Pancreatic Enzyme Levels Research Articles

Analysis of clinical characteristics of tigecycline-induced acute pancreatitis.

The purpose of this study is to explore the clinical characteristics of tigecycline-induced acute pancreatitis. We searched the PubMed/Medline, Web of Knowledge, OVID, Elsevier, Springer Link, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, and Chinese VIP databases from 2005 and identified 19 studies of tigecycline-induced acute pancreatitis involving a total of 22 patients for inclusion in a retrospective analysis. The median (range)age of 22 patients with acute pancreatitis was 58years (range 9-83). Overall, the median (range) time of symptom onset was 6.5days (range 2-28), or 6days (range 2-14) and 6days (range 3-28) in patients with or without a loading dose of tigecycline, respectively. Symptoms included nausea, vomiting and abdominal distension (73%) and abdominal pain (73%); 90% (18/20) of patients developed mild acute pancreatitis (MAP), and 10% (2/20) developed severe acute pancreatitis (SAP). Computed tomography (CT) scans showed oedematous infiltrate in 56% (10/18) of cases and acute pancreatitis in 28% (5/18) of cases. The median (range) level of lipase and amylase was 936U/L (range 382-4089) and 588U/L (range 312-1166), respectively. The median (range) time to recovery of symptoms was 4days (range 1-10), and the time for recovery of pancreatic enzymes to the normal range was 5days (range 1-30) after the withdrawal of tigecycline in all patients. Clinicians should be particularly mindful of clinical signs and symptoms, the level of serum pancreatic enzymes and abdominal CT images in order to monitor the development of pancreatitis when using tigecycline.

A rare case of acute pancreatitis: a diagnostic conundrum and unusual complications

A 63-year-old man with a history of recurrent idiopathic acute pancreatitis (AP) was admitted to our surgical ward due to severe abdominal pain. He denied chronic excessive alcohol use. Other typical causes of AP, such as gallstones, hypertriglyceridemia, and trauma, were ruled out. After considering all possible etiologies, the most likely factor producing AP was medication that had been administered to him two weeks before the very first episode of the disease. Medication should always be considered as a possible trigger of AP, especially if the first episode occurs shortly after drug administration and the etiology is unclear. During patient’s hospitalization, laboratory reports revealed significant fluctuations in the serum levels of pancreatic enzymes, which can be attributed to recurrent bacteriemia. After the 30-day period of hospitalization and long-lasting antibiotic therapy, he was discharged in a good condition with normal levels of serum pancreatic enzymes.

A rare case of acute pancreatitis: a diagnostic conundrum and unusual complications.

A 63-year-old man with a history of recurrent idiopathic acute pancreatitis (AP) was admitted to our surgical ward due to severe abdominal pain. He denied chronic excessive alcohol use. Other typical causes of AP, such as gallstones, hypertriglyceridemia, and trauma, were ruled out. After considering all possible etiologies, the most likely factor producing AP was medication that had been administered to him two weeks before the very first episode of the disease. Medication should always be considered as a possible trigger of AP, especially if the first episode occurs shortly after drug administration and the etiology is unclear. During patient's hospitalization, laboratory reports revealed significant fluctuations in the serum levels of pancreatic enzymes, which can be attributed to recurrent bacteremia. After the 30-day period of hospitalization and long-lasting antibiotic therapy, he was discharged in a good condition with normal levels of serum pancreatic enzymes.

Emerging Phenotype of Severe Acute Respiratory Syndrome-Coronavirus 2–associated Pancreatitis

Emerging Phenotype of Severe Acute Respiratory Syndrome-Coronavirus 2–associated Pancreatitis

Efficacy of intra-arterial lidocaine infusion in the treatment of cerulein-induced acute pancreatitis.

