Altay Celebi

Serum levels of hepatoprotective peptide adiponectin in non-alcoholic fatty liver disease.

Objective Adiponectin is an adipose tissue-specific protein that has anti-inflammatory, antidiabetic and antiobesity effects. It has been suggested that adiponectin has a hepatoprotective role. Non-alcoholic fatty liver disease (NAFLD) is becoming more prevalent with increasingly adverse clinical outcomes. In this study, serum adiponectin levels were investigated in patients with NAFLD to determine its possible role on hepatic inflammation and injury. Methods Twenty-nine biopsy-proven NAFLD patients (14 women, 15 men) with elevated liver enzymes, 20 clinically diagnosed NAFLD patients (13 women, seven men) with normal liver enzymes, and 20 healthy adults (10 women, 10 men) were enrolled. From fasting blood samples, serum adiponectin levels were measured by enzyme-linked immunosorbent assay. The body mass index, serum glucose, insulin, cholesterol and triglyceride levels were determined. Results Serum adiponectin levels were 4.99±2.1, 9.49±3.91 and 7.74±4.41 μ/ml in the NAFLD with elevated liver enzymes, NAFLD with normal liver enzymes and healthy adult control groups, respectively. The mean serum adiponectin level in the NAFLD with elevated liver enzymes group was significantly lower than those of other groups tested (P<0.001). Insulin, cholesterol and triglyceride levels of NAFLD patients with elevated liver enzymes were significantly higher than control groups (P<0.05) but were not significantly different from the NAFLD group with normal liver enzymes (P>0.05). On histopathologic examination, the mean serum adiponectin levels of non-alcoholic steatohepatitis patients with grade 2 or more inflammatory activity was significantly lower than patients with grade 1 inflammatory activity (P=0.013). Conclusion Serum adiponectin levels are significantly lower in NAFLD patients with elevated liver enzymes. Non-alcoholic steatohepatitis patients show lower levels of adiponectin with higher grades of inflammation.

Defining esophageal landmarks, gastroesophageal reflux disease, and Barrett's esophagus

The following paper on gastroesophageal reflux disease (GERD) and Barretts esophagus (BE) includes commentaries on defining esophageal landmarks; new techniques for evaluating upper esophageal sphincter (UES) tone; differential diagnosis of GERD, BE, and hiatal hernia (HH); the use of high‐resolution manometry for evaluation of reflux; the role of fundic relaxation in reflux; the use of 24‐h esophageal pH–impedance testing in differentiating acid from nonacid reflux and its potential inclusion in future Rome criteria; classification of endoscopic findings in GERD; the search for the cell origin that generates BE; and the relationship between BE, Barretts carcinoma, and obesity.

Endoscopic submucosal dissection for premalignant lesions and noninvasive early gastrointestinal cancers.

AIM To investigate the indication, feasibility, safety, and clinical utility of endoscopic submucosal dissection (ESD) in the management of various gastrointestinal pathologies. METHODS The medical records of 60 consecutive patients (34 female, 26 male) who underwent ESD at the gastroenterology department of Kocaeli University from 2006-2010 were examined. Patients selected for ESD had premalignant lesions or non-invasive early cancers of the gastrointestinal tract and had endoscopic and histological diagnoses. Early cancers were considered to be confined to the submucosa, with no lymph node involvement by means of computed tomography and endosonography. RESULTS Sixty ESD procedures were performed. The indications were epithelial lesions (n = 39) (33/39 adenoma with high grade dysplasia, 6/39 adenoma with low grade dysplasia), neuroendocrine tumor (n = 7), cancer (n = 7) (5/7 early colorectal cancer, 2/7 early gastric cancer), granular cell tumor (n = 3), gastrointestinal stromal tumor (n = 2), and leiomyoma (n = 2). En bloc and piecemeal resection rates were 91.6% (55/60) and 8.3% (5/60), respectively. Complete and incomplete resection rates were 96.6% (58/60) and 3.3% (2/60), respectively. Complications were major bleeding [n = 3 (5%)] and perforations [n = 5 (8.3%)] (4 colon, 1 stomach). Two patients with colonic perforations and two patients with submucosal lymphatic and microvasculature invasion (1 gastric carcinoid tumor, 1 colonic adenocarcinoma) were referred to surgery. During a mean follow-up of 12 mo, 1 patient with adenoma with high grade dysplasia underwent a second ESD procedure to resect a local recurrence. CONCLUSION ESD is a feasible and safe method for treatment of premalignant lesions and early malignant gastrointestinal epithelial and subepithelial lesions. Successful en bloc and complete resection of lesions yield high cure rates with low recurrence.

