Acute pancreatitis in Turkey: Results of a nationwide multicenter study.

BACKGROUND: Acute pancreatitis (AP) is the most common gastrointestinal disease requiring hospitalization, with significant mortality and morbidity. We aimed to evaluate the clinical characteristics of AP and physicians' compliance with international guidelines during its management. METHODS: All patients with AP who were hospitalized at 17 tertiary centers in Turkey between April and October 2022 were evaluated in a prospective cohort study. Patients with insufficient data, COVID-19 and those aged below 18 years were excluded. The definitions were based on the 2012 revised Atlanta criteria. RESULTS: The study included 2144 patients (median age:58, 52 % female). The most common etiologies were biliary (n = 1438, 67.1 %), idiopathic (n = 259, 12 %), hypertriglyceridemia (n = 128, 6 %) and alcohol (n = 90, 4.2 %). Disease severity was mild in 1567 (73.1 %), moderate in 521 (24.3 %), and severe in 58 (2.6 %) patients. Morphology was necrotizing in 4.7 % of the patients. The overall mortality rate was 1.6 %. PASS and BISAP had the highest accuracy in predicting severe pancreatitis on admission (AUC:0.85 and 0.81, respectively). CT was performed in 61 % of the patients, with the majority (90 %) being within 72 h after admission. Prophylactic NSAIDs were not administered in 44 % of the patients with post-ERCP pancreatitis (n = 86). Antibiotics were administered to 53.7 % of the patients, and 38 % of those received them prophylactically. CONCLUSIONS: This prospective study provides an extensive report on clinical characteristics, management and outcomes of AP in real-world practice. Mortality remains high in severe cases and physicians' adherence to guidelines during management of the disease needs improvement in some aspects.

CHRM3-Associated miRNAs May Play a Role in Bile Acid-Induced Proliferation of H508 Colon Cancer Cells.

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.

Co-analysis of pancreatic cyst fluid carcinoembryonic antigen and glucose with novel cut-off levels better distinguishes between mucinous and non-mucinous neoplastic pancreatic cystic lesions.

BACKGROUND: Pancreatic cyst fluid analysis plays an important role in distinguishing between mucinous and non-mucinous cyst lesions. We aimed to compare the diagnostic performances of cyst fluid carcinoembryonic antigen (CEA), CA 19-9, and glucose in differentiating mucinous from non-mucinous neoplastic pancreatic cystic lesions (PCLs) and determine the best cut-off levels. METHODS: Patients' data were evaluated retrospectively. 102 patients' PCLs were grouped as non-neoplastic (n = 25), non-mucinous neoplastic (n = 20), mucinous neoplastic (n = 47) and pancreatic adenocarcinomas with cystic degeneration (n = 10); and CEA, CA 19-9, and glucose levels were compared. Receiver-operating characteristic analysis was performed, and the ideal cut-off values were determined. RESULTS: Cyst fluid CEA and CA 19-9, levels were significantly higher (P < 0.001, P < 0.001, respectively) and glucose levels were significantly lower (P = 0.001) in mucinous than in non-mucinous neoplastic PCLs. Area under curve with 95% confidence interval of CEA, glucose and CEA and glucose test combination was 0.939 (95% CI = 0.885-0.993, P = 0.001), 0.809 (95% CI = 0.695-0.924, P < 0.001) and 0.937 (95% CI = 0.879-0.995), respectively. CEA cut-offs to rule-in and rule-out mucinous neoplastic were 135.1 ng/mL (sensitivity = 62%, specificity = 94.7%) and 6.12 ng/mL (sensitivity = 94.1%, specificity = 80.4%), respectively. Glucose cut-off of 2.8 mmol/L was chosen both to rule-in and rule-out mucinous neoplastic PCLs (sensitivity = 78%, specificity = 80%). Co-analysis of CEA and glucose to distinguish mucinous from non-mucinous neoplastic PCLs had sensitivity = 87.8%, specificity = 93.3%, and diagnostic accuracy = 89.3%. CONCLUSIONS: We concluded that co-analysis of cyst fluid CEA (cut-off = 135.1 ng/mL) and glucose (cut-off = 2.8 mmol/L) at novel cut-offs had the best testing performance to rule-in mucinous neoplastic PCLs. To rule-out mucinous PCLs co-analysis of CEA (cut-off = 6.12 ng/mL) and glucose (cut-off = 2.8 mmol/L) added value to prediction.