Disturbances in pancreatic microcirculation, beginning with vasoconstriction, are crucial in early pancreatitis and progression to necrotizing pancreatitis. Thus, vascular-targeted treatment aiming to restore a sufficient level of microcirculation through vasodilation would possibly reduce the severity of pancreatitis. Lidocaine is an anti-arrhythmic and local anesthetic drug, which also acts as a vasodilator at higher concentrations. To evaluate the efficacy of intra-arterial infusion of lidocaine into the celiac trunk in treatment of cerulein-induced acute pancreatitis. Wistar rats (n = 20) were randomly divided into 2 equal groups: the control group (NaCl group, n = 10) and the study group (lidocaine group, n = 10). All subjects underwent surgical intervention with intra-arterial infusion of 0.9% NaCl (control group) or 1% lidocaine hydrochloride (study group) into the celiac trunk. Blood samples were collected 5 times at regular intervals from each rat for amylase and lipase measurements. Histopathological analysis of the pancreas was performed. A total number of 16 rats (control group n = 7, study group n = 9) were included. In the postoperative course, the study group (lidocaine group) revealed lower values of serum amylase and lipase levels compared to the control group (NaCl group), except the values at the 1st treatment point, which appeared 1 h after intraoperative drug injection. Significantly lower treatment endpoint levels of pancreatic enzymes were seen in the lidocaine group. Moreover, no differences were observed between the 1st and the last treatment point in the control group; however, these differences were significant for both enzymes in the study group. Histopathology revealed reduced pancreatitis severity in the study group compared to the controls. Intra-arterial lidocaine infusion into the celiac trunk decreases pancreatitis severity. What is more, this study demonstrates the relevance of early vasodilation in the therapy of acute pancreatitis.

Dulaglutide improves glucocorticoid-induced hyperglycemia in inpatient care and reduces dose and injection frequency of insulin

BackgroundGlucocorticoid (GC)-induced hyperglycemia is characterized by elevated postprandial blood glucose, which commonly requires multiple insulin injections. We investigated whether a long-acting glucagon-like peptide-1 receptor agonist, dulaglutide (Dula), safely improved GC-induced hyperglycemia in inpatients, to reduce insulin injection frequency.MethodsThe data of hospitalized patients with GC-induced hyperglycemia treated with Dula (Dula group, n = 38) or without (non-Dula group, n = 38) were retrospectively evaluated. Baseline data were collected at the beginning of GC treatment. The primary outcome in this study was glycemic control, which was compared between the groups using the six-point blood glucose (before and 2 h after each meal) profiles at discharge. The daily injection frequency of injectable drugs at discharge were also compared between groups.ResultsNo specific trend of underlying diseases was observed between the non-Dula and Dula groups. The proportion of patients previously administered with GC pulse therapy was comparable between the two groups. No significant differences were observed between groups, in the starting maintenance GC dose, GC dose at pretreatment of Dula and discharge, and cumulative GC dose during the observation. Six-point blood glucose levels at pretreatment and discharge were comparable between the two groups. However, daily injection frequency of injectable drugs and insulin dose were significantly lower in the Dula group than that in the non-Dula group. No differences were observed in the number of hypoglycemic events, the elevation of serum pancreatic enzyme levels, or gastrointestinal adverse events.ConclusionThese findings suggest that Dula could provide glycemic control while reducing the insulin dose and injection frequency in inpatients with GC-induced hyperglycemia. The occurrence of adverse events such as gastrointestinal symptoms and hypoglycemia did not increase in the Dula-treated patients compared to those not treated, suggesting its safety.

Pancreatitis aguda

Acute pancreatitis (AP) is a common disease that can be associated with considerably morbidity (15–20% of cases) and can be life-threatening (2%). The most frequent causes of AP are cholelithiasis and alcohol consumption. The diagnosis is based on the presence of 2 of 3 findings: typical abdominal pain, increased levels of pancreatic enzymes in blood and an imaging test compatible with AP. The classification of AP severity is based on the presence of local and/or systemic complications associated with AP. The disease management is based on vital support measures, follow-up during the first days of hospitalisation, pain relief and treatment of complications.

Initial experience of irreversible electroporation for locally advanced pancreatic cancer in a Korean population.

