Characteristics of Newly Diagnosed Hepatocellular Carcinoma Patients Across Turkey: Prospective Multicenter Observational 3K Registry Study.

AIMS: To evaluate patient profile for epidemiological and clinicopathological characteristics and potential risk/prognostic factors in newly diagnosed hepatocellular carcinoma (HCC) patients across Turkey. METHODS: A total of 547 patients (mean (SD) age 62.6 (10.3) years, 81.9% were males) were included in this registry study. Data on patient characteristics, etiologies of HCC, laboratory values, and tumor characteristics and stages were recorded at study enrollment. RESULTS: HBV infection (68.2%) was the leading etiology, followed by HCV infection (17.2%), HDV infection (5.5%), alcohol (6.4%), and NAFLD (3.5%), as the major etiologies. Considering that 51.6% of the patients had >5 cm HCC, 44% were Child-Pugh B/C and 57% were BCLC B-D, it appears that a significant group of HCC patients were diagnosed at advanced stages. Of 540 patients, 271 (50.2%) were referred or applied with the diagnosis of HCC. Patients with HCC at presentation had larger tumor size (median (min-max) 6.6 (0-30) vs. 4.8 (0-90) cm, P < .001) and more advanced BCLC stage (Stage C-D in 40.8% vs. 26.4%, respectively, P = .005), compared to patients who were diagnosed during follow-up. CONCLUSIONS: Our findings revealed that HBV infection was the leading etiology and a moderate-to-advanced disease was evident in more than half of patients at the time of diagnosis. HCC patients diagnosed at follow-up had smaller tumor size and earlier BCLC stage.

Role of endoscopic interventions and electroincision in benign anastomotic strictures following colorectal surgery.

BACKGROUND/AIMS: The anastomotic strictures are one of the most common colorectal surgery complications, and various endoscopic techniques have been defined. Balloon dilation is the most well-known and the simplest procedure. In this article, we aimed to present our series of endoscopic interventions and electroincision management for anastomotic strictures. MATERIALS AND METHODS: The files of 59 patients, who underwent colorectal surgery between January 2010 and September 2017 in our hospital and were diagnosed during the follow-up with anastomotic stricture, were analyzed. The outcomes of endoscopic interventions such as balloon dilation and electroincision were compared and reported. RESULTS: The mean age of the 59 patients included in the study was 59.5±16.26 years. The primary operative indications were colorectal cancer in 46, inflammatory bowel disease in 7, diverticulum in 5, and penetrating trauma in one patient. Single- or multiple-balloon dilations were successful in 48 patients. Electroincision was performed in 11 patients because of the balloon dilation failure. None of the patients needed a secondary surgery. During the mean 33.75 months of the follow-up, the stricture recurred in seven patients who had undergone balloon dilation. Repeated balloon dilation was successful in these patients without any need for an additional surgical intervention. CONCLUSION: Balloon dilation can be performed safely as the primary treatment option, because of its easy access and noninvasive application. Electroincision is also a safe and effective endoscopic technique that can be preferred especially when the balloon dilation fails.

Evaluation of hepatitis A, B, and C serology in patients with cirrhosis and intensive alcohol consumption.

OBJECTIVE: The objective of this study was to evaluate the serology of hepatitis A, B, and C in patients with cirrhosis and intensive alcohol consumption. METHODS: We retrospectively reviewed the viral serology results of 817 patients with cirrhosis and intensive alcohol consumption who presented to the Gastroenterology Clinic of Atatürk Training and Research Hospital of Izmir Katip Çelebi University between April 2008 and December 2017. The diagnosis of cirrhosis was based on clinical and biochemical evaluations and imaging results. Patients consuming absolute alcohol 40 g/day for >10 years were included and those who quit drinking ≥15 years ago were excluded. RESULTS: Of all the patients, 806 (98.7%) were positive for anti-HAV IgG, 159 (19.5%) for HBsAg, and 32 (3.9%) for anti-HCV. Genotyping was performed in 13 patients. Genotype 1 was detected in 10 patients (1a, one patient; 1b, nine patients) and genotype 3 in three patients. Of the patients with HBV, 10.0% had HBeAg and 7.6% had anti-delta. One-hundred and two (12.5%) patients had HCC, and of these, six (5.9%) were HCV-positive and 53 (52.0%) were HBsAg-positive. CONCLUSION: Patients with cirrhosis and intensive alcohol consumption have an increased hepatitis B and C prevalence. Patients with chronic viral hepatitis with alcohol habit are at a higher risk for HCC. Therefore, patients with cirrhosis and intensive alcohol consumption should be screened for hepatitis B and C.

