Category Archives: Pancreatology

NSAIDs for Severe Acute Pancreatitis

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L Huang, et al. Gut 2025;74:1467–1475. doi:10.1136/gutjnl-2024-334038. Open Access! Parecoxib sequential with imrecoxib for occurrence and remission of severe acute pancreatitis: a multicentre, double-blind, randomised, placebo-controlled trial

Background: “COX-2 inhibitors (COX-2-Is) have shown potential in reducing pancreatitis severity and improving renal and respiratory function in animal models.” However, at this time, “there is no effective drug treatment for organ failure (OF) caused by severe acute pancreatitis (SAP)” in humans.

Methods: “In this multicentre, double-blind, randomised, placebo-controlled, investigator-initiated trial, 348 patients with acute pancreatitis aged 18–75 years, <1 week from onset of illness to admission, and Acute Physiology and Chronic Health Evaluation II Score ≥7 or modified Marshall Score ≥2, were randomly assigned (1:1) to the COX-2-Is group (parecoxib sequential with imrecoxib) or the placebo group.”

The authors chose to adopt a sequential regimen of intravenous (3 days) to oral COX-2-Is. “Parecoxib labelling recommends intravenous administration for no more than 3 days due to limited clinical experience beyond this period.”

Key findings:

  • “Compared with the placebo group, SAP occurrence was reduced by 20.7% (77.6% vs 61.5%, p=0.001) and the persistent OF duration in SAP was shortened by 2 days (p<0.001) after COX-2-Is treatment.” 
  • “For patients enrolled within or after 48 hours from symptom onset, SAP occurrence was reduced by 23.8% (p=0.001) and 8.5% (p=0.202), and the persistent OF [organ failure] duration in SAP was shortened by 3 days (p=0.001) and 2 days (p=0.010) after COX-2-Is treatment, respectively.” 
  • “The serum levels of inflammatory mediators and 30-day mortality (from 8.6% to 3.4%) were significantly reduced after COX-2-Is treatment, p<0.05.”
  • “The incidence of adverse events was similar between the two treatment groups.”

My take: This study showed that NSAIDs (starting with IV x 3 days) improved outcomes with severe acute pancreatitis (in adults). Prior studies have also showed reduced pancreatitis with NSAIDs following ERCP.

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How Triglycerides Affect Outcomes in Pediatric Pancreatitis

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ZM Sellers et al. J Pediatr 2025; 276: 114298. Impact of Elevated Serum Triglycerides on Children with Acute Recurrent or Chronic Pancreatitis from INSPPIRE-2

Using the INSPPIRE-2 cohort of children with acute recurrent or chronic pancreatitis (CP) (n = 559), the authors compared the outcomes for children based on their triglyceride levels. Definitions: normal triglycerides (<150 mg/dL), any high triglycerides (HTG) (≥150 mg/dL, mild-moderate HTG (150-499 mg/dL), moderate HTG (500-999 mg/dL), and severe HTG groups (≥1000 mg/dL).

  • Key findings:
    HTG was not associated with an increase in the number of pancreatitis attacks per person-years
  • HTG was not associated with an increase in CP prevalence
  • HTG severity was associated with increased pancreatic inflammation, pancreatic cysts, pain, hospital days, number of hospitalizations, intensive care, and missed school days
  • Interestingly, there were less pancreas gene variants in the severe HTG group which supports the notion that HTG can be a driver of pancreatitis disease

Discussion:

  • “It is well-established that severe HTG levels increase pancreatitis risk by increasing serum chylomicrons and free fatty acids, causing pancreatic ischemia, acidosis and vascular injury…In adults, TG levels >/= 200 mg/dL are independently associated with pancreatic necrosis.”

My take: Checking triglyceride levels, which is in accordance with NASPGHAN recommendations, is a good idea. HTG is a potentially-modifiable risk factor for more severe disease. Levels that substantially increase the pancreatitis severity (500 or higher) merit treatment even in the absence of pancreatitis

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NASPGAN Paper: Surgery for Chronic Pancreatitis: Choose Your Operation and Surgeon Carefully

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JD Nathan et al. JPGN 2022; 74: 706-719. Open Access: The Role of Surgical Management in Chronic Pancreatitis in Children: A Position Paper From the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Pancreas Committee

This society paper provides a terrific review of potential operations and rationale in children with chronic pancreatitis. Some of the highlights from this open access article include figures detailing the anatomical considerations of the operations (eg. Frey, Modified Puestow, TPIAT, Berger, Whipple, and Berne) and an algorithm in choosing which procedure should be considered.

