Idiopathic Recurrent Acute Pancreatitis Research Articles

Antioxidant therapy decreases pain frequency in patients with idiopathic recurrent acute pancreatitis

Antioxidant therapy decreases pain frequency in patients with idiopathic recurrent acute pancreatitis

Роль однонуклеотидных полиморфизмов генов провоспалительных факторов как предикторов риска развития и тяжести течения острого панкреатита

A literature review has been conducted examining the role of single nucleotide polymorphisms of pro-inflammatory factor genes as predictors of risk of developing and severity of acute pancreatitis. The review was conducted on the following databases: Pub Med, Scopus for the period from 2009 to 2021 according to the following keywords: acute pancreatitis, hereditary pancreatitis, severe acute pancreatitis, gene polymorphism, single nucleotide genes, proinflammatory factors. A number of mutations and single nucleotide polymorphisms have been identified, which are the main triggers or cofactors of the initiation of both acute and chronic hereditary pancreatitis. The percentage of cases of idiopathic recurrent acute pancreatitis and idiopathic chronic pancreatitis associated with genetic mutations is 30-60% and 12-43%, respectively. The following genetic variants of the cationic trypsinogen (PRSS1) gene - CFTR, SPINK1 and chymotripsin C (CTRC) - are most often associated with the development of pancreatitis. Inherited pancreatitis associated with gene mutations has SPINK1 autosomal recessive inheritance pattern. When the mutant gene is expressed, the synthesis of a strong trypsin inhibitor prevents premature activation of immature trypsinogen. Data are obtained that IL-6, IL-8, FNOα can activate NF kB transcription factor, inducing, thus, increase in an expression 2 DRIED. It has been found that some COX 2 polymorphisms characterized by increased expression of this enzyme create prerequisites for the progression of the inflammation process, and are possibly predictors of the development of severe acute pancreatitis.

The role of endoscopic ultrasound and magnetic resonance cholangiopancreatography in the diagnosis of idiopathic recurrent acute pancreatitis: a narrative review

Objective: Our aim was to provide a qualitative synthesis of the literature to formulate an evidence-based approach to the diagnostic evaluation of patients with idiopathic recurrent acute pancreatitis (IRAP).

Impact of genetic testing and smoking on the distribution of risk factors in patients with recurrent acute and chronic pancreatitis

Objective The aim of the present study is to assess the impact of smoking dose and duration on the distribution of risk factor(s) in patients with RAP and CP, and the impact of genetic testing on the distribution of risk factor(s) in patients with idiopathic RAP and CP. Methods All adult patients with RAP and CP referred to a multidisciplinary pancreatitis clinic between 2010 and 2017 were evaluated. Risk factors included alcohol and smoking, hypertriglyceridemia, biliary, and other etiologies. Genetic testing was only pursued in patients with idiopathic RAP or CP. Results Among the 1770 patients evaluated, 167 had RAP and 303 had CP. After genetic testing and smoking, the most common risk factors for RAP and CP were pathogenic variant(s) (23%) and the combination of alcohol and smoking (23%), respectively. Genetic testing and smoking assessment decreased the proportion of patients with alcoholic RAP from 17% to 5%, alcoholic CP from 33% to 10%, idiopathic RAP from 49% to 12%, and idiopathic CP from 54% to 14%. Pathogenic CFTR variants were the most common variant in patients with RAP (51%) and CP (43%). Among the 68 patients with pancreas divisum, other risk factor(s) were identified in 72%. Conclusion Genetic testing and a detailed assessment of smoking dose and duration reduce the proportion of patients with alcoholic and idiopathic pancreatitis. Other risk factor(s) for pancreatitis are found in the majority of patients with pancreas divisum further questioning its role as an independent risk factor. 1. What is the current knowledge? Approximately 30% of patients with pancreatitis have no clear risk factor(s) and are categorized as having an idiopathic etiology. Pathogenic variant(s) as well as smoking dose and duration are well-established risk factors for recurrent acute and chronic pancreatitis but are not widely recognized or incorporated into clinical practice. 2. What is new here? Genetic testing and a detailed assessment of smoking dose and duration reduced the proportion of patients with alcoholic and idiopathic acute recurrent and chronic pancreatitis. Approximately three-fourths of patients with pancreas divisum have a risk factor for pancreatitis.

