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Ampulla dilation with different sized balloons to remove common bile duct stones.

AIM
To assess the outcomes of ampulla dilation with different sized balloons to remove common bile duct (CBD) stones.


METHODS
Patients (n = 208) were divided into five groups based on the largest CBD stone size of < 5, 6-8, 8-12, 12-14, and > 14 mm. Patients underwent limited endoscopic sphincterotomy (EST) alone or limited EST followed by endoscopic papillary balloon dilation with 8, 10, 12 and 14 mm balloons, such that the size of each balloon did not exceed the size of the CBD. Short- and long-term outcomes, such as post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, perforation, bleeding, and pneumobilia were compared among the five groups.


RESULTS
The overall rate of successful stone removal in all groups was 100%, and all patients were cured. Eight (3.85%) patients had post-ERCP pancreatitis, none had perforations, and 6 (2.9%) had bleeding requiring transfusion. There were no significant differences in early complication rates among the five groups. We observed significant correlations between increased balloon size and the short- and long-term rates of post-ERCP pneumobilia. Post-ERCP pancreatitis and bleeding correlated significantly with age, with post-ERCP pancreatitis occurring more frequently in patients aged < 60 years, and bleeding occurring more frequently in patients aged > 70 years. We observed a significant correlation between patient age and the diameter of the largest CBD stone, with stones > 12 mm occurring more frequently in patients > 60 years old.


CONCLUSION
Choosing a balloon size based on the largest stone diameter is safe and effective for removing CBD stones. Balloon size should not exceed 15 mm.


INTRODUCTION
Endoscopic sphincterotomy (EST) and endoscopic papillary balloon dilation (EPBD) with balloons < 12 mm in diameter are the methods of choice for the removal of stones from the common bile duct (CBD) [1][2][3][4] . Both methods, however, have distinct advantages and disadvantages. EST is associated with serious short-term complications, such as hemorrhage, perforation, and pancreatitis, and long-term complications such as permanent loss of sphincter of Oddi (SO) function and recurrent bile duct infection [5][6][7] . Although complications of bleeding and perforation seldom occur during EPBD [8][9][10] and SO function can be preserved [11,12] , it is difficult to remove large CBD stones using EPBD because the biliary opening is not as enlarged as it is with EST, and EPBD is associated with a higher rate of post-endoscopic retrograde cholangiopancreatographic (ERCP) pancreatitis.

BRIEF ARTICLE
More recently, EPBD with large sized balloons (12-20 mm) has been used to remove large CBD stones following limited EST [13][14][15][16] . It is unclear, however, whether the increase in balloon size is associated with increased rates of short-term complications, such as perforation and hemorrhage, or with preservation of SO function. Combining the advantages of EST and EPBD, by selecting the correct sized balloon and EST incision length to achieve a high rate of stone extraction, while minimizing complications of both procedures, would be of great benefit to the patients. We therefore prospectively investigated the short-and long-term outcomes of different sized balloons, chosen according to each patient's maximum CBD stone size, to dilate the papilla following limited EST.

Patients
Patients with possible CBD stones, as diagnosed by biliary symptoms and abnormality of biliary enzymes, or whose presence was suspected through imaging modalities, such as ultrasound (US), computed tomography (CT) and/or magnetic resonance imaging (MRI) were screened. Patients were excluded if they had (1) severe acute pancreatitis (APACHE Ⅱ ≥ 8, or Balthazar CT score ≥ 4); (2) severe cholangitis with disturbance of consciousness and shock; (3) coagulopathies; (4) malignant diseases; (5) a history of previous EPBD or EST; (6) age > 85 years; (7) a CBD filled with stones; and (8) had undergone a Billroth Ⅱ gastrectomy. Patients who met these criteria and lived in Shanghai, enabling follow-up, were fully informed about the methods and possible complications of the procedure, and were asked to provide written informed consent before ERCP. The study was approved by the Ethics Committee of Shanghai Gongli Hospital, and was supported by the Shanghai Municipal Health Bureau.
Patients were enrolled if selective deep cannulation to the CBD was successful, CBD stones were diagnosed by ERC, and an incision was made to the mid-portion of the papilla with a pull-type sphincterotomy. The diameter of the largest stone was determined by comparing it with the size of the endoscope tip. Patients were divided into five groups based on the largest CBD stone size, of (1) < 5 mm, (2) 6-8 mm, (3) 8-12 mm, (4) 12-14 mm, and (5) > 14 mm. These groups underwent limited EST alone without EPBD, and EPBD with balloons of 8, 10, 12 and 14 mm in diameter, respectively, such that the size of each balloon did not exceed the size of the CBD.

