Evaluation of the concordance between the stage of the disease and Ki-67 proliferation index in gastroenteropancreatic neuroendocrine tumors.

AIM: This study aimed to determine the degree of concordance between TNM staging used in the determination of the prognosis of gastroenteropancreatic neuroendocrine tumor (GEP-NET) patients and the Ki-67 proliferation index value used in the grading of these tumors and investigate the most reliable prognostic parameter among them. MATERIALS AND METHODS: The medical files of the patients with GEP-NET who were diagnosed or followed up in Erciyes University Faculty of Medicine were retrospectively examined and demographic characteristics, survival times, grade of these tumors, histopathologically detected Ki-67 values, and histopathological characteristics were recorded and evaluated statistically. RESULTS: The mean age (53.09±14.6 years; range, 16-85 years) of all (n=141) the patients was estimated. The patient population included 72 (51.1%) female and 69 (48.9%) male patients, with a male/female ratio of 0.95. The most frequently encountered primary sites were the stomach (33.3%), and then in decreasing oder of frequency the pancreas (27%), colon-rectum (15.6%), the small intestine (12.8%), and the appendix (11.3%). The GEP-NET of the patients was in grade 1 (G1) (n: 103; 73%), grade 2 (G2) (n: 24; 17%), and grade 3 (G3) (n: 14; 10%). The GEP-NET of the patients was stage I (n: 66; 46.8%), stage II (n: 14; 9.9%), stage III (n: 12; 8.5%), and stage IV (n: 49; 34.8%). In the statistical analysis, Ki-67 increased in parallel with the stage of the disease (P<0.001). As Ki-67 increased at a rate of 1%, survival rates of the patients decreased 1.027 times (P=0.01). Five-year survival rates of the patients were 88% in G1, 44% in G2, and 24% in G3. Patients in G2 and G3 had a 6.67 and 12.38 times lower chance of survival compared with G1 patients, respectively. Survival rates of stage IV patients were 5.6 times lower relative to stages I and II patients, respectively (P<0.001). The median 5-year survival rates of the patients were 90% in stage I, 100% in stage II, 47% in stage III, and 46% in stage IV. In univariate analysis, age of the patients, grade, stage of the tumor, and lymph node metastases were found to be parameters that affected overall survival, whereas no significant correlation was found between the sex of the patient and the primary organ from which the tumor originated and survival rates. However, in the multivariate analysis, survival rates decreased inversely with age, whereas no significant correlation was found between grade and stage of the tumor and survival rates. CONCLUSION: In conclusion, a decrease in the average survival rate in parallel with an increase in the grade of the tumor was more prominent compared with a decrease in survival rates in accordance with an increase in the stage of the tumor. This indicates that in the prediction of prognosis in patients with GEP-NET, the Ki-67 value can be a more important evaluation factor relative to staging.

Red blood cell distribution width as a non-invasive marker for the assessment of inflammation in non-alcoholic steatohepatitis.

BACKGROUND/AIMS: The aim of this study was to assess the association between red cell distribution width and inflammation in biopsy proven non-alcoholic steatohepatitis. METHODOLOGY: Fifty four subjects with non-alcoholic steatohepatitis and thirty nine controls were enrolled for the study. Liver biopsy specimens were scored by using non-alcoholic fatty liver disease activity score by a single experienced liver pathologist. RESULTS: Red cell distribution width was higher in the severe inflammation group in non-alcoholic steatohepatitis (p < 0.05). The areas under the receiver operating characteristic curves for the predictive performance of aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase and red cell distribution width in identifying inflammation in non-alcoholic steatohepatitis were 0.55 (0.41-0.68), 0.51 (0.37-0.64), 0.53 (0.39-0.67) and 0.73 (0.59-0.84) respectively and the differences of these values between red cell distribution width and other parameters were found to be statistically significant (p < 0.05). To determine the grading of inflammation, the specificity for using the red cell distribution width as an indicator in non-alcoholic steatohepatitis patients was calculated to be 73.3%, with 79.5% sen- sitivity. CONCLUSION: Red cell distribution width was a sensitive and specific method for the assessment of the inflammation in patients with non-alcoholic steatohepatitis.

Circulating microRNAs in patients with non-alcoholic fatty liver disease.