Comparison of Five Detection Methods for Helicobacter pylori

OBJECTIVE To evaluate which diagnostic test is preferable for the diagnosis of Helicobacter pylori in patients with gastroduodenal disease. STUDY DESIGN H pylori infection was diagnosed prospectively in 101 patients. Diagnosis of H pylori was made by tests based on five different principles: (1) culture, (2) direct histologic demonstration, (3) imprint cytology, (4) brushing cytology, and (5) gram staining of H pylori. Efficacy of each test was compared. RESULTS All the tests were reliable for diagnosing H pylori infection; 73.3% of patients showed concordance in at least two tests. All the tests were positive in > 50% of patients. Significant concordance between brushing and imprint cytology was also determined. These two tests have almost similar specificity when compared to other tests. CONCLUSION When patients undergo upper endoscopy, we recommend taking biopsy specimens for culture and histology. H pylori can be assessed equally well with all the tests, but imprint and brushing cytology have the advantage of rapid response, specificity, much lower cost and reproducibility.

The relationship between fibrosis level and blood neutrophil to lymphocyte ratio in inactive hepatitis B carriers.

Aim Neutrophil–lymphocyte ratio (NLR) has been used as a simple, affordable, and easily accessible marker to predict prognosis in a variety of inflammatory and neoplastic diseases. However, there are few studies investigating their role in patients with hepatitis B. The aim of this study was to investigate the relationship between NLR and liver fibrosis in patients who were being followed as inactive hepatitis B carriers. Materials and methods The study included 78 patients who were followed for 1 year as inactive hepatitis B carriers. Liver biopsy was performed and the fibrosis scores of the histological activity index were assessed according to the Metavir scoring system. The patients were divided into two groups on the basis of the fibrosis scores: those with a score below 2 and those with a score above 2. In both groups, demographic data such as sex, age, and BMI were similar. The NLR of patients was calculated from blood samples taken at the same time as the biopsy. Results Histopathologic analysis of 78 patients showed that 41 (53%) had fibrosis grade 0–1 and 37 (47%) patients had fibrosis grade greater than 2. According to the biopsy results, there were no cirrhotic patients. NLR was found to be statistically significantly lower in the group with fibrosis grade of at least 2 (1.51±0.61 vs. 1.79±0.64, P=0.043). Other biochemical and hematological data were found to be similar in both groups. No correlation was found between laboratory values and NLR. In addition, there was no correlation between NLR with histologic activity. Spearman correlation analysis showed a negative correlation between the fibrosis score and NLR (r=−0.279, P=0.013). Conclusion In inactive hepatitis B carriers, the histological activity index and NLR were found to be correlated negatively. NLR can be used as a predictor of fibrosis in combination with other noninvasive markers.

Comparison of the effects of esomeprazole 40 mg, rabeprazole 20 mg, lansoprazole 30 mg, and pantoprazole 40 mg on intragastrıc pH in extensive metabolizer patients with gastroesophageal reflux disease.

BACKGROUND/AIMS Studies on the therapeutic efficacy of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD) have been recently published. In most of these studies, comparison of only two PPIs have been made. There are few studies on the comparison of four or more PPIs. We aimed to compare the acid inhibitory effects of esomeprazole 40 mg, rabeprazole 20 mg, lansoprazole 30 mg, and pantoprazole 40 mg on days 1 and 5 of treatment in patients with GERD, who were extensive metabolizers in regard to the CYP2C19 genotype. MATERIALS AND METHODS Helicobacter pylori-negative with typical symptoms of GERD patients were randomly divided into four treatment groups. Efficacy analysis on days 1 and 5 were performed on the four groups which comprised 10 (esomeprazole), 11 (rabeprazole), 10 (lansoprazole), and 10 (pantoprazole) patients. RESULTS On day 1 of PPI treatment, the mean percentage of time with intragastric Ph>4 were 54%, 58%, 60%, and 35% for the groups, respectively, and on day 5, these values were 67%, 60%, 68%, and 59%, respectively. Esomeprazole, rabeprazole, and lansoprazole were found to be superior to pantoprazole on the first day of treatment. CONCLUSION Pantoprazole is a less potent proton pump inhibitor than the other PPIs tested on the first day of treatment. When the time needed to raise the intragatric pH to over 4 was evaluated, esomeprazole was found to have the most rapid action, followed by lansoprazole and rabeprazole.

What is proton pump inhibitors unresponsiveness in gastroesophageal reflux disease? How should these cases be managed?

Proton pump inhibitors become the most potent therapeutic option in gastroesophageal reflux disease. Unresponsiveness to this treatment is not uncommon in clinical practice. We reviewed the definition of PPI unresponsiveness and the management of this situation.

Adalimumab-induced psoriasis in a patient with Crohn's disease.

