Sphincter of Oddi dysfunction and bile duct microlithiasis in acute idiopathic pancreatitis

Although there are numerous causes of acute panc-reatitis, an etiology cannot always be found. Two potential etiologies, microlithiasis and sphincter of Oddi dysfunction, are discussed in this review. Gallbladder microlithiasis, missed on transcutaneous ultrasound, is reported as the cause of idiopathic acute pancreatitis in a wide frequency range of 6%-80%. The best diagnostic technique for gallbladder microlithiasis is endoscopic ultrasound although biliary crystal analysis and empiric cholecystectomy remain as reasonable options. In contrast, in patients who are post-cholecystectomy, bile duct microlithiasis does not appear to have a role in the pathogenesis of acute pancreatitis. Sphincter of Oddi dysfunction is present in 30%-65% of patients with idiopathic acute recurrent pancreatitis in whom other diagnoses have been excluded. It is unclear if this sphincter dysfunction was the original etiology of the first episode of pancreatitis although it appears to have a causative role in recurring episodes since sphincter ablation decreases the frequency of recurrent attacks. Unfortunately, this conclusion is primarily based on small retrospective case series; larger prospective studies of the outcome of pancreatic sphincterotomy for SOD-associated acute pancreatitis are sorely needed. Another problem with this diagnosis and its treatment is the concern over potential procedure related complications from endoscopic retrograde cholangiopancreatography (ERCP), manometry and pancreatic sphincterotomy. For these reasons, patients should have recurrent acute pancreatitis, not a single episode, and have a careful informed consent before assessment of the sphincter of Oddi is undertaken.

Review of idiopathic pancreatitis

Recent advances in understanding of pancreatitis and advances in technology have uncovered the veils of idiopathic pancreatitis to a point where a thorough history and judicious use of diagnostic techniques elucidate the cause in over 80% of cases. This review examines the multitude of etiologies of what were once labeled idiopathic pancreatitis and provides the current evidence on each. This review begins with a background review of the current epidemiology of idiopathic pancreatitis prior to discussion of various etiologies. Etiologies of medications,infections,toxins,autoimmune disorders,vascular causes,and anatomic and functional causes are explored in detail. We conclude with management of true idiopathic pancreatitis and a summary of the various etiologic agents. Throughout this review,areas of controversies are highlighted.

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.

Acute idiopathic pancreatitis in pregnancy:A case study

Acute pancreatitis during pregnancy is a rare event,and can be associated with high maternal mortality and fetal loss.Gallstone disease is thought to be the most common causative factor of acute pancreatitis,but,in many cases,the cause remains unclear.We report a case of a 36-year-old woman at 35 wk of gestation,who presented with severe pain confined to the upper abdomen and radiating to the back.The patient was diagnosed with acute idiopathic pancreatitis,which was managed conservatively;she recovered within several days and then delivered a healthy baby.Therefore it is important to consider acute pancreatitis when a pregnant woman presents with upper abdominal pain,nausea and vomiting in order to improve fetal and maternal outcomes for patients with acute pancreatitis.

Machine learning-based decision tool for selecting patients with idiopathic acute pancreatitis for endosonography to exclude a biliary aetiology

BACKGROUND Biliary microlithiasis/sludge is detected in approximately 30%of patients with idiopathic acute pancreatitis(IAP).As recurrent biliary pancreatitis can be prevented,the underlying aetiology of IAP should be established.AIM To develop a machine learning(ML)based decision tool for the use of endosonography(EUS)in pancreatitis patients to detect sludge and microlithiasis.METHODS We retrospectively used routinely recorded clinical and laboratory parameters of 218 consecutive patients with confirmed AP admitted to our tertiary care hospital between 2015 and 2020.Patients who did not receive EUS as part of the diagnostic work-up and whose pancreatitis episode could be adequately explained by other causes than biliary sludge and microlithiasis were excluded.We trained supervised ML classifiers using H_(2)O.ai automatically selecting the best suitable predictor model to predict microlithiasis/sludge.The predictor model was further validated in two independent retrospective cohorts from two tertiary care centers(117 patients).RESULTS Twenty-eight categorized patients’variables recorded at admission were identified to compute the predictor model with an accuracy of 0.84[95%confidence interval(CI):0.791-0.9185],positive predictive value of 0.84,and negative predictive value of 0.80 in the identification cohort(218 patients).In the validation cohort,the robustness of the prediction model was confirmed with an accuracy of 0.76(95%CI:0.673-0.8347),positive predictive value of 0.76,and negative predictive value of 0.78(117 patients).CONCLUSION We present a robust and validated ML-based predictor model consisting of routinely recorded parameters at admission that can predict biliary sludge and microlithiasis as the cause of AP.