Prognosis and risk factors of ERCP pancreatitis in elderly.

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.

Autoimmune Pancreatitis after a Seven-Year History of Suspicious Pancreatic Cancer.

In this case report, we present a case of autoimmune pancreatitis (AIP) diagnosis in a patient after a 7-year history of suspicious pancreatic cancer. Kim's and Japanese criteria were used to diagnose AIP. Our case avoided undesirable invasive procedures and recovered thanks to the proper diagnosis and timely treatment with prednisone. Early and accurate diagnosis of AIP, in this case, had a significant impact on the treatment and prognosis process.

Malnutrition and sarcopenia are prevalent among inflammatory bowel disease patients with clinical remission.

AIM: The aim of this study was to evaluate nutritional status and sarcopenia in patients with inflammatory bowel disease (IBD) in clinical remission. METHODS: A total of 344 patients with IBD in clinical remission were included in this cross-sectional study. Patients with clinical activity (Harvey-Bradshaw index >5 for Crohn's disease and partial Mayo scores ≥5 for ulcerative colitis) were excluded. Sociodemographic, clinical, and anthropometric data were recorded. BMI was categorized according to WHO criteria. Nutritional status was assessed using the Mini Nutritional Assessment (MNA) questionnaire. Body composition included fat-free mass (FFM) analyzed with Tanita-330 ST. Muscle strength was measured with a Takei digital hand grip dynamometer using a standard protocol. Physical performance was measured as 4-m gait speed. Sarcopenia was defined based on the European Working Group on Sarcopenia in Older People 2 criteria. RESULTS: Overall, 5.5% of patients were underweight, 9.9% were malnourished, and 39.5% were at risk of malnutrition. Sarcopenia and probable sarcopenia were diagnosed in 41.3% of patients. Total number of flares requiring hospitalization (100%) was the most important predictor of sarcopenia, followed by total number of flares (80.1%), FFMI (46.5%), age (44.6%), BMI (31.8%), MNA score (27.7%), serum creatinine (23.6%), anti-tumor necrosis factor alpha use (23.3%), and gender (17.8%). CONCLUSION: In conclusion, our findings revealed a considerable proportion of IBD patients in clinical remission to be malnourished or at risk of malnutrition along with a high rate of sarcopenia. This emphasizes the need for concomitant screening for nutritional status and body composition analysis in patients with IBD for provision of appropriate nutritional support, even during the remission period, and prevention of sarcopenia-related surgical and poor clinical outcomes.

Real-life experience of ledipasvir and sofosbuvir single-tablet regimen among chronic hepatitis C patients in Turkey.

BACKGROUND/AIMS: Ledipasvir (LDV) and sofosbuvir (SOF) as single-tablet regimen (STR) has been approved for treatment of chronic HCV infection (CHC) for treatment-naïve or experienced cirrhotic or non-cirrhotic patients. Our aim was to analyse the effectiveness and safety of 12-24 weeks treatment of LDV/SOF (90mg/400 mg)±ribavirin in a real-life setting in Turkey. MATERIALS AND METHODS: Between May-Dec 2016, 104 treatment-naïve or experienced adult patients with CHC and with or without cirrhosis (including decompensated cirrhosis) were included in this observational study. Patients were administered LDV/SOF STR± ribavirin once daily for 12 -24 weeks. SVR12 rates and effects of the baseline characteristics on SVR12 rates were assessed. RESULTS: Out of 104 enrolled patients (61.5% female, mean age 62.0 years); 60.6% were cirrhotic, 76.0% previously used peg-IFN, 94.2% had GT1. At the end of the treatment, 77.8% (77/99, no data for 21 patients) had undetectable HCV-RNA and 98.9% (94/95) had SVR12. In the baseline characteristics subgroups, the SVR12 rates varied between 94.4% and 100%, and none of the baseline characteristics had a significant effect on the SVR12 rates. During the study, 6 (5.8%) patients died and none of the deaths was suspected to be related to the LDV/SOF. No treatment-emergent adverse event was reported. CONCLUSION: In conclusion, LDV/SOF±ribavirin yielded very high SVR12 rates, without any safety or tolerability concern in Turkey. The effectiveness of the LDV/SOF treatment was not affected by the patient demographics or medical characteristics such as fibrosis level, cirrhosis status, previous treatment status, HCV-RNA level or HCV genotype.

