Study Of Effects Of Extracorporeal Shock Wave Lithotripsy On Endoscopic Treatment Of Big And Difficult Common Bile Duct Stones

The prevalence of common bile duct stones increases with age and their treatment is difficult. At present, surgical choledochotomy is no longer always the therapy of choice due to its invasive character and associated morbidity and mortality rates. Since therapeutic endoscopic retrograde cholangiopancreatography (ERCP) replaced surgery as the first approach in cases of choledocolithiasis, a plethora of endoscopic techniques and devices appeared in order to facilitate rapid, safe and effective bile duct stones extraction. Nowadays, endoscopic sphincterotomy combined with balloon catheters and/or baskets is the routine endoscopic technique for stone extraction in the great majority of patients, and clearance rate can be achieved in over90%of cases. Ductal clearance failure by this method (5%-10%) is usually due to characteristics of the stones (shape, size, number and position, i.e. impacted or proximal to a ductal stenosis) or due to anatomic variants of the biliary tree. In these cases, alternative therapeutic approaches include surgical exploration, contact dissolution, electrohydraulic and laser lithotripsy, stenting and extracorporeal shock wave lithotripsy (ESWL).ESWL focuses high-pressure shock-wave energy at a designated target point, while minimizing energy exposure to adjacent tissues. Shock waves can be generated by underwater spark gap (electrohydraulic), piezoelectric crystals, or electromagnetic membrane technologies. This energy can be focused by elliptical reflectors, fixation of piezoelectric crystals to an elliptical dish, or by acoustic lenses, respectively. Spark-gap lithotripters are more powerful and may induce better stone clearance rates. When shock waves traverse the stone, cavitation occurs at the surface, and the changes in acoustic impedance release compressive and tensile forces, resulting in fragmentation. Localization of common duct stones amenable to ESWL is performed under fluoroscopy or ultrasound. When stones are located in the bile duct, a nasobiliary catheter is usually needed for contrast administration. The presence of irrigating fluid around the calculus helped in better fragmentation, as shock waves travel better in liquid medium. Fragmentation was considered satisfactory when the calculi were broken down to<5mm diameter. The number of sessions depended on achievement of good fragmentation. Clearance of the bile duct using a balloon or basket was conducted in the following procedure. The major drawback of ESWL is the time-consuming process which require one or more sessions of treatment:the insertion of a nasobiliary catheter in the interval, and repeated ERCP for fragment extraction. In many studies it has been demonstrated that ESWL combined with endoscopic procedures represents a safe and effective option for removal of difficult bile duct stones, especially in patients with high surgical risk. In our studies we investigate the effect of performing a session of ESWL on the patients who underwent an unsuccessful initial ERCP because of the size of common bile duct (CBD) stones. The result revealed that comparing with patients who underwent only ERCP procedure, a session of ESWL before ERCP can raise stone clearance rate within the second treatment session and total stone clearance. This procedure can not only reduce ERCP procedure time and patient’s hospitalization, but also raise successful rate of mechanical lithotripsy and clearance rate of extreme big stones.Cholecystokinin (CCK) is a member of the’gut-brain’family of peptide hormones. It is secreted by enteroendocrine cells (I cells) located in the mucosa of the duodenum, jejunum, and proximal ileum, as well as by specialized neurons in the myenteric plexus and brain. CCK performs numerous regulatory functions in the gut and the brain. In the gastrointestinal system, CCK has been implicated in gastric emptying and distension, gallbladder contraction, pancreatic secretion, and intestinal motility. In the nervous system, CCK plays a role in learning and memory, anxiogenesis, nociception and satiation. Cholecystokinin (CCK) binds CCK-1receptors located on the smooth muscle wall of the gallbladder, causing gallbladder contraction and secretion of bile into the intestine. It simultaneously relaxes the sphincter of Oddi by binding to its inhibitory receptors. In our studies we found that CCK can aid fragmentation of CBD stones during ESWL by creating a fluid-filled space at the circumference or within stones, thereby enhancing the coupling of shock waves.PART ONEThis study was aimed to determine whether a session of ESWL before ERCP can raise clearance rate of difficult and big CBD stones and the influencing factors. Adult patients of Zi Bo central hospital with CBD stones who underwent an unsuccessful initial ERCP because of the size of CBD stones. A nasobiliary tube (NBT) was placed in all subjects to irrigate the stones and visualize the stones during ESWL. The NBT was also used to opacity the CBD stones with contrast. Radio opaque stones were targeted without the use of contrast. Patients were randomized to ESWL plus ERCP group and ERCP alone group. ESWL were performed on the patients4hours before ERCP even though no difficulty was anticipated in the following endoscopic procedure to remove the stones by means of basket extraction. Clearance of the CBD stones was assessed after each session of ERCP procedure with procedure reports, plain films, ERCP films, and/or abdominal MRCP and/or CT. Separate records were made for each group that included post-ESWL