Acute Recurrent Pancreatitis (ARP) and Chronic Pancreatitis (CP) may cause abdominal pain, malnutrition, opioid dependency, and impairment in quality of life. Total Pancreatectomy with Islet Autotransplantation (TPIAT) is an option when other measures fail. Pancreatitis gastroparesis can be potentiated by surgery. Botulinum toxin (BT) injections into the pylorus have been used in children for gastroparesis. We evaluated outcomes of pyloric injection of BT for TPIAT in children.

Retrospective cohort of children who underwent TPIAT (2021-2023). Twenty with-BT and 20 without-BT were evaluated for time to achieve full oral nutrition, percent weight change at discharge, days with emesis through post op day 14 (POD14), days when gastrostomy tube (G) required drainage for vomiting through POD14, length of stay (LOS). We hypothesized that pyloric BT during TPIAT would decrease post-operative gastroparesis symptoms.

CP diagnosis present in 80 % of with-BT & 65 % of the without-BT patients. The groups were similar by sex (with-BT, 45 % male vs 50 % in without-BT). With-BT patients had fewer days to full PO (29.4 (18.3) vs. 40.9 (15.9), p < 0.01), and fewer G tube days (mean 7.2 SD (2.6) vs 10.1(3.4)) (p < 0.01) but no significant difference in emesis days (2.7 (2.8) vs 4.2 (2.9)) (p = 0.21), percent weight change at discharge (-2.9 % (2.7) vs. -4.6 % (2.7)) (p = 0.07) and LOS (median 15.5 IQR(14-16.5) vs. 16 (13.5-19)) (p = 0.46).

Pyloric BT may improve postoperative gastroparesis symptoms among pediatric patients undergoing TPIAT. To our knowledge, this is the first pediatric study evaluating morbidity associated with gastroparesis after TPIAT in an already high-risk population due to ARP or CP.

Retrospective Cohort Study LEVEL OF EVIDENCE: III.

Pancreatitis poses a growing public health concern among children and adolescents, yet comprehensive data on its prevalence, incidence, mortality, and disability-adjusted life years (DALYs) remain scarce. This study aims to analyze global, regional, and national trends in pancreatitis burden over the past 3 decades.

Using data from the Global Burden of Disease (GBD) 2019 database spanning 1990-2019, we assessed pancreatitis prevalence, incidence, mortality, and DALYs, reporting on numbers, rates, age-standardized prevalence rate (ASPR), age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), age-standardized DALYs rate (ASDR), and average annual percentage changes (AAPCs). Trends were analyzed by age, sex, region, and socio-demographic index (SDI) using jointpoint analysis and predictive modeling.

Globally, pancreatitis prevalence and incidence rates have increased (AAPC prevalence = 0.13, 95% CI: 0.11-0.16; AAPC incidence = 0.30, 95% CI: 0.28-0.32), while mortality and DALYs rates have decreased (AAPC mortality = -1.30, 95% CI: -1.53, -1.07; AAPC DALYs = -1.21, 95% CI: -1.41, -1.01). Both genders showed similar trends. Children under 5 and adolescents 15-19 had higher mortality and DALYs rates. Low SDI regions experienced the greatest increase in ASIR. Eastern Europe exhibited high and rising ASIR, ASMR, and ASDR. Projections indicate continued rise in prevalence with declining mortality and DALYs.

Pancreatitis burden in children and adolescents has surged globally, especially in lower SDI regions. These findings underscore the urgent need for targeted interventions and healthcare resources in affected areas.

To investigate the epidemiology and burden of adult-onset chronic pancreatitis (CP) in South Australia.

Retrospective case-control study; data linkage.

All public adult hospitals in SA.

Administrative data linkage from South Australia-Northern Territory DataLink was used to ascertain an index cohort of all adults with an initial diagnosis of CP aged >19 years between June 2000 and June 2019. Age- and sex-matched controls were drawn from the general population of SA, adults with type 1 diabetes mellitus and adults with type 2 diabetes mellitus (defined by International Classification of Diseases 10th Revision coding).

Hospital visits, days in hospital, emergency department visits, intensive care unit admissions, incidence, prevalence.

A total of 2503 incident index cases with CP were identified. The crude prevalence and incidence were estimated as 195.1 per 100 000 and 10.4 per 100 000 per annum, respectively. Cases of CP averaged more hospital visits for any reason (median 11, IQR 5 to 21.75) than the general population (median 1, IQR 0 to 4) and had a higher healthcare burden than controls with type 1 diabetes or type 2 diabetes (all p<0.001). Indigenous individuals were over-represented in the cohort (n=358; 14.8% vs 1.5% of the general population) and had higher healthcare utilisation than other patients with CP (p<0.001).

CP is a significant burden on the SA healthcare system and was more prevalent and more burdensome in Indigenous adults. CP consumes a disproportionate level of public health services. Our findings support further research and preventive efforts, particularly in the Indigenous population.

We aimed to assess whether patients with rheumatoid arthritis (RA) have a higher risk of developing acute and chronic pancreatitis compared to individuals without RA. We identified 54,910 individuals with RA between 2010 and 2017. After exclusion, they were matched in a 1:3 ratio based on age and gender to control population without RA. Cox regression analyses were performed to estimate hazard ratio. During a median follow-up of 5.5 years, 0.18% of the patients with RA and 0.14% of the matched control developed acute pancreatitis. The risk acute pancreatitis was higher in the RA cohort compared to matched control (adjusted hazard ratio [aHR] 1.33; 95% confidence interval [CI] 1.02-1.74). In the case of chronic pancreatitis, 0.11% of patients with RA and 0.09% of the matched control developed chronic pancreatitis. Patients with RA appear to have a marginally elevated risk of chronic pancreatitis compared to matched controls (aHR 1.25, 95% CI 0.90-1.74), though this increase did not achieve statistical significance. The risk of acute pancreatitis is slightly higher in individuals with RA than in matched controls. The risk of chronic pancreatitis did not show statistical significance, but it tended to increase marginally in patients with RA.

