Strategies to manage hepatitis C virus (HCV) disease burden.

The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.

Liver involvement in patients with brucellosis: results of the Marmara study.

Brucellosis is a zoonotic disease that primarily affects the reticuloendothelial system. But, the extent of liver damage in due course of the disease is unclear. This study included 325 brucellosis patients with significant hepatobiliary involvement identified with microbiological analyses from 30 centers between 2000 and 2013. The patients with ≥5 times of the upper limit of normal for aminotransferases, total bilirubin level ≥2 mg/dl or local liver lesions were enrolled. Clinical hepatitis was detected in 284 patients (87.3 %) and cholestasis was detected in 215 (66.1 %) patients. Fatigue (91 %), fever (86 %), sweating (83 %), arthralgia (79 %), and lack of appetite (79 %) were the major symptoms. Laboratory tests showed anemia in 169 (52 %), thrombocytopenia in 117 (36 %), leukopenia in 81 (25 %), pancytopenia in 42 (13 %), and leukocytosis in 20 (6 %) patients. The most commonly used antibiotic combinations were doxycycline plus an aminoglycoside (n = 73), doxycycline plus rifampicin (n = 71), doxycycline plus rifampicin and an aminoglycoside (n = 27). The duration of ALT normalization differed significantly in three treatment groups (p < 0.001). The use of doxycycline and an aminoglycoside in clinical hepatitis showed better results compared to doxycycline and rifampicin or rifampicin, aminoglycoside, doxycycline regimens (p < 0.05). However, the length of hospital stay did not differ significantly between these three combinations (p > 0.05). During the follow-up, treatment failure occurred in four patients (1 %) and relapse was seen in three patients (0.9 %). Mortality was not observed. Hepatobiliary involvement in brucellosis has a benign course with suitable antibiotics and the use of doxycycline and an aminoglycoside regimen seems a better strategy in select patients.

Evaluation of Barrett's esophagus with CK7, CK20, p53, Ki67, and COX2 expressions using chromoendoscopical examination.

Barrett's esophagus (BE) is a complication of chronic gastroesophageal reflux disease and can be diagnosed when there is an endoscopically irregular Z-line and intestinal metaplasia (IM) in a biopsy obtained lower esophagus. It is still not clear whether IM in the gastric cardia or columnar mucosa without IM in the lower esophagus have any significance as BE, which is considered as preneoplastic. The aim of the study was to determine the immunohistochemical features of BE and columnar mucosa in the distal esophagus and also to evaluate the value of chromoendoscopy in the diagnosis of BE in a prospective manner. A total of 12 chromoendoscopic biopsies (six from normal-looking unstained esophagus and six from esophageal mucosa stained with methyl blue suspicious of BE) were taken from 111 cases who underwent endoscopy because of a variety of upper gastrointestinal symptoms. Immunohistochemical analysis was performed using CK7, CK20, p53, Ki67, and cyclooxygenase 2 (COX2). Of the 111 cases, 19 cases with carcinoma (nine adeno, six squamous, four undifferentiated carcinomas) and 17 cases with normal squamous epithelium were excluded, while 75 cases showing columnar epithelium, including 46 (61.3%) with IM and 29 (38,7%) without IM, were further evaluated immunohistochemically. CK7 was observed in surface, crypt, and glandular epithelium, whereas CK20 was expressed in surface and superficial crypt epithelium. No significant difference was observed between the Barrett and non-Barrett type of CK7/20 staining pattern (P > 0,05). Expression of p53 did not show any difference between BE and columnar mucosa without IM, whereas COX2 expression was significantly increased in BE (P < 0.05) in comparison with columnar mucosa without IM. Ki67 expression was significiantly higher both in upper and lower crypts in BE (P < 0.05). The present study showed that a Barrett pattern does not seem to exist; however, the analysis of COX2 expression and the Ki67 proliferation fraction by immunohistochemistry can be used to separate BE from non-Barrett's metaplasia of the distal esophagus. In our point of view, the immunohistochemical detection of p53 expression in Barrett's metaplasia stage is useless as a marker for early detection of high-risk patients.

Association of methylenetetrahydrofolate reductase C677T-A1298C polymorphisms with risk for esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis.

