), CK19, vimentin, desmin, CD34, and c-kit among adult rat liver hepatocytes after PH at various times just after hepatectomy and after 8, 16, 24, 36, 48, and 60 hour and 6 and 16 days. RESULTS Vimentin, c-kit, and desmin positivity were observed in regenerating hepatocytes in the early stages. Desmin and vimentin staining were also demonstrated in stellate cells. Staining enhancement in stellate cells progressed from day 3 to day 6. No liver sections were stained positive for CD34, CK19, or CK7. CONCLUSION After PH, mature hepatocytes revealed their potential to regain the markers that they do not express when they are quiescent. This result supported the plasticity and differentiation potential of adult hepatocytes during regeneration.

Expression of c-kit protooncogen in hepatitis B virus-induced chronic hepatitis, cirrhosis and hepatocellular carcinoma: has it a diagnostic role?

Aim:  There are more than 350 million people worldwide chronically infected with hepatitis B virus (HBV), who are at high risk for the development of hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Because of the conflicting results about c‐kit expression in HCC and the key role played by c‐kit in gastrointestinal stromal tumours (GIST) and other solid tumours, the aim of this study was to determine c‐kit expression in the course of hepatitis B infection.

Relationship between programmed cell death-1 polymorphisms and clearance of hepatitis B virus

Programmed cell death‐1 (PD‐1) plays a critical role in regulating T‐cell function during hepatitis B virus (HBV) infection. This study investigated the relationship between the polymorphisms of PD‐1 gene and the susceptibility to HBV infection. Single nucleotide polymorphisms (SNPs) in PD‐1 gene at positions +7146 G>A (guanine to adenine substitution) and +7209 C>T (cytosine to thymine substitution) were analysed using a polymerase chain reaction–restriction fragment length polymorphism (PCR‐RFLP) method in 220 subjects with chronic hepatitis B infection and 165 spontaneous clearance of HBV subjects. However, no statistically significant differences were found in the genotype distributions of the PD‐1 +7146 G>A and PD‐1 +7209 C>T polymorphisms among chronic hepatitis B and spontaneous clearance subjects. According to stratified analyses, borderline significance was observed between PD‐1 +7146 GA genotype and risk of HBV chronicity in the subgroup of male gender (OR = 1.88, 95% 0.95–3.71; P = 0.07). Our findings demonstrate for the first time that the PD‐1 +7146 G>A and PD‐1 +7209 C>T polymorphisms have not been any major role in genetic susceptibility to chronicity of HBV infection, at least in the population studied here. Independent studies are needed to validate our findings in a larger series, as well as in patients of different ethnic origins.

Atherosclerosis and acetylsalicylic acid are independent risk factors for hemorrhage in patients with gastric or duodenal ulcer

OBJECTIVE Risk factors for hemorrhage due to gastric and/or duodenal ulcer in patients diagnosed by upper gastrointestinal (GI) endoscopy were investigated in the present study. METHODS Medical records of 350 patients (226 males, 124 females) diagnosed as duodenal or gastric ulcers by GI endoscopy in the gastroenterology clinic were scanned retrospectively. Upper GI hemorrhage was detected in 92 patients by upper endoscopic examination. The medical history of non-steroidal anti-inflammatory drugs (NSAIDs) or acetylsalicylic acid (ASA) usage and the presence of coronary artery disease (CAD) were investigated in all patients with or without hemorrhage. Results were evaluated by Chi-square test and logistic regression analysis. RESULTS The mean age of the patients was 50.4 ± 15.7 years (range: 25 to 82 years). Hemorrhage due to gastric or duodenal ulcer was identified in 92 patients (26%). Mean age was 64.6 ± 11.4 years in patients with hemorrhage and 45.7 ± 13.9 years in patients without hemorrhage. ASA usage was more common than NSAID in patients with ulcer hemorrhage (NSAID usage n=35 (40%); ASA usage n=51 (60%); p=0.035). Hemorrhage was reported in 20% of the females and in 28% of the males who have ulcer (p=0.055). Risk factors for hemorrhage were CAD (OR:24.75, 95% CI=1.6-96.7, p=0.001), ASA usage (OR:9.76, 95% CI=2.1-37.5, p=0.021), NSAID usage (OR: 4.72, 95%CI=1.1-16.5, p=0.032), age (OR: 11.59, 95% CI= 2.7-12.1, p=0.001), and male gender (OR: 2.56, 95% CI= 0.8, 9.6, p=0.052). CONCLUSION Advanced age, atherosclerosis, male gender and NSAID administration (particularly aspirin) are the major risk factors of upper GI hemorrhage in patients with gastric and/or duodenal ulcer.