Diabetes (DM) can occur as a complication of acute, acute recurrent, or chronic pancreatitis, affecting more than 30% of adults with chronic pancreatitis. Data on the pathophysiology and management are limited, especially in pediatric population. Proposed mechanisms include insulin deficiency, insulin resistance, decreased pancreatic polypeptide, and possible beta-cell autoimmunity (in a small subset). Risk factors for developing diabetes in those with pancreatitis may include hypertriglyceridemia, obesity, necrotizing pancreatitis, exocrine pancreatic insufficiency, and pancreatic calcifications, among others. Further studies are required to understand pathophysiology of pancreatogenic DM, in order to define optimal treatment approaches.

Chronic pancreatitis (CP) in children has exhibited an annual increase in incidence in recent years. Pediatric CP presents unique clinical features compared to adult cases. Endoscopic retrograde pancreatography (ERP) serves as a valuable and safe tool for diagnosing and treating CP in adults. However, data on endoscopic treatment of CP in children are still limited.

Demographics, etiology, surgical indications, diagnosis, treatment details, associated complications, and follow-up information were retrospectively studied in consecutive patients (<18 years old) who underwent ERP for CP between January 2020 and October 2024.

A total of 17 children (7 male, 10 female) with a mean age of 10.0 ± 2.7 years were included in the study. A total of 34 endoscopic treatments were conducted. Recurrent abdominal pain was the primary clinical symptom. Imaging predominantly revealed pancreatic duct abnormalities such as tortuous dilatation and the presence of pancreatic duct stones. Notably, 41.2% (7 cases) involved genetic and congenital anatomical variations. Pancreatic duct stent placement was successfully performed in all 17 children (100.0% success rate). Stent replacements occurred on average 2.2 times (range 1-5) at intervals of 3-6 months. Postoperative pancreatitis developed in 2 cases (5.9%, 2/34), and hyperamylasemia occurred in 5 cases (14.7%, 5/34). The postprocedure visual analogue scale (VAS) score for abdominal pain significantly decreased from 6 to 1 (P < 0.001). The annual frequency of pancreatitis episodes showed a significant reduction, decreasing from 2.4 times pre-treatment to 0.6 times post-treatment (P < 0.05). Body mass index (BMI) also showed a significant improvement post-treatment compared to pre-treatment (P < 0.05).

ERP performed by trained endoscopists utilizing standard adult endoscopes and accessories proved a safe and effective treatment option for pediatric CP, with complication rates comparable to those reported in adult cases.

Genetic variants in PRSS1 encoding human cationic trypsinogen are associated with hereditary pancreatitis. The clinically frequent variants exert their pathogenic effect by increasing intrapancreatic trypsin activity, while a distinct subset of variants causes disease via mutation-induced trypsinogen misfolding and endoplasmic reticulum (ER) stress. Here, we report a novel misfolding PRSS1 variant.

We used next-generation and Sanger sequencing to screen the index patient. We performed structural modeling and analyzed the functional effects of the PRSS1 variant.

A heterozygous c.182C>T (p.Ala61Val) PRSS1 variant was identified in a case of suspected intrauterine pancreatitis with pseudocyst formation. Recombinant p.Ala61Val trypsinogen autoactivated to lower trypsin levels, but activity of p.Ala61Val trypsin was similar to wild type. In cell culture experiments, the variant exhibited reduced secretion and intracellular retention. Cells expressing the p.Ala61Val variant showed signs of ER stress, as judged by elevated mRNA expression of Hspa5 encoding the chaperone BiP, and increased mRNA splicing of the transcription factor XBP1.

Taken together, the observations expand the repertoire of misfolding PRSS1 variants and highlight the need for functional analysis to identify this rare form of genetic etiology.

Both the clinical management and study of recurrent acute pancreatitis and chronic pancreatitis are complicated by significant heterogeneity in the etiology, mechanisms, symptoms, and complications of pancreatitis. The National Institutes of Diabetes and Digestive and Kidney Disease recently convened a workshop to address current knowledge and knowledge gaps in the field. Preclinical models that better replicate human disease are important for development of new therapies. Pain is often the most common and most difficult symptom to treat, as the causes are multifactorial and effective treatment may vary depending on whether pain is neuropathic or nociceptive in origin, and the placebo effect can complicate evaluation of the efficacy of medical and procedural interventions. Novel technologies like functional magnetic resonance imaging and virtual reality may offer novel means for assessing and treating pain, respectively. Clinical trial designs will need to consider best approaches to addressing the heterogeneity of chronic pancreatitis, including careful attention to designing eligibility criteria, and establishing accepted and validated core outcomes criteria for the field. The latter may be informed by consensus in pain research. Recruitment of participants into clinical trials has been challenging, often requiring multiple centers. Establishment of a clinical trials network would facilitate greater opportunities for therapeutic trials in pancreatitis.

Chronic pancreatitis (CP) is a quite common disease with an annual incidence of up to 30 new cases per 100,000 persons in Russia, and 9.6 cases per 100,000 persons abroad. Idiopathic pancreatitis associated with genetic mutations ranks second in frequency. When conservative therapy is ineffective, surgical intervention is considered. Total pancreatectomy reduces pain, but leads to pancreatogenic diabetes mellitus. In case of hereditary pancreatitis caused by mutations in the PRSS1, CFTR, SPINK1 genes, pancreatectomy becomes advisable, including for prevention of pancreatic cancer. Isolation of Langerhans islets from the excised pancreas and their autotransplantation (total pancreatectomy with islet autotransplantation, TPIAT) provides additional treatment options. Such surgical interventions are not performed in Russia as of yet. The aim of the study was to assess the effectiveness of total pancreatectomy followed by restoration of glucose tolerance in treatment of patients with chronic genetically determined pain pancreatitis.

