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The literature indicates that acute pancreatitis is a complication of massive hemolysis with a prevalence of about 20%. We describe an experimental model of hemolysis-induced acute pancreatitis. Hemolytic anemia was induced in rats by a single ip injection of 60 mg/kg of 20 mg/ml acetylphenylhydrazine (APH) in 20% (v/v) ethanol on the first experimental day (day 0). One hundred and fifty Wistar albino rats weighing 180-200 g were divided into three groups of 50 animals each: groups 1, 2 and 3 were injected ip with APH, 20% ethanol, and physiological saline, respectively. Ten rats from each group were sacrificed on study days 1, 2, 3, 4 and 5. Serum amylase, lipase levels and pancreatic tissue tumor necrosis factor-alpha (TNF-alpha) and platelet-activating factor (PAF) contents were determined and a histological examination of the pancreas was performed. No hemolysis or pancreatitis was observed in any of the rats in groups 2 and 3. In group 1, massive hemolysis was observed in 35 (70%) of 50 rats, moderate hemolysis in seven (14%), and no hemolysis in eight (16%). Thirty-three of 35 (94.2%) rats with massive hemolysis had hyperamylasemia, and 29 of these rats (82.8%) had histologically proven pancreatitis. The most severe pancreatitis occurred on day 3, as demonstrated by histology. Tissue TNF-alpha and PAF levels were statistically higher in group 1 than in groups 2 and 3. Acute massive hemolysis induced acute pancreatitis, as indicated by histology, in almost 80% of cases. Hemolysis may induce acute pancreatitis by triggering the release of proinflammatory and immunoregulatory cytokines.

Abstract Background Both C reactive protein (CRP) and procalcitonin (PCT) are well known acute phase reactant proteins. CRP was reported to increase in metabolic syndrome and type-2 diabetes. Similarly altered level of serum PCT was found in chronic liver diseases and cirrhosis. The liver is considered the main source of CRP and a source of PCT, however, the serum PCT and CRP levels in non-alcoholic fatty liver disease (NAFLD) were not compared previously. Therefore we aimed to study the diagnostic and discriminative role of serum PCT and CRP in NAFLD. Methods Fifty NAFLD cases and 50 healthy controls were included to the study. Liver function tests were measured, body mass index was calculated, and insulin resistance was determined by using a homeostasis model assessment (HOMA-IR). Ultrasound evaluation was performed for each subject. Serum CRP was measured with nephalometric method. Serum PCT was measured with Kryptor based system. Results Serum PCT levels were similar in steatohepatitis (n 20) and simple steatosis (n 27) patients, and were not different than the control group (0.06 ± 0.01, 0.04 ± 0.01 versus 0.06 ± 0.01 ng/ml respectively). Serum CRP levels were significantly higher in simple steatosis, and steatohepatitis groups compared to healthy controls (7.5 ± 1.6 and 5.2 ± 2.5 versus 2.9 ± 0.5 mg/dl respectively p < 0.01). CRP could not differentiate steatohepatitis from simple steatosis. Beside, three patients with focal fatty liver disease had normal serum CRP levels. Conclusion Serum PCT was within normal ranges in patients with simple steatosis or steatohepatitis and has no diagnostic value. Serum CRP level was increased in NAFLD compared to controls. CRP can be used as an additional marker for diagnosis of NAFLD but it has no value in discrimination of steatohepatitis from simple steatosis.

Abstract Introduction Bronchobiliary fistula is an uncommon complication secondary to hepatobiliary surgery. Bilioptysis is a pathognomic finding for bronchobiliary fistulas. Diagnosis may be easily established in the light of clinical history, which can be aided by imaging studies to pinpoint the exact location. Some diagnostic procedures such as endoscopic retrograde cholangiopancreatectomy are also useful for treatment. Case presentation We present three Turkish patients with bronchobiliary fistula secondary to previous hepatic surgery due to hydatid cyst in two, a 19-year-old and a 47-year-old man, and iatrogenic trauma of the common bile duct by endoscopy in a 35-year-old man. All of the patients were successfully treated by minimally invasive methods including percutaneous drainage and endoscopic retrograde cholangiopancreatography. Conclusion We suggest that bronchobiliary fistula could be managed through conservative treatment methods which do not require in-hospital follow-up, particularly in uncomplicated cases. Otherwise, surgical management can be unavoidable.