New therapeutic option with N-acetylcysteine for primary sclerosing cholangitis: two case reports.

Primary sclerosing cholangitis is a progressive, cholestatic hepatic disease of unknown etiology. It is characterized by progressive inflammation, destruction, and fibrosis of the intrahepatic and extrahepatic bile ducts. Several medical therapies have been tried such as penicilamin, colchicine, methatraxate, cyclosporine, tacrolimus, and ursodeoxycholic acid. Treatment with mucolytic agents in excessively high viscosity conditions appears to have an important role. N-acetylcysteine (NAC), as a mucolytic agent, may fascilitate the drainage in partial obstructions by decreasing the mucous viscosity. We suggest that NAC and ursodeoxycholic acid have markedly positive effects on the clinical course of cholangitis and cholestasis when used together by affecting bile viscosity. Here, we present two cases treated with NAC. NAC capsul therapies at 800 mg/day were administered to two patients with primary sclerosing cholangitis. Clinical and laboratory parameters of patients saw significant improvement.

Relationship between IL28B gene rs8099917 polymorphism and SVR in Turkish patients with hepatitis C virus genotype 1

BACKGROUND AND OBJECTIVE The hepatitis C virus (HCV) which infects 3% of the worlds population is a global challenge. Recently, genome-wide association studies (GWAS) have identified that the IL28B gene rs8099917 polymorphism was associated with the response to the pegylated-interferon alpha/ribavirin (PegIFNα/RBV) combination therapy in patients infected with HCV genotype 1. IL28B gene rs8099917 polymorphism should be determined before beginning treatment of HCV-infected patients to predict an individuals response. The aims of this study were to analyze the correlation between IL28B gene rs8099917 (T/G) polymorphism and PegIFNα/RBV therapy outcome in the Turkish population. METHODS Genotypes of the IL28B gene rs8099917 (T/G) single nucleotide polymorphism (SNP) were determined in 308 patients with HCV infection by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. One group consisted of 148 patients with a sustained virological response (SVR), whereas the second group consisted of 160 nonresponders (non-SVR). RESULTS Allele and genotype associations of IL28B gene rs8099917 polymorphism with a sustained virological response were observed in comparisons between the SVR and non-SVR groups (P<0.001). In addition, the characteristics of the subjects did not differ between these two groups except for age and fibrosis stage (P<0.05). Additionally, neither SVR nor rs80999917 genotypes were associated by HCV RNA levels. CONCLUSIONS In conclusion, the rs8099917 polymorphism was thus found strongly associated with a sustained virological response to therapy in Turkish patients infected with HCV genotype 1. Consequently, we suggest determining IL28B gene rs8099917 polymorphism of patients with HCV genotype 1 before onset of treatment.

Recurrent hypersplenism caused by giant accessory spleen due to portal hypertension after splenectomia.

Splenectomy is one of the primary choices of treatment in immune thrombocytopenic purpura. However, the disease may relapse despite splenectomy. One of the leading causes of relapse is the presence of accessory spleen, which may become enlarged significantly with underlying pathologies such as presence of portal hypertension. The accessory spleen, which will inevitably enlarge in time, may grow significantly within a short period of time in the presence of portal hypertension and may thus be misdiagnosed as a tumoral mass. Presence of ectopic spleen should be borne in mind in patients diagnosed with immune thrombocytopenic purpura with relapsing hypersplenism following splenectomy. This article discusses a patient developing portal hypertension secondary to chronic liver disease and presenting with a significantly enlarged accessory spleen as well as hypersplenism findings.