Incidence of the esophagus adenocarcinoma has been dramatically increasing in Western countries since the last decade. Gastroesophageal reflux disease and Barrett's esophagus are risk factors for adenocarcinoma. Methylenetetrahydrofolate reductase (MTHFR) genes play a key role not only in folate metabolism but also in esophagus, stomach, pancreatic carcinoma, and acute leukemias. Studies have suggested that genetic polymorphisms of MTHFR (C677T) may clarify the causes and events involved in esophageal carcinogenesis. In this study, we evaluated MTHFR C677T and A1298C polymorphisms, and vitamin B12, folate, and plasma homocystein levels in patients with esophageal adenocarcinoma (EAC), Barrett's esophagus (BE), chronic esophagitis, and healthy controls (n = 26, n = 14, n = 30, and n = 30, respectively). The mean age of patients in the EAC and BE groups was significantly higher compared with the control group (P < 0.001, P = 0.003, respectively). In all patient groups, serum folate levels were significantly lower than that of the control group (P < 0.01, P < 0.05, and P < 0.01, respectively). There was no statistically significant association between folate levels and MTHFR gene polymorphisms. No differences were found in terms of MTHFR gene polymorphisms, homocystein, and B12 levels among the groups. MTHFR gene polymorphisms and folate deficiency are not predictors of early esophageal carcinoma. However, further studies using larger series of patients are needed to evaluate the effect of genetic polymorphisms in the folate metabolic pathway and to clarify the role of folate deficiency and folate metabolism in the development of esophagus adenocarcinoma.

The usefulness of chromoendoscopy with methylene blue in Barrett's metaplasia and early esophageal carcinoma.

BACKGROUND: Barrett's esophagus is a condition that is premalignant for adenocarcinoma of the esophagus and the esophagogastric junction. Early detection of Barrett's metaplasia and dysplasia is very important to decrease the mortality and morbidity from esophageal adenocarcinoma cancer. This study aimed to evaluate the effectiveness of methylene blue-targeted biopsies in the differential diagnosis of intestinal metaplasia, dysplasia, and superficial esophageal carcinoma. METHODS: A total of 109 patients (43 women and 66 men; average age, 62.32 +/- 10.61 years; range, 33-82 years) were enrolled for the study. Four groups were designed before endoscopic examinations. The patients for these groups were selected at the conventional endoscopy, and then chromoendoscopy was performed. The esophagus was stained with methylene blue, after which six biopsies were taken from stained and unstained areas. RESULTS: Conventional and chromoendoscopic assessments were compared with histopathologic examination. The sensitivity of chromoendoscopy for Barrett's epithelium was superior to that of conventional endoscopy (p < 0.05). However, there was no statistical difference between the two methods in the diagnosis of esophagitis or esophageal carcinoma (p > 0.05). Stained biopsies were superior to unstained biopsies in terms of sensitivity for Barrett's epithelium and esophageal carcinoma (p < 0.001). CONCLUSION: Chromoendoscopy is useful for delineating Barrett's epithelium and for indicating the correct location for securing biopsies where dysplasia or early esophageal cancer is suspected.

Flow cytometric DNA analysis, and immunohistochemical p53, PCNA and histopathologic study in primary achalasia: preliminary results.

BACKGROUND/AIMS: Primary achalasia is a premalignant disorder of the esophagus. The studies for esophageal cancer pathogenesis may reveal early diagnosis of esophageal cancer. DNA aneuploidy, p53 mutations and cellular proliferation are important factors in cancer development. As far as we know, we have not encountered any study on these factors in achalasia. METHODOLOGY: We studied DNA ploidy by flow cytometry and p53 and PCNA index by immunohistochemical technique and studied histopathology in the esophageal mucosa of primary achalasia and control patients. RESULTS: DNA analysis revealed aneuploidy in 2 of 20 achalasia patients but none of the 18 control patients. Sixty-five percent of achalasia and 22% of normal patients showed p53 positivity (P < 0.05). We have found normal mucosa, basal cell hyperplasia-esophagitis and dysplasia in 13, 22 and 3 patients and p53 positivity in 2, 12 and 3 of these patients, respectively (P < 0.05). PCNA labeling indexes (as % +/- SD) were 34.8 +/- 12.2, and 28.4 +/- 9.3 in achalasia and control groups, respectively (P > 0.05). PCNA labeling index was 28.0 +/- 8.2 in p53(-) and 36.0 +/- 12.9 in p53(+) patients (P < 0.05). PCNA indexes were found 29.3 +/- 9.6 in normal histopathologic group, 31.8 +/- 13.4 in basal cell hyperplasia-esophagitis, and 41.7 +/- 6.5 in dysplasia group (P > 0.05). CONCLUSIONS: DNA aneuploidy, p53 positivity, and higher cellular proliferation index may have important role in the pathogenesis of esophageal cancer in primary achalasia.

