Genetic Investigations in Turkish Idiopathic Pancreatitis Patients Show Unique Characteristics.

BACKGROUND/AIMS: Pancreatitis is one of the leading causes of digestive system-related hospital admissions, and it has a genetic background in a considerable portion of the patients. In this study, we aimed to investigate the genetic risk factors of idiopathic pancreatitis in Turkish patients and the contribution of copy number variations to the pathogenesis. MATERIALS AND METHODS: Idiopathic pancreatitis is defined as failure to detect risk factors despite comprehensive clinical assessments. Next-generation sequencing and multiple ligand-dependent probe amplification of PRSS1, SPINK1, CTRC, and CFTR were performed. For further genotype-phenotype correlations, patients were also questioned for the age of onset, family history, and pancreatic divisum. RESULTS: A total of 68 idiopathic pancreatitis cases were enrolled. Variants with potential clinical significance of PRSS1 were identified in 13.4%, SPINK1 in 6.3%, CTRC in 4.7%, and CFTR in 26.5% of the patients. No copy number variants were seen in any of these genes. At least 7.4% of the participants had complex genetic etiology involving 2 genes. CONCLUSIONS: At least 42.6% of the participants had a potential genetic risk factor. Five novel genetic variants were identified, and distinctive genetic risk factors of Turkish population were shown. The results showed that genetic etiology was frequent in pancreatitis and it was even more prominent in patients with early-onset disease. Considering that genetic risk factors may be informative for decisionmaking in the treatment options in addition to providing extensive prognostic value and familial genetic consultation; clinicians need to be more eager to offer genetic tests to pancreatitis patients.

Incidence, Risk Factors, and Treatment of Proximally Migrated Pancreatic Stents.

AIM: The aim of this study was to investigate the incidence, risk factors, and treatment strategies of proximally migrated pancreatic stents. MATERIALS AND METHODS: The data of 626 sessions of 421 patients with pancreatic duct stenting were retrospectively analyzed between 2010 and 2018, and patients with proximally migrated stents were included in the study. RESULTS: Of 626 stents examined, 77 migrated proximally (12%). The migration rate (MR) was 16%, 2%, and 7%, respectively, in patients treated with chronic pancreatitis, malignancy, and pancreatic leakage indication. The MR was 14% in procedures with pancreatic duct stenosis, 21% in procedures with pancreatic sphincterotomy, and 27% in procedures performed from minor papillae. The MR of the 5, 7, and 10 Fr stents was 4%, 17%, and 10%, respectively. Of the 77 migrated stents, 64 were successfully removed (83%). This success rate (SR) was 84% in procedures with chronic pancreatitis indication, 83% in procedures with pancreatic duct stenosis, 79% in procedures with sphincterotomy, and 75% in procedures performed from minor papillae. The SR of the 5, 7, and 10 Fr stents was 100%, 79%, and 92%, respectively. It was also determined that 33 stents were fractured and migrated (43%). The SR of the fractured stents was 76%. Moreover, of the stents that were successfully removed, 35 were removed with forceps (55%) and 15 (23%) were removed with a balloon. Furthermore, in 47 cases, the stent was removed in the first session (73%). Acute pancreatitis occurred in 5 patients (8%) and perforation occurred in 1 patient (2%). CONCLUSION: In this study, it was shown that proximal migration of pancreatic stents is frequent and most of these stents can be removed successfully.

Endoscopic retrograde cholangiography via a permanent access loop.

BACKGROUND/AIMS: The aim of this study was to investigate the indications, technical and clinical success, and complications of the endoscopic retrograde cholangiography (ERC) via a permanent access loop (PAL). MATERIALS AND METHODS: Twenty patients who underwent ERC through PAL between 2009 and 2017 were included in this study. The technical success was described as achieving access to the bile ducts through PAL and the clinical success was described as the clinical and laboratory improvement of the patients after the procedure. RESULTS: The study was performed with 20 patients. The median follow-up duration was 24 months (3-96) and the median number of ERC sessions was 3.9 (1-10). The most common ERC indications through PAL were stones (40%) and cholangitis (30%). In 16 patients (75%), anastomotic or branched strictures were observed. The improvement of strictures via intermittent stenting and dilatation was observed in 6 patients, but no improvement was observed in 5 patients. The treatment of those 5 patients continues. In this study, the technical success was 100% and clinical success was 85%. While no mortality due to PAL-mediated ERC was observed, free wall perforation was seen in one patient who was referred to surgery. CONCLUSION: PAL-mediated ERC procedure is a technique with high technical and clinical success and low complication rate in patients who require frequent percutaneous procedures and those with difficult access to the biliary tract.