Diagnostic approach to patients with acute idiopathic and recurrent pancreatitis,what should be done?

Acute recurrent pancreatitis (ARP) is a common clinical condition that may be difficult to diagnose. Endoscopic ultrasound (EUS) is proposed to be a safe first line test of choice in the majority of patients. When interventions are needed to remove biliary stones, evaluate sphincter of Oddi or pancreas divisum, endoscopic retrograde cholangiopancreatography (ERCP) is recommended. Magnetic resonance cholangiopancreatography (MRCP) can be a suitable alternative from a diagnostic standpoint although may not be widely available. Finally, genetic testing is increasingly used to detect certain mutations that are associated with this diagnosis.

Endoscopic ultrasound diagnostic gain over computed tomography and magnetic resonance cholang-iopancreatography in defining etiology of idiopathic acute pancreatitis

BACKGROUND About 10%-30%of acute pancreatitis remain idiopathic(IAP)even after clinical and imaging tests,including abdominal ultrasound(US),contrast-enhanced computed tomography(CECT)and magnetic resonance cholangiopancreatography(MRCP).This is a relevant issue,as up to 20%of patients with IAP have recurrent episodes and 26%of them develop chronic pancreatitis.Few data are available on the role of EUS in clarifying the etiology of IAP after failure of one or more cross-sectional techniques.AIM To evaluate the diagnostic gain after failure of one or more previous crosssectional exams.METHODS We retrospectively collected data about consecutive patients with AP and at least one negative test between US,CECT and MRCP,who underwent linear EUS between January 2017 and December 2020.We investigated the EUS diagnostic yield and the EUS diagnostic gain over different combinations of these crosssectional imaging techniques for the etiologic diagnosis of AP.Types and frequency of EUS diagnosis were also analyzed,and EUS diagnosis was compared with the clinical parameters.After EUS,patients were followed-up for a median of 31.5 mo to detect cases of pancreatitis recurrence.RESULTS We enrolled 81 patients(63%males,mean age 61±18,23%with previous cholecystectomy,17%with recurrent pancreatitis).Overall EUS diagnostic yield for AP etiological diagnosis was 79%(20%lithiasis,31%acute on chronic pancreatitis,14%pancreatic solid or cystic lesions,5%pancreas divisum,5%autoimmune pancreatitis,5%ductal abnormalities),while 21%remained idiopathic.US,CECT and MRCP,taken alone or in combination,led to AP etiological diagnosis in 16(20%)patients;among the remaining 65 patients,49(75%)obtained a diagnosis at EUS,with an overall EUS diagnostic gain of 61%.Sixty-eight patients had negative US;among them,EUS allowed etiological diagnosis in 59(87%).Sixty-three patients had a negative CECT;among them,47(74%)obtained diagnosis with EUS.Twenty-four had a negative MRCP;among them,20(83%)had EUS diagnosis.Twenty-one had negative CT+MRCP,of which 17(81%)had EUS diagnosis,with a EUS diagnostic gain of 63%.Patients with biliary etiology and without previous cholecystectomy had higher median values of alanine aminotransferase(154 vs 25,P=0.010),aspartate aminotransferase(95 vs 29,P=0.018),direct bilirubin(1.2 vs 0.6,P=0.015),gammaglutamyl transpeptidase(180 vs 48,P=0.006)and alkaline phosphatase(150 vs 72,P=0.015)Chronic pancreatitis diagnosis was more frequent in patients with recurrent pancreatitis at baseline(82%vs 21%,P<0.001).During the follow-up,AP recurred in 3 patients,one of which remained idiopathic.CONCLUSION EUS is a good test to define AP etiology.It showed a 63%diagnostic gain over CECT+MRCP.In suitable patients,EUS should always be performed in cases of IAP.Further prospective studies are needed.

