Hereditary pancreatitis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Iqra Qamar M.D.[2]

Overview

The goals of chronic pancreatitis management include pain control, management of pancreatic insufficiency by pancreatic enzyme replacement and management of complications. Pain is managed in a stepwise approach of general recommendations, pancreatic enzyme replacement, analgesics and invasive procedures. General recommendations usually include smoking cessation, cessation of alcohol intake, small meals and hydration. Medical therapy includes pancreatic enzyme supplementation, analgesics and antioxidants. Specialized approaches include celiac nerve block, endoscopic therapy, extracorporeal shock wave lithotripsy (ESWL), and radiation. Steatorrhea can be managed by dietary modification, lipase supplementation, vitamin supplementation, and medium chain triglycerides (MCTs). Diabetes is usually managed with a trial of oral hypoglycemic agents followed by insulin therapy.

Chronic pancreatitis management:

The goals of management are:

  • Pain control
  • Management of pancreatic insufficiency by pancreatic enzyme replacement
  • Management of complications[1]

Pain management:

Pain is managed in a stepwise approach of

  • General recommendations
  • Pancreatic enzyme replacement
  • Analgesics
  • Other invasive procedures

General recommendations:

Most of the patients usually improve following the general recommendations with only a few requiring analgesics.

(a) Smoking cessation:
  • Smoking cessation may
    • Delay the progression of chronic pancreatitis
    • Decrease the risk of pancreatic cancer[2]
(b) Cessation of alcohol intake:
  • Alcohol cessation may help in symptomatic improvement particularly in alcohol induced chronic pancreatitis.
  • Alcohol intake is associated with increased mortality in pateints with alcohol induced chronic pancreatitis.[3]
(c) Small meals:
  • Dietary preference in chronic pancreatitis should be small meals with low fat content
  • Medium chain triglyceride (MCTs) supplementation is particularly helpful because;
    • Its antioxidant effects
    •  Minimal increase in plasma CCK levels
    • It may prevent weight loss in patients
(d) Hydration:
  • Keeping the patients well hydrated may help in preventing the development of acute flares pf pancreatitis.

Medical Therapy:

1.Pancreatic Enzyme Supplementation:

  • Pancreatic enzyme supplementation is associated with pain alleviation and may be used when the general recommendations fail.
  • It decreases the release of CCK and thus reduces the stimulation-induced pancreatic pain but mixed results have been observed from various clinical trials.[4][5][6][7][8][9][10][11]
  • It is particularly beneficial in the management of patients with idiopathic chronic pancreatitis.[12][10]

2.Analgesics:

  • Analgesics are usually required when pancreatic enzyme replacement therapy fails to manage pain in chronic pancreatitis.
  • Pain cycle may be disrupted by:
    • Opiates coupled with amitriptyline and an NSAID.[13][14]
    • NPO and short-term hospitalization of the patient.
  • Long-acting agents, such as continuous morphine sulphate or fentanyl patch, are usually recommended for chronic pain management.
  • Adjuvat therapy with Pregabalin is also found to be effective in some clinical trials.[15][16]

3.Antioxidants:

  • Antioxidant therapy has no established effective role in the management of chronic pancreatitis as various studies have shown conflicting results.[17][18][19][20][21]

4.Specialized approaches:

4.1 Celiac nerve block
  • Celiac nerve block is not a proven therapy as [10][22][23][24]
    • It may cause serious complications
    • Recurrence may occur
    • It has limited success in chronic pancreatitis
  • It can be achieved by using alcohol or steroid via
    • Percutaneous approach or
    • Endoscopic approach
4.2 Endoscopic therapy
  • Pain releif can also be acheived by decompression of an obstructed duct via endoscopic approach.[25][26][27][28][29][30]
  • Surgery is more effective when compared to endoscopic therapy.[31]
4.3 Extracorporeal shock wave lithotripsy (ESWL) 
  • Pain can also be relieved by using ESWL.[32]
  • It causes millimetric fragmentation of pancreatic stones.
  • Its role in chronic pancreatitis management is still unclear due to the limited studies done in this area.
4.4 Radiation
  • Radiotherapy is also helpful in pain relief due to its anti-inflammatory properties.[33]

Management of Steatorrhea:

  • In chronic pancreatitis, pancreatic enzyme replacement is usually dependent upon
    • The size and nature of the meal 
    • The residual function of the pancreas
    • The goals of therapy (elimination of steatorrhea, reduction in the abdominal symptoms of maldigestion or acheivement of nutritional goals)
1. Dietary modification
  • The degree of fat intake restriction is usually dependent upon the severity of malabsorption.
  • Medical therapy is considered if steatorrhea persists after dietary restriction.
  • Fat intake of ≤ 20 grams per day is sufficient to prevent steatorrhea.
2. Lipase supplementation
  • The pancreas normally responds with between 700,000 and 1,000,000 lipase units (USP) per meal.[34]
  • 10% of normal pancreatic lipase replacement (70,000 to 100,000 USP) can manage the symptoms of steatorrhea even when all of the pancreatic function has been lost.
  • Usually 30,000 international units (IU) or 90,000 United States Pharmacopeia units (USP) of lipase per meal (5-10%) are sufficient to correct the malabsorption in chronic pancreatitis.
  • 90,000 USP of lipase per meal (5-10%) is sufficient to abolish steatorrhea in chronic pancreatitis.
  • Dosing is usually dependent upon:
    • The individual's weight
    • The degree of pancreatic insufficiency
    • The size and fat content of a meal
  • Creon-24,000 lipase, enteric coated formulations, one to two capsules with meals and one capsule with a snack
  • Viokace Lipase 20,880, non-enteric coated formthree tablets with meals and one to two tablets with a snack
NOTE:
  • Non-enteric supplements may require H2 antagonist or proton pump inhibitor.
  • Non-enteric supplements may be more useful in achlorhydric patients or those with dyssynchronous gastric emptying (eg, Billroth II anatomy).
3. Vitamin supplementation 
  • Patients with severe steatorrhea may require vitamin supplementation.
  • Calcifediol, a naturally occurring analogue of vitamin D (25-hydroxylated form) is more polar and potent than vitamin D2 or D3.
  • It is important to monitor serum cacium levels for the first few week of therapy due to increased risk of developing hypercalcemia.
4. Medium chain triglycerides (MCTs)
  • Medium chain triglycerides are preferred over long chain triglycerides as
    • MCTs do not need the presence of bile for their degradation
    • MCTs may be degraded easily by gastric and pancreatic lipase
    • MCTs can be absorbed directly from the intestinal mucosa
    • MCTs have a weak stimulatory affect on pancreatic secretions

Management of glucose intolerance:

  • Glucose intolerance usually develops in the early course of disease while overt diabetes may develop in the late course of disease.
  • Patients are usually managed with a trial of oral hypoglycemic agents followed by insulin therapy.