Fecal Elastase Levels Predict Honeycombing in Pancreas Detected with Endoscopic Ultrasound.

Background and Study Aims: We aimed to demonstrate the association between fecal elastase levels and Rosemont categories in patients with chronic changes in pancreas detected with endoscopic ultrasound. Patients and Methods: Patients were selected consecutively from endosonography examinations performed for upper gastrointestinal subepithelial lesions and for pancreas evaluation. Pancreas imaging findings were categorized according to the Rosemont criteria using echoendoscope. Patients who were indeterminate of, suggestive of, and consistent with chronic pancreatitis were included in the study. Fecal elastase measurements were performed after the patients were qualified to participate in the study according to endosonography findings. Results: Seventy patients were included in the study. 54 of them were male. Mean age of the patients was 51.7 ± 10.2 year. There were 36 patients in the indetermine group for chronic pancreatitis. Mean fecal elastase level was 507.1 ± 14.6 µg/g in the indeterminate group. There were 24 patients in the suggestive group of chronic pancreatitis. Mean fecal elastase level was 400.4 ± 121.4 µg/g in the suggestive group of chronic pancreatitis. There were 10 patients, in the consistent group with chronic pancreatitis. Mean fecal elastase level was 134.8 ± 86.1. The difference between the three groups of fecal elastase values was statistically significant compared with Kruskal Wallis test. Ordinal logistic regression analysis showed that there was a significant relation between endosonografic categories and fecal elastase values with Nagelkerke value of 0.704. Conclusions: Fecal elastase levels of each of the endosonographic categories were significantly different from each other. Also, fecal elastase values can predict chronic changes in pancreas detected with endoscopic ultrasound.

Evaluation of Laboratory Findings and Mortality in Elderly Patients with Acute Biliary Pancreatitis.

OBJECTIVES: Gallstones are the most common cause of acute biliary pancreatitis. Laboratory and imaging findings as well as age are important predictors for mortality. Hospitalization rate is also higher in elderly patients. In this study, we investigated clinical parameters and total mortality in patients with acute pancreatitis aged >65 years. METHODS: In this study, 852 patients who entered the Gastroenterology Clinic for acute biliary pancreatitis between April 2006 and October 2013 were included. Data were retrospectively collected from the electronic record system. The patients with elevated aspartate aminotransferase levels (i.e. three times higher than normal value), cholelithiasis, cholecystectomy history, or choledocholithiasis were accepted as the patients with acute biliary pancreatitis. Patients were divided into two groups based on their age, i.e., >65 and <65 years. RESULTS: In the group with patients aged <65 years, serum alanine aminotransferase, albumin, hematocrit, and amylase, and in the group with patients aged >65 years, urea, leukocyte, and C-reactive protein levels were significantly different. Median hospital stay was similar in both the groups. The rate of detection of choledocholithiasis was significantly higher in elderly patients (p<0.001). Mortality rate was significantly higher in elderly patients for 28 day (0.21% and 2.95%, p<0.001) and 90 day (1.25% and 5.63%, p<0.001). In logistic regression multivariate analysis, age (OR 2.0, 95% CI 1.54-1.36; p=0.006), elevated urea levels (OR 1.12, 95% CI 1.05-1.19; p=0.001), elevated hematocrit levels (OR 1.42, 95% CI 1.13-1.77; p=0.002), and decreased albumin levels (OR 0.05, 95% CI 0.004-0.652; p=0.022) were found predictors for 90-day mortality. CONCLUSION: Laboratory findings in elderly patients with acute pancreatitis may differ from those in younger patients. Although radiological findings are similar in both the groups, mortality is higher in the group with patients aged >65 years.

Improving the standard sequential treatment of Helicobacter pylori with either extended treatment or by adding bismuth.

