A Study On The Efficacy And Safety Of Endoscopic Sphincterotomy,Endoscopic Papillary Balloon Dilatation And Needle-knife Sphincterotomy

Part1A comparison among endoscopic sphincterotomy, endoscopic papillary balloon dilatation and endoscopic sphincterotomy plus balloon dilatation in the treatment for common bile duct stones Background:During endoscopic retrograde cholangiopancreatography (ERCP), endoscopic sphincterotomy (EST) is the standard method of enlarging the bile duct opening in the duodenum before stone removal. Although ES is effective, it permanently destroys the biliary sphincter. Therefore, subsequent duodenobiliary reflux could occur with bacterial contamination and chronic inflammation of the biliary system, which might lead to long-term sequelae.Recently, endoscopic sphincterotomy plus balloon dilatation (ESBD) has been reported to be used for large common bile duct (CBD) stones.5Endoscopic papillary balloon dilatation (EPBD) is another alternative technique to enlarge the papillary orifice for stone retrieval with the potential advantage of biliary sphincter function preservation. However, EPBD might carry an increased risk of pancreatitis due to edema and/or spasm from dilation trauma.Some previous reports indicated that ESBD reduced the need for mechanical lithotripsy (ML) in large CBD stone extraction, while others did not report any difference. Furthermore, a number of studies along with a meta-analysis on EST vs. EPBD suggested that they were not significantly different in terms of stone clearance rates, while other studies indicated a significant higher stone clearance rate in the EST group. Other published studies and a meta-analysis of three randomized controlled trials (RCTs) on EST vs. ESBD showed that there was no significant difference between ES and ESBD in terms of stone clearance rates.These three methodologies of EST, EPBD, and EPBD have not been previously compared directly for advantages and disadvantages. Therefore, we carried out this study to evaluate the benefits and risks of EST, EPBD, and ESBD in extraction of CBD stones. Furthermore, the surgical efficacy, postprocedural safety, and the economic factors will be compared among these three methods that can potentially eliminate the current ambiguity in the selection of techniques. Methods:This was a prospective randomized, comparative study conducted in the Nanfang Hospital between July2011and December2013. The study protocol was approved by the Medical Ethics Committee of Nanfang Hospital. All patients signed informed consent before ERCP. The study was registered with chictr.org (ChiCTR-TRC-12002341).The inclusion criteria included:Patients aged18years or older; and CBD stones confirmed by cholangiogram (≥10mm in maximum diameter). The exclusion criteria included:Septic shock; Acute pancreatitis; Coagulopathy (international normalized ratio of>1.5, partial thromboplastin time greater than twice that of control); Platelet count of<50,000×103/μL; Prior sphincterotomy or dilation; Biliary strictures; Billrith-II or Roux-en-Y anatomy; Concomitant pancreatic or biliary malignancies; Pregnancy; Requirement of precut sphincterotomy for bile duct access; and Inability to give informed consent.Moderate sedation for the procedure consisted of a combination of meperidine and diazepam along with anisodamine as needed for duodenal relaxation. Lopromide was used as the contrast agent. ERCP was performed in the prostrate position. The patients underwent continuous cardiopulmonary monitoring throughout the procedure. ERCPs were performed by experienced endoscopists (n=5) using side-viewing endoscopes. Selective cannulation of the bile duct was attempted using a20mm cut wire sphincterotome with a0.035inch guide wire. Patients were randomized using computer generated random number table into the EST, EPBD or ESBD groups after bile duct access was achieved and a cholangiogram confirmed the presence of the CBD stones.For the EST group, sphincterotomy was performed with a20mm cut wire sphincterotome. The length of the incision was decided by endoscopist according to the size of the stones. The ERBE generator with a blended current was used.For the EPBD group, dilation of the sphincter was performed with a5.5cm wire-guided balloon dilation catheter. The balloon was passed over a prepsitioned guide wire and was centered at the sphincter. Under endoscopic and fluoroscopic control, the balloon was gradually inflated with diluted contrast until the complete disappearance of the balloon waist. The size of the balloon was gauged by the size of the CBD. The minimum and maximum diameters of the balloon were10and15mm, respectively.For the ESBD group, a limited sphincterotomy measuring