Background and Aims: There are different therapeutic approaches for biliary strictures and reducing portal hypertension in patients with symptomatic portal cavernoma cholangiopathy (PCC). Endoscopic treatment includes endoscopic biliary sphincterotomy (EST), dilation of stricture with a biliary balloon, placement of plastic stent(s) and stone extraction. Fully covered self-expandable metal stent (FCSEMS) is placed as a rescuer in case of haemobilia seen after EST, dilation of stricture and removal of plastic stent rather than the stricture treatment itself. In this retrospective observational study, we sought to assess the clinical outcomes of FCSEMS as the initial treatment for PCC-related biliary strictures., Materials and Methods: Twelve symptomatic patients with PCC both clinically and radiologically between July 2009 and February 2019 were examined. Magnetic resonance cholangiopancreatography (MRCP) and cholangiography were employed as the diagnostic imaging methods. Chandra-Sarin classification was used to distinguish between biliary abnormalities in terms of localization. Llop classification was used to group biliary abnormalities associated with PCC. Endoscopic partial sphincterotomy was performed in all the patients. If patients with dominant strictures 6-8-mm balloon dilation was first performed. This was followed by removal of the stones if exist. Finally, FCSEMS placed. The stents were removed 6-12 weeks later., Results: The mean age of the patients was 40.9 ± 10.3 years, and 91.6% of the patients were male. Majority of the patients (n = 9) were noncirrhotic. Endoscopic retrograde cholangiopancreatography (ERCP) findings showed that 11 of the 12 patients were Chandra Type I and one was Chandra Type IIIa. All the 12 patients were Llop Grade 3. All patients had biliary involvement in the form of strictures. Stent placement was successful in all patients. FCSEMSs were retained for a median period of 45 days (30-60). Seven (58.3%) patients developed acute cholecystitis. There was no occurrence of bleeding or other complications associated with FCSEMS replacement or removal. All patients were asymptomatic during median 3 years (1-10) follow up period., Conclusions: FCSEMS placement is an effective method in biliary strictures in case of PCC. Acute cholecystitis is encountered frequently after FCSEMS, but majority of patients respond to the medical treatment. Patients should be followed in terms of the relapse of biliary strictures., (© 2023. The Author(s).)

Background: It was well defined that proliferative effects of bile acids on colon epithelium are through interaction with muscarinic-3 receptors. Recently, microRNA emerged as an important regulator of gene expression and has been implicated in pathogenesis of many malignancies. However, the interaction of CHRM3 and microRNAs and their potential effects on colon carcinogenesis remains to be elucidated., Methods: In the current study, analysis of cell proliferation for 6 days after treatment with sodium taurolithocholate was analyzed by using WST-1 method. microRNAs which possibly target CHRM3 were identified by in silico analyses. Expression profiling of these microRNAs, expression changes of CHRM3 gene at mRNA level for H508 and SNU-C4 colon cancer cells were analyzed by quantitative polymerase chain reaction; the protein level of CHRM3 was analyzed using Western blot; apoptotic experiments were analyzed using the Annexin V assay. The Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the miRPath v3.0., Results: It was found that the expression level of CHRM3 gene was 6.133 ± 0.698-fold in H508 cells compared with SNU-C4 cells (P =.004). Treatment of H508 cells with sodium taurolithocholate caused 1.34 ± 0.4156-fold change in the expression level of CHRM3 gene (P =.0448). No apoptotic changes were observed in both colon cancer cells after treatment with sodium taurolithocholate. Different expression changes were detected of hsa-miR-129-5p, hsa-miR-30c-5p, hsa-miR-224-5p, hsa-miR-30b-5p, hsa-miR-522-3p, and hsa-miR-1246. Finally, hsa-miR-1246 and hsa-miR-522-3p could play a critical role in tumor development via bile acid-related genes in colon cancer., Conclusion: These findings reflected that CHRM3-dependent oncogenetic pathways might be in charge of colon cancer. We suggest that the microRNA expression profile of each individual colon cancer tissue is a unique digital signature.

Background: Laparoscopic sleeve gastrectomy (LSG) is a frequently performed operation. Leaks are formidable complications; however, the optimal management of these leaks is controversial., Methods: We retrospectively reviewed the medical records of 15 patients referred to our tertiary center between 2012 and 2016 with leaks after LSG., Results: In 12 patients with whom ongoing leaks were identified, stents were inserted with the intent of definitive therapy. In addition to attempts at source control, percutaneous drainage was carried out for intraabdominal collection in 9 patients and pleural effusion in 4 patients. The length of stay in the intensive care unit was significantly shorter in patients referred earlier or in those without any intervention., Conclusion: LSG leaks can be treated nonoperatively in well-organized centers under meticulously designed protocols, depending on the clinical condition of the patient.