BACKGROUND AND STUDY AIMS: Standard sequential treatment for Helicobacter pylori (H. pylori) eradication has less success because of increasing clarithromycin resistance. Extended treatment and bismuth containing regimens were, therefore, investigated. PATIENTS AND METHODS: Consecutive H. pylori-positive patients with dyspepsia were randomly allocated to one of the three sequential regimens: The first group was given lansoprazole 30mg b.i.d. plus amoxicillin 1g b.i.d. for the first 5days, followed by lansoprazole 30mg b.i.d., clarithromycin 500mg b.i.d., and metronidazole 500mg t.i.d. for the second 5days (standard sequential, SS). The second group was given the same regimen but for 7+7days instead of 5+5days (extended sequential, ES). In the third group, colloidal bismuth 600mg b.i.d. was added to the second regimen for 14days (extended sequential+bismuth subcitrate, ES+B). Urea breath test or histology was performed before enrolment and 6weeks after the end of treatment to detect H. pylori. RESULTS: A total of 280 patients were included in the study. Per-protocol eradication rates were 62% (56/90), 72% (56/78), and 75% (54/72) in patients who received SS, ES, and ES+B regimens, respectively. Moreover, intention-to-treat eradication rates were 53% (56/104), 62% (56/90) and 62% (54/86), respectively. The differences in eradication rates between the groups were not statistically significant. CONCLUSION: Although prolonging of the sequential treatment to 14days may be considered, addition of bismuth to the regimen is of no avail.

The association of nonalcoholic fatty liver disease with genetic polymorphisms: a multicenter study.

INTRODUCTION: Growing evidence suggests that multiple factors, such as insulin resistance, nutritional factors, gut microbiota, and hormones released from the adipose tissue, act together on genetically predisposed individuals. We aimed to investigate whether various single-nucleotide polymorphisms (SNPs) play a role in the development of nonalcoholic fatty liver disease (NAFLD) and severity of liver damage in the Anatolian population. METHODS: Two hundred and sixteen patients with biopsy-proven NAFLD and 150 control participants, aged 18-70 years, were consecutively enrolled in this multicenter study. Blood samples were genotyped for the PNPLA3 (rs738409), IL28B (rs12979860, rs12980275, rs8099917), PPAR-α 227 ALA, PPAR-γ pro 12 ALA, SOD2 C47T, and LOX-1 IVS4-14 polymorphisms using the custom-made LightSNiP assays on a LightCycler 480 II instrument. RESULTS: Genotypic distributions of PNPLA3 rs738409 SNPs were different between NAFLD and control participants, but not for other SNPs. The PNPLA3 rs738409 GG polymorphism was associated with a 27-fold increased risk of development of NAFLD (odds ratio=27.8, 95% confidence interval: 3.5-218.4; P=0.002). Patients with the PNPLA3 GG genotype had higher nonalcoholic fatty liver disease activity score levels compared with patients with the PNPLA3 CC genotype (P<0.005). NAFLD patients without fibrosis had a higher frequency of IL28B rs12979860 TT and rs12980275 GG genotypes compared with NAFLD patients with fibrosis (P<0.005). CONCLUSION: The present study proposes that polymorphisms in the PNPLA3 gene have highly predictive value in the development of NAFLD and are independently associated with the severity of liver histology in patients with NAFLD. The results of this study suggest that IL28B rs12979860 TT or rs12980275 GG may play an important protective role against the development of advanced fibrosis and even cirrhosis.

Turkey 2017 Clinical Practice Guidelines on recommendations for screening diagnosing and managing hepatitis C virus.

The present guideline updates the Turkish recommendations for the screening, diagnosis and management of Hepatitis C virus (HCV) infection prepared by the Turkish Association for the Study of the Liver (TASL) and Viral Hepatitis Society (VHS). The aim of this guidance was to provide updates recommendations to physicians, who are interested in HCV care on the optimal screening, diagnosis and pre-treatment management for patients with HCV infection in Turkey. These recommendations, produced by panel experts, were aimed to addresses the management issues ranging from diagnosis and linkage to care, to the optimal treatment regimen in patients with HCV infection. Recommendations are based on evidence and opinions of more than 70% of the panelists. This guidance is supported by the memberships of two societies and not by pharmaceutical companies. This guidance will be updated frequently as new data become available.

Propofol-Based Sedation Versus General Anesthesia for Endoscopic Submucosal Dissection.

The main objective of this study is to evaluate general anesthesia or propofol-based sedation methods at gastric endoscopic submucosal dissection (ESD) procedures.The anesthetic method administered to cases undergoing upper gastrointestinal ESD between 2013 and 2015 was retrospectively investigated. Procedure time, lesion size, dissection speed, anesthesia time, adverse effects such as gag reflex, nausea, vomiting, cough, number of desaturation episodes (SpO2 < 90%), oropharyngeal suctioning requirements, hemorrhage, perforation, and amount of anesthetic medications were recorded.There were 54 and 37 patients who were administered sedation (group S) and general anesthesia (group G), respectively. The demographics of the groups were similar. The calculated dissection speed was significantly high in group G (36.02 ±â€Š20.96 mm/min) compared with group S (26.04 ±â€Š17.56 mm/min; P = 0.010). The incidence of nausea, cough, number of oropharyngeal suctioning, and desaturation episodes were significantly high in group S compared with that in group G (P < 0.5). While there was no difference between the groups in terms of hemodynamic parameters, in group S the use of propofol and in group G the use of midazolam and fentanyl were significantly higher (P < 0.05). Anesthesia time, postoperative anesthesia care unit, and hospital stay durations were not significantly different between the groups.General anesthesia increased dissection speed and enhanced endoscopist performance when compared with propofol-based sedation technique.