complications, post-ERCP complications, number of mechanical lithotripsy use, duration of each ERCP procedure and each patient’s hospitalization. The results were as follows:1. ESWL plus ERCP compared with ERCP alone resulted in similar outcomes in terms of successful stone removal after the first ERCP procedure (74.2%vs71.0%, P=0.135) 2. Successful stone clearance rate after the second ERCP procedure and total stone clearance was higher in ESWL plus ERCP group (84.4%vs51.6%, P=0.018;96.0%vs86.0%, P=0.029).3. ESWL plus ERCP reduced ERCP procedure time (43+21min vs59±28min, P=0.034). The rate of mechanical lithotripsy use was similar between the two groups (47.3%vs52.9%, P=0.253), but successful rate of mechanical lithotripsy during ERCP procedure was higher in ESWL plus ERCP group (90.1%vs74.0%, P=0.041).4. Extremely big stones (≥30mm) clearance rate were higher in ESWL plus ERCP group than ERCP alone group (80.0%vs40.0%, P=0.016).5. Post-ERCP complications between ESWL plus ERCP and ERCP alone group were similar(6.7%vs6.5%, P=0.673), post-ESWL complications were mild and no severe complications and death were occurred.6. Duration about patients’ hospitalization has significant difference between ESWL plus ERCP and ERCP alone group (12.4±2.1d vs15.6±3.1d, P=0.042)In conclusion, a session of ESWL before ERCP is an excellent therapeutic modality of difficult and big common bile duct stones which offers high clearance rate, especially in the removal of extreme big CBD stones. Furthermore, this measure raise the successful rate of mechanical lithotripsy but reduce duration of ERCP procedure and patients’ hospitalization. We suggest that a session of ESWL before ERCP is an effective and safe treatment for endoscopic removal of difficult and big CBD stones.PART TWOCCK is a member of the’gut-brain’family of peptide hormones. It performs numerous regulatory functions in the gut and the brain. An important role of CCK is to stimulate gallbladder contraction, pancreatic secretion, and intestinal motility. We hypothesized that CCK may aid fragmentation of CBD stones by creating a fluid-filled space at the circumference or within stones, thereby enhancing the coupling of shock waves. In this study we aimed to evaluate the effect of CCK during on clearance of CBD stones at ERCP procedure. Patients with large CBD stones who were treated with ESWL and ERCP were identified retrospectively. They were randomized in equal numbers to CCK group and no CCK group. For each CCK case, a dose(3ng/kg/min for10min) of CCK-8was administered intravenous near the beginning of ESWL. ERCP was performed4hours after a session of ESWL. Clearance of the CBD were assessed between the two groups. Separate records were made for each group that included post-ESWL complications, post-ERCP complications, number of mechanical lithotripsy use, duration of each ERCP procedure and each patient’s hospitalization. The results were as follows:7. Stone passed spontaneously in6patients after ESWL treatment,4patients in the CCK group and2patients in the no CCK group, there was no significant difference between the two groups.8. CCK group showed significantly higher rate of successful stone removal after first ESWL and ERCP procedure (71.6%vs55.4%, P=0.035).9. CCK group resulted in similar outcomes in the second, third session of ESWL and ERCP procedure (42.8%vs39.4%, P=0.218;41.7%vs40.0%, P=0.346).10. Patients in CCK group had a similar stone clearance after three sessions of ESWL and ERCP procedure (90.5%vs83.8%, P=0.178).11. Stone removal by a conventional method were similar between both groups (64/69,92.8%vs55/61,90.2%, P=0.315), but the use of mechanical lithotripsy was reduced in CCK group (45.6%vs62.4%, P=0.027). The successful rate of mechanical lithotripsy was higher in CCK group (91.5%vs80.8%, P=0.031).12. Extremely big stone (≥30mm) removal was higher in CCK group than no CCK group (8/11,72.7%vs5/12,41.7%, P=0.038).13. Post-ERCP complication rates were similar between2groups (9/103,8.7%vs10/125,8.0%, P=0.528) and post-ESWL complications were mild and had no significant difference between the two groups (8/107,7.5%vs10/127,7.9%, P=0.673).14. Duration of ERCP procedure between CCK group and no CCK group had significant difference(39±17min vs50±22min, P=0.024), and patients in CCK group had shorter hospitalization (16.4±2.9dvs21.8±3.5d, P=0.032).In conclusion, these results suggested CCK during ESWL appears to aid clearance of CBD in the first ESWL/ERCP session. The presence of a fluid interface between the fluid wall and the stone was an important factor for successful stone fragmentation mechanical lithotripsy usage was reduced in CCK group and extremely big stone (^30mm) clearance rate can also be raised. Duration of ERCP procedure and patients’hospitalization were reduced in CCK group.In summary, our study indicated that as for the treatment of difficult and big common bile duct stones, comparing with ERCP alone, a session of ESWL before ERCP could raise stone clearance after the second ERCP procedure, total stone clearance and successful rate of mechanical lithotripsy use. Also it reduce ERCP procedure time and patients’ hospitalization. CCK can aid clearance of CBD in the first ESWL/ERCP session comparing with no CCK group. Mechanical lithotripsy usage was reduced and extremely big stone (≥30mm) clearance rate can also be raised in CCK group. CCK also reduce duration of ERCP procedure and patients’ hospitalization. Therefore, in view of its high efficiency, non-invasive nature and low complication rates, ESWL combing CCK can be offered as the first-line therapy for selected patients with large CBD stones.