up to one-third to two-thirds of the papilla was first performed, followed by dilation. After the procedure, stones were removed by standard methods, including retrieval baskets and extraction balloon. ML was used to crush the stones, when necessary. An occlusion cholangiogram was obtained at the end of ERCP, followed by nasobiliary drain insertion for drainage, which was performed in all patients. After ERCP, patients were kept in the ward to be monitored for any complications. Patients were discharged when the acute condition was settled.All patients were telephone-interviewed30days after ERCP in order to assess the potential complications. The primary outcome was the stone clearance rate at the initial ERCP. Secondary outcomes included cannulation time, procedural time, ML use frequency,30-day complications and mortalities, and procedural cost. Complete stone clearance was defined as the absence of filling defects on occlusion cholangiogram. The cannulation time was calculated from the time of sphincterotome touching papilla up to a successful selective cannulation of bile duct. The procedural time was the time from a successful selective cannulation of bile duct up to the nasobiliary drain insertion. Complications were based on intention to treat and were defined and graded according to Cotton et al.’s system.Data was analyzed with the statistical software package for Windows Version13(SPSS Inc., Chicago, IL). The normality of the data was assessed by the Kolmogorov-Smimov test. The data were expressed as the mean±standard deviation (SD) or frequencies. The differences between groups were compared using analysis of variance (one-way ANOVA) for parametric data, Kruskal-Wallis test for nonparametric data, and Fisher’s exact or Pearson chi-square tests for comparison in the differences in proportions. Differences were considered statistically significant if the2-sided P value was less than0.05. Results:From July2011and December2013, a total of255consecutive patients were enrolled in the study. There were no differences in the background demographics among the three groups except that more patients undergoing ESBD had periampullary diverticulum. There were no differences in cannulation time, guidewire injection time into pancreatic duct, and time to complete the procedure. Similar rates of stone clearance were observed among the three groups. A total of92.9%,91.8%, and96.5%of the patients in the EST, EPBD, and ESBD groups had stones cleared at the initial ERCP (P=0.519). ML was used in9.4%,14.1%, and8.2%of the patients in the EST, EPBD, and ESBD groups (P=0.419), respectively without any significant differences in the ML use frequency among the groups. The procedural cost was also compared between the groups, where the cost of EPBD was more than ES and less than ESBD (P<0.001). Subgroup analysis was therefore undertaken with the patients classified according to the stone size and stone number. The stone clearance rates and frequency of ML use were also similar among the groups. The procedure cost of EPBD is higher than that of EST, and lower than that of ESBD.None of the patients died after the procedures. Complications occurred in4.7%,4.7%, and5.9%of the patients in the EST, EPBD, and ESBD groups (P=1.000), respectively. The grade proportion in severity were similar (P=0.693) with no significant differences in the rates of post-ERCP pancreatitis, cholangitis, and bleeding among the groups.Conclusion:Similar stone clearance rates were achieved with EST, EPBD, and ESBD. There was no difference among the groups except for the cost factor. Perhaps a larger sample size in future studies can further elaborate on any further potential differences among these three techniques. Part2A retrospective study on the efficacy and safety of needle-knife sphincterotomy in difficult biliary cannulation of endoscopic retrograde cholangiopancreatography Background:Endoscopic retrograde cholangiopancreatography (ERCP) has become the mainstay procedure in the management of biliary and pancreatic diseases. And deep biliary cannulation is the prerequisite to a successful ERCP. Access to the desired duct using standard accessories approaches90%. But conventional cannulation fails in approximately10%of patients, even in experienced hands. Fortunately, precut sphincterotomy can be employed as a rescue technique in this situation. This technique usually refers to needle-knife sphincterotomy (NKS).NKS is performed with a free-hand, so it is more difficult to control. Since the introduction of NKS as a technique for precut in the early1980s, there has been controversies over its use. Several prospective multicenter studies have reported an increased risk of complications