Methods
Pharyngeal anesthesia and premedication before the procedure, including the intravenous administration of diazepam, meperidine hydrochloride, and scopolamine, were performed in the same manner as for general endoscopy. ERCP was performed with a side-viewing endoscope (JF240; JF260V; Olympus, Tokyo, Japan).
Limited EST was performed according to the standard methods using a pull-type sphincterotomy. The incision was made up to the mid-portion of the papilla.

Endoscopic papillary balloon dilation
A balloon dilation catheter of 8, 10, 12 or 14 mm in diameter (Wilson-Cook Medical Inc., NC, United States), was inserted and inflated slowly with diluted contrast fluid until the waistline was obliterated under fluoroscopic monitoring and maintained for one min at 6 atm or 8 atm as required. After the balloon was deflated, the stones were extracted using a retrieval basket (Wilson-Cook Medical Inc., NC, United States) and/or a retrieval balloon (Extracter XL; Boston Scientific Corporation, MA, United States).
When the stone diameter was > 16 mm, as shown by diagnostic ERCP, a mechanical lithotripter (ML; BML-4Q; Olympus Corporation, Tokyo, Japan) was used to break the stones into fragments.

Follow-up
All patients were seen at the outpatient clinic six months to one year after discharge and every year thereafter. At each visit, blood and liver function tests, abdominal US and CT were performed. Other relevant examinations were performed when deemed necessary. If stone recurrence was suspected from symptoms, laboratory data, and/or images, ERCP was performed, and the recurrent stone was removed.

Outcome measures
Short-term outcomes included the rates of post-ERCP pancreatitis, bleeding requiring transfusion, perforation, pneumobilia and mortality. Long-term (2-5 years) outcomes included the rates of reflux cholangitis, pneumobilia, and recurrence of CBD stones.

Statistical analysis
Statistical analyses were performed using statistical software (SPSS 12.0 for Windows; SPSS Inc., Chicago, IL, United States). Quantitative data were presented as the mean ± SD. The χ

Patient characteristics and early complications
We enrolled 208 consecutive patients (95 males and 113 females), all of whom were diagnosed with CBD stones by ERC and underwent successful selective deep cannulation to the CBD at our institution between January 1, 2006, and January 1, 2008. Mean patient age was 62.4 ± 15.0 years. Stones were successfully removed from all the patients in all 5 groups. The demographic data and baseline characteristics of the 5 groups are shown in Table 1.
We observed a significant correlation between patient age and the diameter of the largest stone, with stones > 12 mm occurring more frequently in patients > 60 years old. The ML was used more often in patients with larger CBD stones, especially for stones > 16 mm in diameter. Although the overall success rate of stone removal was 100% in all groups, two patients in the 14 mm balloon group and one in the 12 mm group each required 2 sessions for stone removal due to patient intolerance of a long operation time to remove large stones.

Early complications
All patients were cured, none died, and none had a perforation. We found that 8 (3.85%) patients had post-ERCP pancreatitis, including 1 in the 10 mm balloon dilation group who had severe pancreatitis. All patients were cured by conservative treatments. Six (2.9%) patients experienced upper gastrointestinal bleeding requiring transfusions, including 2 patients with bleeding in the stomach and 4 with bleeding in the duodenal papilla. Two patients were cured by angiographic embolization and 1 by laparotomy to ligate the bleeding vessel after 2 attempts of endoscopic clamping and 1 of angiographic embolization all failed. The other 3 patients were cured conservatively. There were no significant differences in early complication rates among the five groups.
Pneumobilia occurred in 55 (26.4%) patients at a mean of 4.9 ± 0.7 d (range, 3-7 d) after ERCP. We observed a significant correlation between increased balloon size and the incidence of pneumobilia, suggesting that dilation with a large balloon may cause more damage to SO function. Details of early complications are described in Table 2.
Interestingly, post-ERCP pancreatitis and bleeding correlated significantly with age, with post-ERCP pancreatitis occurring more frequently in patients aged < 60 years, and bleeding occurring more frequently in patients aged > 70 years. The 8 patients with post-ERCP pancreatitis were significantly younger than the 200 who did not develop post-ERCP pancreatitis (51.1 ± 8.3 years vs 63.5 ± 15.1 years, P = 0.026). Conversely, the 6 patients with bleeding were significantly older than the 202 who did not develop bleeding (75.7 ± 7.1 years vs 61.4 ± 15.0 years, P = 0.024).