AIM: To identify novel non-invasive biomarkers for non-alcoholic fatty liver disease (NAFLD). METHODS: Twenty patients with histologically proven NAFLD and 20 controls were included. All NAFLD cases were scored using the NAFLD activity score. The relative expressions of miR-197, miR-146b, miR-10b, miR-181d, miR-34a, miR-122, miR-99a and miR-29a were analyzed using real-time polymerase chain reaction. RESULTS: Serum levels of miR-181d, miR-99a, miR-197 and miR-146b were significantly lower in biopsy-proven NAFLD patients than in the healthy controls. Serum levels of miR-197 and miR-10b were inversely correlated with degree of inflammation and miR-181d and miR-99a were inversely correlated with serum gamma glutamyl transferase levels in non-alcoholic steatohepatitis patients. CONCLUSION: NAFLD is associated with altered serum miRNA expression pattern. This study provides clues for defining the non-invasive diagnosis of NAFLD.

Noninvasive assessment of liver damage in chronic hepatitis B.

AIM: To evaluate the efficacy of the aspartate aminotransferase/platelet ratio index (APRI) and neutrophil-lymphocyte (N/L) ratio to predict liver damage in chronic hepatitis B (CHB). METHODS: We analyzed 89 patients diagnosed with CHB by percutaneous liver biopsy and 43 healthy subjects. Liver biopsy materials were stained with hematoxylin-eosin and Masson's trichrome. Patients' fibrosis scores and histological activity index (HAI) were calculated according to the Ishak scoring system. Fibrosis score was recognized as follows: F0-1 No /early-stage fibrosis, F2-6 significant fibrosis, F0-4 non-cirrhotic and F5-6 cirrhotic. Significant liver fibrosis was defined as an Ishak score of ≥ 2. APRI and N/L ratio calculation was made by blood test results. RESULTS: The hepatitis B and control group showed no difference in N/L ratios while there was a significant difference in terms of APRI scores (P < 0.001). Multiple logistic regression analysis revealed that the only independent predictive factor for liver fibrosis in CHB was platelet count. APRI score was significantly higher in cirrhotic patients than in non-cirrhotic patients. However, this significance was not confirmed by multiple logistic regression analysis. The optimum APRI score cut-off point to identify patients with cirrhosis was 1.01 with sensitivity, specificity, positive predictive value and negative predictive value of 62% (36%-86%), 74% (62%-83%), 29% (13%-49%) and 92% (82%-97%), respectively. In addition, correlation analyses revealed that N/L ratio has a negative and significant relationship with HAI (r = -0.218, P = 0.041). CONCLUSION: N/L ratio was negatively correlated with HAI. APRI score may be useful to exclude cirrhosis in CHB patients.

Investigation of genome instability in exfoliated colonic epithelial cells and in mitogen-stimulated lymphocytes of patients with ulcerative colitis.

OBJECTIVE: The present study aimed to evaluate the micronucleus (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in the mitogen-stimulated lymphocytes of patients with ulcerative colitis (UC). In addition, we assessed MN frequency in exfoliated colonic epithelial cells obtained from both the diseased and healthy colonic mucosa of patients. DESIGN: The study was conducted in 22 newly diagnosed patients with UC and in 22 healthy controls. MN, NPB and NBUD values scored in binucleated (BN) cells were obtained from the mitogen-stimulated lymphocytes of patients and control subjects. In addition, the MN values in exfoliated epithelial cells obtained from the diseased and healthy colonic mucosa of patients were evaluated. RESULTS: We found significantly higher MN, NPB and NBUD frequencies in the BN cells of patients with UC than in those of the control subjects (1.61 ± 0.75 vs. 0.89 ± 0.29, 3.93 ± 1.91 vs. 1.39 ± 1.10, and 1.55 ± 0.89 vs. 0.64 ± 0.48, p = 0.001). Also, a statistically significant difference was found between MN frequencies obtained from the diseased and healthy colonic mucosa of patients (1.07 ± 0.46 vs. 0.59 ± 0.21, p = 0.001). No significant relationship was found between age and MN frequency in patients with UC (r = 0.076, p = 0.735). CONCLUSION: Increased MN, NPB and NBUD frequencies observed in both the lymphocytes and exfoliated colonic epithelial cells obtained from patients with UC may reflect genomic instability.

Endoscopic topical application of Ankaferd Blood Stopper® in gastrointestinal bleeding.