Locally advanced pancreatic cancer (LAPC) is one of the most aggressive malignancies. Irreversible electroporation (IRE) is a novel technique that uses a non-thermal ablation to avoid vessel or duct injury. To investigate the safety and efficacy of IRE for the management of LAPC in a Korean population. Twelve patients (median age 64 years; age range 46-73 years) treated between December 2015 and March 2017 underwent intraoperative IRE for LAPC. Technical success and clinical outcomes, including complications, serum pancreatic enzyme levels, overall survival (OS), and progression-free survival (PFS), were evaluated. Tumors were located in the pancreas head in 7 (58.3%) patients and in the body/tail in 5 (41.7%) patients. The median tumor diameter in the longest axis was 3.1 cm. Vascular invasion was observed in all patients and bowel abutment in 3 (25%) patients. Technical success was achieved in all patients. The median serum levels of amylase and lipase were 55 U/L and 31 U/L, respectively, at baseline, increased to 141.5 U/L (P = 0.008) and 53 U/L (P = 0.505), respectively, one day after IRE, and normalized after one week. The rate of 30-day mortality of unknown relation was 8.3% (one individual experienced massive hematemesis 12 days after IRE). The median OS from diagnosis and IRE was 24.5 months and 13.5 months, respectively. The median PFS from diagnosis and IRE was 19.2 months and 8.6 months, respectively. For patients with LAPC, IRE appears to be a promising treatment modality with an acceptable safety profile.

Serum Trypsinogen and Lipase as Biomarkers of Exocrine Pancreatic Function in Newly Diagnosed Children and Adolescents with Type 1 Diabetes Mellitus

Type 1 diabetes mellitus (T1DM) in literature has usually been associated with laboratory decrease in pancreatic exocrine enzymes levels. Nevertheless, the exact onset of decreased pancreatic enzymes levels in sera of patients is still unknown. We measured pancreatic serum levels of trypsinogen and lipase in Egyptian children and adolescents with newly diagnosed T1DM to reveal their role in diagnosis and their relation to HbA1c as a marker of glycemic control, lipid profile and fasting c-peptide as a marker of endocrine pancreatic insufficiency.

Effect of thyroid hormones on rat exocrine pancreas morphology and function

AimThe influence of thyroid hormones on exocrine pancreas function is poorly understood, and limited to the postnatal development period. Here, we evaluated the effects of hypo- and hyperthyroidism on the morphology and enzyme content of this tissue. Main methodsTo induce hypothyroidism male Wistar rats were subjected to a thyroidectomy (Tx) or sham operated (SO). After 40 days, some of the Tx and SO rats were treated with T3 for 7 days. Following euthanization, the pancreas was removed and evaluated for morphology, as well as amylase, lipase and trypsin content, using histological and immunoreactive techniques analyses, respectively. Serum amylase levels were also evaluated. Key findingsThe pancreatic acinar cells of Tx rats were smaller, exhibited reduced Haematoxyllin stained areas, and contained lower amylase and lipase levels, indicative of low cell activity. Tx rats also presented higher collagen levels, and high trypsin content in pancreatic extracts. Interestingly, T3 administration reversed the observed acinar cell alterations and restored pancreatic enzyme content, by augmenting amylase and lipase and attenuating trypsin levels, but failed to change collagen content. Increased levels of lipase and decreased trypsin were also observed in T3-treated SO rats. SignificanceThyroid hormones play an important role in acinar cell morphology and function. In the hypothyroid state there is a decrease in pancreatic enzyme levels that is restored with T3 treatment. In addition to participating in insulin sensitivity and glycemic control, THs also modulate enzyme expression and activity in the exocrine pancreas, consequently, delivering metabolic substrates to specific organs and tissues.