Background: Psychometric hepatic encephalopathy score (PHES) needs local standardization., Aims: This study aimed at standardizing PHES for Turkish patients and compare them with German norms; to determine minimal hepatic encephalopathy (mHE) prevalence with two different methods [PHES battery and Critical Flicker Frequency (CFF)] and to assess whether sub-tests of the battery can be used for screening for mHE., Methods: Healthy volunteers (n = 816; 400 male) and cirrhotics (n = 124; 58 male) were included. For mHE diagnosis PHES score threshold was set at ≤ - 5 points and that of CFF at < 39 Hz. For comparing German and Turkish norms, datasets were combined. Multiple backward procedure was applied to assess effects of age, sex and education on single tests of the battery. Receiver operating characteristic (ROC) curves were created for assessing diagnostic capabilities of subtests of the battery., Results: PHES norms for Turks were developed. MHE prevalence in compensated cirrhotics was 29.8% and 27.4% with PHES and CFF tests, respectively, with low compatibility (kappa coefficient 0.389); mHE prevalence decreased to 16% when both tests were combined. Turks performed worse vs Germans in the digit symbol (DS) and serial dotting (SD) subtests but performed better in other subtests. In ROC analyzes of subtests, the combination of DS + SD tests achieved an AUROC of 0.974 versus PHES., Conclusions: Use of two methods for diagnosing mHE is important for research purposes. From a clinical perspective, sensitivity with acceptable specificity may suffice for screening instruments for mHE. Combined use of DS and SD subtests of the PHES battery appears suitable for this purpose., (© 2021. Asian Pacific Association for the Study of the Liver.)

Post Endoscopic Retrograde Cholangiopancreatography (ERCP) pancreatitis is one of the most serious complications of ERCP. Our study aims to investigate the risk, predisposing factors and prognosis of pancreatitis after ERCP in elderly patients. Patients referred to the ERCP unit between April 2008 and 2012 and admitted to the hospital at least 1 day after the ERCP procedure were included to the study. Information including patient's demographics, diagnosis, imaging findings, biochemical analysis, details of the ERCP procedure and complications were recorded. The severity of post ERCP pancreatitis (PEP) was determined by revised Atlanta Criteria as well as APACHE II and Ranson scores. A total of 2902 ERCP patients were evaluated and 988 were included to the study. Patients were divided into two groups as ≥ 65 years old (494 patients, 259 F, 235 M) and < 65 years old (494 patients, 274 F, 220 M). PEP was diagnosed in 4.3% of patients aged 65 years and older. The female gender was risk factors in elderly for PEP. The Sphincter Oddi Dysfunction (SOD) and Juxta papillary diverticula (JPD) were higher in elderly patients with PEP. Age did not increase the risk of PEP development. The most important post ERCP pancreatitis risk factor in the elderly is the female gender, while the risk is enhanced slightly by SOD and JPD., (© 2021. The Author(s).)

Background/aims: This study aimed to compare the causes of nonvariceal upper gastrointestinal bleeding (NVUGB), demographics, risk factors, and outcomes of patients during two periods between 1993 and 2016 in a tertiary health-care center in Turkey., Materials and Methods: We compared the causes of NVUGB and clinical outcomes in 421 patients hospitalized between January 1993 and December 1995 with those of 231 patients with NVUGB hospitalized between January 2015 and September 2016. We also compared epidemiological characteristics, risk factors, and the rates of endoscopic hemostatic procedures., Results: We observed significant increases in patients' mean age, in the percentage of patients with comorbid conditions, and in the percentage of patients who received direct-acting oral anticoagulants before bleeding. We also observed a statistically nonsignificant increase in the diagnoses of gastric ulcer, along with a significant concordant decrease in diagnoses of duodenal ulcer as a cause of bleeding. The use of emergency surgical hemostasis decreased among cases of peptic ulcer bleeding. The overall rate of mortality from bleeding did not significantly change between the two periods., Conclusion: Over the 23 years studied, the causes of NVUGB changed, probably because the population was increasingly elderly population and because of the use of anticoagulants and better therapeutic approaches to chronic duodenal ulcers. The use of emergency surgical hemostasis reduced, but mortality rate did not significantly change between the two specific periods.

