|Year : 2020 | Volume
| Issue : 1 | Page : 22-27
Pediatric pancreatitis: Outcomes and current understanding
Department of Pediatric Surgery, Bangalore Medical College and Research Institute, Bengaluru, Karnataka, India
|Date of Submission||09-Nov-2018|
|Date of Decision||12-Jan-2019|
|Date of Acceptance||02-Feb-2019|
|Date of Web Publication||27-Nov-2019|
Dr. Deepti Vepakomma
Department of Pediatric Surgery, 3rd Floor, BMCRI Superspeciality Hospital (PMSSY), Victoria Hospital Campus, Bengaluru - 560 002, Karnataka
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Aim: The aim of this study was to analyze the clinical spectrum of pediatric pancreatitis and review current literature with regard to concepts of disease and management approaches.
Materials and Methods: This is a retrospective analysis of pancreatitis patients admitted to a tertiary referral pediatric surgical unit from March 2013 to September 2018.
Results: There were 106 patients from 1 year to 18 years with median age group between 11 and 15 years and equal gender distribution. Sixty-two children had acute pancreatitis (AP), with 13 of them having recurrent episodes. Forty-four patients had chronic pancreatitis (CP). Definite etiology was found in 11 AP patients. All patients had radiological changes. All AP patients were treated symptomatically except those with correctable underlying etiology. Sixteen with CP required intervention in the form of endoscopic retrograde cholangiopancreatography sphincterotomy/stenting or surgery. There were two mortalities. One with acute necrotizing pancreatitis and one CP girl due to the complication of diabetes mellitus, unrelated to episode of pancreatitis. All others are well at the last follow-up.
Conclusion: Pediatric pancreatitis is a disease with a wide spectrum, but management can be standardized. Newer studies reveal that certain genetic mutations make children more susceptible to pancreatitis. Increasing incidence must prompt us to evaluate further so as to better equip ourselves to managing this disease entity in all its forms and evolve preventive strategies.
Keywords: Amylase, endoscopic retrograde cholangiopancreatography, lipase, pancreaticojejunostomy, pancreatitis
|How to cite this article:|
Vepakomma D. Pediatric pancreatitis: Outcomes and current understanding. J Indian Assoc Pediatr Surg 2020;25:22-7
| Introduction|| |
Pancreatitis is seen with increasing frequency in the pediatric population and reaching adult incidence. Whether this is due to increased awareness, focused evaluation (greater frequency of doing serum lipase and amylase), increased referrals to tertiary hospitals, or true increase in disease prevalence is unclear and could be multifactorial. Unlike in adults, the etiology of pancreatitis in children is varied and so is the disease spectrum. This warrants a different approach to evaluation and treatment, but the data on management guidelines are limited.
This study aims to analyze the clinical spectrum of pediatric pancreatitis in a tertiary-level pediatric surgery unit and review literature on the current understanding of this entity with a focus on etiology, diagnosis, and treatment options.
| Materials and Methods|| |
This is a retrospective analysis of pancreatitis patients admitted to a tertiary referral pediatric surgical unit from March 2013 to September 2018. All patients who fulfilled the diagnostic criteria of pancreatitis were included in the study. Case records were used to collect data on demographics, investigations, and treatment details where possible patients were called back for an update on present health status if previous admission was over 2 years. Follow-up ranged from 2 months to 5 years.
| Results|| |
There were a total of 106 patients with 54 males and 52 females. Age ranged from 1 year to 18 years. The most affected age group was between 11 and 15 years (60 patients) [Table 1].
All children presented with acute-onset pain abdomen. Sixty-two percent had associated nausea and nonbilious vomiting. Only one patient had symptoms of steatorrhea, and one girl was diagnosed to have brittle diabetes and started on insulin.
All patients with acute pancreatitis (AP) (62) and 17/44 with chronic pancreatitis (CP) (which in records is referred to as acute on chronic) had significantly raised serum amylase and lipase enzymes at admission. All 106 had positive radiological findings on evaluation. No patient was evaluated for exocrine pancreatic insufficiency (EPI), but random blood sugar was checked in CP patients above 10 years.