Two patients with chronic pain pancreatitis with the SPINK1 and PRSS1 genetic mutations were examined and underwent surgical total pancreatectomy. Islets were isolated from the excised glands and implanted into the liver. Postoperative followup included an assessment of quality of life and pain intensity based on questionnaires, as well as determination of the glycemic level.

Following total pancreatoduodenectomy and autotransplantation, a significant decrease in pain and an improvement in quality of life were noted. Transplanted islets' function was reduced, due to their insufficient number, which required administration of exogenous insulin.

The described experience demonstrates the TPIAT effectiveness in treatment of chronic pancreatitis, which can become a basis for further research and introduction of the technique into domestic clinical practice.

Necrotizing gallstone pancreatitis is a rare and severe form of pancreatitis, particularly uncommon in the pediatric population. While gallstone pancreatitis is increasingly recognized in children, necrotizing cases remain exceptional. We report a four-and-a-half-year-old Pakistani American male presenting with generalized weakness, abdominal pain, and vomiting. Initial symptoms followed a recent upper respiratory infection. Clinical evaluation revealed an intermittently drowsy-appearing patient with a Glasgow Coma Scale (GCS) of 15 when fully alert, hypotension, diffuse abdominal tenderness, and signs of possible sepsis. Laboratory tests showed elevated lipase levels and conjugated hyperbilirubinemia. Ultrasound identified gallstones and necrotizing changes in the pancreas, which were later confirmed by CT imaging. The patient was admitted to the pediatric intensive care unit for aggressive management of necrotizing pancreatitis, including fluid resuscitation, antibiotic therapy, and nutritional support. He underwent laparoscopic cholecystectomy and developed Clostridium difficile colitis, which was managed with targeted antibiotics. The patient had a 26-day hospital stay and was followed up with negative results from clinical exome sequencing for related disorders. This case underscores the diagnostic and management complexities associated with pediatric necrotizing gallstone pancreatitis. The need for a multidisciplinary approach and adherence to clinical guidelines is emphasized. This report contributes valuable insights into the rare presentation of necrotizing pancreatitis in children and highlights the importance of early and comprehensive intervention.

Among children who suffer from acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP), acute pancreatitis (AP) episodes are painful, often require hospitalization, and contribute to disease complications and progression. Despite this recognition, there are currently no interventions to prevent AP episodes. In this retrospective cohort study, we assessed the impact of pancreatic enzyme therapy (PERT) use on clinical outcomes among children with pancreatic-sufficient ARP or CP.

Children with pancreatic-sufficient ARP or CP in the INSPPIRE-2 cohort were included. Clinical outcomes were compared for those receiving vs not receiving PERT, as well as frequency of AP before and after PERT. Logistic regression was used to study the association between development of AP episodes after starting PERT and response predictors.

Among 356 pancreatic-sufficient participants, 270 (76%) had ARP, and 60 (17%) received PERT. Among those on PERT, 42% did not have a subsequent AP episode, during a mean 2.1 years of follow-up. Children with a SPINK1 mutation ( P = 0.005) and those with ARP (compared with CP, P = 0.008) were less likely to have an AP episode after starting PERT. After initiation of PERT, the mean AP annual incidence rate decreased from 3.14 down to 0.71 ( P < 0.001).

In a retrospective analysis, use of PERT was associated with a reduction in the incidence rate of AP among children with pancreatic-sufficient ARP or CP. These results support the need for a clinical trial to evaluate the efficacy of PERT to improve clinical outcomes among children with ARP or CP.

Objectives: To evaluate the role of ERCP (endoscopic retrograde cholangio-pancreatography) and EUS (endoscopic ultrasound) and to describe the efficacy and safety of these procedures in a paediatric cohort with chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP). Methods: All patients (<18 years) undergoing an ERCP or EUS for ARP and CP between January 2008 and December 2022 were included. Data collection included indications for the procedure, technical success, adverse events and outcome data. Results: A total of 222 ERCPs were performed in 98 patients with CP and ARP (60% female, median age 10 years). The commonest indications were a main pancreatic duct stricture (PD) with or without a stone within the main PD. Successful cannulation was achieved in 98% of cases. Improved stricture resolution was demonstrated in 63% of patients. The overall adverse event rate for ERCP was low (n = 8/222, 3.6%). An improvement in abdominal pain was demonstrated in (75/98) 76% of patients. Their Body Mass Index also significantly improved post ERCP (15.5 ± 1.41 vs. 12.9 ± 1.16 kg/m2, p = 0.001). A total of 54 EUS procedures were undertaken in 48 individuals. Moreover, 35 individuals underwent a therapeutic EUS procedure, for which the commonest indication was the drainage of a pancreatic fluid collection. The overall complication rate was low (n = 2.4%) in all EUS cases. Conclusions: ERCP and EUS can be safely and effectively used in a paediatric population with indications analogous to an adult cohort.

The impact of chronic pancreatitis (CP) on quality of life (QOL) of children is not well established. Our objective was to evaluate the QOL, identify contributing factors, and determine the prevalence of anxiety and depression in children with CP in India.

Children (8-18y old) with CP were prospectively enrolled across three pediatric gastroenterology centres in India. QOL was assessed using the pediatric QOL inventory (PedsQL 4.0) scale, administered to both children and their parents. Anxiety and depression was studied using the Revised Children's Anxiety and Depression Scale (RCADS 25). Contributing factors were identified using binary logistic regression analysis. The data was compared against published QOL data in healthy Indian children.

