Randomized controlled trial of pancreatic stenting to prevent pancreatitis after endoscopic retrograde cholangiopancreatography

AIM:To determine the effectiveness of pancreatic duct(PD) stent placement for the prevention of pancreatitis after endoscopic retrograde cholangiopancreatography(ERCP) in high risk patients.METHODS:Authors conducted a single-blind,randomized controlled trial to evaluate the effectiveness of a pancreatic spontaneous dislodgement stent against post-ERCP pancreatitis,including rates of spontaneous dislodgement and complications.Authors defined high risk patients as having any of the following:sphincter of Oddi dysfunction,difficult cannulation,prior history of post-ERCP pancreatitis,pre-cut sphincterotomy,pancreatic ductal biopsy,pancreatic sphincterotomy,intraductal ultrasonography,or a procedure time of more than 30 min.Patients were randomized to a stent group(n = 60) or to a non-stent group(n = 60).An abdominal radiograph was obtained daily to assessspontaneous stent dislodgement.Post-ERCP pancreatitis was diagnosed according to consensus criteria.RESULTS:The mean age(± standard deviation) was 67.4 ± 13.8 years and the male:female ratio was 68:52.In the stent group,the mean age was 66 ± 13 years and the male:female ratio was 33:27,and in the non-stent group,the mean age was 68 ± 14 years and the male:female ratio was 35:25.There were no significant differences between groups with respect to age,gender,final diagnosis,or type of endoscopic intervention.The frequency of post-ERCP pancreatitis in PD stent and non-stent groups was 1.7%(1/60) and 13.3%(8/60),respectively.The severity of pancreatitis was mild in all cases.The frequency of post-ERCP pancreatitis in the stent group was significantly lower than in the non-stent group(P = 0.032,Fisher's exact test).The rate of hyperamylasemia were 30%(18/60) and 38.3%(23 of 60) in the stent and non-stent groups,respectively(P = 0.05,χ2 test).The placement of a PD stent was successful in all 60 patients.The rate of spontaneous dislodgement by the third day was 96.7%(58/60),and the median(range) time to dislodgement was 2.1(2-3) d.The rates of stent migration,hemorrhage,perforation,infection(cholangitis or cholecystitis) or other complicationss were 0%(0/60),0%(0/60),0%(0/60),0%(0/60),0%(0/60),respectively,in the stent group.Univariate analysis revealed no significant differences in high risk factors between the two groups.The pancreatic spontaneous dislodgement stent safely prevented post-ERCP pancreatitis in high risk patients.CONCLUSION:Pancreatic stent placement is a safe and effective technique to prevent post-ERCP pancreatitis.Therefore authors recommend pancreatic stent placement after ERCP in high risk patients.

Multicenter study of endoscopic preoperative biliary drainage for malignant distal biliary obstruction

AIM: To determine the optimal method of endoscopic preoperative biliary drainage for malignant distal biliary obstruction.METHODS: Multicenter retrospective study was conducted in patients who underwent plastic stent(PS) or nasobiliary catheter(NBC) placement for resectable malignant distal biliary obstruction followed by surgery between January 2010 and March 2012. Procedurerelated adverse events, stent/catheter dysfunction(occlusion or migration of PS/NBC, developmentof cholangitis, or other conditions that required repeat endoscopic biliary intervention), and jaundice resolution(bilirubin level < 3.0 mg/d L) were evaluated. Cumulative incidence of jaundice resolution and dysfunction of PS/NBC were estimated using competing risk analysis. Patient characteristics and preoperative biliary drainage were also evaluated for association with the time to jaundice resolution and PS/NBC dysfunction using competing risk regression analysis.RESULTS: In total, 419 patients were included in the study(PS, 253 and NBC, 166). Primary cancers included pancreatic cancer in 194 patients(46%), bile duct cancer in 172(41%), gallbladder cancer in three(1%), and ampullary cancer in 50(12%). The median serum total bilirubin was 7.8 mg/d L and 324 patients(77%) had ≥ 3.0 mg/d L. During the median time to surgery of 29 d [interquartile range(IQR), 30-39 d]. PS/NBC dysfunction rate was 35% for PS and 18% for NBC [Subdistribution hazard ratio(SHR) = 4.76; 95%CI: 2.44-10.0, P < 0.001]; the pig-tailed tip was a risk factor for PS dysfunction. Jaundice resolution was achieved in 85% of patients and did not depend on the drainage method(PS or NBC).CONCLUSION: PS has insufficient patency for preoperative biliary drainage. Given the drawbacks of external drainage via NBC, an alternative method of internal drainage should be explored.

