Tag Archives: pancreatitis

INSPPIRE for pancreatitis

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While anyone who follows this blog knows that I like acronyms, I must say that many investigators have taken lessons from Krispy Kreme on spelling.  INSPPIRE is named for the International Study Group of Pediatric Pancreatitis: In Search for a Cure.  A study from this group reports on definitions of pediatric pancreatitis & surveys current practice (JPGN 2012; 55: 261-65).

The literature regarding acute recurrent pancreatitis and chronic pancreatitis in children is limited.  This consortium hopes to change this.  As a start, the authors assigned subcommittees to establish definitions, reviewed the literature, and assessed current practice.

Definitions:

  • Acute pancreatitis (AP): requires at least 2 of 3 criteria:
  1. Abdominal pain consistent with AP
  2. Serum amylase and/or lipase activity at least 3 times ULN
  3. Imaging findings compatible with AP
  • Acute recurrent pancreatitis (ARP): requires at least two episodes of AP along with

Complete resolution of pain (≥ 1-month pain-free interval) OR complete normalization of pancreatic enzyme levels along with resolution of pain (can be shorter interval than 1 month)

  • Chronic pancreatitis (CP): requires one of the following:
  1. Abdominal pain and imaging suggestive of chronic pancreatic damage
  2. Exocrine pancreatic insufficiency and imaging suggestive of chronic pancreatic damage
  3. Endocrine  pancreatic insufficiency and imaging suggestive of chronic pancreatic damage
  4. Surgical/histologic specimen consistent with chronic pancreatitis

Managing pancreatitis:

Typical tests for these three conditions are shown in figure 2 and vary widely.  For AP, most respondents (63%) routinely checked liver enzymes, triglycerides, calcium and abdominal ultrasound.  For ARP and CP, most respondents (69%) obtained additional imaging modalities (eg. MRCP), genetic testing, and sweat chloride. If ERCP was needed, 88% of practices relied on adult gastroenterology colleagues.

Related blog posts:

Recurrent pancreatitis and genetic underpinnings | gutsandgrowth

Does pancreas divisum cause pancreatitis? | gutsandgrowth

How helpful are antioxidants for chronic pancreatitis pain …

Does pancreas divisum cause pancreatitis?

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The role of pancreas divisum (PD) as a cause of either acute recurrent or chronic pancreatitis (AR/CP) remains a matter of debate.  A recent study suggests that pancreas divisum serves as a cofactor but does not cause pancreatitis independently (Am J Gastroenterol 2012; 107: 311-17).

PD occurs due to failure of fusion of the dorsal and ventral pancreatic buds during gestation.  The frequency of PD has been estimated to be between 5-10% of the general population based on large post-mortem studies.  There is an increased frequency of PD in patients with idiopathic pancreatitis (12-26%).  The referenced study from France examined the frequency of genetic mutations vis-a-vis relationship with PD.  PD was determined using MRCP.

Findings–percentage with PD among subgroups:

  • 7% of subjects without pancreatic disease, n=45
  • 7% of alcohol-associated pancreatitis patients, n=29
  • 5% of idiopathic pancreatitis patients, n=40
  • 16% of patients with PRSS-1-associated pancreatitis, n=19
  • 16% of patients with SPINK-1-associated pancreatitis, n=25
  • 47% of patients with CFTR-associated pancreatitis, n=30

The study has several limitations.  Overall, the numbers of patients with pancreatitis are fairly low.  In addition, these genetic mutations are not typically examined in individuals without pancreatitis.  As such, the effect of these mutations with PD still is difficult to know in comparison to a larger population.