AIM: This was a prospective study investigating the efficacy of Ankaferd Blood Stopper(®) (ABS), an herbal preparation, in patients with upper gastrointestinal (UGI) bleeding. MATERIALS AND METHODS: A total of 30 patients (22 male, 8 female) who had UGI bleeding (with differing causes) were included in the study. ABS was used to stop the bleeding. RESULTS: Primary hemostasis was achieved in 26 of the 30 cases. CONCLUSIONS: ABS is an effective and safe agent to use in patients with UGI bleeding.

Molecular characterization of a novel entecavir mutation pattern isolated from a multi-drug refractory patient with chronic hepatitis B infection.

BACKGROUND: Prolonged antiviral treatment results in selection and accumulation of resistant strains in quasispecies pool in hepatitis B virus (HBV) infection. OBJECTIVES: The aim of this study was to characterise a novel HBV pattern which shows resistance to lamivudine, adefovir dipivoxil and entecavir using in vitro phenoyping assay. STUDY DESIGN: A male 36 years old patient diagnosed with anti HBe-positive chronic hepatitis B (CHB) had received lamivudine treatment for 7 years following an initial unsuccessfull interferon treatment. The therapy had been switched to adefovir and then to entecavir when breakthrough occcured during each treatment. This led only to a temporary HBV DNA decline which soon was followed by viral breakthrough despite the lack of known entecavir resistance mutations. Patient died after 9 months of entecavir treatment from liver failure. A total of 434 clones from 6 different serum samples were analysed retrospectively. HBV genomes bearing mutation patterns suggestive of antiviral resistance were analysed by in vitro phenotyping assay. RESULTS: Dominance of a clone carrying L80LV, L91I, M204I, S219A, N238D, Y245H changes was detected in the last serum sample of the patient just before his death. This pattern displayed 30.4 fold resistance to entecavir when compared with the wild type HBV by in vitro phenotyping assay. CONCLUSION: A novel mutation pattern showing a high degree of resistance to entecavir was documented. In this pattern, the S219A and Y245H mutations mainly seem to contribute to the emergence of ETV resistance.

Effects of testosterone gel treatment in hypogonadal men with liver cirrhosis.

INTRODUCTION: Hypogonadism characterized by low serum testosterone level, loss of libido, small testes, impotence and gynecomastia is a common clinical situation in male patients with advanced chronic liver disease. The aim of the study was to assess the efficacy and safety of testosterone replacement on muscle strength, bone mineral density (BMD), body composition and gynecomastia in hypogonadal men with liver cirrhosis. METHODS: Sixteen hypogonadal male cirrhotic patients were included and twelve completed the study. Abdominal USG and/or MRI were performed to exclude hepatocellular cancer. Testogel 50mg/day was administered for 6 months. Liver enzymes, hormone profiles and muscle strength were evaluated monthly. Body composition parameters, BMD and gynecomastia were evaluated before and after 6 months. RESULTS: Serum free testosterone level was higher (20.13 ± 10.06 pmol/L; 57.26 ± 39.56 pmol/L, P=0.002) after treatment. Testosterone replacement resulted in an increase in muscle strength (34.03 ± 7.24 kg; 39.18 ± 5.99 kg, P<0.001), the subscapular site subcutaneous fat tissue (P=0.012) and the sum of the four regions (P=0.04). Subareolar breast tissue was lower (28.83 ± 17.18 mm; 15.00 ± 6.74 mm, P=0.007) after treatment. No significant adverse effects were detected. DISCUSSION: Testosterone gel 50mg/day raises free testosterone to values below supraphysiological levels in cirrhotic men. Transdermal testosterone replacement improves muscle strength, ameliorates gynecomastia, alters body fat distribution and causes upper body adiposity in hypogonadal men with cirrhosis. Application of testosterone gel, which undergoes no hepatic first-pass metabolism, seems as a safe and well-tolerated agent in liver cirrhosis as compared to other anabolic steroids, which may be associated with various adverse events.

Is increased colon subepithelial collagen layer thickness in diabetic patients related to collagenous colitis? An immunohistochemical study.