Sir: Inappropriate secretion of tumor necrosis factor alpha (TNF-α) leads to inflammation and tissue damage by causing excessive secretion of inflammatory cytokines especially IL-1 [1]. AntiTNF-α agents are used to treat a myriad of immune-based diseases. Although indicated in treating certain forms of psoriasis, TNF inhibitors have paradoxically been shown to cause or worsen psoriasis primarily in patients with underlying rheumatologic disease and inflammatory bowel diseases (IBD) [2, 3]. We present a case of plaque psoriasis in a patient with Crohn’s disease during adalimumab treatment. A 32-year-old female patient with the diagnosis of ileal Crohn’s disease for 5 years was started on adalimumab therapy (160 mg initially on day 1, followed by 80 mg on day 15, and a maintenance dose of 40 mg every other week) due to refractory disease. Following the loading dose, a marked improvement was seen in both clinical and laboratory indices (defined as a decrease in CDAI ≥100 points). In the fourth month of treatment, itchy irregular white desquamated plaques with surrounding hyperemia appeared on the extensor and partly flexor surfaces of the extremities and also on the scalp. Plaques with fissures were seen on the thenar parts of the hands (Fig. 1a, b). The patient was diagnosed with psoriasis. As psoriasis was believed to occur as a side effect of adalimumab, therapy was stopped and switched to methotrexate 15 mg/week plus infliximab 5 mg/kg/week in the 12th week of the treatment, laboratory findings were within normal range, and the patient suffered only from mild abdominal pain. Plaques were judged to show an improvement to a degree of approximately 90 % on the extremities and 50 % on the scalp. Treatment was maintained by adding topical therapies. Anti-TNF-α drugs play a key role in the treatment of IBD. Psoriasis is rarely seen in IBD patients using anti-TNF drugs and most of these cases are related to infliximab therapy [3–5]. The most common anti-TNF-α-related forms of psoriasis are plaque psoriasis and palmoplantar pustulosis [3, 5]. Signs occur after 1 to 96 months from the implementation of therapy [5]. Psoriasis development during anti-TNF-α therapy is believed to be a result of the disruption of the balance between TNF-α and interferon alpha [6]. Inhibition of TNF-α also leads to hyperproliferation of keratinocytes by decreasing levels of cytokines such as IL-6, IL-8, etc. [7]. Although there is no established treatment modality for such cases, stopping the offending drug provides a marked improvement. Switching to another drug from the same class, adding an immunomodulatory drug like methotrexate, and topical therapies (including vitamin D) are also recommended [3, 5, 6]. Although lesions might also heal during continuation of therapy, stopping the therapy yielded better responses [5]. In our case, both IBD and skin lesions (except scalp lesions) could be treated by stopping the offending drug and starting methotrexate along with infliximab (as Crohn’s disease was unresponsive to previous immunomodulatory therapies). Vitamin Dwhich has immunomodulatory effects (especially in plaque psoriasis) permits to lower the doses of other drugs used for the treatment of psoriasis [8]. Healing of plaques by vitamin D replacement is reported in adalimumab-induced psoriasis [9]. As skin lesions seen in IBD might be a manifestation of the disease, it should be always kept in mind that they might be the side effect of the drugs used for the treatment of the disease. U. Korkmaz (*) :A. E. Duman :G. Dindar :H. Yilmaz : A. Celebi :O. Senturk : S. Hulagu Department of Gastroenterology, Kocaeli University Medical Faculty, Umuttepe, 41900 Kocaeli, Turkey e-mail: drkorkmazugur@yahoo.com

A rare gastric outlet anomaly: pyloric ostium on incissura angularis.

Congenital gastric outlet anomalies are rarely seen defects resulting from early embryologic development of foregut. We report a case of congenital pyloric outlet anomaly in a 60-year-old man with mild postprandial epigastric discomfort of approximately 3 months’ duration. Endoscopic examination of the stomach showed a pyloric ostium on incissura angularis connecting the stomach to the duodenum. Usual site of pylorus at the end of antrum was closed like a sac. No signs of acute or chronic peptic ulcer were noted. A biopsy was taken from the region showed normal mucosal layers with a mild gastritis. There was no history of surgery, ulcer disease, or use of any medication. The case was considered to be congenital in origin and was successfully treated conservatively with proton-pump inhibitors and gastrokinetics.

Differential diagnosis of Crohn’s disease using antibodies to glycoprotein 2 and Saccharomyces cerevisiae

BACKGROUND/AIMS Glycoprotein 2 (GP2), the major autoantigen of Crohns disease (CD)-specific pancreatic autoantibodies, is reportedly correlated with several characteristics of CD. We investigated this serological marker in Turkish patients with CD and assessed its utility in combination with anti-Saccharomyces cerevisiae antibodies (ASCAs) for differential diagnosis of CD. MATERIALS AND METHODS A total of 60 patients with CD, 62 patients with ulcerative colitis (UC), and 46 healthy controls with a definite diagnosis who were similar in age and sex were enrolled in the study conducted from November 2011 to October 2012. ASCA and anti-GP2 levels were measured using commercially available kits. RESULTS Anti-GP2 IgA and IgG levels were higher in patients with CD (25%) than in those with UC (5%) and controls (2%). The seroprevalence of anti-GP2 IgA was markedly higher than that of IgG in patients with CD in contrast to previous studies. The specificity and positive predictive value of seropositivity for both ASCA and anti-GP2 were 100%. ASCA IgA seropositivity was correlated with a complicated disease course and a history of surgery. There was no correlation between anti-GP2 seropositivity and disease location, disease behavior, or a history of surgery. CONCLUSION The combination of ASCA and anti-GP2 may enable differentiation of CD from UC. As ASCA seropositivity is associated with a more complicated disease course, patients seropositive for ASCA at the initial diagnosis should undergo more intense therapy.