Variants That Affect Function of Calcium Channel TRPV6 Are Associated With Early-Onset Chronic Pancreatitis

Changes in pancreatic calcium levels affect secretion and might be involved in development of chronic pancreatitis (CP). We investigated the association of CP with the transient receptor potential cation channel subfamily V member 6 gene (TRPV6), which encodes a Ca2+-selective ion channel, in an international cohort of patients and in mice. We performed whole-exome DNA sequencing from a patient with idiopathic CP and from his parents, who did not have CP. We validated our findings by sequencing DNA from 300 patients with CP (not associated with alcohol consumption) and 1070 persons from the general population in Japan (control individuals). In replication studies, we sequenced DNA from patients with early-onset CP (20 years or younger) not associated with alcohol consumption from France (n= 470) and Germany (n= 410). We expressed TRPV6 variants in HEK293 cells and measured their activity using Ca2+ imaging assays. CP was induced by repeated injections of cerulein in TRPV6mut/mut mice. We identified the variants c.629C>T (p.A210V) and c.970G>A (p.D324N) in TRPV6 in the index patient. Variants that affected function of the TRPV6 product were found in 13 of 300 patients (4.3%) and 1 of 1070 control individuals (0.1%) from Japan (odds ratio [OR], 48.4; 95% confidence interval [CI], 6.3-371.7; P= 2.4× 10-8). Twelve of 124 patients (9.7%) with early-onset CP had such variants. In the replication set from Europe, 18 patients with CP (2.0%) carried variants that affected the function of the TRPV6 product compared with 0 control individuals (P= 6.2× 10-8). Variants that did not affect the function of the TRPV6 product (p.I223T and p.D324N) were overrepresented in Japanese patients vs control individuals (OR, 10.9; 95% CI, 4.5-25.9; P= 7.4× 10-9 for p.I223T and P= .01 for p.D324N), whereas the p.L299Q was overrepresented in European patients vs control individuals (OR, 3.0; 95% CI, 1.9-4.8; P= 1.2× 10-5). TRPV6mut/mut mice given cerulein developed more severe pancreatitis than control mice, as shown by increased levels of pancreatic enzymes, histologic alterations, and pancreatic fibrosis. We found that patients with early-onset CP not associated with alcohol consumption carry variants in TRPV6 that affect the function of its product, perhaps by altering Ca2+ balance in pancreatic cells. TRPV6 regulates Ca2+ homeostasis and pancreatic inflammation.

Factors Associated With Frequent Opioid Use in Children With Acute Recurrent and Chronic Pancreatitis.

The aim of the study was to understand the association of frequent opioid use with disease phenotype and pain pattern and burden in children and adolescents with acute recurrent (ARP) or chronic pancreatitis (CP). Cross-sectional study of children <19 years with ARP or CP, at enrollment into the INSPPIRE cohort. We categorized patients as opioid "frequent use" (daily/weekly) or "nonfrequent use" (monthly or less, or no opioids), based on patient and parent self-report. Of 427 children with ARP or CP, 17% reported frequent opioid use. More children with CP (65%) reported frequent opioid use than with ARP (41%, P = 0.0002). In multivariate analysis, frequent opioid use was associated with older age at diagnosis (odds ratio [OR] 1.67 per 5 years, 95% confidence interval [CI] 1.13-2.47, P = 0.01), exocrine insufficiency (OR 2.44, 95% CI 1.13-5.24, P = 0.02), constant/severe pain (OR 4.14, 95% CI 2.06-8.34, P < 0.0001), and higher average pain impact score across all 6 functional domains (OR 1.62 per 1-point increase, 95% CI 1.28-2.06, P < 0.0001). Children with frequent opioid use also reported more missed school days, hospitalizations, and emergency room visits in the past year than children with no frequent use (P < 0.0002 for each). Participants in the US West and Midwest accounted for 83% of frequent opioid users but only 56% of the total cohort. In children with CP or ARP, frequent opioid use is associated with constant pain, more healthcare use, and higher levels of pain interference with functioning. Longitudinal and prospective research is needed to identify risk factors for frequent opioid use and to evaluate nonopioid interventions for reducing pain and disability in these children.

Should the Oddis sphincter be retained? A clinical analysis of biliary metal stent implantation in patients with malignant obstructive jaundice.