Later complications
Of the 208 patients, 192 (92.3%) were followed up for at least 2 years, with a mean follow-up time of 3.2 ± 1.1 years (range, 2-5 years). There were no significant differences in the rates of later complications, including reflux cholangitis and recurrence of CBD stones, among the 5 patient groups.
The incidence of pneumobilia one year after ERCP was significantly lower than shortly after ERCP, suggesting that SO function had recovered, at least partially, in these patients. We observed a significant correlation between the size of the dilation balloon and the 1-year incidence of pneumobilia, suggesting that larger balloons may cause more damage to SO function. The details of later complications in each group are shown in Table 2.

DISCUSSION
As no standard endoscopic procedure has been developed to date to maximize the effects and minimize the complications of EST and EPBD [17,18] , we prospectively assessed a method combining EPBD with limited EST. CBD stone sizes vary, from 3-5 mm in diameter to 15-30 mm in diameter, or even larger, suggesting that an endoscopic treatment method should be based on stone size. We therefore utilized limited EST alone for CBD stones < 5 mm in diameter, and limited EST followed by EPBD with balloons of 8, 10, 12 and 14 mm for CBD stones 6-8, 8-12, 12-14 and > 14 mm, respectively. We found that tailoring balloon size to stone size was safe and effective, 905 February 14, 2013|Volume 19|Issue 6| WJG|www.wjgnet.com mm was safe, with no perforations, whereas balloons > 15 mm was associated with a significantly higher rate of perforation [22] . In contrast, the use of 8 mm balloons in animals showed that EPBD was not associated with fibrosis or altered papillary architecture [23] and many clinical reports have shown that EPBD with large balloons > 15 mm was effective and safe [13][14][15][16] . However, the risk of perforation is higher with large balloons, prolonging hospitalization and increasing costs. We also found that increased dilation size was significantly associated with an increased incidence of pneumobilia, indicating that dilation with large balloons may cause more damage to SO function. Although we found no significant differences in later complications, such as reflux cholangitis and recurrence of CBD stones among the 5 patient groups, follow-up time may not have been sufficiently long. SO function is important in preventing biliary diseases, such as acute cholecystitis, cholangitis and recurrence of CBD stones [24] , suggesting that preserving SO physiological function may be advantageous, especially in younger patients. Our findings also indicate that 14 mm balloons were large enough to remove CBD stones > 15 mm, assisted by an ML. Taken together, our findings indicate that limited EST, followed by EPBD with balloons < 15 mm is safe. We found that the rate of post-ERCP pancreatitis and bleeding correlated with patient age, with patients < 60 years more frequently having post-ERCP pancreatitis and patients > 70 years more prone to bleeding. The progressive decline in pancreatic exocrine function with age may protect older patients from pancreatic injury [25,26] . In contrast, the Oddi muscle may be stronger in younger than in older patients, resulting in more difficult dilation in the former and a higher rate of pancreatitis. Although bleeding has seldom been reported after EBPD, we found that 6 (2.9%) of our patients had upper gastrointestinal bleeding requiring transfusions. All 6 were > 65 years old, with a mean age of 76 years. Older patients may be more prone to bleeding due to the relative inelasticity of their blood vessels. We also observed a correlation between CBD stone size and patient age, with stones > 12 mm occurring more frequently in patients > 60 years old.
with low rates of short-and long-term complications.
Limited EST was sufficient to remove CBD stones < 5 mm in diameter, as the biliary opening was large enough to remove these stones. EBPD was not required as balloons larger than CBD stones can cause more damage to SO function. We found that limited EST did not cause any perforations, an often fatal complication and even more serious than pancreatitis and bleeding, and preserved SO function.
We also found that limited EST followed by EPBD with balloons < 12 mm in size could partially preserve SO function. Although limited EST plus EPBD with balloons 12-14 mm in size did not cause any perforations, it was associated with higher rates of pneumobilia, both shortly after ERCP and ≥ 2 years later, compared with limited EST alone or followed by EPBD with smaller balloons, suggesting that large balloons result in greater damage to SO function.
Limited EST followed by EPBD has several benefits, including a lower incidence of post-ERCP pancreatitis. After EST, the openings of the pancreatic duct and common bile duct separate, decreasing the pressure on the pancreatic duct caused by EPBD and papillary edema [19] . Using limited EST in all our patients with CBD stones, we found that the overall incidence of post-ERCP pancreatitis was 3.85%, lower than previously reported [5][6][7]10] . Limited EST combined with EPBD can also make cannulation easier and reduce the procedure and fluoroscopy times [20] by shortening the cannulation length, and is safer than full EST or EPBD alone, because full EST may lead to perforation, while EPBD alone may lead to post-ERCP pancreatitis. Furthermore, limited EST is easier to perform than full EST. We have successfully utilized this method to remove large CBD stones since 1999 [21] , and have found that it is a good choice for different sized CBD stones.
Large balloon dilation of the papilla may make the removal of CBD stones easier, reducing the need for an ML, and shortening cannulation and stone removal times, thus decreasing the incidence of post-ERCP pancreatitis. However, we did not use a balloon > 15 mm. A recent study in animals showed that EPBD with balloons < 15 ERCP: Endoscopic retrograde cholangiopancreatography; EST: Endoscopic sphincterotomy; CBD: Common bile duct. The main limitation of this study was that we evaluated SO function by pneumobilia incidence, and not by endoscopic manometry. Manometry requires cannulation to the CBD, making it painful for patients and unacceptable during follow-up. Other limitations include the performance of this study at a single center, the relatively small number of patients, and the relatively short followup period.
In conclusion, limited EST, alone or followed by EPBD with balloons 8-14 mm, is safe and effective for the removal of different sized CBD stones. Choosing balloon size based on CBD stone size can maximize outcomes and minimize the complications of both EST and EPBD. Balloons > 15 mm in size are not necessary.