121 children with CP (boys-57.9 %, age at QOL-14 ± 3.2years) were enrolled. A majority (82.7 %) had pain and advanced disease (Cambridge grade IV- 63.6 %). Children with CP had poorer QOL compared to controls (total score 74.6 ± 16 vs. 87.5 ± 11.1, p < 0.0001). QOL scores were similar across centres. Older children were similar to younger ones, except for a poorer emotional QOL. Taking QOL < -2 standard deviation (SD) of controls, ∼35 % had poor physical (50.9 ± 11.9) and 20 % had poor psychosocial (PS) QOL score (52.1 ± 7.2). On analysis, presence of pain and lower socio-economic status (SES) adversely affected both physical and PS-QOL. Additionally, girls had poorer PS-QOL than boys (Odds ratio 3.1, 95%CI:1.23-7.31). Anxiety and depression were uncommon (2,1.6 %).

Patients with CP had impaired physical and psycho-social QOL. Presence of pain and lower SES adversely affected QOL. Psychiatric comorbidities were uncommon.

Necrotizing pancreatitis is an uncommon diagnosis in pediatric patients. Early diagnosis is difficult as the presentation varies significantly. However, it should be in the differential diagnosis of abdominal pain in the pediatric age group.

An 8-year-old girl arrived with a 1-day history of vomiting, constipation, and abrupt, increasing epigastric discomfort. She didn't have any noteworthy family or medical background. Upon examination, she seemed to be afebrile but also had discomfort in her stomach and symptoms of dehydration. An enlarged pancreas with necrotizing pancreatitis was seen in the first imaging. She received intravenous fluids, antibiotics, and analgesics as a treatment for her acute severe pancreatitis diagnosis. Since the patient continued to have fever, meropenem was prescribed in place of ceftriaxone at first. After 10 days of uncomplicated hospitalization, she was released from the hospital.

Once rare, pediatric pancreatitis now affects 3-13 out of every 100 000 people yearly. Although it is uncommon (<1% in children), necrotizing pancreatitis can happen. Its causes are similar to those of acute pancreatitis, involving genetic abnormalities and certain drugs. Abdominal discomfort, fever, vomiting, and nausea are among the symptoms. Imaging methods like contrast-enhanced CT are used in diagnosis. Surgery has given way to less intrusive techniques like catheter drainage as a form of treatment. Surgery is seldom required in pediatric instances, which are often handled conservatively.

Childhood necrotizing pancreatitis is uncommon but dangerous; prompt diagnosis and prompt treatment are essential.

Chymotrypsin C (CTRC) protects the pancreas against unwanted intrapancreatic trypsin activity through degradation of trypsinogen. Loss-of-function CTRC variants increase the risk for chronic pancreatitis (CP). The aim of the present study was to characterize novel CTRC variants found during genetic testing of CP cases at a pediatric pancreatitis center.

We used next-generation sequencing to screen patients. We analyzed the functional effects of CTRC variants in HEK 293T cells and using purified enzymes.

In 5 separate cases, we detected 5 novel heterozygous CTRC variants: c.407C>T (p.Thr136Ile), c.550G>A (p.Ala184Thr), c.627Cdup (p.Ser210Leufs∗?, where the naming indicates a frame shift with no stop codon), c.628T>C (p.Ser210Pro), and c.779A>G (p.Asp260Gly). Functional studies revealed that with the exception of p.Ser210Leufs∗?, the CTRC variants were secreted normally from transfected cells. Enzyme activity of purified variants p.Thr136Ile, p.Ala184Thr, and p.Asp260Gly was similar to that of wild-type CTRC, whereas variant p.Ser210Pro was inactive. The frame-shift variant p.Ser210Leufs∗? was not secreted but accumulated intracellularly, and induced endoplasmic reticulum stress, as judged by elevated mRNA levels of HSPA5 and DDIT3, and increased mRNA splicing of XBP1.

CTRC variants p.Ser210Pro and p.Ser210Leufs∗? abolish CTRC function and should be classified as pathogenic. Mechanistically, variant p.Ser210Pro directly affects the amino acid at the bottom of the substrate-binding pocket while the frame-shift variant promotes misfolding and thereby blocks enzyme secretion. Importantly, 3 of the 5 novel CTRC variants proved to be benign, indicating that functional analysis is indispensable for reliable determination of pathogenicity and the correct interpretation of genetic test results.

This is the third paper in the series providing updated information and recommendations for people with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorder (CFTR-RD). This paper covers the individual disorders, including the established conditions - congenital absence of the vas deferens (CAVD), diffuse bronchiectasis and chronic or acute recurrent pancreatitis - and also other conditions which might be considered a CFTR-RD, including allergic bronchopulmonary aspergillosis, chronic rhinosinusitis, primary sclerosing cholangitis and aquagenic wrinkling. The CFTR functional and genetic evidence in support of the condition being a CFTR-RD are discussed and guidance for reaching the diagnosis, including alternative conditions to consider and management recommendations, is provided. Gaps in our knowledge, particularly of the emerging conditions, and future areas of research, including the role of CFTR modulators, are highlighted.

Total pancreatectomy with islet autotransplantation (TPIAT) is an established and effective treatment modality for patients diagnosed with intractable chronic pancreatitis (CP) and recurrent acute pancreatitis (RAP). TPIAT primarily aims to manage debilitating pain leading to impaired quality of life among patients with CP or RAP, which can be successfully managed with medical, endoscopic, or surgical interventions. TPIAT is significantly successful in relieving pain associated with CP and improving health-related quality of life outcomes. Furthermore, the complete loss of pancreatic endocrine function attributed to total pancreatectomy (TP) can be compensated by autologous islet transplantation (IAT). Patients receiving IAT can achieve insulin independence or can be less dependent on exogenous insulin compared with those receiving TP alone. Historically, TPIAT has been mainly used in the United States, and its outcomes have been improving due to technological advancements. Despite some challenges, TPIAT can be a promising treatment for patients with CP-related intractable pain. Thus far, TPIAT is not commonly performed in Japan. Nevertheless, it may improve health-related quality of life in Japanese patients with CP, similar to Western patients. This review article aimed to provide an overview of the indications, related procedures, and outcomes of TPIAT and to discuss future prospects in Japan.