In this study, we evaluated immunohistochemically whether increased thickness of the colon subepithelial collagen layer in diabetic patients relates to collagenous colitis. A total of 100 patients (25 in each group) were included in this study. There were diabetic patients with chronic diarrhea in the first group, diabetic patients without chronic diarrhea in the second group, non-diabetic patients with chronic diarrhea in the third group, and control patients in the fourth group. The endoscopic biopsy specimens were obtained from the rectum, sigmoid colon, and descending colon. The thickness of the subepithelial collagen layer was measured using the ocular micrometer method. The immunohistochemical staining was performed with type 1 collagen and fibronectin antibody. The thickness of the colon subepithelial collagen layer in diabetic patients with or without diarrhea was significantly greater than that in control patients. This thickened subepithelial collagen layer in diabetic patients was stained with fibronectin antibody, but not with type 1 collagen antibody in the immunohistochemical study. These immunohistochemical staining characteristics were not similar to those in collagenous colitis, but were similar to those in normal subjects. Increased colon subepithelial collagen layer thickness in diabetic patients does not relate to collagenous colitis.

Clostridium difficile infection frequency in patients with nosocomial infections or using antibiotics.

BACKGROUND/AIMS: Clostridium difficile is the most common cause of nosocomial infectious diarrhea. The frequency of colonization in hospitalized patients varies between 10 and 43%. METHODOLOGY: Clostridium difficile common antigen was investigated in stool samples of 50 patients who developed nosocomial diarrhea (group 1), 65 outpatients who attended the clinic after development of diarrhea during antibiotic use (group 2), 18 patients with active chronic inflammatory bowel disease (group 3), and 30 control patients were studied. The Latex agglutination test and the toxin A was performed to investigate the presence of the Clostridium difficile common antigen in stool samples. The possible predisposing factors for nosocomial infection were analyzed. RESULTS: Clostridium difficile common antigen was found positive in 27.7% and 14% of group 2 and group 1, respectively while negative in stools of patients with inflammatory bowel disease. Asymptomatic fecal Clostridium difficile carriage in healthy volunteers was 3.3%. The antibiotic that induced diarrhea the most was clindamycin in group 1, and ampicillin-sulbactam in group 2. Enema was found to be the most important risk factor for C. difficile in hospitalized patients. CONCLUSIONS: The Clostridium difficile common antigen was detected more frequently in antibiotic-associated diarrhea patients than in nosocomial diarrhea patients. Clostridium difficile-associated diarrhea was also more frequent in immunosuppressive patients with uremia and diabetes mellitus.

An uncommon lesion: gastric xanthelasma.

Although the clinical significance of gastric xanthelasmas is unclear, they are important lesions because they may be confused with malignant lesions. The etiopathogenesis is also unclear, but chronic gastritis, Helicobacter pylori (H. pylori) infection, diabetes mellitus and hyperlipidemia have been implicated. Xanthelasma is more frequent in women and its incidence increases with age. The lesions are frequently located in the stomach, and less frequently in the esophagus, duodenum and the colon. The lesions have a yellowish-white appearance, are between 0.5 and 10 mm in size and can be single or multiple. Xanthelasmas were found to be associated with chronic gastritis, gastrointestinal anastomoses, intestinal metaplasia, and H. pylori infection. These lesions are predisposing conditions for gastric cancer. Therefore, endoscopic biopsy is mandatory and careful follow-up is required. In this paper, four patients who attended hospital with abdominal pain and dyspepsia and by chance were found to have xanthelasmas on endoscopic examination are presented, and gastric xanthelasmas are discussed.

The prevalence of unrecognized adult celiac disease in Central Anatolia.

BACKGROUND: The aim of this study is to assess the prevalence of unrecognized adult celiac disease in Central Anatolia of Turkey and establish if prevalence figures are similar to other reports in the international literature. METHODS: Subjects were randomly selected from patients at the time of blood sampling because of a routine examination or suspicion of some disorder other than celiac diseases and were screened with anti-tissue transglutaminase IgA and serum IgA measurements. Duodenal biopsies were taken from the patients who were found positive for anti-tissue transglutaminase IgA and had low IgA levels. RESULTS: A total of 906 subjects between 20 and 59 years of age were included. Small bowel biopsies were performed for 55 of the 906 participants. Fifty-two of 55 participants taken biopsies had anti-tissue transglutaminase IgA levels greater than 15 IU/mL and 3 of them had low IgA levels. Celiac disease was diagnosed as 9 of 906 (0.99%). The majority of the patients with celiac disease had nonspecific gastrointestinal symptoms. There was no correlation between the titers of anti-tissue transglutaminase IgA and the severity of histopathologic findings. CONCLUSIONS: In this study, we found that unrecognized adult celiac disease in Central Anatolia affects approximately 1% of the population, and the major constellation of symptoms are nonspecific gastrointestinal related. Serologic data are not adequate for a definite diagnosis, but the anti-tissue transglutaminase IgA test has high diagnostic value and may be used as screening tool. Confirmation with intestinal biopsy is required for a definite diagnosis.