DNA methylation profiling identifies novel markers of progression in hepatitis B-related chronic liver disease.

BACKGROUND: Chronic hepatitis B infection is characterized by hepatic immune and inflammatory response with considerable variation in the rates of progression to cirrhosis. Genetic variants and environmental cues influence predisposition to the development of chronic liver disease; however, it remains unknown if aberrant DNA methylation is associated with fibrosis progression in chronic hepatitis B. RESULTS: To identify epigenetic marks associated with inflammatory and fibrotic processes of the hepatitis B-induced chronic liver disease, we carried out hepatic genome-wide methylation profiling using Illumina Infinium BeadArrays comparing mild and severe fibrotic disease in a discovery cohort of 29 patients. We obtained 310 differentially methylated regions and selected four loci comprising three genes from the top differentially methylated regions: hypermethylation of HOXA2 and HDAC4 along with hypomethylation of PPP1R18 were significantly linked to severe fibrosis. We replicated the prominent methylation marks in an independent cohort of 102 patients by bisulfite modification and pyrosequencing. The timing and causal relationship of epigenetic modifications with disease severity was further investigated using a cohort of patients with serial biopsies. CONCLUSIONS: Our findings suggest a linkage of widespread epigenetic dysregulation with disease progression in chronic hepatitis B infection. CpG methylation at novel genes sheds light on new molecular pathways, which can be potentially exploited as a biomarker or targeted to attenuate inflammation and fibrosis.

Radial EUS Examination Can be Helpful in Predicting the Severity of Acute Biliary Pancreatitis.

We investigated the utility of noncontrast enhanced endosonography (EUS) in predicting the severity of acute pancreatitis (AP) during the first 72 to 96 h of admission.In total, 187 patients with acute biliary pancreatitis were included. The patients were classified into 2 groups as having severe and mild AP according to the Modified Glasgow scoring and computerized tomography severity index (SI). The 158 cases with mild and 29 cases with severe AP had a similar age and sex distribution.Although none of the cases with mild AP developed morbidity and death, of the cases with severe AP, 16 developed serious morbidities and 5 died. On EUS examination, we looked for parenchymal findings, peripancreatic inflammatory signs, free or loculated fluid collections, and abnormalities of the common bile duct and the pancreatic channel. Statistical analysis indicated a significant relationship between the severity of AP with diffuse parenchymal edema, periparenchymal plastering, and/or diffuse retroperitoneal free fluid accumulation, and peri-pancreatic edema. We also defined an EUSSI and found that the EUSSI had sensitivity of 89.7%, specificity of 84.2%, positive predictivity value (PPV) of 88.9%, negative predictivity value (NPV) of 91.2%, and an accuracy of 87.9% in the differentiation of mild and severe AP. We found that the EUSSI had an accuracy of 72.4%, sensitivity of 75.4%, specificity of 65.1%, PPV of 69.3%, and NPV of 73.1% for determining mortality.Our data suggest that EUS allowed us to accurately predict the severity and mortality in nearly 90% of cases with AP.

Endoscopic ultrasound-guided tissue sampling: How can we improve the results?

Endoscopic ultrasound (EUS) enables a gastroenterologist to sample the masses of the middle and inferior mediastinum, which are adjacent to the esophagus; cystic or solid lesions of the pancreas, which are adjacent to the stomach and duodenum; and perirectal lesions. Needles used for EUS sampling include aspiration (19, 20, and 22 Gauge) or core biopsy needles (ProCore and Trucut) (19, 20, and 22 Gauge). The type and size of EUS needles do not alter the diagnostic results. Rapid on-site cytopathological evaluation will increase the diagnostic efficacy to 100% without prolonging the procedure time. Diagnostic efficacy of EUS-guided fine-needle aspiration or core biopsy depends on the experience of an endoscopist and a cytopathologist. In the presence of an experienced endoscopist and cytopathologist, the size of the needle does not have any significant impact on the diagnostic success.