Utility of endoscopic ultrasound in pancreatitis:A review

The close proximity of the endoscopic ultrasound probe to the pancreas results in superior spatial resolution compared to CT scan and MRI. In addition, endoscopic ultrasound (EUS) is a minimally invasive procedure that does not share the relatively high complication rate of ERCP. Due to these advantages, EUS has evolved into an important technique to assess pancreatobiliary disease. This review will discuss the role of EUS in patients with pancreatitis. The indications can be divided into acute pancreatitis and chronic pancreatitis. In acute pancreatitis, EUS is used to determine the etiology; in suspected chronic pancreatitis it is helpful to establish the diagnosis. Lastly, this review will discuss biliary pancreatitis with suspicion for persistent choledocholithiasis.

Malignant lymphoma of spleen presenting as acute pancreatitis: A case report

This is a case report of a patient who presented with acute pancreatitis without the common causes. A pancreatic biopsy revealed large B cell lymphoma. Spleen lymphoma with pancreatic involvement inducing acute pancreatitis, which is a rare disorder, was diagnosed. Here we also review the few similar cases reported in the literature.

Drug induced acute pancreatitis: Does it exist?

As the incidence of acute pancreatitis continues to rise, establishing the etiology in order to prevent recurrence is important. Although the etiology of acute pancreatitis is not difficult in the majority of patients, almost a quarter of patients are initially labeled as having idiopathic acute pancreatitis. When confronted with a patient with acute pancreatitis and no clear etiology defined as an absence alcoholism, gallstones(ultrasound and/or MRI), a normal triglyceride level, and absence of tumor, it often appears reasonable to consider a drug as the cause of acute pancreatitis. Over 100 drugs have been implicated by case reports as causing acute pancreatitis. While some of these case reports are well written, many case reports represent poorly written experiences of the clinician simply implicating a drug without a careful evaluation. Over-reliance on case reports while ignoring randomized clinical trials and large pharmacoepidemiologic surveys has led to confusion about drug induced acute pancreatitis. This review will explain that drug induced acute pancreatitis does occur, but it is rare, and over diagnosis leads to misconceptions about the disease resulting in inappropriate patient care, increased litigation and a failure to address the true entity: idiopathic acute pancreatitis.

Endoscopic ultrasound-guided fine needle aspiration in the differentiation of type 1 and type 2 autoimmune pancreatitis

AIM:To investigate the usefulness of endoscopic ultrasound-guided fine needle aspiration(EUS-FNA) in the differentiation of autoimmune pancreatitis(AIP).METHODS:We retrospectively reviewed 47 of 56 AIP patients who underwent EUS-FNA and met the Asian diagnostic criteria.On 47 EUS-FNA specimens,we evaluated the presence of adequate material and characteristic features of lymphoplasmacytic sclerosing pancreatitis(LPSP) and idiopathic duct-centric pancreatitis(IDCP) mentioned in the International Consensus Diagnostic Criteria and examined if these findings make a contribution to the differential diagnosis of type 1 and type 2 AIP.A disposable 22-gauge needle was used for EUS-FNA.RESULTS:Adequate specimens including pancreatic tissue for differentiating AIP from cancer were obtained from 43 of 47 patients who underwent EUSFNA.EUS-FNA was performed from the pancreatic head in 21 cases,which is known to be technically difficult when performed by core biopsy;there was no significant difference in the results compared with pancreatic body-tail.Nine of 47 patients met level 1 findings of LPSP and 5 patients met level 2 findings of LPSP.No one met level 1 findings of IDCP,but 3 patients met level 2 findings of IDCP.Of 10 seronegative cases,2 cases were diagnosed with "definitive type 1 AIP",and 3 cases were diagnosed with "probable type 2 AIP" when considering both the level 2 histological findings and response to steroids.CONCLUSION:EUS-FNA is useful in the differentiation of type 1 and type 2 AIP,particularly in seronegative cases.

