Abdurrahman Kadayifci

Metformin in the treatment of patients with non‐alcoholic steatohepatitis

Background : Increased insulin resistance is the major pathogenic mechanism in the development of non‐alcoholic steatohepatitis.

Impact of next-generation sequencing on the clinical diagnosis of pancreatic cysts

BACKGROUND AND AIMS The value of next-generation sequencing (NGS) of pancreatic cyst fluid relative to the clinical and imaging impression has not been well-studied. The aim of this study was to assess the impact of NGS on the clinical diagnosis from imaging and carcinoembryonic antigen (CEA) and thus the management of pancreatic cysts. METHODS Ninety-two pancreatic cyst fluids from 86 patients were analyzed by cytology, CEA, and targeted NGS. Cysts were classified by imaging as nonmucinous, mucinous, or not specified. NGS results were compared with the imaging impression stratified by CEA and cytology. RESULTS NGS impacted the clinical diagnosis by defining a cyst as mucinous in 48% of cysts without elevated CEA levels. The VHL gene in 2 intraductal papillary mucinous neoplasms (IPMNs) supported a serous cystadenoma. Twenty percent of cysts that were nonmucinous by imaging were mucinous by NGS. Of the 14 not-specific cysts, CEA levels were not elevated in 12 (86%), and NGS established a mucinous etiology in 3 (25%). A KRAS or GNAS mutation supported an IPMN with nonmucinous CEA in 71%. A KRAS mutation reclassified 19% of nonneoplastic cysts with nonmucinous CEA as mucinous. Seven cyst fluids (8%) had either a TP53 mutation or loss of CDKN2A or SMAD4 in addition to KRAS and/or GNAS mutations; 5 of 7 (71%) were clinically malignant, and high-grade cytology was detected in all 5. Overall, CEA was more specific for a mucinous etiology (100%), but NGS was more sensitive (86% vs 57%). CONCLUSIONS NGS of pancreatic cyst fluid impacts clinical diagnosis and patient management by defining, supporting, or changing the clinical diagnosis based on imaging and CEA. NGS was most valuable in identifying mucinous cysts with nonmucinous CEA. An added benefit is the potential to detect mutations late in the progression to malignancy that may increase the risk classification of the cyst based on imaging and cytology.

Comparison of sequential and standard triple-drug regimen for Helicobacter pylori eradication: a 14-day, open-label, randomized, prospective, parallel-arm study in adult patients with nonulcer dyspepsia.

BACKGROUND The eradication rates of Helicobacter pylori with standard treatments are decreasing worldwide. OBJECTIVES The primary aim of this study was to compare the eradication success of a 14-day sequential regimen with proton pump inhibitor (PPI)-based triple treatment. The secondary objectives of the study were to evaluate the effect of gastritis score and smoking on eradication rates as well as evaluation of compliance and tolerability of both regimens. METHODS Consecutive H pylori-positive patients with nonulcer dyspepsia were randomized into 1 of 2 groups in this 14-day, open-label, randomized, prospective, parallel-arm study. An upper endoscopy with biopsy and (14)C-urea breath test ((14)C-UBT) were performed before enrollment. The first group was administered a sequential regimen consisting of pantoprazole 40 mg and amoxicillin 1 g for 7 days, followed by pantoprazole 40 mg, tetracycline 500 mg, and metronidazole 500 mg for the next 7 days. The second group was administered pantoprazole 40 mg, amoxicillin 1 g, and clarithromycin 500 mg (PAC group) for 14 days. All drugs were administered BID, with the exception of tetracycline, which was administered QID. Eradication was confirmed by (14)C-UBT 6 weeks after the end of the treatment. Histologic examination and (14)C-UBT were conducted by investigators blinded to the protocols. Patients were asked to report any adverse events (AEs) during the treatment period. RESULTS Three hundred white patients were enrolled in the study and evenly randomized into the sequential treatment group (98 males and 52 females; mean age, 40.2 years) and the PAC group (86 males and 64 females; mean age, 41.2 years). A total of 274 patients completed the study per protocol (PP). Twenty-six patients discontinued: lost to follow-up (16), withdrawn due to AEs (9); and noncompliance (1). The intent-to-treat (ITT) and PP H pylori eradication rates were 72.6% and 80.1% in the sequential group, and 58% and 63% in the PAC group, respectively. The eradication rate was significantly higher in the sequential group compared with the PAC group in both the ITT and PP populations (P=0.01 and P=0.002, respectively). The eradication rates were higher in nonsmoking patients compared with smoking patients both in the sequential group (85.8% vs 70.5%) and the PAC group (67.7% vs 53.3%), but the results were not statistically significant when the groups were analyzed separately. Overall, 32 patients (10.7%) reported an AE. Treatment was discontinued in 9 patients because of serious AEs (sequential group--abdominal pain [2 patients], diarrhea [1], chest pain [1], and vaginal pruritus [1]; PAC group--nausea/vomiting [2], chest pain [1], and numbness [1]). There were no significant between-group differences in regard to compliance or AEs. Univariate analyses found no significant effect of sex, age, alcohol consumption, antacid usage, or gastritis score on the eradication rates. CONCLUSIONS A 14-day sequential treatment regimen achieved a significantly higher eradication rate of H pylori compared with standard PPI-based triple regimen in this small selected population. Large, double-blind, controlled studies are needed to confirm these results.