Background/aims: Patients with ulcerative colitis (UC) are at increased risk of colorectal cancer (CRC). High-grade dysplasia (HGD) and low-grade dysplasia (LGD) are premalignant conditions. The aim of this study is to evaluate the risk of CRC/dysplasia in patients with UC, and the related risk factors., Materials and Methods: Medical records of 1659 patients dating between 1993 and 2016 were scanned from an inflammatory bowel disease database. A total of 801 patients with UC who underwent at least one colonoscopic procedure with at least 1-year follow-up period were included in the study. Clinical, endoscopic, and histopathological data were assessed., Results: The mean disease duration was 6.7±6.6 years. The total disease duration was 5334 person-years duration (pyd), and 34% of patients had the disease for 8 years or longer. The prevalence of UC-associated CRC was 0.7%, and the prevalence of dysplasia was 0.85%. The overall incidence of CRC was determined to be 1.1/1000 pyd. The cumulative risk of CRC was 0.3% at 10 years, 1.3% at 20 years, and 5.9% at 30 years. The Cox regression analysis indicated that primary sclerosing cholangitis (HR:13.677, 95% CI:2.6-70.8, p = 0.012) was an independent risk factor for developing UC-associated CRC., Conclusion: This study underlined the low risk of CRC and dysplasia in patients with UC in a tertiary referral center in the western part of Turkey. Primary sclerosing cholangitis was found to be the most important risk factor for the development of CRC in patients with UC. Identification of risk factors is important to categorize patients into subgroups to know which patients will require frequent surveillance.

Background/aims: Liver transplantation (LT) is now the standard of care for most end-stage liver diseases. Over the next 30 years, advances in medicine and technology will greatly improve the survival rates of patients after this procedure. The aim of the present study was to analyze retrospectively the results of 1001 patients withLT., Materials and Methods: Medical reports of 989 patients were analyzed retrospectively. Data were obtained from the patient's data chart. Descriptive statistics were used to describe continuous variables (mean, median, and standard deviation)., Results: A total of 1001 LTs for 989 recipients were performed at Ege University Organ Transplantation and Research Center between 1994 and 2017. Therewere 639 male and 350 female recipients. Among 1001 LTs, there were 438 deceased donors and 563 living donors. The age interval of the patients was 4 months to 71 years old. The median Model for End-Stage Liver Disease score was 20. There were 12 deceased liver donors using the split method. There were 12 cases subject to retransplantation. In living donor LT grafts, 423 right lobes, 46 left lobes, and 94 left lateral sectors were used. In the first monitoring,the total annual mortality rate was 130 cases (13%). The mortality rate in retransplantation was found to be 66%. A 1-year survival rate of 87% was generally stablished., Conclusion: LThas been improving consistently over the last two decades. Ege University is one of the biggest liver transplant centers in Turkey for both technical and educational perspective.

Objective: Iatrogenic bile duct injuries remain a challenge for the surgeons to overcome. The predictive factors affecting morbidity and mortality are important for determining the best management modality., Material and Methods: The patients who referred to Ege University Faculty of Medicine after laparoscopy associated iatrogenic bile duct injury are grouped according to Strasberg-Bismuth classification system. The type and number of prior attempts, concomitant complications, and treatment modalities are analyzed using the SPSS version 18 (IBM, Chicago, IL, USA). The variables with p<0.10 were considered for univariate analysis and then evaluated for predictive factors by forward Logistic Regression method using multiple logistic regression analysis., Results: According to the analysis of 105 patients who were referred during 2004-2014, the type and number of prior attempts are considered predictive factors in sepsis. In multiple logistic regression analysis, abscess formation, concomitant vascular injury, and serum bilirubin level are significantly effective in predicting mortality., Conclusion: The management of iatrogenic bile duct injuries should be carefully planned with a multidisciplinary approach. The predictive factors affecting morbidity and mortality are important in determining the best modality for managing iatrogenic bile duct injuries. Abscess formation, vascular injury, and serum bilirubin level are the potential risk factors. Therefore, we can strongly recommend immediate assessment of patients for prompt diagnosis and referring to an HPB center, to avoid further injuries.