Can red cell distribution width be a marker of disease activity in ulcerative colitis?

AIM: The current study aimed to investigate the association between disease activity and red cell distribution width (RDW) levels in ulcerative colitis and to determine whether RDW can be used as a marker of disease activity in non-anemic ulcerative colitis. METHODS: The RDW levels of 310 ulcerative colitis patients who underwent colonoscopy were analyzed retrospectively. The patients were divided into two groups (active disease and remission) according to the endoscopic activity index. In addition, the accuracy of RDW in determining disease activity in non-anemic patients was assessed. The efficacy of RDW in determining disease activity was compared to that of white blood cell count, platelet count, C-reactive protein, and erythrocyte sedimentation rate. RESULTS: Two hundred and six (66.5%) patients had active disease, and 104 (33.5%) were in remission. The mean RDW levels in patients with active ulcerative colitis and in those in remission were 16.8±2.9 and 15.5±1.4, respectively (P<0.001). Ninety-six (46.6%) patients in the active disease group and 89 (85.6%) in the remission group were non-anemic, and their respective RDW levels were 15.4±1.2 and 15.3±1.1 (P=0.267). The sensitivity and specificity of RDW in determining inflammation were 41% and 91%, respectively (AUC 0.65, P<0.001). CONCLUSIONS: This study demonstrated that RDW can be used as a marker for disease activity in ulcerative colitis, but it did not have the same efficacy in the non-anemic group.

Bactericidal permeability increasing protein gene polymorphism is associated with inflammatory bowel diseases in the Turkish population.

BACKGROUND/AIMS: Inflammatory bowel disease, a chronic inflammatory disease with unknown etiology, affects the small and large bowel at different levels. It is increasingly considered that innate immune system may have a central position in the pathogenesis of the disease. As a part of the innate immune system, bactericidal permeability increasing protein has an important role in the recognition and neutralization of gram-negative bacteria. The aim of our study was to investigate the involvement of bactericidal permeability increasing protein gene polymorphism (bactericidal permeability increasing protein Lys216Glu) in inflammatory bowel disease in a large group of Turkish patients. PATIENTS AND METHODS: The present study included 528 inflammatory bowel disease patients, 224 with Crohn's disease and 304 with ulcerative colitis, and 339 healthy controls. RESULTS: Bactericidal permeability increasing protein Lys216Glu polymorphism was found to be associated with both Crohn's disease and ulcerative colitis (P = 0.0001). The frequency of the Glu/Glu genotype was significantly lower in patients using steroids and in those with steroid dependence (P = 0.012, OR, 0.80; 95% confidence interval [CI]: 0.68-0.94; P = 0.0286, OR, 0.75; 95% CI: 0.66-0.86, respectively). There was no other association between bactericidal permeability increasing protein gene polymorphism and phenotypes of inflammatory bowel disease. CONCLUSIONS: Bactericidal permeability increasing protein Lys216Glu polymorphism is associated with both Crohn's disease and ulcerative colitis. This is the first study reporting the association of bactericidal permeability increasing protein gene polymorphism with steroid use and dependence in Crohn's disease.

Serum Syndecan-1 Levels and Its Relationship to Disease Activity in Patients with Crohn's Disease.

Background. Syndecan-1 (SDC-1), a member of the family of heparan sulfate proteoglycans, plays an important role in the resolution of inflammation. This study aimed to investigate the relationship between SDC-1 and disease activity in Crohn's disease (CD). Methods. Serum samples of 54 patients with CD and 30 healthy controls were obtained. First, SDC-1 levels of the CD patients were compared to the control group. Subsequently, SDC-1 levels were analyzed in patients with CD in active and remission periods. Finally, SDC-1 efficacy in predicting disease activity was evaluated by performing correlation analysis between SDC-1 and C-reactive protein (CRP) and Crohn's disease activity index (CDAI). Results. SDC-1 level was higher in the CD group (61.9 ± 42.6 ng/mL) compared with the control group (34.1 ± 8.0 ng/mL) (p = 0.03). SDC-1 levels were higher in active CD patients (97.1 ± 40.3 ng/mL) compared with those in remission (33.7 ± 13.5 ng/mL) (p < 0.001). A significant positive correlation was found between SDC-1 and CRP (r = 0.687, p < 0.001) and between SDC-1 and CDAI (r = 0.747, p < 0.001). Conclusion. Serum levels of SDC-1 are higher in CD compared to the normal population and can be an effective marker of disease severity.