The EFFect of dietary fat content on the recurrence of pancreaTitis (EFFORT): Protocol of a multicenter randomized controlled trial

BackgroundAround 20% of patients with acute pancreatitis (AP) will develop acute recurrent pancreatitis (ARP) and 10% will progress to chronic pancreatitis. While interventions to avoid recurrences exist for the two most common causes – abstinence for alcoholic and cholecystectomy for biliary pancreatitis – the are no known preventive measures in idiopathic ARP. Though it is not included in any of the guidelines, a low-fat diet is often recommended.Our aim is to test dietary fat reduction's effect on AP recurrence in a randomized controlled setting, in order to provide high-quality evidence for the validity of such an intervention. Methods, designParticipants with at least 2 episodes of AP in the preceding 2 years of which the last episode was idiopathic will be randomized to one of two diets with different fat contents: a ‘reduced fat diet’ (15% fat, 65% carbohydrate, 20% protein) and a ‘standard healthy diet’ (30% fat, 50% carbohydrate, 20% protein; based on WHO recommendations). Participants will be followed-up for 2 years (visits will be scheduled for months 3, 6, 12, 18 and 24) during which they will receive a repeated session of nutritional guidance, complete food frequency questionnaires and data on relapse, mortality, BMI, cardiovascular parameters and serum lipid values will be collected. DiscussionThis study will determine the effect of modifying the dietary fat content on AP recurrence, mortality, serum lipids and weight loss in idiopathic cases.

Comparison of idiopathic recurrent acute pancreatitis [IRAP] and recurrent acute pancreatitis with genetic mutations

BackgroundIdiopathic recurrent acute pancreatitis (IRAP) describes frequent episodes of pancreatitis without an etiology found using current testing. We compared the natural history of IRAP with recurrent acute pancreatitis with genetic mutations. MethodsRetrospective cohort of patients with recurrent acute pancreatitis (≥2 episodes) and negative conventional testing. All patients had ≥1 episode after cholecystectomy and completed genetic testing. Primary outcomes were chronic pancreatitis incidence, pancreatic cancer, and mortality. Secondary outcomes included opioid and ERCP utilization. Results128 patients met criteria for presumed IRAP. 35 patients met criteria for true IRAP. 12 patients had recurrent acute pancreatitis with gene mutations. Chronic pancreatitis developed in 27 (77.1%) IRAP patients over a median of 6 years. Chronic pancreatitis incidence was similar in IRAP and CFTR mutation carriers; but developed later in SPINK1 carriers. No patients developed pancreatic cancer or died from pancreatic-related causes. Patients were frequently treated with oral opioids and ERCP, without significant differences within or between groups. ConclusionIRAP and pancreatitis in mutation carriers is associated with chronic pancreatitis. Important differences in natural history were observed, but no association was found with cancer or pancreas-related mortality. Efforts to understand the genetic contributions to IRAP, minimize opioids and unnecessary ERCPs are encouraged.

Disfunción del esfínter de Oddi: un reporte de caso

La disfunción del esfínter de Oddi es un síndrome clínico causado por una enfermedad funcional (discinesia) o estructural (estenosis). La prevalencia estimada de disfunción del esfínter de Oddi en la población en general es del 1 %; aumentando a 20 % para pacientes con dolor persistente posterior a colecistectomía y a 70 % en pacientes con pancreatitis aguda recurrente idiopática. Se caracteriza clínicamente por la presencia de dolor abdominal, similar al cólico biliar o dolor tipo pancreático en ausencia de patología biliar orgánica; así como en pacientes con pancreatitis recurrente idiopática asociada con elevación de enzimas pancreáticas o hepáticas, y dilatación del conducto biliar o pancreático. El tratamiento para la disfunción del esfínter de Oddi tipo I se basa en la realización de esfinterotomía endoscópica, pero existe controversia en el manejo de la disfunción del esfínter de Oddi tipo II y III. En este artículo se presenta el caso clínico de una paciente de 67 años con antecedente de colecistectomía por laparotomía. Después del procedimiento quirúrgico refirió un dolor abdominal de predominio en el hipocondrio derecho tipo cólico asociado con emesis de características biliares. En el reporte de colangiorresonancia se encontró una ligera dilatación de la vía biliar intrahepática y gammagrafía con ácido iminodiacético hepatobiliar (HIDA) diagnóstica de disfunción del esfínter de Oddi. Se realizó una esfinterotomía endoscópica. En el seguimiento, dos años después, la paciente se encontraba asintomática con la disfunción del esfínter de Oddi resuelta.