De novo isolated gastrointestinal tract vasculitis without associated systemic disease in renal transplant recipients successfully treated with rituximab.

Systemic vasculitic diseases can show recurrence after kidney transplantation, but de novo systemic vasculitis is rarely seen after kidney transplantation, and in literature, there are only a few cases. In general population, the incidence of isolated organ vasculitis is unknown, and according to the best of our knowledge, there is no information about de novo isolated organ vasculitis after renal transplantation. We report, most probably, the first case of a 40-year-old woman who was restarted on dialysis treatment after renal transplantation and developed isolated gastrointestinal vasculitis and intestinal hemorrhage under immunosuppressive treatment. She was treated successfully with rituximab.

Can the treatment duration be shortened in bismuth-containing therapies for Helicobacter pylori eradication?

BACKGROUND/AIMS: The duration of Helicobacter pylori (H. pylori) eradication therapy as a range (e.g., 10-14 days) is an ignored problem. There is no any particular treatment duration described in current guidelines, and the conditions for when to use 10-day therapy vs. 14-day therapy have not been elucidated. The aim of this study is to determine an effective and reliable H. pylori treatment duration in clinical practice. There were four different treatment modalities administered to groups, and success rates were compared. MATERIALS AND METHODS: Patients were eligible to participate in the study if they had a biopsy-proven H. pylori infection. Each patient was randomly assigned to one of the four treatment groups according to a predetermined sequence: 14-day or 10-day bismuth-containing quadruple therapy (BQT) groups and 14-day or 10-day moxifloxacin-bismuth-combined treatment (MBCT) groups. RESULTS: A total of 216 patients (54 per group) were enrolled. Two-hundred six patients (95.3%) completed therapy. There was no significant difference in the eradication rates between those patients who received 10- and 14-days BQT regimens (p=0.67). The 14-BQT protocol had the highest eradication rate, the MBCT regimes had the highest compliance, and the 10-MBCT protocol had the poorest results for H. pylori eradication. The posttreatment questionnaire on adverse effects identified nausea/vomiting as the most common side effect (35.7%). CONCLUSION: Overall, the results of our study suggest that shortening the BQT protocol duration to 10 days does not weaken the H. pylori eradication rate. Moreover, quinolone-containing therapies with the lowest eradication rate among the groups should not be offered as a salvage treatment in case of the BQT failure.

Genome-wide Association Study Identifies Genetic Variants Associated With Early and Sustained Response to (Pegylated) Interferon in Chronic Hepatitis B Patients: The GIANT-B Study.

BACKGROUND: (Pegylated) Interferon ([Peg]IFN) therapy leads to response in a minority of chronic hepatitis B (CHB) patients. Host genetic determinants of response are therefore in demand. METHODS: In this genome-wide association study (GWAS), CHB patients, treated with (Peg)IFN for at least 12 weeks ± nucleos(t)ide analogues within randomized trials or as standard of care, were recruited at 21 centers from Europe, Asia, and North America. Response at 24 weeks after (Peg)IFN treatment was defined as combined hepatitis B e antigen (HBeAg) loss with hepatitis B virus (HBV) DNA <2000 IU/mL, or an HBV DNA <2000 IU/mL for HBeAg-negative patients. RESULTS: Of 1144 patients, 1058 (92%) patients were included in the GWAS analysis. In total, 282 (31%) patients achieved the response and 4% hepatitis B surface antigen (HBsAg) loss. GWAS analysis stratified by HBeAg status, adjusted for age, sex, and the 4 ancestry components identified PRELID2 rs371991 (B= -0.74, standard error [SE] = 0.16, P = 3.44 ×10-6) for HBeAg-positive patients. Importantly, PRELID2 was cross-validated for long-term response in HBeAg-negative patients. G3BP2 rs3821977 (B = 1.13, SE = 0.24, P = 2.46 × 10-6) was associated with response in HBeAg-negative patients. G3BP2 has a role in the interferon pathway and was further examined in peripheral blood mononuclear cells of healthy controls stimulated with IFNα and TLR8. After stimulation, less production of IP-10 and interleukin (IL)-10 proteins and more production of IL-8 were observed with the G3BP2 G-allele. CONCLUSIONS: Although no genome-wide significant hits were found, the current GWAS identified genetic variants associated with (Peg)IFN response in CHB. The current findings could pave the way for gene polymorphism-guided clinical counseling, both in the setting of (Peg)IFN and the natural history, and possibly for new immune-modulating therapies. CLINICAL TRIALS REGISTATION: NCT01401400.