Solid pseudopapillary neoplasms of the pancreas: Case series with a review of the literature.

BACKGROUND/AIMS: The solid pseudopapillary neoplasms are quite rare tumors of the pancreas, comprising roughly 1-2% of all pancreatic neoplasms. It has a low malignant potential and usually affects young females. Despite increasing number of articles in the last decade, there is still debate on the pathogenesis, malignant potential and optimal surgical strategy for the solid pseudopapillary neoplasms. MATERIALS AND METHODS: Medical recordings of 326 patients who were operated due to pancreatic mass were retrospectively analyzed. Patient demographics, presenting symptoms, surgical and pathologic characteristics of the tumor, postsurgical course, long-term survival, and other relevant data were extracted from patients' charts. RESULTS: Majority of the patients were female in consistency with the classic data in the literature. All the patients underwent curative intent resections. Tumors were commonly localized in the tail of the pancreas making distal pancreatectomy the most commonly performed surgical procedure. Mean tumor diameter was 5.8 centimeters with tumor sizes ranging from 1 to 19 cm. CONCLUSION: The solid pseudopapillary neoplasms of the pancreas is a rare tumor with low malignant potential, which is more common in females of reproductive age, with abdominal pain being their most common presentation. The short-term outcomes in patients following surgical R0 resection are excellent. However, proximal placement of the tumor and female gender may have slightly worse prognosis. We hope that our findings from a series of patients represent a contribution to the existing literature on SPN, and authors declare their willingness to provide further details for future meta-analyses.

Anti-Inflammatory Effect of Crude Momordica charantia L. Extract on 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis Model in Rat and the Bioaccessibility of its Carotenoid Content.

Momordica charantia L., known as bitter melon (BM), is a plant that belongs to the family Cucurbitaceae. Aims of this study are to investigate the anti-inflammatory effect of crude BM extract on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis model in rat. It was also aimed to determine the content and bioaccessibility of carotenoids of BM. BM was purchased from local markets in Izmir, Turkey. Fruits of BM were lyophilized, powdered, and used in the experiment. Carotenoids were determined by high-performance liquid chromatography. To determine the bioaccessibility of ß-carotene, in vitro digestion was performed. Wistar albino rats were divided into four groups: group A (BM+TNBS), group B (BM), group C (TNBS), and group D (control). BM solution was given 300 mg/(kg·day) for 6 weeks orally. Colitis was induced by 0.25 mL of a solution containing 100 mg/kg 5% (w/v) TNBS in 50% ethanol (w/v) intrarectally after 6 weeks. After sacrification, macroscopic and microscopic evaluations were performed. Myeloperoxidase, cytokines levels (interleukin-17 [IL-17], TNF-alpha, and interleukin-10 [IL-10]) were measured in serum and colonic samples by ELISA test. Institutional Animal Ethics Committee approval was obtained. Total carotenoid content of BM was determined 11.7 mg/g dry weight as ß-carotene equivalents. Bioaccessibility of total carotenoids was determined as 2.1% with in vitro digestion. Pretreatment with crude BM extract significantly reduced weight loss, macroscopic, and microscopic colitis damages in colonic samples (P = .000), (P = .015), and (P = .026), respectively. Serum anti-inflammatory cytokine IL-10 increased significantly in both treatment groups (P = .000). BM is a rich source of carotenoids, but the bioaccessibility of its carotenoids is low. This study displays that BM has protective anti-inflammatory effects on TNBS-induced colitis.

Changing patterns of upper gastrointestinal bleeding over 23 years in Turkey.

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.

Gastroenteropancreatic neuroendocrine tumors: recommendations of Turkish multidisciplinary neuroendocrine tumor study group on diagnosis, treatment and follow-up.

Gastroenteropancreatic neuroendocrine tumors (GEPNETs) are a relatively rare, heterogeneous group of diseases in which important advances have been observed in the diagnosis and treatment as well as in our understanding of the biology and genetics of the disease in recent years. Given the insufficient scientific data available on evidence-based management of GEPNETs and the differences in circumstances in individual countries, a multidisciplinary study group was established to provide guidelines for the management of GEPNETS. This study group consisted of a medical oncologist, endocrinologist, surgeon, pathologist, gastroenterologist, and a nuclear medicine specialist, who aimed to prepare a practical guide in the light of existing scientific data and international guidelines, to be used in common clinical practice.