Efficacy of five days of subcutaneous octreotide treatment after sclerotherapy in preventing rebleeding from esophageal varices.

BACKGROUND/AIMS: Acute variceal bleeding is the most severe consequence of portal hypertension. Mortality due to bleeding among cirrhotic patients is high; between 30 and 50% die within six weeks of the first bleeding episode. This dismal outcome has led to attempts both to stop acute bleeding and to prevent rebleeding. The aim of this study was to investigate the efficacy of subcutaneous octreotide treatment, administered after emergency sclerotherapy, in preventing rebleeding of esophageal varices METHODS: After a bolus injection of 50 microgram octreotide, 34 patients, forming the standard therapy (ST) group, received octreotide infusion at a rate of 50 microgram/h until endoscopic sclerotherapy performed within 36 hours. The same procedure was applied to another 27 patients in the maintenance therapy (MT) group in which octreotide was given at 100 microgram/8h via subcutaneous (sc) route after sclerotherapy for five days. In both groups, sclerotherapy was repeated on the 5th-7th day. Patients were followed for three weeks for rebleeding. RESULTS: Nine patients rebled in the ST group but only one patient bled in the MT group (3.7% vs. 26.5% vs. 3.7%; p<0.05). Transfusion requirement and duration of hospitalization period were similar in both groups. CONCLUSIONS: This study suggests that maintenance subcutaneous octreotide therapy is effective in controlling rebleeding episodes.

Spontaneous bacterial peritonitis due to Brucella infection.

Brucella infection is a systemic disease, but the microorganism rarely causes infections in the gastrointestinal system such as hepatitis, cholecystitis, colitis and pancreatitis. Spontaneous bacterial peritonitis due to Brucella is extremely rare. Herein, we report a case of cirrhosis complicated with nongranulomatous hepatitis and peritonitis, both due to Brucella. A 63 year-old man with diabetes mellitus was admitted to hospital with complaints of weakness, backache, abdominal pain and abdominal swelling. On the basis of physical examination and laboratory findings, cryptogenic cirrhosis and spontaneous bacterial peritonitis were diagnosed. Due to persistent fever and backache, serum Brucella agglutination test was performed and found to be positive. Brucella melitensis was isolated from ascitic fluid culture. Liver biopsy findings revealed cirrhosis and a nongranulomatous hepatitis which was thought might be due to Brucella infection. Doxycycline and rifampicin, in addition to diuretics were administered for spontaneous ascites infection due to Brucella. A week later, the patient's condition improved and he became afebrile. After two months of therapy, the ascites had almost disappeared.

Detection of Helicobacter pylori using nested polymerase chain reaction and rapid urease test in gastric biopsy samples.

BACKGROUND/AIMS: The purpose of this study was to compare nested polymerase chain reaction and rapid urease test findings in the diagnosis of Helicobacter pylori infection. METHODS: Two gastric biopsy specimens were obtained from each of 64 patients and polymerase chain reaction and rapid urease test were performed. DNA extraction was followed by amplification with two primer pairs from the urease A gene of Helicobacter pylori genome. RESULTS: Fourty two patients (65.6%) had a positive rapid urease test result while 22 (34.4%) had a negative result for Helicobacter pylori. Sixty of 64 patients (93.8 %) had a positive result with the nested polymerase chain reaction method. Four patients with negative nested polymerase chain reaction results also had negative rapid urease test results. All of the eighteen patients with rapid urease test-negative results were positive with nested polymerase chain reaction. The number of nested polymerase chain reaction-positive patients (93.8%) was significantly higher than rapid urease test-positive (65.6%) and first round polymerase chain reaction-positive (53.1%) patients (P<0.001). CONCLUSIONS: Our results indicate that the nested polymerase chain reaction is more specific and sensitive than the rapid urease test for detecting Helicobacter pylori in gastric biopsy samples.