We sought to analyze the efficacy and safety of preserving the Oddis sphincter during metallic biliary stent implantation in patients with malignant obstructive jaundice. In a retrospective analysis, 133 patients with malignant obstructive jaundice who were admitted to our hospital from January 2010 to January 2017 and who underwent metallic biliary stent implantation were divided into two groups - the Oddis sphincter retention group (n = 55) and the Oddis sphincter nonretention group (n = 78) - according to whether the Oddis sphincter was left untouched during stent placement. The patient clinical data as well as information on complications, time of stent patency, improvement in liver function, and decline of serum bilirubin were reviewed and evaluated. Statistical analysis was performed using the Statistical Package for the Social Sciences version 19.0 (IBM Corp., Armonk, NY, USA, USA) and Prism version 7 (GraphPad Software, San Diego, CA, USA). The median follow-up time was 9.6 months (range: 1-20 months) and there was no significant difference in general clinical information between the two groups. However, the incidence rates of acute biliary infection, recurrent biliary infection, acute pancreatitis, chronic pancreatitis, and asymptomatic pancreatic enzyme levels were higher in the Oddis sphincter retention group and the differences were all statistically significant (P < 0.05). Conversely, there were no significant differences in bilirubin decline, liver function improvement, and stent patency between the two groups (P > 0.05). Leaving the Oddis sphincter untouched during biliary stent placement can reduce the incidence of postoperative complications, while there was no effect on stent patency or jaundice relief. Therefore, it is recommended to preserve the Oddis sphincter when the stenosis is more than 3 cm above the duodenal papilla.

Case Report: Acute pancreatitis as a complication for the use of furosemide during transurethral resection of the prostate

Background: Pancreatitis caused after transurethral resection of the prostate (TURP) is an uncommon complication, with few reports found in the literature. Here we present the case of a middle-aged patient without comorbidities with this pathology. Clinical case: A 66-year-old male patient with no prior medical history underwent TURP surgery due to benign prostatic hyperplasia. The evolution was unfavourable, leading to post TURP syndrome. On the fifth day after surgery, the patient was admitted for emergency dialysis. During his emergency stay, the patient was unstable; he was diagnosed with pancreatitis, moving to an intensive care unit for management The patient progressed favourably from renal failure and pancreatitis, and on the 5th day the patient was discharged, tolerating oral feeding and stabilized renal failure. Conclusions: Pancreatitis caused by TURP is very rare. This complication has been reported in the literature infrequently and should be suspected when there is pain in the epigastrium. If this complication is suspected, imaging tests and pancreatic enzyme levels should be immediately requested, as it can have an unfavourable evolution until death.

Retrospective Matched-Cohort Analysis of Acute Pancreatitis Induced by 5-Aminosalicylic Acid-Derived Drugs.

This study aimed to compare the clinical course of 5-aminosalicylic acid-derived, drug-induced acute pancreatitis (5-ASA-DIAP) to acute pancreatitis (AP) caused by other etiologies. A cohort of patients with 5-ASA-DIAP was established through literature search. As a control AP (CAP) group, a cohort was generated from a registry. Data on the diagnostic procedure, symptoms, enzyme elevation, imaging, severity, and recovery parameters were collected. Causality was assessed using the Naranjo algorithm. Twenty-nine articles were included, which describe 36 patients with fifty-one 5-ASA-DIAP episodes (60.78% female, 39.22% male). There were 88.2% mild, 3.92% moderate, and 7.84% severe cases of AP in the 5-ASA-DIAP group, and 70.6%, 25.5%, and 3.92% such cases in the CAP population, respectively. Symptoms improved significantly faster (mean ± SE, 2.5 ± 0.34 vs 3.74 ± 0.42 days; P = 0.018); however, pancreatic enzyme levels normalized significantly more slowly (6.27 ± 1.53 vs 3.63 ± 0.61 days, P = 0.008) in the 5-ASA-DIAP cohort compared with the CAP group. This study confirms that there are no diagnostic differences between 5-ASA-DIAP and AP of other etiologies. Fewer moderate but more severe cases were found in the 5-ASA-DIAP group; therefore, 5-ASA-DIAP must be taken as seriously as AP of other etiologies.

Clinical characteristics of anti-glutamic acid decarboxylase antibody-positive fulminant type 1 diabetes.

