Abstract

Background: Early detection of stones in the common bile duct (CBD) in patients with chronic calcular cholecystitis and adequate management of them are important to decrease patients’ morbidity. In some patients a spasm in sphincter of oddi might lead to entrapment of a small stone which could be managed medically without surgical intervention. Glyceryl trinitrate (GTN) was found to dilate blood vessels and sphincter of oddi. 

Aims: To evaluate the benefits of using GTN in management of a small stone in the CBD in patients with chronic calcular cholecystitis aiming to avoid unnecessary surgery.

Patients and Methods: We performed our study on 30 patients having chronic calcular cholecystitis with CBD stone. We give them GTN as medical treatment daily for about one week. We followed them for 7 days for clinical, laboratory and sonographic improvement.

Results: We found that 25 (83.3%) of our patients have clinical, laboratory and sonographic evidence of improvement of symptoms in a median time of 4 - 5 days (p = 0.001) and then ERCP and cholecystectomy was done later on. While 5 (16.7%) cases revealed elevated pancreatic enzymes which denoted failed medical management with persistence of the stone and needed ERCP then cholecystectomy later on (p = 0.001). There was a significant association between patients with succeeded medical treatment and patients with failed medical treatment regarding size of the stone and age of the patient (p = 0.001). Ultrasonography showed significant reduction in CBD diameter (p = 0.001) during GTN treatment. 

Conclusion: Small stone in the CBD might be resulted from a spasm in sphincter of oddi and could be effectively managed by medical treatment using GTN which could result in a clinical recovery of most patients and ERCP and cholecystitis could be done later on.

Keywords: Chronic Calcular Cholecystitis; Common Bile Duct Stone; Spasm in Sphincter of Oddi GTN Therapy

References

1. Dasari BVM., et al. “Surgical versus endoscopic treatment of bile duct stones”. Cochrane Database of Systematic Reviews (2013).
2. Bansal VK., et al. “Single-stage laparoscopic common bile duct exploration and cholecystectomy versus two-stage endoscopic stone extraction followed by laparoscopic cholecystectomy for patients with concomitant gallbladder stones and common bile duct stones: a randomized controlled trial”. Surgical Endoscopy 28 (2014): 875-885.
3. Staritz M., et al. “Effect of glyceryl trinitrate on the sphincter of Oddi motility and baseline pressure”. Gut 26 (1985): 194-197.
4. Afghani E., et al. “Sphincter of Oddi Function and Risk Factors for Dysfunction”. Frontiers in Nutrition 4 (2017): 1.
5. Thomas WR., et al. “Endoscopic retrograde cholangiography: Complications, emergencies, and related topics”. IJAM 4.2 (2018): 124-141.
6. Williams E., et al. “Updated guideline on the management of common bile duct stones (CBDS)”. Gut 66 (2017): 765-782. 
7. Cox MR., et al. “Timing and nature of presentation of unsuspected retained common bile duct stones after laparoscopic cholecystectomy: a retrospective study”. Surgical Endoscopy 29 (2015): 2033-2038.
8. Collins C., et al. “A prospective study of common bile duct calculi in patients undergoing laparoscopic cholecystectomy: natural history of choledocholithiasis revisited”. Annals of Surgery 239 (2004): 28-33.
9. Lefemine V and Morgan RJ. “Spontaneous passage of common bile duct stones in jaundiced patients”. Hepatobiliary and Pancreatic Diseases International 10 (2011): 209-213.
10. Möller M., et al. “Natural course vs interventions to clear common bile duct stones: data from the Swedish Registry for Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography”. The Journal of the American Medical Association Surgery 149 (2014): 1008-1013.
11. Wu SD., et al. “Nitroester drug’s effects and their antagonistic effects against morphine on human sphincter of Oddi motility”. World Journal of Gastroenterology 11 (2005): 2319-2323.
12. Bistritz L and Bain VG. “Sphincter of Oddi dysfunction: Managing the patient with chronic biliary pain”. World Journal of Gastroenterology 12.24 (2006): 3793-3802 .
13. Ding J., et al. “Glyceryl Trinitrate for Prevention of Post-ERCP Pancreatitis and Improve the Rate of Cannulation: A Meta-Analysis of Prospective, Randomized, Controlled Trials”. Plos One 8.10 (2013): 75645. 
14. Xiao-wei C., et al. “Nitroglycerin for prevention of post-ERCP pancreatitis and hyperamylasemia”. Chinese Journal of Digestive Endoscopy 29 (2012): 181-184.
15. Sudhindran S., et al. “Prospective randomized double-blind placebo-controlled trial of glyceryl trinitrate in endoscopic retrograde cholangiopancreatography-induced pancreatitis”. British Journal of Surgery 88 (2001): 1178-1182. 
16. Hao JY., et al. “Prophylactic effect of glyceryl trinitrate on post-endoscopic retrograde cholangiopancreatography pancreatitis: A randomized placebocontrolled trial”. World Journal of Gastroenterology 15 (2009): 366-368. 
17. Meckeler KJH and Borow M. “Direct manometric study of the sphincter of Oddi in man”. Gastroenterology 68 (1975): 1038.
18. Hopton DS and Torrance HB. “Action of various analgesic drugs on the human common bile duct”. Gut 8 (1967): 296-300.
19. Armstrong PW., et al. “Blood levels after sublingual nitroglycerin”. Circulation 59 (1979): 585-588.
20. W Luman., et al. “Topical glyceryl trinitrate relaxes the sphincter of Oddi”. Gut 40 (1997): 541-543.
21. Shoji M., et al. “Topical nitrate drip infusion using cystic duct tube for retained bile duct stone: A six patients case series”. World Journal of Gastrointestinal Surgery 5.6 (2013): 210-215.