Utility of endoscopic ultrasound in idiopathic acute recurrent pancreatitis

Idiopathic acute recurrent pancreatitis (IARP) is defined as at least two episodes of acute pancreatitis with the complete or near-complete resolution of symptoms and signs of pancreatitis between episodes, without...

S1414 Successful Endoscopic Management of Necrotizing Pancreatitis Due to Rare Anatomical Variants

INTRODUCTION: Pancreatic divisum (PD) is an embryological failure of fusion of the ventral and dorsal pancreatic ducts. Meandering main pancreatic duct (MMPD) is another rare developmental loop-type anomaly in the main duct. PD and MMPD are more prevalent in idiopathic recurrent acute pancreatitis (IRAP). We report a case of recurrent necrotizing pancreatitis in a patient with these anatomical variants, fascinatingly resulting in complete resolution after staged direct endoscopic necrosectomies. CASE DESCRIPTION/METHODS: A 51-year-old male presented with epigastric pain and vomiting. Physical examination, complete blood count, complete metabolic panel, lipase and lactic acid were unremarkable. Abdominal CT showed acute pancreatitis with 10% parenchymal necrosis and 7 × 8 × 15 cm peripancreatic walled-off necrosis. He was managed with fluids, pain and anti-emetics and tolerated diet advancement. The etiology of his pancreatitis was unclear given absence of alcohol abuse and biliary pathology and negative autoimmune work-up. He was discharged with plans to repeat imaging 6 weeks later at which time he was readmitted for fevers and pain recurrence. Abdominal CT showed increase in size of the walled-off necrosis to 15 × 10 × 20 cm (Figure 1). He was treated with antibiotics and underwent endoscopic cystogastrostomy. His clinical course was complicated by splenic vein and upper extremity deep venous thrombi and a pulmonary embolism requiring anticoagulation. While on anticoagulation, he underwent 14 careful staged endoscopic necrosectomies over two months until complete resolution (Figure 2). Subsequent ERCP demonstrated incomplete PD and reverse-Z MMPD (Figure 3). A stent was placed into the ventral pancreatic duct and he was managed with pancreatic enzyme replacement, remaining asymptomatic on 1-year follow-up. DISCUSSION: PD and MMPD are rare embryological errors, carrying ∼40% prevalence in cases of IRAP and are thought to play a role in disease onset. Necrosis complicates 20% of acute pancreatitis cases with a 25% mortality rate. While two thirds of cases resolve with conservative measures, the remainder require intervention with endoscopic necrosectomy to avoid open surgical approaches with high mortality. Large multi-center studies have demonstrated successful resolution with endoscopic necrosectomy in ∼90% of cases with significantly lower mortality. This case serves to illustrate the effectiveness of endoscopic necrosectomy even in the face of anticoagulation and to prompt physicians to consider PD and MMPD in IRAP.Figure 1.: CT showing necrotic collection.Figure 2.: Endoscopic necrosectomy.Figure 3.: ERCP showing PD and MMPD anatomical variants.

Acoustic radiation force impulse imaging of pancreas in patients with early onset idiopathic recurrent acute pancreatitis.