Effect of microemulsion formulation on biodistribution of 99mTc-Aprotinin in acute pancreatitis models induced rats.

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 (99mTc)-Aprotinin solution (99mTc-Aprotinin-S) and 99mTc-Aprotinin loaded microemulsion, which was prepared for the aim of treatment for acute pancreatitis. METHOD: Aprotinin was radiolabeled with 99mTc. Radiochemical purity was determined with radioactive thin layer chromatography studies. 99mTc-Aprotinin-S and 99mTc-Aprotinin loaded microemulsion (99mTc-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 99mTc 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 99mTc-Aprotinin-S distributed mostly in kidneys and bladder, 99mTc-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.

Cystic fluid chromogranin A levels in different pancreatic cystic lesions.

BACKGROUND/AIMS: Pancreatic cystic lesions have a broad spectrum of differential diagnosis. There is an ongoing demand to identify specific and sensitive cystic fluid markers for the differential diagnosis of pancreatic cysts. We aimed to evaluate the diagnostic value of cystic fluid chromogranin A (CgA) in the differential diagnosis of pancreatic cysts. MATERIALS AND METHODS: Patients who underwent endoscopic ultrasound (EUS)-guided aspiration for pancreatic cysts were included in the study. Cytopathological analysis and biochemical analysis, including cystic fluid carcinoembryonic antigen (CEA), amylase, Ca 19-9, and CgA, were performed. RESULTS: Fifty-three patients were included in the study. The final diagnosis of patients was 14 pancreatic pseudocysts, 10 intraductal papillary mucinous neoplasms (IPMNs), 8 mucinous cystic neoplasms (MCN), 8 serous cystadenomas (SCAs), 2 cystic pancreatic neuroendocrine tumors (PNETs), and 11 others. The mean CgA levels were 50.51±130.04 ng/mL in pseudocysts, 12.38±8.59 in MCN, and 13.76±10.90 in cystic PNET. There was only one patient with a very high cystic fluid CgA (515.49 ng/mL) and was diagnosed as pseudocyst developed in chronic pancreatitis patient. Two patients with cystic PNET had normal levels of cystic fluid CgA. CONCLUSION: Cystic fluid CgA is not a useful marker for the differential diagnosis of cystic PNETs. It also has no value in the differential diagnosis of other pancreatic cysts.

Disruption of HNF1α binding site causes inherited severe unconjugated hyperbilirubinemia.

Crigler-Najjar syndrome presents as severe unconjugated hyperbilirubinemia and is characteristically caused by a mutation in the UGT1A1 gene, encoding the enzyme responsible for bilirubin glucuronidation. Here we present a patient with Crigler-Najjar syndrome with a completely normal UGT1A1 coding region. Instead, a homozygous 3 nucleotide insertion in the UGT1A1 promoter was identified that interrupts the HNF1α binding site. This mutation results in almost complete abolishment of UGT1A1 promoter activity and prevents the induction of UGT1A1 expression by the liver nuclear receptors CAR and PXR, explaining the lack of a phenobarbital response in this patient. Although animal studies have revealed the importance of HNF1α for normal liver function, this case provides the first clinical proof that mutations in its binding site indeed result in severe liver pathology stressing the importance of promoter sequence analysis.

Multidisciplinary clinical management of paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disease caused by clonal expansion of one or more hematopoietic stem cell (HSC) lines due to a somatic mutation of the phosphatidylinositol glycan anchor (PIG-A) gene located on Xp22.1. PNH incidence is 1.5-2 cases per million of the population per year. PNH can affect multiple systems in the body and requires multidisciplinary clinical management. Patients can manifest with severe pancytopenia, life-threatening thrombosis affecting the hepatic, abdominal, cerebral, and subdermal veins, and high requirements for blood transfusion due to haemolytic anemia. PNH can also be associated with bone marrow failure. Advances in diagnostic techniques and a targeted therapeutic approach for PNH have emerged in the last two decades. Eculizumab, a promising humanized monoclonal antibody against C5, is the first approved therapy for PNH.

Aprotinin revisited: formulation, characterization, biodistribution and therapeutic potential of new aprotinin microemulsion in acute pancreatitis.

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.