Evaluation of gastrointestinal involvement of Behçet's disease by nuclear medical techniques.

To evaluate the value of nuclear medicine procedures in the diagnosis of gastrointestinal involvement of Behcet's disease in asymptomatic patients, Tc-99m human immunoglobulin (HIG) and Tc-99m leucocyte (LC) whole body scintigraphies were performed on 30 patients with major symptoms of the disease. Comparison of the results with other diagnostic techniques showed that Tc-99m HIG whole body scanning can be a useful diagnostic aid before the disease becomes clinically active in the gastrointestinal system.

The effectiveness of omeprazole versus lansoprazole along with amoxicillin and clarithromycin in Turkish population with duodenal ulcer.

AIM: To compare the effectiveness of omeprazole versus lansoprazole with amoxicillin and clarithromycin in the Turkish populations with duodenal ulcer. METHODS: Helicobacter pylori positive 108 patients with active duodenal ulcer randomized double blindly into 2 groups. In the group of omeprazole, amoxicillin and clarithromycin (OAC), 54 patients; 34 male, 20 female, average age (+/-SD) 43.89+/-11.77 years. Omeprazole was given 20 mg b.i.d, half an hour before meals for 14 days and then 20 mg preceeding breakfast for 6 weeks along with 1 g amoxicillin and 500 mg clarythromycin b.i.d. for both antibiotics for 14 days while lansoprazole 30 mg b.i.d. was administered half an hour preceeding food intake for 14 days and then 30 mg prebreakfast for 6 weeks with concordant 1 g b.i.d. amoxicillin and clarythromycin 500 mg, b.i.d. for 14 days in the group of lansoprazole with amoxicillin and clarithromicin (LAC) (54 patients; 31 male, 23 female, average age (+/-SD) 40.85+/-12.80 years. The patients were evaluated in clinical terms and by endoscopic parameters for healing, H. pylori eradication and drug side effects before and after 8 weeks of treatment. RESULTS: There were no significant differences in age, sex and smoking between the 2 groups (p=0.20, p=0.56, p=0.85), respectively. In the LAC group, the ulcer healing rate was 94.4% (51 out of 54 patients). H. pylori was eradicated in 49 patients out of 54 (90.7%). The H. pylori eradication rate was 89.7% (26 out of 29) among the smokers. In the OAC group the ulcer healing rate was 90.7% (49 out of 54 patients). H. pylori was eradicated in 43 patients out of 54 (79.6%). The H. pylori eradication rate was 80.0% (24 out of 30 patients) among the smokers. There was no statistical difference between the 2 groups for ulcer healing (p=0.72). There was also no statistical difference for H. pylori eradication between the LAC and OAC groups (p=0.10). Although mild side effects were observed in both groups, there was no indication for stopping the therapy. CONCLUSIONS: This study has shown that the 2 regimens (LAC and OAC) are highly effective in healing duodenal ulcers and eradicating H. pylori. Lansoprazole does not appear to have a significant advantage over omeprazole either in ulcer healing or in H. pylori eradication. Both lansoprazole and omeprazole are well tolerated, but with mild adverse effects.

Tc-99m dextran and Tc-99m HIG findings in patients with ulcerative colitis.

PURPOSE: Various radionuclide methods have been studied for the evaluation of the disease activity and extent of ulcerative colitis and other protein-losing enteropathies. Recently, Tc-99m dextran and Tc-99m human immunoglobulin (HIG) have been used to detect inflammation and protein loss into the intestine, but only a few studies have been reported with these agents. MATERIALS AND METHODS: In this study, Tc-99m dextran and Tc-99m HIG were used to evaluate disease activity and extent in patients with ulcerative colitis. These agents were used in 12 patients with active disease and in five patients in remission, and five healthy control participants also were included. RESULTS: Large bowel activity was detected in 11 of the 12 patients with active ulcerative colitis using Tc-99m dextran and in 10 patients using Tc-99m HIG. Fifty-eight bowel segments were found to be active with endoscopy, 39 with Tc-99m dextran, and 31 with Tc-99m HIG. No intestinal activity was detected in the control participants. Grade 1 activity localization in the large bowel was detected in three patients with ulcerative colitis in remission using Tc-99m dextran and in one patient using Tc-99m HIG. CONCLUSION: Tc-99m dextran is more sensitive for detecting disease activity and extent than is Tc-99m HIG.

