INTRODUCTION
Sickle cell anemia (SCA) is one of the commonest hemoglobinopathies in the Eastern Province of Saudi Arabia with a sickle cell trait frequency of about 25% and a sickle cell disease frequency of about 2% in some areas[1,2]. One of the common complications of SCA is cholelithiasis and choledocholithiasis. The prevalence of cholelithiasis in patients with SCA is variable, ranging from 17% to 55%, but the frequency increases with age[3-5]. In the Eastern Province of Saudi Arabia, an overall frequency of cholelithiasis of 19.7% was reported in children with SCA. This frequency however, increased to 36% in those 15-18 years of age[6]. The incidence of choledocholithiasis in patients with SCA undergoing cholecystectomy was reported to be around 30%[7,8]. In the past, and based on this high incidence of common bile duct (CBD) stones, routine intraoperative cholangiography (IC) was recommended during cholecystectomy as this may necessitate CBD exploration[7]. This however is not the case in the era of LC. Laparoscopic IC and CBD exploration, although feasible, is not easy to perform, requires expertise, and may be time-consuming. Add to this the possibility of converting a LC into an open one once CBD stones are diagnosed and found to be difficult to retrieve laparoscopically. The question now is whether routine laparoscopic IC is necessary for patients with SCA undergoing LC.
MATERIALS AND METHODS
Two hundred and twenty four patients with SCA underwent endoscopic retrograde cholangiopancreatography (ERCP) as part of their evaluation for cholestatic jaundice (CJ). Their medical records were reviewed for: age at diagnosis, sex, indication for ERCP, hemoglobin (Hb) electrophoresis, liver function tests, including total and direct bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase, and abdominal ultrasound. The indications for ERCP were divided into 3 categories based on ultrasound findings: (1) patients with CJ and normal ultrasound; (2) patients with CJ and dilated bile ducts on ultrasound; and (3) patients with CJ and CBD stones on ultrasound. All ERCPs were performed in the radiology department using Olympus TJF 240 or JF 260 side-viewing duodenoscopes under general anesthesia, with nasotracheal intubation for children less than 10 years old, and under deep sedation using meperidine (1 mg/kg) and diazepam (midazolam) (0.1-0.2 mg/kg) for those above 10 years of age. The ampulla of Vater was cannulated with tapered or regular catheters and the biliary ducts were visualized under fluoroscopy using Hexabrix (320 mg diluted to 50%). Appropriate radiographs were obtained and, where indicated, sphincterotomy was performed using a 5F sphincterotomy (Olympus); bile duct stones, if found, were extracted with a basket, balloon extractor or mechanical lithotripter.
RESULTS
There were 144 male and 80 female patients, mean age 22.4 years (range, 5-70 years). Mean HbS was 76.8% (range, 64.7%-92.3%); their mean HbF was 20.4% (range, 5.1%-34.0%); mean total bilirubin was 224 mg/L (range, 55-395 mg/L); mean direct bilirubin was 134 mg/L (range, 40-263 mg/L); mean alkaline phosphatase was 486 IU/mL (range, 81-1189 IU/mL; normal: 50-136 IU/mL); mean ALT was 234.3 IU/mL (range, 50-761 IU/mL; normal: 30-50 IU/mL) and mean AST was 206.3 IU/mL (range, 63-317 IU/mL; normal: 15-37 IU/mL). The indications for ERCP were: CJ only in 97 patients, CJ and dilated bile ducts on ultrasound in 103, and CJ and CBD stones on ultrasound in 42. In those with CJ only, ERCP revealed CBD stones in 18 (18.6%), and the ampulla of Vater was edematous and inflamed in 4, suggestive of recent stone passage. In those with CJ and dilated bile ducts, ERCP revealed CBD stones in 48 (46.6%), and inflamed edematous ampulla in 8. In those with CJ and CBD stones, ERCP revealed stones in 22 (52.4%), and the ampulla was inflamed and edematous in 4. In total, CBD stones were found in 88 (39.3%) patients, and there was evidence of recent stone passage in 16. Fifteen of these were post-cholecystectomy patients, who had endoscopic sphincterotomy and stone extraction. The remaining 73 had endoscopic sphincterotomy and stone extraction followed by LC without an IC. Two (2.3%) patients developed minor bleeding from the sphincterotomy site. This was controlled with local diluted adrenaline injection. Two (2.3%) developed transient mild pancreatitis.