Biliary microlithiasis,sludge,crystals, microcrystallization,and usefulness of assessment of nucleation time

BACKGROUND:The process of microcrystallization,its sequel and the assessment of nucleation time is ignored.This systematic review aimed to highlight the importance of biliary microlithiasis,sludge,and crystals,and their association with gallstones,unexplained biliary pain,idiopathic pancreatitis, and sphincter of Oddi dysfunction.DATA SOURCES:Three reviewers performed a literature search of the PubMed database.Key words used were'biliary microlithiasis','biliary sludge','bile crystals','cholesterol crystallisation','bile microscopy','microcrystal formation of bile','cholesterol monohydrate crystals','nucleation time of cholesterol','gallstone formation','sphincter of Oddi dysfunction'and'idiopathic pancreatitis'.Additional articles were sourced from references within the studies from the PubMed search.RESULTS:We found that biliary microcrystals account for almost all patients with gallstone disease,7%to 79%with idiopathic pancreatitis,83%with unexplained biliary pain, and 25%to 60%with altered biliary and pancreatic sphincter function.Overall,the detection of biliary microcrystals in gallstone disease has a sensitivity ranging from 55%to 87%and a specificity of 100%.In idiopathic pancreatitis,the presence of microcrystals ranges from 47%to 90%.A nucleation time less than 10 days in hepatic bile or ultra-filtered gallbladder bile has a specificity of 100%for cholesterol gallstone disease.CONCLUSIONS:Biliary crystals are associated with gallstone disease,idiopathic pancreatitis,sphincter of Oddi dysfunction, unexplained biliary pain,and post-cholecystectomy biliary pain.Pathways of cholesterol super-saturation,crystallisation, and gallstone formation have been described with scientificsupport.Bile microscopy is a useful method to detect microcrystals and the assessment of nucleation time is a good method of predicting the risk of cholesterol crystallisation.

A potpourri of pancreatic issues

Autoimmune pancreatitis has emerged over the last 40 years from a proposed concept to a well established and recognized entity. As an efficient mimicker of pancreatic carcinoma, its early and appropriate recognition are crucial. With mounting understanding of its pathogenesis and natural history, significant advances have been made in the diagnosis of autoimmune pancreatitis. The characteristic laboratory features and imaging seen in autoimmune pancreatitis are reviewed along with some of the proposed diagnostic criteria and treatment algorithms.

Steroid-responsive pancreatitides

Autoimmune pancreatitis has received considerable attention,especially due to the marked effect of corticosteroid therapy on its clinical course.Knowledge,especially regarding type 1 autoimmune pancreatitis,has significantly increased over the last decades,and despite significant differences in pathophysiology and outcomes,both type 1 and 2 autoimmune pancreatitis are still considered different types of the same disease.Some have proposed a different nomenclature reflecting these differences.Although the term steroid-responsive pancreatitides may be interpreted as synonymous to type 1 and 2 autoimmune pancreatitis,these are not the only pancreatic conditions that show a response to steroid therapy.Acute pancreatitis caused by vasculitis and connective tissue diseases and acute pancreatitis secondary to checkpoint inhibitors or programmed cell death receptor antibody-mediated blockage cancer therapy may also benefit from steroid treatment.This review presents current concepts on these disorders,aiming to increase awareness,analyze similarities and differences,and propose a new nomenclature that reflects their specific particularities,clustering them under the term"steroid-responsive pancreatitides".