with NKS. However, other studies have reported a complication rate similar to non-NKS-assisted procedure.The objective of this retrospective study was to evaluate the efficacy and safety of NKS for difficult bile duct access. Methods:During a period of3years (between May2009and May2012), a total of852patients were enrolled into this study, and NKS was attempted after failed conventional biliary access in123patients. All the procedures were performed only by the most experienced endoscopist. The included patients were divided into two chronological groups:initial group (61) and subsequent group (62).Conscious sedation for the procedures consisted of a combination of meperidine and diapezam with anisodamine as need for duodenal relaxation. Lopromide was used as contrast agent. ERCP was performed in the prostrate position. The patients underwent continuous cardiopulmonary monitering throughout the procedure. All procedures were done using Olympus video duodenoscopes. Selective cannulation of common bile duct was initially attempted using a standard sphincterotome with or without a guide wire. If repeated cannulation attempts (usually no more than15minutes or5times insertion of guide wire into pancreatic duct) were unsuccessful, the NKS was performed.All procedures were used a standard needle-knife and the ERBE generator. Following successful biliary cannulation, the sphincterotomy was extended, if needed using the standard sphincterotome and the ERBE generator with the Endo-Cut feature turned on. After the completion of ERCP, patients were observed in the inpatient department and the majority were discharged from hospital within three days after ERCP. Data of ERCP was taken from the endoscopy documentation system. Follow-up was determined by a retrospective review of the patients’computerized medical records. Post-procedure complications were based on intention to treat and defined and graded according to the system of Cotton et al.NKS was attempted in two manners:1. As has been previously described, it is also known as the needle-knife fistulotomy. A small incision was made on the bulging intraduodenal segment of the common bile duct, and the needle was moved in an upward direction starting3to5mm above the papillary orifice. If cannulation of the common bile duct through the opening was not possible, the incision was progressively extended in the same direction. The total length of the incision varied according to the size of the papilla, and cutting with the needle was always stopped when the common bile duct was entered. If cannulation was not achieved, one or two additional small incisions were made and the angle was changed slightly in the direction of the presumed course of the common bile duct. Attempts to cannulate the common bile duct were made after each step of the procedure with a standard sphincterotome. If the attempt was successful, the opening was extended cephalad with the sphincterotome and blended current to complete the papillotomy.2. It was based on the classic technique described by Huibregtse et al. and initiated with an incision started at the papillary orifice and extended upward between the11and1o’clock positions. Step by step the incision was extended until cannulation of the common bile duct was achieved. The papillotomy was completed with a standard sphincterotome and blended current.Data was analyzed using the statistical software package for Windows Version13(SPSS, Inc, Chicago, Illinois, USA). Continuous variables were described as the mean (standard deviation) and compared by the Student’s t test. Differences of categorical variables between groups were analyzed using the chi-square test. Differences were considered statistically significant if the P value was less than0.05. The hospital’s Ethics Committee approved this study.Results:During the study period,123NKS were performed out of a total of852(14.4%) patients. The most frequent indications for NKS were, in order of prevalence: stone, benign stenosis, others and malignant stenosis; while stone, benign stenosisi, malignant stenosis and others in non-NKS procedure. The NKS had a higher proportion of pancreatic duct injection and lower proportion of lithotripsy. The common bile duct was cannulated immediately after NKS in106of the123(86.2%) patients. Of the17who failed initial ERCP with NKS, only two (11.8%) returned for a repeat ERCP. Fortunately, biliary access was obtained in both patients. No patients experienced new clinical problems while waiting a second ERCP. Four subjects were preferred for surgery, and four individuals were performed using the percutaneous transhepatic choledochus drainage method. Seven patients were discharged from hospital when