References

  1. ↑ Callery MP, Freedman SD (2008). "A 21-year-old man with chronic pancreatitis". JAMA. 299 (13): 1588–94. doi:10.1001/jama.299.9.jrr80001. PMID 18319401.
  2. ↑ Maisonneuve P, Lowenfels AB, Müllhaupt B, Cavallini G, Lankisch PG, Andersen JR, Dimagno EP, Andrén-Sandberg A, Domellöf L, Frulloni L, Ammann RW (2005). "Cigarette smoking accelerates progression of alcoholic chronic pancreatitis". Gut. 54 (4): 510–4. doi:10.1136/gut.2004.039263. PMC 1774435. PMID 15753536.
  3. ↑ Steer ML, Waxman I, Freedman S (1995). "Chronic pancreatitis". N. Engl. J. Med. 332 (22): 1482–90. doi:10.1056/NEJM199506013322206. PMID 7739686.
  4. ↑ Owyang C (1994). "Negative feedback control of exocrine pancreatic secretion: role of cholecystokinin and cholinergic pathway". J. Nutr. 124 (8 Suppl): 1321S–1326S. PMID 7914921.
  5. ↑ Singh VV, Toskes PP (2003). "Medical therapy for chronic pancreatitis pain". Curr Gastroenterol Rep. 5 (2): 110–6. PMID 12631450.
  6. ↑ Isaksson G, Ihse I (1983). "Pain reduction by an oral pancreatic enzyme preparation in chronic pancreatitis". Dig. Dis. Sci. 28 (2): 97–102. PMID 6825540.
  7. ↑ Halgreen H, Pedersen NT, Worning H (1986). "Symptomatic effect of pancreatic enzyme therapy in patients with chronic pancreatitis". Scand. J. Gastroenterol. 21 (1): 104–8. PMID 3633631.
  8. ↑ Mössner J, Secknus R, Meyer J, Niederau C, Adler G (1992). "Treatment of pain with pancreatic extracts in chronic pancreatitis: results of a prospective placebo-controlled multicenter trial". Digestion. 53 (1–2): 54–66. PMID 1289173.
  9. ↑ Brown A, Hughes M, Tenner S, Banks PA (1997). "Does pancreatic enzyme supplementation reduce pain in patients with chronic pancreatitis: a meta-analysis". Am. J. Gastroenterol. 92 (11): 2032–5. PMID 9362186.
  10. ↑ 10.0 10.1 10.2 Leung JW, Bowen-Wright M, Aveling W, Shorvon PJ, Cotton PB (1983). "Coeliac plexus block for pain in pancreatic cancer and chronic pancreatitis". Br J Surg. 70 (12): 730–2. PMID 6640255.
  11. ↑ Warshaw AL, Banks PA, Fernández-Del Castillo C (1998). "AGA technical review: treatment of pain in chronic pancreatitis". Gastroenterology. 115 (3): 765–76. PMID 9721175.
  12. ↑ Slaff J, Jacobson D, Tillman CR, Curington C, Toskes P (1984). "Protease-specific suppression of pancreatic exocrine secretion". Gastroenterology. 87 (1): 44–52. PMID 6202586.
  13. ↑ Gilron I, Bailey JM, Tu D, Holden RR, Jackson AC, Houlden RL (2009). "Nortriptyline and gabapentin, alone and in combination for neuropathic pain: a double-blind, randomised controlled crossover trial". Lancet. 374 (9697): 1252–61. doi:10.1016/S0140-6736(09)61081-3. PMID 19796802.
  14. ↑ Fioramonti J, Bueno L (2002). "Centrally acting agents and visceral sensitivity". Gut. 51 Suppl 1: i91–5. PMC 1867729. PMID 12077076.
  15. ↑ Olesen SS, Bouwense SA, Wilder-Smith OH, van Goor H, Drewes AM (2011). "Pregabalin reduces pain in patients with chronic pancreatitis in a randomized, controlled trial". Gastroenterology. 141 (2): 536–43. doi:10.1053/j.gastro.2011.04.003. PMID 21683078.
  16. ↑ Graversen C, Olesen SS, Olesen AE, Steimle K, Farina D, Wilder-Smith OH, Bouwense SA, van Goor H, Drewes AM (2012). "The analgesic effect of pregabalin in patients with chronic pain is reflected by changes in pharmaco-EEG spectral indices". Br J Clin Pharmacol. 73 (3): 363–72. doi:10.1111/j.1365-2125.2011.04104.x. PMC 3370341. PMID 21950372.
  17. ↑ Uden S, Bilton D, Nathan L, Hunt LP, Main C, Braganza JM (1990). "Antioxidant therapy for recurrent pancreatitis: placebo-controlled trial". Aliment. Pharmacol. Ther. 4 (4): 357–71. PMID 2103755.
  18. ↑ Banks PA, Hughes M, Ferrante M, Noordhoek EC, Ramagopal V, Slivka A (1997). "Does allopurinol reduce pain of chronic pancreatitis?". Int. J. Pancreatol. 22 (3): 171–6. doi:10.1007/BF02788381. PMID 9444547.
  19. ↑ Bhardwaj P, Garg PK, Maulik SK, Saraya A, Tandon RK, Acharya SK (2009). "A randomized controlled trial of antioxidant supplementation for pain relief in patients with chronic pancreatitis". Gastroenterology. 136 (1): 149–159.e2. doi:10.1053/j.gastro.2008.09.028. PMID 18952082.