Carcinoid tumor of the biliary duct.

Carcinoid tumors which arise from enterochromaffin cells are usually found in the appendix, ileum, bronchus and rectum. Biliary duct carcinoids are exceedingly rare. Pre-operative diagnosis is very difficult because they mimic the signs and symptoms of choledocholithiasis. We report a case of biliary duct carcinoid. A 38-year-old woman admitted with signs and symptoms of obstructive jaundice. ERCP demonstrated an obstruction in the common bile duct. A choledochotomy T drainage was performed. Histopathologically the mass which was removed from the common bile duct was a carcinoid tumor. There are only nine cases of biliary duct carcinoid in the literature to date. These cases are reviewed.

Hepatic fascioliasis and biliary surgery.

This series represents seven cases of hepatic fascioliasis (HF), two diagnosed as the sequelae of the disease and five showing the parasite itself at the time of the primary surgical intervention. The mean history of the symptoms was 42.6 mths. All of the patients were initially misdiagnosed as having cholecysto- and/or coledocho-lithiasis or hepatitis. Definite diagnosis was established intraoperatively in each instant. At surgery cholecystectomy, choledochotomy with extirpation of the flukes from the biliary tree and T-tube biliary drainage was performed without any complications in five patients. The remaining two patients were suffering from recurrent cholangitic episodes and were regarded as sequelae and therefore treated with hepatic peri-arterial neurectomy with favourable results. Six patients received medical treatment involving emetine hydrochloride. Two patients failed to return for follow-up while others were seen to be well 6, 12, 24 mths and 13 and 24 yrs postoperatively, implying promising long-term results both in the active and chronic stages of HF.

Treatment of biliary fistulas and cholelithiasis: is endoscopic sphincterotomy acceptable in the paediatric age group?

Two children, both girls, aged 11 and 16 with a postoperative biliary fistula and cholelithiasis, choledochal cyst and common bile duct stones have undergone endoscopic sphincterotomy (EST), leading to a rapid recovery from their pathologies, thanks to cooperative work. In reviewing the literature we have not come across any cases of EST in our patients' age group. There were no complications during or immediately after endoscopic sphincterotomies. We believe that it has become an important and valuable rival to conventional surgical means with correct indications and in experienced hands.

The diagnostic value of on-site cytopathological evaluation and cell block preparation in fine-needle aspiration cytology of liver masses.

OBJECTIVE: The aims of this study were to evaluate the typing accuracy of conventional smear (CS), cell block (CB) preparations and combined use of both procedures (CS + CB) for the diagnosis of hepatic malignancies and to determine whether immediate on-site cytopathological evaluation improves the diagnostic yield of liver fine-needle aspiration cytology (FNAC). METHODS: Ultrasound-guided FNABs were performed on 323 consecutive cases with liver masses between December 2002 and December 2004. Histologically and/or clinically correlated 167 cases were included in the study. Preliminary FNAB results, results of CS, CB, and combined use of CS and CB were compared regarding diagnostic sensitivity, specificity, and accuracy for the diagnosis of malignancy. Subtyping accuracies of different methods were also compared. RESULTS: The sensitivity of on-site cytopathological examination and CS were both 92.8%. The sensitivity of CS + CB was slightly better than that of CB (93.5% versus 84.8%). Specificity of all procedures was achieved 100%. Diagnostic accuracy of on-site cytopathological evaluation, CS, CB, and CS + CB were 93.9%, 93.9%, 87.2%, and 94.5%, respectively. A specific subtype diagnosis of malignant tumours could be rendered accurately on the basis of preliminary diagnosis in 71%, CS in 75.4%, CB in 78.3% and combined approach in 92% of cases. In terms of typing accuracy, 87.5% of HCCs, 93.2% of adenocarcinomas, 92.3% of neuroendocrine carcinomas, 100% of lymphomas and 100% of other malignant tumours were correctly subclassified in the final cytopathological diagnosis. The agreement between preliminary diagnosis and final cytopathological diagnosis was 77.2%. CONCLUSION: With use of on-site cytopathological evaluation and combined use of CS and CB, the diagnostic accuracy of liver tumours approaches 100% and also significantly improve diagnostic and subtyping accuracy of liver malignancies.

DNA analysis and DNA ploidy in gastric cancer and gastric precancerous lesions.