Key points:

  • Surgery is indicated for children with debilitating CP who have failed maximal medical and endoscopic interventions.
  • A conventional surgical approach (eg, drainage operation, partial resection, combination drainage-resection) may be considered in the presence of significant and uniform pancreatic duct dilation or an inflammatory head mass.
  • Total pancreatectomy with islet autotransplantation is the best surgical option in patients with small duct disease.
  • The presence of genetic risk factors often portends a suboptimal outcome following a conventional operation.

My take: Fortunately, very few children need operations for chronic pancreatitis. As such, surgical expertise/judgement is particularly important.

Figure 1

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition

Why I Care About Another Biomarker for Pancreatitis Severity

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PR Farrell et al. J Pediatr 2021; 238: 33-41. Open Access: Cytokine Profile Elevations on Admission Can Determine Risks of Severe Acute Pancreatitis in Children

Methods: In this single center pediatric study, interleukin 6 (IL -6), monocyte chemotactic protein-1 (MCP-1) and CRP were obtained within 48 hours of admission in 66 subjects (20 controls, 36 with mild acute pancreatitis (AP), and 10 with severe AP) in a derivation cohort. and then in a validation cohort with 35 subjects (10 controls, 19 mild AP and 6 severe AP)

Key findings:

  • In both the derivation and vaildation cohorts, IL-6 (P = 0.02, P= 0.02 respectively) and MCP-1 (P= 0.02, P = .007) were found to differentiate mild acute pancreatitis from severe acute pancreatitis.
  • CRP values were obtained from 53 of the subjects, revealing a strong association between elevated CRP values and progression to severe disease (P < .0001). CRP were stratifed into 3 distinct groups, <0.4 mg/dL, 0.4-2.5 mg/dL, and >2.5 mg/dL

The discussion notes a few points:

  1. “BUN as part of a standard initial clinical biochemical evaluation on admission, as well as the response of the patient’s BUN to fluid resuscitation can help predict disease severity with high specificity and a high negative predictive value which can help to determine those patients least likely to progress to severe disease”
  2. “There is adult literature showing the benefit of placing patients at highest risk of progression to severe disease on Cox-2 inhibitors and monitoring, among other measures, the response of IL-6. Patients who received the investigational drug had significantly lower levels of IL-6, and the therapy was associated with an almost 50% reduction in the progression of patients to severe disease.”

My take: In clinical practice, both elevated CRP and BUN are associated with a higher risk of progression to severe pancreatitis. The reason why I was interested in this study was the potential for targeting IL-6 to improve outcomes.

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Siesta Key, FL

Ketorolac After ERCP -Pediatric Study

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JA Mark, RE Kramer. JPGN 2021; 73: 542-547. Ketorolac Is Safe and Associated With Lower Rate of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis in Children With Pancreatic Duct Manipulation

Methods: This retrospective chart review (n=298) examined the outcomes of pediatric patients who receivied ketorolac during ERCP compared to those who did not; ketorolac, was dosed using weight-based dosing (0.5 mg/kg/dose max 30 mg).

Key findings:

  • Most common indications for ERCP were choledocholithiasis, biliary stricture, and chronic/recurrent pancreatitis
  • Therapeutic ERCP: 91% of ketorolac group and 89% of non-ketorolac group; sphincterotomy was performed in 55% of both groups
  • Post-ERCP bleeding rates were not significantly different between ketorolac and non-ketorolac groups (0.6% vs 0%, P = 1)
  • PEP (post-ERCP pancreatitis) rates were not significantly different between the ketorolac and no ketorolac group 15/166 vs 17/132 (9% vs 13%, P = 0.29)
  • Patients who had cannulation and/or injection of the PD had significantly higher rates of PEP (23/140 (16%) vs 9/158 (6%), P < 0.003)
  • For high-risk pediatric patients with injection of contrast into and/or cannulation of the pancreatic duct, the rates of PEP were significantly lower for patients who received ketorolac (11% vs 25%, P = 0.035). In Table 2, the authors indicate that PEP in this high risk group occurred in 11/88 (12.5%) [mild discrepancy from abstract of 11%] of ketorolac group and 13/52 (25%)

It is possible that ketorolac (or other NSAIDs) in all patients may be beneficial but difficult to demonstrate without a larger cohort. In adults, “indomethacin reduces risk and severity of PEP in both high and average risk adults…and there is some evidence that NSAIDS given before ERCP may be more effective than those given later.” Thus, the authors state that use of ketorolac could be administered to all ERCP patients beforehand (w/o contraindication) or limited to the higher risk patients.