  20. ↑ Burton F, Alkaade S, Collins D, Muddana V, Slivka A, Brand RE, Gelrud A, Banks PA, Sherman S, Anderson MA, Romagnuolo J, Lawrence C, Baillie J, Gardner TB, Lewis MD, Amann ST, Lieb JG, O'Connell M, Kennard ED, Yadav D, Whitcomb DC, Forsmark CE (2011). "Use and perceived effectiveness of non-analgesic medical therapies for chronic pancreatitis in the United States". Aliment. Pharmacol. Ther. 33 (1): 149–59. doi:10.1111/j.1365-2036.2010.04491.x. PMC 3142582. PMID 21083584.
  21. ↑ Siriwardena AK, Mason JM, Sheen AJ, Makin AJ, Shah NS (2012). "Antioxidant therapy does not reduce pain in patients with chronic pancreatitis: the ANTICIPATE study". Gastroenterology. 143 (3): 655–663.e1. doi:10.1053/j.gastro.2012.05.046. PMID 22683257.
  22. ↑ Busch EH, Atchison SR (1989). "Steroid celiac plexus block for chronic pancreatitis: results in 16 cases". J Clin Anesth. 1 (6): 431–3. PMID 2624751.
  23. ↑ Gress F, Schmitt C, Sherman S, Ikenberry S, Lehman G (1999). "A prospective randomized comparison of endoscopic ultrasound- and computed tomography-guided celiac plexus block for managing chronic pancreatitis pain". Am. J. Gastroenterol. 94 (4): 900–5. doi:10.1111/j.1572-0241.1999.01042.x. PMID 10201454.
  24. ↑ Gress F, Schmitt C, Sherman S, Ciaccia D, Ikenberry S, Lehman G (2001). "Endoscopic ultrasound-guided celiac plexus block for managing abdominal pain associated with chronic pancreatitis: a prospective single center experience". Am. J. Gastroenterol. 96 (2): 409–16. doi:10.1111/j.1572-0241.2001.03551.x. PMID 11232683.
  25. ↑ Okolo PI, Pasricha PJ, Kalloo AN (2000). "What are the long-term results of endoscopic pancreatic sphincterotomy?". Gastrointest. Endosc. 52 (1): 15–9. doi:10.1067/mge.2000.106669. PMID 10882956.
  26. ↑ Geenen JE, Rolny P (1991). "Endoscopic therapy of acute and chronic pancreatitis". Gastrointest. Endosc. 37 (3): 377–82. PMID 2070994.
  27. ↑ Choudari CP, Nickl NJ, Fogel E, Lehman GA, Sherman S (2002). "Hereditary pancreatitis: clinical presentation, ERCP findings, and outcome of endoscopic therapy". Gastrointest. Endosc. 56 (1): 66–71. PMID 12085037.
  28. ↑ Rösch T, Daniel S, Scholz M, Huibregtse K, Smits M, Schneider T, Ell C, Haber G, Riemann JF, Jakobs R, Hintze R, Adler A, Neuhaus H, Zavoral M, Zavada F, Schusdziarra V, Soehendra N (2002). "Endoscopic treatment of chronic pancreatitis: a multicenter study of 1000 patients with long-term follow-up". Endoscopy. 34 (10): 765–71. doi:10.1055/s-2002-34256. PMID 12244496.
  29. ↑ Gabbrielli A, Pandolfi M, Mutignani M, Spada C, Perri V, Petruzziello L, Costamagna G (2005). "Efficacy of main pancreatic-duct endoscopic drainage in patients with chronic pancreatitis, continuous pain, and dilated duct". Gastrointest. Endosc. 61 (4): 576–81. PMID 15812411.
  30. ↑ Adler DG, Lichtenstein D, Baron TH, Davila R, Egan JV, Gan SL, Qureshi WA, Rajan E, Shen B, Zuckerman MJ, Lee KK, VanGuilder T, Fanelli RD (2006). "The role of endoscopy in patients with chronic pancreatitis". Gastrointest. Endosc. 63 (7): 933–7. doi:10.1016/j.gie.2006.02.003. PMID 16733106.
  31. ↑ Cahen DL, Gouma DJ, Nio Y, Rauws EA, Boermeester MA, Busch OR, Stoker J, Laméris JS, Dijkgraaf MG, Huibregtse K, Bruno MJ (2007). "Endoscopic versus surgical drainage of the pancreatic duct in chronic pancreatitis". N. Engl. J. Med. 356 (7): 676–84. doi:10.1056/NEJMoa060610. PMID 17301298.
  32. ↑ Parsi MA, Stevens T, Lopez R, Vargo JJ (2010). "Extracorporeal shock wave lithotripsy for prevention of recurrent pancreatitis caused by obstructive pancreatic stones". Pancreas. 39 (2): 153–5. doi:10.1097/MPA.0b013e3181bb1733. PMID 19820418.
  33. ↑ Guarner L, Navalpotro B, Molero X, Giralt J, Malagelada JR (2009). "Management of painful chronic pancreatitis with single-dose radiotherapy". Am. J. Gastroenterol. 104 (2): 349–55. doi:10.1038/ajg.2008.128. PMID 19190609.
  34. ↑ Keller J, Layer P (2005). "Human pancreatic exocrine response to nutrients in health and disease". Gut. 54 Suppl 6: vi1–28. doi:10.1136/gut.2005.065946. PMC 1867805. PMID 15951527.


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