Patients with recurrent acute pancreatitis (RAP) may progress to chronic pancreatitis (CP). A critical step in this progression is the development of fibrosis. Elastography has been used to assess degree of fibrosis by measurement of shear wave velocity (SWV). The aim of this study was to measure the stiffness of pancreas as a surrogate for pancreatic fibrosis in patients with RAP and compare it with a group of individuals without any history of pancreatic disorders. Using acoustic radiation force impulse (ARFI) imaging SWV was calculated in 31 patients with idiopathic RAP having disease onset ≤30 years. A control group of 31 individuals with no history pancreatic disorder and no features of CP on endosonography was selected for comparison. ARFI imaging was done by a single radiologist who was blinded to the cases and controls RESULTS:: Mean age of patients with RAP was 24.8 (SD 9.86) years, disease duration was 3.45 (interquartile range 1-5) years, mean number of episodes 4.9 (SD 2.72). There was a significant difference in SWV between patients (1.27 ± 0.50 m/s) and controls (1.00 ± 0.17 m/s) (P = 0.001)). There was a positive correlation between SWV and number of pain episodes (P = 0.026) and negative correlation with BMI (P = 0.002). SWV was high in patients with RAP indicating a stiff pancreas. The stiffness increases with the number of episodes of pancreatitis.

Genetic Evaluation of Children with Idiopathic Recurrent Acute Pancreatitis.

Several genetic risk factors have been identified in adults with idiopathic acute recurrent pancreatitis (IARP). However, the literature regarding the genetics of IARP is sparse in children. In this study, we aimed to analyze the genetic risk factors in children with IARP. All children (< 18years) with ARP from January 2015 to May 2018 were prospectively enrolled in the study. Children with a known cause of ARP like obstructive, toxic/metabolic, and autoimmune were excluded from the final analysis. Children with IARP underwent genetic testing for mutations/polymorphisms in genes known to predispose to pancreatitis including cationic trypsinogen protease serine 1 (PRSS1), serine protease inhibitor Kazal type 1 (SPINK1), cystic fibrosis transmembrane conductance regulator gene (CFTR), chymotrypsin C (CTRC), claudin-2 (CLDN2) and cathepsin B (CTSB). A total of 239 children (116 boys, 10.3 ± 3.7years) were enrolled during the study period. Of these, 204 (85.35%) children were identified as IARP. The mean age of symptom onset and the number of pancreatitis episodes were 8.3 ± 3.7years and 3.3 ± 1.8, respectively. A family history of pancreatitis was noted in 4.6% children. Mutations/polymorphisms in at least 1 gene were identified in 89.5% (129/144) children including SPINK1 in 41.9%, PRSS1 (rs10273639) in 58.2%, CTRC in 25.6%, CTSB in 54.9%, CLDN2 in 72.9%, and CFTR in 2.3%. There was no significant incidence of genetic mutations/polymorphisms in IARP with or without pancreas divisum (95.7 vs 88.4%; p = 0.467). Genetic alterations are present in the majority of the children with IARP. The incidence of genetic mutations is similar in children with or without pancreas divisum.

SpHincterotomy for Acute Recurrent Pancreatitis Randomized Trial: Rationale, Methodology, and Potential Implications.

In patients with acute recurrent pancreatitis (ARP), pancreas divisum, and no other etiologic factors, endoscopic retrograde cholangiopancreatography (ERCP) with minor papilla endoscopic sphincterotomy (miES) is often performed to enlarge the minor papillary orifice, based on limited data. The aims of this study are to describe the rationale and methodology of a sham-controlled clinical trial designed to test the hypothesis that miES reduces the risk of acute pancreatitis. The SpHincterotomy for Acute Recurrent Pancreatitis (SHARP) trial is a multicenter, international, sham-controlled, randomized trial comparing endoscopic ultrasound + ERCP with miES versus endoscopic ultrasound + sham for the management of ARP. A total of 234 consented patients having 2 or more discrete episodes of acute pancreatitis, pancreas divisum confirmed by magnetic resonance cholangiopancreatography, and no other clear etiology for acute pancreatitis will be randomized. Both cohorts will be followed for a minimum of 6 months and a maximum of 48 months. The trial is powered to detect a 33% risk reduction of acute pancreatitis frequency. The SHARP trial will determine whether ERCP with miES benefits patients with idiopathic ARP and pancreas divisum. Trial planning has informed the importance of blinded outcome assessors and long-term follow-up.