DISCUSSION
In the general population with cholelithiasis the incidence of CBD stones has been reported as 5%-15% whereas in those with SCA it ranges from 18% to 30%[7-10]. Because of the high incidence of choledocholithiasis in patients with SCA, routine IC was advocated[7]. With the recent advances in LC, exclusion of CBD stones is of great importance. This is specially so in patients with SCA who frequently present with CJ and are known to have a high incidence of cholelithiasis and choledocholithiasis. There are those who advocate routine laparoscopic IC to delineate the anatomy and to detect CBD stones[11-16]. Lillemoe et al[17] on the other hand advocate the selective use of laparoscopic cholangiography. Although laparoscopic IC is feasible, it has several disadvantages. It requires operators who are experienced in laparoscopic surgery, it is not technically easy, and it is known to increase the operative time. It also makes it difficult to decide, when CBD stones are diagnosed and difficult to retrieve, whether to convert the operation to open or wait and do a post-LC ERCP. Add to this a 20%-25% false positive rate of IC that may lead to unnecessary CBD exploration or conversion to open cholecystectomy[16]. In a prospective study of CBD calculi in patients undergoing cholecystectomy, Nathanson et al[18] found choledocholithiasis in 3.4%, and concluded that laparoscopic IC would result in unnecessary interventions in 50% of patients who had either false positive results or subsequently passed the stones. Another study in 343 patients who underwent LC concluded that routine IC should be discouraged in view of the low yield and significant rate of false positive results[19]. However, Targarona et al[20] stated that the choice of diagnostic and therapeutic strategies for CBD stones should depend on local circumstances and available expertise. We found ERCP to be valuable both for the diagnosis and management of CBD stones in patients with SCA who were scheduled to have LC, or in those who presented with retained CBD stones following LC. Our policy is that all SCA patients with cholelithiasis who have a dilated CBD on ultrasound, biochemical evidence of obstructive jaundice (elevated alkaline phosphatase, elevated total bilirubin of more than 50 mg/L), or a history of pancreatitis either alone or in combination, and those who have choledocholithiasis detected on ultrasound, should undergo ERCP to confirm and extract the stones, followed by LC. We, like others, support a policy of preoperative ERCP for those with risk factors for CBD stones followed by LC[21,22]. However, magnetic resonance cholangiopancreatography and or endoscopic ultrasound, if available, should replace ERCP as a diagnostic method to detect CBD stones as this will reduce the number of negative ERCPs and avoid the risks and complications of ERCP particularly for those with dilated CBD without stones.
In conclusion, considering the high incidence of CBD stones in patients with SCA, it is important to exclude them as a cause of CJ whether pre- or post-cholecystectomy. This is specially so in the era of LC. Laparoscopic IC, although feasible, is not easy to perform, is time-consuming, requires expertise, and may necessitate conversion to open surgery if CDB stones are identified. We found ERCP valuable in this regard whether pre- or post-LC, and in none of our patients was there a need to perform laparoscopic IC. Sequential endoscopic sphincterotomy and stone extraction followed by LC is beneficial in these patients[23,24]. Since we started using ERCP, none of our patients required CBD exploration and all CBD stones, whether diagnosed preoperatively or postoperatively, were managed by endoscopic sphincterotomy and stone extraction. Endoscopic sphincterotomy may also prove to be useful in these patients as it may prevent the future development of biliary sludge and bile duct stones.
COMMENTS
Background
Cholelithiasis and choledocholithiasis are common in patients with sickle cell anemia, and it is important to exclude choledocholithiasis in those undergoing cholecystectomy. In the past and at the time of open cholecystectomy, routine intraoperative cholangiography (IC) was part of the operative procedure as they have a high incidence of choledocholithiasis. The question now is whether routine laparoscopic IC is necessary for patients with Sickle cell anemia (SCA) undergoing laparoscopic cholecystectomy.
Research frontiers
Common bile duct (CBD) stones were found in 88 (39.3%) of 224 patients and there was evidence of recent stone passage in 16. Fifteen of these were post-laparoscopic cholecystectomy patients and had endoscopic sphincterotomy and stone extraction. The remaining 73 had endoscopic sphincterotomy and stone extraction followed by laparoscopic cholecystectomy without IC.
Innovations and breakthroughs
Laparoscopic IC, although feasible, is not easy to perform, is time-consuming, requires expertise, and may necessitate conversion to open surgery if bile duct stones are identified. We found endoscopic retrograde cholangiopancreatography (ERCP) valuable whether pre- or post-laparoscopic cholecystectomy and in none of our patients was there a need to perform laparoscopic IC. Sequential endoscopic sphincterotomy and stone extraction followed by laparoscopic cholecystectomy are beneficial in these patients. Since we started using ERCP, none of our patients required CBD exploration and all CBD stones whether diagnosed preoperatively or postoperatively were managed by endoscopic sphincterotomy and stone extraction. Endoscopic sphincterotomy may also prove to be useful in these patients as it may prevent the future development of biliary sludge and bile duct stones.
Applications
All patients with SCA and cholelithiasis who have a dilated CBD on ultrasound, elevated alkaline phosphatase, elevated total bilirubin of more than 50 mg/L, or a history of pancreatitis either alone or in combination, and those who have choledocholithiasis detected on ultrasound should undergo ERCP to confirm and extract stones followed by laparoscopic cholecystectomy. However, magnetic resonance cholangiopancreatography and or endoscopic ultrasound should replace ERCP as a diagnostic method to detect CBD stones as this will reduce the number of negative ERCPs and avoid the risks and complications of ERCP particularly for those with dilated CBD without stones.
Terminology
ERCP: Endoscopic retrograde cholangio pancreatography.SCA: Sickle cell anemia, a hereditary hemoglobinopathy resulting from a single change of one amino acid, valine instead of glutamic acid of the hemoglobin B-chain. This will lead to a change in the shape of red blood cells causing their adherence together, blocking the small blood vessels and their hemolysis.
Peer review
The authors discussion of routine cholangiography in patients with SCA with high suspicion of choledocholithiasis is highly appreciated.
Peer reviewer: Ashok Kumar, MD, Department of Surgical Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, 226014, India
S- Editor Tian L L- Editor Cant MR E- Editor Ma WH