Insulin sensitizers for the treatment of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in the Western world and is closely associated with metabolic syndrome, which includes hypertension, central obesity, dyslipidemia and insulin resistance. NAFLD includes a wide spectrum of liver alterations, ranging from simple hepatic steatosis to variable degrees of fibrosis, cirrhosis and even hepatocellular carcinoma. Although the etiology and progression of the disorder remain poorly understood, insulin resistance is considered to play a pivotal role in the pathogenesis. Insulin sensitizers such as biguanides, thiazolidinediones (TZDs), glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase 4 inhibitors have been studied as therapeutic approaches for NAFLD in recent years. Metformin improves insulin sensitivity and serum alanine transaminase and aspartate transaminase (ALT/AST) levels in the majority of subjects; however, it has no significant effect on liver histology. TZDs improve insulin sensitivity, serum ALT/AST levels and histology in some cases, but there are some concerns about the safety of long-term therapy. Selection of appropriate patients for avoiding side effects and the treatment of underlying disease are the main points. These drugs are the best choice for the treatment of NAFLD in patients with type 2 DM who are also candidates for treatment with an insulin sensitizer. The present review provides an overview of insulin sensitizers in the treatment of NAFLD.

The efficacy of bismuth containing quadruple therapy as a first-line treatment option for Helicobacter pylori.

BACKGROUND:  Helicobacter pylori eradication rates have tended to decrease recently, mostly due to increasing antibiotic‐resistance. The present study aimed to compare the efficacy of bismuth‐based quadruple regimen with proton pump inhibitor‐based triple regimen for eradication of H. pylori.

Comparison of levofloxacin-containing sequential and standard triple therapies for the eradication of Helicobacter pylori

BACKGROUND There is an important concern about the success of standard triple treatment for Helicobacter pylori (H. pylori) in recent years. Better eradication rates have been reported with sequential treatment in current studies. This study aimed to compare the success of a novel levofloxacin-containing sequential regimen with standard triple therapy. METHODS H. pylori-positive patients with non-ulcer dyspepsia were randomly allocated to one of the study groups. The patients on sequential arm were given esomeprazole 40 mg BID and amoxicillin 1g BID for the first week followed by esomeprazole 40 mg BID, levofloxacin 500 mg QD and metronidazole 500 mg TID for the second week. The patients on standard triple arm were given esomeprazole 40 mg BID, amoxicillin 1g BID and clarithromycin 500 mg BID for 2 weeks. Eradication was assessed by urea breath test on 6th weeks. RESULTS Seventy-five patients were enrolled in each group; 72 in sequential arm and 67 in standard arm completed the protocols. H. pylori eradication rate of per protocol was 90% in sequential versus 57% in standard treatment groups with a statistical significance (p<0.000). Both regimens were similarly well tolerated and side effects were comparable. Only one patient in sequential arm stopped the treatment because of side effects. CONCLUSION The levofloxacin-containing sequential therapy is a significantly better strategy than the standard triple treatment for H. pylori eradication. Standard triple treatment is no more effective for H. pylori in our population and levofloxacin-containing sequential regimen might be used as a first-line eradication option.