Jaundice is an important physiologic manifestation of both benign and insidious diseases. We report on the case of an 11-year-old male who presented with diffuse pruritis, jaundice, and later abdominal pain. Initial work-up revealed an obstructive cholestatic pattern, warranting investigation for structural anomalies. Extensive imaging revealed a lesion on the pancreatic head, and biopsy of the lesion confirmed the diagnosis of idiopathic fibrosing pancreatitis (IFP). Temporary stenting of the common bile duct successfully treated our patient's symptomatic IFP.

The event-rate of recurrent acute pancreatitis (RAP) in patient populations is critical for powering research studies. We hypothesize that some patients manage RAP attacks at home, reducing event rate estimations based on counting emergency department (ED) visits and hospitalizations only. The aim of this study was to determine the rates of home self-management of recurrent acute pancreatitis compared to ED visits and hospitalizations.

An anonymous 8-question survey was sent to 1825 individuals on an email list of individuals with a history of acute pancreatitis (AP) or chronic pancreatitis or interest in pancreatic diseases. Question were designed to identify subjects with RAP within the past 2 years and to subdivide patients based on having a chronic pain syndrome or not.

After an initial email request and one reminder a total of 194 subjects responded with 98 RAP subjects suitable for analysis. Annual AP events included an average of 1.44 hospitalizations, 1.37 ED visits, 2.46 disrupted work/school/social engagements, and 3.95 pancreatitis-like pain attacks per year. Patients with RAP average 6.8 RAP events per year with 58.4 % managed at home.

The burden of disease in patients with RAP is significantly underestimated, especially for patients with chronic pain. Future studies should include measures to capture RAP events managed at home and utilize methods of documenting RAP events.

For children with diminished quality of life and chronic pain caused by acute recurrent or chronic pancreatitis who are undergoing total pancreatectomy with islet autotransplantation, postoperative nutrition support has several unique characteristics. Surgical complications may lead to delays in nutrition support initiation or require modifications to the regimen. Early postoperative dysmotility requires the use of temporary enteral nutrition until this improves. The resultant complete exocrine pancreatic insufficiency necessitates lifelong pancreatic enzyme replacement therapy and fat-soluble vitamin supplementation. A low-oxalate diet is recommended to prevent kidney stones. Carbohydrate counting is needed for the provision of short-term insulin dosing and possibly long-term as well, depending on the transplanted islet yield. Children should have careful nutrition assessment and monitoring at several follow-up visits during the first year, then annually, and at any time with concerns.

To compare factor(s) contributing to aetiology, management and clinical outcome(s) of paediatric patients acquiring acute pancreatitis (AP) at two major university paediatric surgical centres in Liverpool and Bangkok.

All patients (<18 years) with an index diagnosis of AP (ICD 10 coding) during 2006-2016 were studied.

121 patients included n = 79 (65.3%) in Thailand versus n = 42 (34.7%) in the UK centre with no difference(s) in age at diagnosis at 10.4 ± 4.5 and 11.7 ± 6 years. (P = 0.12). Major AP aetiology(s) in Thailand were medications (39.2%) and choledochal cysts (8.9%). In the UK-gallstone disease (21.4%), and medications (16.7%) were leading factors (P < 0.01). Ultrasonography was deployed more frequently in the UK versus Thai centre (74.3% vs. 49.1%; P < 0.01). Pancreatitis was confirmed by imaging in 67.9% (Thai) and 62.9% (UK) patients (P = 0.47). Most patients at both centres had a mild-grade pancreatitis illness (95% Thai vs. 90.5% UK; P = 0.28) while 12.7% of Thai and 19% of UK children developed pancreatitis-related complication (P = 0.37). Overall mortality rate (%) was significantly higher in the Thai versus UK centre (27.8% vs. 9.5%; P = 0.02).

Aetiology of acute pancreatitis appears to vary between UK and Thailand children. Timely early diagnosis and healthcare pathways may be driven by local patient-related factor(s). The higher mortality (%) observed in Thailand versus UK in this comparative study was linked to underlying co-existent chronic medical condition(s) in vulnerable patient cohorts.

Paediatric chronic pancreatitis (CP) is a rare and debilitating pathology that often requires invasive diagnostics and therapeutic interventions either to address a primary cause such as a pancreaticobiliary malunion or to deal with secondary complications such as chronic pain. Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) are two endoscopic modalities that have an established diagnostic role in paediatric CP, and their therapeutic utilisation is increasing in popularity. Surgical decompression of the obstructed and dilated pancreatic duct plays a role in alleviating pancreatic duct hypertension, a common association in CP. Surgery equally has a role in certain anatomical abnormalities of the pancreaticobiliary draining system, or occasionally in some CP complications such as drainage of a symptomatic pancreatic pseudocyst.