Of the 62 cases of AP, 11 had predisposing factors. Four had pancreatitis following blunt trauma to the abdomen (three sustained handlebar injury after fall from bicycle and one was hit by two-wheeler). Six had abnormal pancreatobiliary junction and associated choledochal cysts, and one was drug induced (valproate). No specific etiology was noted in the remaining patients with AP and was considered idiopathic.
Seven other patients had necrotizing pancreatitis and stormy hospital course with SIRS. All except one of these seven recovered. One teenage girl progressed to multiorgan failure and irreversible shock and died.
Thirteen children were admitted with acute recurrent pancreatitis (ARP) with maximum of three episodes each in two children. In one of these, the three episodes occurred 1 month apart, and in another, 1 and 2 years later. In a majority, the duration of normalcy before a second attack varied from 1 to 3 months. However, two patients were well for 2½ years before they had another AP. Subsequently, all are symptom-free and none in this series progressed to CP. There was no difference in the patient profile between these children and those with AP. Neither history nor evaluation revealed any predisposing factor for multiple episodes.
Forty-four presented with acute-onset pain abdomen and at evaluation were found to have radiological changes suggestive of CP. Only 11 of these children gave a history of similar episodes of pain in the past and these were the patients who were evaluated at secondary centers and referred to us. Although there were significant changes on imaging, the rest did not have a past history of pain/admissions. None of these patients had nutritional sequelae as there was no history suggestive of malabsorption/steatorrhea and weight was above the 5th centile for age. No fecal elastase test or other tests of maldigestion was done in any patient.
Genetic markers to look for probable etiological factors and other biomarkers (besides serum amylase and lipase) for severity scoring were not done for any patient. Markers such as C-reactive protein, serum calcium, and other investigations nonspecific to pancreatitis but required for management and to assess severity and course were, however, done in those with necrotizing pancreatitis.
While all patients had an ultrasound abdomen, contrast-enhanced computed tomography (CT) was done in necrotizing pancreatitis, traumatic pancreatitis, and CP. All patients demonstrated some radiological changes suggestive of acute or CP. This varied from bulky pancreas with peripancreatic fat stranding/peripancreatic fluid collections/pancreatic necrosis/ascites in AP and calcifications (ductal/parenchymal) with or without atrophy of gland in all CP.
All children with AP were treated with initial bowel rest (varying from 24 to 48 h), analgesics, and supportive measures. In a majority, only intravenous (IV) paracetamol (15 mg/kg/dose 6th hourly) was given for pain relief. In children above 12 years who had intractable pain, tramadol (1 mg/kg/dose) was added but used in very few patients. If tramadol was given, ondansetron was also administered IV. All received proton pump inhibitor pantoprazole and IV fluids. No patient was given nasogastric (NG) or nasojejunal (NJ) feeds. Once oral feed commenced, it was supplemented with IV fluids till feeds were fully established, which took 2–3 days more.
Two patients needed parenteral nutrition support as they had severe pain, nausea, and vomiting persisting for >4 days. All seven with pancreatic necrosis on imaging were given bowel rest for longer period with the addition of antibiotics and total parenteral nutrition (TPN). In all, nine patients received TPN. None of these patients needed surgical intervention.
Patients with AP with predisposing etiological factors were treated accordingly. Those with choledochal cyst underwent excision and hepaticoenterostomy. One child with forme fruste choledochal cyst and pancreatic ductal calculus underwent endoscopic retrograde cholangiopancreatography (ERCP) as a diagnostic and also therapeutic measure to remove the calculus and subsequently a laparotomy and surgery for choledochal cyst. None had postoperative pancreatitis and are well.
Of the four with pancreatic injury following trauma, one child developed pancreatic ascites and needed drainage. A pigtail catheter was introduced under ultrasound guidance. The child then underwent an ERCP, but stent could not be placed. One child developed a localized peripancreatic collection that was drained by inserting pigtail catheter laparoscopically. The other two had AP with peripancreatic collections that settled with conservative management [Table 2].