Importance of Serum CA 125 Levels in Malignant Peritoneal Mesothelioma

Elevated levels of CA 125 have been shown to be present in the serum of patients with ovarian carcinoma, non-gynaecological cancers and some benign diseases. However, the value of CA 125 in malignant peritoneal mesothelioma has not been studied in detail. Therefore, 7 patients with diffuse malignant mesothelioma were included in this study. Median age was 52.4 (range 16-73), and 6 of them were women. The mean serum CA 125 level was 308 kU/l (range 8-1,300 kU/l). Serum CA 125 concentrations were found to be elevated in all 6 female patients. In 3 patients, serum CA 125 levels were followed prospectively and showed a very close correlation with the response to chemotherapy. In 2 responder patients, initially elevated CA 125 levels returned to normal during remission after chemotherapy. In 1 non-responder patient, the serum CA 125 level continued to rise. In conclusion, the serum CA 125 level might be helpful in the diagnosis and follow-up of malignant peritoneal mesothelioma.

Value of adding GNAS testing to pancreatic cyst fluid KRAS and carcinoembryonic antigen analysis for the diagnosis of intraductal papillary mucinous neoplasms.

Molecular analysis of pancreatic cyst fluid (PCF) has been proposed as a novel method for differentiating pancreatic cystic lesions (PCL). The present study aimed to investigate the value of GNAS testing when added to KRAS and carcinoembryonic antigen (CEA) testing of PCF for the diagnosis of intraductal papillary mucinous neoplasms (IPMN).

The effect of fatty pancreas on serum glucose parameters in patients with nonalcoholic steatohepatitis

OBJECTIVE Fatty pancreas (FP) is related to obesity, and may have some clinical implications on glucose metabolism. The frequency and importance of FP in patients with nonalcoholic steatohepatitis (NASH) are not clear. This study aimed to investigate: the frequency of FP in patients with NASH, and its effects on serum glucose parameters. METHODS FP was detected and graded by transabdominal ultrasonography (USG) in patients with biopsy-proven NASH and healthy controls. Body Mass Index and waist circumference were recorded, and serum lipids, fasting serum glucose, HbA1c, OGTT 2-h, insulin level, insulin resistance, type 2 diabetes mellitus (DM) and prediabetes rates were detected. RESULTS Eighty-four subjects with NASH and 35 healthy controls were enrolled in the study. There was no FP in 41 (48.8%) of the NASH patients according to the study criteria. Forty-three of the NASH patients and 5 of the controls had different grades of fat in their pancreas (51.2% vs. 14%, p=0.001). The HbA1c and OGTT 2-h results were significantly higher in NASH patients with FP compared to those without FP (p=0.003 and p=0.018). The rates of both prediabetes and DM were also found to be significantly increased in NASH patients with FP (p=0.004). The mean waist circumference was higher in patients with FP (p=0.027). Grade of FP by USG showed no effect on study parameters in subgroup analysis. CONCLUSION FP is common in patients with NASH and increases the rate of prediabetes and DM. The coexistence of both NASH and FP has a further impact on glucose metabolism and DM frequency.

The Value of Adding GNAS Testing to Pancreatic Cyst Fluid KRAS and CEA Analysis for the Diagnosis of Intraductal Papillary Mucinous Neoplasms

Molecular analysis of pancreatic cyst fluid (PCF) has been proposed as a novel method for differentiating pancreatic cystic lesions (PCL). The present study aimed to investigate the value of GNAS testing when added to KRAS and carcinoembryonic antigen (CEA) testing of PCF for the diagnosis of intraductal papillary mucinous neoplasms (IPMN).