Cyclophosphamide-induced severe acute hepatitis in a rheumatic disease: case-based review.

In rheumatology practice, the risk of hepatotoxicity from medications, including non-steroidal anti-inflammatory drugs, notably, and methotrexate, sulfasalazine, leflunomide, and azathioprine is highly recognized by the rheumatologists. On the other hand, hepatotoxicity is neither a commonly expected nor a well-known side effect of cyclophosphamide (CYC) which is particularly used for vital organ involvements in systemic lupus erythematosus (SLE) and systemic vasculitis. Here we reported a 19-year-old case of SLE who, while on oral CYC treatment of 100 mg/day, was detected to have asymptomatic liver enzyme elevation and then developed acute hepatitis due to intravenously administered high-dose (1 g) CYC for neuro-lupus. Results of liver biopsy indicated drug-related toxicity. We discussed here with the other, although rare, cases available in the literature with an attempt to highlight the risk of hepatotoxicity and acute hepatitis due to CYC.

A New Marker to Determine Prognosis of Acute Pancreatitis: PLR and NLR Combination.

BACKGROUND: We aimed to investigate the prognostic importance of platelet-lymphocyte ratio (PLR) and neutro - phil-lymphocyte ratio(NLR) combination for patients diagnosed with acute pancreatitis and its relationship with mortality. METHODS: This retrospective study was included 142 patients diagnosed with acute pancreatitis. Ranson, Atlanta and BISAP 0h, 24h and 48h scores of the patients were calculated by examining their patient files. The patients were divided into three groups as low-risk, medium-risk and high-risk patients according to their PLR and NLR levels. RESULTS: The number of patients with acute pancreatitis complications such as necrotizing pancreatitis, acute renal failure, sepsis and cholangitis was significantly higher in the high-risk group compared to other groups. Mortality rate was found to be 90% in the high-risk group, 16% in the medium-risk group, and 1.9% in the low-risk group. The number of patients with a Ranson score of 5 and 6, a severe Atlanta score, a BISAP 0h score of 3 and 4, a BISAP 24h and 48h score of 4 and 5 was higher in the high-risk group compared to other groups. PLR-NLR combination, Atlanta and Ranson scores, and C-reactive protein level were determined to be independent risk factors predicting mortality in stepwise regression model. PLR-NLR combination had the highest area under curve value in terms of predicting acute claspancreatitis prognosis and had a similar diagnostic discrimination with other scoring systems. CONCLUSION: In our study it was found that PLR-NLR combination had a similar prognostic importance with other scoring systems used to determine acute pancreatitis prognosis.

Endoscopic Treatment of the Coloanal Anastomotic Dehiscence and Stricture: Stenting Via Rendezvous Technique.

An anastomotic leak is a serious complication of colorectal surgery. Leak management is often grueling, and a definitive stoma is often mandatory for rescue therapy. Herein, we present a patient who experienced coloanal anastomotic dehiscence and complete stricture at the proximal part of the anastomosis. This case was successfully treated with a fully covered self-expandable metallic stent placement via the combined endoscopic (per ileostomy) and manual (per anal channel) rendezvous technique.

Endoscopic Treatment of the Zenker Diverticulum With Flexible Endoscopic Myotomy: A Single Tertiary Center Experience.

