Retreatment of Chronic Hepatitis C Infection with Telaprevir : Turkey Experience.

BACKGROUND AND AIMS: Patients with genotype 1 chronic hepatitis C virus (HCV) who do not have a sustained virologic response to therapy with peginterferon alfa and ribavirin have a low likelihood of success with retreatment. MATERIALS AND METHODS: Voluntary patients aged 18 and older with genotype-1 chronic HCV and with no exclusion criteria were -included. Treatment was organized as following: telaprevir was administered at a dose of 750 mg every 8 hours ; Peg-IFN α-2a was administered at a dose of 180 mcg per week and ribavirin was -administered at a dose of 1000-1200 mg per day. HCV-RNA levels were measured before treatment, at 4, 12, 24 weeks of treatment, after treatment and after 24 weeks of treatment. Sustained virologic response was defined as undetectable HCV-RNA after 24 weeks of treatment. RESULTS: Sustained virologic response was obtained in 37 patients (74%). Breakthrough (BT) or early relapse was seen in 6 patients (12%) in total. Treatment had to be discontinued because of treatment related adverse events in 7 patients (14%). CONCLUSION: Triple combination therapy including telaprevir is significantly better than classical Peg-IFN α and ribavirin therapy in patients with chronic hepatitis-C infection.

Baseline and salt-stimulated paraoxonase and arylesterase activities in patients with chronic liver disease: relation to disease severity.

BACKGROUND: It has been recently reported that serum paraoxonase (PON1) and arylesterase (ARE) activities may be significantly reduced in patients with chronic liver disease. The aim of the study was to investigate the relations between serum PON1 and ARE activities and the degree of liver damage in patients with chronic liver injury. METHODS: We studied a total of 75 patients with chronic liver disease (50 patients with cirrhosis and 25 patients with chronic hepatitis) and 25 healthy comparison subjects. Baseline and salt-stimulated PON1 and ARE activities were determined in all study participants. RESULTS: Baseline and stimulated PON1 and ARE activities were significantly lower in patients with chronic liver disease than in controls. Cirrhotic patients in Child-Pugh classes B and C subgroups had significantly reduced PON1 and ARE activities compared with Child-Pugh class A patients (both P-values <0.01). Receiver operating characteristic curve analysis showed that serum ARE activity was the most efficient test for identifying the presence and severity of chronic liver injury. CONCLUSION: Baseline and stimulated PON1 and ARE activities are reduced in patients with chronic liver disease. Serum ARE activity could be a suitable biomarker for the evaluation of the presence and severity of chronic liver damage.

The role of triple therapy, age, gender and smoking on the genotoxic effects of Helicobacter pylori infection.

The role of age, gender and smoking on both the genotoxic effects of Helicobacter pylori and the efficacy of eradication therapy in a group of patients with gastritis was investigated. Gastritis was confirmed by endoscopy and biopsy, and the presence of H. pylori by urease testing. Pre- and post-treatment peripheral blood lymphocyte cultures were prepared from 17 patients and 25 metaphases per patients were analysed for sister chromatid exchange (SCE), a well-established technique for the evaluation of human exposure to toxic agents. Treatment with omeprazole, clarithromycin and amoxycillin triple therapy eradicated H. pylori in 94% of patients and significantly reduced the SCE frequency. Pre-treatment SCE frequency was found to be positively correlated with age. Female smokers tended to have higher post-treatment SCE frequencies than male smokers, and pre- and post-treatment SCE frequencies were higher in older males than in older females. Eradication therapy decreased the genotoxicity of H. pylori, but age in males and smoking in females may decrease treatment efficacy.

The relationship between c-erbB-2 oncogene expression and clinicopathological factors in gastric cancer.