Natural history of Idiopathic Recurrent Acute Pancreatitis (IRAP): a prospective “real world” cohort study

Acute and chronic pancreatitis are common gastroenterological disorders that have a fairly unpredictable long-term course often associated with unplanned hospital readmissions. Little is known about the factors that increase or decrease the risk for a hospital readmission. The aim of this study was to identify positive and negative predictive factors for hospital readmissions of patients with acute and chronic pancreatitis after in-hospital treatment.In a retrospective analysis data from the hospital information and reimbursement data system (HIS) were evaluated for 606 hospital stays for either acute or chronic pancreatitis between 2006 and 2011. Additional clinical data were obtained from a questionnaire covering quality of life and socio-economic status. A total of 973 patient variables were assessed by bivariate and multivariate analysis.Between 2006 and 2011, 373 patients were admitted for acute or chronic pancreatitis; 107 patients of them were readmitted and 266 had only one hospitalization. Predictors for readmission were concomitant liver disease, presence of a pseudocyst or a suspected tumor of the pancreas as well as alcohol, tobacco or substance abuse or coexisting mental disorders. Patients who had undergone a CT-scan were more susceptible to readmission. Lower readmissions rates were found in patients with diabetes mellitus or gallstone disease as co-morbidity.While factors like age and severity of the initial disease cannot be influenced to reduce the readmission rate for pancreatitis, variables like alcohol, tobacco and drug abuse can be addressed in outpatient programs to reduce disease recurrence and readmission rates for pancreatitis.

Mo1394 – Role of Genetic Evaluation in Children with Idiopathic Acute Recurrent Pancreatitis

Mo1394 – Role of Genetic Evaluation in Children with Idiopathic Acute Recurrent Pancreatitis

Role of Diagnostic Endoscopic Ultrasound in Idiopathic Acute Pancreatitis and Acute Recurrent Pancreatitis in Children.

Endoscopic ultrasound (EUS) is a minimally invasive pancreatic imaging modality. We evaluated children with idiopathic acute pancreatitis (IAP) and acute recurrent pancreatitis (ARP) for changes of chronicity (Rosemont criteria) and biliary risk factors. Diagnostic yield of simultaneously performed transabdominal ultrasonography (TUS) was compared with EUS. This was a prospective observational study. Patients underwent EUS and TUS after 2 months of pancreatitis attack. Forty-five (18 IAP, 27 ARP) patients underwent EUS and TUS. Mean (standard deviation) age and weight were 9.1 (2.6) years and 32.66 (12.43) kg in IAP, whereas these were 12.2 (3.1) years and 44.84 (15.12) kg in ARP, respectively. Endoscopic ultrasound demonstrated morphological abnormality in 33.3% and 40.7% of IAP and ARP, respectively (P = 0.61), whereas 16.6% and 25.9% were abnormal in TUS. Endoscopic ultrasound showed unequivocal changes of chronicity (11.1% vs 0%) and risk factors only among ARP (25.9% vs 0%; P = 0.03) and demonstrated slightly higher odds ratio (95% confidence interval) as compared with TUS to detect abnormalities in both IAP (2.43 [0.49-14.17], P = 0.28) and ARP (1.94 [0.60-6.47], P = 0.26). Applying EUS, changes of chronicity and risk factors were noted only in ARP. Endoscopic ultrasound performed better than TUS in detecting chronicity.

Recurrent Acute Pancreatitis: Current Concepts in the Diagnosis and Management.

