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)
In this issue of Gastroenterology, Masamune et al report a landmark discovery, the genetic association of functionally defective TRPV6 channel variants and chronic pancreatitis. The authors investigated the TRPV6 gene in Japanese and European patients with nonalcoholic chronic pancreatitis using targeted sequencing followed by functional analysis of the identified variants. In the Japanese discovery cohort, they found functionally defective variants in 4.3% of the patients and in 0.1% of the controls (odds ratio 48). In the European replication cohort, 2% of the patients carried a defective variant and none was found in controls.
TRPV6 variants are globally associated with early-onset nonalcoholic CP. To our knowledge, TRPV6 is a novel pancreatitis-associated gene beyond the pancreatic digestive enzyme/enzyme inhibitor system, and it is the first gene that directly regulates Ca2+ homeostasis. Our findings open a completely new avenue by emphasizing the potential role of ductal cells and, especially, calcium channels in the pathophysiology of pancreatitis, which might lead to the development of personalized medicine targeting TRPV6 channel activity.
From editorial by Sahin-Toth
Visual abstract for research study by Masamne et al.
M Abu-El-Haija et al. JPGN 2018; 67: 131-43. This working group made ~27 recommendations (summarized in Table 1) and indicated the quality of evidence supporting the recommendation as well as the agreement among team members –virtually all received at least 12 of 13 votes.
Here are the ones that grabbed my attention:
For Acute Pancreatitis (AP):
1a & 1aa. Children with mild AP should be started on a regular diet –preferably via mouth as compared to nasogastric route
1b. Enteral nutrition (EN) should be attempted in children with severe AP within 72 hours from presentation, once deemed hemodynamically stable.
1.4 Even in severe AP, jejunal tube feeding should be reserved for those unable to tolerate oral or NG tube feeding
For Acute Recurrent Pancreatitis (ARP):
2.1a & 2.1b. Children should receive a regular-fat diet in between bouts of ARP and a regular-fat diet can safely be started within 1 week after the onset of a bout of AP (except in those with very elevated triglycerids (>1000 mg/dL)
2.2a & 2.3a. PERT is NOT recommended in children with ARP without eocrine pancreatic insufficiency (EPI). Antioxidants are NOT recommended (insufficient supporting evidence)
For Chronic Pancreatitis (CP):
3.1b & 3.12a. Recommends routine followup every 3-6 months and a regular diet
3.3a, 3.4a, & 3.5a Monitoring: recommends checking fat-soluble vitamin levels every 6 to 12 months, checking for EPI with elastase (or 72 hr fecal fat) every 6-12 months, and BMD (bone mineral density) if CP and malnutrition (especially if Vit D deficiency or hx/o fractures)
My take: This report provides a methodical approach for the care of children with these pancreatic disorders.
Another study (MJ Giefer et al. J Pediatr 2017; 186: 95-100) from the INSPPIRE group provides data on early-onset pancreatitis. Specifically, the group presents clinical information on 342 children with acute recurrent pancreatitis or chronic pancreatitis regarding disease burden and associations with genetic mutations.
Genetic disease is much more common in younger ages:
In subset younger than 6 years, 72 of 102 had genetic diseases identified: PRSS1 in 42, CFTR in 27, SPINK1 in 12, and CTRC in 8.
In subset 6-11 years of age, 52 of 90 had genetic diseases identified: PRSS1 in 20, CFTR in 23, SPINK1 in 22, and CTRC in 1.
In subset greater than 12 years of age, 39 of 72 had genetic diseases identified: PRSS1 in 13, CFTR in 24, SPINK1 in 6, and CTRC in 1.
Testing for newer susceptibility genes were not evaluated as they had not become commercially available: carboxypeptidase 1, claudin 2, carboxylesterlipase, and carboxyesterlipase-hybrid
SPINK1 is noted to be present in 1-3% of general population; CTRC mutation occur in 0.7% of healthy controls.
Obstructive causes were common. Pancreas divisum was identified in 38 patients but there was not a great deal of difference among the age groups; similarly, other obstructive causes were identified in about one-third of patients and included sphincter of Oddi dysfunction (n=9), gallstones (n=17), pancreaticobiliary malunion (n=12), biliary cyst (n=11), pancreatic stricture (n=2), annular pancreas (n=3), and duodenal diverticulum.
Exocrine insufficiency noted in 52 (no strong age predilection)
Diabetes in 18 (11 of the cases occurred in those >12 years)
Constant moderate pain noted in 82 (25 in group <6, 27 in 6-12 group, and 30 in group >12 years)
Constant severe pain noted in 18 (4 in group <6, 5 in 6-12 group, and 9 in group >12 years)
Average number of hospitalizations in past year was 1 in those ≤12 and 2 in those older than 12.