Chronic pancreatitis (CP) as a progressive inflammatory disorder, remains untreatable. The novel treatment strategy for CP is imperative. We attempted to explore the therapeutic biomarkers for CP. The single-cell sequencing data were retrieved from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in idiopathic CP were identified, followed by function and pathway annotation, and PPI network established. DEGs of interest were verified in human tissue samples. The function of candidate biomarker was determined in the murine model with CP. A total of 208 genes were specially differentially expressed in idiopathic patients. Functional enrichment analysis showed DEGs were mainly enriched in glycogen catabolic process, RNA splicing, and glucagon signaling pathway. A PPI network centered on HDAC1 was constructed. HDAC1 was overexpressed in CP patients. The murine model with CP was induced by repetitive cerulein treatment. Silencing sh-HDAC1 treatment reversed cerulein-induced inflammatory cells accumulation, high expression of TGF-β1, and collagen 1 in pancreas in vivo. HDAC1 might be served as potential biomarker for CP. The present study provided insights into the molecular mechanism of CP that may be useful in further investigations.

The incidence of pancreatitis in children has increased over the past two decades. With advances in molecular biological techniques and clinical research, genetic variations have emerged as a pivotal etiological factor in pediatric pancreatitis. This review aims to summarize recent clinical research advancements in understanding pediatric pancreatitis caused by various gene mutations. As of the year 2020, researchers had identified 12 genes implicated in the pathogenesis of pancreatitis. These genes primarily contributed to the development of pancreatitis through three mechanisms. Pancreatitis resulting from these gene mutations exhibits several distinct characteristics, including early onset, a heightened risk of developing pancreatic duct stones, rapid disease progression, and a significantly increased risk of pancreatic endocrine and exocrine dysfunction, as well as pancreatic cancer in the future. Genetic sequencing is recommended for children with pancreatitis based on six indications. The sequencing not only assists in the clinical diagnosis but also enhances our understanding of the pathophysiology of pancreatitis.

Cystic fibrosis (CF) is the leading etiology for exocrine pancreatic insufficiency (EPI) in children, followed by chronic pancreatitis, Shwachman-Diamond syndrome, and other genetic disorders. Management of EPI in children poses several unique challenges such as difficulties in early recognition, lack of widespread availability of diagnostic tests and limited number of pediatric-specific pancreatic centers. Pancreatic enzyme replacement therapy is the cornerstone of EPI management and in young children difficulties in administering pancreatic enzymes are frequently encountered. Patients with EPI also should be screened for fat-soluble vitamin deficiencies and receive appropriate supplementation. Among disorders with EPI in children, CF is the relatively well-studied condition, and most management recommendations for EPI in children come from expert consensus and conventional practice guidelines. The impact of EPI can be greater in children given their high metabolic demands and rapid growth. Early diagnosis and aggressive management of EPI prevent consequences of complications such as malnutrition, fat-soluble vitamin deficiencies, and poor bone health and improve outcomes. Management by multi-disciplinary team is the key to success.

Asparaginase (ASP) is an important drug in combined chemotherapy regimens for pediatric acute lymphoblastic leukemia (ALL); ASP-associated pancreatitis (AAP) is the main adverse reaction of ASP. Recurrent pancreatitis is a complication of AAP, for which medication is ineffective.

To evaluate the efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) in treating recurrent pancreatitis due to AAP.

From May 2018 to August 2021, ten children (five males and five females; age range: 4-13 years) with AAP were treated using ERCP due to recurrent pancreatitis. Clinical data of the ten children were collected, including their sex, age, weight, ALL risk grading, clinical symptoms at the onset of pancreatitis, time from the first pancreatitis onset to ERCP, ERCP operation status, and postoperative complications. The symptomatic relief, weight change, and number of pancreatitis onsets before and after ERCP were compared.

The preoperative symptoms were abdominal pain, vomiting, inability to eat, weight loss of 2-7 kg, and 2-9 pancreatitis onsets. After the operation, nine of ten patients did not develop pancreatitis, had no abdominal pain, could eat normally; the remaining patient developed three pancreatitis onsets due to the continuous administration of ASP, but eating was not affected. The postoperative weight gain was 1.5-8 kg. There was one case of post ERCP pancreatitis and two cases of postoperative infections; all recovered after medication.

ERCP improved clinical symptoms and reduced the incidence of pancreatitis, and was shown to be a safe and effective method for improving the management of recurrent pancreatitis due to AAP.

Pediatric acute pancreatitis is an infrequent but potentially serious condition in children. Most have mild cases with spontaneous resolution, but up to one-third of patients can have moderate or severe disease or progress to recurrent or chronic pancreatitis.

Significant advances have been made in the field of pediatric pancreatology with a recognition that pediatric acute pancreatitis can vary significantly from adult disease with different risk factors and outcomes. There is better understanding of appropriate management for pediatric pancreatitis as well as growing literature in complications of pancreatitis.

The most common risk factors for pediatric acute pancreatitis include biliary disease, drug/toxin and idiopathic. Management involves adequate fluid resuscitation, early enteral nutrition and appropriate pain control. Systemic and local complications, including SIRS, necrosis and fluid collections, can occur in up to one-third of patients and care is largely supportive with a careful step-up approach to fluid collections and necrosis.

Drug-associated acute pancreatitis (DAP) studies typically focus on single acute pancreatitis (AP) cases. We aimed to analyze the (1) characteristics, (2) co-risk factors, and (3) reliability of the Naranjo scoring system for DAP using INSPPIRE-2 (the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2) cohort study of acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) in children.

Data were obtained from ARP group with ≥1 episode of DAP and CP group with medication exposure ± DAP. Physicians could report multiple risk factors. Pancreatitis associated with Medication (Med) (ARP+CP) was compared to Non-Medication cases, and ARP-Med vs CP-Med groups. Naranjo score was calculated for each DAP episode.

Of 726 children, 392 had ARP and 334 had CP; 51 children (39 ARP and 12 CP) had ≥1 AP associated with a medication; 61% had ≥1 AP without concurrent medication exposure. The Med group had other risk factors present (where tested): 10 of 35 (28.6%) genetic, 1 of 48 (2.1%) autoimmune pancreatitis, 13 of 51 (25.5%) immune-mediated conditions, 11 of 50 (22.0%) obstructive/anatomic, and 28 of 51 (54.9%) systemic risk factors. In Med group, 24 of 51 (47%) had involvement of >1 medication, simultaneously or over different AP episodes. There were 20 ARP and 4 CP cases in "probable" category and 19 ARP and 7 CP in "possible" category by Naranjo scores.

