BILIARY DYSFUNCTION
Prof. J. Reichen

Gallbladder dysfunction

 

Episodes of severe steady pain located in the epigastrium and right upper quadrant and all of the following: Episodes lasting 30 minutes or more Symptoms once or more in the past 12 months The pain is steady, interrups daily activity and/or leads to consultation No evidence of structural abbnormalities Abnormal gallbladder emptying

Treatment options include cholecystectomy which will reveal pathological gallbladders in 45 - 70 % and relief of symptoms in 80 - 90 % (3-5); in similar patients not undergoing cholecystectomy improvement of symptoms usually does not occur (5). Nowadays, laparoscopic cholecystectomy is the treatment of choice; 94 % had relief of symptoms (6). Medical therapy including motility agents, ursodeoxycholate or nonsteroidal antiinflammatory agents have not been subjected to rigorous trials in this setting. Gallbladder contraction in response to CCK is pathological; in contrast to cholesterol gallstone disease this is due to a defect in the contractile apparatus (7).
 
 

Based on the Rome II criteria (1) all of the following criteria must be met:
 

In addition the pain may be associated with one or more of the following:

• Elevated liver and/or pancreatic enzymes and/or conjugated bilirubin (4)
• Acute recurrent pancreatitis (8). This is particularly germane in patients with MDR deficiciencies who present with recurrent biliary colic and/or pancreatitis (9,10).
  

The criteria used were the following:
1. ALT and alkaline phosphatase over twice upper limit of normal
2. Dilated bile duct on sonography
3. Delayed drainage of contrast material at ERCP

Recently, a randomized controlled trial demonstrated, that only patients with the manometric presentation of stenosis benefitted from sphincterotomy (11):

Recommended work-up (1) includes

Treatment options include the following:

• Spasmolytic agents in particular nitrates and dipyrone may be useful; no randomized trials exist. Nonsteroidal antiinflammatory drugs are superior to spasmolytics (13) and equal to meperidine in controlled trials (14).
  
• Calcium antagonists - actually nifedipine - have been shown to reduce episodes of pain in randomized trials (15).
  
• Recently, injection of botulinus toxin has been described with good results (16).
• Sphincterotomy provides good relief in selected patients (1, 2). A recent review concluded that this decision is based best on manometry (17).
  
• Ursodeoxycholate in patients with MDR3 deficiences and the like (9, 10).
  

References
1. Corazziari E, Shaffer EA, Hogan WJ, Sherman S, Toouli J. Functional disorders of the biliary tract and pancreas. Gut 1999; 45:48-54.
2. Behar J, Corazziari E, Guelrued M et al. Functional gallbladder and sphincter of Oddi disorders. Gastroenterology 130: 1498-1509.
3. Misra DC, Blossom GB, Fink Bennett D, Glover JL. Results of surgical therapy for biliary dyskinesia. Arch Surg 1991; 126:957-960.
4. Yap L, Wycherley AG, Morphett AD, Toouli J. Acalculous biliary pain: cholecystectomy alleviates symptoms in patients with abnormal cholescintigraphy. Gastroenterology 1991; 101:786-793.
5. Yost F, Margenthaler J, Presti M et al. Cholecystectomy is an effective treatment for biliary dyskinesia. Am J Surg 1999; 178: 462-465.
6. Patel NA et al. Therapeutic efficacy of laparoscopic cholecystectomy in the treatment of biliary dyskinesia. Am J Gastroenterol 2004; 187: 209-212
7. Amaral J, Xiao ZL, Chen Q et al. Gallbladder muscle dysfunction in patients with chronic acalculous disease. Gastroenterology 2001; 120: 506-511.
8. Lin OS, Soetikno RM, Young HS. The utility of liver function test abnormalities concomitant with biliary symptoms in predicting a favorable response to endoscopic sphincterotomy in patients with presumed sphincter of Oddi dysfunction. American Journal of Gastroenterology 93, 1833-1836. 1998.
9. Rosmorduc O, Hermelin B, Poupon R. MDR3 gene defect in adults with symptomatic intrahepatic and gallbladder cholesterol cholelithiasis. Gastroenterology 2001; 120:1459-1471.
10. Rosmorduc O, Hermelin B, Boelle PY et al. ABCB4 gene mutation-associated cholelithiasis in adults. Gastroenterology 2003; 125: 452-459.
11. Allescher HD. Clinical impact of sphincter of Oddi dyskinesia. Endoscopy 30 (Suppl. 2), A231-A236. 1998.
12. Geenen JE, Hogan WJ, Dodds WJ, Toouli J, Venu RP. The efficacy of endoscopic sphincterotomy after cholecystectomy in patients with sphincter of Oddi dysfunction. N Engl J Med 1989; 320:82-87.
13. Al Waili N, Saloom KY. The analgesic effect of intravenous tenoxicam in symptomatic treatment of biliary colic: a comparison with hyoscine N-butylbromide. Eur J Med Res 1998; 3: 475-479.
14. Dula DJ, Anderson R, Wood GC. A prospective study comparing i.m. ketorolac with i.m. meperidine in the treatment of acute biliary colic. J Emerg Med 2001; 20: 121-124.
15. Khuroo MS, Zargar SA, Yattoo GN. Efficacy of nifedipine therapy in patients with sphincter of Oddi dysfunction: a prospective- double-blind- randomized- placebo-controlled- cross over trial. Br J Clin Pharmacol 1992; 33:477-485.
16. Pasricha PJ, Miskovsky EP, Kallo AN. Intrasphincteric injection of botulinum toxin for suspected sphincter of Oddi dysfunction. Gut 1996; 35: 1329-1331.
17. Freeman ML, Gill M, Overby C, Cen YY. Predictors of outcomes after biliary and pancreatic sphincterotomy for sphincter of Oddi dysfunction. J Clin Gastroenterol 2007; 41: 94-102.
    
<>