Gastric carcinoma is one of the most common carcinomas and a leading cause of death from cancer in Turkey. The relationship between clinicopathological features of the disease and oncogenes is under investigation. In this retrospective study we investigated the relationships between expression of c-erbB-2 oncoprotein and grade, stage and pathological characteristics of the tumour, and prognosis. Formalin-fixed, paraffin-embedded tissue sections were prepared from gastrectomy specimens from 55 patients with gastric carcinoma. The tissue sections were stained immunohistochemically to reveal c-erbB-2 protein. Six (10%) of the tumours stained positively for c-erbB-2 protein. There was no statistically significant association (P > 0.5) between c-erbB-2 staining and tumour grade, stage or pathological characteristics (necrosis, lymph-node infiltration), or between staining and prognosis. The results suggest that overexpression of c-erb-B-2 protein is not related to the pathological characteristics of the tumour in gastric carcinoma and is not an important prognostic indicator.

Expression of p53 protein and prognosis in gastric carcinoma.

A study was carried out to assess whether p53 expression is related to tumour type, grade or pathological characteristics, or to prognosis, in gastric cancer. Immunohistochemical studies were performed to detect p53 protein in sections from 55 consecutive gastrectomy or partial gastrectomy specimens. Tumours were classified for T-stage, histopathological grade and pathological characteristics. Immunohistochemical staining detected p53 protein in 11 (19%) of the 55 specimens. There was no statistically significant difference between patients with p53 positively staining tumours and patients with p53 negatively staining tumours with regard to tumour grade, stage or pathological characteristics (lymph-node infiltration, depth of invasion, necrosis, or necrosis of vessels). Survival time was statistically significantly lower in patients with positively staining tumours (mean survival times 12.0 and 23.4 months, respectively). These results suggest that expression of p53 protein is related to poor prognosis in gastric carcinoma.

High expression of multidrug resistance-1 (MDR-1) and its relationship with multiple prognostic factors in gastric carcinomas in patients in Turkey.

Drug resistance remains a major problem in the treatment of gastric cancer. In Turkey, gastric carcinoma is the second most common cancer and, because the rate of early diagnosis is low, chemotherapy plays an important role in the treatment of the disease. We aimed to investigate expression of the multidrug resistance-1 gene (MDR-1) and its relationship with multiple prognostic factors in gastric cancers. Between 1996 and 1998, a total of 55 patients (37 men and 19 women; median age 55 years) were studied. Sections from specimens of gastric carcinomas were immunohistochemically stained to detect P-glycoprotein (which is associated with MDR-1 expression). We found MDR-1 expression in 48 (87%) of the patients. None of the multiple prognostic factors, including histological type of tumour, correlated with expression of MDR-1. Patients who had low MDR-1 expression had better survival. We conclude that the expression of MDR-1 in gastric cancer is high in Turkey, and this may be related to poor prognosis.

The epidemiology of gastrointestinal cancer in Turkey: a review of our accumulated experience.

Among all organ cancers, gastrointestinal tract cancers present an interesting pattern in distribution over the world. There are several hundred differences between some incidences of cancer. Probably due to different geographical and climatic differences between western and eastern regions of Turkey, we found varying incidences in esophageal, gastric, and colonic carcinomas. The type of diet, and an excess or lack of some essential nutrients and vitamins are probably the main causes in determining what kind of gastrointestinal tumor might occur. Besides diet, living areas, socioeconomic status, salinity of soil, drinking water and many other factors may play a role. Contrary to the findings of some authors, excessive tea and alcohol consumption has not been found to be a risk factor in our study.

Helicobacter pylori and intestinal metaplasia.