My take: PRSS1 and CTRC mutations are associated with early onset pancreatitis.
Our group received a very helpful update on pancreatitis from Maisam Abu-El-Haija (GI) and Jaime Nathan (surgery). My notes may include some errors in transcription and errors of omission. Some pictures of the slides are included below as well.
About 30% of acute pancreatitis patients have a 2nd bout of pancreatitis. Obesity is a risk factor for recurrence.
There has been a recent increase in incidence of acute pancreatitis.
Cincinnati has a gene panel to examine the four most common mutations which cause hereditary pancreatitis (PRSS1, SPINK1, CFTR, and CRTC) along with 6 other relevant genes. (28 day turnaround) In addition, there is a pancreatitis insufficiency panel.
Discussed screening for pancreatic insufficiency. Directly measuring pancreatic enzymes are more sensitive for early insufficiency, but may be unnecessary if good growth and normal stool elastase.
There are NO proven medical/dietary therapies to prevent recurrent or chronic pancreatitis and eliminate pain symptoms.
The INSPPIRE Group (CE Gariepy et al. JPGN 2017; 64: 95-103) has published consensus recommendations for acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP).
While the authors acknowledge the need for high-level evidence/further research, they provide a large number of consensus recommendations. These recommendations are succinctly summarized in Table 1 and Table 2. From a reader’s perspective, my preference would have been to separate the recommendations for ARP and CP rather than to intermix them (though many of the recommendations are the same for both conditions).
ARP specific recommendations:
“Initial evaluation should include AST,ALT, GGT, Total bilirubin (fractionate if elevated), fasting lipids, and total serum calcium.”
Evaluate for fat-soluble vitamin deficiency, and pancreatic exocrine insufficiency at least annually
ARP and CP recommendations:
Consider ammonia and urine organic acids if there is a concern for undiagnosed metabolic disease.
Check for celiac disease.
Check for O&P if immunosuppressed, travel to endemic areas of Ascaris, or if peripheral eosinophilia.
Evaluation of genetic causes: should include sweat chloride test and PRSS1 gene testing. Consider SPINK1, CFTR, and CTRC evaluation.
Evaluate with MRCP (not ultrasound) acutely if GGT >2 x ULN or if direct bilirubin is elevated.
Non-acutely, MRCP recommended to evaluate pancreatic ductal abnormalities. “When available, secretin-enhanced MRCP …should be obtained.” sMRCP can provide dynamic images of the pancreatic duct allowing differentiation of fixed from nonfixed lesions; this technique has not been widely adopted by pediatric radiologists compared with adult radiologists.
CP specific recommendations:
Evaluate for fat-soluble vitamin deficiency, pancreatic exocrine insufficiency, and pancreatic endocrine insufficiency at least annually
The authors did not recommend checking serum IgG4 in the absence of associated systemic disease or suggestive imaging for autoimmune pancreatitis.
Briefly noted: J-H Choi et al. Clin Gastroenterol Hepatol; 2017: 15: 86-92. This study indicated that vigorous hydration with lactated ringer’s (LR) reduces risk of pancreatitis after ERCP. A potential inference would be that LR would be an optimal fluid for pancreatitis more broadly. (Related: Why an ERCP Study Matters to Pediatric Care | gutsandgrowth)
A recent study (MD Bellin et al. Clin Gastroenterol Hepatol 2016; 14: 1317-23) describes the use of Total Pancreatectomy with Islet Autotransplantation (TPIAT) in 49 patients (mean age 32.8 years). This study included 6 children.
All of these patients met strict criteria for recurrent acute pancreatitis and lacked imaging or functional evidence for chronic pancreatitis. All 49 required narcotics for pain management prior to TPIAT.
The surgical technique for TPIAT is well-described in the report. Patients underwent total pancreatectomy, splenectomy, cholecystectomy and partial duodenectomy with continuity restored via doudenoduodenostomy or Roux-en-Y duodenojejunostomy. The islets were isolated and then infused intraportally.
At 1 year following TPIAT, 22 (46%) reported no use of narcotic pain medications.
Health-related quality of life scores improved (see Figure 3)
Diabetes is a common post-op concern. Approximately half were insulin-independent at 1 and 2 years out from surgery, with one-third remaining so at 5 years.
Histopathology was consistent with chronic pancreatitis in 37 (76%) indicating that current imaging/functional features do not reliably identify chronic pancreatitis with adequate sensitivity.
In the discussion, the authors note the selected patients, due to having normal caliber pancreatitis ducts, were not candidates for surgical drainage procedures like the Puestow procedure. They also note that the Puestow procedure can compromise later islet cell isolation.
My take: TPIAT is an important option in those with severe recurrent or persistent pancreatitis disease.