My take: In pediatric patients needing an ERCP, those with high-risk features (eg. injection of contrast into and/or cannulation of the pancreatic duct), use of ketorolac is likely to reduce the frequency of post-ERCP pancreatitis.

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Is A Sphincterotomy a Good Idea for Pediatric Pancreas Divisum?

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A recent retrospective single-center study (TK Lin et al. JPGN 2021; 72: 300-305. Clinical Outcomes Following Therapeutic Endoscopic Retrograde Cholangiopancreatography in Children With Pancreas Divisum) indicated that a minor papilla endoscopic sphicterotomy (mPES) may be beneficial for children with pancreas divisum and pancreatitis. The study included 27 children who had a total of 58 ERCPs.

Key findings:

  • After a median follow-up of ~32 months, 13 of 20 responders (65%) reported clinical improvement from endotherapy/mPES.
  • A genetic variant was identified in 19/26 (73%) tested patients
  • Post-ERCP pancreatitis (PEP) was the only observed adverse event; 21% (12/58)

Discussion:

The authors note that the beneficial finding of improvement after mPES in children is contrary to findings in adults. In addition, there is an active sham-controlled randomized clinical trial ongoing in adults (NCT03609944). They speculate that this could be related to longer disease burden in adults. In addition, they note that their findings had limitations:

  • this was a retrospective study with a small sample size
  • the results were based on a subjective non-validated questionnaire with concerns for recall bias

My take: I am not convinced that sphincterotomy is beneficial in most children with pancreatitis and pancreas divisum –the majority of whom have an underlying genetic variant which likely triggers pancreatitis. The only way to answer this question definitely is to perform a randomized clinical trial similar to the sham-controlled study in adults.

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Sunrise in Sandy Springs (no filter)

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Medical Management of Chronic Pancreatitis in Children

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AJ Freeman et al. JPGN 2021; 72: 324-340. Full text: Medical Management of Chronic Pancreatitis in Children: A Position Paper by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Pancreas Committee

Some of the recommendations:

  • Patients with CP are at risk for macro- and micronutrient deficiencies. Patients should be monitored for growth and pubertal devolvement, dietary intake, and fat-soluble vitamin deficiencies. Growth and dietary intake should be reviewed at every clinic visit, a minimum of every 6 to 12 months. Fat-soluble vitamin laboratory analysis should occur every 12 to 18 months or as clinically indicated. (Grade 1B)
  • There is a clear role for PERT in children with CP who have EPI with steatorrhea, poor growth and/or nutritional deficiencies. PERT dosing for CP associated EPI (see Table 1) is similar to that used in patients with CF. (Grade 1B). EPI screening can be done with stool elastase (Figure 1).
  • Screen yearly with HbA1c level (GRADE 1C). OGTT should be performed annually once a patient is considered to have pre-diabetes. (GRADE 1C)
  • Insufficient data exists to recommend the use of antioxidants as a treatment to prevent EPI or other disease progression in children with CP. (GRADE 2C)
  • There is insufficient data to recommend PERT as therapy for pain in children without EPI. (GRADE 1B); there is insufficient data to recommend antioxidants, steroids, leukotriene antagonists, or somatostatins in the management of pain for children with CP. (GRADE 2C)
  • Recommends advising patients to avoid alcohol abuse and smoking
  • The majority of pancreatic fluid collections will resolve spontaneously with supportive care. Intervention is reserved for complications from mass-effect, infection/necrosis or if spontaneous regression of the collection is thought to be unlikely. (GRADE 1B)

Related blog post: Pediatric Pancreatitis -Working Group Nutritional Recommendations

 An “analgesic ladder” that incorporates the layering of nonopioid and opioid medications –ideally this should be directed by a pain specialist

Endoscopic Pancreatic Function Testing -NASPGHAN Position Paper

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N Patel et al. JPGN 2021; 72: 144-150. full text Endoscopic Pancreatic Function Testing (ePFT) in Children: A Position Paper From the NASPGHAN Pancreas Committee

This articles serves as a good review of exocrine pancreatic insufficiency (EPI).