Gastric carcinoma of the intestinal type is assumed to develop from precancerous gastric lesions. It is now widely accepted that Helicobacter pylori (HP) infection causes chronic gastritis and, after a period of time, intestinal metaplasia (IM). It was suggested that these gastric lesions may evolve into gastric carcinoma after a lengthy latency period. HP seropositivity is high in Turkey at early ages. This may explain the high incidence of gastric carcinoma in this geographic region. In this study, we examine the relationship between HP and IM in endoscopic gastric biopsy specimens. We examined 840 biopsies taken from 210 patients. HP positivity and the presence of IM were examined in these specimens by histopathologic methods. HP positivity was also determined by CLO testing. HP was positive in 156 of the 210 patients examined (74.3%). The distribution of HP seropositivity did not differ between age groups (p > 0.05). IM was present in 101 patients in the entire study group (48%). Among the 156 HP-positive patients, the rate of IM was 44.8% (n = 70). The rate of IM among the 54 HP-negative patients was 57.4% (n = 31), which was not statistically significant (p > 0.05). IM positivity has been shown to increase in older age, which was statistically significant (p < 0.001). We were not able to show a relationship between HP seropositivity and IM. Increased HP seropositivity at an early age is a common risk factor in our population. We must consider other factors that may contribute to the increased rate of IM in older age groups.

Subtypes of intestinal metaplasia and their relationship to Helicobacter pylori.

The presence of incomplete colonic type of intestinal metaplasia (IM) is regarded as a risk factor for gastric carcinoma. In this study, we attempted to classify the subtypes of IM in our patients and examine their relationship to Helicobacter pylori (HP). Gastric biopsies were obtained from 210 patients. The HP positivity and the presence and type of IM were determined by histopathologic methods. HP positivity was also tested by the CLO test. The subtypes of IM were classified according to Ming's classification. IM was present in 101 of 210 patients (48%). Complete type intestinal metaplasia was present in 72 of 101 patients (71.3%), incomplete type IM was seen in 29 of 101 patients (28.7%), and incomplete colonic type (Type IIc) was found in 7 of 101 patients (6.9%). No significant relationship was found between subtypes of IM and HP positivity (p > 0.05). Although our patient group is small, our findings suggest that the carcinogenity of HP is mostly related to its own mutagenic activity as well as the mutagenic activity of the inflammatory cells present in response to HP rather than to its supposed effect on precancerous gastric lesions.

[Evaluation of the ELISA method for the diagnosis of Helicobacter pylori]. / Helicobacter pylori tanisinda ELISA yönteminin degerlendirilmesi.

Antibodies to H.pylori were investigated in the serum of 50 patients with dyspepsia and 25 healthy controls with ELISA method. The antibody positivity was found in all of the 40 cases (100%) for whom H.pylori was demonstrated in at least two tests of rapid urease, Gram stain, culture and silver staining and in eight of the ten cases (80%) whom H.pylori tests were all negative. Twenty-two of the 25 healthy controls (88%) had also antibodies to H.pylori. The sensitivity of the test was found high (100%), but the specificity was found too low (20%).

Gastric carcinoma in northwestern Turkey: epidemiologic characteristics.

We studied 252 newly diagnosed gastric cancer patients seen at our institution between 1977 and 1991 and compared the findings with 609 age- and gender-matched controls. There was no difference in the mean age and the M:F ratio. Most of our patients were rural dwellers from a low socio-economic group. The proximal portion of the stomach was most often involved. No statistically significant differences were found with regard to the use of coffee, alcohol, starchy food, and fresh fruits. The relative risk for gastric cancer was significantly higher statistically in individuals who consumed only small amounts of vegetables and bread. Although an increased relative risk was noted between gastric cancer and the amount of milk and meat consumed, this appears to have been fortuitous: an increased consumption of milk may have been due to patients attempts to alleviate symptoms, and a low meat intake most likely was due to the low income level of the majority of our patients.

The etiological role of diet, smoking, and drinking habits of patients with esophageal carcinoma in Turkey.

Esophageal cancer has a known high incidence in areas adjacent to the Caspian Sea and in northeastern Turkey. This study compares the incidence of esophageal cancer in Bursa (northwestern Turkey) with an age-matched control population. Factors associated with esophageal cancer and significantly at variance with controls include: age over 70, low income, smoking more than one pack of cigarettes per day, and low vegetable and fresh fruit intake.