INTRODUCTION: The Zenker diverticulum (ZD) is the most common type of esophageal diverticula. Management of ZD has different options; however, there is a recent increase in treatment with flexible endoscopic myotomy (FEM). In our study, we aimed to investigate the efficacy and safety of FEM among patients with ZD. MATERIALS AND METHODS: The data of patients who underwent FEM for ZD in our clinic between January 2008 and May 2016 were retrospectively analyzed. Myotomy was performed with a needle-knife sphincterotome by using pulse-cut or forced coagulation electrocautery mode. Myotomy was performed on the common wall of the diverticulum up to 0.5 to 1 cm of the distal end. A handmade diverticuloscope, which was modified from an overtube, was used in most of the patients to focus more carefully on the septum. Dysphagia scores of the patients before and after the procedure were compared and complications were evaluated. RESULTS: A total of 17 patients were enrolled in the study. The mean age was 65.3 years, and mean diverticular diameter was 3.2 cm. The most common symptoms were dysphagia and regurgitation. The mean in-hospital stay was 5 days. The dysphagia score was significantly decreased after FEM among the patients (0.17±0.39 vs. 2±0.79; P=0.0001). Complications were observed in 3 patients (17.6%); however, there was no procedure-related mortality. DISCUSSION: FEM is an efficient and safe procedure as a treatment modality for ZD. However, lack of a standard algorithm is a remarkable disadvantage.

Management of suspected common bile duct stone: diagnostic yield of current guidelines.

BACKGROUND: The American Society for Gastrointestinal Endoscopy (ASGE) has recently published a guideline for suspected CBDS with the intention of reducing unnecessary ERCP and thereby complications. The aim of this study was to assess the diagnostic efficacy of the ASGE guideline. METHODS: Data of patients who underwent ERCP with suspected CBDS were analyzed retrospectively. Patients were classified into high, intermediate and low risk groups based on predictors that have been suggested by the ASGE. Very strong predictors of the presence of ductal stones included: CBDS on transabdominal ultrasonography (US), clinical ascending cholangitis or total bilirubin (TBIL) >4 mg/dL). Strong predictors included dilated CBD >6 mm on US with gallbladder in situ and TBIL level of 1.8-4.0 mg/dL whereas moderate predictor included abnormal liver biochemical test other than bilirubin, age more than 55 years and clinical findings of biliary pancreatitis. RESULTS: Of 888 enrolled patients, 704 had CBDS demonstrated by ERCP and the remainder did not. All very strong and strong predictors were found to be significantly higher among patients who had CBDS. Detection of CBDS by ultrasonography and a dilated common biliary duct were observed to be independent risk factors associated with the existence of CBDS. The high risk group had a high (86.7%) positive predictive value (PPV), however, sensitivity and specificity were observed to be moderate (67.8% and 60.3% respectively). PPV was 67.9% in the intermediate risk group and the sensitivity and specificity were very low (31.9% and 42.3%). DISCUSSION: The probability of CBDS was observed to be high in the intermediate and high risk groups. However due to low sensitivity and specificity values, the ASGE guideline needs additional or different predictors.

Endoscopic Management of the Difficult Bile Duct Stones: A Single Tertiary Center Experience.

Background. Most common bile duct (CBD) stones can be removed with standard techniques using endoscopic retrograde cholangiopancreatography (ERCP), but in some cases additional methods are needed. In this study we aimed to investigate the management of patients with difficult stones and the factors that affect the outcome of patients that have undergone periodic endobiliary stenting. Materials and Methods. Data of 1529 patients with naive papilla who had undergone ERCP with an indication of CBD stones was evaluated retrospectively. Stones that could not be removed with standard techniques were defined as "difficult stones." Cholangiograms of patients who had difficult stones were revised prospectively. Results. Two hundred and eight patients (13.6%) had difficult stones; 150 of these patients were followed up with periodic endobiliary stenting and successful biliary clearance was achieved in 85.3% of them. Both CBD (p < 0.001) and largest stone size (p < 0.001) were observed to be significantly reduced between the first and the last procedure. This difference was even more significant in successfully treated patients. Conclusions. Periodic endobiliary stenting can be used as an effective treatment for patients with difficult stones. Sizes of the CBD and of the largest stone are independent risk factors that affect the success rate.