Purpose: The activity of epithelial lactase (LCT) is associated with a polymorphism 13910 bp upstream in the lactase encoding gene. Because the association between the LCT-13910 polymorphism and the risk for colorectal cancer is not clear, we investigated the role of the LCT-13910 polymorphism as a potential risk factor for colorectal cancer and colorectal polyps in the Turkish population., Methods: One hundred sixty-six subjects (74 with polyps, 44 with colorectal cancer, 48 controls), who had undergone a total colonoscopy between January 2012 and November 2012 in our endoscopy unit were genotyped for the LCT-13910 polymorphism by using the polymerase chain reaction and minisequencing., Results: The CC genotype in the lactose gene 13910 locus, which is accepted as the genetic indicator of lactase deficiency, was determined as 83.7%. The CC genotype rate was determined as 89.1% in patients who had a history of lactose intolerance and 81.5% in those without a history of lactose intolerance (P = 0.236). No difference was detected between the patients who had colorectal polyp(s) and/or cancer and the controls with regard to the LCT-13910 polymorphism. No differences were determined between groups when they were compared with regard to the C or the T allele., Conclusion: No differences were detected between the patients who had colorectal polyp(s) and/or cancer and those with normal colonoscopy findings with regard to lactase gene polymorphisms. No differences were determined between the groups when they were compared with regard to the C or the T allele., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported.

Background: Aprotinin is a monomeric globular polypeptide, which derived from bovine lung tissue and theoretically attractive molecule in ameliorating the effects of acute pancreatitis. Acute pancreatitis is an inflammatory condition of the pancreas that is painful and at times deadly. Over the following two decades Aprotinin therapeutic potential on pancreatitis is proven experimentally, its clinical therapeutic success is limited due to low targeting to pancreas., Objective: The aim of this study was to evaluate the biodistribution of Technetium-99m ( 99m Tc)-Aprotinin solution ( 99m Tc-Aprotinin-S) and 99m Tc-Aprotinin loaded microemulsion, which was prepared for the aim of treatment for acute pancreatitis., Method: Aprotinin was radiolabeled with 99m Tc. Radiochemical purity was determined with radioactive thin layer chromatography studies. 99m Tc-Aprotinin-S and 99m Tc-Aprotinin loaded microemulsion ( 99m Tc-Aprotinin-M) was administered to acute edematous, severe necrotizing pancreatitis and air pouch model induced rats. Tissue distribution of Aprotinin was investigated with gamma scintigraphy and biodistribution studies., Results: Aprotinin was radiolabeled by 99m Tc with high radiochemical purity (95.430 ± 0.946%). The complex was found to be stable at room temperature up to 6 h. Animal studies have shown that similar to that of other small proteins Aprotinin is accumulated primarily in the kidney. The scintigraphy and biodistribution studies showed that, while i.v. administration of 99m Tc-Aprotinin-S distributed mostly in kidneys and bladder, 99m Tc-Aprotinin-M, with droplet size of 64.550 ± 3.217 nm, has high uptake in liver, spleen and pancreas., Conclusion: This might be concluding that microemulsions may be suggested as promising formulations for selectively targeting Aprotinin to pancreas inflammation.

The aim of this study was to develop aprotinin-loaded microemulsion (MA) for intravenous administration and evaluate the biodistribution and therapeutic potential of developed formulation in acute pancreatitis models in rats. Phase diagrams were constructed to identify microemulsion region and the optimal microemulsion was evaluated for physicochemical properties and treatment effect in rats, and comparisons made with the solution of aprotinin (SA). To evaluate the biodistribution of the drug by gamma scintigraphy aprotinin was radiolabeled with (99m)Tc radionuclide. Mild and severe acute pancreatitis was induced in rats by subcutaneous injections of cerulein and introductal infusion of 3% sodium taurocholate into the bile-pancreatic duct, respectively. In addition, serum amylase and pancreatic tissue myeloperoxidase activities were measured to evaluate the pancreatic damage. According to gamma scintigraphy and biodistribution studies, accumulation times and distribution of (99m)Tc-MA and SA were different. While MA was highly uptake by reticuloendothelial system, SA was mostly excreted by kidneys and bladder. Compared with the mild acute pancreatitis group, treatment with MA significantly decreased the serum amylase activity and pancreas myeloperoxidase activity. Furthermore, the protease inhibitor molecule aprotinin has therapeutic potential in acute pancreatitis. Finally, MA may be suggested as a promising alternative for treatment of acute pancreatitis.