This research aimed to examine the relationship between anti-glutamic acid decarboxylase antibody (GADA) titers and clinical parameters at onset and to clarify the association between clinical severity and GADA titers in GADA-positive fulminant type 1 diabetes. This cross-sectional observational study included 20 cases with GADA-positive fulminant type 1 diabetes (4 cases from our hospital and 16 from cases reported in the literature). The association between GADA titers and clinical parameters [age, sex, body weight, body mass index, period from appearance of any prodromal symptoms to diagnosis, period from development of hyperglycemic symptoms to diagnosis, GADA titer, HbA1c level, blood pH and HCO3- level, serum levels of ketone bodies and pancreatic exocrine enzymes] were analyzed. Spearman's rank correlation coefficient (rs) was used for the correlation analysis. The results showed that there was a significant inverse correlation between GADA titers and the "period from appearance of any prodromal symptoms to diagnosis" (rs = -0.559, p < 0.05). Moreover, GADA titers were inversely correlated with blood pH and HCO3- level (rs = -0.576, p < 0.05, rs = -0.578, p < 0.05, respectively), and positively correlated with serum levels of total ketone bodies, acetoacetate, and 3-hydroxybutyrate (rs = 0.661, p < 0.05; rs = 0.700, p < 0.05; and rs = 0.782, p < 0.01, respectively). These findings suggest that higher GADA titers may be linked to more severe clinical severity of GADA-positive fulminant type 1 diabetes at onset. This association may be attributed to possible pre-existence of autoimmunity-related β-cell damage before the onset of fulminant type 1 diabetes.

Pancreatitis, Panniculitis, and Polyarthritis Syndrome Simulating Cellulitis and Gouty Arthritis

Pancreatitis, panniculitis, and polyarthritis (PPP) syndrome is a rare but critical disease with a high mortality rate. The diagnostic dilemma of PPP syndrome is the fact that symptoms occur unexpectedly. A 48-year-old man presented with fever and painful swelling of the left foot that was initially mistaken for cellulitis and gouty arthritis. The diagnosis of PPP syndrome was made based on the abdominal CT findings and elevated pancreatic enzyme levels, lobular panniculitis with ghost cells on a skin biopsy, and polyarthritis on a bone scan. The pancreatitis and panniculitis disappeared spontaneously over time, but the polyarthritis followed its own course despite the use of anti-inflammatory agents. In addition to this case, 30 cases of PPP syndrome in the English literature were reviewed. Most of the patients had initial symptoms other than abdominal pain, leading to misdiagnosis. About one-third of them were finally diagnosed with a pancreatic tumor, of which pancreatic acinar cell carcinoma was the most dominant. They showed a mortality rate of 32.3%, associated mainly with the pancreatic malignancy. Therefore, PPP syndrome should be considered when cutaneous or osteoarticular manifestations occur in patients with pancreatitis. Active investigation and continued observations are needed for patients suspected of PPP syndrome.

Observational study of comparison of BISAP score with Ranson’s score and APACHE II scores in assessing severity and prognosis in patients of acute pancreatitis

Background: Acute pancreatitis is one of the most common diseases of gastrointestinal tract, leading to tremendous emotional, physical and financial burden. Acute pancreatitis is an acute inflammation of the prior normal gland parenchyma which is usually reversible (but acute attack can occur in a pre-existing chronic pancreatitis) with raised pancreatic enzyme levels in blood and urine. It may be first attack or relapsing attacks with an apparently normal gland in between. Biliary tract disease and alcoholism are the commonest cause of pancreatitis.Methods: It was an observational study at Surat municipal institute of medical education and research (SMIMER), Department of Surgery. In present study authors used BISAP score, RANSON’S score and APACHE II score to evaluate the severity and mortality in cases of pancreatitis. In present study authors have compare all the scoring system on the basis of CT scan findings. In present study authors have included all patients above age of 18 years. Patient below 18 years of age, acute on chronic pancreatitis and hereditary pancreatitis were not included.Results: In this retrospective study, we found that incidence of colorectal carcinoma is more between 40-60 years of age with male predominance; lymph node metastasis is more than metastasis in any other sites. CT scan can diagnose lymphatic metastasis and infiltration in surrounding tissue more accurately. Percentage of sphincter saving procedure were low in rectal malignancies in our study.Conclusions: All three-scoring system assess the prognosis of the patient, but the prognosis assessed by APACHE II score is better, but for quick and easy assessment, BISAP score is good for prognosis because APACHE II score uses more parameters to assess the prognosis and BISAP score uses less parameters to assess the prognosis.