One teenage girl with necrotizing pancreatitis progressed to multiorgan failure and irreversible shock and died.
All patients admitted with CP were started on graded pain management based on the severity of pain. Analgesics were started by parenteral route and subsequently converted to oral. A majority responded to only paracetamol, few needed narcotics (tramadol) in the initial period, including morphine in 2.
Sixteen of 44 CP required intervention due to intractable pain leading to repeated admissions. ERCP was selected as the procedure of choice in five patients, who were amenable to close follow-up. Three patients underwent ERCP, sphincterotomy, and stent placement. Two underwent ERCP and sphincterotomy alone. Ten patients with CP opted for upfront drainage surgery and a lateral pancreaticojejunostomy (Puestow procedure) was performed. One patient underwent distal pancreatectomy with splenectomy. This patient did not have a dilated duct but atrophic pancreas with numerous calculi in the body and tail. At follow-up, all operated patients were doing well. Two were readmitted twice for pain abdomen (not pancreatitis) and responded to analgesics. One girl with tropical pancreatitis and diabetes, from a remote village, had an uneventful hospital course when admitted for lateral pancreaticojejunostomy; but, 2 months later, she was brought to hospital emergency room unresponsive, following intractable seizures and could not be revived [Table 3].
One girl with CP with atrophic gland with calculi had intractable pain requiring a celiac plexus block. Her parents refused any surgical intervention.
The other children with CP have been recommended oral pancreatic enzyme supplements at 500–1000 IU/Kg of lipase with each meal and are on regular follow-up. However, compliance to medication has been poor. They are not on routine long-term analgesics except oral paracetamol in case of severe pain but advised to report to hospital if pain persists >2–3 days.
| Discussion|| |
Pancreatitis in children is a problem of increasing magnitude and a disease with a significant health-care burden. Data from this series show that about 15–20 new cases are diagnosed annually. Indian data are limited and one study quotes an incidence of 4–7 new cases annually detected in referral centers.
Pancreatitis is clinically classified into AP, ARP, or CP. AP is a reversible inflammation of pancreas. The diagnostic criteria for AP include any two of the triad of abdominal pain, imaging consistent with the disease, and serum amylase or lipase >3 times the normal. A patient is classified as having ARP if there are at least two discrete episodes of AP with intervening normal period. Like in AP and ARP, there are no irreversible structural changes to the pancreas though imaging may show changes during the course of the illness. CP, on the other hand, is a progressive inflammation of the pancreas characterized by fibrosis and irreversible acinar and ductal changes on imaging, resulting in endocrine, and/or exocrine insufficiency with/without rise in amylase or lipase enzymes.
What remains unclear is whether the natural history of pediatric pancreatitis involves a gradual progression from one to the other. As per Pant et al., forty-two percent index cases of AP experienced recurrence. Other studies estimate that 9%–35% of children with AP suffer from recurrent episodes. Twenty-one percent of children in this series had ARP.
Data from the INSPPIRE consortium state that 84% of CP patients had prior episodes of ARP. Median time for progression from ARP to CP was 1 year. However, this study found that only 11 of 44 CP had previous history of episodes of pain. It can only be assumed that the other patients ignored pain as nonspecific and were not evaluated in peripheral rural centers. However, neither did anyone demonstrate obvious malnutrition to suggest chronicity. Furthermore, none of those with ARP in this series progressed to CP. The longest follow-up of ARP patient is 5 years and those that had episodes of ARP this year are still on follow-up. Acharya et al. studied pancreatic histology from autopsy specimens of patients with AP, CP, and acute on CP. They evaluated the effects of fibrosis on acinar-adipocyte interactions and concluded that fibrosis reduces the severity of acute exacerbations of CP by reducing lipolytic flux between adipocytes and acinar cells. This also probably explains the fact that those with extensive fibrosis and contracted glands did not present to us with acute symptoms.