Additional references:

  • Recurrent pancreatitis and genetic underpinnings (previous blog post)
  • -Clin Gastro & Hep 2009; 7:141.  Review -case of recurrent pancreatitis -suggests checking ANA, Trig, IgG4 (also TTG)
  • – J Pediatr 2008; 152: 106.  Acute pancreatitis in young children; 109 cases.  systemic dz in 29, drugs in 7, gallstones in 3, annular pancreas in 1, trauma in 7, infections in 16, CF in 2, Idiopathic in 15.
  • -NEJM 2006; 354: 2142.  Review of acute pancreatitis mgt.
  • -Clin Gastro & Hep 2006; 4: 455.  Elevated pancreatic enzymes frequently identified in celiac disease.
  • -Clin Gastro & Hep 2007; 5: 1347. Celiac is a risk factor for acute & chronic pancreatitis. n=14,239 & 69,381 reference population (Sweden).
  • -Pediatrics 2005; 115: e463. CF & pancreatitis
  • -JPGN 2003; 37: 5591. Systemic dz 14%, Trauma 14%, drugs 12%, metabolic 6%, structural 5%, infectious 8%, ERCP 6%, Biliary 12%, Familial 3% (but accounted for 20% of episodes) Transplant 8%, idiopathic 8%
  • -Clin Perspectives in Gastro 2002; 5: 73. Pancreas divisum

Recurrent pancreatitis and genetic underpinnings

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While the absolute number of patients with genetic causes of pancreatitis is small, due to frequent hospitalizations, this remains a significant problem.  This month additional information on genetic predisposition for pancreatitis is available (JPGN 2012; 54: 645-50).

Sultan et al (Milwaukee, WI) reviewed the charts of children <18 years with recurrent acute pancreatitis (RAP) and patients with chronic pancreatitis (CP) from 2000-2009.   RAP was considered if patient had a minimum of two distinct episodes of acute pancreatitis.  Acute pancreatitis was considered the diagnosis if patient had typical symptoms associated with 3-fold elevation of amylase or lipase or imaging changes consistent with acute pancreatitis. CP was defined as a minimum of 2 episodes of acute pancreatitis associated with pancreatic duct abnormalities or pancreatic insufficiency.

Among this cohort of 29 children, 23 (79%) had mutations which have been associated with genetic pancreatitis (GP).  Family history was positive in only five patients.

  • CFTR mutation in 14 (48%): two had homozygous mutations, six heterozygous, and four had 5 T variants.  The importance of a single CFTR mutation in contributing towards pancreatitis is unclear.  However, the Wisconsin population has a carrier frequency of 1:32; the striking difference in frequency  indicates that even a single mutation may be important in the pathogenesis of RAP.
  • SPINK1 (serine protease inhibitor Kazal type 1) in 8 (27%).  SPINK1 mutations occur in 1-3% of the general population.  It is often a modifying factor rather than an isolated causal factor in the development of RAP.  Four of the patients with SPINK1 mutations also had a CFTR mutation.
  • PRSS1 (cationic trypsinogen gene) in 7 (24%).  Individuals with these mutations are considered to have hereditary pancreatitis, an autosomal disease with incomplete penetrance.
  • Only one patient was tested for chymotrypsin C gene (CTRC) –tested negative.

Seven patients with RAP did not undergo genetic testing & were excluded from the study.  These patients had other known causes of RAP: 3 had gallstones, 2 had pancreas divisum, 1 had a metabolic disorder, and 1 had a medication-induced pancreatitis.  The authors note, however, that patients with pancreas divisum have had genetic mutations identified in other studies.

Additional References:

  • www.uni-leipzig.de/pancreasmutation. This link will take you to the hereditary pancreatitis database where you can search for the specific mutation you identified and find articles dealing with a variety of aspects of that particular mutation.
  • 2011 Naspghan Postgraduate Course:
    Pancreatitis Workup
    -1st bout, check U/S, trig
    -if 2nd bout, suggested to check MRI, genetics (SPINK1, PRSS1, CFTR), sweat test, fecal elastase, possibly IgG4/ANA
  • OMIM#167800/276000
  • -Gastroenterology 2006; 131: 1844.  Mouse model w R122H Trypsiongen expression.
  • -Whitcomb DC. Gut 2004; 53: 1710-17. test for PRSS1 (cationic trypsinogen), SPINK1 (Serine protease inhibitor, Kazal Type 1), and CFTR gene.
  • -JPGN 2002; 34: 1A pg 444. n=108 with hereditary or idiopathic pancreatitis. (28% had + fhx)  12 c PRSS1 mutation, 24 c SPINK1 (21 s fhx); 22 had + CFTR mutation.
    -Pancreatology 2001; 1: 405-415.  Consensus guidelines for testing for H. Pancreatitis. PRSS1 gene -cationic trypsinogen
    http://www.pancreas.org/assets/pdfs/Pancreatology/HPgeneTestConsensus.pdf
  •  David Whitcomb’s laboratory at the University of Pittsburgh. The test is commercially available there. Their web site for the forms is:
    http://www.pitt.edu/~whitcomb/HPINFO/MolGenTest.html
  • -JPGN 2011; 52: 262. Review.
  • -J Pediatrics 2011; 158: 612.  Acute pancreatitis can result in diabetes.
  • -Clin Gastro & Hep 2010; 8: 410-416, 417. REVIEW of acute pancreatitis.  Rec NJ generally over TPN.
  • -Clin Gastro Hep 2010; 8: xxii.  Anomalous pancreatobiliary jxn as a cause.
  • -JPGN 2009; 49: 137.  Pancreatitis assoc w celiac
  • -Clin Gastro & Hep 2009; 7: 702.  Harmless Acute pancreatitis score.  Nonsevere when NL hgb, NL creatitine, and no rebound tenderness/guarding
  • -Alim Pharm Ther 2008; 28: 777-781.  Use of a low fat diet helped shorten hospital stay among adult pts with acute pancreatitis.
  • -Clin Gastro & Hep 2008; 6: 1070, 1077.   Fluids and imaging in acute pancreatitis.  With imaging, CT probably best.
  • – J Pediatrics 2008; 152: 106.  Acute pancreatitis in young children

Related blog entry:

Indomethacin to prevent post-ERCP pancreatitis

Indomethacin to prevent post-ERCP pancreatitis

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“Take two and call me in the morning” may now apply to the use of indomethacin in preventing post-ERCP pancreatitis.  A multicenter, randomized, placebo-controlled, double-blind clinical trial has shown that rectal indomethacin (two 50 mg suppositories) can reduce the rate of post-ERCP pancreatitis (NEJM 2012; 366: 1414-22).

A total of 602 adult patients were enrolled.  Patient selection favored those at increased risk for post-ERCP pancreatitis (eg. suspicion of sphincter of Oddi dysfunction) and excluded those at low risk for this complication (eg. routine biliary stent exchange, chronic calcific pancreatitis, or a pancreatic head mass).  Other exclusion criteria included active pancreatitis, elevated creatinine (>1.4 mg/dL), active peptic ulcer disease, and those already receiving a NSAID.

The suppositories (or placebo) were administered immediately after ERCP while the patient remained in the procedure room.

Post-ERCP pancreatitis developed in 27 of 295 patients (9.2%) in indomethacin group and in 52 of 307 patients (16.9%) in placebo group.  In addition, moderate-to-severe pancreatitis was reduced as well 4.4% compared with 8.8% respectively.  In addition, there were no increased adverse events in the treatment arm; there was no increased risk of bleeding in particular.

While the mechanism of improvement is unclear, NSAIDs are potent inhibitors of phospholipase A2, cyclooxygenase, and neutrophil-endothelial interactions, all of which are known to play a role in the pathogenesis of acute pancreatitis.

Additional references:

  • -Am J Gastroenterol 2007; 102: 978-83.  Use of indomethacin to reduce pancreatitis after ERCP
  • -Gut 2008; 57: 1262-7.  Meta-analysis of rectal NSAIDs to prevent post-ERCP pancreatitis