Medications were involved in 51 of 726 (7%) of ARP or CP patients in INSPPIRE-2 cohort; other pancreatitis risk factors were present in most, suggesting a potential additive role of different risks. The Naranjo scoring system failed to identify any cases as "definitive," raising questions about its reliability for DAP.

Patients with chronic pancreatitis (CP) often have a debilitating clinical course characterized by high disease burden, and poor quality of life and these factors adversely affect mental health. However, there is paucity of literature on the prevalence and impact of psychiatric disorders on hospitalized pediatric patients with CP.

ology: We analyzed the Kids Inpatient Database, and National Inpatient Sample, between 2003 and 2019 and included patients up to 21 years of age. Pediatric CP patients with psychiatric disorders were compared with patients without any of the psychiatric disorders using the ICD diagnostic codes. Various demographic and clinical factors were compared between the groups. Length of hospitalization and total hospital charges were used as surrogates to compare the hospital resource utilization between the groups.

We analyzed a total of 9,808 hospitalizations with CP and the overall prevalence rate of psychiatric disorders was 19.8%. The prevalence rate increased from 19.1% in 2003 to 23.4% in 2019, p = 0.006. The peak prevalence rate of 37.2% was noted at 20 years of age. Depression was noted at 7.6% of the total hospitalizations followed by substance abuse (6.5%), and anxiety (4.4%). Multivariate linear regression analysis showed that among CP patients, psychiatric disorders were independently associated with 1.3 additional days of stay and incurred $15,965 higher charges.

The prevalence of psychiatric disorders is increasing in pediatric CP. The concomitant presence of psychiatric disorders was found to be associated with prolonged hospital stay and incurred higher healthcare charges than those CP patients without psychiatric disorders.

Over the past decades, the incidence of acute pancreatitis is increasing, but the progression of acute recurrent pancreatitis and chronic pancreatitis is still not well documented in children. The aim of this multicenter study is to delineate the changes that occur in a certain time period in the course of childhood pancreatitis.

The data of consecutive patients hospitalized with acute pancreatitis between 2010 and 2017 in 4 different pediatric gastroenterology units were reviewed. The clini- cal characteristics of the disease were defined.

A total of 165 patients (55.2% female) were included. Over the years, the rate of acute pancreatitis admissions increased while the duration of hospitalization decreased (P < .05). Nearly two-thirds of the patients with acute pancreatitis resolved spontaneously, 30.9% and 4.3% of the cases developed acute recurrent pancreatitis and chronic pancreatitis, respectively. Furthermore, 27.4% patients with acute recurrent pancreatitis progressed to chronic pancre- atitis, and eventually, 12.7% of cases developed chronic pancreatitis within 3-4 years. Local complications developed in 13.3% of the patients with pancreatitis in this cohort.

The result of this study confirmed the increased incidence of acute pancreatitis in recent years. Conversely, the length of hospital stay decreased over the years. Patients with pancreaticobiliary abnormalities or genetic risk factors had a higher rate of progression to acute recurrent pancreatitis or chronic pancreatitis. Therefore, genetic testing and radiological imaging should be considered early in the follow-up of patients with acute pancreatitis having risk factors for progression to acute recurrent pancreatitis/chronic pancreatitis.

Acute pancreatitis (AP) is an inflammatory disease of the pancreas, which can progress to severe AP, with a high risk of death. It is one of the most complicated and clinically challenging of all disorders affecting the abdomen. The main causes of AP are gallstone migration and alcohol abuse. Other causes are uncommon, controversial and insufficiently explained. The disease is primarily characterized by inappropriate activation of trypsinogen, infiltration of inflammatory cells, and destruction of secretory cells. According to the revised Atlanta classification, severity of the disease is categorized into three levels: Mild, moderately severe and severe, depending upon organ failure and local as well as systemic complications. Various methods have been used for predicting the severity of AP and its outcome, such as clinical evaluation, imaging evaluation and testing of various biochemical markers. However, AP is a very complex disease and despite the fact that there are of several clinical, biochemical and imaging criteria for assessment of severity of AP, it is not an easy task to predict its subsequent course. Therefore, there are existing controversies regarding diagnostic and therapeutic modalities, their effectiveness and complications in the treatment of AP. The main reason being the fact, that the pathophysiologic mechanisms of AP have not been fully elucidated and need to be studied further. In this editorial article, we discuss the efficacy of the existing diagnostic and therapeutic modalities, complications and treatment failure in the management of AP.

Young adults who have experienced recurrent acute pancreatitis and chronic pancreatitis as children or adolescents are vulnerable to poor follow-up and disease management during the transfer from the pediatric to adult healthcare system. Although formalized transition programs for young adults have been developed and described for other disease conditions, no such program has been described for young adults with pancreatic disease. This document is the first expert opinion outlining the important aspects of a transitional care and transfer program tailored to youth with recurrent acute and chronic pancreatitis. We emphasize the unique needs of these patients as they transfer to adult health care and the need for further research. The goal of improved transitional care and transfer is to enhance the services provided to adolescents/young adults with pancreatic disease in both healthcare settings and improve continuity of follow-up care.