Major recognized etiologies for AP include biliary causes in 33%, medications in 26% (valproic acid, prednisolone, 6-mercaptopurine, L-asparaginase, and antiretrovirals), systemic in 10% (sepsis and systemic diseases), trauma in 9%, and others. Nearly 20% are idiopathic. There is evidence that pancreas divisum, particularly in combination with genetic factors, can predispose to pancreatitis. However, in this series, majority were considered idiopathic pancreatitis with very few having the above-listed etiologies. This highlights the great need for deeper evaluation of the role of dietary toxins, microbes, and other epigenetic factors in the causation of AP in children.
When it comes to ARP and CP recognizing the importance of genetic or environmental, predisposing etiological factors is essential. Cost constraints prevented us from evaluating for these at our institution. One of the initial triggering events in the cascading pathway to pancreatitis is premature intracellular activation of trypsinogen. About 20% of prematurely activated trypsin is inhibited by a protein coded by SPINK1 gene, and remaining trypsin is split by another protein coded by the PRSS1 gene. Poddar et al. studied mutations in PRSS1 gene, SPINK1 gene, and CFTR gene. Thirty-three percent children with AP, 45.4% with acute recurrent, and 54.4% with CP of unknown origin were genetically predisposed. SPINK1 was the predominant marker seen in 87% of cases with genetic mutations. They conclude that acute and ARP children with genetic mutations have significantly higher risk of developing CP on follow-up than those without any genetic mutations. In another study by Giefer et al., they conclude that early-onset pancreatitis (before age 6) is highly associated with PRSS1 or CTRC gene mutation or family history of pancreatitis.
Tropical pancreatitis was a term used to describe a nonalcoholic CP seen in Southern India, mainly Kerala, consisting of younger age-onset pain abdomen, large intraductal calculi, diabetes mellitus, and/or steatorrhea with high susceptibility to pancreatic cancer. Etiology of tropical pancreatitis is speculated to be a combination of malnutrition, dietary toxins, oxidative stress, trace element deficiency, and genetic factors. Although the patients in this series come from low socioeconomic strata, malnutrition was not observed in any (as seen by documented weight and dietary history). However, no specific evaluation for nutritional markers or EPI was done in this series of patients to confirm that biochemically due to cost constraints.
Steatorrhea or excess fat in stool secondary to fat malabsorption can manifest as diarrhea, bulky greasy stools, increased gas content, or stool floating on toilet water. Patients with fat malabsorption can have weight loss, failure to thrive, and nutritional deficiencies. Measuring the zymogen elastase-1 in stool is now the most widely used indirect pancreatic function test and can be done in a spot sample.
Nutritional markers associated with EPI include fat-soluble vitamins, apolipoproteins, total cholesterol, magnesium, calcium, and trace elements. Patients with EPI can also have abnormal levels of hemoglobin, albumin, prealbumin, and HbA1C and diminished bone density.
Only one teenage girl from Andhra Pradesh fulfilled the criteria of tropical pancreatitis. All others in this series were considered as idiopathic CP.
Apart from the usual biochemical parameters, radiology is essential in pancreatitis. The pediatric pancreas is relatively larger than the adult pancreas. The normal pancreatic duct in children is not necessarily visible on ultrasound. These may be potential pitfalls in inexperienced hands. On ultrasound, dilatation of the pancreatic duct is measured as follows: 1–6 years old >1.5 mm; 7–12 years old >1.9 mm; and 13–18 years >2.2 mm. CT scan is more sensitive. However, its use may be of more valuable later in the course of AP (if there is a lack of improvement clinically), in evaluating disease severity (when pancreatic necrosis is suspected), or if the diagnosis is uncertain (inadequately visualized glands on ultrasound). In children, CT severity index is a better predictor of acute severe pancreatitis than clinical scores. MRCP has a role when biliary pathology is suspected.