Risk factors for proximal migration of biliary tube stents

AIM: To analyze the risk factors for biliary stent migration in patients with benign and malignant strictures. METHODS: Endoscopic stent placement was performed in 396 patients with bile duct stenosis, at our institution, between June 2003 and March 2009. The indications for bile duct stent implantation included common bile duct stone in 190 patients, malignant lesions in 112, chronic pancreatitis in 62, autoimmune pancreatitis in 14, trauma in eight, surgical complications in six, and primary sclerosing cholangitis(PSC) in four. We retrospectively examined the frequency of stent migration, and analyzed the patient factors(disease, whether endoscopic sphincterotomy was performed, location of bile duct stenosis and diameter of the bile duct) and stent characteristics(duration of stent placement, stent type, diameter and length). Moreover, we investigated retrieval methods for migrated stents and their associated success rates. RESULTS: The frequency of tube stent migration inthe total patient population was 3.5%. The cases in which tube stent migration occurred included those with common bile duct stones(3/190; 1.6%), malignant lesions(2/112; 1.8%), chronic pancreatitis(4/62; 6.5%), autoimmune pancreatitis(2/14; 14.3%), trauma(1/8; 12.5%), surgical complications(2/6; 33.3%), and PSC(0/4; 0%). The potential risk factors for migration included bile duct stenosis secondary to benign disease such as chronic pancreatitis and autoimmune pancreatitis(P = 0.030); stenosis of the lower bile duct(P = 0.031); bile duct diameter > 10 mm(P = 0.023); duration of stent placement > 1 mo(P = 0.007); use of straight-type stents(P < 0.001); and 10-Fr sized stents(P < 0.001). Retrieval of the migrated stents was successful in all cases. The grasping technique, using a basket or snare, was effective for pig-tailed or thin and straight stents, whereas the guidewire cannulation technique was effective for thick and straight stents. CONCLUSION: Migration of tube stents within the bile duct is rare but possible, and it is important to determine the risk factors involved in stent migration.

Endoscopic papillary large balloon dilation for removal of bile duct stones

AIM:To investigate the efficacy and outcomes of endoscopic papillary large balloon dilation(EPLBD)for bile duct stones in a multicenter prospective study.METHODS:Lithotomy by EPLBD was conducted in 124patients with bile duct stones≥13 mm in size or with three or more bile duct stones≥10 mm.After endoscopic sphincterotomy,the papilla was dilated using balloons 12-20 mm in diameter fitting the bile duct diameter.RESULTS:The success rate of first-time lithotomy was 86.3%(107/124)and the final lithotomy success rate was 100%(124/124).Lithotripsy was needed in10 of the 124(13.6%)patients.Adverse events due to the treatment procedure occurred in 6(4.8%)patients,all of which were mild.Performing large balloon dilation after endoscopic sphincterotomy in patients with large stones or multiple stones in the bile duct is considered to ensure the safety of treatment and to reduce the need for lithotripsy.CONCLUSION:It is suggested that treatment by EPLBD for large bile duct stones may be safe and useful.

Synchronous pancreatic solid pseudopapillary neoplasm and intraductal papillary mucinous neoplasm

Solid pseudopapillary neoplasm (SPN) is a rare and low-grade malignant pancreatic neoplasm composed of poorly cohesive monomorphic neoplastic cells forming solid and pseudopapillary structures with frequent hemorrhagic-cystic degeneration. Intraductal papillary mucinous neoplasm (IPMN) is a pancreatic exocrine tumor composed of intraductal papillary growth of mucin containing neoplastic cells in the main pancreatic duct or its major branches. In the case presented here, a 53-year-old, Japanese man was found to have multiple cystic lesions and dilatation of the main pancreatic duct in the neck of the pancreas. Histological examination revealed a main-duct and branch-duct type IPMN, of the gastric-type, involving the neck of the pancreas, associated with a 0.5 cm SPN in the caudal side of the IPMN. We diagnosed this case as synchronous SPN and IPMN. As far as we know, only one other case of synchronous SPN and IPMN has been reported. Both the present case and the previously reported case showed abnormal nuclear expression of β-catenin in SPN, whereas IPMN showed no abnormal nuclear expression. These results suggest that β-catenin abnormality is not a common pathogenetic factor of synchronous SPN and IPMN.