ACKNOWLEDGMENTS
We thank Medjaden Bioscience Limited for assisting in the preparation of this manuscript.

Background
Common bile duct (CBD) stones are very common, and patients are traditionally treated by open CBD exploration. With the advent of invasive endoscopic techniques, more patients are being treated endoscopically. However, endoscopists are often faced with difficult treatment decisions: endoscopic sphincterotomy (EST) or endoscopic papillary balloon dilation (EPBD)? Both methods have distinct advantages and disadvantages. The authors of this study prospectively investigated the short-and long-term outcomes of different sized balloons to dilate the papilla following limited EST.

Research frontiers
Both EST and EPBD are used for patients with CBD stones. Limited EST combined with EPBD has become popular for the removal of CBD stones in recent years, as it is thought to maximize outcomes and minimize the complications of both EST and EPBD.

Innovations and breakthroughs
This study investigated the short-and long-term outcomes of different sized balloons, chosen according to each patient's maximum CBD stone size, to dilate the papilla following limited EST. The authors found that choosing a balloon size no more than 15 mm based on the diameter of each patient's largest CBD stone is a good choice for removing CBD stones.

Applications
EPBD using a balloon size no more than 15 mm based on the diameter of patient's largest CBD stone following limited EST was proven to be a safe and effective treatment for CBD stones, and should be recommended for patients with CBD stones.

Terminology
ERCP: endoscopic retrograde cholangiopancreatography, a technique that combines the use of endoscopy and fluoroscopy to diagnose and treat certain problems of the biliary or pancreatic ductal systems; EST: endoscopic sphincterotomy, a minimally invasive surgery that was developed on the basis of ERCP to treat biliary or pancreatic ductal disease, the incision is made up to the full-portion of the papilla; Limited EST: like EST, the incision is made up to the mid-portion of the papilla; EPBD: endoscopic papillary balloon dilation, the papilla is dilated with a balloon to facilitate the removal of CBD stones.

Peer review
This is a good study in which authors evaluate the short-and long-term outcomes of different sized balloons to dilate the papilla following limited EST. The results are interesting and suggest that choosing balloon size no more than 15 mm based on the diameter of each patient's largest CBD stone is a good choice for removing CBD stones.