There have been significant developments in the diagnosis, clinical approach, and management of patients with recurrent acute pancreatitis (RAP) in the last decade. This review systematically summarizes our current understanding of RAP. Gallstones and alcohol are common causes of RAP. Non-alcohol non-biliary RAP (nAnB RAP) is a difficult group of patients after excluding these two causes because extensive workup is required to elucidate the etiology. Idiopathic RAP is diagnosed after excluding all the known causes and recurrence is noted to be higher in such patients. Patients with non-biliary RAP are prone to develop chronic pancreatitis (CP) suggesting a continuum from acute to recurrent to chronic pancreatitis. Often, patients destined to develop CP present at an earlier stage with RAP. Endoscopic ultrasound and magnetic resonance cholangiopancreatography (MRCP) are the investigations of choice to detect microlithiasis, choledocholithiasis, ductal abnormalities, peri-ampullary malignancies, and early changes of chronic pancreatitis. The role of pancreas divisum, sphincter of Oddi dysfunction, and anomalous pancreatobiliary union in causing RAP is controversial. Genetic testing may be advisable in younger patients. With a focused approach and appropriate investigations, the etiology of RAP can be identified in a significant proportion of patients. Therapeutic options are limited and future research is needed to improve understanding of the disease.

Adverse Events and Reinterventions Following Pancreatic Endoscopic Sphincterotomy.

Pancreatic endoscopic sphincterotomy (PES) is an independent risk factor for short- and long-term adverse events (AEs) of endoscopic retrograde cholangiopancreatography. We sought to measure PES-specific AEs and trends in the use of PES. This was a retrospective cohort of consecutive patients who underwent first-time PES between June 2008 and June 2015. Indications for PES were dichotomized: (1) structural pathology (chronic pancreatitis and local complications of acute pancreatitis) and (2) suspected sphincter pathology (idiopathic recurrent acute pancreatitis and sphincter of Oddi dysfunction). Rates of AEs and pancreatic orifice reinterventions were measured, with reintervention rates limited to those having a minimum of 12-month follow-up. Of 567 patients, 198 (34.9%) underwent PES for structural and 369 (65.1%) for suspected sphincter pathology. Rates of post-endoscopic retrograde cholangiopancreatography pancreatitis and unplanned hospitalization were high when PES was originally performed for suspected sphincter pathology (12.6% and 14.6%, respectively). The overall reintervention rate was 28.9% and significantly greater for sphincter (41.7%) compared with structural pathology (13.5%, P = 0.005). The likelihood of reintervention after PES is high, particularly when the primary indication is suspected sphincter pathology such as idiopathic recurrent acute pancreatitis. Further prospective studies are needed to clarify if and when this maneuver confers significant benefit to patients.

The SPINK1 p.N34S variant is associated with early onset idiopathic recurrent acute pancreatitis progressing to chronic disease, but not with more rapid progression to other disease outcomes such as diabetes mellitus

The SPINK1 p.N34S variant is associated with early onset idiopathic recurrent acute pancreatitis progressing to chronic disease, but not with more rapid progression to other disease outcomes such as diabetes mellitus

Endoscopic Ultrasonography Reveals Occurrence of Chronic Pancreatitis in Patients with Idiopathic Recurrent Acute Pancreatitis

Endoscopic Ultrasonography Reveals Occurrence of Chronic Pancreatitis in Patients with Idiopathic Recurrent Acute Pancreatitis

Role of endoscopic ultrasound in idiopathic pancreatitis.

Recurrent acute pancreatitis (RAP) is defined based on the occurrence of two or more episodes of acute pancreatitis. The initial evaluation fails to detect the cause of RAP in 10%-30% of patients, whose condition is classified as idiopathic RAP (IRAP). Idiopathic acute pancreatitis (IAP) is a diagnostic challenge for gastroenterologists. In view of associated morbidity and mortality, it is important to determine the aetiology of pancreatitis to provide early treatment and prevent recurrence. Endoscopic ultrasound (EUS) is an investigation of choice for imaging of pancreas and biliary tract. In view of high diagnostic accuracy and safety of EUS, a EUS based management strategy appears to be a reasonable approach for evaluation of patients with a single/recurrent idiopathic pancreatitis. The most common diagnoses by EUS in IAP is biliary tract disease. The present review aims to discuss the role of EUS in the clinical management and diagnosis of patients with IAP. It elaborates the diagnostic approach to IAP in relation to EUS and other different modalities. Controversial issues in IAP like when to perform EUS, whether to perform after first episode or recurrent episodes, comparison among different investigations and the latest evidence significance are detailed.