getting better without any subsequent procedure. Ultimately, the overall success rate of NKS was87.8%(108/123). NKS increased the overall success rate from85.6%(729/852, success rate without NKS) to98.2%(837/852, success rate with NKS).Twelve of the123(9.8%) patients experienced post-procedure complications, and this incidence was not significantly different (P=0.093) compared with that of non-NKS-assisted procedure (5.8%). The rate of pancreatitis with NKS was significantly higher (P=0.008) at8.1%(10of123patients) compared with3.2%(23of729patients) without. All ten pancreatitis of the patients with NKS were mild. All these patients were managed conservatively and discharged from hospital within three days after ERCP. However, in the non-NKS-assisted procedure, one developed severe pancreatitis and two had moderate panncteatitis. Bleeding occurred in two patients: one severely, requiring one additional session of endoscopic argon plasma coagulation therapy and10units of packed red blood cells transfusion; and one with moderate bleeding that required one additional session of endoscopic clips therapy and no transfusion. In both two patients, the NKS incision had been extended with a standard sphincterotomy. The rates of bleeding between the NKS and non-NKS-assisted procedure were not significantly different (P=0.285,1.6%vs.0.7%). None of patients developed cholangitis and perforation. No mortality related to the use of NKS occurred.Successful cannulation after NKS was achieved in77.0%and95.2%, respectively, of patients in each chronological group. There was an increase in success rate (P=0.004). And complication rates between the two groups were similar (13.1%and6.5%, respectively, P=0.213).Conclusion:NKS is an effective maneuver when traditional cannulation is difficult in experienced hand for a therapeutic purpose. For diagnosis, we’d better use magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasonography (EUS). Although NKS may have a higher risk for post-procedure pancreatitis, it is still a safe technique in experienced hands. Part3Effects comparison between endoscopic papillary large balloon dilatation and endoscopic sphincterotomy for common bile duct stone removal:a meta-analysisBackground:During endoscopic retrograde cholangiopancreatography (ERCP), endoscopic sphincterotomy (EST) is the standard method of enlarging the bile duct opening in the duodenum before stone removal. Recently, endoscopic papillary large balloon dilatation (EPLBD) has been reported to be used for large common bile duct (CBD) stones. There has been controversies over the efficacy and safety of EST and EPLBD. Therefore, we carried out this study to evaluate the benefits and risks of EST and EPLBD in extraction of CBD stones.Methods:Trials comparing the effects between EPLBD and EST treatment were searched according to the study protocol, from many databases, such as PubMed, Web of Science, Medline, and Cochrane Central Register of Controlled Trials (CENTRAL). Overall stone removal rate, complete removal rate in1st session, Comparison of the overall stone removal rate of EPLBD and EST treatments, treatment duration, mechanical lithotripsy using rate, and overall/each complications rate were compared using the risk ratio (RR), mean difference (MD) and their95%confidence interval (CI) using Revman5.2software.Results:As for overall stone removal rate, EPLBD and EST therapy showed similar effect (RR:1.01,95%CI:0.99-1.03; P=0.35), but for the patient with stone>10mm in diameter, EPLBD treatment showed better overall stone removal rate of (RR:1.05,95%CI:1.02-1.09, P<0.05). For complete stone removal rate in1st session, there was no difference between the two therapies (RR:1.07,95%CI:0.98-1.16, P=0.11), even for those with stone>10mm in diameter (RR:1.11,95%CI:0.99-1.24, P=0.08); however, EPLBD showed longer treatment duration (MD:-5.05,95%CI: -9.55-0.54, P=0.03), and higher mechanical lithotripsy using rate (RR:0.47,95%CI:0.37-0.60, P<0.00001). What’s more, EPLBD showed obvious overall complications rate (RR:0.57,95%CI:0.44-0.75, P<0.0001) and more serious bleeding (RR:0.53,95%CI:0.34-0.84, P=0.007) than EST, while there were no significant differences between these two treatment for perforation (RR:0.36,95%CI:0.13-2.08, P=0.36), hyperamylasemia (RR:0.66,95%CI:0.31-1.40, P=0.28), pancreatitis (RR:0.71,95%CI=0.44-1.15, P=0.16), and cholecystitis/cholangitis (RR:0.62,95%CI:0.28-1.37, P=0.24).Conclusion:For patients with stones>10mm in diameter, EPLBD could give better overall stone removal rate; however, this treatment need more duration and will induce higher mechanical lithotripsy using rate with more serious overall complications rate and bleeding, compared with EST.