Gastric cancer (GCa) is still a common cause of cancer-related deaths worldwide, despite improved diagnostic and therapeutic implications. Hence, early diagnosis has critical importance. Flow cytometry reveals rapid and reproducible quantification of nuclear DNA content of disaggregated tissues and assessment of its significance in various malignant and precancerous lesions. A total of 121 patients with GCa, chronic atrophic gastritis (CAG), gastric polyps, intestinal metaplasia (IM) and gastric dysplasia and 36 healthy controls were enrolled in this study. Flow cytometric measurements of DNA ploidy, total S-phase, G2M-phase and proliferative indexes (PIs) were analysed on fresh gastric biopsy specimens obtained by gastroscopy. DNA aneuploidy was present in 43.75% of the GCas (p < 0.05). We found a DNA aneuploidy rate of 15.38% in CAG, 15.38% in IM and 25% in epithelial dysplasia. One of nine polyps had aneuploidy. None of the normal gastric mucosa samples showed aneuploidy. The controls had lower rates of total S-phase and PIs (p < 0.05). In conclusion, DNA flow cytometry may be offered as an objective diagnostic tool for early detection of malignant transformation in gastric lesions.

Adenosine deaminase, 5'-nucleotidase, xanthine oxidase, superoxide dismutase, and catalase activities in gastric juices from patients with gastric cancer, ulcer, and atrophic gastritis.

Adenosine deaminase (ADA), 5'-Nucleotidase (5NT), Xanthine oxidase (XO), Cu-Zn Superoxide dismutase (SOD) and Catalase (CAT) activities were determined in gastric juices from patients with gastric cancer, ulcer, gastritis and from healthy subjects. Enzyme activities were given as units per ml gastric juice and units per mg protein in gastric juice. ADA, 5NT and XO activities were found lower and protein concentrations were found higher in the cancer group than controls. There was however no significant difference between Cu-Zn SOD activities of the cancer and control groups. In all groups including control one, we could not find catalase activities in most of the samples. On the other hand, ADA, 5NT activities and protein concentrations in the gastric juice were lower in the gastritis group than control group. In the ulcer group, we found higher Cu-Zn SOD and XO activities and lower 5NT activity and protein concentrations compared with control values. In an attempt to establish statistical correlations between mean enzyme activities, pH and protein concentrations in the gastric juices of the groups, we found noticeable intra and inter-correlations, which indicated possible relations between DNA and free radical metabolizing enzymes.

A new percutaneous approach for the treatment of hydatid cysts of the liver.

OBJECTIVES: The aims of this study were to investigate the efficacy of a new percutaneous treatment modality of hydatid disease of the liver and to present the results of long term follow-up. METHODS: Eighty-seven patients (55 female, mean age 43.5 yr) with 98 hydatid cysts (73 type I, 15 type II, and 10 type III) in the liver underwent percutaneous treatment. All patients were examined by ultrasonography and some of them were examined by CT. They were all positive by indirect hemagglutination test. Sonographic guidance was used in all patients. The procedure included the puncture and free drainage of the cyst fluid. After free drainage was stopped, absolute alcohol and polidocanol 1% were used as sclerosing agents. The patients were followed-up with periodic ultrasonographic examinations. RESULTS: The mean follow-up time was 33 months. The mean diameter of the cysts decreased from 77.0+/-2.7 mm to 63.0+/-2.5 mm (p < 0.001). The entire cyst cavity filled with a solid echo pattern in 32 cysts, two-thirds of the cyst cavity showed a pseudotumor echo pattern in 34 cysts, and one-third of the cyst cavity showed a pseudotumor pattern in 23 cysts, whereas no pseudotumor appearence was observed in eight cysts. Apart from an anaphylactoid reaction observed in one patient, no major complication occurred during the follow-up period. CONCLUSIONS: Long term results indicate that this new percutaneous treatment modality of the hydatid disease of the liver is an effective and safe method without causing major complications. Percutaneous treatment of hydatid cysts of the liver offers good results and should be the first choice, especially for patients who are contraindicated to surgery.

Successful medical treatment of an epithelioid hemangioendothelioma of liver.

Hepatic epithelioid hemangioendothelioma (HEH) is a rare vascular tumor of the liver of unknown etiology. Although HEH is usually characterized by a low grade malignancy and a good long-term prognosis, its growth can be progressive and lead to hepatic failure, extrahepatic metastasis and death. Several different antineoplastic agents have been proposed for cases of nonresectable HEH. We report the case of a 45-year-old man with HEH successfully treated with intravenous infusion of Adriamycin.