Heiko Witt et al. suggest that treatment of uncomplicated CP is usually conservative, with the major aim being to effectively alleviate pain, maldigestion, and diabetes, and consequently, to improve the patient's quality of life. They recommend surgical and endoscopic intervention only for complications such as pseudocysts or abscesses.
Nutrition has emerged as an important treatment modality in AP, and early feeding reduces complications of pancreatitis in addition to shortening hospital course. Enteral feeds may be oral, NG, or NJ. Tube feeding is recommended if adequate oral feeding is not tolerated or if it does not meet the energy requirements by 72 h of initiation. Eatock et al. state that NG feeding is simpler, easier, and a practical therapeutic approach to enteral nutrition in acute severe pancreatitis. They found no difference between NG and NJ feeding with regard to complications. A meta-analysis by Chang et al. also showed that safety and tolerance were not significantly different in NG and NJ feeding. Conventionally, it was thought that aspiration pneumonitis was more in NG tube feeding, but evidence disproved it. NJ feeding tubes are more expensive and require fluoroscopy, endoscopy, or medications (prokinetics) to position them. However, NJ feeds have shown better tolerance in few adults who have delayed gastric emptying and pain. However, there are no studies comparing these in children. None of the patients in this series, however, received tube feeding and those who had intolerance to orals were given parenteral nutritional support.
Párniczky et al. provide the latest evidence-based guidelines for the management of various forms of pancreatitis which are mentioned below.
Early aggressive dextrose-containing crystalloids at 1.5–2 times maintenance is recommended at least in the first 24 h of AP. Oral feeding can be started as soon as tolerated regardless of systemic inflammation. Parenteral nutrition is initiated if feeding is not established by 72 h.
Routine use of antibiotics is not recommended.
Asymptomatic pseudocysts complicating AP may be observed.
Acute on CP may be treated as in cases of AP.
ERCP can be safely performed in children. In the presence of obstruction with concomitant signs or the presence of stones in the pancreatic duct, therapeutic intervention (sphincterotomy, stent insertion, dilatation of duct strictures, or stone extraction) by ERCP can be chosen. Six patients in our series underwent ERCP. Enzyme replacement must be initiated for EPI in CP. Children <4 years of age should receive 1000 lipase units/kg per meal, 1000–2500 lipase units/kg per meal for those >4 years of age, and 40,000–50,000 units lipase/meal for children of adult size.
Pain in CP causes a drop in quality of life and loss of school days. Treatment ideally starts with conventional analgesics (acetaminophen) and nonsteroidal anti-inflammatory drugs. If pain is intractable, narcotics are prescribed. However, apart from potential addiction, opioids have side effects such as decreased gastrointestinal motility and central nervous system depression. In the INSPPIRE cohort of 72 children with CP, 36% were on narcotics for their pain. In an INSPPIRE questionnaire for pediatric gastroenterologists in North America, 75% provided narcotics for CP-associated pain, with or without centrally acting agents such as gabapentin. Sixty-nine percent of respondents “often” or “always” referred children with CP to a pain clinic or pain specialist.
Celiac plexus block, as tried in one patient in this series, provides pain relief but not permanent and there are no large studies comparing the efficacy of this with medications. When main pancreatic duct is obstructed and dilated, a drainage procedure either endoscopic or surgically is therapeutic and provides pain relief.
In adults, ERCP has been combined with ESWL to fragment ductal stones and aid their drainage poststenting. However, literature in the pediatric age group is limited.
Managed appropriately, children can have a good quality of life. In this series, there were two mortalities, one acute necrotizing pancreatitis and another CP patient probably due to hypoglycemic convulsions. Large series report overall current mortality for AP at 0.4%.
| Conclusion|| |
Pediatric pancreatitis is a disease with a wide spectrum; however, management follows a common pathway. When underlying etiology can be diagnosed, treatment involves correcting the primary cause. Newer studies reveal that certain genetic mutations make children more susceptible to pancreatitis. Increasing incidence must prompt us to evaluate further so as to better equip ourselves to managing this disease entity in all its forms and evolve preventive strategies.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]