Etiologies:

  • “Cystic fibrosis is the most common cause of EPI in children .” Other congenital causes include  aberrant embryonic development of the pancreas, “Shwachman-Diamond syndrome, Johanson-Blizzard syndrome, Pearson marrow pancreas syndrome, and Jeune syndrome”
  • “Acquired causes of EPI can be transient, such as in the aftermath of acute pancreatitis (which can persist weeks to months)”
  • Also, infants, compared to adults, have “physiological” EPI. Lipase output is 5–10% of adult values during the 1st 6 months of life.

Advantages/Disadvantages of Endoscopic Testing for EPI:

  • Advantages:
    • • Safe, technically easy, and quick procedure to perform in conjunction to routine investigative EGD
    • • Allows assessment of acinar and ductal function
    • • High sensitivity and specificity in detection of isolated and generalized enzyme deficiencies
    • • Can diagnose minor and more severe degrees of EPI and aid in early diagnosis of CP in patients with unremarkable radiological changes
  • Disadvantages:
    • • Can be done only in conjunction with EGD and the patient will likely require sedation• Prolongs routine EGD
    • • Assesses peak enzyme activity and bicarbonate concentrations rather than total secretory capacity
    • • No standardized pancreatic fluid collection frequency or duration in pediatrics
    • • Lack of age-specific standardized reference ranges in pediatrics

Endoscopic Testing Caveats:

  • Any sample with a pH less than 7 may be unreliable as it is below the pH optimum of the enzymes and may reflect contamination with gastric fluid; however, ” the inability to increase pH, or bicarbonate, upon secretin stimulation may be reflective of loss of cystic fibrosis transmembrane conductance regulator (CFTR) function”
  • Samples need to be frozen or placed on dry ice
  • “Commonly used laboratory (Kaleida Health Children’s Hospital Laboratory, Buffalo, NY) are: trypsin >55.4 nmol · mL−1 · minute−1, amylase >32 μmol · mL−1 · minute−1, lipase >146 μmol · mL−1 · minute−1, and chymotrypsin >2.5 μmol · mL−1 · minute−1“

My take: With careful clinical judgement, endoscopic EPI testing is rarely needed. First of all, fecal elastase measurements can detect most patients with EPI. In addition, a lot of patients with poor growth and suspected malabsorption are too young for reliable endoscopic EPI testing.

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Imaging Recommendations for Pediatric Pancreatitis

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AT Trout et al. JPGN 2021; 72: doi: 10.1097/MPG.0000000000002964 Free full text: North American Society for Pediatric Gastroenterology, Hepatology and Nutrition and the Society for Pediatric Radiology Joint Position Paper on Noninvasive Imaging of Pediatric Pancreatitis: Literature Summary and Recommendations. Also, I want to give a shout out to Jay Freeman who is one of the authors and a very appreciated colleague.

Some of the recommendations:

  • Acute Pancreatitis:
    • Transabdominal ultrasound is recommended as a first-line noninvasive imaging modality for suspected AP
    • If ultrasound is negative for AP and an imaging diagnosis of AP is needed, either CT or MRI is recommended
      • “MRI, particularly MRCP, has also been shown to be more sensitive than CT for biliary etiologies of pancreatitis”
      • “In clinical practice, MRI is often used for assessment and monitoring of late complications of AP, such as fluid collections, to time and guide therapeutic interventions.”
  • Acute Recurrent Pancreatitis:
    • MRI is recommended to identify structural or obstructive causes for ARP
  • Chronic Pancreatitis:
    • MRI is the recommended modality for imaging of suspected CP
    • When imaging is needed to assess a suspected or known episode of AP in a child with CP, transabdominal ultrasound is the preferred first-line imaging modality

My take: This report provides a great deal of detail regarding the imaging modalities, terminology and diagnostic considerations for pediatric pancreatitis.

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