Introduction Anomalous pancreaticobiliary duct union (APBDU) is defined by the abnormal position of the junctional union of the common bile duct and the pancreatic duct, outside the duodenal wall above the influence of sphincter of Oddi, associated with choledochal cysts and biliary malignancies. APBDU may rarely present as recurrent acute pancreatitis (RAP) or chronic pancreatitis (CP). We aimed to study the prevalence of patients with APBDU presenting as RAP or CP and their response to endotherapy. Methods A retrospective audit of the prospectively maintained endoscopy database at our institute between January 2018 and November 2020 was conducted to identify cases of APBDU presenting as RAP or CP. Details of investigations, endoscopic retrograde cholangiopancreatography (ERCP) findings, and follow-up till six months were noted. Results We identified 26 cases of APBDU, of which five (19.2%) cases presented as RAP or CP. Of these five patients, two had RAP, while three presented with CP (median: 11 years; range: 4-25 years). Magnetic resonance cholangiopancreatography (MRCP) showed APBDU in three patients. One patient with RAP had a Komi type IIIB anomaly. Another patient with RAP had a rare anomaly with absent ventral PD, with the bile duct communicating and draining through the dorsal duct. Two patients with CP had a long common channel with Komi IIA anomaly. One patient with CP had IIIC2 anomaly. Pancreas divisum was noted in three patients, all of whom underwent minor-papilla sphincterotomy. Successful pancreatic stent placement was performed in all patients. Over one year of follow-up, patients with CP had a significant decrease in pain as measured by the visual analog scale. Those with RAP had no further episodes of pancreatitis. Conclusion APBDU is a rare cause of RAP and CP in young patients, occasionally missed on MRCP. RAP and CP caused by APBDU show good response to endotherapy.

This study aims to describe the prevalence of gastrointestinal (GI) symptoms following the first time occurrence of acute pancreatitis (AP) and to measure the impact of the episode on patient health-related quality of life (HRQOL) from the perspectives of patients and parents.

Questionnaires regarding GI symptoms 1 year following the initial occurrence of AP were obtained from 74 pediatric patients. Thirty of these patients completed both the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales and the PedsQL Gastrointestinal Symptoms and Worry Scales. These data were compared to legacy-matched healthy controls.

Children with a standalone occurrence of AP experienced a similar rate of GI symptoms compared to those who progressed to acute recurrent pancreatitis (ARP) within 1 year. PedsQL 4.0 Generic Core Scales scores were significantly lower for children self-report and parent proxy-report for patients that experienced AP compared to healthy controls. AP patients also demonstrated significantly more symptoms than healthy controls in the Gastrointestinal Symptoms and Worry Scales across multiple domains.

Gastrointestinal symptoms affect many children who experience a single AP event even without recurrent attacks. The burden of symptoms is not significantly different from those who develop ARP. This is a novel study that evaluates patient-reported outcomes in children following an AP attack and demonstrates there is a significant impact on HRQOL in children and family experiences post AP. More data are needed to study the progression of disease and the extended impact of AP following an initial AP attack in pediatric patients.

Increasing evidence implicates mutation-induced protein misfolding and endoplasm reticulum (ER) stress in the pathophysiology of chronic pancreatitis (CP). The paucity of animal models harbouring genetic risk variants has hampered our understanding of how misfolded proteins trigger CP. We previously showed that pancreatic triglyceride lipase (PNLIP) p.T221M, a variant associated with steatorrhoea and possibly CP in humans, misfolds and elicits ER stress in vitro suggesting proteotoxicity as a potential disease mechanism. Our objective was to create a mouse model to determine if PNLIP p.T221M causes CP and to define the mechanism.

We created a mouse model of Pnlip p.T221M and characterised the structural and biochemical changes in the pancreas aged 1-12 months. We used multiple methods including histochemistry, immunostaining, transmission electron microscopy, biochemical assays, immunoblotting and qPCR.

We demonstrated the hallmarks of human CP in Pnlip p.T221M homozygous mice including progressive pancreatic atrophy, acinar cell loss, fibrosis, fatty change, immune cell infiltration and reduced exocrine function. Heterozygotes also developed CP although at a slower rate. Immunoblot showed that pancreatic PNLIP T221M misfolded as insoluble aggregates. The level of aggregates in homozygotes declined with age and was much lower in heterozygotes at all ages. The Pnlip p.T221M pancreas had increased ER stress evidenced by dilated ER, increased Hspa5 (BiP) mRNA abundance and a maladaptive unfolded protein response leading to upregulation of Ddit3 (CHOP), nuclear factor-κB and cell death.

Expression of PNLIP p.T221M in a preclinical mouse model results in CP caused by ER stress and proteotoxicity of misfolded mutant PNLIP.

Human wellbeing has been linked with lifestyle factors such as physical activity, diet balance, sleep quality, depression, and anxiety. However, few studies illustrate the relationship between such lifestyle factors and HPV infection. In this study, we investigated the association between lifestyle factors, age, disease status and HPV infection.

Participants were recruited through a digital eHealth platform in Shenzhen, Mainland China. Both lifestyle factors and cervicovaginal mucus (CVM) samples to test for HPV outcomes were collected from each participant as a cross-sectional study. In addition, the eHealth platform recorded age and current or history diseases, which were adjusted to apply for both univariable and multivariable logistic regression. Furthermore, lifestyle factors were categorized as different levels to conduct stratification analysis.

We recruited 149 HPV positive and 346 HPV negative participants through HPV detection. Physical activity and diet balance were significantly associated with HPV infection in lifestyle factors (P values < 0.001) after adjusting for age and current or history diseases. However, stratified analysis showed three factors were insignificant for HPV infection - namely, sleep quality, depression, and anxiety. Most HPV infections involved a sole HPV serotype (83%), and diet balance was the most significant difference between sole and multiple HPV infections.

Among lifestyle factors, physical inactivity or diet imbalance can significantly increase HPV infection risk. In particular, diet balance might be related to the number of HPV serotypes. Our results suggest that exercising and regulating diet may reduce the risk of HPV infection.