Isolated intrapancreatic Ig G4-related sclerosing cholangitis

Immunoglobulin G4-related sclerosing cholangitis(Ig G4-SC) is frequently associated with type 1 autoimmune pancreatitis(AIP). Association with AIP can be utilized in the diagnosis of Ig G4-SC. However, some cases of Ig G4-SC are isolated from AIP, which complicates the diagnosis. Most of the reported cases of isolated Ig G4-SC displayed hilar biliary strictures, whereas isolated Ig G4-SC with intrapancreatic biliary stricture is very rare. Recently, we have encountered 5 isolated intrapancreatic Ig G4-SC cases that were not associated with AIP, three of which were pathologically investigated after surgical operation. They all were males with a mean age of 74.2 years. The pancreas was not enlarged in any of these cases. No irregular narrowing of the main pancreatic duct was found. Bile duct wall thickening in lesions without luminal stenosis was detected by abdominal computed tomography in all five cases, by endoscopic ultrasonography in two out of four cases and by intraductal ultrasonography in all three cases. In three cases, serum Ig G4 levels were within the normal limits. The mean serum Ig G4 level measured before surgery was 202.1 mg/d L(4 cases). Isolated intrapancreatic Ig G4-SC is difficult to diagnose, especially if the Ig G4 level remains normal. Thus, this type of Ig G4-SC should be suspected in addition to cholangiocarcinoma and pancreatic cancer if stenosis of intrapancreatic bile duct is present.

Amenorrhea as a rare drug-related adverse event associated with everolimus for pancreatic neuroendocrine tumors

The patient was an asymptomatic 43-year-old woman. Abdominal ultrasonography and enhanced computed tomography showed a tumor lesion accompanied by multiple cystic changes in the liver and the pancreatic tail. Endoscopic ultrasound-fine needle aspiration was performed on the pancreatic tumor lesion and revealed pancreatic neuroendocrine tumor(PNET). As it was unresectable due to multiple liver metastases, the decision was made to initiate treatment with everolimus and transcatheter arterial chemoembolization. The patient ceased menstruating after the start of everolimus administration. When the administration was discontinued due to interstitial lung disease, menstruation resumed, but then again stopped with everolimus resumption. An association between everolimus and amenorrhea was highly suspected. Amenorrhea occurred as a rare adverse event of everolimus. As the younger women might be included in PNETs patients, we should put this adverse event into consideration.

Small serotonin-positive pancreatic endocrine tumors caused obstruction of the main pancreatic duct

We report 2 cases of pancreatic endocrine tumors that caused obstruction of the main pancreatic duct(MPD).A 49-year-old asymptomatic man was referred to our institution because dilation of the MPD was revealed by abdominal ultrasonography(US).No tumor was detected by endoscopic ultrasonography,computed tomography(CT),and magnetic resonance imaging(MRI).The diameter of the MPD was > 20 mm at the body,and no dilation was noted at the head.Although malignancy was not confirmed through cytology or imaging,pancreatic cancer was strongly suspected.Pancreaticoduo-denectomy was performed.Pathological and immunohistochemical examination revealed a 5 mm × 3 mm serotonin-positive endocrine tumor.Fibrosis was present around the MPD and seemed to cause stricture.A 32-year-old asymptomatic man had elevated serum amylase,and US demonstrated dilation of the MPD.No tumor was detected by CT and MRI.Pancreatic cancer was suspected due to stricture and dilation of the MPD.Pancreatectomy of middle part of pancreas was performed.Pathological and immunohistochemical examination revealed a serotonin-positive endocrine tumor sized 5 mm × 4 mm.We report 2 cases of serotonin-positive pancreatic endocrine tumors that caused stricture of the MPD in spite of the small size of the tumor.

Endoscopic approach to the diagnosis of pancreatic cystic tumor

Because of the aging of the population,prevalence of medical checkups,and advances in imaging studies,the number of pancreatic cystic lesions detected has increased. Once these lesions are detected,neoplastic cysts should be differentiated from non-neoplastic cysts. Furthermore,because of the malignant potential of some neoplastic pancreatic cysts,further differentiation between benign and malignant cysts should be made regardless of their size. Although endoscopic ultrasound(EUS) has a very high diagnostic performance for pancreatic cystic lesions among the various imaging modalities,EUS findings alone are insufficient for the differentiation of pancreatic cysts and diagnosis of malignancy. In addition,cytology by EUS-guided fine-needle aspiration(FNA) has a high specificity but a low sensitivity for diagnosing malignancy in pancreatic cystic tumors. The levels of amylase,lipase,and tumor markers in pancreatic cystic fluid are considered auxiliary parameters for diagnosis of benign and malignant cysts,and a definitive diagnosis of malignancy using these parameters is difficult. Thus,in addition to EUS,cytology by EUS-FNA,and cystic fluid analysis,new techniques based on EUS-guided through-the-needle imaging,such as confocal laser endomicroscopy and cystoscopy,have been explored in recent years.