Successful diagnosis of acute pancreatitis caused by impacted gallstone at the ampulla of Vater using endoscopic ultrasonography: a case report

A 69-year-old woman with a history of chronic pancreatitis and gallbladder stone was emergently transported to our hospital for sudden epigastric pain after ingesting alcohol. Her blood test showed elevated pancreatic enzyme levels, including amylase at 3515U/L. Although jaundice was not observed, there was a mild increase in hepatobiliary enzyme levels. Abdominal ultrasonography and computed tomography showed no stone in the common bile duct; however, we observed a fat stranding around the pancreas and made a diagnosis of acute pancreatitis. Although alcoholic pancreatitis was strongly suspected, we performed endoscopic ultrasonography (EUS) to rule out gallstone pancreatitis. On EUS, a 6-mm hyperechoic lesion with acoustic shadow was observed at the papilla; the patient was diagnosed with an impacted stone at the ampulla of Vater. Emergency endoscopic sphincterotomy and removal of the impacted stone were performed. EUS is useful for evaluating biliary obstruction in cases with gallstone pancreatitis and can diagnose impacted stone at the papilla. We strongly recommend EUS in cases with pancreatitis for which an indication of endoscopic retrograde cholangiopancreatography is uncertain.

Trypsin-encoding PRSS1-PRSS2 variations influence the risk of asparaginase-associated pancreatitis in children with acute lymphoblastic leukemia: a Ponte di Legno toxicity working group report.

Asparaginase-associated pancreatitis is a life-threatening toxicity to childhood acute lymphoblastic leukemia treatment. To elucidate genetic predisposition and asparaginase-associated pancreatitis pathogenesis, ten trial groups contributed remission samples from patients aged 1.0−17.9 years treated for acute lymphoblastic leukemia between 2000 and 2016. Cases (n=244) were defined by the presence of at least two of the following criteria: (i) abdominal pain; (ii) levels of pancreatic enzymes ≥3 × upper normal limit; and (iii) imaging compatible with pancreatitis. Controls (n=1320) completed intended asparaginase therapy, with 78% receiving ≥8 injections of pegylated-asparaginase, without developing asparaginase-associated pancreatitis. rs62228256 on 20q13.2 showed the strongest association with the development of asparaginase-associated pancreatitis (odds ratio=3.75; P=5.2×10−8). Moreover, rs13228878 (OR=0.61; P=7.1×10−6) and rs10273639 (OR=0.62; P=1.1×10−5) on 7q34 showed significant association with the risk of asparaginase-associated pancreatitis. A Dana Farber Cancer Institute ALL Consortium cohort consisting of patients treated on protocols between 1987 and 2004 (controls=285, cases=33), and the Children’s Oncology Group AALL0232 cohort (controls=2653, cases=76) were available as replication cohorts for the 20q13.2 and 7q34 variants, respectively. While rs62228256 was not validated as a risk factor (P=0.77), both rs13228878 (P=0.03) and rs10273639 (P=0.04) were. rs13228878 and rs10273639 are in high linkage disequilibrium (r2=0.94) and associated with elevated expression of the PRSS1 gene, which encodes for trypsinogen, and are known risk variants for alcohol-associated and sporadic pancreatitis in adults. Intra-pancreatic trypsinogen cleavage to proteolytic trypsin induces autodigestion and pancreatitis. In conclusion, this study finds a shared genetic predisposition between asparaginase-associated pancreatitis and non-asparaginase-associated pancreatitis, and targeting the trypsinogen activation pathway may enable identification of effective interventions for asparaginase-associated pancreatitis.